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Promethazine Hydrochloride / Codeine Phosphate

Pronunciation: (proe-METH-a-zeen HYE-droe-KLOR-ide/KOE-deen FOS-fate)
Class: Antitussive combination

Trade Names

Promethazine with Codeine
- Syrup codeine phosphate 10 mg/promethazine hydrochloride 6.25 mg per 5 mL

Pharmacology

Promethazine

Competitively antagonizes histamine at H ₁ -receptor sites and produces sedative as well as antiemetic effects.

Codeine

Stimulates opiate receptors in the CNS in addition to causing respiratory depression, peripheral vasodilation, inhibition of intestinal peristalsis, stimulation of the chemoreceptors that cause vomiting, increased bladder tone, and suppression of cough.

Indications and Usage

Temporary relief of coughs and upper respiratory tract symptoms associated with allergies or the common cold.

Contraindications

Treatment of lower respiratory tract symptoms, including asthma; known hypersensitivity or idiosyncratic reaction to promethazine or other phenothiazines; hypersensitivity to any component of the product.

According to some manufacturers, promethazine/codeine is contraindicated in children younger than 16 yr of age because of the risk of fatal respiratory depression. Other manufacturers state that this combination is contraindicated in children younger than 6 yr of age. According to the FDA, this combination is contradicted in children younger than 6 yr of age (written communication January 2010).

Dosage and Administration

Maximum dose

Adults and Children 6 yr of age and older

Codeine 60 mg/day; promethazine 37.5 mg/day (30 mL/day).

Cough and upper respiratory tract symptoms
Adults Usual dosage

5 mL every 4 to 6 h.

Maximum dose

Codeine 60 mg/day; promethazine 37.5 mg/day (30 mL/day).

Children

According to some manufacturers, promethazine/codeine is contraindicated in children younger than 16 yr of age because of the risk of fatal respiratory depression. Other manufacturers state that this combination is contraindicated in children younger than 6 yr of age. According to the FDA, this combination is contradicted in children younger than 6 yr of age (written communication January 2010).

Consult the manufacturer's prescribing information for more information.

Cough and respiratory tract symptoms
12 yr of age and older Usual dosage

5 mL every 4 to 6 h.

Maximum dose

Codeine 60 mg/day; promethazine 37.5 mg/day (30 mL/day).

6 to younger than 12 yr of age Usual dosage

2.5 to 5 mL every 4 to 6 h.

Maximum dose

Codeine 60 mg/day; promethazine 37.5 mg/day (30 mL/day).

Elderly

Start at the low end of the dosage range.

Renal function impairment

Use with caution in patients with significant renal function impairment.

Hepatic function impairment

Use with caution in patients with significant hepatic function impairment.

General Advice

Give with food or milk if GI upset occurs.
Use dosing spoon or syringe for pediatric doses.

Storage/Stability

Store syrup at controlled room temperature (68° to 77°F). Keep tightly capped and protect from light.

Drug Interactions

Codeine CNS depressants (eg, alcohol, sedatives, tranquilizers)

Additive CNS depression.

MAOIs (eg, isocarboxazid)

Excessive narcotic effects or MAOI interaction may occur.

Quinidine

May decrease the analgesic effect of codeine by interference with metabolism of codeine to morphine.

Promethazine Alcohol, barbiturates, narcotic analgesics, sedative-hypnotics, tricyclic antidepressants, tranquilizers, or other CNS depressants

Sedative action of promethazine is additive with these agents.

Anticholinergics

May decrease action of promethazine.

Barbiturate anesthetics

Coadministration with promethazine may increase risk of neuromuscular excitation and hypotension.

Epinephrine

Because promethazine may reverse vasopressor effect of epinephrine, do not use epinephrine to treat promethazine-associated overdose.

MAOIs

Coadministration with promethazine may prolong and intensify anticholinergic effects; may cause hypotension and extrapyramidal effects.

Laboratory Test Interactions

Codeine

Codeine

Antidiuretic effect; oliguria; urinary retention.

Hematologic-Lymphatic

Promethazine

Agranulocytosis; leukopenia; thrombocytopenia.

Hypersensitivity

Codeine

Angioneurotic edema; giant urticaria; laryngeal edema; pruritus.

Respiratory

Codeine

Respiratory depression.

Precautions

Warnings

Because of the potential for fatal respiratory depression, do not administer promethazine and codeine concurrently to children less than 16 yr of age. Some manufacturers state that this combination is contraindicated in children younger than 6 yr of age. According to the FDA, this combination is contradicted in children younger than 6 yr of age (written communication January 2010). In addition, postmarketing cases of respiratory depression, including fatalities, have been reported with the use of promethazine in children younger than 2 yr of age.

Pregnancy

Category C .

Lactation

Codeine

Excreted in breast milk.

Promethazine

Undetermined.

Children

According to some manufacturers, this combination is contraindicated in children younger than 16 yr of age. Some manufacturers state that this combination is contraindicated in children younger than 6 yr of age. According to the FDA, this combination is contraindicated in children younger than 6 yr of age (written communication January 2010).

Elderly

Use with caution, usually starting at low end of dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Special Risk Patients

Use with caution in the very young, elderly, or debilitated patient. Use with caution in patients with acute abdominal conditions, convulsive disorders, significant hepatic or renal function impairment, bone marrow depression, fever, hypothyroidism, Addison disease, ulcerative colitis, prostatic hypertrophy, CV disease, recent GI or urinary tract surgery, head injury or increased intracranial pressure, narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, narrowing of the bladder neck. Use with caution in atopic children because of possible histamine release.

Cholestatic jaundice

May occur.

Dependency

Codeine has abuse potential. Psychological and physical dependence as well as tolerance may occur.

Extrapyramidal symptoms

Extrapyramidal symptoms that can occur secondary to promethazine and codeine may be confused with the CNS signs of undiagnosed primary disease (eg, encephalopathy, Reye syndrome). Avoid use in children whose signs and symptoms may suggest Reye syndrome or other hepatic diseases.

Respiratory conditions

Codeine should not be used in acute febrile illness associated with productive cough or in chronic respiratory disease where interference with ability to clear the tracheobronchial tree of secretion would be deleterious to respiratory function.

Seizure threshold

Seizure threshold may be lowered; use with caution in patients with known seizure disorders or when giving in combination with narcotics or local anesthetics that may also affect seizure threshold.

Sleep apnea

Avoid use in patients with history of sleep apnea.

Overdosage

Symptoms

Codeine

Apnea, bradycardia, cardiac arrest, circulatory collapse, cold clammy skin, death, extreme somnolence progressing to stupor or coma, hypotension, respiratory depression, skeletal muscle flaccidity; promethazine is additive to depressant effects of codeine.

Promethazine

Signs range from mild depression of the CNS and CV system to profound hypotension, respiratory depression, and unconsciousness; stimulation (especially in children and elderly patients); paradoxical hyperexcitability and nightmares in children; convulsions; dry mouth; fixed, dilated pupils; flushing; GI symptoms.

Patient Information

Advise patient to take prescribed dose every 4 to 6 h as needed.
Advise caregiver to use dosing spoon or syringe when giving suspension to children.
Advise patient to take with food or milk if GI upset occurs.
Advise patient that if a dose is missed to take as soon as remembered unless it is nearing time for the next dose. Caution patient to not double the dose to catch up.
Advise patient that if cough, allergy, or cold symptoms are not controlled, not to increase the dose of medication but to inform health care provider.
Caution patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
Advise patient to avoid alcohol and other CNS depressants because of risk of excessive sedation.
Caution patient not to take any OTC antihistamines or decongestants while taking this medication unless advised by health care provider.
If patient is to have allergy skin testing, advise to not take the medication for at least 6 days before the skin testing.
Instruct patient to stop taking drug and immediately report any of these symptoms to health care provider: abnormal muscle movements, dizziness, excessive drowsiness, unusual sensitivity to sunlight.