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.
The combination of promethazine hydrochloride, phenylephrine hydrochloride and codeine phosphate is contraindicated in pediatric patients less than 16 years of age, because the combination may cause fatal respiratory depression in this age population.
Antihistamines and codeine are both contraindicated for use in the treatment of lower respiratory tract symptoms, including asthma.
Phenylephrine is contraindicated in patients with hypertension or with peripheral vascular insufficiency (ischemia may result with risk of gangrene or thrombosis of compromised vascular beds). Phenylephrine should not be used in patients known to be hypersensitive to the drug or in those receiving a monoamine oxidase inhibitor (MAOI).
Codeine:
Dosage of codeine SHOULD NOT BE INCREASED if cough fails to respond; an unresponsive cough should be reevaluated in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease.
Codeine may cause or aggravate constipation.
Respiratory depression leading to arrest, coma and death has occurred with the use of codeine antitussives in young children, particularly in the under-one-year infants whose ability to deactivate the drug is not fully developed.
Administration of codeine may be accompanied by histamine release and should be used with caution in atopic children.
Head Injury And Increased Intracranial Pressure: The respiratory-depressant effects of narcotic analgesics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, intracranial lesions, or a preexisting increase in intracranial pressure. Narcotics may produce adverse reactions which may obscure the clinical course of patients with head injuries.
Asthma And Other Respiratory Conditions: Narcotic analgesics or cough suppressants, including codeine, should not be used in asthmatic patients (see CONTRAINDICATIONS). Nor should they 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 secretions would have a deleterious effect on the patient’s respiratory function.
Hypotensive Effect: Codeine may produce orthostatic hypotension in ambulatory patients.
Promethazine:
CNS Depression – Promethazine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine HCl (see PRECAUTIONS-Information for Patients and Drug Interactions).
Respiratory Depression – Promethazine may lead to potentially fatal respiratory depression.
Use of Promethazine in patients with compromised respiratory function (e.g., COPD, sleep apnea) should be avoided.
Lower Seizure Threshold – Promethazine may lower seizure threshold. It should be used with caution in persons with seizure disorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, which may also affect seizure threshold.
Bone-Marrow Depression – Promethazine should be used with caution in patients with bone-marrow depression. Leukopenia and agranulocytosis have been reported, usually when promethazine HCl has been used in association with other known marrow-toxic agents.
Neuroleptic Malignant Syndrome – A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with promethazine HCl alone or in combination with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmias).
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g. pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.
The management of NMS should include 1) immediate discontinuation of promethazine HCl, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.
Since recurrences of NMS have been reported with phenothiazines, the reintroduction of promethazine HCl should be carefully considered.
Use In Pediatric Patients
THE COMBINATION OF PROMETHAZINE HYDROCHLORIDE, PHENYLEPHRINE HYDROCHLORIDE AND CODEINE PHOSPHATE IS CONTRAINDICATED IN PEDIATRIC PATIENTS LESS THAN 16 YEARS OF AGE. CONCOMITANT ADMINISTRATION OF PROMETHAZINE PRODUCTS WITH OTHER RESPIRATORY DEPRESSANTS HAS AN ASSOCIATION WITH RESPIRATORY DEPRESSION, AND SOMETIMES DEATH, IN PEDIATRIC PATIENTS. THE ASSOCIATION DOES NOT DIRECTLY RELATE TO INDIVIDUALIZED WEIGHT-BASED DOSING, WHICH MIGHT OTHERWISE PERMIT SAFE ADMINISTRATION.
Excessively large dosages of antihistamines, including promethazine hydrochloride, in pediatric patients may cause sudden death (see OVERDOSAGE). Hallucinations and convulsions have occurred with therapeutic doses and overdoses of promethazine hydrochloride in pediatric patients. In pediatric patients who are acutely ill associated with dehydration, there is an increased susceptibility to dystonias with the use of promethazine HCl.
Other Considerations
Administration of promethazine has been associated with reported cholestatic jaundice.
Phenylephrine:
Because phenylephrine is an adrenergic agent, it should be given with caution to patients with thyroid diseases, diabetes mellitus and heart diseases or those receiving tricyclic antidepressants.
Men with symptomatic, benign prostatic hypertrophy can experience urinary retention when given oral nasal decongestants.
Phenylephrine can cause a decrease in cardiac output, and extreme caution should be used when administering the drug parenterally or orally to patients with arteriosclerosis, to elderly individuals and/or to patients with initially poor cerebral or coronary circulation.
Phenylephrine should be used with caution in patients taking diet preparations, such as amphetamines or phenylpropanolamine, because synergistic adrenergic effects could result in serious hypertensive response and possible stroke.