Promethazine

Name: Promethazine

Promethazine Overview

Promethazine is a prescription medication used to treat allergic reactions and nausea. Promethazine belongs to a group of drugs called antihistamines. It blocks the effect of histamine, a chemical in the body that causes symptoms of allergic reactions. Promethazine also belongs to another group of drugs called antiemetics, which reduce feelings of nausea.

Promethazine comes as a tablet, oral solution (liquid), rectal suppository, and a liquid to be injected into a muscle.  It is usually taken once daily at bedtime or before meals every six to twelve hours as needed to relieve symptoms of allergy or nausea. 

Common side effects of promethazine include blurred vision, and dry mouth. It can also cause dizziness and drowsiness. Do not drive or operate heavy machinery until you know how promethazine affects you. Limit alcoholic beverages.  

Promethazine Brand Names

Promethazine may be found in some form under the following brand names:

  • Adgan

  • M-Phen

  • Mepergan

  • Mepergan Fortis

  • Meprozine

  • Pentazine

  • Phenadoz

  • Phenergan

  • Phenergan Fortis

  • Phenergan VC

  • Phenergan VC with Codeine

  • Phenergan with Codeine

  • Phenergan with Dextromethorphan

  • Phenerzine

  • Pro-Med

  • Promacot

  • Promethegan

  • Prorex

Promethazine and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy.  Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy. Promethazine falls into category C.  Studies in animals have shown a harmful and undesired effect on the unborn baby, yet there are no adequate and well-controlled studies in pregnant women.  This medication may be given to a pregnant woman if her healthcare provider believes that its benefits to the pregnant woman outweigh any possible risks to her unborn baby.

Precautions

General

Drugs having anticholinergic properties should be used with caution in patients with narrow-angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, and bladder-neck obstruction. Promethazine should be used cautiously in persons with cardiovascular disease or with impairment of liver function.

Information for Patients

Promethazine may cause marked drowsiness or impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. The use of alcohol or other central-nervous-system depressants such as sedatives/ hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers, may enhance impairment (see WARNINGS - CNS Depressionand PRECAUTIONS - Drug Interactions). Pediatric patients should be supervised to avoid potential harm in bike riding or in other hazardous activities.

Patients should be advised to report any involuntary muscle movements.

Avoid prolonged exposure to the sun.

Drug Interactions

CNS Depressants-Promethazine may increase, prolong, or intensify the sedative action 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 be avoided or administered in reduced dosage to patients receiving Promethazine HCl. When given concomitantly with Promethazine Hydrochloride Oral Solution, the dose of barbiturates should be reduced by at least one-half, and the dose of narcotics should be reduced by one-quarter to one-half. Dosage must be individualized. Excessive amounts of Promethazine HCl relative to a narcotic may lead to restlessness and motor hyperactivity in the patient with pain; these symptoms usually disappear with adequate control of the pain.

Epinephrine

Because of the potential for Promethazine to reverse epinephrine’s vasopressor effect, epinephrine should NOT be used to treat hypotension associated with Promethazine Hydrochloride Oral Solution overdose.

Anticholinergics

Concomitant use of other agents with anticholinergic properties should be undertaken with caution.

Monoamine Oxidase Inhibitors (MAOI)

Drug interactions, including an increased incidence of extrapyramidal effects, have been reported when some MAOI and phenothiazines are used concomitantly. This possibility should be considered with Promethazine Hydrochloride Oral Solution

Drug/Laboratory Test Interactions

The following laboratory tests may be affected in patients who are receiving therapy with Promethazine HCl:

Pregnancy Tests

Diagnostic pregnancy tests based on immunological reactions between HCG and anti-HCG may result in false-negative or false-positive interpretations.

Glucose Tolerance Test

An increase in blood glucose has been reported in patients receiving Promethazine.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to assess the carcinogenic potential of Promethazine, nor are there other animal or human data concerning carcinogenicity, mutagenicity, or impairment of fertility with this drug. Promethazine was nonmutagenic in the Salmonella test system of Ames.

Pregnancy

Teratogenic Effects- Pregnancy Category C

Pregnancy Category C Teratogenic effects have not been demonstrated in rat-feeding studies at doses of 6.25 and 12.5 mg/kg of Promethazine HCl. 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, including Promethazine, 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 in pregnant women.

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

Nonteratogenic Effects

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

Labor and Delivery

Promethazine HCl, may be used alone or as an adjunct to narcotic analgesics during labor (see "DOSAGE AND ADMINISTRATION"). Limited data suggest that use of Promethazine during labor and delivery does not have an appreciable effect on the duration of labor and delivery and does not increase the risk of need for intervention in the newborn. The effect on later growth and development of the newborn is unknown. (See also Nonteratogenic Effects.)

Nursing Mothers

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 Hydrochloride Oral Solution, 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.

Pediatric Use

Promethazine HYDROCHLORIDE ORAL SOLUTION IS CONTRAINDICATED FOR USE IN PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE (see WARNINGS - Black Box Warningand Use in Pediatric Patients ). Promethazine Hydrochloride Oral Solution should be used with caution in pediatric patients 2 years of age and older (see WARNINGS - Use in Pediatric Patients).

Geriatric Use

Clinical studies of Promethazine formulations did not include sufficient numbers of subjects aged 65 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 and observed closely

Pronunciation

(proe METH a zeen)

Pharmacologic Category

  • Antiemetic
  • Histamine H1 Antagonist
  • Histamine H1 Antagonist, First Generation
  • Phenothiazine Derivative

Pharmacology

Phenothiazine derivative; blocks postsynaptic mesolimbic dopaminergic receptors in the brain; exhibits a strong alpha-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones; competes with histamine for the H1-receptor; muscarinic-blocking effect may be responsible for antiemetic activity; reduces stimuli to the brainstem reticular system

Absorption

Oral: Rapid and complete; large first pass effect limits systemic bioavailability (Sharma, 2003)

Distribution

Vd: 13.4 ± 3.6 L/kg (Brunton 2011)

Metabolism

Hepatic; hydroxylation via CYP2D6 and N-demethylation via CYP2B6; significant first-pass effect (Sharma, 2003)

Excretion

Urine, feces as inactive metabolites

Test Interactions

Pregnancy tests (hCG-based) may result in false-negatives or false-positives; increased serum glucose may be seen with glucose tolerance tests; may result in false-positives with urine detection of amphetamine/methamphetamine (Melanson 2006); may alter the flare response in intradermal allergen tests (Melanson 2006)

ALERT U.S. Boxed Warning

Respiratory depression - Pediatrics:

Promethazine should not be used in pediatric patients younger than 2 years because of the potential for fatal respiratory depression.

Postmarketing cases of respiratory depression, including fatalities, have been reported with the use of promethazine in pediatric patients younger than 2 years. A wide range of weight-based doses of promethazine have resulted in respiratory depression in these patients.

Exercise caution when administering promethazine to pediatric patients 2 years and older. It is recommended that the lowest effective dose of promethazine be used in pediatric patients 2 years and older and that coadministration with other drugs with respiratory-depressant effects be avoided.

Severe tissue injury, including gangrene (injection):

Promethazine can cause severe chemical irritation and damage to tissues regardless of the route of administration. Irritation and damage can result from perivascular extravasation, unintentional intra-arterial injection, and intraneuronal or perineuronal infiltration. Adverse reactions include burning, pain, thrombophlebitis, tissue necrosis, and gangrene. In some cases, surgical intervention, including fasciotomy, skin graft, and/or amputation have been required.

Due to the risks of intravenous (IV) injection, the preferred route of administration of promethazine is deep intramuscular (IM) injection. Subcutaneous injection is contraindicated.

Pregnancy Risk Factor C Pregnancy Considerations

Adverse effects have not been observed in animal reproduction studies. Promethazine crosses the placenta (Potts 1961). Platelet aggregation may be inhibited in newborns following maternal use of promethazine within 2 weeks of delivery. Promethazine is approved for use as an antiemetic; however, other agents are recommended as initial therapy for the treatment of nausea and vomiting of pregnancy (ACOG 2015). Promethazine is indicated for use during labor for obstetric sedation and may be used alone or as an adjunct to opioid analgesics. Although promethazine is approved for the treatment of allergic conditions (eg, allergic rhinitis, urticaria), other agents are preferred for use in pregnant women (Scadding 2008; Wallace 2008; Zuberbier 2014).

(web3)