Amoxicillin (Amoxil, Amoxi-Tabs)

By | 2013-07-18

Aminopenicillin

Highlights Of Prescribing Information

Bactericidal aminopenicillin with same spectrum as ampicillin (ineffective against bacteria that produce beta-lactamase)

Most likely adverse effects are GI-related, but hypersensitivity & other adverse effects rarely occur

Available in oral & parenteral dosage forms in USA

What Is Amoxicillin Used For?

The aminopenicillins have been used for a wide range of infections in various species. FDA-approved indications/species, as well as non-approved uses, are listed in the Dosages section below.

Pharmacology / Actions

Like other penicillins, amoxicillin is a time-dependent, bactericidal (usually) agent that acts by inhibiting cell wall synthesis. Although there may be some slight differences in activity against certain organisms, amoxicillin generally shares the same spectrum of activity and uses as ampicillin. Because it is better absorbed orally (in non-ruminants), higher serum levels maybe attained than with ampicillin.

Penicillins are usually bactericidal against susceptible bacteria and act by inhibiting mucopeptide synthesis in the cell wall resulting in a defective barrier and an osmotically unstable spheroplast. The exact mechanism for this effect has not been definitively determined, but beta-lactam antibiotics have been shown to bind to several enzymes (carboxypeptidases, transpeptidases, endopeptidases) within the bacterial cytoplasmic membrane that are involved with cell wall synthesis. The different affinities that various beta-lactam antibiotics have for these enzymes (also known as penicillin-binding proteins; PBPs) help explain the differences in spectrums of activity the drugs have that are not explained by the influence of beta-lactamases. Like other beta-lactam antibiotics, penicillins are generally considered more effective against actively growing bacteria.

The aminopenicillins, also called the “broad-spectrum” or ampicillin penicillins, have increased activity against many strains of gram-negative aerobes not covered by either the natural penicillins or penicillinase-resistant penicillins, including some strains of E. coli, Klebsiella, and Haemophilus. Like the natural penicillins, they are susceptible to inactivation by beta-lactamase-producing bacteria (e.g., Staph aureus). Although not as active as the natural penicillins, they do have activity against many anaerobic bacteria, including Clostridial organisms. Organisms that are generally not susceptible include Pseudomonas aeruginosa, Serratia, Indole-positive Proteus {Proteus mirahilis is susceptible), Enterobacter, Citrobacter, and Acinetobacter. The aminopenicillins also are inactive against Rickettsia, mycobacteria, fungi, Mycoplasma, and viruses.

In order to reduce the inactivation of penicillins by beta-lactamases, potassium clavulanate and sulbactam have been developed to inactivate these enzymes and thus extend the spectrum of those penicillins. When used with a penicillin, these combinations are often effective against many beta-lactamase-producing strains of otherwise resistant E. coli, Pasturella spp., Staphylococcus spp., Klebsiella, and Proteus. Type I beta-lactamases that are often associated with E. coli, Enterobacter, and Pseudomonas are not generally inhibited by clavulanic acid.

Pharmacokinetics

Amoxicillin trihydrate is relatively stable in the presence of gastric acid. After oral administration, it is about 74-92% absorbed in humans and monogastric animals. Food will decrease the rate, but not the extent of oral absorption and many clinicians suggest giving the drug with food, particularly if there is concomitant associated GI distress. Amoxicillin serum levels will generally be 1.5-3 times greater than those of ampicillin after equivalent oral doses.

After absorption, the volume of distribution for amoxicillin is approximately 0.3 L/kg in humans and 0.2 L/kg in dogs. The drug is widely distributed to many tissues, including liver, lungs, prostate (human), muscle, bile, and ascitic, pleural and synovial fluids. Amoxicillin will cross into the CSF when meninges are inflamed in concentrations that may range from 10-60% of those found in serum. Very low levels of the drug are found in the aqueous humor, and low levels found in tears, sweat and saliva. Amoxicillin crosses the placenta, but it is thought to be relatively safe to use during pregnancy. It is approximately 17-20% bound to human plasma proteins, primarily albumin. Protein binding in dogs is approximately 13%. Milk levels of amoxicillin are considered low.

Amoxicillin is eliminated primarily through renal mechanisms, principally by tubular secretion, but some of the drug is metabolized by hydrolysis to penicilloic acids (inactive) and then excreted in the urine. Elimination half-lives of amoxicillin have been reported as 45-90 minutes in dogs and cats, and 90 minutes in cattle. Clearance is reportedly 1.9 mL/kg/min in dogs.

Before you take Amoxicillin

Contraindications / Precautions / Warnings

Penicillins are contraindicated in patients with a history of hyper-sensitivity to them. Because there may be cross-reactivity, use penicillins cautiously in patients who are documented hypersensitive to other beta-lactam antibiotics (e.g., cephalosporins, cefamycins, carbapenems).

Do not administer penicillins, cephalosporins, or macrolides to rabbits, guinea pigs, chinchillas, hamsters, etc. or serious enteritis and clostridial enterotoxemia may occur.

Do not administer systemic antibiotics orally in patients with septicemia, shock, or other grave illnesses as absorption of the medication from the GI tract may be significantly delayed or diminished. Parenteral (preferably IV) routes should be used for these cases.

Adverse Effects

Adverse effects with the penicillins are usually not serious and have a relatively low frequency of occurrence.

Hypersensitivity reactions unrelated to dose can occur with these agents and can manifest as rashes, fever, eosinophilia, neutropenia, agranulocytosis, thrombocytopenia, leukopenia, anemias, lymphadenopathy, or full-blown anaphylaxis.

When given orally, penicillins may cause GI effects (anorexia, vomiting, diarrhea). Because the penicillins may alter gut flora, antibiotic-associated diarrhea can occur and allow the proliferation of resistant bacteria in the colon (superinfections).

High doses or very prolonged use have been associated with neurotoxicity (e.g., ataxia in dogs). Although the penicillins are not considered hepatotoxic, elevated liver enzymes have been reported. Other effects reported in dogs include tachypnea, dyspnea, edema and tachycardia.

Reproductive / Nursing Safety

Penicillins have been shown to cross the placenta; safe use during pregnancy has not been firmly established, but neither have there been any documented teratogenic problems associated with these drugs. However, use only when the potential benefits outweigh the risks. In humans, the FDA categorizes this drug as category B for use during pregnancy () In a separate system evaluating the safety of drugs in canine and feline pregnancy (), this drug is categorized as in class: A (Probably 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

Acute oral penicillin overdoses are unlikely to cause significant problems other than GI distress but other effects are possible (see Adverse Effects). In humans, very high dosages of parenteral penicillins, especially in patients with renal disease, have induced CNS effects.

How to use Amoxicillin

Amoxicillin dosage for dogs:

For susceptible infections:

a) For Gram-positive infections: 10 mg/kg PO, IM, SC twice daily for at least 2 days after symptoms subside.

For Gram-negative infections: 20 mg/kg PO three times daily or IM, SC twice daily for at least 2 days after symptoms subside ()

b) For susceptible UTI’s: 10-20 mg/kg PO q12h for 5-7 days. For susceptible systemic infections (bacteremia/sepsis): 22-30 mg/kg IV, IM, SC q8h for 7 days.

For susceptible orthopedic infections: 22-30 mg/kg IV, IM, SC, or PO q6-8h for 7-10 days. ()

c) For Lyme disease: 22 mg/kg PO q12h for 21-28 days ()

Amoxicillin dosage for cats:

For susceptible infections:

a) For Gram-positive infections: 10 mg/kg PO, IM, SC twice daily for at least 2 days after symptoms subside.

For Gram-negative infections: 20 mg/kg PO three times daily or IM, SC twice daily for at least 2 days after symptoms subside ()

b) For susceptible UTI’s and soft tissue infections: 50 mg (total dose per cat) or 11-22 mg/kg PO once daily for 5-7 days. For sepsis: 10-20 mg/kg IV, SC, or PO q12h for as long as necessary. Note: Duration of treatment are general guidelines, generally treat for at least 2 days after all signs of infection are gone. ()

c) C. perfringens, bacterial overgrowth (GI): 22 mg/kg PO once daily for 5 days ()

d) C. perfringens enterotoxicosis: 11-22 mg/kg PO two to three times daily for 7 days ()

e) For treating H. pylori infections using triple therapy: amoxi-cillin 20 mg/kg PO twice daily for 14 days; metronidazole 10-15 mg/kg PO twice daily; clarithromycin 7.5 mg/kg PO twice daily ()

Amoxicillin dosage for ferrets:

For eliminating Helicobacter gastritis infections:

a) Using triple therapy: Metronidazole 22 mg/kg, amoxicillin 22 mg/kg and bismuth subsalicylate (original Pepto-Bismol) 17.6 mg/kg PO. Give each 3 times daily for 3-4 weeks. ()

b) Using triple therapy: Metronidazole 20 mg/kg PO q12h, amoxicillin 20 mg/kg PO q12h and bismuth subsalicylate 17.5 mg/kg PO q8h. Give 21 days. Sucralfate (25 mg/kg PO q8h) and famotidine (0.5 mg/kg PO once daily) are also used. Fluids and assisted feeding should be continued while the primary cause of disease is investigated. ()

For susceptible infections:

a) 10-35 mg/kg PO or SC twice daily ()

Amoxicillin dosage for rabbits, rodents, and small mammals:

Note: See warning above in Contraindications a) Hedgehogs: 15 mg/kg IM or PO q12h ()

Amoxicillin dosage for cattle:

For susceptible infections:

a) 6-10 mg/kg SC or IM q24h (Withdrawal time = 30 days) ()

b) For respiratory infections: 11 mg/kg IM or SC q12h ()

c) Calves: Amoxicillin trihydrate: 7 mg/kg PO q8-12h ()

Amoxicillin dosage for horses:

For susceptible infections:

a) For respiratory infections: 20-30 mg/kg PO q6h ()

b) Foals: Amoxicillin Sodium: 15-30 mg/kg IV or IM q6-8h; amoxicillin trihydrate suspension: 25-40 mg/kg PO q8h; amoxicillin/clavulanate 15-25 mg/kg IV q6-8h ()

Amoxicillin dosage for birds:

For susceptible infections:

a) For most species: 150-175 mg/kg PO once to twice daily (using 50 mg/mL suspension) ()

b) 100 mg/kg q8h PO ()

c) 100 mg/kg q8h, IM, SC, PO ()

d) Ratites: 15-22 mg/kg PO twice daily; in drinking water: 250 mg/gallon for 3-5 days ()

Amoxicillin dosage for reptiles:

For susceptible infections:

a) For all species: 22 mg/kg PO ql2 -24h; not very useful unless used in combination with aminoglycosides ()

Client Information

■ The oral suspension should preferably be refrigerated, but refrigeration is not absolutely necessary; any unused oral suspension should be discarded after 14 days

■ Amoxicillin may be administered orally without regard to feeding status

■ If the animal develops gastrointestinal symptoms (e.g., vomiting, anorexia), giving with food may be of benefit

Chemistry / Synonyms

An aminopenicillin, amoxicillin is commercially available as the trihydrate. It occurs as a practically odorless, white, crystalline powder that is sparingly soluble in water. Amoxicillin differs structurally from ampicillin only by having an additional hydroxyl group on the phenyl ring.

Amoxicillin may also be known as: amoxycillin, p-hydroxyampicillin, or BRL 2333; many trade names are available.

Storage / Stability / Compatibility

Amoxicillin capsules, tablets, and powder for oral suspension should be stored at room temperature (15-30°C) in tight containers. After reconstitution, the oral suspension should preferably be refrigerated (refrigeration not absolutely necessary) and any unused product discarded after 14 days.

Dosage Forms / Regulatory Status/Withdrawal Times

Veterinary-Labeled Products:

Amoxicillin Oral Tablets: 50 mg, 100 mg, 150 mg, 200 mg, & 400 mg; Amoxi-Tabs (Pfizer); (Rx). Approved for use in dogs and cats.

Amoxicillin Powder for Oral Suspension 50 mg/mL (after reconstitution) in 15 mL or 30 mL bottles; Amoxi-Drop (Pfizer); (Rx). Approved for use in dogs and cats.

Amoxicillin Intramammary Infusion 62.5 mg/syringe in 10 mL syringes; Amoxi-Mast (Schering-Plough); (Rx). Approved for use in lactating dairy cattle. Slaughter withdrawal (when administered as labeled) = 12 days; Milk withdrawal (when administered as labeled) = 60 hours.

Human-Labeled Products:

Amoxicillin Tablets (chewable) (as trihydrate): 125 mg, 200 mg, 250 mg, & 400 mg; Amoxf/(GlaxoSmithKline); generic; (Rx)

Amoxicillin Tablets (as trihydrate): 500 mg & 875 mg; Amoxil (GlaxoSmithKline); generic; (Rx)

Amoxicillin Capsules (as trihydrate): 250 mg, & 500 mg; Amoxil (GlaxoSmithKline); generic; (Rx)

Amoxicillin (as trihydrate) Powder for Oral Suspension: 50 mg/mL (in 15 and 30 mL bottles), 125 mg/5 mL in 80 mL & 150 mL; 200 mg/5 mL in 50 mL, 75 mL & 100 mL; 250 mg/5 mL in 80 mL, 100 mL & 150 mL; 400 mg/5 mL in 50 mL, 75 mL & 100 mL; Amoxil & Amoxil Pediatric Drops (GlaxoSmithKline); (Apothecon), Trimox (Sandoz); generic; (Rx)

AmoxiciUin Tablets for Oral Suspension: 200 mg & 400 mg; Disper-Mox (Ranbaxy); (Rx)