Usage
Cyproheptadine is primarily prescribed for the symptomatic relief of various allergic conditions such as seasonal and perennial allergic rhinitis, vasomotor rhinitis, allergic conjunctivitis, uncomplicated allergic skin manifestations of urticaria and angioedema, and amelioration of allergic reactions to blood or plasma. It is also used to treat cold urticaria and dermatographism. Off-label uses include migraine prophylaxis, appetite stimulation (particularly in anorexia nervosa or cachexia related to chronic diseases like cancer), and management of serotonin syndrome.
It is pharmacologically classified as a first-generation antihistamine, with additional antiserotonergic, anticholinergic, and sedative properties.
Cyproheptadine’s mechanism of action involves competitive antagonism at histamine H1 receptors and serotonin 5-HT2 receptors. This dual action helps alleviate allergy symptoms and provides additional benefits in certain conditions involving serotonin dysregulation.
Alternate Names
Cyproheptadine hydrochloride is the chemical name. A popular brand name under which it is marketed is Periactin®.
How It Works
Pharmacodynamics: Cyproheptadine exerts its therapeutic effects by binding to and blocking H1 histamine receptors and 5-HT2 serotonin receptors. This inhibits the actions of histamine and serotonin, reducing allergy symptoms like itching, sneezing, runny nose, and watery eyes. The antiserotonergic activity also contributes to its effectiveness in migraine prophylaxis and appetite stimulation. The anticholinergic effects can lead to side effects like dry mouth, blurred vision, and constipation.
Pharmacokinetics: Cyproheptadine is well-absorbed after oral administration. It undergoes extensive first-pass metabolism in the liver, primarily through CYP enzymes. The drug and its metabolites are eliminated mainly through renal excretion, with a smaller fraction excreted in the feces. Elimination is reduced in patients with renal impairment.
Mode of Action: Cyproheptadine functions as a competitive antagonist at H1 and 5-HT2 receptors. This competitive binding prevents histamine and serotonin from binding to these receptors and triggering their downstream effects.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Cyproheptadine primarily binds to H1 histamine receptors and 5-HT2 serotonin receptors. There is no significant inhibition of specific enzymes or modulation of other neurotransmitters directly. The anticholinergic effects may be due to indirect effects or non-specific binding to muscarinic receptors.
Elimination Pathways: Primarily renal excretion of metabolites. A small fraction is excreted in the feces.
Dosage
Standard Dosage
Adults:
- Allergic conditions: Initial dose: 4 mg orally three times a day. Maintenance dose: 4-20 mg/day orally, in divided doses. Maximum dose: 32 mg/day or 0.5 mg/kg/day, whichever is less.
- Migraine prophylaxis: 2-4 mg orally twice daily.
Children:
- Allergic conditions: 2-6 years: 2 mg orally two or three times a day (maximum: 12 mg/day). 7-14 years: 4 mg orally two or three times a day (maximum: 16 mg/day). Alternatively, 0.25 mg/kg/day or 8 mg/m²/day in divided doses.
- Migraine Prophylaxis: >3 years and adolescents: 0.2-0.4 mg/kg/day orally divided BID (maximum: 0.5 mg/kg/day)
Special Cases:
- Elderly Patients: Start with a lower dose (e.g., 4 mg twice daily) and titrate cautiously due to increased risk of adverse effects.
- Patients with Renal Impairment: Reduce dosage and monitor closely.
- Patients with Hepatic Dysfunction: Reduce dosage and monitor closely.
- Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease, hyperthyroidism, or bronchial asthma.
Clinical Use Cases
Cyproheptadine is not typically indicated for use in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations (except for off-label use in serotonin syndrome).
Dosage Adjustments
Dosage adjustments are based on patient response, age, renal and hepatic function, and concomitant medications. Close monitoring is recommended, especially in elderly patients and those with renal or hepatic impairment.
Side Effects
Common Side Effects:
Drowsiness, dizziness, dry mouth, blurred vision, constipation, and fatigue.
Rare but Serious Side Effects:
Confusion, hallucinations, tremors, seizures, difficulty urinating, fast or irregular heartbeats, easy bruising or bleeding, and jaundice.
Long-Term Effects:
Chronic complications from prolonged use are rare, but potential blood dyscrasias (e.g., leukopenia, thrombocytopenia) may occur.
Adverse Drug Reactions (ADR):
Any signs of hypersensitivity (e.g., rash, angioedema, difficulty breathing) should be treated as a medical emergency. Serotonin syndrome (when used in high doses or with interacting drugs) can also occur.
Contraindications
- Hypersensitivity to cyproheptadine
- Narrow-angle glaucoma
- Stenosing peptic ulcer, pyloroduodenal obstruction
- Symptomatic prostatic hypertrophy, bladder neck obstruction
- Concurrent use of MAOIs
- Newborn or premature infants
- Elderly, debilitated patients (relative contraindication)
- Acute asthma attack
Drug Interactions
Cyproheptadine interacts with numerous medications, including:
- MAOIs: Contraindicated due to the risk of serotonin syndrome.
- CNS depressants: Additive sedative effects.
- Anticholinergics: Increased anticholinergic effects.
- CYP450 inhibitors/inducers: May affect cyproheptadine metabolism.
Interactions can also occur with alcohol and other substances. Always review a patient’s medication list for potential interactions.
Pregnancy and Breastfeeding
- Pregnancy: Pregnancy Category B. While animal studies have not shown fetal harm, human studies are limited. Use only if clearly needed and after careful risk-benefit assessment.
- Breastfeeding: Contraindicated. Cyproheptadine is excreted in breast milk and can potentially cause adverse effects in infants.
Drug Profile Summary
- Mechanism of Action: H1 and 5-HT2 receptor antagonist.
- Side Effects: Drowsiness, dizziness, dry mouth, blurred vision, constipation; rarely, seizures, blood dyscrasias.
- Contraindications: Hypersensitivity, glaucoma, bladder/prostate obstruction, MAOI use, newborns/premature infants, breastfeeding.
- Drug Interactions: MAOIs, CNS depressants, anticholinergics.
- Pregnancy & Breastfeeding: Use with caution in pregnancy; contraindicated during breastfeeding.
- Dosage: See detailed dosage guidelines above.
- Monitoring Parameters: Observe for adverse effects, particularly in elderly patients and those with renal/hepatic impairment.
Popular Combinations
Cyproheptadine is not typically used in combination with other drugs for its primary indications.
Precautions
Screen patients for relevant contraindications and drug interactions. Use cautiously in patients with cardiovascular disease, hyperthyroidism, or bronchial asthma. Avoid activities requiring mental alertness while taking cyproheptadine.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cyproheptadine?
A: See detailed dosage guidelines above.
Q2: Can Cyproheptadine be used in children?
A: Yes, but with careful dosing adjustments based on age and weight. It is not recommended for children under 2 years old.
Q3: What are the most common side effects of Cyproheptadine?
A: Drowsiness, dizziness, dry mouth, blurred vision, and constipation.
Q4: Is Cyproheptadine safe during pregnancy?
A: Pregnancy Category B; use only if clearly needed.
Q5: Can Cyproheptadine be used while breastfeeding?
A: No, it is contraindicated during breastfeeding.
Q6: What are the serious side effects to watch out for with Cyproheptadine?
A: Confusion, hallucinations, seizures, difficulty urinating, and cardiac arrhythmias.
Q7: Does Cyproheptadine interact with other medications?
A: Yes, significant interactions can occur with MAOIs, CNS depressants, and anticholinergic drugs.
Q8: How does Cyproheptadine help with migraine prophylaxis?
A: Its antiserotonergic properties are thought to contribute to its effectiveness in migraine prophylaxis.
Q9: Can Cyproheptadine be used to stimulate appetite?
A: Yes, it is sometimes used off-label for appetite stimulation in conditions like anorexia nervosa.
