CODEINE PHOSPHATE

Chemistry - A phenanthrene-derivative opiate agonist, codeine is available as the base and threeseparate salts. Codeine base is slightly soluble in water and freely soluble in alcohol. Codeinephosphate occurs as fine, white, needle-like crystals or white, crystalline powder. It is freely solublein 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 inlight-resistant, well-closed containers at room temperature. Codeine phosphate injection should bestored at room temperature (avoid freezing) and protected from light. Do not use the injection if it isdiscolored or contains a precipitate.
Codeine phosphate injection is reportedly compatible with glycopyrrolate or hydroxyzine HCl. Itis reportedly incompatible with aminophylline, ammonium chloride, amobarbital sodium, chlorothiazide sodium, heparin sodium, methicillin sodium, pentobarbital sodium, phenobarbitalsodium, phenytoin sodium, secobarbital sodium, sodium bicarbonate, sodium iodide, and thiopentalsodium.

Pharmacology - CODEINE PHOSPHATE

Codeine possesses activity similar to other opiate agonists. It is a good antitussiveand a mild analgesic. It produces similar respiratory depression as does morphine at equianalgesicdosages. For further information on opiate pharmacology, refer to: Opiate Agonists, Pharmacology.
Uses, Indications - In small animal medicine, codeine is used principally as an oral analgesic whensalicylates are not effective and parenteral opiates are not warranted. It may also be useful as anantitussive or as an antidiarrheal.

Pharmacokinetics - CODEINE PHOSPHATE

No information was located specifically for domestic animals. The followinginformation is human data unless otherwise noted. After oral administration, codeine salts arerapidly 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 analgesiceffects 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 cautionin patients with hypothyroidism, severe renal insufficiency, adrenocortical insufficiency (Addison'sdisease) and in geriatric or severely debilitated patients. Codeine is contraindicated in cases wherethe patient is hypersensitive to narcotic analgesics, or in patients taking monamine oxidaseinhibitors (MAOIs). It is also contraindicated in patients with diarrhea caused by a toxic ingestionuntil the toxin is eliminated from the GI tract or when used repeatedly in patients with severeinflammatory bowel disease.
Codeine should be used with caution in patients with head injuries or increased intracranialpressure and acute abdominal conditions (e.g., colic) as it may obscure the diagnosis or clinicalcourse 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 smokeinhalation).
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 duringpregnancy only when the benefits outweigh the risks, particularly with chronic use. Althoughcodeine enters maternal milk, no documented problems have been associated with its use in nursingmothers.

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. Potentialgastrointestinal effects include anorexia, vomiting, constipation, ileus, and biliary and pancreatic ductspasms. Respiratory depression is generally not noted unless the patient receives high doses or is atrisk (see contraindications above).
In cats, opiates may also cause CNS stimulation with hyperexcitability, tremors and seizurespossible.

Overdosage, Acute Toxicity

Opiate overdosage may produce profound respiratory and/or CNSdepression in most species. Other effects can include cardiovascular collapse, hypothermia, andskeletal muscle hypotonia. Oral ingestions of codeine should be removed when possible usingstandard gut removal protocols. Because rapid changes in CNS status may occur, inducingvomiting should be attempted with caution. Naloxone is the agent of choice in treating respiratorydepression. In massive overdoses, naloxone doses may need to be repeated and animals should beclosely 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 tocontact an animal poison center for further information.

Drug Interactions

Other CNS depressants (e.g., anesthetic agents, antihistamines, phenothiazines, barbiturates, tranquilizers, alcohol, etc.) may cause increased CNS or respiratory depressionwhen used with meperidine. Anticholinergic drugs used with codeine may increase the chancesof constipation developing.
In humans, meperidine (a compound related to codeine) is contraindicated in patients for at least14 days after receiving monamine oxidase (MOA) inhibitors (rarely used in veterinarymedicine). Some human patients have exhibited signs of opiate overdose after receiving therapeuticdoses of meperidine while on these agents.
Laboratory Considerations - Plasma amylase and lipase values may be increased for up to 24hours following administration of opiate analgesics as they may increase biliary tract pressure.