Promethazine

Promethazine Overview

Promethazine is an antihistamine that is used to alleviate symptoms of allergic reactions, control nausea and vomiting, as a sedative, and for preoperative and postoperative adjunctive therapy. It is available under various brand names and can be administered orally, rectally, or via injection.

Chemical Composition

Promethazine hydrochloride is the primary active ingredient, with the chemical name 10H-Phenothiazine-10-ethanamine, N,N,alpha-trimethyl-, monohydrochloride. Its molecular formula is C₁₇H₂₀N₂S·HCl with a molecular weight of 320.88.

Pharmacological Class

Promethazine belongs to the phenothiazine class of antihistaminic agents. It is not a curative agent but is used for symptomatic relief.

Therapeutic Indications

Indications for promethazine include allergy symptoms, motion sickness, nausea and vomiting prevention, sedation, and as an adjunct to analgesics for postoperative pain.

Pharmacodynamics

With H₁ receptor antagonism, promethazine prevents the action of histamine in the body, displaying pronounced sedative and antiemetic properties. Its effects may be evident within 20 minutes of administration and can last for up to 12 hours.

Pharmacokinetics Overview

Orally administered promethazine is well-absorbed from the gastrointestinal tract. It undergoes extensive first-pass metabolism and is metabolized in the liver, predominantly by the enzyme cytochrome P450. The half-life ranges between 16 to 19 hours and its metabolites are primarily excreted via urine.

Dosage Forms and Strengths

Promethazine is available in various formulations: oral tablets typically in 12.5 mg, 25 mg, and 50 mg strengths; oral syrup generally at 6.25 mg/5ml; rectal suppositories usually in 12.5 mg, 25 mg, and 50 mg; and injectable solutions often at 25 mg/ml and 50 mg/ml concentrations.

Dosing Information

Adult dosing varies by indication, typically starting with 12.5 mg to 25 mg orally or rectally before bedtime or every 4 to 6 hours for allergy symptoms. For preoperative sedation, a common dose is 25 mg to 50 mg. Specific dosing will depend on factors such as the patient’s age, weight, and clinical condition.

Pediatric Dosing

Pediatric doses are carefully calculated based on the child’s weight. Promethazine is not recommended for children under two years of age due to the risk of fatal respiratory depression.

Administration Guidelines

When taking orally, promethazine can be administered with or without food. If gastrointestinal upset occurs, taking it with food may mitigate discomfort. Suppositories should be stored in a refrigerator and allowed to warm to room temperature before use.

Contraindications

Patients with hypersensitivity to promethazine, other phenothiazines, or any component of the formulation should not use this medication. It is also contraindicated in comatose states, and in individuals with lower respiratory tract symptoms including asthma.

Drug Interactions

Promethazine can potentiate the effects of certain CNS depressants, such as alcohol, sedatives, and narcotics. It may also interact with MAO inhibitors leading to hypertensive crises or potentiate the anticholinergic effects when used with anticholinergic drugs.

Adverse Reactions

Common side effects include drowsiness, dizziness, dry mouth, blurred vision, or constipation. Rarer, more serious adverse reactions can include respiratory depression, seizure, agranulocytosis, and neuroleptic malignant syndrome.

Symptoms of Overdose

Overdose symptoms may include severe drowsiness, confusion, hallucinations, seizures, shallow breathing, and loss of consciousness. Immediate medical attention is necessary in the event of suspected overdose.

Storage Conditions

Promethazine should be stored at controlled room temperature, away from light and moisture. Oral tablets and liquid should not be stored in the bathroom, and all forms of the medication should be kept out of the reach of children and pets.

Monitoring Parameters

Patient response should be monitored, with particular attention to blood pressure, mental status, and signs of hypersensitivity. In cases of prolonged usage, complete blood counts and liver function tests may be recommended.

Counseling Points

Patients should be advised to avoid activities requiring mental alertness, such as driving or operating hazardous machinery, until they know how promethazine affects them. Consumption of alcohol should be avoided as it may increase the sedative effect of the drug.

Pregnancy and Lactation

Promethazine is classified under FDA pregnancy category C, indicating that risk cannot be ruled out. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution is advised when prescribing to nursing mothers due to the drug’s presence in breast milk.