Cyproheptadine also has been used to counter vascular headaches, which many believe are caused by changes in serotonin activity. It is unclear how cyproheptadine, a serotonin-receptor antagonist, exerts a beneficial effect on this condition, since sumatriptan, a newer agent specifically indicated for treating migraine, acts as an agonist at serotonin receptors. Peak concentration of cyproheptadine occurs in about 6-9 hours, and the duration of action is about 8 hours. Distribution of cyproheptadine has not been elucidated. Hepatic metabolism of cyproheptadine appears to be extensive, producing a number of metabolites that are conjugated primarily with glucuronic acid or sulfate.
Excretion is mainly renal, with no apparent excretion of unchanged drug.
Some unchanged drug and metabolites are excreted in feces. Cyproheptadine is relatively contraindicated in patients with asthma and COPD, especially during acute attacks, because anticholinergic actions can thicken secretions and reduce expectoration. Cyproheptadine is classified as pregnancy category B. Antihistamines generally are not recommended for use in pregnancy, especially during the third trimester, because there is a risk of seizures in the fetus. Risks-benefits should be considered during pregnancy and in women expecting to become pregnant. Cyproheptadine should be used cautiously in women who are breast-feeding because it can induce hyperexcitability in the infant, seizures in premature infants, and inhibited lactation in the mother.