Codeine Phosphate

By | 2010-07-23


A phenanthrene-derivative opiate agonist, codeine is available as the base and three separate salts. Codeine base is slightly soluble in water and freely soluble in alcohol. Codeine phosphate occurs as fine, white, needle-like crystals or white, crystalline powder. It is freely soluble in water. Codeine sulfate’s appearance is similar to codeine phosphate, but it is soluble in water.

Storage – Stability – Compatibility

Codeine phosphate and sulfate tablets should be stored in light-resistant, well-closed containers at room temperature. Codeine phosphate injection should be stored at room temperature (avoid freezing) and protected from light. Do not use the injection if it is discolored or contains a precipitate.

Codeine phosphate injection is reportedly compatible with glycopyrrolate or hydroxyzine HCl. It is reportedly incompatible with aminophylline, ammonium chloride, amobarbital sodium, chlorothiazide sodium, heparin sodium, methicillin sodium, pentobarbital sodium, phenobarbital sodium, phenytoin sodium, secobarbital sodium, sodium bicarbonate, sodium iodide, and thiopental sodium.


Codeine possesses activity similar to other opiate agonists. It is a good antitussive and a mild analgesic. It produces similar respiratory depression as does morphine at equianalgesic dosages. For further information on opiate pharmacology, refer to: Opiate Agonists. Pharmacology.

Codeine phosphate: Uses – Indications

In small animal medicine, codeine is used principally as an oral analgesic when salicylates are not effective and parenteral opiates are not warranted. It may also be useful as an antitussive or as an antidiarrheal.


No information was located specifically for domestic animals. The following information is human data unless otherwise noted. After oral administration, codeine salts are rapidly absorbed. It is about 2/3’s as effective after oral administration when compared with parenteral administration. After oral dosing, onset of action is usually within 30 minutes and analgesic effects persist for 4-6 hours. Codeine is metabolized in the liver and then excreted into the urine.

Contraindications – Precautions – Reproductive Safety

All opiates should be used with caution in patients with hypothyroidism, severe renal insufficiency, adrenocortical insufficiency (Addison’s disease) and in geriatric or severely debilitated patients. Codeine is contraindicated in cases where the patient is hypersensitive to narcotic analgesics, or in patients taking monamine oxidase inhibitors (MAOIs). It is also contraindicated in patients with diarrhea caused by a toxic ingestion until the toxin is eliminated from the GI tract or when used repeatedly in patients with severe inflammatory bowel disease.

Codeine should be used with caution in patients with head injuries or increased intracranial pressure and acute abdominal conditions (e.g., colic) as it may obscure the diagnosis or clinical course of these conditions. It should be used with extreme caution in patients suffering from respiratory disease or from acute respiratory dysfunction (e.g., pulmonary edema secondary to smoke inhalation).

Opiate analgesics are also contraindicated in patients who have been stung by the scorpion species Centruroides sculpturatus Ewing and C. gertschi Stahnke as they may potentiate these venoms.

Do not use the combination product containing acetaminophen in cats.

Opiates cross the placenta. Very high doses in mice have caused delayed ossification. Use during pregnancy only when the benefits outweigh the risks, particularly with chronic use. Although codeine enters maternal milk, no documented problems have been associated with its use in nursing mothers.

Adverse Effects – Warnings

Codeine generally is well tolerated, but adverse effects are possible, particularly at higher dosages or with repeated use. Sedation is the most likely effect seen. Potential gastrointestinal effects include anorexia, vomiting, constipation, ileus, and biliary and pancreatic duct spasms. Respiratory depression is generally not noted unless the patient receives high doses or is at risk (see contraindications above).

In cats, opiates may also cause CNS stimulation with hyperexcitability, tremors and seizures possible.

Codeine phosphate: Overdosage – Acute Toxicity

Opiate overdosage may produce profound respiratory and/or CNS depression in most species. Other effects can include cardiovascular collapse, hypothermia, and skeletal muscle hypotonia. Oral ingestions of codeine should be removed when possible using standard gut removal protocols. Because rapid changes in CNS status may occur, inducing vomiting should be attempted with caution. Naloxone is the agent of choice in treating respiratory depression. In massive overdoses, naloxone doses may need to be repeated and animals should be closely observed as naloxone’s effects may diminish before subtoxic levels of codeine are attained. Mechanical respiratory support should also be considered in cases of severe respiratory depression. Serious overdoses involving any of the opiates should be closely monitored; it is suggested to contact an animal poison center for further information.

Drug Interactions

Other CNS depressants (e.g., anesthetic agents, antihistamines, phenofhiazines, barbiturates, tranquilizers, alcohol, etc.) may cause increased CNS or respiratory depression when used with meperidine. Anticholinergic drugs used with codeine may increase the chances of constipation developing. In humans, meperidine (a compound related to codeine) is contraindicated in patients for at least 14 days after receiving monamine oxidase (MOA) inhibitors (rarely used in veterinary medicine). Some human patients have exhibited signs of opiate overdose after receiving therapeutic doses of meperidine while on these agents.

Laboratory Considerations

Plasma amylase and lipase values may be increased for up to 24 hours following administration of opiate analgesics as they may increase biliary tract pressure.

Codeine phosphate: Doses

Doses for dogs:

As an antitussive:

a) 0.1 – 0.3 mg/kg PO q6-8h

b) l-2mg/kg PO q6-12h

As an analgesic:

a) 0.5 – 1 mg/kg PO q6-8h

b) In combination with acetaminophen: Using a 60 mg codeine and 300 mg acetaminophen fixed-dose tablet (e.g., Tylenol® #4), give 1 – 2 mg/kg (of the codeine) PO q6-8h. Using codeine alone: 1 – 4 mg/kg PO ql-6 hours

As an antidiarrheal:

a) 0.25 – 0.5 mg/kg PO q6-8h

Monitoring Parameters

1) Efficacy; 2) Adverse Effects (see above)

Client Information

Keep out of reach of children. Have client monitor for efficacy and changes in mentition or GI effects.

Dosage Forms – Preparations – FDA Approval Status – Withholding Times

Veterinary-Approved Products:


Human-Approved Products:

There are many products available containing codeine. The following is a partial listing:

Codeine Phosphate Oral Tablets 30 mg, 60 mg; generic (Rx) C-II

Codeine Sulfate Oral Tablets 15 mg, 30 mg, 60 mg; (Generic); (Rx) C-II

Codeine Phosphate Parenteral Injection 30 mg/ml, 60 mg/ml; generic. (Rx) C-II

Codeine Phosphate 7.5 mg (#1), 15 mg (#2), 30 mg (#3), 60 mg (#4) with Acetaminophen 300 mg tablets; Tylenol® with Codeine #’s 1, 2, 3, 4 (McNeil), Generic; (Rx); C-III

Codeine Phosphate 15 mg (#2), 30 mg (#3), 60 mg (#4) with Aspirin 320 mg tablets; Empirin with Codeine #’s 2, 3, 4 (Glaxo Wellcome), Generic; (Rx); C-III

Note: Codeine-only products are Class-II controlled substances. Combination products with aspirin or acetaminophen are Class-Ill. Codeine containing cough syrups are either Class-V or Class-Ill, depending on the state.