This article is about combination drugs and polypills as treatments. For two synergistic drugs chemically linked together, see codrug. For use of multiple separate and individual drugs for treatment, see polypharmacy.
Fixed-dose combination drugs were initially developed to target a single disease, as with antiretroviral FDCsindicated for treating AIDS and HIV.[4] Combination drug treatment conceptually emphasizes simplified treatment plans, reduced pill burden and increased patient compliance by offering accessible and affordable ingredients, generally generic 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 universally available 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]
hydrocodonebitartrate (opioid agonist, tablet) and acetaminophen, Vicodin by AbbVie contains 325mg acetaminophen as a tablet, currently the only brand form in the United States. Norco is a tablet containing 300mg acetaminophen, with limited availability in select countries.[11]LorTab by UCB is now solely available as a syrup in the U.S.[12]
Coricidin by Bayer, a line of cough medicine combining chlorpheniramine and dextromethorphan; chlorpheniramine, dextromethorphan, guaifenesin, and acetaminophen is Coricidin Cold + Cough; chlorpheniramine, phenylephrine, guaifenesin, and acetaminophen is Coricidin HBP High Blood Pressure[22]
aspirin, caffeine, and acetaminophen, Excedrin by Bayer[23]
Robitussin, a line of cough medicine encompassing various combinations including dextromethorphan, acetaminophen, chlorpheniramine, doxylamine succinate, and/or guaifenesin.
guaifenesin and phenylephrine, Sudafed PE by Merck
Temaril-P combines alimemazine (antitussive) and prednisolone (antipruritic), approved for use in dogs, generic drug since 2024, and substitutes alimemazine for trimeprazine, leaving in place prednisolone, equivalent to branded formula in efficacy
Organized according to the pharmaceutical manufacturer..
Abbott
Obetrol by Abbott Laboratories was a mixture of methamphetamine and dextroamphetamine salts, discontinued 1973,[32] later re-branded Oby-Rex, swapping methamphetamine for levoamphetamine, the (s) isomer of racemic amphetamine.
Tuinal by AbbVie was a capsule containing amobarbital and secobarbital (double barbiturate); voluntarily discontinued by AbbVie in 2008, citing widespread substance abuse as well as declining sales due to a decrease in prescriptions, and thus, demand.[33]
Bontril Timed No. 1 combined 2.5mg dextroamphetamine and 7.5mg butabarbital
Bontril Timed No. 2 5mg dexamphetamine and 15mg butabarbital
Bontril Timed No. 3 10mg dexamphetamine and 30mg butabarbital
Bontril Timed No. 4 15mg dexamphetamine with 60mg butabarbital.[39]
Lemmon (defunct)
Delcobese, racemic amphetamine molecule with each enantiomer bonded to sulfate and adipate, "withdrawn voluntarily in 1984, unrelated to safety or legal concerns"[40]
Daprisal tablet combined dextroamphetamine, amobarbital, and aspirin
Dexamyl tablet combined dextroamphetamine and amobarbital, discontinued 1982
Mallinkcrodt (previously Irwin, Neisler & Co.)
Durophet was a racemic mixture of amphetamine salts combining combined 12.5mg amphetamine and 400mg methaqualone (sedative-hypnotic), discontinued 1984
Durabond, tablet combining 8mg chlorpheniramine tannate (first-generation antihistamine/FGA), 25mg pyrilamine tannate (first-generation antihistamine), and "10 mg Tanphetamin (racemic amphetamine tannate)" "General Practice American Academy(20)". 1959.
Obocell combined 5mg dextroamphetamine phosphate and 25mg methapyrilene phosphate (antihistamine); Obocell-TF was identical in composition with the addition of a high-viscosity methylcellulose supplement, also by Neisler and listed as "160mg Nitrin on the label)[43]
OboTan-S: formerly SynaTan-S[44][45][46]) combined 10mg dextroamphetamine tannate with 35mg secobarbital[47]
Obolip combined dextroamphetamine, phenobarbital, choline, dimethionine, and methylcellulose
Euphoramin, 5mg methamphetamine and 300mg meprobamate (non-barbiturate, barbiturate-adjacent GABergic minor tranquilizer
Dysonil combined methamphetamine, pentobarbital, and salicylamide (analgesic)
DuoDex, combination barbaloin (laxative),[48] dextroamphetamine (stimulant), pentobarbital (barbiturate), thyroid (hormone); The U.S. FDA declared in May 2002 that "aloin-containing laxatives are no longer GRAS [nor] effective for OTC use" upon the IARC classifying whole-leaf herbal extracts of aloe vera as "possibly carcinogenic to humans" due to presence of latex.
Biphetamine by R.J. Strausenburgh (1964-66), by Fisons (1966-79) (inscribed RJS) containing equal parts dextroamphetamine and levoamphetamine. Later acquired by Fisons, then R.P. Rorer and rebranded Biphetamine-T[58][59][60][61]
Teva Pharmaceuticals
Lamital combined acetaminophen, amobarbital, and methamphetamine
Winston Pharmaceuticals
ANOXcapsulepolypill combining a fixed dose of three barbiturate salts (20mg each of phenobarbital, butabarbital, and secobarbital) and two amphetamine salts (7.5mg each of methamphetamine hydrochloride and dextroamphetamine sulfate)[62]
Medical use and justification of discontinued combination drugs
Most of the combination drugs which have been discontinued since the twentieth century were simultaneously indicated and utilized for treatment of various conditions, with medical use justified as part of a multifaceted, comprehensive approach to patient health care and medical treatment. Substituted amphetamines (stimulants) simultaneously functioned as appetite suppressant, antidepressant, and eugeroic agents, also increasing mental alertness and concentration and physical stamina, while a GABAergic depressant (e.g. a barbiturate, benzodiazepine, antipsychotic, or quinazolone) offered tranquilizing, muscle relaxant, sedative properties to ease overstimulation, paranoia, anxiety without eliminating the stimulant's therapeutic benefits. Patients are empowered with the capability of alleviating symptoms of multiple medical conditions with the ingestion of a single dosage form, reducing the patient's pill burden and consistently showing improved medication compliance scores. The American Association of Orthodontists asserts that fixed-dose combinations "limit clinicians' ability to customize dosing regimens."[63]
Scientists formulating combination drugs face challenges in the development stages of multi-drug formulations such as compatibility issues among active ingredients and excipients affecting solubility and dissolution.[64] For prescribers, if one constituent of the combination is contraindicated for a patient, the product cannot be prescribed.[65][66]
Limitations of polypharmacy for multi-faceted disorders
Example with Tourette Syndrome (tics and excessive motor activity, anxieties, ADHD, autism, etc.)
The limitations of combination formulations currently available for treating the large number of overlapping neurological symptoms inherent to most neurological conditions is a hindrance to properly treating disruptive, concurrent symptoms. Tourette's is a stellar example of this dilemma, because the minimum diagnostic criteria is habitual, repeated physical movements, muscle spasms, the compulsive need to repeat motions and succumb to the premonitory urge to release perform needless, disruptive central nervous system] motor activity ("motor tics").
↑ 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."
↑ 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
↑ "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. Retrieved June 26, 2025.
↑ https://pmc.ncbi.nlm.nih.gov/articles/PMC7289498/ National Institutes of Health -- Premonitory Urge phenomenon as a related to the compulsion to tic in obsessive-compulsive anxiety stemming from Tourette's
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