Combination drug
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Fixed-dose combination
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A combination drug is an
hormones may also be included for the maximum treatment potential. Either ingredient may be an over-the-counter drug or a prescription drug, and some combination drugs include additional synthetic pharmaceutical drugs or hormones, while others may balance pharmaceuticals with naturally-occurring, plant-based alkaloids or herbal extract
.
Fixed-dose combination drugs were initially developed to target a single disease, as with
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.
A polypill is a
essential minerals.[4]
Current prescription combination drugs
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]
- brand name Triavil
- amitriptyline and chlordiazepoxide (benzodiazepine), Limbitrol-H, available in the United States, India,[6][7][8] and Bangladesh
- amlodipine (calcium channel blocker) and benazepril (ACE inhibitor), Lotrel
- amlodipine and atorvastatin (statin), Conduet
- amlodipine and celecoxib (nonsteroidal anti-inflammatory drug), Consensai
- amlodipine and lisinopril (ACE inhibitor), Lisonorm
- amlodipine and olmesartan (ACE inhibitor), Azor
- amlodipine and valsartan (ACE inhibitor), Exforge
- Shire Pharmaceuticals, MyDayis with slightly varying formulation
- Contrave
- butalbital (barbiturate, CNS depressant) and caffeine (eugeroic), Butapap
- butalbital, caffeine, and aspirin (NSAID), Fiorinal
- butalbital, caffeine, and Fioricet
- butalbital, caffeine, acetaminophen, and codeine (opioid), Fioricet with Codeine
- chlordiazepoxide (benzodiazepine) and clidinium bromide (anticholinergic), Librax[9][10]
- sympathomimetic) and ethylmorphine (opioid) Lephotan
- flupentixol (typical antipsychotic) and melitracen (tricyclic antidepressant), available outside of the U.S. as Deanxit by Lundbeck
- hydrocodone and aspirin, Azdone
- hydrocodone and expectorant), Obedron, Flowtuss
- hydrocodone and ibuprofen (nonsteroidal anti-inflammatory]])NSAID), Ibudone
- ibuprofen and acetaminophen
- antiviral) and ritonavir (antiviral), combination drug for treatment and management of COVID-19), Paxlovid[14]
- olanzapine (atypical antipsychotic) and fluoxetine (selective serotonin reuptake inhibitor), Symbyax
- Percocet
- oxycodone and aspirin, Percodan
- oxycodone and ibuprofen (nonsteroidal anti-flammatory), Combunol
- tramadol and paracetamol, Ultram
Combination drugs accessible over the counter (OTC)
Fixed-dose combination drugs for sale
over the counter exist around the world, constituting doses that are tolerable to a mainstream consumer population. In the United States, items containing ephedrine, pseudoephedrine, or phenylpropanolamine can be purchased without a prescription, albeit under strict oversight and from behind the pharmacy counter, per the U.S. Federal drug law titled the Combat Methamphetamine Epidemic Act of 2005.[17]
Fixed-dose combination drugs for sale
over the counter
internationally, including medicine indicated for various purposes:
- aspirin and caffeine, Anacin by Bayer, tablet widely available since 1916[18]
- chlorpheniramine (sympathomimetic), marketed as Vernate Injection by Tutag Pharmaceuticals, a liquid solution for intramuscular injection;[19][20][21] available as the tablet Tri-Nefrin, and a syrup elixirAltec Syrup, all available in Asia, all discontinued in U.S. by 2007.
- Coricidin by 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]
- fenproporex and diazepam, Esbelcaps available in Central and South America[26]
- GlaxoSmithKline
- glucose, fructose and phosphoric acid, Emetrol for Nausea
- ibuprofen and famotidine (proton pump inhibitor), Duexis[27]
- ibuprofen and diphenhydramine Advil PM
- Claritin-D by AstraZeneca
- naproxen sodium and pseudoephedrine, Aleve-D
- Aventis, available in dosage forms including tablet, tincture, elixir and suppository, oxomemazine and guaifenesin, approved and available in France, Algeria, and Morocco[29]
- 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
Combination drugs under development
- Phase II clinical trials[30] for treatment of post-traumatic stress disorder.
Combinations drugs for veterinary use
- Temaril-P combines trimeprazine, leaving in place prednisolone, equivalent to branded formula in efficacy
- Titzeol combines rhinoceroses[31]
Combination drugs no longer widely available
- Acutran by G.W. Carnrick Laboratories is composed of amfecloral, a compound molecule pairing dextroamphetamine sulfate and chloral hydrate,[32] discontinued 1973[33]
- Ambar by Wyeth Pharmaceuticals combined methamphetamine hydrochloride and phenobarbital; Ambar Extentab was the extended-release formulation
- Amphaplex 10 by Laderle Laboratories (later acquired by Wyeth) combined 2.5 mg methamphetamine saccharate, 2.5 mg methamphetamine hydrochloride, and 5 mg racemic amphetamine sulfate; Amphaplex 20 combined 5 mg methamphetamine saccharate, 5 mg methamphetamine hydrochloride, and 10 mg racemic amphetamine sulfate.[34]
- Amplus Now by Roehrig Laboratories combined 5 mg dextroamphetamine sulfate with 5 mg hydroxyzine (first-generation antihistamine)[35][36]
- Amvicel by Roehrig Laboratories combined 10 mg dextroamphetamine, 40 mg essential minerals[37]
- Apamead by Laderle Laboratories combined dextroamphetamine sulfate, amobarbital, aspirin, and phenacetin (racetin)
- ANOX by Winston Pharmaceuticals,encapsulated polypill combining a fixed dose of three barbiturate salts (20 mg each of phenobarbital, butabarbital, and secobarbital) and two amphetamine salts (7.5 mg each of methamphetamine hydrochloride and dextroamphetamine sulfate)[38]
- Anxine by Behlen Manufacturing[39][40] combined 120 mg mephenesin (muscle relaxant), 35 mg cyclobarbital, and 2.5 mg dextroamphetamine sulfate
- Bama-Dex by Behlen Manufacturing combined 5 mg dextroamphetamine and 400 mg meprobamate[41]
- Biphetamine T-12.5' and Biphetamine T-20 by 1:1, equally-proportioned ratio (racemic) proptionate ratio of the stereoisomers dextroamphetamine and levoamphetamine.
- Bontril Timed No. 1 combined 2.5 mg dextroamphetamine and 7.5 mg butabarbital; Bontril Timed No. 2 5 mg dexamphetamine and 15 mg butabarbital; Bontril Timed No. 3 10 mg dexamphetamine and 30 mg butabarbital; Bontril Timed No. 4 15 mg dexamphetamine with 60 mg butabarbital, all manufactured and marketed by G.W. Carnrick Laboratories.[42]
- Delcobese by Lemmon Drug Company was a balanced combination of racemic amphetamine sulfate and adipate, "withdrawn voluntarily in 1984, unrelated to safety or legal concerns"[43]
- doing business as Neisler Labs, 5 mg methamphetamine and 30 mg pentobarbital, discontinued 1973[33]
Open market of dextroamphetamine and amylbarbitone tablets
- Dexytal by Eli Lilly, combination dextroamphetamine and amobarbital elixir;
- GlaxoSmith Kline), discontinued 1982
- Daprisal by GSK, dextroamphetamine, amobarbital, and aspirin as a tablet
Irwin, Neisler & Co. (D/B/A Neisler Laboratories), now a division of Union Carbide
- Durophet (racemic amphetamine salts) became pyrilamine tannate (first-generation antihistamine), and "10 mg Tanphetamin (racemic amphetamine tannate) [also by Neisler]""General Practice American Academy(20)". 1959.
- Direcel combination dextroamphetamine, butabarbital, carboxymethylcellulose
- DuoDex, combination .
- Dysonil combined methamphetamine, pentobarbital, and salicylamide (analgesic)
Wyeth Pharmaceuticals (now Pfizer)=
- Edrisal by Wyeth, combined 160 mg aspirin, 160 mg phenacetin, 2.5 mg amphetamine sulfate; Edrisal with Codeine included an additional 16 mg codeine[citation needed]
- Ethobral by Wyeth, Triple-Barbiturate Tablets
- Eskatrol by Smith, French & Kline combined dextroamphetamine and prochlorperazine (first-generation antipsychotic, discontinued 1981
- Euphoramin, 5 mg methamphetamine and 300 mg meprobamate, Euphoramin
- Lamital by Teva Pharmaceuticals combines acetaminophen, amobarbital, and methamphetamine
- Mandrax by Lemmon Drug Company, tablet comprising first-generation antihistamine), available in South Africauntil 1993
- Mediatric by vitamin c, b vitamins, and 1 mg methamphetamine
- NalerTan by Neisler combined 12.5 mg dextroamphetamine
- dextroamphetamine, amobarbital, nutritional supplements, brandedNexorin
- Obocell by Neisler combined 5 mg dextroamphetamine phosphate and 25 mg methapyrilene phosphate (antihistamine); Obocell-TF was identical in composition with the addition of a high-viscosity methylcellulose supplement, also by Neisler and listed as "160 mg Nitrin on the label)[49]
- (s) isomerof racemic amphetamine.
- Obolip combined dextroamphetamine, phenobarbital, choline, dimethionine, and methylcellulose
- Phelantin by Parke-Davis combined 100 mg phenytoin (anticonvulsant), 32 mg pentobarbital, and 2.5 mg methamphetamine[50]
- Phenephen by A.H. Robins combined hyoscyamine sulfate, phenacetin, and aspirin; Phenephen with Codeine was the aforementioned formula with codeine as a fourth active ingredient
- Pondimin, better known as "fen-phen," a colloquialism for combination fenfluramine and phentermine, discontinued 1997[51]
- SynaTan-S by Neisler (later acquired by Mallinckrodt and re-branded OboTan-S)[52][53][54]) combined 10 mg dextroamphetamine tannate with 35 mg secobarbital[55]
- Pre M.T.[pyrilamine maleate with a microdose of theobromine
- Reladorm combined 100 mg
- 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.[57]
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.
amphetamine derivative or analog; the tranquilizing component was either one or more barbiturate salts, or non-barbiturate GABAergic drugs (e.g. meprobamate, methaqualone) with a similar mechanism of action, with tranquilizing, muscle relaxant, and sedating
effects.
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
Monoamine Oxidase Inhibitors (MAOIs) in patients with treatment-resistant depression
where MAOI treatment is appropriate, but where the MAOI-related dietary restrictions would otherwise hinder patient compliance.
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.[59] For prescribers, if one constituent of the combination is contraindicated for a patient, the product cannot be prescribed.[60][61]
Limitations of currently-available combinations
The limitations of combination formulations currently available for treating a widely-inclusive collection of symptoms such as Tourette's is highlighted by there not being a
psychostimulants to both treat ADHD and counteract the sleep inertia
, grogginess or hangover caused by the other evening medications).
ADHD, as well as insomnia, depression, and traits of high-functioning autism (formerly "Asperger syndrome
").
Illicit "street" drug combinations
So-called "powder cocaine" often contains
synthetic cathinones, MDMA, methamphetamine, caffeine, and increasingly the flesh-eating veterinary antibiotic levamisole have been found in "powder cocaine."[64]
Since the forced closure of so many
Other
U.S. Attorney General Pam Bondi stated a desire to regulate xylazine under U.S. federal drug law) as a Schedule III controlled substance.[69] Xylazine is currently a controlled substance under state statutes in Michigan and New York.[70]
Mandrax is the trade name of a pharmaceutical combination drug consisting of methaqualone and diphenhydramine.,[71] once prescribed in South Africa, but banned in 1993. "Mandrax" is now synthesized via clandestine chemistry as a free base preparation, which is smoked for an intense, short-lived "high".[72]
See also
References
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External links
Media related to Combination drugs at Wikimedia Commons
