A combination drug is a combination of two or more pharmaceutical

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

s as

active ingredients An active ingredient is any ingredient that provides biologically active or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the body of humans or animals. ...

combined into a single

dosage form Dosage forms (also called unit doses) are pharmaceutical drug products presented in a specific form for use. They contain a mixture of active ingredients and inactive components ( excipients), configured in a particular way (such as a capsule she ...

, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fixed-dose combinations are

mass-produced Mass production, also known as mass production, series production, series manufacture, or continuous production, is the production of substantial amounts of standardized products in a constant flow, including and especially on assembly lines. ...

and mass marketed, intended to serve as a near universal treatment for a large patient population with diverse medical histories, conditions, predisposition thereof, and treatment requirements. A '' polypill'' is a

pharmacy Pharmacy is the science and practice of discovering, producing, preparing, dispensing, reviewing and monitoring medications, aiming to ensure the safe, effective, and affordable use of medication, medicines. It is a miscellaneous science as it ...

or capsule containing four or more active ingredients, often needing to be compounded at a specialized pharmacy in order to satisfy the specifications of a patient's personalized prescription and treatment plan, including

, medicinal dosing, and/or mechanism of release. Polypills encompass

approved Approved may refer to: *Approved drug, a preparation that has been validated for a therapeutic use by a ruling authority of a government *''Approved'', a 2013 album by Chester Thompson Chester Thompson (born December 11, 1948) is an American dr ...

prescription drugs and

over the counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid pres ...

drugs, at times including

nutritional supplements A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources, or that are synthetic ( ...

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

vitamins Vitamins are organic molecules (or a set of closely related molecules called vitamers) that are essential to an organism in small quantities for proper metabolic function. Essential nutrients cannot be synthesized in the organism in suff ...

minerals In geology and mineralogy, a mineral or mineral species is, broadly speaking, a solid substance with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure form.John P. Rafferty, ed. (2011): M ...

, and

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

s. Fixed-dose combination drugs were initially developed to target a single disease, as with antiretroviral FDCs

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for treating

AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...

and

HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...

. Over time, the concept of combination drugs has come to include reducing

pill burden Polypharmacy (polypragmasia) is an umbrella term to describe the simultaneous use of multiple medicines by a patient for their conditions. The term polypharmacy is often defined as regularly taking five or more medicines but there is no standard ...

for patients, thereby encouraging

patient compliance In medicine, patient compliance (also adherence, capacitance) describes the degree to which a person correctly follows medical advice. Most commonly, it refers to medication or drug compliance, but it can also apply to other situations such as me ...

, and generally simplifying treatment plan with one product containing easily accessible (often available

without a prescription requirement), relatively affordable (often

generic drugs A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

) ingredients with established therapeutic efficacy and a broad capacity for treating a variety of symptoms and conditions, thus ensuring maximum appeal to a majority of patients amongst a large population with varying needs.

Current prescription combination drugs

The combination drugs listed below are typically 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: *

amitriptyline/perphenazine Amitriptyline/perphenazine (Duo-Vil, Etrafon, Triavil, Triptafen) is a formulation that contains the tricyclic antidepressant amitriptyline and the medium-potency typical (first-generation) antipsychotic, perphenazine. In the United States am ...

, brand

brand A brand is a name, term, design, symbol or any other feature that distinguishes one seller's goods or service from those of other sellers. Brands are used in business, marketing, and advertising for recognition and, importantly, to create and ...

Triavil *

amlodipine/benazepril Amlodipine/benazepril, sold under the brand name Lotrel among others, is a fixed-dose combination medication used to treat high blood pressure. It is a combination of amlodipine, as the besilate, a calcium channel blocker, and benazepril, an ...

: Lotrel *

amitriptyline/chlordiazepoxide Amitriptyline/chlordiazepoxide, sold under the brand names Limbitrol and Limbitrol DS, is a combination of amitriptyline (Elavil), a tricyclic antidepressant, and chlordiazepoxide (Librium), a benzodiazepine, which is approved for the treatme ...

Limbitrol in

India India, officially the Republic of India, is a country in South Asia. It is the List of countries and dependencies by area, seventh-largest country by area; the List of countries by population (United Nations), most populous country since ...

, Limbix (

Bangladesh Bangladesh, officially the People's Republic of Bangladesh, is a country in South Asia. It is the List of countries and dependencies by population, eighth-most populous country in the world and among the List of countries and dependencies by ...

) * amlodipine/atorvastatin brand Conduet * Amlodipine/celecoxib: brand Consensai * amlodipine/olmesartan: brand Azor * amlodipine/valsartan: brand Exforge * bupropion/naltrexone, 450 mg

bupropion Bupropion, formerly called amfebutamone, and sold under the brand name Wellbutrin among others, is an atypical antidepressant that is indicated in the treatment of major depressive disorder, seasonal affective disorder, and to support smo ...

hydrochloride and

naltrexone Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol use or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been ...

, brand Contrave * butalbital/acetaminophen, brand Butapap *

butalbital Butalbital is a barbiturate with an intermediate duration of action. Butalbital is often combined with other medications, such as paracetamol (acetaminophen) (as butalbital/acetaminophen) or aspirin, for the treatment of pain and headache. The ...

and

caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class and is the most commonly consumed Psychoactive drug, psychoactive substance globally. It is mainly used for its eugeroic (wakefulness pr ...

, branded Fioricet * butalbital combined with

aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...

and caffeine, branded Fiorinal * butalbital, caffeine, acetaminophen, and

codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...

: Fioricet with Codeine *

chlordiazepoxide Chlordiazepoxide hydrochloride, sold under the brand name Librium is a sedative and hypnotic medication of the benzodiazepine class. It is used to treat anxiety, insomnia and symptoms of withdrawal from alcohol, benzodiazepines, and other drug ...

combined with

clidinium bromide Clidinium bromide (INN) is an anticholinergic (specifically a muscarinic antagonist) drug. It may help symptoms of cramping and abdominal/stomach pain by decreasing stomach acid, and slowing the intestines. It is commonly prescribed in combinati ...

: * ephedrine/ethylmorphine: Lephotan * lisinopril/amlodipine: Lisonorm' * lisinopril/hydrochlorothiazide: Zestorenic * Paxlovid: combination of nirmatrelvir and

ritonavir Ritonavir, sold under the brand name Norvir, is an antiretroviral medication used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhi ...

for

treatment and management of COVID-19 The treatment and management of COVID-19 combines both supportive care, which includes treatment to relieve symptoms, fluid therapy, oxygen support as needed, and a growing list of approved medications. Highly effective vaccines have reduced ...

. * hydrocodone/acetaminophen, common brands Norco and Vicodin * Deanxit by

Lundbeck H. Lundbeck A/S, commonly referred to as Lundbeck, is a Denmark, Danish international pharmaceutical company engaged in the research, development, manufacturing, marketing and sale of pharmaceuticals across the world. The company’s products ar ...

, available in India and Bangladesh: combination of flupentixol and melitracen * hydrocodone/aspirin: Azdone * hydrocodone/guaifenesin: Obedron * hydrocodone/ibuprofen: Ibudone * omeprazole/amoxicillin/rifabutin, brand Talicia * olanzapine/fluoxetine, branded Symbyax * oxycodone/acetaminophen, common brand

Percocet Oxycodone/paracetamol, sold under the brand name Percocet among others, is a fixed-dose combination of the opioid oxycodone with paracetamol (acetaminophen), used to treat moderate to severe pain. In 2022, it was the 98th most commonly presc ...

* oxycodone/aspirin:

Percodan Oxycodone/aspirin (trade name Percodan) is a combination drug marketed by Endo Pharmaceuticals. It is a tablet containing a mixture of 325 mg (5 Grain (unit), grains) of aspirin and 4.8355 mg of oxycodone, oxycodone HCl (equivalent t ...

* oxycodone/ibuprofen: Combunol *

phentermine/topiramate Phentermine/topiramate, sold under the brand name Qsymia, is a combination drug of phentermine and topiramate used to treat obesity. It is used together with dietary changes and exercise. If less than 3% weight loss is seen after 3 months it i ...

, under patent as Qsymia: combination of 37.5 mg

phentermine Phentermine, sold under the brand name Adipex-P among others, is a medication used together with diet and exercise to treat obesity. It is available by itself or as the combination phentermine/topiramate. Phentermine is taken by mouth. Com ...

hydrochloride and 150 mg

topiramate Topiramate, sold under the brand name Topamax among others, is a medication used to treat epilepsy and prevent migraines. It has also been used for alcohol dependence and essential tremor. For epilepsy, this includes treatment for generali ...

* phenylephrine/ketorolac brand

Omidria Phenylephrine/ketorolac, sold under the brand name Omidria, is a combination drug used during cataract surgery or intraocular lens replacement to prevent intraoperative miosis and to reduce postoperative pain. It contains phenylephrine and keto ...

Amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

mixed salts of the

racemic In chemistry, a racemic mixture or racemate () is a mixture that has equal amounts (50:50) of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as r ...

: dextroamphetamine

sulfate The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...

, dextroamphetamine saccharate,

levoamphetamine Levoamphetamine is a stimulant medication which is used in the treatment of certain medical conditions. It was previously marketed by itself under the brand name Cydril, but is now available only in combination drug, combination with dextroam ...

aspartate Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. The L-isomer of aspartic acid is one of the 22 proteinogenic amino acids, i.e., the building blocks of protein ...

monohydrate In chemistry, a hydrate is a substance that contains water or its constituent elements. The chemical state of the water varies widely between different classes of hydrates, some of which were so labeled before their chemical structure was understo ...

, levoamphetaminee sulfate, commonly Adderall and Mydayis * pseudoephedrine/carbinoxamine, Rondec syrup

Combination drugs accessible over the counter (OTC)

Fixed-dose combination drugs for sale

(OTC) exist around the world, constituting doses that are tolerable to a mainstream consumer population. In the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

, items containing

ephedrine Ephedrine is a central nervous system (CNS) stimulant and sympathomimetic agent that is often used to prevent hypotension, low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred ...

pseudoephedrine Pseudoephedrine, sold under the brand name Sudafed among others, is a sympathomimetic medication which is used as a decongestant to treat nasal congestion. It has also been used off-label for certain other indications, like treatment of lo ...

, or

phenylpropanolamine Phenylpropanolamine (PPA), sold under many brand names, is a sympathomimetic agent used as a decongestant and appetite suppressant. It was once common in prescription and over-the-counter cough and cold preparations. The medication is taken ...

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. Fixed-dose combination drugs for sale

internationally, including medicine indicated for various purposes: * Bayer

Anacin Anacin is an American brand of analgesic that is manufactured by Prestige Consumer Healthcare. Anacin's active ingredients are aspirin and caffeine. History Anacin was invented by William Milton Knight and was first to be used as stated in the ...

pill Pill or The Pill may refer to: Drugs * Pill (pharmacy), referring to anything small for a specific dose of medicine * "The Pill", a general nickname for the combined oral contraceptive pill Film and television * ''The Pill'' (film), a 2011 fil ...

available since 1916, constituting 400 mg

and 32 mg

. * Bayer

Coricidin Coricidin, Coricidin 'D' (decongestant), or Coricidin HBP (for high blood pressure), is the name of an over-the-counter cough and cold combination drug containing dextromethorphan (a cough suppressant) and chlorpheniramine maleate (a first-genera ...

: a product line sold OTC combinations at least 2 mg of an antihistamine (

chlorpheniramine Chlorphenamine (CP, CPM), also known as chlorpheniramine, is an antihistamine used to treat the symptoms of allergic conditions such as allergic rhinitis (hay fever). It is taken orally (by mouth). The medication takes effect within two hour ...

dextromethorphan Dextromethorphan, sold under the brand name Robitussin among others, is a cough suppressant used in many cough and Common cold, cold medicines. In 2022, the US Food and Drug Administration (FDA) approved the combination dextromethorphan/bupropi ...

hydrobromide: **Coricidin Cold + Cough: antihistamine chlorpheniramine combined with 200 mg

guaifenesin Guaifenesin, also known as glyceryl guaiacolate, sold under the brand name Mucinex, among others, is an expectorant medication taken by mouth and marketed as an aid to eliminate sputum from the respiratory tract. Chemically, it is an ether of ...

(

expectorant Mucoactive agents are a class of pharmacologic agents that include expectorants, mucolytics, mucoregulators, and mucokinetics that can affect the volume, viscosity, transportation, and composition of mucus or sputum. They often aid in clearing ...

) and acetaminophen; and **Coricidin High Blood Pressure is a combination of chlorpheniramine, guaifenisin or phenylephrine, 325 mg. *

diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...

+ 8-chlorotheophylline produces

dimenhydrinate Dimenhydrinate, also known as diphenhydramine/8-chlorotheophylline salt and sold under the brand names Dramamine and Gravol, among others, is an over-the-counter medication used to treat motion sickness and nausea. Dimenhydrinate is a theocl ...

, generally branded Dramamine.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." * fexofenadine/pseudoephedrine by

GlaxoSmithKline GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...

: combination of 12 mg

fexofenadine Fexofenadine, sold under the brand name Allegra among others, is an antihistamine medication used in the treatment of allergy symptoms such as allergic rhinitis and urticaria. Therapeutically, fexofenadine is a selective peripheral H1 blocke ...

and 120 mg

hydrochloride, Allegra-D * glucose/fructose/phosphoric acid, Emetrol for Nausea: combines

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

with

fructose Fructose (), or fruit sugar, is a Ketose, ketonic monosaccharide, simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and gal ...

and

phosphoric acid Phosphoric acid (orthophosphoric acid, monophosphoric acid or phosphoric(V) acid) is a colorless, odorless phosphorus-containing solid, and inorganic compound with the chemical formula . It is commonly encountered as an 85% aqueous solution, ...

aspirin/paracetamol/caffeine Aspirin/paracetamol/caffeine is a combination drug for the treatment of pain, especially tension headache and migraine. It contains aspirin, a non-steroidal anti-inflammatory drug; paracetamol (acetaminophen), an analgesic; and caffeine, a st ...

(primary brand Excedrin) b: product line combining 250 mg aspirin, 400 mg acetaminophen, and 35 mg caffeine * ibuprofen/famotidine: combination of

ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...

and

famotidine Famotidine, sold under the brand name Pepcid among others, is a histamine H2 receptor antagonist medication that decreases stomach acid production. It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–E ...

, brand Duexis. * ibuprofen/diphenhydramine: combination of 400 mg

with 25 mg diphenhydramine

citrate Citric acid is an organic compound with the formula . It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry Biochemistry, or biological chemistry, is the study of chemical processes within and relati ...

Advil PM * loratadine/pseudoephedrine: combination of 10 mg

loratadine Loratadine, sold under the brand name Claritin among others, is a medication used to treat allergies. This includes allergic rhinitis (hay fever) and hives. It is also available in drug combinations such as loratadine/pseudoephedrine, in whic ...

and pseudoephedrine hydrochloride, Claritin-D * naproxen/diphenhydramine by Bayer: combination of 220 mg

naproxen Naproxen, sold under the brand name Aleve among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, and inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It ...

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

and 25 mg diphenhydramine hydrochloride * naproxen/pseudoephedrine (branded Aleve-D): 220 mg

naproxen sodium Naproxen, sold under the brand name Aleve among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, and inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It is ...

and 120 mg

hydrochloride * oxomemazine/guaifenesin (primarily branded Toplexil by

Aventis Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. The corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Synthélabo merg ...

): most frequently taken orally in liquid syrup

, but generically is also available in

suppository A suppository is a dosage form used to deliver pharmaceutical drug, medications by insertion into a body orifice (any opening in the body), where it dissolves or melts to exert local or systemic effects. There are three types of suppositories, eac ...

and pill

s. Aventis' fixed-dose preparation, Toplexil, constitutes oxomemazine exactified to a dose of 1.65 mg/5ml and guaifenesin exactified to 33.3 mg/5ml. Utilized in

France France, officially the French Republic, is a country located primarily in Western Europe. Overseas France, Its overseas regions and territories include French Guiana in South America, Saint Pierre and Miquelon in the Atlantic Ocean#North Atlan ...

Algeria Algeria, officially the People's Democratic Republic of Algeria, is a country in the Maghreb region of North Africa. It is bordered to Algeria–Tunisia border, the northeast by Tunisia; to Algeria–Libya border, the east by Libya; to Alger ...

Morocco Morocco, officially the Kingdom of Morocco, is a country in the Maghreb region of North Africa. It has coastlines on the Mediterranean Sea to the north and the Atlantic Ocean to the west, and has land borders with Algeria to Algeria–Morocc ...

, oxomemazine itself has never been

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

- approved for medical use in the

. * Robitussin: a product line of

cough medicine Cold medicines are a group of medications taken individually or in combination as a treatment for the symptoms of the common cold and similar conditions of the upper respiratory tract. The term encompasses a broad array of drugs, including a ...

s containing the

antitussive Cold medicines are a group of medications taken individually or in combination as a treatment for the symptoms of the common cold and similar conditions of the upper respiratory tract. The term encompasses a broad array of drugs, including ana ...

/cough suppressant,

; antipyretic analgesic acetaminophen/paracetamol; either the antihistamine chlorpheniramine maleate, or doxylamine succinate; and the expectorant/mucus thinner, guaifenesin. * Sudafed PE: combination of 300 mg

and 50mg

phenylephrine Phenylephrine, sold under the brand names Neosynephrine and Sudafed PE among others, is a medication used as a decongestant for uncomplicated nasal congestion in the form of a nasal spray or oral tablet, to dilate the pupil, to increase bloo ...

hydrochloride * Tylenol PM by

Johnson & Johnson Johnson & Johnson (J&J) is an American multinational pharmaceutical, biotechnology, and medical technologies corporation headquartered in New Brunswick, New Jersey, and publicly traded on the New York Stock Exchange. Its common stock is a c ...

: combination of 500 mg acetaminophen and 25 mg diphenhydramine * Vernate by Tutag Pharmaceuticals is an injectable

elixir An elixir is a sweet liquid used for medical purposes, to be taken orally and intended to cure one's illness. When used as a dosage form, pharmaceutical preparation, an elixir contains at least one active ingredient designed to be taken orall ...

or liquid: 8mg

maleate Maleic acid or ''cis''-butenedioic acid is an organic compound that is a dicarboxylic acid, a molecule with two carboxyl groups. Its chemical formula is HO2CCH=CHCO2H. Maleic acid is the ''cis'' isomer of butenedioic acid, whereas fumaric acid ...

and 50 mg

per serving. * Tri-Nefrin for tablet forms; Altec Syrup (primary brand name for liquid

tincture A tincture is typically an extract of plant or animal material dissolved in ethanol (ethyl alcohol). Solvent concentrations of 25–60% are common, but may run as high as 90%.Groot Handboek Geneeskrachtige Planten by Geert Verhelst In chemistr ...

formulation) available in Asia * Vernate Liquid, injectable liquid formulation by Tutag Pharmaceuticals

Combination drugs under development, not yet approved for medical use

* MDMA/citalopram: an

empathogen Entactogens, also known as empathogens or connectogens, are a class of psychoactive drugs that induce the production of experiences of emotional communion, oneness, connectedness, emotional openness—that is, empathy—as particularly observe ...

called "Ecstasy" combined with

citalopram Citalopram, sold under the brand name Celexa among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive compulsive disorder, panic disorder, and soci ...

(

SSRI Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by ...

); currently under development in FDA Phase II clinical trials.

Combinations drugs for veterinary use

* Temaril-P: alimemazine and

prednisolone Prednisolone is a corticosteroid, a steroid hormone used to treat certain types of allergies, inflammation, inflammatory conditions, autoimmune disorders, and cancers, Electrolyte imbalance, electrolyte imbalances and skin conditions. Some of ...

; indicated as

and

antipruritic Antipruritics, abirritants, or anti-itch drugs, are medications that inhibit itching (Latin: ''pruritus''). Itching is often associated with sunburns, allergic reactions, eczema, psoriasis, chickenpox, Fungal infection in animals, fungal infections ...

in dogs, generic since 2024. The generic alternative to the brand version substitutes alimemazine with

trimeprazine Alimemazine (INN), also known as trimeprazine, commonly provided as a tartrate salt, is a phenothiazine derivative that is used as an antipruritic (it prevents itching from causes such as eczema or poison ivy, by acting as an antihistamine). It ...

, but is otherwise identical in terms of formulation and efficacy. * Titzeol: combination of

tiletamine Tiletamine is a dissociative anesthetic and pharmacologically classified as an NMDA receptor antagonist. It is related chemically to ketamine. Tiletamine hydrochloride exists as odorless white crystals. It is used in veterinary medicine in th ...

and

zolazepam Zolazepam (Flupyrazapon) is a pyrazolodiazepinone derivative structurally related to the benzodiazepine drugs, which is used as an anaesthetic for a wide range of animals in veterinary medicine. Zolazepam is usually administered in combination wi ...

both major tranquilizers, intended to sedate large animals

Combination drugs no longer widely available

* Acutran by G.W. Carnrick Laboratories:

amfecloral Amfecloral (INN) or amphecloral (USAN) is a combination drug containing a central nervous system (CNS) stimulant and anorectic drug, dextroamphetamine, as well as a CNS depressant and sedative-hypnotic, chloral hydrate. Widely used for its a ...

, a chemical compound constituting

dextroamphetamine Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...

and

chloral hydrate Chloral hydrate is a geminal diol with the formula . It was first used as a sedative and hypnotic in Germany in the 1870s. Over time it was replaced by safer and more effective alternatives but it remained in use in the United States until at ...

, discontinued 1973 * Ambar by

Wyeth Wyeth Pharmaceuticals Inc. was a pharmaceutical company until it was purchased by Pfizer in 2009. The company was founded in Philadelphia, Pennsylvania, in 1860 as John Wyeth and Brother. Its headquarters moved to Collegeville, Pennsylvania, a ...

: combination of

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

hydrochloride In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternati ...

and

phenobarbital Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ...

sodium; Ambar Extentab is the extended-release formulation * Amphaplex 10 and Amphaplex 20 by Laderle Laboratories: combination of 2.5 mg methamphetamine saccharate, 2.5 mg methamphetamine

, 2.5 mg

sulfate, and 2.5 mg dextroamphetamine sulfate; the latter comprised 20 mg in aggregate: combining 5 mg methamphetamine saccharate, 5 mg methamphetamine hydrochloride, 5 mg

sulfate, and 5 mg dextroamphetamine sulfate. * Amplus Now by Roehrig Laboratories, Inc.–combined 5 mg dextroamphetamine sulfate and 5 mg

hydroxyzine Hydroxyzine, sold under the brand names Atarax and Vistaril among others, is an antihistamine medication. It is used in the treatment of itchiness, anxiety, insomnia, and nausea (including that due to motion sickness). It is used either by mou ...

* Amvicel by Roehrig Laboratories: 10 mg dextroamphetamine sulfate, 30 mg

nicotinamide Nicotinamide (International nonproprietary name, INN, British Approved Name, BAN ) or niacinamide (United States Adopted Name, USAN ) is a form of vitamin B3, vitamin B3 found in food and used as a dietary supplement and medication. As a suppl ...

, 40 mg

amobarbital Amobarbital (formerly known as amylobarbitone or sodium amytal as the soluble sodium salt) is a drug that is a barbiturate derivative. It has sedative-hypnotic properties. It is a white crystalline powder with no odor and a slightly bitter taste. ...

, 15 mg phenobarbital sodium, and essential

and

* Artogesic by Cole Pharmaceuticals: combination of dextroamphetamine,

mephobarbital Methylphenobarbital (INN), also known as mephobarbital (USAN, JAN) and mephobarbitone ( BAN), marketed under brand names such as Mebaral, Mephyltaletten, Phemiton, and Prominal, is a drug which is a barbiturate derivative and is used primarily ...

phenacetin Phenacetin (; acetophenetidin, ''N''-(4-ethoxyphenyl)acetamide) is a pain-relieving and fever-reducing drug, which was widely used following its introduction in 1887. It was withdrawn from medicinal use as dangerous from the 1970s (e.g., withdra ...

, and salicylamide. Name since recycled by Glenmark of India for a brand of ibuprofen. * Apamead by Lederle Laboratories: combination of dextroamphetamine sulfate, amobarbital sodium, aspirin, and phenacetin * Anox by Winston-Salem Pharmaceuticals were encapsulated polypills containing a fixed dose combination of three barbiturate salts (each measured at 20 mg for a total of 60 mg

barbiturates Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as ...

) combined with two amphetamine salts, each measured at 7.5 mg, for a total quantity of 15 mg

amphetamines Substituted amphetamines, or simply amphetamines, are a chemical class, class of compounds based upon the amphetamine structure; it includes all derivative (chemistry), derivative compounds which are formed by replacing, or substitution reacti ...

. Anox encompassed

butabarbital Butabarbital (brand name Butisol) is a prescription barbiturate sleep aid and anxiety medication. Butabarbital has a particularly fast onset of effects and short duration of action compared to other barbiturates, which makes it useful for cer ...

secobarbital Secobarbital, sold under the brand name Seconal among others, is a short-acting barbiturate drug originally used for the treatment of insomnia. It was patented by Eli Lilly and Company in 1934 in the United States. It possesses anesthetic, antic ...

, methamphetamine hydrochloride, dextroamphetamine sulfate, respectively measured at 7.5 mg, 7.5 mg,. **Diacels is the extended release version of this. **Ethobral was Wyeth's combination. * Anxine by Behlen Manufacturing: combination of 120 mg mephenesin, 35 mg cyclobarbital sodium, and 2.5 mg dextroamphetamine sulfate, and * BamaDex by Behlen: combination of 5 mg dextroamphetamine and 400 mg meprobamate * Biphetamine T-12.5 and Biphetamine T-20 by

Fisons Fisons plc was a British Multinational corporation, multinational pharmaceutical, scientific instruments and horticultural chemicals company headquartered in Ipswich, United Kingdom. It was listed on the London Stock Exchange and was once a cons ...

: combination of 6.25 mg

and 6.25 mg dextroamphetamine (1/2.5 mg

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

; 10 mg levoamphetamine and 10 mg dextroamphetamine (20 mg racemic amphetamine) * Delcobese by the Lemmon Drug Company: combination of mixed salts of amphetamine sulfate and adipate: 50% levoamphetamine sulfate and adipate combined with 50% dextroamphetamine sulfate and adipate, voluntarily withdrawn from production by the Lemmon Company in 1984 * Bontril Timed product line by Carnrick: Bontril Timed No. 1 combined 2.5 mg dextroamphetamine and 7.5 mg butabarbital sodium; Bontril Timed No. 2 5 mg dexamphetamine and 15 mg butabarbital; Bontril Timed No. 3 10 mg dexamphetamine with 30 mg butabarbital; and Bontril Timed No. 4 15 mg dexamphetamine with 60 mg butabarbital. * Desbutal Neisler Laboratories: combination 5 mg methamphetamine hydrochloride and 30 mg

pentobarbital Pentobarbital (US) or pentobarbitone (British and Australian) is a short-acting barbiturate typically used as a sedative, a preanesthetic, and to control convulsions in emergencies. It can also be used for short-term treatment of insomnia but ...

sodium, discontinued 1973 * Dexytal by Eli Lilly & Co., as a liquid

: dextroamphetamine and

sodium *

Dexamyl Dexamyl (or Drinamyl in the UK) was the brand name of a combination drug composed of amobarbital (previously called amylbarbitone) and dextroamphetamine (Dexedrine) within the same pill. It was widely abused and is no longer manufactured. First ...

Smith, Kline & French Smith, Kline & French (SKF) was an American pharmaceutical company that is now a part of the British group GSK plc. History In 1830, John K. Smith opened a drugstore in Philadelphia, and his younger brother, George, joined him in 1841 to form ...

, as tablets: and dextroamphetamine and amobarbital sodium, discontinued 1982 * Durophet M by/ Neisler Labs: combination of 6.5 mg levoamphetamine and 6.5 mg dextroamphetamine (13 mg racemic amphetamine) with 400 mg

methaqualone Methaqualone is a hypnotic sedative. It was sold under the brand names Quaalude ( ) and Sopor among others, which contained 300 mg of methaqualone, and sold as a combination drug under the brand name Mandrax, which contained 250 mg me ...

hydrochloride; available in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...

until 1984, amidst international crackdown on methaqualone * Durabond by Neisler Laboratories: * Daprisal by GlaxoSmithKline: dextroamphetamine sulfate, 32.5 mg amobarbital sodium, and 162.5 mg aspirin * Direcel: combined dextroamphetamine, butabarbital, and carboxymethylcellulose; Direcel-T added

thyroid hormone File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones triiodothyronine, T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus r ...

* Duodex: combination of 16.25 mg

aloin Aloin, also known as barbaloin, is a bitter, yellow-brown colored compound noted in the exudate of at least 68 ''Aloe'' species at levels from 0.1 to 6.6% of leaf dry weight (making between 3% and 35% of the total exudate), and in another 17 spec ...

, 15 mg amphetamine sulfate, 16.25 mg pentobarbital, and thyroid hormone * Dysonil: combination of methamphetamine hydrochloride,

sodium, and salicylamide * Edrisal: combination 160 mg

and 160 mg

with 2.5 mg

sulfate; a formulation containing 16 mg

as an additional active ingredient was branded Edrisal with Codeine * Elpanal Lamital by

Teva Pharmaceuticals Teva Pharmaceutical Industries Ltd. (also known as Teva Pharmaceuticals) is an Israeli multinational Pharmaceutical industry, pharmaceutical company. Teva specializes primarily in generic drugs, but other business interests include branded-drug ...

: combination of 500 mg acetaminophen, 15 mg amobarbital sodium, and 2.5 mg methamphetamine hydrochloride * Esbelcap ( fenproporex/

diazepam Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is used to treat a range of conditions, including anxiety disorder, anxiety, seizures, alcohol withdrawal syndr ...

): combination of 20 mg fenproporex with 6 mg

; never approved foruse in the JU.S., but is available over the counter in Central and

South America South America is a continent entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a considerably smaller portion in the Northern Hemisphere. It can also be described as the southern Subregion#Americas, subregion o ...

n countries until 2020 * Eskatrol by Smith, French & Kline: combination of dextroamphetamine and prochlorperazine; discontinued 1981 * Euphoramin: 5 mg methamphetamine hydrochloride and 300 mg

meprobamate Meprobamate—marketed as Miltown by Wallace Laboratories and Equanil by Wyeth, among others—is a carbamate derivative used as an anxiolytic drug. It was the best-selling minor tranquilizer for a time, but has largely been replaced by the benz ...

* NalerTan by Neisler: combination of 12.5 mg dextroamphetamine tannate, 8 mg

tannate, and 25 mg pyrilamine tannate * Mandrax by Lemmon Company:

hydrochloride and

, commercially available in

South Africa South Africa, officially the Republic of South Africa (RSA), is the Southern Africa, southernmost country in Africa. Its Provinces of South Africa, nine provinces are bounded to the south by of coastline that stretches along the Atlantic O ...

until 1990s * Mediatric by Janssen: combination of two

hormones A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior. Hormones a ...

, 0.25 mg Premarin (Conjugated Estrogens USP) and 2.5 mg

methyltestosterone Methyltestosterone, sold under the brand names Android, Metandren, and Testred among others, is an androgen and anabolic steroid (AAS) medication which is used in the treatment of low testosterone levels in men, delayed puberty in boys, at low ...

, along with 100 mg

vitamin c Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits, berries and vegetables. It is also a generic prescription medication and in some countries is sold as a non-prescription di ...

b vitamins B vitamins are a class of water-soluble vitamins that play important roles in Cell (biology), cell metabolism and synthesis of red blood cells. They are a chemically diverse class of compounds. Dietary supplements containing all eight are referr ...

, and 1 mg methamphetamine hydrochloride * Nexorin: combination of dextroamphetamine sulfate, amobarbital sodium,

methylcellulose Methyl cellulose (or methylcellulose) is a compound derived from cellulose. It is sold under a variety of trade names and is used as a thickener and emulsifier in various food and cosmetic products, and also as a bulk-forming laxative. Like cell ...

, and supplements * Obocell by Neisler: combination of 5 mg dextroamphetamine

phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

and 25 mg

methapyrilene Methapyrilene is an antihistamine and anticholinergic of the pyridine chemical class which was developed in the early 1950s. It was sold under the trade names Co-Pyronil and Histadyl EC in the UK. It has relatively strong sedative effects, to the ...

phosphate; Obocell-TF was nearly identical but with an additional 160 mg high-viscosity methylcellulose *

Obetrol Obetrol was the brand name of a drug combining several amphetamine salts indicated for the treatment of exogenous obesity. It was originally sold by the American company Obetrol Pharmaceuticals. Obetrol was a popular diet pill in America in the ...

Abbott Laboratories Abbott Laboratories is an American multinational medical devices and health care company with headquarters in Abbott Park, Illinois, in the United States. The company was founded by Chicago physician Wallace Calvin Abbott in 1888 to formulate k ...

: combination of various mixed salts of the substances, methamphetamine and dextroamphetamine; discontinued in 1973 * Obolip: dextroamphetamine and phenobarbital, with

choline Choline is a cation with the chemical formula . Choline forms various Salt (chemistry), salts, such as choline chloride and choline bitartrate. An essential nutrient for animals, it is a structural component of phospholipids and cell membrane ...

bitartrate , Section2 = {{Chembox Properties , C=4 , H=5 , O=6 , Formula_Charge = − , ConjugateAcid = Tartaric acid , ConjugateBase = Tartrate Bitartrate is an anion which is the conjugate base of tartaric acid. It may also refer to any salt ...

, di-

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other non-essential amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine play ...

, and

* Phelantin by

Parke-Davis Parke-Davis is a subsidiary of the pharmaceutical company Pfizer. Although Parke, Davis & Co. is no longer an independent corporation, it was once America's oldest and largest drug maker, and played an important role in medical history. In 1970 ...

: combination of 100 mg

phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anticonvulsant, anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence se ...

sodium, 32 mg pentobarbital sodium, and 2.5 mg methamphetamine hydrochloride. * Phenephen: by A.H. Robins: combination of hyoscamine sulfate, phenacetin, and aspirin, * Phenephen with Codeine by A.H. Robins: combination of hyoscamine sulfate, phenacetin, aspirin, codeine * Pondimin (

Fen-Phen The medication, drug combination fenfluramine/phentermine, usually called fen-phen, is an anti-obesity medication that is no longer widely available. It was sold in the early 1990s, and utilized two anorectics. Fenfluramine was marketed by Americ ...

): combination of

fenfluramine Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome. It was formerly used as an appetite suppressant in the treat ...

and

, discontinued 1997 * SynaTan-S by Neisler Laboratories: combined 10 mg dextroamphetamine tannate with 35 mg secobarbital sodium, since 1955 * OboTan-S by

Mallinckrodt Mallinckrodt Pharmaceuticals plc is an American-Irish domiciled manufacturer of specialty pharmaceuticals (namely, adrenocorticotropic hormone), generic drugs and imaging agents. In 2017, it generated 90% of its sales from the U.S. healthcare s ...

: combination 10 mg dexamphetamine tannate and secobarbital sodium * Pre M.T. by Behlen Manufacturing, a polypill and tablet containing:

sulfate, dextroamphetamine sulfate,

sodium, pyrilamine maleate, and a micro-dose of

theobromine Theobromine, also known as xantheose, is the principal alkaloid of ''Theobroma cacao'' (cacao plant). Theobromine is slightly water-soluble (330 mg/L) with a bitter taste. In industry, theobromine is used as an additive and precursor to ...

. * Reladorm by unknown domestic Russian manufacturer: combination of 100 mg cyclobarbital sodium and 10 mg

, available in

Russia Russia, or the Russian Federation, is a country spanning Eastern Europe and North Asia. It is the list of countries and dependencies by area, largest country in the world, and extends across Time in Russia, eleven time zones, sharing Borders ...

until 2019 * Tuinal by Abott: combination of two barbiturate salts, amobarbital and

, discontinued 1999

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.

Central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

s (

colloquially Colloquialism (also called ''colloquial language'', ''colloquial speech'', ''everyday language'', or ''general parlance'') is the linguistic style used for casual and informal communication. It is the most common form of speech in conversation am ...

called "uppers") were used as

appetite suppressant An anorectic is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desi ...

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

s, and

wakefulness-promoting agent A wakefulness-promoting agent (WPA), or wake-promoting agent, is a drug that increases wakefulness and arousal. They are similar to but distinct from psychostimulants, which not only promote wakefulness but also produce other more overt central ...

s, and further effects include increased mental alertness and concentration/focus, as well as physical energy and motivation. The addition of a central nervous system

depressant Depressants, also known as central nervous system depressants, or colloquially known as "downers", are drugs that lower neurotransmission levels, decrease the electrical activity of brain cells, or reduce arousal or stimulation in various ...

mitigated the stimulant's adverse effects without eliminating therapeutic benefits. In most cases, the "upper" component of these combination drugs was a salt, or mixed salts, of

amphetamine, dextroamphetamine, or methamphetamine, while the "downer" was typically one or more barbiturates (most commonly

, and/or

) or similar

GABAergic In molecular biology and physiology, something is GABAergic or GABAnergic if it pertains to or affects the neurotransmitter gamma-aminobutyric acid (GABA). For example, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a GABAergic ...

, non-barbiturate tranquilizers or sedatives, frequently

, respectively, which provided anxiolytic, muscle relaxant, and hypnotic effects. Upper and downer combination drugs were often capable of substituting for

Monoamine Oxidase Inhibitors Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espe ...

(MAOIs) in patients with

treatment-resistant depression Treatment-resistant depression (TRD) is often defined as major depressive disorder in which an affected person does not respond adequately to at least two different antidepressant medications at an adequate dose and for an adequate duration. Inad ...

where MAOIs are indicated, but where MAOI-related dietary restrictions would impact patient's life. Combination drugs offer the advantage over

polypharmacy Polypharmacy (polypragmasia) is an umbrella term to describe the simultaneous use of multiple medicines by a patient for their conditions. The term polypharmacy is often defined as regularly taking five or more medicines but there is no standard ...

by decreasing patients' pill burden. Overall, giving patients the ability to take control and alleviate symptoms, and potentially treat or cure multiple conditions by consuming all of their medical treatments efficacious treatment options by the ingestion of a single pill, which consistently improves patient medication compliance by reducing their

. The

American Association of Orthodontists Founded in 1900, the American Association of Orthodontists (AAO) is the world's oldest and largest dental specialty organization. It represents nearly 19,000 orthodontist members throughout the United States, Canada and abroad. All orthodontists are ...

asserts that fixed-dose combinations "limit clinicians' ability to customize dosing regimens." 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 For prescribers, if one constituent of the combination is contraindicated for a patient, the product cannot be prescribed.

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 polypill or any combination formula period approved for treating the condition. Medication available, and sometimes used in the context of

involves various individual medicines for treating tics and/or generalized anxiety or

social anxiety disorder Social anxiety disorder (SAD), also known as social phobia, is an anxiety disorder characterized by sentiments of fear and anxiety in social situations, causing considerable distress and impairing ability to function in at least some asp ...

and/or obsessive-compulsive anxieties with use of individual

benzodiazepines Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat co ...

s for the former two conditions, and

fluvoxamine Fluvoxamine, sold under the brand name Luvox among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is primarily used to treat major depressive disorder and, perhaps more-especially, obsessive–compu ...

clomipramine Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used in the treatment of various conditions, most notably obsessive–compulsive disorder but also many other disorders, including hyper ...

first-line treatments for OCD and related disorders, such as

hoarding Hoarding is the act of engaging in excessive acquisition of items that are not needed or for which no space is available. Civil unrest or the threat of natural disasters may lead people to hoard foodstuffs, water, gasoline, and other essentials ...

or compulsive decluttering. But, where

Attention-Deficit Hyperactivity Disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple con ...

, depression, or insomnia become a primary concern to the patient, it is only through polypharmacy (in this case, adding another antidepressant or a "booster, alongside a

hypnotic A hypnotic (from Ancient Greek, Greek ''Hypnos'', sleep), also known as a somnifacient or soporific, and commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to sleep induction, induce sleep and to trea ...

soporific agent, and/or

psychostimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition ...

s to both treat ADHD and counteract the

sleep inertia Sleep is a state of reduced mental and physical activity in which consciousness is altered and certain sensory activity is inhibited. During sleep, there is a marked decrease in muscle activity and interactions with the surrounding environme ...

, grogginess or hangover caused by the other evening medications).

Tourette syndrome Tourette syndrome (TS), or simply Tourette's, is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) tic. Common tics are blinkin ...

is a

neurological Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...

tic disorder Tic disorders are defined in the ''Diagnostic and Statistical Manual of Mental Disorders'' (DSM) based on type (motor or phonic) and duration of tics (sudden, rapid, nonrhythmic movements). Tic disorders are defined similarly by the World Health ...

whose only FDA-approved treatment is the neuroleptic

pimozide Pimozide (sold under the brand name Orap) is a neuroleptic medication, drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weigh ...

, a drug only used for tics due Tourette's disorder; every other treatment is an off-label use. While Tourette's is typically identified by chronic motor and vocal

tics A tic is a sudden and repetitive motor movement or vocalization that is not rhythmic and involves discrete muscle groups. Tics are typically brief and may resemble a normal behavioral characteristic or gesture. Tics can be invisible to the obs ...

–"semi-voluntary" movements and noises made in response to a "

premonitory urge A premonitory urge is a sensory phenomenon associated with Tourette syndrome and other tic disorders. Premonitory urges are "uncomfortable feelings or sensations preceding tics that usually are relieved by particularmovement". "Individuals ...

," an internal buildup of compulsive tension that can only be temporarily upon performing/making the motion/sound demanded by compulsion. Tourette's, however, is an all-encompassing

umbrella term Hypernymy and hyponymy are the wikt:Wiktionary:Semantic relations, semantic relations between a generic term (''hypernym'') and a more specific term (''hyponym''). The hypernym is also called a ''supertype'', ''umbrella term'', or ''blanket term ...

that includes not just chronic physical and phonic

tic A tic is a sudden and repetitive motor movement or vocalization that is not rhythmic and involves discrete muscle groups. Tics are typically brief and may resemble a normal behavioral characteristic or gesture. Tics can be invisible to the obs ...

s, but also presents with such

comorbid In medicine, comorbidity refers to the simultaneous presence of two or more medical conditions in a patient; often co-occurring (that is, concomitant or concurrent) with a primary condition. It originates from the Latin term (meaning "sicknes ...

symptoms as

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

(often OCD,

social anxiety Social anxiety is the anxiety and fear specifically linked to being in social settings (i.e., interacting with others). Some categories of disorders associated with social anxiety include anxiety disorders, mood disorders, autism spectrum dis ...

, schizoid personality,

avoidant personality disorder Avoidant personality disorder (AvPD), or anxious personality disorder, is a cluster C personality disorder characterized by excessive social anxiety and inhibition, fear of intimacy (despite an intense desire for it), severe feelings of inade ...

, or generalized anxiety),

ADHD Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple ...

, insomnia, depression, and traits of high-functioning autism formerly called

Asperger syndrome Asperger syndrome (AS), also known as Asperger's syndrome or Asperger's, is a diagnostic label that has historically been used to describe a neurodevelopmental disorder characterized by significant difficulties in social interaction and no ...

Illicit streets as de facto drug combinations

Illicit stimulants

Illicit drugs are formulated as powder, paste, or counterfeit "pressed" pills intended to resemble their pharmaceutical-grade counterparts. Since 2018, ABC News of Houston reports that product described as "

powder cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

" originating from a clandestine laboratory are increasingly analyzed and found to contain other

s, which may provide similar excitement in order to mimic cocaine's effects in a cost-effective, deceptive manner; many of the batches analyzed did not contain any cocaine or coca alkaloids whatsoever; instead, they were blends of various

designer drugs A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. ...

and

research chemicals Research chemicals are chemical substances which scientists use for medical and scientific research purposes. One characteristic of a research chemical is that it is for laboratory research use only; a research chemical is not intended for human ...

, typically synthetic cathinones,

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with stimulant and minor Psychedelic drug, psychedelic properties. In studies, it has been used ...

; and in recent years, the flesh-eating veterinary antibiotic

levamisole Levamisole, sold under the brand name Ergamisol among others, is a medication used to treat parasitic worm infections, specifically ascariasis and hookworm infections. It is taken by mouth. Side effects may include abdominal pain, vomiting, ...

Illicit depressants (opiates, sedative, tranquilizers)

Due to the crackdown of pill mills between 2007 and 2012, the

opioid epidemic The opioid epidemic, also referred to as the opioid crisis, is the rapid increase in the overuse, misuse or abuse, and overdose deaths attributed either in part or in whole to the class of drugs called opiates or opioids since the 1990s. It inc ...

frequently includes

drug deal The illegal drug trade, drug trafficking, or narcotrafficking is a global black market dedicated to the cultivation, manufacture, distribution and sale of drug prohibition, prohibited drugs. Most jurisdictions prohibitionism, prohibit trade, exce ...

s whereby a substance may often be sold as "

heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a morphinan opioid substance synthesized from the Opium, dried latex of the Papaver somniferum, opium poppy; it is mainly used as a recreational drug for its eupho ...

" or legitimate pharmaceutical pills ("pressed," counterfeit, often adulterated pills). Mandrax in

is now produced via

clandestine chemistry Clandestine chemistry is chemistry carried out in secret, and particularly in illegal drug laboratories. Larger labs are usually run by gangs or organized crime intending to produce for distribution on the black market. Smaller labs can be run by ...

as a

free base In chemistry, a free base (freebase, free-base) is a term for the neutral form of an amine or other Lewis base. The term is used in the pharmaceutical industry in contrast to salt-based formulations like hydrochlorides. The amine is often an ...

form of methaqualone, which is smoked for a quick, intense, short-lived "high". Proportionate to an illicit substance's active ingredient or alkaloid,

cutting agent Cutting is the separation or opening of a physical object, into two or more portions, through the application of an acutely directed force. Implements commonly used for cutting are the knife and saw, or in medicine and science the scalpel and m ...

s have risen in quantities present. In the United States, analyzed samples of products declared upon sale/drug transacting to be "heroin" 97% contained, at minimum, trace amounts of adulerating "cutting agents", generally a synthetic opioid such as

fentanyl Fentanyl is a highly potent synthetic piperidine opioid primarily used as an analgesic (pain medication). It is 30 to 50 times more Potency (pharmacology), potent than heroin and 50 to 100 times more potent than morphine. Its primary Medici ...

carfentanil Carfentanil or carfentanyl, formerly sold under the brand name Wildnil, is an extremely potent opioid analgesic used in veterinary medicine to anesthetize large animals such as elephants and rhinoceroses. It is a structural analogue of the ...

nitazene Benzimidazole opioids are a class of synthetic opioids that contain a benzimidazole core structure. The analgesic, pain-relieving properties of these substances were discovered in the mid-1950s by the Swiss company Ciba Specialty Chemicals, Ciba ...

. Mislabeled products containing non-opioid ingredients will likely comprise clobromazolam, etizolam, or another

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

. Several other

central nervous system depressant Depressants, also known as central nervous system depressants, or colloquially known as "downers", are drugs that lower neurotransmission levels, decrease the electrical activity of brain cells, or reduce arousal or stimulation in various are ...

s have been identified in samples of products sold as "heroin," intended to mimic sedative and analgesic properties of opioids, including major tranquilizers such as drowsiness-inducing typical, first generation antipsychotics (e.g.

haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychos ...

, e.g.

chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar d ...

) or the

atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as tranquilizers and neurol ...

s quetiapine or olanzapine, as both are "neuroleptics") or a particularly sedating

first-generation antihistamine H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of his ...

s such as

, and increasingly

xylazine Xylazine is a structural analog of clonidine and an α2-adrenergic receptor, α2-adrenergic receptor agonist, sold under many trade names worldwide, most notably the Bayer brand name Rompun, as well as Anased, Sedazine and Chanazine. Xylazine ...

–which is only approved forveterinary use via prescription. In April 2025,

U.S. Attorney General The United States attorney general is the head of the United States Department of Justice and serves as the chief law enforcement officer of the federal government. The attorney general acts as the principal legal advisor to the president of the ...

Pam Bondi Pamela Jo Bondi ( ; born November 17, 1965) is an American attorney, lobbyist, and politician who has served as the 87th United States attorney general since 2025. A member of the Republican Party, she served as the 37th attorney general of Fl ...

stated a goal of making xylazine a federally-controlled Schedule III

controlled substance A controlled substance is generally a drug or chemical whose manufacture, possession and use is regulated by a government, such as illicitly used drugs or prescription medications that are designated by law. Some treaties, notably the Sing ...

per the Controlled Substances Act, xylazine is currently a controlled substance at the state level in

Michigan Michigan ( ) is a peninsular U.S. state, state in the Great Lakes region, Great Lakes region of the Upper Midwest, Upper Midwestern United States. It shares water and land boundaries with Minnesota to the northwest, Wisconsin to the west, ...

and

New York New York most commonly refers to: * New York (state), a state in the northeastern United States * New York City, the most populous city in the United States, located in the state of New York New York may also refer to: Places United Kingdom * ...

References

External links

* {{Combined substance use and adulteration Dosage forms