PRANOK

Promethazine, originally known as 3,277 R.P., is an N-dimethylaminopropyl derivative of phenothiazine that was developed in France in 1946.

Promethazine antagonizes a variety of receptors, allowing it to be used for a number of indications including allergic reactions, pain, sedation, nausea, and vomiting. 2, 8, 9, 7, 10 Promethazine was granted FDA approval before 29 March 1951. 11, 12.

Promethazine tablets and suppositories are indicated to treat rhinitis, allergic conjunctivitis, allergic reactions to blood or plasma, dermographism, anaphylactic reactions, sedation, nausea, vomiting, pain, motion sickness, and allergic skin reactions. 2, 12 Promethazine cough syrup with phenylephrine and codeine is indicated to relieve cough and upper respiratory symptoms, and nasal congestion associated with allergy or the common cold.

Promethazine is is a histamine

H1 antagonist that can be used for it's ability to induce sedation, reduce pain, and treat allergic reactions.

Promethazine's effects generally last 4-6h but can last up to 12h.

Patients should be counselled regarding

CNS and respiratory depression, reduce seizure threshold, and bone marrow depression.

H1 receptor Antagonist D dopamine receptor Antagonist Muscarinic acetylcholine receptor M1 Antagonist + 11 more targets.

A 25 mg dose of intramuscular promethazine reaches a C max of 22ng/mL.

Intravenous promethazine reaches a

C max of 10.0ng/mL, with a T max of 4-10h, and an AUC of 14,466ng*h/mL.

Oral promethazine is only 25% bioavailable due to first pass metabolism.

Oral promethazine reaches a

C max of 2.4-18.0ng/mL, with a T max of 1.5-3h, and an AUC of 11,511ng*h/mL.

The volume of distribution of promethazine is approximately 970 L or 30 L/kg.

Promethazine is predominantly metabolized to promethazine sulfoxide, and minorly to desmethylpromethazine and a hydroxy metabolite. 3, 4 Hydroxylation of promethazine is predominantly mediated by CYP2D6.

Hover over products below to view reaction partners Promethazine Promethazine Sulphoxide Desmethylpromethazine Promethazine Hydroxy Metabolite.

An intravenous dose of promethazine is 0.64% eliminated in the urine as the unchanged parent drug, 0.02-2.02% in the urine as desmethylpromethazine, 10% in the urine as promethazine sulfoxide.

The elimination half life of promethazine is approximately 12-15h.

The intravenous clearance of promethazine is approximately 1.14 L/min.

The renal clearance of promethazine is 5.9 mL/min and the renal clearance of promethazine sulfoxide is 90.4 mL/min.

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The intraperitoneal

LD in rats is 170 mg/kg and in mice is 160 mg/kg.

The subcutaneous

LD in rats is 400 mg/kg and in mice is 240 mg/kg.

The oral

LD in mice is 255 mg/kg.

Patients experiencing an overdose of promethazine may present with mild central nervous system and cardiovascular depression, hypotension, respiratory depression, unconciousness, hyperreflexia, hypertonia, ataxia, athetosis, extensor-plantar reflexes, convulsions, dry mouth, flushing, gastrointestinal symptoms, and fixed, dilated pupils.

Treat overdoses with symptomatic and supportive treatment, which may include activated charcoal, sodium sulfate, magnesium sulfate, controlled ventilation, diazepam, intravenous fluids, vasopressors, norepinephrine, phenylephrine, anticholinergic antiparkinsonian agents, diphenhydramine, barbiturates, or oxygen.

HCl SUPPOSITORIES SHOULD NOT BE USED IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE BECAUSE OF THE POTENTIAL FOR FATAL RESPIRATORY DEPRESSION.

DEPRESSION, INCLUDING FATALITIES, HAVE BEEN REPORTED WITH USE OF PROMETHAZINE HCl SUPPOSITORIES IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE.

A WIDE RANGE OF WEIGHT-BASED DOSES OF PROMETHAZINE HCl SUPPOSITORIES HAVE RESULTED IN RESPIRATORY DEPRESSION IN THESE PATIENTS.

CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE HCl TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER.

IT IS RECOMMENDED THAT THE LOWEST EFFECTIVE DOSE OF PROMETHAZINE HCl BE USED IN PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER AND CONCOMITANT ADMINISTRATION OF OTHER DRUGS WITH RESPIRATORY DEPRESSANT EFFECTS BE AVOIDED.

• Promethazine HCl Suppositories 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.

• Promethazine HCl Suppositories may lead to potentially fatal respiratory depression.

Suppositories in patients with compromised respiratory function (e.g., COPD, sleep apnea) should be avoided.

• Promethazine HCl Suppositories 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.

• Promethazine HCl Suppositories 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.

• 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 PROMETHAZINE HCl SUPPOSITORIES ARE CONTRAINDICATED FOR THE USE IN PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE.

CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE HCl SUPPOSITORIES TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER BECAUSE OF THE POTENTIAL FOR FATAL RESPIRATORY DEPRESSION.

APNEA, SOMETIMES ASSOCIATED WITH DEATH, ARE STRONGLY ASSOCIATED WITH PROMETHAZINE PRODUCTS AND ARE NOT DIRECTLY RELATED TO INDIVIDUALIZED WEIGHT-BASED DOSING, WHICH MIGHT OTHERWISE PERMIT SAFE ADMINISTRATION.

CONCOMITANT ADMINISTRATION OF PROMETHAZINE PRODUCTS WITH OTHER RESPIRATORY DEPRESSANTS HAS AN ASSOCIATION WITH RESPIRATORY DEPRESSION, AND SOMETIMES DEATH, IN PEDIATRIC PATIENTS.

ANTIEMETICS ARE NOT RECOMMENDED FOR TREATMENT OF UNCOMPLICATED VOMITING IN PEDIATRIC PATIENTS, AND THEIR USE SHOULD BE LIMITED TO PROLONGED VOMITING OF KNOWN ETIOLOGY.

THE EXTRAPYRAMIDAL SYMPTOMS WHICH CAN OCCUR SECONDARY TO PROMETHAZINE HCl SUPPOSITORIES ADMINISTRATION MAY BE CONFUSED WITH THE CNS SIGNS OF UNDIAGNOSED PRIMARY DISEASE, e.g., ENCEPHALOPATHY OR REYE'S SYNDROME.

THE USE OF PROMETHAZINE HCl SUPPOSITORIES SHOULD BE AVOIDED IN PEDIATRIC PATIENTS WHOSE SIGNS AND SYMPTOMS MAY SUGGEST REYE'S SYNDROME OR OTHER HEPATIC DISEASES.

Excessively large dosages of antihistamines, including Promethazine HCl Suppositories, in pediatric patients may cause sudden death.

Hallucinations and convulsions have occurred with therapeutic doses and overdoses of promethazine HCl 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.

• Administration of promethazine HCl has been associated with reported cholestatic jaundice.

Suppositories are contraindicated for use in pediatric patients less than two years of age.

Suppositories are 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 are contraindicated for use in the treatment of lower respiratory tract symptoms including asthma.

Suppositories are contraindicated for children under 2 years of age See WARNINGS - Black Box Warning and Use in Pediatric Patients.

Suppositories are for rectal administration only.

• The average dose is 25 mg taken before retiring; however, 12.5 mg may be taken before meals and on retiring, if necessary.

Single 25 mg doses at bedtime or 6.25 to 12.5 mg taken three times daily will usually suffice.

After initiation of treatment in children or adults, dosage should be adjusted to the smallest amount adequate to relieve symptoms.

The administration of promethazine hydrochloride in 25 mg doses will control minor transfusion reactions of an allergic nature.

• The average adult dose is 25 mg taken twice daily.

The initial dose should be taken one-half to one hour before anticipated travel and be repeated to 12 hours later, if necessary.

On succeeding days of travel, it is recommended that 25 mg be given on arising and again before the evening meal.

For children, Promethazine HCl Rectal Suppositories, 12.5 to 25 mg, twice daily, may be administered.

Nausea and

• Antiemetics should not be used in vomiting of unknown etiology in children and adolescents See WARNINGS - Use In Pediatric Patients.

The average effective dose of promethazine

HCl for the active therapy of nausea and vomiting in children or adults is 25 mg; 12.5 to 25 mg doses may be repeated, as necessary, at to 6 hour intervals.

For nausea and vomiting in children, the usual dose is 0.5 mg per pound of body weight, and the dose should be adjusted to the age and weight of the patient and the severity of the condition being treated.

For prophylaxis of nausea and vomiting, as during surgery and the postoperative period, the average dose is 25 mg repeated at to 6 hour intervals, as necessary.

• This product relieves apprehension and induces a quiet sleep from which the patient can be easily aroused.

Administration of 12.5 to 25 mg Promethazine HCl by rectal suppository at bedtime will provide sedation in children.

Adults usually require to 50 mg for nighttime, presurgical, or obstetrical sedation.

• Promethazine HCl in 12.5 to 25 mg doses for children and 50 mg doses for adults the night before surgery relieves apprehension and produces a quiet sleep.

For preoperative medication, children require doses of 0.5 mg per pound of body weight in combination with an appropriately reduced dose of narcotic or barbiturate and the appropriate dose of an atropine-like drug.

Usual adult dosage is 50 mg promethazine HCl with an appropriately reduced dose of narcotic or barbiturate and the required amount of a belladonna alkaloid.

Postoperative sedation and adjunctive use with analgesics may be obtained by the administration of 12.5 to 25 mg in children and to 50 mg doses in adults.

Suppositories are not recommended for children under 2 years of age.

USP, are available as follows: Promethazine HCl Suppositories USP, 12.5 mg carton of 12 suppositories (NDC 45802 - 758 -30) Promethazine HCl Suppositories USP, 25 mg carton of 12 suppositories (NDC 45802 - 759 -30).

Store refrigerated between 2°-8°C (36°-46°F).

Dispense in well-closed container.

Teratogenic effects have not been demonstrated in rat-feeding studies at doses of 6.25 and 12.5 mg/kg of promethazine.

These doses are from approximately 2.1 to 4.2 times the maximum recommended total daily dose of promethazine for a 50-kg subject, depending upon the indication for which the drug is prescribed.

Daily doses of 25 mg/kg intraperitoneally have been found to produce fetal mortality in rats.

Specific studies to test the action of the drug on parturition, lactation, and development of the animal neonate were not done, but a general preliminary study in rats indicated no effect on these parameters.

Although antihistamines have been found to produce fetal mortality in rodents, the pharmacological effects of histamine in the rodent do not parallel those in man.

There are no adequate and well-controlled studies of Promethazine HCl Suppositories in pregnant women.

Suppositories should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Promethazine HCl Suppositories administered to a pregnant woman within two weeks of delivery may inhibit platelet aggregation in the newborn.

It is not known whether promethazine

HCl is excreted in human milk.

Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Promethazine HCl Suppositories, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

PROMETHAZINE HCl SUPPOSITORIES ARE CONTRAINDICATED FOR USE IN PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE See WARNINGS - Black Box Warning and Use in Pediatric Patients.

Suppositories should be used with caution in pediatric patients 2 years of age and older See WARNINGS - Use in Pediatric Patients.

Clinical studies of promethazine formulations did not include sufficient numbers of subjects aged and over to determine whether they respond differently from younger subjects.

Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Sedating drugs may cause confusion and over-sedation in the elderly; elderly patients generally should be started on low doses of Promethazine HCl Suppositories and observed closely.