Codeprex Pennkinetic (Codeine Polistirex / Chlorpheniramine Polistirex) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Drug Interactions

Anticholinergics

Additive adverse effects resulting from cholinergic blockade (e.g., xerostomia, blurred vision, constipation) may occur when anticholinergic drugs are administered with chlorpheniramine. Codeine and chlorpheniramine should be administered cautiously to persons receiving other anticholinergic drugs in order to avoid paralytic ileus and excessive anticholinergic effects.

OVERDOSAGE

Signs and Symptoms

Serious overdose with codeine is characterized by respiratory depression (a decrease in respiratory rate and or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, miosis (mydriasis may occur in terminal narcosis or severe hypoxia), skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur.

The estimated lethal dose of codeine in adults is 7 to 14 mg/kg body weight. Ingestion of more than 5 mg/kg of codeine has caused respiratory arrest in children. Ingestion of greater than 1 mg/kg of codeine may produce symptoms in children. Infants and children may demonstrate unusual sensitivity to opioids and habituated adults may have extreme tolerance to opioids.

Manifestations of chlorpheniramine overdosage may vary from central nervous system depression to stimulation. Central toxic effects are characterized by agitation, anxiety, delirium, disorientation, hallucinations, hyperactivity, sedation, and seizures. Severe overdosage may produce coma, medullary paralysis, and death. Peripheral toxicity includes hypertension, tachycardia, dysrhythmias, vasodilation, hyperpyrexia, mydriasis, urinary retention, and diminished gastrointestinal motility. Dry mouth, pharynx, bronchi, and nasal passages may be observed. Impaired secretion from sweat glands following toxic doses of drugs with anticholinergic side effects may predispose to hyperthermia.

Oral lethal doses of chlorpheniramine maleate were 130, 306 and 198 mg/kg in mice, rats and guinea pigs, respectively (approximately 35, 170 and 150 times, respectively, the maximum recommended daily dose for adults and children on a mg/m² basis). An adult ingested 400 mg chlorpheniramine with no reported serious adverse effects. Toxic psychosis, a possible class effect from overdose of sedating antihistamines, has been reported with accidental overdose of chlorpheniramine.

Treatment

Treatment of overdosage should provide symptomatic and supportive care. Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation as necessary. Oxygen, intravenous fluid, vasopressors, and other supportive measures should be employed as indicated. Induction of emesis is not recommended because of the potential for CNS depression and seizures. Gastric lavage may be useful in removing unabsorbed drug. Activated charcoal is recommended if the patient is awake and able to protect his/her airway. In persons who are at risk for abrupt onset of seizures or mental status depression, activated charcoal should be administered by medical or paramedical personnel capable of airway management to prevent aspiration in the event of spontaneous emesis. Severe agitation or seizures should be treated with an intravenous benzodiazepine.

The narcotic antagonist naloxone hydrochloride is a specific antidote against respiratory depression resulting from overdosage or unusual sensitivity to opiate agonists, including codeine. Therefore, an appropriate dose of naloxone hydrochloride (see prescribing information for naloxone hydrochloride) should be administered, preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation. Since the duration of action of codeine in this formulation may exceed that of the antagonist, the patient should be kept under continued surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. A narcotic antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression.

Hemodialysis is not routinely used to enhance the elimination of codeine or chlorpheniramine from the body. Urinary excretion of chlorpheniramine is increased when the pH of the urine is acidic (see CLINICAL PHARMACOLOGY), however acid diuresis is NOT recommended to enhance elimination in overdose, as the risks of acidemia and acute tubular necrosis in patients with rhabdomyolysis far outweigh any potential benefits.

CONTRAINDICATIONS

Codeprex should not be administered to persons known to be hypersensitive to codeine, chlorpheniramine, or other components of the product. Persons known to be hypersensitive to certain other opioids may exhibit cross-sensitivity to codeine.

DRUG ABUSE AND DEPENDENCE

Controlled Substance

Codeprex is a controlled narcotic in Schedule III of the Controlled Substances Act (CSA).

Abuse and Dependence

Codeine must be administered under close supervision to patients with a history of drug abuse or dependence. Codeine can produce drug dependence and therefore has the potential for abuse. Dependence and tolerance may develop upon repeated administration. An opioid withdrawal syndrome, indicating the development of dependence, may appear if the drug product is administered continuously for an extended time period.

Neonatal codeine withdrawal has occurred in infants born to addicted and non-addicted mothers who had been taking codeine-containing medications in the days prior to delivery. Typical symptoms of narcotic withdrawal include irritability, excessive crying, tremors, hyperreflexia, seizures, fever, vomiting, diarrhea, and poor feeding. These signs occur shortly after birth and may require specific treatment.