Promethazine with Codeine

PROMETHAZINE WITH CODEINE- promethazine hydrochloride and codeine phosphate solution
Lohxa

DESCRIPTION

Each 5 mL (one teaspoonful), for oral administration contains: Promethazine hydrochloride 6.25 mg; codeine phosphate 10 mg in a flavored oral solution base with a pH between 4.7 and 5.2. Alcohol 7%.

Inactive Ingredients: Artificial raspberry flavor, ascorbic acid, citric acid anhydrous, D&C Red #33, dehydrated alcohol, edetate disodium, FD&C Blue #1, glycerin, liquid sugar, methylparaben, purified water, saccharin sodium, sodium benzoate, sodium citrate dihydrate and sodium propionate.

Codeine is one of the naturally occurring phenanthrene alkaloids of opium derived from the opium poppy; it is classified pharmacologically as a narcotic analgesic. Codeine phosphate may be chemically designated as 7,8-Didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol phosphate (1:1)(salt) hemihydrate.

The phosphate salt of codeine occurs as white, needle-shaped crystals or white crystalline powder. Codeine phosphate is freely soluble in water and slightly soluble in alcohol. It has a molecular weight of 406.37, a molecular formula of C ₁₈ H ₂₁ NO ₃ •H ₃ PO ₄ •½H ₂ O, and the following structural formula:

Promethazine hydrochloride, a phenothiazine derivative, is chemically designated as (±)-10-[2-(Dimethylamino)propyl] phenothiazine monohydrochloride.

Promethazine hydrochloride occurs as a white to faint yellow, practically odorless, crystalline powder which slowly oxidizes and turns blue on prolonged exposure to air. It is soluble in water and freely soluble in alcohol. It has a molecular weight of 320.88, a molecular formula of C ₁₇ H ₂₀ N ₂ S•HCl, and the following structural formula:

CLINICAL PHARMACOLOGY

Codeine

Narcotic analgesics, including codeine, exert their primary effects on the central nervous system and gastrointestinal tract. The analgesic effects of codeine are due to its central action; however, the precise sites of action have not been determined, and the mechanisms involved appear to be quite complex. Codeine resembles morphine both structurally and pharmacologically, but its actions at the doses of codeine used therapeutically are milder, with less sedation, respiratory depression, and gastrointestinal, urinary, and pupillary effects. Codeine produces an increase in biliary tract pressure, but less than morphine or meperidine. Codeine is less constipating than morphine.

Codeine has good antitussive activity, although less than that of morphine at equal doses. It is used in preference to morphine, because side effects are infrequent at the usual antitussive dose of codeine.

Codeine in oral therapeutic dosage does not usually exert major effects on the cardiovascular system.

Narcotic analgesics may cause nausea and vomiting by stimulating the chemoreceptor trigger zone (CTZ); however, they also depress the vomiting center, so that subsequent doses are unlikely to produce vomiting. Nausea is minimal after usual oral doses of codeine.

Narcotic analgesics cause histamine release, which appears to be responsible for wheals or urticaria sometimes seen at the site of injection on parenteral administration. Histamine release may also produce dilation of cutaneous blood vessels, with resultant flushing of the face and neck, pruritus, and sweating.

Codeine and its salts are well absorbed following both oral and parenteral administration. Codeine is about 2/3 as effective orally as parenterally. Codeine is metabolized primarily in the liver by enzymes of the endoplasmic reticulum, where it undergoes O-demethylation, N-demethylation, and partial conjugation with glucuronic acid. The drug is excreted primarily in the urine, largely as inactive metabolites and small amounts of free and conjugated morphine. Negligible amounts of codeine and its metabolites are found in the feces.

Following oral or subcutaneous administration of codeine, the onset of analgesia occurs within 15 to 30 minutes and lasts for four to six hours.

The cough-depressing action, in animal studies, was observed to occur 15 minutes after oral administration of codeine, peak action at 45 to 60 minutes after ingestion. The duration of action, which is dose-dependent, usually did not exceed 3 hours.

Promethazine

Promethazine is a phenothiazine derivative which differs structurally from the antipsychotic phenothiazines by the presence of a branched side chain and no ring substitution. It is thought that this configuration is responsible for its lack (1/10 that of chlorpromazine) of dopamine antagonist properties.

Promethazine is an H ₁ receptor blocking agent. In addition to its antihistaminic action, it provides clinically useful sedative and antiemetic effects.

Promethazine is well absorbed from the gastrointestinal tract. Clinical effects are apparent within 20 minutes after oral administration and generally last four to six hours, although they may persist as long as 12 hours. Promethazine is metabolized by the liver to a variety of compounds; the sulfoxides of promethazine and N-demethylpromethazine are the predominant metabolites appearing in the urine.

INDICATIONS AND USAGE

Promethazine HCl and Codeine Phosphate Oral Solution is indicated for the temporary relief of coughs and upper respiratory symptoms associated with allergy or the common cold.

CONTRAINDICATIONS

Promethazine HCl and Codeine Phosphate Oral Solution is contraindicated in all children younger than 12 years of age. (See WARNINGS — Ultra- Rapid Metabolism of Codeine and Respiratory Depression).

Promethazine HCl and Codeine Phosphate Oral Solution is contraindicated for postoperative management in children younger than 18 years who have undergone tonsillectomy and/or adenoidectomy. (See WARNINGS — Ultra- Rapid Metabolism of Codeine and Respiratory Depression).

Codeine is contraindicated in patients with a known hypersensitivity to the drug.

Promethazine is contraindicated in comatose states, and in individuals known to be hypersensitive or to have had an idiosyncratic reaction to promethazine or to other phenothiazines.

Antihistamines and codeine are both contraindicated for use in the treatment of lower respiratory tract symptoms, including asthma