This article is about combination drugs and polypills as treatments. For two synergistic drugs chemically linked together, seecodrug. For use of multiple separate and individual drugs for treatment, seepolypharmacy.
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Fixed-dose combination drugs were initially developed to target a single disease, as withantiretroviral FDCsindicated for treatingAIDS andHIV.[4] Combination drug treatment conceptually emphasizes simplified treatment plans, reducedpill burden and increasedpatient compliance by offeringaccessible and affordable ingredients, generallygeneric drugs with established therapeutic efficacy, and the ability to treat a variety of symptoms and conditions amongst a large patient population with varying treatment needs.
The combination drugs listed below are universallyavailable by prescription only, but specific circumstances regarding a given combination's legal accessibility, or any specific regulation pertinent to ingredient quality, quantities, production standards, sourcing, etc. will vary by jurisdictions, and include:[5]
Temaril-P combinesalimemazine (antitussive) andprednisolone (antipruritic), approved for use in dogs,generic drug since 2024, and substitutes alimemazine fortrimeprazine, leaving in place prednisolone, equivalent to branded formula in efficacy
Several fixed-dose combination drugs marketed in the mid-20th century were later withdrawn due to safety concerns, changing regulatory standards, or abuse potential. Notable examples include:
Dexamyl – a combination of dextroamphetamine and amobarbital, used as a stimulant-sedative preparation, withdrawn in the early 1980s.
Tuinal – a combination of two barbiturates, amobarbital and secobarbital, prescribed as a sedative and hypnotic; it became notable both for medical use and recreational abuse. * Ethobral by Wyeth combined secobarbital,butabarbital, and phenobarbital[32][33]
Anox (Anox Diacels) – a triple barbiturate plus stimulant combination (phenobarbital, butabarbital, secobarbital, with methamphetamine and dextroamphetamine), reflecting the mid-century trend of “upper-lower” formulations.[34]
Fenfluramine/phentermine (fen-phen) – an appetite suppressant combination withdrawn in 1997 after reports of cardiac valve toxicity.[35]
Mandrax and Durophet – a combination ofmethaqualone and diphenhydramine, widely used recreationally in South Africa until 1993.
Obetrol and Biphetamine –mixed amphetamine salts used historically for obesity and attention disorders.
Eskatrol – combined dextroamphetamine with prochlorperazine, historically prescribed for appetite suppression.
These examples illustrate a period when pharmaceutical companies marketed combination drugs to address multiple therapeutic effects simultaneously, often combining stimulants and sedatives in the same formulation. Many such products were eventually withdrawn due to safety, abuse potential, or evolving regulatory standards.[43][44]
Fixed-dose combination drugs are used to simplify treatment regimens by delivering multiple active ingredients in a single dosage form. This approach may reduce pill burden, improve medication adherence, and enhance convenience for patients with chronic conditions, though combination products also have limitations. The fixed ratio of ingredients may restrict dose adjustment for individual components, and contraindication to one constituent may preclude use of the entire product. Formulation can also present technical challenges, including compatibility, stability, and dissolution differences among active ingredients and excipients.[45]
Outside regulated pharmaceutical products, some illicit drugs are distributed or consumed as mixtures of multiple psychoactive substances. Examples include cocaine adulterated with levamisole, counterfeit opioid tablets containing fentanyl or other synthetic opioids, and “Mandrax,” a preparation combining methaqualone and diphenhydramine. Such products are not standardized and may contain unpredictable quantities of their components. The veterinary anthelminticlevamisole has been widely detected as an adulterant in cocaine supplies and has been associated with serious adverse effects such as agranulocytosis and vasculitis.[46]
^https://www.ebi.ac.uk/chebi/searchId.do?chebiId=8461 "The anti-emetic action of both the hydrochloride and the teoclate (8-chlorotheophylline) salts is used for the prevention of nausea in cases of motion sickness and post-operative vomiting."
^"Index to Volume V"(PDF).Journal of J.J. Group of Hospitals and Grant.5 (N/A). Editorial Board of the Journal of J.J. Group of Hospitals & Grant Medical College: 94. 1960. RetrievedJune 26, 2025.
^Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 368
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