INTAMINE ELIXIR

Indications

• Allergic reactions
• Motion sickness
• Nausea and vomiting
• Sedation
• Anxiety and tension

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing guidelines.

Adults: Refer to the BNF for detailed dosing recommendations based on specific indications.

Mechanism of action

Promethazine acts as an antagonist of histamine H1 receptors, as well as post-synaptic mesolimbic dopamine, alpha adrenergic, muscarinic, and NMDA receptors. This broad receptor antagonism contributes to its effectiveness in treating allergic reactions, inducing sedation, and managing nausea and vomiting. While it does not block the release of histamine, it mitigates the effects of histamine at the receptor level, resulting in its therapeutic benefits.

Pharmacodynamics

Promethazine's antihistaminic effects result in the induction of sedation and reduction of pain, with a typical duration of action ranging from 4 to 6 hours, although effects can last up to 12 hours. The drug can cause CNS and respiratory depression, reduce seizure threshold, and may lead to bone marrow depression. Due to its sedative properties, caution is advised regarding activities requiring alertness.

Pharmacokinetics

Promethazine is well absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is extensively metabolized in the liver, primarily by CYP450 enzymes, and has a half-life of approximately 10 to 19 hours. The drug is primarily excreted in urine as metabolites, with minimal unchanged drug excreted. The pharmacokinetics may vary between individuals based on factors such as age and hepatic function.

Contra-indications

• Hypersensitivity to promethazine or any component of the formulation
• Children under 2 years of age
• Severe respiratory depression

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Blurred vision
• Constipation
• Tachycardia
• Hypotension
• Extrapyramidal symptoms
• Severe allergic reactions (e.g., anaphylaxis)

Interactions

• CNS depressants may enhance the sedative effects of promethazine
• Monoamine oxidase inhibitors (MAOIs) may increase the effects of promethazine
• Anticholinergic drugs may have additive effects
• Antihypertensive agents may have their effects potentiated by promethazine

Precautions

• Use with caution in patients with cardiovascular disease
• Caution in patients with a history of seizures
• Avoid use in patients with glaucoma
• Use with caution in elderly patients due to increased sensitivity to sedative effects

Pregnancy

Promethazine is classified as category C. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Promethazine is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place, protect from light. Keep out of reach of children.

Formulations

• Tablets: 10 mg, 25 mg
• Syrup: 5 mg/5 mL
• Injection: 25 mg/mL

Mechanism of action

Promethazine is a an antagonist of histamine H1, post-synaptic mesolimbic dopamine, alpha adrenergic, muscarinic, and NMDA receptors. The antihistamine action is used to treat allergic reactions. Antagonism of muscarinic and NMDA receptors contribute to its use as a sleep aid, as well as for anxiety and tension. Antagonism of histamine H1, muscarinic, and dopamine receptors in the medullary vomiting center make promethazine useful in the treatment of nausea and vomiting. Promethazine is a phenothiazine derivative with potent sedative properties. Although the drug can produce either CNS stimulation or CNS depression, CNS depression manifested by sedation is more common with therapeutic doses of promethazine. The precise mechanism of the CNS effects of the drug is not known. Although it has been reported that the drug has slight antitussive activity, this may result from its anticholinergic and CNS depressant effects. In therapeutic doses, promethazine appears to have no substantial effect on the cardiovascular system. Although rapid IV administration of promethazine may produce a transient fall in blood pressure, blood pressure usually is maintained or slightly elevated when the drug is given slowly. Promethazine hydrochloride is a phenothiazine derivative which possesses antihistaminic, sedative, antimotion-sickness, antiemetic, and anticholinergic effects. Promethazine is a competitive H1 receptor antagonist, but does not block the release of histamine. Structural differences from the neuroleptic phenothiazines result in its relative lack (1/10 that of chlorpromazine) of dopamine antagonist properties. The development of phenothiazine derivatives as psychopharmacologic agents resulted from the observation that certain phenothiazine antihistaminic compounds produced sedation. In an attempt to enhance the sedative effects of these drugs, promethazine and chlorpromazine were synthesized. Chlorpromazine is the pharmacologic prototype of the phenothiazines. The pharmacology of phenothiazines is complex, and because of their actions on the central and autonomic nervous systems, the drugs affect many different sites in the body. Although the actions of the various phenothiazines are generally similar, these drugs differ both quantitatively and qualitatively in the extent to which they produce specific pharmacologic effects. /Phenothiazine General Statement/ For more Mechanism of Action (Complete) data for Promethazine (18 total), please visit the HSDB record page.

Pharmacodynamics

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.