Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers. The development of longer-acting H2 receptor antagonists with fewer drug interactions and adverse effects, such as ranitidine and famotidine, decreased the use of cimetidine, and though it is still used, cimetidine is no longer among the more widely used of the H2 receptor antagonists. Cimetidine was developed in 1971 and came into commercial use in 1977. Cimetidine was approved in the United Kingdom in 1976, and was approved in the United States by the Food and Drug Administration for prescriptions in 1979. Medical uses Cimetidine is used to inhibit stomach acid production and is used in the treatment of heartburn and peptic ulcers. Other uses Some evidence suggests cimetidine could be effective in the treatment of common warts, but more rigorous double-blind clinical trials found it to be no more effective than a placebo. Tentative evidence supports a beneficial role as add-on therapy in colorectal cancer. Cimetidine inhibits ALA synthase activity and hence may have some therapeutic value in preventing and treating acute porphyria attacks. There is some evidence supporting the use of Cimetidine in the treatment of PFAPA. Side effects Reported side effects of cimetidine include diarrhea, rashes, dizziness, fatigue, constipation, and muscle pain, all of which are usually mild and transient. It has been reported that mental confusion may occur in the elderly. Because of its hormonal effects, cimetidine rarely may cause sexual dysfunction including loss of libido and erectile dysfunction and gynecomastia (0.1–0.2%) in males during long-term treatment. Rarely, interstitial nephritis, urticaria, and angioedema have been reported with cimetidine treatment. Cimetidine is also commonly associated with transient raised aminotransferase activity; hepatotoxicity is rare. Overdose Cimetidine appears to be very safe in overdose, producing no symptoms even with massive overdoses (e.g., 20 g). Interactions Due to its non-selective inhibition of cytochrome P450 enzymes, cimetidine has numerous drug interactions. Examples of specific interactions include the following: Cimetidine affects the metabolism of methadone, sometimes resulting in higher blood levels and a higher incidence of side effects, and may interact with the antimalarial medication hydroxychloroquine. Cimetidine can also interact with a number of psychoactive medications, including tricyclic antidepressants and selective serotonin reuptake inhibitors, causing increased blood levels of these drugs and the potential of subsequent toxicity. Following administration of