Amphotericin B Desoxycholate, Amphotericin B Lipid-Based (Abelcet, Fungizone)


Highlights Of Prescribing Information

Systemic antifungal used for serious mycotic infections

Must be administered IV

Nephrotoxicity is biggest concern, particularly with the deoxycholate form; newer lipid based products are less nephrotoxic & penetrate into tissues better, but are more expensive

Renal function monitoring essential

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based interactions

What Is Amphotericin B Desoxycholate, Amphotericin B Lipid-Based Used For?

Because the potential exists for severe toxicity associated with this drug, it should only be used for progressive, potentially fatal fungal infections. Veterinary use of amphotericin has been primarily in dogs, but other species have been treated successfully. For further information on fungal diseases treated, see the Pharmacology and Dosage sections.

The liposomal form of amphotericin B can be used to treat Leishmaniasis.

Pharmacology / Actions

Amphotericin B is usually fungistatic, but can be fungicidal against some organisms depending on drug concentration. It acts by binding to sterols (primarily ergosterol) in the cell membrane and alters the permeability of the membrane allowing intracellular potassium and other cellular constituents to “leak out.” Because bacteria and rickettsia do not contain sterols, amphotericin B has no activity against those organisms. Mammalian cell membranes do contain sterols (primarily cholesterol) and the drug’s toxicity may be a result of a similar mechanism of action, although amphotericin binds less strongly to cholesterol than ergosterol.

Amphotericin B has in vitro activity against a variety of fungal organisms, including Blastomyces, Aspergillus, Paracoccidioides, Coccidioides, Histoplasma, Cryptococcus, Mucor, and Sporothrix. Zygomycetes is reportedly variable in its response to amphotericin. Aspergillosis in dogs and cats does not tend to respond satisfactorily to amphotericin therapy. Additionally, amphotericin B has in vivo activity against some protozoa species, including Leishmania spp. and Naegleria spp.

It has been reported that amphotericin B has immunoadjuvant properties but further work is necessary to confirm the clinical significance of this effect.


Pharmacokinetic data on veterinary species is apparently unavailable. In humans (and presumably animals), amphotericin B is poorly absorbed from the GI tract and must be given parenterally to achieve sufficient concentrations to treat systemic fungal infections. After intravenous injection, the drug reportedly penetrates well into most tissues but does not penetrate well into the pancreas, muscle, bone, aqueous humor, or pleural, pericardial, synovial, and peritoneal fluids. The drug does enter the pleural cavity and joints when inflamed. CSF levels are approximately 3% of those found in the serum. Approximately 90-95% of amphotericin in the vascular compartment is bound to serum proteins. The newer “lipid” forms of amphotericin B have higher penetration into the lungs, liver and spleen than the conventional form.

The metabolic pathways of amphotericin are not known, but it exhibits biphasic elimination. An initial serum half-life of 24-48 hours, and a longer terminal half-life of about 15 days have been described. Seven weeks after therapy has stopped, amphotericin can still be detected in the urine. Approximately 2-5% of the drug is recovered in the urine in unchanged (biologically active) form.

Before you take Amphotericin B Desoxycholate, Amphotericin B Lipid-Based

Contraindications / Precautions / Warnings

Amphotericin is contraindicated in patients who are hypersensitive to it, unless the infection is life-threatening and no other alternative therapies are available.

Because of the serious nature of the diseases treated with systemic amphotericin, it is not contraindicated in patients with renal disease, but it should be used cautiously with adequate monitoring.

Adverse Effects

Amphotericin B is notorious for its nephrotoxic effects; most canine patients will show some degree of renal toxicity after receiving the drug. The proposed mechanism of nephrotoxicity is via renal vasoconstriction with a subsequent reduction in glomerular filtration rate. The drug may directly act as a toxin to renal epithelial cells. Renal damage may be more common, irreversible and severe in patients who receive higher individual doses or have preexisting renal disease. Usually, renal function will return to normal after treatment is halted, but may require several months to do so.

Newer forms of lipid-complexed and liposome-encapsulated amphotericin B significantly reduce the nephrotoxic qualities of the drug. Because higher dosages may be used, these forms may also have enhanced effectiveness. A study in dogs showed that amphotericin B lipid complex was 8-10 times less nephrotoxic than the conventional form.

The patient’s renal function should be aggressively monitored during therapy. A pre-treatment serum creatinine, BUN (serum urea nitrogen/SUN), serum electrolytes (including magnesium if possible), total plasma protein (TPP), packed cell volume (PCV), body weight, and urinalysis should be done prior to starting therapy. BUN, creatinine, PCV, TPP, and body weight are rechecked before each dose is administered. Electrolytes and urinalysis should be monitored at least weekly during the course of treatment. Several different recommendations regarding the stoppage of therapy when a certain BUN is reached have been made. Most clinicians recommend stopping, at least temporarily, amphotericin treatment if the BUN reaches 30-40 mg/dL, serum creatinine >3 mg/dL or if other clinical signs of systemic toxicity develop such as serious depression or vomiting.

At least two regimens have been used in the attempt to reduce nephrotoxicity in dogs treated with amphotericin desoxycholate. Mannitol (12.5 grams or 0.5-1 g/kg) given concurrently with amphotericin B (slow IV infusion) to dogs may reduce nephrotoxicity, but may also reduce the efficacy of the therapy, particularly in blasto-mycosis. Mannitol treatment also increases the total cost of therapy. Sodium loading prior to treating has garnered considerable support in recent years. A tubuloglomerular feedback mechanism that induces vasoconstriction and decreased GFR has been postulated for amphotericin B toxicity; increased sodium load at the glomerulus may help prevent that feedback. One clinician (Foil 1986), uses 5 mL/kg of normal saline given in two portions, before and after amphotericin B dosing and states that is has been “… helpful in averting renal insufficiency….”

Cats are apparently more sensitive to the nephrotoxic aspects of amphotericin B, and many clinicians recommend using reduced dosages in this species (see Dosage section).

Adverse effects reported in horses include: tachycardia, tachyp-nea, lethargy, fever, restlessness, anorexia, anemia, phlebitis, polyuria and collapse.

Other adverse effects that have been reported with amphotericin B include: anorexia, vomiting, hypokalemia, distal renal tubular aci-dosis, hypomagnesemia, phlebitis, cardiac arrhythmias, non-regenerative anemia and fever (may be reduced with pretreatment with NSAIDs or a low dosage of steroids). Calcinosis cutis has been reported in dogs treated with amphotericin B. Amphotericin B can increase creatine kinase levels.

Reproductive / Nursing Safety

The safety of amphotericin B during pregnancy has not been established, but there are apparently no reports of teratogenicity associated with the drug. The risks of therapy should be weighed against the potential benefits. In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, hut there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, hut adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters.) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: A (Prohahly safe. Although specific studies may not have proved the safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women.)

Overdosage / Acute Toxicity

No case reports were located regarding acute intravenous overdose of amphotericin B. Because of the toxicity of the drug, dosage calculations and solution preparation procedures should be double-checked. If an accidental overdose is administered, renal toxicity maybe minimized by administering fluids and mannitol as outlined above in the Adverse Effects section.

How to use Amphotericin B Desoxycholate, Amphotericin B Lipid-Based

All dosages are for amphotericin B desoxycholate (regular amphotericin B) unless specifically noted for the lipid-based products.

Note: Some clinicians have recommended administering a 1 mg test dose (less in small dogs or cats) IV over anywhere from 20 minutes to 4 hours and monitoring pulse, respiration rates, temperature, and if possible, blood pressure. If a febrile reaction occurs some clinicians recommend adding a glucocorticoid to the IV infusion solution or using an antipyretic prior to treating, but these practices are controversial.

A published study () demonstrated less renal impairment and systemic adverse effects in dogs who received amphotericin BIV slowly over 5 hours in 1 L of D5W than in dogs who received the drug IV in 25 mL of D5W over 3 minutes.

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for dogs:

For treatment of susceptible systemic fungal infections:

a) Two regimens can be used; after diluting vial (as outlined below in preparation of solution section), either:

1) Rapid-Infusion Technique: Dilute quantity of stock solution to equal 0.25 mg/kg in 30 mL of 5% dextrose. Using butterfly catheter, flush with 10 mL of D5W. Infuse amphotericin B solution IV over 5 minutes. Flush catheter with 10 mL of D5W and remove catheter. Repeat above steps using 0.5 mg/kg 3 times a week until 9-12 mg/kg accumulated dosage is given.

2) Slow IV Infusion Technique: Dilute quantity of stock solution to equal 0.25 mg/kg in 250-500 mL of D5W. Place indwelling catheter in peripheral vein and give total volume over 4-6 hours. Flush catheter with 10 mL of D5W and remove catheter. Repeat above steps using 0.5 mg/kg 3 times a week until 9-12 mg/kg accumulated dosage is given. ()

b) In dehydrated, sodium-depleted animals, must rehydrate before administration. Dosage is 0.5 mg/kg diluted in D5W. In dogs with normal renal function, may dilute in 60-120 mL of D5W and give by slow IV over 15 minutes. In dogs with compromised renal function, dilute in 500 mL or 1 liter of D5W and give over slowly IV over 3-6 hours. Re-administer every other day if BUN remains below 50 mg/dl. If BUN exceeds 50 mg/dl, discontinue until BUN decreases to at least 35 mg/dl. Cumulative dose of 8 -10 mg/kg is required to cure blastomycosis or histoplasmosis. Coccidioidomycosis, aspergillosis and other fungal diseases require a greater cumulative dosage. ()

c) For treating systemic mycoses using the lipid-based products: AmBisome, Amphocil or Abelcet Give test dose of 0.5 mg/ kg; then 1-2.5 mg/kg IV q48h (or Monday, Wednesday, Friday) for 4 weeks or until the total cumulative dose is reached. Use 1 mg/kg dose for susceptible yeast and dimorphic fungi until a cumulative dose of 12 mg/kg is reached; for more resistant filamentous fungal infections (e.g., pythiosis) use the higher dose 2-2.5 mg/kg until a cumulative dose of 24-30 mg/kg is reached. ()

d) For treating systemic mycoses using the amphotericin B lipid complex (ABLC; Abelcet) product: 2-3 mg/kg IV three days per week for a total of 9-12 treatments (cumulative dose of 24-27 mg). Dilute to a concentration of 1 mg/mL in dextrose 5% (D5W) and infuse over 1-2 hours ()

e) For systemic mycoses using amphotericin B lipid complex (Abelcet): Dilute in 5% dextrose to a final concentration of 1 mg/mL and administer at a dosage of 2-3 mg/kg three times per week for 9-12 treatments or a cumulative dosage of 24-27 mg/kg ()

For blastomycosis (see general dosage guidelines above):

a) Amphotericin B 0.5 mg/kg 3 times weekly until a total dose of 6 mg/kg is given, with ketoconazole at 10-20 mg/kg (30 mg/kg for CNS, bone or eye involvement) divided for 3-6 months ()

b) Amphotericin B 0.15-0.5 mg/kg IV 3 times a week with ketoconazole 20 mg/day PO once daily or divided twice daily; 40 mg/kg divided twice daily for ocular or CNS involvement (for at least 2-3 months or until remission then start maintenance). When a total dose of amphotericin B reaches 4-6 mg/kg start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month or use ketoconazole at 10 mg/kg PO either once daily, divided twice daily or ketoconazole at 2.5-5 mg/kg PO once daily. If CNS/ocular involvement use ketoconazole at 20-40 mg/kg PO divided twice daily ()

c) For severe cases, using amphotericin B lipid complex (Abelcet): 1-2 mg/kg IV three times a week (or every other day) to a cumulative dose of 12-24 mg/kg ()

For cryptococcosis (see general dosage guidelines above):

a) Amphotericin B 0.5 – 0.8 mg/kg SC 2 – 3 times per week. Dose is diluted in 0.45% NaCl with 2.5% dextrose (400 mL for cats, 500 mL for dogs less than 20 kg and 1000 mL for dogs greater than 20 kg). Concentrations greater than 20 mg/L result in local irritation and sterile abscess formation. May combine with flucytosine or the azole antifungals. ()

For histoplasmosis (see general dosage guidelines above):

a) Amphotericin B 0.15 – 0.5 mg/kg IV 3 times a week with ketoconazole 10-20 mg/day PO once daily or divided twice daily (for at least 2-3 months or until remission then start maintenance). When a total dose of amphotericin B reaches 2-4 mg/kg, start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month or use ketoconazole at 10 mg/kg PO either once daily, divided twice daily or at 2.5-5 mg/kg PO once daily ()

b) As an alternative to ketoconazole treatment: 0.5 mg/kg IV given over 6-8 hours. If dose is tolerated, increase to 1 mg/ kg given on alternate days until total dose of 7.5-8.5 mg/kg cumulative dose is achieved ()

For Leishmaniasis:

a) Using the liposomal form of Amphotericin B: 3-3.3 mg/kg IV 3 times weekly for 3-5 treatments)

b) Using AmBisome (lipid-based product): Give initial test dose of 0.5 mg/kg, then 3-3.3 mg/kg IV every 72-96 hours until a cumulative dose of 15 mg/kg is reached. May be possible to give the same cumulative dose with a lower level every 48 hours. ()

For gastrointestinal pythiosis:

a) Resect lesions that are surgically removable to obtain 5 – 6 cm margins. Follow-up medical therapy using the amphotericin B lipid complex (ABLC; Abelcet) product: 1-2 mg/kg IV three times weekly for 4 weeks (cumulative dose 12-24 mg). May alternatively use itraconazole at 10 mg/kg PO once daily for 4-6 months. ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for cats:

For treatment of susceptible systemic fungal infections: a) Rapid-Infusion Technique: After diluting vial (as outlined below in preparation of solution section), dilute quantity of stock solution to equal 0.25 mg/kg in 30 mL of 5% dextrose. Using butterfly catheter, flush with 10 mL of D5W Infuse amphotericin B solution IV over 5 minutes. Flush catheter with 10 mL of D5W and remove catheter. Repeat above steps using 0.25 mg/kg 3 times a week until 9-12 mg/kg accumulated dosage is given. ()

For cryptococcosis (see general dosage guidelines above):

a) As an alternative therapy to ketoconazole: Amphotericin B: 0.25 mg/kg in 30 mL D5WIV over 15 minutes q48h with flucytosine at 200 mg/kg/day divided q6h PO. Continue therapy for 3-4 weeks after clinical signs have resolved or until BUN >50 mg/dl. (Legendre 1989)

b) Amphotericin B 0.15-0.4 mg/kg IV 3 times a week with flucytosine 125-250 mg/day PO divided two to four times a day. When a total dose of amphotericin B reaches 4-6 mg/ kg, start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month with flucytosine at dosage above or with ketoconazole at 10 mg/kg PO once daily or divided twice daily ()

c) Amphotericin B 0.5-0.8 mg/kg SC 2-3 times per week. Dose is diluted in 0.45% NaCl with 2.5% dextrose (400 mL for cats, 500 mL for dogs less than 20 kg and 1000 mL for dogs greater than 20 kg). Concentrations greater than 20 mg/L result in local irritation and sterile abscess formation. May combine with flucytosine or the azole antifungals. ()

d) For treating systemic mycoses using the amphotericin B lipid complex (ABLC; Abelcet) product: 1 mg/kg IV three days per week for a total of 12 treatments (cumulative dose of 12 mg). Dilute to a concentration of 1 mg/mL in dextrose 5% (D5W) and infuse over 1-2 hours ()

For histoplasmosis (see general dosage guidelines above):

a) Amphotericin B: 0.25 mg/kg in 30 mL D5WIV over 15 minutes q48h with ketoconazole at 10 mg/kg q12h PO. Continue therapy for 4-8 weeks or until BUN >50 mg/dl. If BUN increases greater than 50 mg/dl, continue ketoconazole alone. Ketoconazole is used long-term (at least 6 months of duration. ()

b) Amphotericin B 0.15-0.5 mg/kg IV 3 times a week with ketoconazole 10 mg/day PO once daily or divided twice daily (for at least 2-3 months or until remission, then start maintenance). When a total dose of amphotericin B reaches 2-4 mg/ kg, start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month or use ketoconazole at 10 mg/kg PO either once daily, divided twice daily or at 2.5-5 mg/kg PO once daily ()

For blastomycosis (see general dosage guidelines above):

a) Amphotericin B: 0.25 mg/kg in 30 mL D5WIV over 15 minutes q48h with ketoconazole: 10 mg/kg q12h PO (for at least 60 days). Continue amphotericin B therapy until a cumulative dose of 4 mg/kg is given or until BUN >50 mg/dl. If renal toxicity does not develop, may increase dose to 0.5 mg/ kg of amphotericin B. ()

b) Amphotericin B 0.15-0.5 mg/kg IV 3 times a week with ketoconazole 10 mg/day PO once daily or divided twice daily (for at least 2-3 months or until remission then start maintenance). When a total dose of amphotericin B reaches 4-6 mg/ kg start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month or use ketoconazole at 10 mg/kg PO either once daily, divided twice daily or ketoconazole at 2.5 – 5 mg/kg PO once daily. If CNS/ocular involvement, use ketoconazole at 20-40 mg/kg PO divided twice daily. ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for rabbits, rodents, and small mammals:

a) Rabbits: 1 mg/kg/day IV ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for horses:

For treatment of susceptible systemic fungal infections:

a) For fungal pneumonia: Day 1: 0.3 mg/kg IV; Day 2: 0.4 mg/kg IV; Day 3: 0.6 mg/kg IV; days 4-7: no treatment; then every other day until a total cumulative dose of 6.75 mg/kg has been administered ()

b) For phycomycoses and pulmonary mycoses: After reconstitution (see below) transfer appropriate amount of drug to 1L of D5W and administer using a 16 g needle IV at a rate of 1 L/ hr. Dosage schedule follows: Day 1: 0.3 mg/kg IV; Day 2: 0.45 mg/kg IV; Day 3: 0.6 mg/kg IV; then every other day for 3 days per week (MWF or TTHSa) until clinical signs of either improvement or toxicity occur. If toxicity occurs, a dose may be skipped, dosage reduced or dosage interval lengthened. Administration may extend from 10-80 days. ()

For intrauterine infusion: 200-250 mg. Little science is available for recommending doses, volume infused, frequency, diluents, etc. Most intrauterine treatments are commonly performed every day or every other day for 3-7 days. ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for Llamas:

For treatment of susceptible systemic fungal infections: a) A single case report. Llama received 1 mg test dose, then initially at 0.3 mg/kg IV over 4 hours, followed by 3 L of LRS with 1.5 mL of B-Complex and 20 mEq of KC1 added. Subsequent doses were increased by 10 mg and given every 48 hours until reaching 1 mg/kg q48h IV for 6 weeks. Animal tolerated therapy well, but treatment was ultimately unsuccessful (Coccidioidomycosis). ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for birds:

For treatment of susceptible systemic fungal infections:

a) For raptors and psittacines with aspergillosis: 1.5 mg/kg IV three times daily for 3 days with flucytosine or follow with flucytosine. May also use intratracheally at 1 mg/kg diluted in sterile water once to 3 times daily for 3 days in conjunction with flucytosine or nebulized (1 mg/mL of saline) for 15 minutes twice daily. Potentially nephrotoxic and may cause bone marrow suppression. ()

b) 1.5 mg/kg IV q12h for 3-5 days; topically in the trachea at 1 mg/kg q12h; 0.3-1 mg/mL nebulized for 15 minutes 2-4 times daily ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for reptiles:

For susceptible fungal respiratory infections: a) For most species: 1 mg/kg diluted in saline and given intratracheally once daily for 14-28 treatments ()

Client Information

■ Clients should be informed of the potential seriousness of toxic effects that can occur with amphotericin B therapy

■ The costs associated with therapy

Chemistry / Synonyms

A polyene macrolide antifungal agent produced by Streptomyces nodosus, amphotericin B occurs as a yellow to orange, odorless or practically odorless powder. It is insoluble in water and anhydrous alcohol. Amphotericin B is amphoteric and can form salts in acidic or basic media. These salts are more water soluble but possess less antifungal activity than the parent compound. Each mg of amphotericin B must contain not less than 750 micrograms of anhydrous drug. Amphotericin A may be found as a contaminant in concentrations not exceeding 5%. The commercially available powder for injection contains sodium desoxycholate as a solubilizing agent.

Newer lipid-based amphotericin B products are available that have less toxicity than the conventional desoxycholate form. These include amphotericin B cholesteryl sulfate complex (amphotericin B colloidal dispersion, ABCD, Amphotec), amphotericin B lipid complex (ABLC, Abelcet), and amphotericin B liposomal (ABL, L-AMB, Ambisome).

Amphotericin B may also be known as: amphotericin; amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, amphotericin B liposome, amphotericin B phospholipid complex, amphotericin B-Sodium cholesteryl sulfate complex, anfotericina B, or liposomal amphotericin B; many trade names are available.

Storage / Stability / Compatibility

Vials of amphotericin B powder for injection should be stored in the refrigerator (2-8°C), protected from light and moisture. Reconstitution of the powder must be done with sterile water for injection (no preservatives — see directions for preparation in the Dosage Form section below).

After reconstitution, if protected from light, the solution is stable for 24 hours at room temperature and for 1 week if kept refrigerated. After diluting with D5W (must have pH >4.3) for IV use, the manufacturer recommends continuing to protect the solution from light during administration. Additional studies however, have shown that potency remains largely unaffected if the solution is exposed to light for 8-24 hours.

Amphotericin B deoxycholate is reportedly compatible with the following solutions and drugs: D5W, D5W in sodium chloride 0.2%, heparin sodium, heparin sodium with hydrocortisone sodium phosphate, hydrocortisone sodium phosphate/succinate and sodium bicarbonate.

Amphotericin B deoxycholate is reportedly incompatible with the following solutions and drugs: normal saline, lactated Ringer’s, D5-normal saline, Ds-lactated Ringer’s, amino acids 4.25%-dextrose 25%, amikacin, calcium chloride/gluconate, carbenicillin disodium, chlorpromazine HCL, cimetidine HCL, diphenhydramine HCL, dopamine HCL, edetate calcium disodium (Ca EDTA), gentamicin sulfate, kanamycin sulfate, lidocaine HCL, metaraminol bitartrate, methyldopate HCL, nitrofurantoin sodium, oxytetracycline HCL, penicillin G potassium/sodium, polymyxin B sulfate, potassium chloride, prochlorperazine mesylate, streptomycin sulfate, tetracycline HCL, and verapamil HCL. Compatibility is dependent upon factors such as pH, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific information.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

Human-Labeled Products:

Amphotericin B Desoxycholate Powder for Injection: 50 mg in vials; Amphocin (Gensia Sicor); Fungizone Intravenous (Apothecon); generic (Pharma-Tek); (Rx)

Directions for reconstitution/administration: Using strict aseptic technique and a 20 gauge or larger needle, rapidly inject 10 mL of sterile water for injection (without a bacteriostatic agent) directly into the lyophilized cake; immediately shake well until solution is clear. A 5 mg/mL colloidal solution results. Further dilute (1:50) for administration to a concentration of 0.1 mg/mL with 5% dextrose in water (pH >4.2). An in-line filter may be used during administration, but must have a pore diameter >1 micron.

Amphotericin B Lipid-Based Suspension for Injection: 100 mg/20 mL (as lipid complex) in 10 mL & 20 mL vials with 5 micron filter needles: Abelcet (Enzon); (Rx)

Amphotericin B Lipid-Based Powder for Injection: 50 mg/vial (as cholesteryl) in 20 mL vials; 100 mg (as cholesteryl) in 50 mL vials; Amphotec (Sequus Pharmaceuticals); 50 mg (as liposomal) in single-dose vials with 5-micron filter; AmBisome (Fujisawa; (Rx)

Amphotericin B is also available in topical formulations: Fungizone (Apothecon); (Rx)


Ammonium Chloride (Uroeze)

Acidifying Agent

Highlights Of Prescribing Information

Urinary acidifier; treatment of metabolic alkalosis

Contraindicated in patients with hepatic failure or uremia

Potential adverse effects are primarily GI distress; IV use may lead to metabolic acidosis

May increase excretion of quinidine; decrease efficacy of erythromycin or aminoglycosides in urine

What Is Ammonium Chloride Used For?

The veterinary indications for ammonium chloride are as a urinary acidifying agent to help prevent and dissolve certain types of uroliths (e.g., struvite), to enhance renal excretion of some types of toxins (e.g., strontium, strychnine) or drugs (e.g., quinidine), or to enhance the efficacy of certain antimicrobials (e.g., chlortetracycline, methenamine mandelate, nitrofurantoin, oxytetracycline, penicillin G or tetracycline) when treating urinary tract infections. Ammonium chloride has also been used intravenously for the rapid correction of metabolic alkalosis.

Because of changes in feline diets to restrict struvite and as struvite therapeutic diets (e.g., s/d) cause aciduria, ammonium chloride is not commonly recommended for struvite uroliths in cats.

Pharmacology / Actions

The acidification properties of ammonium chloride are caused by its dissociation into chloride and ammonium ions in vivo. The ammonium cation is converted by the liver to urea with the release of a hydrogen ion. This ion combines with bicarbonate to form water and carbon dioxide. In the extracellular fluid, chloride ions combine with fixed bases and decrease the alkaline reserves in the body. The net effects are decreased serum bicarbonate levels and a decrease in blood and urine pH.

Excess chloride ions presented to the kidney are not completely reabsorbed by the tubules and are excreted with cations (principally sodium) and water. This diuretic effect is usually compensated for in the kidneys after a few days of therapy.


No information was located on the pharmacokinetics of this agent in veterinary species. In humans, ammonium chloride is rapidly absorbed from the GL

Before you take Ammonium Chloride

Contraindications / Precautions / Warnings

Ammonium chloride is contraindicated in patients with severe hepatic disease as ammonia may accumulate and cause toxicity. In general, ammonium chloride should not be administered to uremic patients since it can intensify the metabolic acidosis already existing in some of these patients. As sodium depletion can occur, ammonium chloride should not be used alone in patients with severe renal insufficiency and metabolic alkalosis secondary to vomiting hydrochloric acid. In these cases, sodium chloride repletion with or without ammonium chloride administration should be performed to correct both sodium and chloride deficits. Ammonium chloride is contraindicated in patients with urate calculi or respiratory acidosis and high total CO2 and buffer base. Ammonium chloride alone cannot correct hypochloremia with secondary metabolic alkalosis due to intracellular potassium chloride depletion; potassium chloride must be administered to these patients.

Do not administer subcutaneously, rectally or intraperitoneally Use ammonium chloride with caution in patients with pulmonary insufficiency or cardiac edema.

Adverse Effects

Development of metabolic acidosis (sometimes severe) can occur unless adequate monitoring is performed. When used intravenously, pain at the injection site can develop; slow administration lessens this effect. Gastric irritation, nausea and vomiting may be associated with oral dosing of the drug. Urinary acidification is associated with an increased risk for calcium oxalate urolith formation in cats.

Overdosage / Acute Toxicity

Clinical signs of overdosage may include: nausea, vomiting, excessive thirst, hyperventilation, bradycardias or other arrhythmias, and progressive CNS depression. Profound acidosis and hypokalemia maybe noted on laboratory results.

Treatment should consist of correcting the acidosis by administering sodium bicarbonate or sodium acetate intravenously. Hypokalemia should be treated by using a suitable oral (if possible) potassium product. Intense acid-base and electrolyte monitoring should be performed on an ongoing basis until the patient is stable.

Reproductive / Nursing Safety

In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, hut there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, hut adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters.) In a separate system evaluating the safety of drugs in canine and feline pregnancy (), this drug is categorized as in class: B (Safe for use if used cautiously. Studies in laboratory animals may have uncovered some risk, hut these drugs appear to he safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term.)

How to use Ammonium Chloride

Ammonium Chloride dosage for dogs:

For urine acidification:

a) As adjunctive therapy for struvite uroliths: 20 mg/kg PO three times daily ()

b) To enhance the renal elimination of certain toxins/drugs: 200 mg/kg/day divided four times daily ()

c) To enhance elimination of strontium: 0.2-0.5 grams PO 3-4 times a day (used with calcium salts) ()

For ATT (ammonia tolerance testing):

a) 2 mL/kg of a 5% solution of ammonium chloride deep in the rectum, blood sampled at 20 minutes and 40 minutes; or oral challenge with ammonium chloride 100 mg/kg (maximum dose = 3 grams) either in solution: dissolved in 20-50 mL warm water or in gelatin capsules, blood sampled at 30 and 60 minutes. Test may also be done by comparing fasting and 6-hour postprandial samples without giving exogenous ammonium chloride. (Center 2004)

Ammonium Chloride dosage for cats:

For urine acidification:

a) In struvite dissolution therapy if diet and antimicrobials do not result in acid urine or to help prevent idiopathic FUS in a non-obstructed cat: 20 mg/kg PO twice daily ()

b) As adjunctive therapy for struvite uroliths: 20 mg/kg PO twice daily ()

c) 800 mg per day given in the food once daily (if diet and antimicrobials do not reduce pH) ()

Ammonium Chloride dosage for horses:

a) 4-15 grams PO ()

b) Ammonium chloride as a urinary acidifier: 60-520 mg/kg PO daily. Ammonium salts are unpalatable and will have to be dosed via stomach tube or dosing syringe. Alternatively, ammonium sulfate at 165 mg/kg PO per day is more palatable and may be accepted when mixed with grain or hay. ()

c) As a urinary acidifier to enhance renal excretion of strychnine: 132 mg/kg PO ()

Ammonium Chloride dosage for cattle:

For urolithiasis prevention:

a) 200 mg/kg PO ()

b) 15-30 grams PO ()

Ammonium Chloride dosage for sheep and goats:

For urolithiasis prevention:

a) 200 mg/kg PO ()

b) 1-2 grams PO ()

Client Information

■ Contact veterinarian if animal exhibits signs of nausea, vomiting, excessive thirst, hyperventilation or progressive lethargy

■ Powders may have a bitter taste and patients may not accept their food after mixing

Chemistry / Synonyms

An acid-forming salt, ammonium chloride occurs as colorless crystals or as white, fine or course, crystalline powder. It is somewhat hygroscopic, and has a cool, saline taste. When dissolved in water, the temperature of the solution is decreased. One gram is soluble in approximately 3 mL of water at room temperature; 1.4 mL at 100°C. One gram is soluble in approximately 100 mL of alcohol.

One gram of ammonium chloride contains 18.7 mEq of ammonium and chloride ions. The commercially available concentrate for injection (26.75%) contains 5 mEq of each ion per mL and contains disodium edetate as a stabilizing agent. The pH of the concentrate for injection is approximately 5.

Ammonium chloride may also be known as muriate of ammonia and sal ammoniac.

Storage / Stability / Compatibility

Ammonium chloride for injection should be stored at room temperature; avoid freezing. At low temperatures, crystallization may occur; it may be resolubolized by warming to room temperature in a water bath.

Ammonium chloride should not be titrated with strong oxidizing agents etc. potassium chlorate) as explosive compounds may result.

Ammonium chloride is reported to be physically compatible with all commonly used IV replacement fluids and potassium chloride. It is incompatible with codeine phosphate, dimenhydrinate, methadone HCL, nitrofurantoin sodium, sulfisoxazole diolamine, and warfarin sodium. It is also reportedly incompatible with alkalis and their hydroxides.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products:

Ammonium Chloride Tablets: 200 mg, 400 mg; UriKare 200, 400 Tablets (Neogen); (Rx). Approved for use in cats and dogs.

Ammonium Chloride Granules: 200 mg per V4 teaspoonful powder; Uroeze200 (Virbac), UriKare 200 (Neogen); (Rx) Approved for cats and dogs.

Ammonium Chloride Granules: 400 mg per V4 teaspoonful powder; Uroeze (Virbac), UriKare 400 (Neogen); (Rx) Approved for cats and dogs.

Ammonium chloride is also found in some veterinary labeled cough preparations e.g., Spect-Aid Expectorant Granules (7% guaifenesin, 75% ammonium chloride, potassium iodide 2%) and in some cough syrups (also containing guaifenesin, pyrilamine and phenylephrine).

When used in large animals, feed grade ammonium chloride can be obtained from feed mills.

Human-Labeled Products:

Ammonium Chloride Injection: 26.75% (5 mEq/mL) in 20 mL (100 mEq) vials. Must be diluted before infusion; generic; (Rx). Preparation of solution for IV administration: Dilute 1 or 2 vials (100-200 mEq) in either 500 or 1000 mL of sodium chloride 0.9% for injection. Do not administer at a rate greater than 5 mL/min (human adult).


Aminophylline Theophylline

Phosphodiesterase Inhibitor Bronchodilator

Highlights Of Prescribing Information

Bronchodilator drug with diuretic activity; used for bronchospasm & cardiogenic pulmonary edema

Narrow therapeutic index in humans, but dogs appear to be less susceptible to toxic effects at higher plasma levels

Therapeutic drug monitoring recommended

Many drug interactions

What Is Aminophylline Theophylline Used For?

The theophyllines are used primarily for their broncho dilatory effects, often in patients with myocardial failure and/or pulmonary edema. While they are still routinely used, the methylxanthines must be used cautiously due to their adverse effects and toxicity.


The theophyllines competitively inhibit phosphodiesterase thereby increasing amounts of cyclic AMP which then increase the release of endogenous epinephrine. The elevated levels of cAMP may also inhibit the release of histamine and slow reacting substance of anaphylaxis (SRS-A). The myocardial and neuromuscular transmission effects that the theophyllines possess maybe a result of translocating intracellular ionized calcium.

The theophyllines directly relax smooth muscles in the bronchi and pulmonary vasculature, induce diuresis, increase gastric acid secretion and inhibit uterine contractions. They have weak chronotropic and inotropic action, stimulate the CNS and can cause respiratory stimulation (centrally-mediated).


The pharmacokinetics of theophylline have been studied in several domestic species. After oral administration, the rate of absorption of the theophyllines is limited primarily by the dissolution of the dosage form in the gut. In studies in cats, dogs, and horses, bioavail-abilities after oral administration are nearly 100% when non-sustained release products are used. One study in dogs that compared various sustained-release products (), found bioavailabilities ranging from approximately 30-76% depending on the product used.

Theophylline is distributed throughout the extracellular fluids and body tissues. It crosses the placenta and is distributed into milk (70% of serum levels). In dogs, at therapeutic serum levels only about 7-14% is bound to plasma proteins. The volume of distribution of theophylline for dogs has been reported to be 0.82 L/kg. The volume of distribution in cats is reported to be 0.46 L/kg, and in horses, 0.85-1.02 L/kg. Because of the low volumes of distribution and theophylline’s low lipid solubility, obese patients should be dosed on a lean body weight basis.

Theophylline is metabolized primarily in the liver (in humans) to 3-methylxanthine which has weakbronchodilitory activity. Renal clearance contributes only about 10% to the overall plasma clearance of theophylline. The reported elimination half-lives (mean values) in various species are: dogs = 5.7 hours; cats = 7.8 hours, pigs = 11 hours; and horses = 11.9 to 17 hours. In humans, there are very wide interpatient variations in serum half-lives and resultant serum levels. It could be expected that similar variability exists in veterinary patients, particularly those with concurrent illnesses.

Before you take Aminophylline Theophylline

Contraindications / Precautions / Warnings

The theophyllines are contraindicated in patients who are hypersensitive to any of the xanthines, including theobromine or caffeine. Patients who are hypersensitive to ethylenediamine should not take aminophylline.

The theophyllines should be administered with caution in patients with severe cardiac disease, seizure disorders, gastric ulcers, hyperthyroidism, renal or hepatic disease, severe hypoxia, or severe hypertension. Because it may cause or worsen preexisting arrhythmias, patients with cardiac arrhythmias should receive theophylline only with caution and enhanced monitoring. Neonatal and geriatric patients may have decreased clearances of theophylline and be more sensitive to its toxic effects. Patients with CHF may have prolonged serum half-lives of theophylline.

Adverse Effects

The theophyllines can produce CNS stimulation and gastrointestinal irritation after administration by any route. Most adverse effects are related to the serum level of the drug and may be symptomatic of toxic blood levels; dogs appear to tolerate levels that may be very toxic to humans. Some mild CNS excitement and GI disturbances are not uncommon when starting therapy and generally resolve with chronic administration in conjunction with monitoring and dosage adjustments.

Dogs and cats can exhibit clinical signs of nausea and vomiting, insomnia, increased gastric acid secretion, diarrhea, polyphagia, polydipsia, and polyuria. Side effects in horses are generally dose related and may include: nervousness, excitability (auditory, tactile, and visual), tremors, diaphoresis, tachycardia, and ataxia. Seizures or cardiac dysrhythmias may occur in severe intoxications.

Reproductive / Nursing Safety

In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, hut there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.)

Overdosage / Acute Toxicity

Clinical signs of toxicity (see above) are usually associated with levels greater than 20 mcg/mL in humans and become more severe as the serum level exceeds that value. Tachycardias, arrhythmias, and CNS effects (seizures, hyperthermia) are considered the most life-threatening aspects of toxicity. Dogs appear to tolerate serum levels higher than 20 mcg/mL.

Treatment of theophylline toxicity is supportive. After an oral ingestion, the gut should be emptied, charcoal and a cathartic administered using the standardized methods and cautions associated with these practices. Patients suffering from seizures should have an adequate airway maintained and treated with IV diazepam. The patient should be constantly monitored for cardiac arrhythmias and tachycardia. Fluid and electrolytes should be monitored and corrected as necessary. Hyperthermia may be treated with phenothiazines and tachycardia treated with propranolol if either condition is considered life threatening.

How to use Aminophylline Theophylline

Note: Theophyllines have a low therapeutic index; determine dosage carefully. Because of aminophylline/theophylline’s pharmacokinet-ic characteristics, it should be dosed on a lean body weight basis in obese patients. Dosage conversions between aminophylline and theophylline can be easily performed using the information found in the Chemistry section below. Aminophylline causes intense local pain when administered IM and is rarely used or recommended via this route.

Aminophylline Theophylline dosage for dogs:

a) Using Theochron Extended-Release Tablets or Theo-Cap Extended-Release Capsules: Give 10 mg/kg PO every 12 hours initially, if no adverse effects are observed and the desired clinical effect is not achieved, give 15 mg/kg PO q12h while monitoring for adverse effects. ()

b) For adjunctive medical therapy for mild clinical signs associated with tracheal collapse (<50% collapse): aminophylline: 11 mg/kg PO, IM or IV three times daily. ()

c) For adjunctive therapy of severe, acute pulmonary edema and bronchoconstriction: Aminophylline 4-8 mg/kg IV or IM, or 6-10 mg/kg PO every 8 hours. Long-term use is not recommended. ()

d) For cough: Aminophylline: 10 mg/kg PO, IV three times daily ()

e) As a broncho dilator tor collapsing trachea: 11 mg/kg PO or IV q6- 12h ()

Aminophylline Theophylline dosage for cats:

a) Using Theo-Dur 20 mg/kg PO once daily in the PM; using Slo-Bid 25 mg/kg PO once daily in the PM (Johnson 2000) [Note: The products Theo-Dur and Slo-Bid mentioned in this reference are no longer available in the USA. Although hard data is not presently available to support their use in cats, a reasonable alternative would be to cautiously use the dog dose and products mentioned above in the reference by Bach et al — Plumb]

b) Using aminophylline tablets: 6.6. mg/kg PO twice daily; using sustained release tablets (Theo-Dur): 25-50 mg (total dose) per cat PO in the evening ()

c) For adjunctive medical therapy for mild clinical signs associated with tracheal collapse (<50% collapse): aminophylline: 5 mg/kg PO, two times daily. ()

d) For adjunctive therapy for bronchoconstriction associated with fulminant CHF: Aminophylline 4-8 mg/kg SC, IM, IV q8-12h. ()

e) For cough: Aminophylline: 5 mg/kg PO twice daily ()

Aminophylline Theophylline dosage for ferrets:

a) 4.25 mg/kg PO 2-3 times a day ()

Aminophylline Theophylline dosage for horses:

(Note: ARCI UCGFS Class 3 Aminophylline Theophylline)

NOTE: Intravenous aminophylline should be diluted in at least 100 mL of D5W or normal saline and administered slowly (not >25 mg/min). For adjunctive treatment of pulmonary edema:

a) Aminophylline 2-7 mg/kg IV q6- 12h; Theophylline 5-15 mg/kg PO q12h ()

b) 11 mg/kg PO or IV q8-12h. To “load” may either double the initial dose or give both the oral and IV dose at the same time. IV infusion should be in approximately 1 liter of IV fluids and given over 20-60 minutes. Recommend monitoring serum levels. ()

For adjunctive treatment for heaves (RAO):

a) Aminophylline: 5-10 mg/kg PO or IV twice daily. ()

b) Aminophylline: 4-6 mg/kg PO three times a day. ()


■ Therapeutic efficacy and clinical signs of toxicity

■ Serum levels at steady state. The therapeutic serum levels of theophylline in humans are generally described to be between 10-20 micrograms/mL. In small animals, one recommendation for monitoring serum levels is to measure trough concentration; level should be at least above 8-10 mcg/mL (Note: Some recommend not exceeding 15 micrograms/mL in horses).

Client Information

■ Give dosage as prescribed by veterinarian to maximize the drug’s benefit

Chemistry / Synonyms

Xanthine derivatives, aminophylline and theophylline are considered to be respiratory smooth muscle relaxants but, they also have other pharmacologic actions. Aminophylline differs from theophylline only by the addition of ethylenediamine to its structure and may have different amounts of molecules of water of hydration. 100 mg of aminophylline (hydrous) contains approximately 79 mg of theophylline (anhydrous); 100 mg of aminophylline (anhydrous) contains approximately 86 mg theophylline (anhydrous). Conversely, 100 mg of theophylline (anhydrous) is equivalent to 116 mg of aminophylline (anhydrous) and 127 mg aminophylline (hydrous).

Aminophylline occurs as bitter-tasting, white or slightly yellow granules or powder with a slight ammoniacal odor and a pKa of 5. Aminophylline is soluble in water and insoluble in alcohol.

Theophylline occurs as bitter-tasting, odorless, white, crystalline powder with a melting point between 270-274°C. It is sparingly soluble in alcohol and only slightly soluble in water at a pH of 7, but solubility increases with increasing pH.

Aminophylline may also be known as: aminofilina, aminophyllinum, euphyllinum, metaphyllin, theophyllaminum, theophylline and ethylenediamine, theophylline ethylenediamine compound, or theophyllinum ethylenediaminum; many trade names are available.

Theophylline may also be known as: anhydrous theophylline, teofillina, or theophyllinum; many trade names are available.

Storage / Stability/Compatibility

Unless otherwise specified by the manufacturer, store aminophylline and theophylline oral products in tight, light-resistant containers at room temperature. Do not crush or split sustained-release oral products unless label states it is permissible.

Aminophylline for injection should be stored in single-use containers in which carbon dioxide has been removed. It should also be stored at temperatures below 30°C and protected from freezing and light. Upon exposure to air (carbon dioxide), aminophylline will absorb carbon dioxide, lose ethylenediamine and liberate free theophylline that can precipitate out of solution. Do not inject aminophylline solutions that contain either a precipitate or visible crystals.

Aminophylline for injection is reportedly compatible when mixed with all commonly used IV solutions, but may be incompatible with 10% fructose or invert sugar solutions.

Aminophylline is reportedly compatible when mixed with the following drugs: amobarbital sodium, bretylium tosylate, calcium gluconate, chloramphenicol sodium succinate, dexamethasone sodium phosphate, dopamine HCL, erythromycin lactobionate, heparin sodium, hydro cortisone sodium succinate, lidocaine HCL, mephentermine sulfate, methicillin sodium, methyldopate HCL, metronidazole with sodium bicarbonate, pentobarbital sodium, phenobarbital sodium, potassium chloride, secobarbital sodium, sodium bicarbonate, sodium iodide, terbutaline sulfate, thiopental sodium, and verapamil HCL

Aminophylline is reportedly incompatible (or data conflicts) with the following drugs: amikacin sulfate, ascorbic acid injection, bleomycin sulfate, cephalothin sodium, cephapirin sodium, clindamycin phosphate, codeine phosphate, corticotropin, dimenhydrinate, dobutamine HCL, doxorubicin HCL, epinephrine HCL, erythromycin gluceptate, hydralazine HCL, hydroxyzine HCL, insulin (regular), isoproterenol HCL, levorphanol bitartrate, meperidine HCL, methadone HCL, methylprednisolone sodium succinate, morphine sulfate, nafcillin sodium, norepinephrine bitartrate, oxytetracycline, penicillin G potassium, pentazocine lactate, procaine HCL, prochlorperazine edisylate or mesylate, promazine HCL, promethazine HCL, sulfisoxazole diolamine, tetracycline HCL, vancomycin HCL, and vitamin B complex with C. Compatibility is dependent upon factors such as pH, concentration, temperature, and diluent used and it is suggested to consult specialized references for more specific information.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information.

Human-Labeled Products:

The listing below is a sampling of products and sizes available; consult specialized references for a more complete listing.

Aminophylline Tablets: 100 mg (79 mg theophylline) & 200 mg (158 mg theophylline); generic; (Rx)

Aminophylline Injection: 250 mg (equiv. to 197 mg theophylline) mL in 10 mL & 20 mL vials, amps and syringes; generic; (Rx)

Theophylline Time Released Capsules and Tablets: 100 mg, 125 mg 200 mg, 300 mg, 400 mg, 450 mg, & 600 mg. (Note: Different products have different claimed release rates which may or may not correspond to actual times in veterinary patients; Theophylline Extended-Release (Dey); Theo-24 (UCB Pharma); Theophylline SR (various); Theochron (Forest, various); Theophylline (Able); Theocron (Inwood); Uniphyl (Purdue Frederick); generic; (Rx)

Theophylline Tablets and Capsules: 100 mg, 200 mg, & 300 mg; Bronkodyl (Winthrop); Elixophyllin (Forest); generic; (Rx)

Theophylline Elixir: 80 mg/15 mL (26.7 mg/5 mL) in pt, gal, UD 15 and 30 mL, Asmalix (Century); Elixophyllin (Forest); Lanophyllin (Lannett); generic; (Rx)

Theophylline & Dextrose Injection: 200 mg/container in 50 mL (4 mg/mL) & 100 mL (2 mg/mL); 400 mg/container in 100 mL (4 mg/ mL), 250 mL (1.6 mg/mL), 500 mL (0.8 mg/mL) & 1000 mL (0.4 mg/mL); 800 mg/container in 250 mL (3.2 mg/mL), 500 mL (1.6 mg/mL) & 1000 mL (0.8 mg/mL); Theophylline & 5% Dextrose (Abbott & Baxter); (Rx)


Amikacin Sulfate (Amikin, Amiglyde-V)

Aminoglycoside Antibiotic

Highlights Of Prescribing Information

Parenteral aminoglycoside antibiotic that has good activity against a variety of bacteria, predominantly gram-negative aerobic bacilli

Adverse Effects: Nephrotoxicity, ototoxicity, neuromuscu-lar blockade

Cats may be more sensitive to toxic effects

Risk factors for toxicity: Preexisting renal disease, age (both neonatal & geriatric), fever, sepsis & dehydration

Now usually dosed once daily when used systemically

What Is Amikacin Sulfate Used For?

While parenteral use is only approved in dogs, amikacin is used clinically to treat serious gram-negative infections in most species. It is often used in settings where gentamicin-resistant bacteria are a clinical problem. The inherent toxicity of the aminoglycosides limit their systemic use to serious infections when there is either a documented lack of susceptibility to other, less toxic antibiotics or when the clinical situation dictates immediate treatment of a presumed gram-negative infection before culture and susceptibility results are reported.

Amikacin is also approved for intrauterine infusion in mares. It is used with intra-articular injection in foals to treat gram-negative septic arthritis.


Amikacin, like the other aminoglycoside antibiotics, act on susceptible bacteria presumably by irreversibly binding to the 30S ribosomal subunit thereby inhibiting protein synthesis. It is considered a bactericidal concentration-dependent antibiotic.

Amikacin’s spectrum of activity includes: coverage against many aerobic gram-negative and some aerobic gram-positive bacteria, including most species of E. coli, Klebsiella, Proteus, Pseudomonas, Salmonella, Enterobacter, Serratia, and Shigella, Mycoplasma, and Staphylococcus. Several strains of Pseudomonas aeruginosa, Proteus, and Serratia that are resistant to gentamicin will still be killed by amikacin.

Antimicrobial activity of the aminoglycosides is enhanced in an alkaline environment.

The aminoglycoside antibiotics are inactive against fungi, viruses and most anaerobic bacteria.


Amikacin, like the other aminoglycosides is not appreciably absorbed after oral or intrauterine administration, but is absorbed from topical administration (not from skin or the urinary bladder) when used in irrigations during surgical procedures. Patients receiving oral aminoglycosides with hemorrhagic or necrotic enteritises may absorb appreciable quantities of the drug. After IM administration to dogs and cats, peak levels occur from ½1 hour later. Subcutaneous injection results in slightly delayed peak levels and with more variability than after IM injection. Bio availability from extravascular injection (IM or SC) is greater than 90%.

After absorption, aminoglycosides are distributed primarily in the extracellular fluid. They are found in ascitic, pleural, pericardial, peritoneal, synovial and abscess fluids; high levels are found in sputum, bronchial secretions and bile. Aminoglycosides are minimally protein bound (<20%, streptomycin 35%) to plasma proteins. Aminoglycosides do not readily cross the blood-brain barrier nor penetrate ocular tissue. CSF levels are unpredictable and range from 0-50% of those found in the serum. Therapeutic levels are found in bone, heart, gallbladder and lung tissues after parenteral dosing. Aminoglycosides tend to accumulate in certain tissues such as the inner ear and kidneys, which may help explain their toxicity. Volumes of distribution have been reported to be 0.15-0.3 L/kg in adult cats and dogs, and 0.26-0.58 L/kg in horses. Volumes of distribution may be significantly larger in neonates and juvenile animals due to their higher extracellular fluid fractions. Aminoglycosides cross the placenta; fetal concentrations range from 15-50% of those found in maternal serum.

Elimination of aminoglycosides after parenteral administration occurs almost entirely by glomerular filtration. The approximate elimination half-lives for amikacin have been reported to be 5 hours in foals, 1.14-2.3 hours in adult horses, 2.2-2.7 hours in calves, 1-3 hours in cows, 1.5 hours in sheep, and 0.5-2 hours in dogs and cats. Patients with decreased renal function can have significantly prolonged half-lives. In humans with normal renal function, elimination rates can be highly variable with the aminoglycoside antibiotics.

Before you take Amikacin Sulfate

Contraindications / Precautions / Warnings

Aminoglycosides are contraindicated in patients who are hypersensitive to them. Because these drugs are often the only effective agents in severe gram-negative infections, there are no other absolute contraindications to their use. However, they should be used with extreme caution in patients with preexisting renal disease with concomitant monitoring and dosage interval adjustments made. Other risk factors for the development of toxicity include age (both neonatal and geriatric patients), fever, sepsis and dehydration.

Because aminoglycosides can cause irreversible ototoxicity, they should be used with caution in “working” dogs (e.g., “seeing-eye,” herding, dogs for the hearing impaired, etc.).

Aminoglycosides should be used with caution in patients with neuromuscular disorders (e.g., myasthenia gravis) due to their neuromuscular blocking activity.

Because aminoglycosides are eliminated primarily through renal mechanisms, they should be used cautiously, preferably with serum monitoring and dosage adjustment in neonatal or geriatric animals.

Aminoglycosides are generally considered contraindicated in rabbits/hares as they adversely affect the GI flora balance in these animals.

Adverse Effects

The aminoglycosides are infamous for their nephrotoxic and ototox-ic effects. The nephrotoxic (tubular necrosis) mechanisms of these drugs are not completely understood, but are probably related to interference with phospholipid metabolism in the lysosomes of proximal renal tubular cells, resulting in leakage of proteolytic enzymes into the cytoplasm. Nephrotoxicity is usually manifested by: increases in BUN, creatinine, nonprotein nitrogen in the serum, and decreases in urine specific gravity and creatinine clearance. Proteinuria and cells or casts may be seen in the urine. Nephrotoxicity is usually reversible once the drug is discontinued. While gentamicin may be more nephrotoxic than the other aminoglycosides, the incidences of nephrotoxicity with all of these agents require equal caution and monitoring.

Ototoxicity (8th cranial nerve toxicity) of the aminoglycosides can manifest by either auditory and/or vestibular clinical signs and may be irreversible. Vestibular clinical signs are more frequent with streptomycin, gentamicin, or tobramycin. Auditory clinical signs are more frequent with amikacin, neomycin, or kanamycin, but either form can occur with any of these drugs. Cats are apparently very sensitive to the vestibular effects of the aminoglycosides.

The aminoglycosides can also cause neuromuscular blockade, facial edema, pain/inflammation at injection site, peripheral neuropathy and hypersensitivity reactions. Rarely, GI clinical signs, hematologic and hepatic effects have been reported.

Reproductive / Nursing Safety

Aminoglycosides can cross the placenta and while rare, may cause 8th cranial nerve toxicity or nephrotoxicity in fetuses. Because the drug should only be used in serious infections, the benefits of therapy may exceed the potential risks. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, hut there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.) In a separate system evaluating the safety of drugs in canine and feline pregnancy (), this drug is categorized as in class: C (These drugs may have potential risks. Studies in people or laboratory animals have uncovered risks, and these drugs should he used cautiously as a last resort when the benefit of therapy clearly outweighs the risks.)

Aminoglycosides are excreted in milk. While potentially, amikacin ingested with milk could alter GI flora and cause diarrhea, amikacin in milk is unlikely to be of significant concern after the first few days of life (colostrum period).

Overdosage / Acute Toxicity

Should an inadvertent overdosage be administered, three treatments have been recommended. Hemodialysis is very effective in reducing serum levels of the drug but is not a viable option for most veterinary patients. Peritoneal dialysis also will reduce serum levels but is much less efficacious. Complexation of drug with either carbenicillin or ticarcillin (12-20 g/day in humans) is reportedly nearly as effective as hemodialysis. Since amikacin is less affected by this effect than either tobramycin or gentamicin, it is assumed that reduction in serum levels will also be minimized using this procedure.

How to use Amikacin Sulfate

Note: Most infectious disease clinicians now agree that aminoglycosides should be dosed once a day in most patients (mammals). This dosing regimen yields higher peak levels with resultant greater bacterial kill, and as aminoglycosides exhibit a “post-antibiotic effect”, surviving susceptible bacteria generally do not replicate as rapidly even when antibiotic concentrations are below MIC. Periods where levels are low may also decrease the “adaptive resistance” (bacteria take up less drug in the presence of continuous exposure) that can occur. Once daily dosing may decrease the toxicity of aminoglycosides as lower urinary concentrations may mean less uptake into renal tubular cells. However, patients who are neutropenic (or otherwise immunosuppressed) may benefit from more frequent dosing (q8h). Patients with significantly diminished renal function who must receive aminoglycosides may need to be dosed at longer intervals than once daily. Clinical drug monitoring is strongly suggested for these patients.

Amikacin Sulfate dosage for dogs:

For susceptible infections:

a) Sepsis: 20 mg/kg once daily IV ()

b) 15 mg/kg (route not specified) once daily (q24h). Neutropenic or immunocompromised patients may still need to be dosed q8h (dose divided). ()

c) 15-30 mg/kg IV, IM or SC once daily (q24h) ()

Amikacin Sulfate dosage for cats:

For susceptible infections:

a) Sepsis: 20 mg/kg once daily IV ()

b) 15 mg/kg (route not specified) once daily (q24h). Neutropenic or immunocompromised patients may still need to be dosed q8h (dose divided). ()

c) 10-15 mg/kg IV, IM or SC once daily (q24h) ()

Amikacin Sulfate dosage for ferrets:

For susceptible infections:

a) 8-16 mg/kg IM or IV once daily ()

b) 8-16 mg/kg/day SC, IM, IV divided q8-24h ()

Amikacin Sulfate dosage for rabbits, rodents, and small mammals:

a) Rabbits: 8-16 mg/kg daily dose (may divide into q8h-q24h) SC, IM or IV Increased efficacy and decreased toxicity if given once daily. If given IV, dilute into 4 mL/kg of saline and give over 20 minutes. ()

b) Rabbits: 5-10 mg/kg SC, IM, IV divided q8-24h Guinea pigs: 10-15 mg/kg SC, IM, IV divided q8-24h Chinchillas: 10-15 mg/kg SC, IM, IV divided q8-24h Hamster, rats, mice: 10 mg/kg SC, IM q12h Prairie Dogs: 5 mg/kg SC, IM q12h ()

c) Chinchillas: 2-5 mg/kg SC, IM q8- 12h ()

Amikacin Sulfate dosage for cattle:

For susceptible infections:

a) 10 mg/kg IM q8h or 25 mg/kg q12h ()

b) 22 mg/kg/day IM divided three times daily ()

Amikacin Sulfate dosage for horses:

For susceptible infections:

a) 21 mg/kg IV or IM once daily (q24h) ()

b) In neonatal foals: 21 mg/kg IV once daily ()

c) In neonatal foals: Initial dose of 25 mg/kg IV once daily; strongly recommend to individualize dosage based upon therapeutic drug monitoring. ()

d) Adults: 10 mg/kg IM or IV once daily (q24h)

Foals (<30 days old): 20-25 mg/kg IV or IM once daily (q24h).

For uterine infusion:

a) 2 grams mixed with 200 mL sterile normal saline (0.9% sodium chloride for injection) and aseptically infused into uterus daily for 3 consecutive days (Package insert; Amiglyde-V — Fort Dodge)

b) 1-2 grams IU ()

For intra-articular injection as adjunctive treatment of septic arthritis in foals:

a) If a single joint is involved, inject 250 mg daily or 500 mg every other day; frequency is dependent upon how often joint lavage is performed. Use cautiously in multiple joints as toxicity may result (particularly if systemic therapy is also given). ()

For regional intravenous limb perfusion (RILP) administration in standing horses:

a) Usual dosages range from 500 mg-2 grams; dosage must be greater than 250 mg when a cephalic vein is used for perfusion and careful placement of tourniquets must be performed. ()

Amikacin Sulfate dosage for birds:

For susceptible infections:

a) For sunken eyes/sinusitis in macaws caused by susceptible bacteria: 40 mg/kg IM once or twice daily. Must also flush sinuses with saline mixed with appropriate antibiotic (10-30 mL per nostril). May require 2 weeks of treatment. ()

b) 15 mg/kg IM or SC q12h ()

c) For gram-negative infections resistant to gentamicin: Dilute commercial solution and administer 15-20 mg/kg (0.015 mg/g) IM once a day or twice a day ()

d) Ratites: 7.6-11 mg/kg IM twice daily; air cell: 10-25 mg/egg; egg dip: 2000 mg/gallon of distilled water pH of 6 ()

Amikacin Sulfate dosage for reptiles:

For susceptible infections:

a) For snakes: 5 mg/kg IM (forebody) loading dose, then 2.5 mg/kg q72h for 7-9 treatments. Commonly used in respiratory infections. Use a lower dose for Python curtus. ()

b) Study done in gopher snakes: 5 mg/kg IM loading dose, then 2.5 mg/kg q72h. House snakes at high end of their preferred optimum ambient temperature. ()

c) For bacterial shell diseases in turtles: 10 mg/kg daily in water turtles, every other day in land turtles and tortoises for 7-10 days. Used commonly with a beta-lactam antibiotic. Recommended to begin therapy with 20 mL/kg fluid injection. Maintain hydration and monitor uric acid levels when possible. ()

d) For Crocodilians: 2.25 mg/kg IM q 72-96h ()

e) For gram-negative respiratory disease: 3.5 mg/kg IM, SC or via lung catheter every 3-10 days for 30 days. ()

Amikacin Sulfate dosage for fish:

For susceptible infections:

a) 5 mg/kg IM loading dose, then 2.5 mg/kg every 72 hours for 5 treatments. ()


■ Efficacy (cultures, clinical signs, WBC’s and clinical signs associated with infection). Therapeutic drug monitoring is highly recommended when using this drug systemically. Attempt to draw samples at 1,2, and 4 hours post dose. Peak level should be at least 40 mcg/mL and the 4-hour sample less than 10 mcg/mL.

■ Adverse effect monitoring is essential. Pre-therapy renal function tests and urinalysis (repeated during therapy) are recommended. Casts in the urine are often the initial sign of impending nephrotoxicity.

■ Gross monitoring of vestibular or auditory toxicity is recommended.

Client Information

■ With appropriate training, owners may give subcutaneous injections at home, but routine monitoring of therapy for efficacy and toxicity must still be done

■ Clients should also understand that the potential exists for severe toxicity (nephrotoxicity, ototoxicity) developing from this medication

■ Use in food producing animals is controversial as drug residues may persist for long periods

Chemistry / Synonyms

A semi-synthetic aminoglycoside derived from kanamycin, amikacin occurs as a white, crystalline powder that is sparingly soluble in water. The sulfate salt is formed during the manufacturing process. 1.3 grams of amikacin sulfate is equivalent to 1 gram of amikacin. Amikacin may also be expressed in terms of units. 50,600 Units are equal to 50.9 mg of base. The commercial injection is a clear to straw-colored solution and the pH is adjusted to 3.5-5.5 with sulfuric acid.

Amikacin sulfate may also be known as: amikacin sulphate, amikacini sulfas, or BB-K8; many trade names are available.

Storage / Stability/Compatibility

Amikacin sulfate for injection should be stored at room temperature (15 – 30°C); freezing or temperatures above 40°C should be avoided. Solutions may become very pale yellow with time but this does not indicate a loss of potency.

Amikacin is stable for at least 2 years at room temperature. Autoclaving commercially available solutions at 15 pounds of pressure at 120°C for 60 minutes did not result in any loss of potency.

Note: When given intravenously, amikacin should be diluted into suitable IV diluent etc. normal saline, D5W or LRS) and administered over at least 30 minutes.

Amikacin sulfate is reportedly compatible and stable in all commonly used intravenous solutions and with the following drugs: amobarbital sodium, ascorbic acid injection, bleomycin sulfate, calcium chloride/gluconate, cefoxitin sodium, chloramphenicol sodium succinate, chlorpheniramine maleate, cimetidine HCl, clindamycin phosphate, colistimethate sodium, dimenhydrinate, diphenhydramine HCl, epinephrine HCl, ergonovine maleate, hyaluronidase, hydrocortisone sodium phosphate/succinate, lincomycin HCl, metaraminol bitartrate, metronidazole (with or without sodium bicarbonate), norepinephrine bitartrate, pentobarbital sodium, phenobarbital sodium, phytonadione, polymyxin B sulfate, prochlorperazine edisylate, promethazine HCL, secobarbital sodium, sodium bicarbonate, succinylcholine chloride, vancomycin HCL and verapamil HCL.

The following drugs or solutions are reportedly incompatible or only compatible in specific situations with amikacin: aminophylline, amphotericin B, ampicillin sodium, carbenicillin disodium, cefazolin sodium, cephalothin sodium, cephapirin sodium, chlorothiazide sodium, dexamethasone sodium phosphate, erythromycin gluceptate, heparin sodium, methicillin sodium, nitrofurantoin sodium, oxacillin sodium, oxytetracycline HCL, penicillin G potassium, phenytoin sodium, potassium chloride (in dextran 6% in sodium chloride 0.9%; stable with potassium chloride in “standard” solutions), tetracycline HCL, thiopental sodium, vitamin B-complex with C and warfarin sodium. Compatibility is dependent upon factors such as pH, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific information.

In vitro inactivation of aminoglycoside antibiotics by beta-lac-tam antibiotics is well documented. While amikacin is less susceptible to this effect, it is usually recommended to avoid mixing these compounds together in the same syringe or IV bag unless administration occurs promptly. See also the information in the Amikacin Sulfate Interaction and Amikacin Sulfate/Lab Interaction sections.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products:

Amikacin Sulfate Injection: 50 mg (of amikacin base) per mL in 50 mL vials; Amiglyde-V (Fort Dodge), AmijectD (Butler), Amikacin K-9 (RXV), Amikacin C (Phoenix), Amtech Amimax C (IVX), Caniglide (Vedco); generic (VetTek); (Rx); Approved for use in dogs.

Amikacin Sulfate Intrauterine Solution: 250 mg (of amikacin base) per mL in 48 mL vials; Amifuse E (Butler), Amiglyde-V (Fort Dodge), Amikacin E (Phoenix), Amikacin E (RXV), Amtech Amimax E (IVX), Equi-phar Equiglide (Vedco); (Rx); Approved for use in horses not intended for food.

WARNING: Amikacin is not approved for use in cattle or other food-producing animals in the USA. Amikacin Sulfate residues may persist for long periods, particularly in renal tissue. For guidance with determining use and withdrawal times, contact FARAD (see Phone Numbers & Websites in the appendix for contact information).

Human-Labeled Products:

Amikacin Injection: 50 mg/mL and 250 mg/mL in 2 mL and 4 mL vials and 2 mL syringes; Amikin (Apothecon); generic; (Rx)


Acetylcysteine (N-acetylcysteine, Mucomyst, NAC)

Antidote; Mucolytic

Highlights Of Prescribing Information

Used primarily as a treatment for acetaminophen or phenol toxicity & for its mucolytic effect; used anecdotally for treating degenerative myelopathy

Also used as a topical ophthalmic ()

Has caused hypersensitivity & bronchospasm when used in pulmonary tree

Administer via gastric- or duodenal tube for acetaminophen poisoning in animals

What Is Acetylcysteine Used For?

Acetylcysteine is used in veterinary medicine as both a mucolytic agent in the pulmonary tree and as a treatment for acetaminophen or phenol toxicity in small animals. It has been used anecdotally with aminocaproic acid to treat degenerative myelopathy in dogs.

In horses with strangles, acetylcysteine instilled into the gutteral pouch has been used to help break up chondroids and avoid the need for surgical removal. Acetylcysteine enemas have been used in neonatal foals to break up meconium refractory to repeated enemas.

Before you take Acetylcysteine

Contraindications / Precautions / Warnings

Acetylcysteine is contraindicated (for pulmonary indications) in animals hypersensitive to it. There are no contraindications for its use as an antidote.

Because acetylcysteine may cause bronchospasm in some patients when used in the pulmonary system, animals with bronchospastic diseases should be monitored carefully when using this agent.

Adverse Effects

When given orally for acetaminophen toxicity, acetylcysteine can cause GI effects (nausea, vomiting) and rarely, urticaria. Because the taste of the solution is very bad, use of taste masking agents {e.g., colas, juices) have been used. Since oral dosing of these drugs may be very difficult in animals, gastric or duodenal tubes may be necessary.

Rare adverse effects reported when acetylcysteine is administered into the pulmonary tract, include: hypersensitivity, chest tightness, bronchoconstriction, and bronchial or tracheal irritation.

Overdosage / Acute Toxicity

The LD50 of acetylcysteine in dogs is 1 g/kg (PO) and 700 mg/kg (IV). It is believed that acetylcysteine is quite safe (with the exception of the adverse effects listed above) in most overdose situations.

How to use Acetylcysteine

Acetylcysteine dosage for dogs:

For acetaminophen toxicity:

a) A 2-3 hour wait between activated charcoal and PO administration of acetylcysteine (NAC) is necessary. Give NAC as an initial oral loading dose of 140 mg/kg (dilute to 5% in dextrose or sterile water), followed by 70 mg/kg PO four times daily (q6h) for 7 treatments. With ingestion of massive quantities, some authors suggest using a 280 mg/kg loading dose and continuing treatment for 12-17 doses. May also be given IV after diluting to 5% and given via slow IV over 15-20 minutes. Additional therapy may include IV fluids, blood or Oxyglobin, ascorbic acid and SAMe. ()

b) 150 mg/kg PO or IV initially, then 50 mg/kg q4h for 17 additional doses ()

c) Loading dose of 140 mg/kg PO, then 70 mg/kg PO every 6 hours for 7 treatments ()

For phenol toxicity:

a) 140 mg/kg PO or IV initially, then 50 mg/kg q4h for 3 days. May be partially effective to reduce hepatic and renal injury. Resultant methemoglobinemia should be treated with ascorbic acid or methylene blue. ()

For respiratory use:

a) 50 mL/hr for 30-60 minutes every 12 hours by nebulization ()

For degenerative myelopathy:

a) 25 mg/kg PO q8h for 2 weeks, then q8h every other day. The 20% solution should be diluted to 5% with chicken broth or suitable diluent. Used in conjunction with aminocaproic acid (500 mg per dog PO q8h indefinitely). Other treatments may include prednisone (0.25-0.5 mg/kg PO daily for 10 days then every other day), Vitamin C (1000 mg PO q12h) and Vitamin E (1000 Int. Units PO q12h). Note: No treatment has been shown to be effective in published trials. ()

Acetylcysteine dosage for cats:

For acetaminophen toxicity:

a) A 2-3 hour wait between activated charcoal and PO administration of acetylcysteine (NAC) is necessary. Give NAC as an initial oral loading dose of 140 mg/kg (dilute to 5% in dextrose or sterile water), followed by 70 mg/kg PO four times daily (q6h) for 7 treatments. With ingestion of massive quantities, some authors suggest using a 280 mg/kg loading dose and continuing treatment for 12-17 doses. May also be given IV after diluting to 5% and given via slow IV over 15-20 minutes. Additional therapy may include IV fluids, blood or Oxyglobin9, ascorbic acid and SAMe. ()

b) 150 mg/kg PO or IV initially, then 50 mg/kg q4h for 17 additional doses ()

For phenol toxicity:

a) 140 mg/kg PO or IV initially, then 50 mg/kg q4h for 3 days. May be partially effective to reduce hepatic and renal injury. Resultant methemoglobinemia should be treated with ascorbic acid or methylene blue. ()

For respiratory use:

a) 50 mL/hr for 30-60 minutes every 12 hours by nebulization ()

For adjunctive treatment of hepatic lipidosis (see also Carnitine):

a) Identify underlying cause of anorexia and provide a protein replete feline diet, give acetylcysteine (NAC) at 140 mg/kg IV over 20 minutes, then 70 mg/kg IV q12h; dilute 10% NAC with saline 1:4 and administer IV using a 0.25 micron filter; correct hypokalemia and hypophosphatemia, beware of electrolyte changes with re-feeding phenomenon ()

Acetylcysteine dosage for horses:

To help break up chondroids in the gutteral pouch:

a) Instill 20% solution ()

In neonatal foals to break up meconium refractory to repeated enemas:

a) 8 grams in 20 g sodium bicarbonate in 200 mL water (pH of 7.6), give as enema as needed to effect ()

b) With foal in lateral recumbency, insert a 30 french foley catheter with a 30 cc bulb for a retention enema. Using gravity flow, infuse slowly 100-200 mL of 4% acetylcysteine solution and retain for 30-45 minutes. IV fluids and pain medication should be considered. Monitor for possible bladder distention. ()


When used for acetaminophen poisoning:

■ Hepatic enzymes (particularly in dogs)

■ Acetaminophen level, if available (particularly in dogs)

■ Hemogram, with methemoglobin value (particularly in cats)

■ Serum electrolytes, hydration status

Client Information

■ This agent should be used in a clinically supervised setting only

Chemistry / Synonyms

The N-acetyl derivative of L-cysteine, acetylcysteine occurs as a white, crystalline powder with a slight acetic odor. It is freely soluble in water or alcohol.

Acetylcysteine may also be known as: N-acetylcysteine or N-acetyl-L-cysteine, NAC, 5052 acetylcysteinum, NSC-111180, Acetadote, Mucomyst or ACC.

Storage / Stability/Compatibility

When unopened, vials of sodium acetylcysteine should be stored at room temperature (15-30°C). After opening, vials should be kept refrigerated and used within 96 hours. The product labeled for IV use states to use within 24 hours.

Acetylcysteine is incompatible with oxidizing agents; solutions can become discolored and liberate hydrogen sulfide when exposed to rubber, copper, iron, and during autoclaving. It does not react to aluminum, stainless steel, glass or plastic. If the solution becomes light purple in color, potency is not appreciably affected, but it is best to use non-reactive materials when giving the drug via nebulization. Acetylcysteine solutions are incompatible with amphotericin B, ampicillin sodium, erythromycin lactobionate, tetracycline, oxytetracycline, iodized oil, hydrogen peroxide and trypsin.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

Human-Labeled Products:

Acetylcysteine injection: 20% (200 mg/mL), (0.5 mg/mL EDTA in 30 mL single-dose vials, preservative free; Acetadote (Cumberland); (Rx)

Acetylcysteine Solution: 10% & 20% (as sodium) in 4 mL, 10 mL, 30 mL & 100 mL (20% only) vials; Mucomyst (Apothecon); (Rx) Note: If using this product for dilution and then intravenous dosing, it is preferable to use a 0.2 micron in-line filter.


Treatment of Vasculitis

Treatment of purpura hemorrhagica and similar idiopathic vasculitides consists of the following: (1) removing the antigenic stimulus; (2) suppressing the immune response; (3) reducing vessel wall inflammation; and (4) providing supportive care. Any drugs given when the clinical signs occurred should be discontinued, or, if continued medication is necessary, an alternate drug should be chosen from a chemically unrelated class. A thorough examination should be performed to identify a primary disease process. Any bacterial pathogens should be cultured and an in vitro sensitivity performed. Because most cases of purpura hemorrhagica are a sequela of Streptococcus equi infection, penicillin (procaine penicillin G 22,000-44,000 U/kg IM q12h or sodium or potassium penicillin 22,000-44,000 U/kg IV q6h) should be administered for a minimum of 2 weeks unless specifically contraindicated. Any accessible abscess should be drained. If gram-negative bacteria are suspected or isolated, additional appropriate antimicrobial therapy should be used. Antimicrobial therapy is also indicated to limit or prevent secondary septic complications such as cellulitis, tenosynovitis, arthritis, pneumonia, and thrombophlebitis.

Systemic glucocorticoids are warranted because purpura hemorrhagica and other undefined vasculitides are most likely immune-mediated. In addition, systemic glucocorticoids reduce inflammation of the affected vessel walls and subsequent edema formation. Dexamethasone (0.05-0.2 mg/kg IM or IV q24h) or prednisolone (0.5-1.0 mg/kg IM or IV q24h) may be used; however, clinical experience indicates that dexamethasone is more effective during initial therapy. The minimum dose that provides a decrease in clinical signs should be used. After substantial reduction and stabilization of clinical signs, the dose of glucocorticoids may be decreased by 10% per day over 10 to 21 days. When the dose of dexamethasone is 0.01 to 0.04 mg/kg per day, it may be given orally; alternatively, prednisolone may be substituted at ten times the dexamethasone dose. The bioavailability of oral prednisolone is 50%; thus an effective parenteral dose administered orally may result in relapse of clinical signs. Prednisone is poorly absorbed from the gastrointestinal tract and is not detectable in the blood of most horses after oral administration; thus its use is not recommended. Hydrotherapy, application of pressure bandages, and hand-walking should be used to decrease or prevent edema. Furosemide (1 mg/kg IV q12h) may help reduce edema in severe cases. A tracheostomy may be indicated if respiratory stridor is present from edema of the nasal passages, pharynx, and/or larynx. Dysphagic horses should be supported with intravenous or nasogastric administration of fluids. Nutritional support may be necessary in horses with prolonged dysphagia. Nonsteroidal antiinflammatory drugs (flunixin meglumine 1.1 mg/kg IV, IM or PO q12h or phenylbutazone 2.2-4.4 mg/kg IV or PO q12h) are indicated to provide analgesia in horses with lameness, colic, myalgia, or other painful conditions. NSAIDs may also help reduce the inflammation in affected vessel walls.

Horses with equine viral arteritis do not require specific therapy because the majority of cases recover uneventfully. Glucocorticoids are contraindicated because vessel wall damage results from direct viral injury. Occasionally horses with severe clinical signs of lower respiratory disease will need antimicrobial therapy to prevent or treat secondary bacterial pneumonia. Horses with EIA are infected for life. Glucocorticoids are contraindicated because they may result in increased viral replication and occurrence of clinical disease. Horses with equine ehrlichiosis may benefit from glucocorticoid therapy; however, they should be treated with oxytetracycline to eliminate the organism (see: “Equine Monocytic Ehrlichiosis” and: “Hemolytic Anemia”). Horses with photoactivated vasculitis should be stabled during daylight hours to prevent any further exposure to sunlight. The vascular inflammation should be treated with systemic glucocorticoids in a regimen similar to that for purpura hemorrhagica. Topical applications of glucocorticoids with or without antibiotics are not effective. Irritating topical solutions should not be used.


Diseases That Primarily Cause Extravascular Hemolysis

Neonatal Isoerythrolysis

The primary differential diagnosis for a neonatal foal observed to have evidence of anemia and intense icterus during the first week of life is neonatal isoerythrolysis (NI). Incompatible blood group antigens between the mare and stallion combined with maternal exposure to fetal erythrocytes during gestation results in maternal production of antigen specific antibodies targeted against the foal’s red blood cells, if the foal inherited the sire’s red blood cell phenotype. The most common blood types associated with NI in foals are Aa and Qa. Foals with NI most commonly suffer from extravascular hemolysis, although rare intravascular hemolysis occurs concurrently. A positive direct Coombs’ test provides a presumptive diagnosis of neonatal isoerythrolysis. However, the most sensitive diagnostic technique for identification of surface-associated immunoglobulin (Ig) molecules on suspect foal red blood cells involves a new direct immunofmorescence (DIF) assay using flow cytometry. In this assay, isotype specific antibodies bind to red blood cells that contain surface-associated antibodies, thus providing a quantitative measure of erythrocytes in the circulation that are bound with antibody. Site provides more information on the pathophysiology and treatment of neonatal isoerythrolysis.

Immune-Mediated Hemolytic Anemia

Equine Infectious Anemia


Equine Ehrlichiosis

Equine ehrlichiosis is caused by the rickettsial organism A. phagocytophila (formerly known as Ehrlichia equi), which belongs to the phagocytophilia complex of ehrlichial agents. A. phagocytophila, is the causative agent of tick-borne fever of ruminants that reside in Europe and human granulocytic ehrlichiosis (HGE) in Europe and America. This organism has DNA sequence homology with A. phagocytophila recovered from horses in Connecticut and California and HGE. Blood from people with HGE given to horses induces disease and imparts protective immunity to future challenge with A. phagocytophila. Equine ehrlichiosis is most common in the northern California foothills; however, ehrlichiosis has been reported in other regions of the United States, including the upper Midwest and the northeastern United States.

Clinical Signs and Diagnosis

Clinical signs include fever, depression, petechiae, ventral edema, and ataxia, with reluctance to move. Differential diagnoses for these signs include purpura hemorrhagica, equine viral arteritis, and encephalitis. Granulocytopenia, anemia, and thrombocytopenia are common abnormalities detected on hematology. Horses that are younger than 3 years of age exhibit a less severe form of the disease. Diagnosis of A. phagocytophila may be made from identification of morula in circulating granulocytes. Seroconversion (fourfold rise in serum antibodies in a convalescent sample) can be detected with an indirect fluorescent antibody test. A polymerase chain reaction assay has been developed for A. phagocytophila and has improved sensitivity and specificity in comparison to conventional diagnostic tests.

Supportive care for affected patients should include NSAID therapy, intravenous fluids, and lower limb sweat wraps. Intravenous oxytetracycline (7 mg/kg diluted in 1 liter of saline IV q24h x 5-7 days) is effective for clearance of equine granulocytic ehrlichiosis. Response to therapy is extremely rapid, thus supporting the diagnosis in suspect cases. Carrier phases have not been recognized; in fact, once-infected horses acquire strong immunity for up to 2 years, thus providing resistance to reinfection.

Veterinary Drugs

Drugs Acting On The Reproductive System

  • Drugs used to promote gonadal function
  • Sex hormones
  • Prostaglandins
  • Myometrial stimulants
  • Myometrial relaxants
  • Prolactin antagonists
  • Non-hormonal abortificants
  • Drugs for uterine infections

Many drugs are used at different stages of the oestrous cycle to manage the response of the reproductive system; these are summarised in Table Drags affecting the reproductive system.

Table Drags affecting the reproductive system

Indications Species Drug
Synchronisation and regulation of the oestrous cycle and ovulation Horses Altrenogest, Buserelin, Cloprostenol, Dinoprost, Luprostiol
Cattle Buserelin, Cloprostenol, Dinoprost, Etiproston, Gonadorelin, Luprostiol, Progesterone (Eazi-Breed CIDR), Progesterone + estradiol benzoate (Prid)
Sheep, Goats Flugestone acetate, Medroxyprogesterone acetate
Pigs Altrenogest
Stimulation of the onset of cyclical ovarian activity Horses Altrenogest, Buserelin, Chorionic gonadotrophin, Cloprostenol, Deslorelin, Dinoprost, Luprostiol, Serum gonadotrophin
Cattle Buserelin, Chorionic gonadotrophin, Cloprostenol, Dinoprost, Etiproston, Gonadorelin, Luprostiol, Progesterone, Progesterone + estradiol benzoate (Prid), Serum gonadotrophin
Sheep, Goats Flugestone acetate, Medroxyprogesterone acetate, Melatonin, Serum gonadotrophin
Pigs Altrenogest, Chorionic gonadotrophin + serum gonadotrophin (PG600)
Dogs Chorionic gonadotrophin, Serum gonadotrophin
Rabbits Buserelin
Superovulation Cattle Chorionic gonadotrophin, Menotrophin, Serum gonadotrophin, Follicle stimulating hormone (porcine, ovine, recombinant)
Misalliance and pregnancy termination Horses Cloprostenol, Dinoprost, Luprostiol
Cattle Cloprostenol, Dinoprost, Etiproston, Luprostiol
Dogs Aglepristone, Cabergoline, Estradiol benzoate
Induction of parturition Horses Cloprostenol, Dinoprost, Luprostiol
Cattle Cloprostenol, Dexamethasone, Dinoprost, Etiproston, Luprostiol
Sheep Dexamethasone
Pigs Cloprostenol, Dinoprost, Luprostiol
Overt pseudopregnancy Horses (type 1 only) Cloprostenol, Dinoprost
Goats Cloprostenol, Dinoprost
Dogs Cabergoline, Methyltestosterone, Proligestone, Testosterone esters (Durateston)
Suppression of ovarian activity Dogs Medroxyprogesterone acetate, Megestrol acetate, Methyltestosterone, Proligesterone, Testosterone esters (Durateston)
Cats Megestrol acetate, Proligesterone


Drugs used to promote gonadal function


Gonadotrophin-releasing hormones


Melatonin advances the time of onset of cyclical ovarian activity in the ewe and doe goat by mimicking the natural production of melatonin by the pineal gland. This gives improved reproductive performance in sheep flocks mated early in the season. A single dose of 18 mg, in a modified-release formulation, is implanted behind the ear. This is carried out 30 to 40 days before the introduction of the ram. It is important that ewes are kept completely separate from rams and also male goats for no less than 30 days after implantation.

In the UK, for Suffolk and Suffolk cross-breeds, the drug should be administered from mid-May to late June, for ram introduction in late June and July. For Mule and Half-bred flocks, melatonin should be administered from early June to late July, for ram introduction from mid-July to late August.


Indications. Induction of ovulation

Contra-indications. Sexually immature animals

Warnings. Use of drug in ewes suckling lambs at foot may not give optimum results. The drug should not be used at times other than recommended, see notes above


Sheep: by subcutaneous administration, 1 implant

PML Regulin (Ceva) UK Implant, m/r, melatonin 18 mg, for sheep

Withdrawal Periods.

Sheep: slaughter withdrawal period nil, milk withdrawal period nil

Sex hormones


Myometrial stimulants

Myometrial relaxants

Prolactin antagonists

Pregnancy in bitches is maintained by the presence of corpora lutea; if they regress, pregnancy will be terminated. The presence of corpora lutea is probably dependent upon the luteotrophic support of pituitary-derived prolactin during the second half of the luteal phase of metoestrus and pregnancy.

The prolactin inhibitor cabergoline exerts its effect by inhibiting prolactin release by direct stimulation of dopamine receptors in prolactin-releasing cells in the anterior pituitary. As a consequence, the corpora lutea regress. Towards the end of metoestrus, as the corpora lutea start to regress, there is a concomitant rise in prolactin which is responsible for the overt signs of pseudopregnancy such as behavioural signs and mammary development and lactation. Cabergoline reduces prolactin release and is used for the treatment of overt pseudopregnancy in the bitch. Bromocriptine is a potent dopamine receptor agonist (dopamine receptor stimulant), which inhibits prolactin release from the anterior pituitary gland. Bromocriptine commonly causes side-effects such as vomiting, anorexia, and behavioural changes, which may be severe. Metergoline is a serotonin agonist with actions similar to bromocriptine; it is used to suppress lactation.


Indications. Pseudopregnancy; suppression of lactation; termination of pregnancy ; behavioural modification

Contra-indications. Pregnant animals unless pregnancy termination required; lactating animals unless suppression of lactation required; use directly after surgery while animal still recovering from anesthesia

Side-effects. Transient hypotension, occasionally vomiting or anorexia, transient drowsiness

Warnings. Drug Interactions.

Dose: Doe goats, to suppress lactation, by mouth, 5 micrograms/kg

Dogs: by mouth, 5 micrograms/kg once daily for 4-6 days.

May be mixed with food

Prescription-only medicine: Galastop (Ceva) UK

Oral solution, cabergoline 50 micrograms/mL, for dogs (3 drops = cabergoline 5 micrograms)

Non-hormonal abortificants

Lotrifen is a phenyltriazole isoquinoline which causes embryopathy and abortion in many species such as rats, hamsters, guinea pigs, and dogs. It is most effective in dogs when administered around 20 days of gestation and it is used in dogs for pregnancy termination. The mode of action is unclear: the drug may be embryotoxic, it may reduce blood supply to the gravid uterus, or modify the animal’s immune response.

Drugs for uterine infections

Bacteria will contaminate the uterus of most individuals after normal parturition. However these micro-organisms will soon be eliminated by natural defence mechanisms. The bacteria may originate from the environment and are opportunist pathogens or may be specific venereal pathogens; failure to eliminate them due to impaired defence mechanisms will result in infection. In addition, trauma associated with dystocia and heavy bacterial contamination are also likely to predispose to infection. Uterine infection may be acute, frequently involving all layers of the uterine wall (metritis) or chronic, usually involving the endometrium (endometritis). The former may be fatal. Treatment of metritis includes the use of systemic antimicrobials such as potentiated sulphonamides, oxytetracycline, or semisynthetic penicillins, NSAIDs, and supportive therapy. Chronic infection involving the endometrium can be treated by the intra-uterine infusion of broad-spectrum antimicrobials, administered at the usual therapeutic dosage. In the cow, if a corpus luteum is present, endometritis is best treated by administration of prostaglandin F2alpha or an analogue. In bitches, cystic endometrial hyperplasia and pyometra most commonly occur in the luteal phase of the oestrous cycle (metoestrus). In animals with ‘open’ pyometra with dilated cervix and vaginal discharge, dinoprost is administered at a dose of 250 micrograms/kg for at least 5 days. It is contra-indicated in bitches with very enlarged uteri, animals with heart conditions, and patients with ‘closed’ pyometra. Side-effects occur within 15 minutes of administration and include panting, salivation, vomiting, and whimpering. These symptoms are transient and cease within one hour.

In the UK, the Horserace Betting Levy Board publishes Codes of Practice on contagious equine metritis (CEM) Klebsiella pneumoniae, Pseudomonas aeruginosa; equine viral arteritis (EVA); and equid herpesvirus-1 (EHV-1), which include recommendations for disease prevention and control in breeding horses.

Prescription-only medicine: Metricure (Intervet) UK

Intra-uterine suspension, cephapirin (as cephapirin benzathine) 500 mg, for cattle; dose applicator

Withdrawal Periods.

Cattle: slaughter 2 days, milk withdrawal period nil


Cattle: by intra-uterine administration, contents of one applicator. May be repeated after 7-14 days

Prescription-only medicine: Utocyl (Novartis) UK

Pessaries, benzylpenicillin 62.7 mg, formosulphathiazole 1.75 g, streptomycin (as sulfate) 50 mg, for cattle

Withdrawal Periods.

Cattle: slaughter 2 days, milk withdrawal period nil


Cattle: by intra-uterine administration, 6 pessaries for prophylaxis only

Veterinary Drugs



An ethanolamine derivative antihistamine, dimenhydrinate contains approximately 54% diphenhydramine and 46% 8-chlorotheophylline. It occurs as an odorless, bitter and numbing-tasting, white crystalline powder with a melting range of 102°-107°C. Dimenhydrinate is slightly soluble in water and is freely soluble in propylene glycol or alcohol. The pH of the commercially available injection ranges from 6.4 to 7.2.

Storage – Stability – Compatibility

Dimenhydrinate products should be stored at room temperature; avoid freezing the oral solution and injectable products. The oral solution should be stored in tight containers and tablets stored in well-closed containers.

Dimenhydrinate injection is reportedly compatible with all commonly used intravenous replenishment solutions and the following drugs: amikacin sulfate, atropine sulfate, calcium gluconate, chloramphenicol sodium succinate, corticotropin, ditrizoate meglumine and sodium, diphenhydramine HCl, droperidol, fentanyl citrate, heparin sodium, iothalamate meglumine and sodium, meperidine HCl, methicillin sodium, metoclopramide, morphine sulfate, norepinephrine bitartrate, oxytetracycline HCl, penicillin G potassium, pentazocine lactate, perphenazine, phenobarbital sodium, potassium chloride, scopolamine HBr, vancomycin HCl and vitamin B-complex w/ vitamin C.

The following drugs are either incompatible or compatible only in certain concentrations with dimenhydrinate: aminophylline, ammonium chloride, amobarbital sodium, butorphanol tartrate, glycopyrrolate, hydrocortisone sodium succinate, hydroxyzine, iodipamide meglumine, pentobarbital sodium, prochlorperazine edisylate, promazine HCl, promethazine HCl, tetracycline HCl, and thiopental sodium. Compatibility is dependent upon factors such as pH, concentration, temperature, and diluents used and it is suggested to consult specialized references for more specific information.

Dimenhydrinate: Pharmacology

Dimenhydrinate has antihistaminic, antiemetic, anticholinergic, CNS depressant and local anesthetic effects. These principle pharmacologic actions are thought to be a result of only the diphenhydramine moiety. Used most commonly for its antiemetic/motion sickness effects, dimenhydrinate’s exact mechanism of action for this indication is unknown, but the drug does inhibit vestibular stimulation. The anticholinergic actions of dimenhydrinate may play a role in blocking acetylcholine stimulation of the vestibular and reticular systems. Tolerance to the CNS depressant effects can ensue after a few days of therapy and antiemetic effectiveness also may diminish with prolonged use.

Dimenhydrinate: Uses – Indications

In veterinary medicine, dimenhydrinate is used primarily for its antiemetic effects in the prophylactic treatment of motion sickness in dogs and cats.


The pharmacokinetics of this agent have apparently not been studied in veterinary species. In humans, the drug is well absorbed after oral administration with antiemetic effects occurring within 30 minutes of administration. Antiemetic effects occur almost immediately after IV injection. The duration of effect is usually 3-6 hours.

Diphenhydramine is metabolized in the liver, and the majority of the drug is excreted as metabolites into the urine. The terminal elimination half-life in adult humans ranges from 2.4 – 9.3 hours.


Dimenhydrinate is contraindicated in patients who are hypersensitive to it or to other antihistamines in its class. Because of their anticholinergic activity, an-tihistamines should be used with caution in patients with angle closure glaucoma, prostatic hypertrophy, pyloroduodenal or bladder neck obstruction, and COPD if mucosal secretions are a problem. Additionally, they should be used with caution in patients with hyperthyroidism, seizure disorders, cardiovascular disease or hypertension. It may mask the symptoms of ototoxicity and should therefore be used with this knowledge when concomitantly administering with ototoxic drugs.

Dimenhydrinate: Adverse Effects – Warnings

Most common adverse reactions seen are CNS depression (lethargy, somnolence) and anticholinergic effects (dry mouth, urinary retention). GI effects (diarrhea, vomiting, anorexia) are less common, but have been noted.

The sedative effects of antihistamines, may adversely affect the performance of working dogs. The sedative effects of antihistamines may diminish with time.

Dimenhydrinate: Overdosage

Overdosage may cause CNS stimulation (excitement to seizures) or depression (lethargy to coma), anticholinergic effects, respiratory depression and death. Treatment consists of emptying the gut if the ingestion was oral. Induce emesis if the patient is alert and CNS status is stable. Administration of a saline cathartic and/or activated charcoal may be given after emesis or gastric lavage. Treatment of other symptoms should be performed using symptomatic and supportive therapies. Phenytoin (IV) is recommended in the treatment of seizures caused by antihistamine overdose in humans; use of barbiturates and diazepam are avoided.

Dimenhydrinate: Drug Interactions

Increased sedation can occur if dimenhydrinate (diphenhydramine) is combined with other CNS depressant drugs. Antihistamines may partially counteract the anticoagulation effects of heparin or warfarin. Diphenhydramine may enhance the effects of epinephrine. Dimenhydrinate may potentiate the anticholinergic effects of other anticholinergic drugs. Dimenhydrinate has been demonstrated to induce hepatic microsomal enzymes in animals (species not specified); the clinical implications of this effect are unclear.

Laboratory Interactions – Antihistamines can decrease the wheal and flare response to antigen skin testing. In humans, it is suggested that antihistamines be discontinued at least 4 days before testing.

Dimenhydrinate: Doses

Doses for dogs:

For prevention and treatment of motion sickness:

a) 8 mg/kg PO q8h

b) 25 – 50 mg PO once to 3 times a day

c) 4 – 8 mg/kg PO q8h

Doses for cats:

For prevention and treatment of motion sickness:

a) 12.5 mg (total dose) PO q8h

b) 12.5 mg PO once to 3 times a day

c) 8 mg/kg PO q8h

d) 4 – 8 mg/kg PO q8h

Monitoring Parameters

1) Clinical efficacy and adverse effects (sedation, anticholinergic signs, etc.)

Dosage Forms – Preparations – FDA Approval Status – Withholding Times

Veterinary-Approved Products:


Human-Approved Products:

Dimenhydrinate Tablets or capsules 50 mg; Commonly known as Dramamine® (Upjohn) (OTC); Many other OTC products also available

Dimenhydrinate Oral Liquid 12.5 mg/4 ml, 12.5 mg/5 ml and 15.62 mg/5 ml; in pints and gallons and in 90 ml, 120 ml and 480 ml bottles Children’s Dramamine® (Upjohn) (OTC); generic (OTC)

Dimenhydrinate Injection 50 mg/ml; in 1 ml amps and vials, 5 & 10 ml vials; Dramamine® (Upjohn); Generic; (Rx)


Small Intestinal Disease



Diarrhea is an increase in fecal mass caused by an increase in fecal water and / or solid content. It is accompanied by an increase in frequency and / or fluidity and / or volume of feces. Yet it must be remembered that the absence of recognizable diarrhea does not preclude the possibility of significant small intestine disease.

Classifications of Diarrhea


  • Osmotic
  • Secretory
  • Permeability (exudative)
  • Dysmotility
  • Mixed


  • Acute
  • Chronic


  • Extraintestinal
  • Small intestinal
  • Large intestinal
  • Diffuse


  • Biochemical
  • Allergic
  • Inflammatory
  • Neoplastic


  • Diet; bacterial, viral, parasitic causes; other


  • Exocrine pancreatic insufficiency, salmonellosis, lymphoma, other


  • Acute, nonfatal, self-limiting
  • Acute potentially fatal
  • Acute systemic disease
  • Chronic

Diarrhea can be classified in several ways (Box Classifications of Diarrhea). These categories are not mutually exclusive, and they allow the problem to be viewed from different perspectives, facilitating diagnosis and the choice of appropriate treatment. A mechanistic approach is simple, and many small intestine diseases have a component of osmotic diarrhea, but even in a situation as simple as lactase deficiency, other mechanisms become involved. Osmotic diarrhea in lactose malabsorption causes intestinal distension, which induces peristalsis and rapid transit, and bacterial fermentation products in the colon cause secretion. Bacterial fermentation of unabsorbed solutes is often a complicating factor in malabsorption. The fecal pH is often low because of the production of volatile fatty acids, and some products of fermentation (e. g., hydroxylated fatty acids, unconjugated bile acids) can cause colonic inflammation and secretion, and therefore signs of large intestinal diarrhea frequently accompany prolonged small intestine disease.

Osmotic diarrhea Excess water-soluble molecules in the intestinal lumen retain water osmotically and overwhelm the absorptive capacity of the small intestine and colon (e. g., sudden diet change, overeating, and malabsorption). The diarrhea typically resolves when food or laxatives are withheld.

Secretory diarrhea Stimulation of small intestine secretion such that the reserve absorptive capacity is overwhelmed results in diarrhea even though the absorptive ability of the small intestine and colon may not actually be impaired. Treatment with oral rehydration fluids containing glucose and amino acids (e. g., glycine) to increase water absorption is appropriate.

Typically secretory diarrhea does not resolve with fasting but does not cause weight loss unless anorexia, vomiting, or additional small intestine damage is a factor. Morbidity and even mortality are associated with the dehydration that results from excessive fluid loss. Secretory diarrhea typically is caused by chemical toxins and toxins elaborated by enteric bacteria (Box Causes of Secretory Diarrhea).

Causes of Secretory Diarrhea
  • Bacterial enterotoxins and endotoxins (e. g., Clostridium perfringens, Escherichia coli. Salmonella spp., Shigella spp., Yersinia enterocolitica)
  • Unconjugated bile acids from bacterial fermentation
  • Hydroxylated fatty acids from bacterial fermentation
  • Ciardia infection
  • Possibly hyperthyroidism
  • Laxatives (castor oil, dioctyl sodium sulfosuccinate, bisacodyl)
  • Cardiac glycosides
  • Amine precursor uptake and decarboxylation (APUD) neoplasms (excess vasoactive intestinal polypeptide, serotonin, prostaglandins, substance P)
  • Intestinal inflammation

Permeability (exudative) diarrhea Intestinal inflammation can stimulate increased fluid and electrolyte secretion and impair absorption. Leakage of tissue fluid, serum proteins, blood, and mucus may occur from sites of inflammation, ulceration, or infiltration or if portal hypertension or lymphatic obstruction is present. Increased permeability severe enough to cause loss of plasma proteins in excess of their rate of synthesis results in a protein-losing enteropathy.


Failure of food assimilation is sometimes classified as primary failure to digest (maldigestion) or primary failure to absorb (malabsorption). However, such a classification is misleading, because failure of absorption is an inevitable consequence of failure to digest. The preferred use of the term malabsorption is to describe defective absorption of dietary constituent resulting from interference with the digestive and / or absorptive phases in the processing of that molecule.

Within this broad definition, the site of the primary abnormality may be found in the luminal, mucosal, or transport phase (Table Pathophysiologic Mechanisms of Malabsorption). Also, the reserve capacity of the distal small intestine and colon may prevent overt diarrhea despite significant malabsorption and weight loss. The clinical manifestations of malabsorption, namely diarrhea, weight loss, and altered appetite (polyphagia, coprophagia, pica), are largely a result of the lack of nutrient uptake and the losses in feces. Animals are often systemically healthy and have an increased appetite unless an underlying neoplastic or a severe inflammatory condition is present. Only when the patient is quite malnourished or develops hypoproteinemia does it become ill.

Pathophysiologic Mechanisms of Malabsorption
Mechanism Example
Luminal Phase
Rapid intestinal transit Hyperthyroidism
Defective substrate hydrolysis
Enzyme inactivation Gastric hypersecretion
Lack of pancreatic enzymes Exocrine pancreatic insufficiency
Fat maldigestion
Decreased bile salt delivery Cholestatic liver disease, biliary obstruction
Increased bile salt loss Heal disease
Bile salt deconjugation Bacterial overgrowth
Fatty acid hydroxylation Bacterial overgrowth
Impaired release of CCK, secretin Impairment of pancreatic secretion due to severe small intestine disease
Cobalamin malabsorption
Intrinsic factor deficiency Exocrine pancreatic insufficiency Giant schnauzer defect
Competition for cobalamin Bacterial overgrowth
Mucosal Phase
Brush border enzyme deficiency
Congenital Trehalase (cats)
Acquired Relative lactose deficiency
Brush border transport protein deficiency
Congenital Intrinsic factor receptor
Acquired Secondary to diffuse small intestine disease
Enterocyte defects
Enterocyte processing defects Abetalipoproteinemia
Reduction in surface area Villus atrophy
Immature enterocytes Increased enterocyte turnover
Mucosal inflammation Inflammatory bowel disease
Transport Phase
Lymphatic obstruction
Primary Lymphangiectasia
Secondary Obstruction caused by neoplasia, infection, or inflammation
Vascular compromise
Vasculitis Infection, immune mediated
Portal hypertension Hepatopathy, right heart failure, cardiac tamponade

The presence of dark, tarry, oxidized blood in feces, a condition called melena, reflects either swallowed blood or generalized or localized gastrointestinal bleeding, which usually occurs proximal to the large intestine (Table Causes of Melena). Medication with ferrous sulfate or bismuth subsalicylate (Pepto-Bismol) also can impart a black color to the feces. It has been estimated that the loss of 350 to 500 mg / kg of hemoglobin into the gastrointestinal tract is required for melena to be visible. The presence of microcytosis with or without thrombocytosis is suggestive of iron deficiency secondary to chronic blood loss. An increased blood urea nitrogen (BUN) to creatinine ratio (from bacterial digestion of blood) provides supporting evidence. Hypoproteinemia may indicate significant blood loss or the presence of a protein-losing enteropathy.

Causes of Melena
Mechanism Source
Ingestion of blood Oral, nasal, pharyngeal, or pulmonary bleeding
Coagulopothies Thrombocytopenia, factor deficiencies, DIC
Gastrointestinal erosion / ulceration
Metabolic Uremia, liver disease
Inflammatory Gastritis, enteritis, hemorrhagic gastroenteritis
Neoplastic Leiomyoma, adenocarcinoma, lymphosarcoma
Paraneoplastic Mastocytosis, hypergastrinemia and other APUDomas
Vascular A-V fistula, aneurysms, angiodysplasia
Ischemia Hypovolemic shock, hypoadrenocorticism, thrombosis / infarction, reperfusion
Drug induced Nonsteroidal and steroidal anti-inflammatory agents
Foreign objects

APUD, amine precursor uptake and decarboxylation tumor; A-V, arteriovenous; DIC, disseminated intravascular coagulation

The general approach to melena is to rule out bleeding diatheses, ingestion of blood, and underlying metabolic disorders before pursuing primary gastrointestinal causes. Ultrasonography is particularly useful for detecting gastrointestinal masses and thickening. The next step for investigating upper gastrointestinal blood loss is endoscopy. If the source of gastrointestinal bleeding is still undetermined, lagged red cell scintigraphy, exploratory laparotomy, angiog-raphy. and enteroscopy may be used to localize the site.

Borborygmi and Flatulence

Borborygmus is a rumbling noise caused by the propulsion of gas through the intestines. Swallowed air and bacterial fermentation of ingesta are the main causes of borborygmi and flatulence. Feeding a diet that is highly digestible, with a low fiber content (e. g., cottage cheese and rice in a 1:2 ratio) leaves little material present in the intestine for bacterial fermentation and can effect a cure in some cases. If borborygmi or flatulence continues despite dietary modification, the animal may be excessively aerophagic or may have malabsorption, especially if diarrhea or weight loss are also present.

Weight Loss or Failure to Thrive

General causes of weight loss are reduced nutrient intake, increased nutrient loss, and increased catabolism or ineffective metabolism. The history should reveal whether the type and amount of diet fed is adequate and whether anorexia, dysphagia, or vomiting is a potential cause. Weight loss or failure to thrive accompanied by diarrhea often is a feature of mal-absorption, and the diagnostic approach is the same as for chronic diarrhea. However, diarrhea does not invariably accompany malabsorption that causes weight loss.

Protein-Losing Enteropalhy

When small intestine disease is severe enough for protein leakage into the gut lumen to exceed protein synthesis, hypoproteinemia develops. Chronic diarrhea associated with hypoproteinemia usually requires intestinal biopsy to define the cause of the protein-losing enteropathy (Table Protein-Losing Enteropathies). Nonintestinal diseases, which may potentially be associated with intestinal protein loss (e. g., portal hypertension), usually present with ascites before diarrhea. Hypoproteinemia associated with gastrointestinal disease is much less common in cats than in dogs and most often accompanies gastrointestinal lymphoma.

Protein-Losing Enteropathies
Causes Examples
Lymphangiectasia Primary lymphatic disorder, venous hypertension (e. g., right heart failure, hepatic cirrhosis)
Infectious Parvovirus, salmonellosis, histoplasmosis, phycomycosis
Structural Intussusception
Neoplasia Lymphosarcoma
Inflammation Lymphocytic-plasmacytic, eosinophilic, granulomatous
Endoparasites Ciardia, Ancylostoma spp.
Gastrointestinal hemorrhage hemorrhagic gastroenteritis, neoplasia, ulceration


Clinical presentation Breeds that appear to be predisposed to protein-losing enteropathy are the basenji, lundehund, soft-coated wheaten terrier, Yorkshire terrier, and Shar Pei. Clinical signs associated with protein-losing enteropathy include weight loss, diarrhea, vomiting, edema, ascites, and pleural effusion. Weight loss frequently is the predominant feature, and diarrhea is not invariably present, particularly with lymphangiectasia and focal intestinal neoplasia. Physical findings may include edema, ascites, emaciation, thickened intestines, and melena. Thromboembolism is a feature of some cases of protein-losing enteropathy.

Diagnosis The serum concentrations of both albumin and globulin are reduced in most patients with protein-losing enteropathy. Exceptions are raised hyperglobulinemia with hypoalbuminemia found in histoplasmosis and immunoproliferative small intestine disease in the basenji. Renal and hepatic causes of hypoalbuminemia are eliminated by assay of serum bile acids and urinary protein loss respectively. Hypocholesterolemia and lymphopenia are common in protein-losing enteropathy. Hypocalcemia and hypomagnesemia are also reported. Measurement of fecal loss of alpha, -protease inhibitor may be a sensitive test for protein-losing enteropathy.

Survey abdominal radiographs often are normal in patients with protein-losing enteropathy, but ultrasound scans may reveal intestinal thickening, mesenteric lymphadenopathy, or abdominal effusion. Thoracic radiographs may show pleural effusion, metastatic neoplasia, or evidence of histoplasmosis. Although intestinal function tests may confirm the presence of malabsorption, they rarely provide a definitive diagnosis, and intestinal biopsy is more appropriate. Because many intestinal causes of protein-losing enteropathy are diffuse, endoscopy is the safer way to obtain biopsies, but surgical biopsy may be required to obtain a definitive diagnosis for lymphoma and for diseases that cause secondary lymphangiectasia (Box Relative Advantages of Endoscopic and Surgical Intestinal Biopsy).

Relative Advantages of Endoscopic and Surgical Intestinal Biopsy



  • Minimally invasive
  • Allows visualization and biopsy of focal lesions
  • Permits multiple biopsies
  • Minimal adverse reactions
  • Allows steroids to be started early


  • Requires general anesthesia
  • Permits access only to duodenum (and distal ileum?)
  • Allows only small, superficial (and crushed) biopsies
  • Requires expensive equipment
  • Technically demanding



  • Allows biopsy of multiple sites
  • Permits large, full-thickness biopsies
  • Allows inspection of other organs
  • Offers potential for corrective surgery


  • Requires general anesthesia
  • Poses a surgical risk
  • Requires convalescence
  • Requires delay before steroids can be started

Treatment Plasma transfusion may be indicated during the perioperative period when collecting biopsy specimens, and diuretics may reduce ascites. Spironolactone (1 to 2 mg / kg given orally twice daily) may be more effective than furosemide for treating ascites. Thromboembolism is a feature of some cases of protein-losing enteropathy. Specific treatments are discussed later.

Diagnosis of Small Intestinal Disease

Occult blood

These tests are used to search for intestinal bleeding from ulcerated mucosa and benign or malignant tumors. Unfortunately, all versions nonspecifically test for hemoglobin and are very sensitive, reacting with any meat diet and not just patient blood. Therefore the patient must be fed a meat-free diet for at last 72 hours for a positive result to have any reliability.

Alpha1-protease inhibitor This test assays the presence in feces of a naturally occurring endogenous serum protein that is resistant to bacterial degradation if it is lost into the intestinal lumen. To improve diagnostic accuracy, three fresh fecal samples should be sampled. The assay is valid only if used on fecal samples collected after voluntary evacuation, because abrasion of the colonic wall during manual evacuation is enough to elevate alpha1-protease inhibitor (alpha1-PI) concentrations. It appears to be of value for the diagnosis of protein-losing enteropathy and may prove to be more a sensitive marker than measurement of serum albumin for the detection of early disease.

Rectal cytology At the end of the rectal examination, the recta] wall is mildly abraded, the gloved finger rolled on a microscope slide, and the smear stained. Although the result is often negative and, when positive, probably more representative of large intestinal disease, an increased number of neutrophils may be suggestive of a bacterial problem, indicating the need for fecal culture. Clostridial endospore elements (Histoplasma, Aspergillus, Pythium, and Candida spp. ) may be identified. The test is fast and simple but in all cases confirmatory tests are indicated.

Small Intestine: Imaging

Small Intestine: Special Tests


Flexible endoscopy allows gross examination of the small intestine mucosa and collection of tissue samples without the need for invasive surgery. The proximal small intestine can be viewed during gastroduodenoscopy, and the distal small intestine often can be visualized by passing the endoscope retrograde through the ileocolic valve. Therefore only the midjejunum cannot be satisfactorily examined by routine endoscopy. However, given that most cases of malabsorption involve diffuse disease, this limitation may not be significant. Enteroscopy, which was developed in humans and which uses a much narrower, thinner endoscope, may allow examination of most of the jejunum.

Abnormal findings on gross endoscopic examination include mucosal granularity and friability, erosions / ulcers, retained food, mass lesions, and hyperemia / erythema. However, none of these characteristics is pathognomonic for particular disease conditions, and gross findings frequendy do not correlate with those of the histopathologic examination. A milky white appearance or a milky exudate is suggestive of lymphangiectasia, and the presence of intraluminal parasites may be diagnostic in some cases.

Small Intestine: Intestinal Biopsy

Acute Small Intestinal Disease

Viral Enteritides

Bacterial Enteritides

Rickettsial Diarrhea (Salmon Poisoning)

Neorickettsia helminthoeca and Neorickettsia elokominica are found in the metacercariae of the fluke Nanophyetus salmonicola, which is present in salmon in the western regions of the Cascade Mountains from northern California to central Washington. About a week after ingestion of infected salmon by dogs, the rickettsiae emerge from the mature fluke and cause a disease characterized by high fever, hemorrhagic gastroenteritis, vomiting, lethargy, anorexia, polydipsia, nasal-ocular discharge, and peripheral lymphadenopathy. Mortality is extremely high in untreated patients.

The diagnosis is based on a history of ingestion of raw fish in an endemic area, the detection of operculated fluke eggs in feces, and the presence of intracytoplasmic inclusion bodies in macrophages from lymph node aspirates. Oxytetracycline (7 mg / kg given intravenously three times a day) is the treatment of choice and should be continued for at least 5 days. The trematode vector is eradicated with praziquantel.

Algal Infections

Toxic algal blooms can lead to acute gastroenteritis and death in animals that drink contaminated water. Blue-green algae can synthesize an anticholinesterase that induces vomiting, diarrhea, ataxia, and rapid death in dogs. Prototheca spp. are achlorophyllous algae that cause protothecosis. Typically a cutaneous infection in cats, in dogs it can involve the intestine. Large intestinal disease is more common, but fatal disseminated disease affecting the small intestine has been reported.

Fungal Infections



Chronic Idiopathic Enteropathies

Adverse Reactions To Food

Small Intestinal Bacterial Overgrowth

Inflammatory Bowel Disease


Miscellaneous Causes Of Protein-Losing Enteropathy

Common causes of protein-losing enteropathy include lymphoma and IBD. However, there have also been recent reports of protein-losing enteropathy associated with intestinal crypt lesions without evidence of lymphangiectasia or inflammation in most cases. The underlying etiology of such lesions is not known. Response to therapy with antibacterials and immunosuppressive medication is variable; some dogs deteriorate suddenly and can die from thromboembolic disease

Intestinal Neoplasia

Adynamic Ileus And Intestinal Pseudo-Obstruction

Adynamic ileus is a common sequel to parvoviral enteritis, abdominal surgery, pancreatitis, peritonitis, endotoxemia, hypokalemia, and dysautonomia. The term intestinal pseudo-obstruction describes a condition in which patients show clinical evidence consistent with an obstruction, but no mechanical cause can be found. The condition has been associated with both visceral neuropathies and myopathies in humans, and such causes may occur in small animals. Most canine cases are associated with idiopathic sclerosing enteropathy, with fibrosis and a mononuclear cell infiltrate of the tunica muscularis. A case of feline intestinal pseudo-obstruction occurred secondary to intestinal lymphoma. After the possibility of a mechanical obstruction has been eliminated, management of both adynamic ileus and intestinal pseudo-obstruction is aimed at identifying any underlying cause and providing specific treatment. Symptomatic therapy to stimulate intestinal motility is also indicated. Suitable prokinetic agents include the 5-HT4 receptor agonist cisapride, the D2 dopaminergic antagonist metoclopramide, and motilin-like drugs such as erythromycin. In dogs and cats cisapride appears to be the most effective agent, but it is no longer marketed in many countries. Antibacterials may also be appropriate, given the probability of secondary SIBO, and immunosuppressive medication may be appropriate if an underlying inflammatory bowel disease is suspected. Feeding is beneficial in humans, and nutritional support can be continued indefinitely, although vomiting, constipation, and diarrhea usually continue. Unfortunately, most cases reported in the veterinary literature responded poorly to therapy, and the prognosis is grave.

Intestinal Obstruction

Intestinal obstruction can be classified as acute or chronic, partial or complete, and simple or strangulated. Obstruction can be the result of extraluminal, intramural, or intraluminal mass lesions. The most common extraluminal cause of obstruction is intussusception. Younger animals are more likely to develop intussusception after a case of gastroenteritis or after having intestinal surgery, although an increased risk in postparturient queens has also been reported. Intestinal neoplasia is the more frequent cause of intussusception in middle-aged and older animals. Intramural causes include intestinal neoplasia (most common), hematomas, granulomas (e. g., focal FIP), inflammatory bowel disease, stricture, and phycomycosis. Most intraluminal obstructions are caused by foreign objects, such as stones, fruit pits, and toys in dogs and linear foreign objects in cats. Intestinal volvulus describes a condition in which the intestines rotate around the mesenteric axis, compromising the cranial mesenteric artery, and complete vascular obstruction may lead to strangulation. Reports are sporadic, but a predisposition in German shepherds has been reported.

The prognosis depends on the cause of the obstruction and the severity of associated abnormalities. The outcome is likely to be favorable with simple foreign bodies, but it is grave for animals with volvulus or metastatic intestinal neoplasia. The patient may be at risk of developing short bowel syndrome if a significant length of intestine must be removed.

Short Bowel Syndrome

Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is characterized by recurrent, usually acute, episodes of abdominal pain, borborygmi, and diarrhea. In the absence of morphologic changes, a functional disorder is considered the cause of this enigmatic problem. Disordered intestinal motility may be of primary importance, and a number of mechanisms have been proposed for irritable bowel syndrome in humans (Box Causes of Irritable Bowel Syndrome). However, it is not known whether any are responsible in dogs and cats. A variety of treatments, including antispasmodics (anticholinergics and also smooth muscle relaxants, such as mebeverine), anxiolytics (e. g., diazepam, chlordiazepoxide) and dietary modification (low-fat diet, increased fiber) have been tried with no consistent results. IBS probably will remain a frustrating condition to diagnose and treat successfully until its etiology is better understood.

Causes of Irritable Bowel Syndrome

  • Primary motility disorders
  • Visceral hyperalgesia
  • Psychosomatic disorders
  • Food intolerance
  • Undiagnosed inflammatory disease