Promethazine Hydrochloride / Phenylephrine Hydrochloride / Codeine Phosphate

Pronunciation: proe-METH-a-zeen HYE-droe-KLOR-ide/fen-il-EF-rin HYE-droe-KLOR-ide/KOE-deen FOS-fate
Class: Antihistamine, Decongestant, Antitussive, Narcotic analgesic

Trade Names

Promethazine VC w/Codeine
- Syrup 6.25 mg promethazine hydrochloride/5 mg phenylephrine hydrochloride/10 mg codeine phosphate per 5 mL

Pharmacology

Promethazine

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

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Phenylephrine

Stimulates postsynaptic alpha-receptors, resulting in rise in arterial peripheral vasoconstriction.

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, including nasal congestion, associated with allergy or common cold.

Contraindications

Hypertension; peripheral vascular insufficiency; known hypersensitivity to any component of the product; hypersensitivity or idiosyncratic reaction to promethazine or other phenothiazines; patients receiving MAOIs; treatment of lower respiratory tract symptoms, including asthma; comatose states.

According to some manufacturers, codeine/promethazine/phenylephrine 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 contraindicated 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; phenylephrine 30 mg/day (30 mL/day).

Adults

For specific dosing by product, refer to the individual manufacturer's prescribing information.

Cough and upper respiratory tract symptoms Usual dosage

5 mL every 4 to 6 h.

Maximum dose

Codeine 30 mg/day; promethazine 18.75 mg/day; phenylephrine 15 mg/day (30 mL/day).

Children

According to some manufacturers, codeine/promethazine/phenylephrine 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 contraindicated in children younger than 6 yr of age (written communication January 2010).

Consult the manufacturer's prescribing information for more information.

Cough and upper 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; phenylephrine 30 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; phenylephrine 30 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

• Take with food or milk if GI upset occurs.

Storage/Stability

Store between 68° and 77°F. Protect from light.

Drug Interactions

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

Causes additive CNS depression.

MAOIs (eg, isocarboxazid)

Excessive narcotic 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 effects of promethazine are additive with these agents.

Phenylephrine Alpha-adrenergic blockers (eg, phentolamine)

Decreased pressor response.

Anorexiants (eg, amphetamines, phenylpropanolamine)

Synergistic adrenergic response.

Anticholinergics

May decrease action of promethazine.

Atropine

Reflex bradycardia may be blocked or pressor response enhanced.

Barbiturate anesthetics

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

Beta-adrenergic blockers (eg, propranolol)

Cardiostimulating effects may be blocked.

Bronchodilators, sympathomimetic agents

Tachycardia or other arrhythmias may occur.

Epinephrine

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

Ergot derivatives

Excessive increase in BP may occur.

MAOIs

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

Tricyclic antidepressants

Pressor effects of phenylephrine may be increased.

Laboratory Test Interactions

Codeine

Increased plasma levels of amylase or lipase, making determination of these enzyme levels unreliable for 24 h after taking codeine.

Promethazine

False-negative or false-positive interpretations of diagnostic pregnancy tests based on immunological reactions between human chorionic gonadotropin (hCG) and anti-hCG; increased blood glucose tests.

Adverse Reactions

Cardiovascular

Codeine

Bradycardia; circulatory depression; faintness; orthostatic hypotension; palpitation; syncope; weakness; tachycardia.

Phenylephrine

Hypertension.

Promethazine

Bradycardia; decreased and increased BP; faintness; tachycardia.

CNS

Codeine

CNS depression; seizures; disorientation; dizziness; dysphoria; euphoria; headache; light-headedness; sedation; transient hallucinations.

Phenylephrine

Anxiety; dizziness; nervousness; restlessness; tremor; weakness.

Promethazine

Catatonic-like states; confusion; convulsive seizures; disorientation; dizziness; drowsiness; euphoria; excitation; extrapyramidal symptoms (including oculogyric crisis, tongue protrusion, and torticollis); fatigue; hallucinations; hysteria; incoordination; insomnia; lassitude; nervousness; sedation; somnolence; tremor.

Dermatologic

Codeine

Facial flushing (allergic); sweating.

Promethazine

Dermatitis; photosensitivity; urticaria.

EENT

Codeine

Visual disturbances.

Promethazine

Blurred vision; diplopia; nasal stuffiness; tinnitus.

GI

Codeine

Biliary tract spasm; constipation; nausea; toxic dilation in patients with acute ulcerative colitis; vomiting.

Phenylephrine

Precordial pain.

Promethazine

Dry mouth; nausea; vomiting.

Genitourinary

Codeine

Antidiuretic effect; oliguria; urinary retention.

Hematologic-Lymphatic

Promethazine

Agranulocytosis; leukopenia; thrombocytopenia; thrombocytopenic purpura.

Hepatic

Promethazine

Jaundice (including cholestatic).

Hypersensitivity

Codeine

Angioneurotic edema, laryngeal edema, giant urticaria, pruritus.

Respiratory

Codeine

Respiratory depression.

Phenylephrine

Respiratory distress.

Promethazine

Asthma; potentially fatal apnea and respiratory depression.

Miscellaneous

Promethazine

Angioneurotic edema, paradoxical reactions (including abnormal movements and hyperexcitability with agitated behavior, delirium, nightmares, and respiratory distress in some patients); potentially fatal neuroleptic malignant syndrome.

Precautions

Warnings Because of the potential for fatal respiratory depression, do not administer codeine, phenylephrine, and promethazine concurrently to 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). 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 and phenylephrine

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 the low end of the 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 patients with acute abdominal conditions; Addison disease; bone marrow depression; convulsive disorders; CV disease; diabetes mellitus; fever; head injury or increased intracranial pressure; narrow-angle glaucoma; prostatic hypertrophy; pyloroduodenal obstruction caused by symptomatic prostatic hypertrophy or narrowing of the bladder; recent GI or urinary tract surgery; significant hepatic or renal function impairment; stenosing peptic ulcer; thyroid disease; ulcerative colitis; atopic children (because of possible histamine release); arteriosclerosis; or those with initially poor cerebral or coronary circulation; receiving tricyclic antidepressants or diet preparations (eg, amphetamines) and in very young, elderly, or debilitated patients.

Benign prostatic hypertrophy (BPH)

Men with symptomatic BPH can experience urinary retention when given oral nasal decongestants.

Dependency

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

Neuroleptic Malignant Syndrome

Has occurred and is potentially fatal. Signs and symptoms include altered mental status, diaphoresis, hyperpyrexia, irregular BP and pulse, muscle rigidity, and tachycardia.

Seizure threshold

Seizure threshold may be lowered; use with caution in persons with known seizure disorders or when given 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

Bradycardia, cardiac arrest, circulatory collapse, cold clammy skin, death, extreme somnolence progressing to stupor or coma, hypotension, apnea. Promethazine is additive to depressant effects of codeine, such as respiratory depression, skeletal muscle flaccidity.

Phenylephrine

Bradycardia, cerebral hemorrhage, seizures, headache, hypertension, short paroxysms of ventricular tachycardia, ventricular premature beats, vomiting.

Promethazine

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; (ataxia; athetosis; seizures; dry mouth; extensor-plantar reflexes; fixed dilated pupils; flushing; GI symptoms; hyperreflexia; hypertonia).

Patient Information

• Advise patient to take prescribed dose every 4 to 6 h as needed.
• 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 not to double the dose to catch up.
• Advise patient that if allergy symptoms are not controlled, not to increase the dose of medication but to inform health care provider.
• Caution patient that medication may cause sensitivity to sunlight and to avoid unnecessary exposure to ultraviolet (UV) light (eg, sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light until tolerance is determined.
• 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 against taking the medication for at least 6 days before the skin testing.
• Instruct patient to stop taking drug and immediately report any of the following symptoms to health care provider: abnormal muscle movements, unusual sensitivity to sunlight, nervousness, dizziness, excessive drowsiness.

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