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
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 ...
,
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
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 ...
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 ...
:
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 ...
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 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:
*
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, 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
*
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, levoamphetaminee sulfate, commonly Adderall and Mydayis
*
pseudoephedrine/carbinoxamine, Rondec syrup
Combination drugs accessible over the counter (OTC)
Fixed-dose combination drugs for sale
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 ...
(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
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 ...
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
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 32 mg
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 ...
.
* Bayer
Coricidin: 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 (
expectorant) 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
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 ...
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
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, ...
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 and 120 mg
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 ...
hydrochloride
*
oxomemazine/guaifenesin (primarily branded Toplexil by
Aventis): most frequently taken orally in
liquid syrup 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 ...
, 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
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 ...
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
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 ...
.
* Robitussin: a product line of
cough medicines 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,
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 ...
; antipyretic analgesic acetaminophen/paracetamol; either the antihistamine chlorpheniramine maleate, or doxylamine succinate; and the expectorant/mucus thinner, guaifenesin.
* Sudafed PE: combination of 300 mg
guaifenesin 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
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 ...
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
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 ...
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 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
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 ...
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, but is otherwise identical in terms of formulation and efficacy.
* Titzeol: combination of
tiletamine and
zolazepam both major tranquilizers, intended to sedate large animals
Combination drugs no longer widely available
* Acutran by
G.W. Carnrick Laboratories:
amfecloral, 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 ...
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 ...
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 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
hydrochloride, 2.5 mg
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 ...
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
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 ...
sulfate, and 5 mg dextroamphetamine sulfate.
* Amplus Now by
Roehrig Laboratories, Inc.–combined 5 mg dextroamphetamine sulfate and 5 mg
hydroxyzine
* 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
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 ...
and
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 ...
* Artogesic by Cole Pharmaceuticals: combination of dextroamphetamine,
mephobarbital,
phenacetin, 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
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 ...
,
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
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 ...
and 6.25 mg dextroamphetamine (1/2.5 mg
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 ...
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
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 ...
: dextroamphetamine and
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. ...
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 ...
by
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,
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, and
salicylamide
* Edrisal: combination 160 mg
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 160 mg
phenacetin with 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 ...
sulfate; a formulation containing 16 mg
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 ...
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
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 ...
; 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
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 ...
tannate, and 25 mg
pyrilamine tannate
* Mandrax by Lemmon Company:
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 and
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 ...
, 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 phosphate; Obocell-TF was nearly identical but with an additional 160 mg high-viscosity methylcellulose
*
Obetrol by
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
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 ...
* 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
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 ...
, 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:
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 ...
sulfate, dextroamphetamine sulfate,
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,
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
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 ...
, 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
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 ...
, 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 ...
s,
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
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 ...
amphetamine, dextroamphetamine, or methamphetamine, while the "downer" was typically one or more barbiturates (most commonly
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. ...
,
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 ...
,
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 ...
, and/or
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 ...
) 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
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 ...
or
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 ...
, 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
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 ...
. 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
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 ...
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 ...
or
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 ...
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 ...
or
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, 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
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, 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 ...
,
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 ...
,
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 ...
,
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 ...
or
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 ...
; 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
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 ...
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 form of methaqualone, which is smoked for a quick, intense, short-lived
"high". Proportionate to an illicit substance's active ingredient or alkaloid,
cutting agents 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.
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 depressants 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
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 ...
, 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
* ...
.
See also
*
Codrugs
*
Synergy#Drug synergy
References
External links
*
{{Combined substance use and adulteration
Dosage forms