A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more

active ingredient 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. The ...

s combined in a single

dosage form Dosage forms (also called unit doses) are pharmaceutical drug products in the form in which they are marketed for use, with a specific mixture of active ingredients and inactive components (excipients), in a particular configuration (such as a ca ...

. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC product (since most combination drug products are currently FDCs), although the latter is more precise if in fact referring to a mass-produced product having a predetermined combination of drugs and respective dosages (as opposed to ''customized'' polypharmacy via

compounding In the field of pharmacy, compounding (performed in compounding pharmacies) is preparation of a custom formulation of a medication to fit a unique need of a patient that cannot be met with commercially available products. This may be done for me ...

). And it should also be distinguished from the term "combination product" in medical contexts, which without further specification can refer to products that combine different ''types'' of medical products—such as device/drug combinations as opposed to drug/drug combinations. Note that when a combination drug product (whether fixed-dose or not) is a "pill" (i.e., a tablet or capsule), then it may also be a kind of "

polypill A polypill is a type of drug combination consisting of a single drug product in pill form (i.e., tablet or capsule) and thus ''combines'' multiple medications (that is, more than one active pharmaceutical ingredient). The prefix "poly" means "mu ...

" or combopill. Initially, fixed-dose combination drug products were developed to target a single disease (such as with antiretroviral FDCs used against AIDS). However, FDCs may also target multiple diseases/conditions. In cases of FDCs targeting multiple conditions, such conditions might often be related—in order to increase the number of prospective patients who might be likely to use a given FDC product. This is because each FDC product is mass-produced, and thus typically requires having a critical mass of potentially applicable patients in order to justify its manufacture, distribution, stocking, etc.

Common combination drugs

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 prescr ...

medicines: *

Dimenhydrinate Dimenhydrinate, sold under the brand name Dramamine, among others, is an over-the-counter drug used to treat motion sickness and nausea. Dimenhydrinate is a theoclate salt composed of diphenhydramine, an ethanolamine derivative, and 8-chloroth ...

(

8-chlorotheophylline 8-Chlorotheophylline, also known as 1,3-dimethyl-8-chloroxanthine, is a stimulant drug of the xanthine chemical class, with physiological effects similar to caffeine. Its main use is in combination (salt) with diphenhydramine in the antiemetic d ...

diphenhydramine Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremor in parkinsonism, and nausea. It is taken by mouth, injected into ...

) — used to treat

motion sickness Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include de ...

and

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

* Glucose/fructose/phosphoric acid —

antiemetic An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They m ...

taken to relieve

and

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteri ...

Prescription drugs: *

Adderall Adderall and Mydayis are trade names for a combination drug called mixed amphetamine salts containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio ...

(

dextroamphetamine Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance an ...

sulfate/ amphetamine sulfate/dextroamphetamine saccharate/amphetamine aspartate monohydrate) — treatment of

attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...

(ADHD) and

narcolepsy Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affect ...

. *

Aspirin/paracetamol/caffeine Aspirin(acetylsalicylic acid) / paracetamol(acetaminophen) / caffeine is a combination drug for the treatment of pain, especially tension headache and migraine. It is sold in the US under the trade names Goody's Powder and Excedrin, although n ...

— pain treatment, especially

tension headache Tension headache, also known as stress headache, or tension-type headache (TTH), is the most common type of primary headache. The pain can radiate from the lower back of the head, the neck, eyes or other muscle groups in the body typically affect ...

and migraine *

Caffeine/ergotamine Caffeine/ergotamine (trade name Cafergot) is the proprietary name of a medication consisting of ergotamine tartrate and caffeine. This combination is used for the treatment of headaches, such as migraine headache. Use Correct timing of use ...

— treatment of headaches, such as migraine headache. * Nirmatrelvir/ritonavir (Paxlovid) — granted

emergency use authorization An Emergency Use Authorization (EUA) in the United States is an authorization granted to the Food and Drug Administration (FDA) under sections of the Federal Food, Drug, and Cosmetic Act as added to and amended by various Acts of Congress, includ ...

(EUA) by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) for the

treatment and management of COVID-19 Although several medications have been approved in different countries as of April 2022, not all countries have these medications. Patients with mild to moderate symptoms who are in the risk groups can take nirmatrelvir/ritonavir (marketed as Pa ...

Advantages

In addition to simply being a means of facilitating the general advantages of

combination therapy Combination therapy or polytherapy is therapy that uses more than one medication or modality. Typically, the term refers to using multiple therapies to treat a ''single'' disease, and often all the therapies are pharmaceutical (although it can also ...

, specific advantages of fixed-dose combination (FDC) drug products include: *Improved medication compliance by reducing the

pill burden Polypharmacy (polypragmasia) is the simultaneous use of multiple medicines by a patient for their conditions. Most commonly it is defined as regularly taking five or more medicines but definitions vary in where they draw the line for the minimum ...

of patients. Note that pill burden is not only the number of pills needing to be taken, but also the associated burdens such as keeping track of several medications, understanding their various instructions, etc. *Ability to compose combined profiles of for example pharmacokinetics, effects and

adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a " side effect", when judged to be secondary to a main or therapeutic effect. The term compl ...

s that may be specific for the relative dosages in a given FDC product, providing a simpler overview compared to when looking at the profiles of each single drug individually. Such combined profiles can also include effects caused by interaction between the individual drugs that may be omitted in individual drug profiles. *Since FDCs are reviewed by regulating agencies (such as the

in the United States), the active ingredients used in the FDCs are unlikely to exhibit adverse

drug interaction Drug interactions occur when a drug's mechanism of action is disturbed by the concomitant administration of substances such as foods, beverages, or other drugs. The cause is often the inhibition of the specific receptors available to the drug, ...

s with each other. However, FDCs may interact with other drugs that a patient is taking, so the usual medical and pharmaceutical precautions against drug-drug interactions or DDIs remain warranted. *FDC drug products may be developed by a

pharmaceutical company The pharmaceutical industry discovers, develops, produces, and markets drugs or pharmaceutical drugs for use as medications to be administered to patients (or self-administered), with the aim to cure them, vaccinate them, or alleviate sympto ...

as a way to in effect extend proprietary rights and marketability of a drug product. Since FDCs may be protected by

patent A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A p ...

s, a company may obtain exclusive rights to sell a particular FDC or formulation thereof, even though the individual active ingredients and many therapeutic uses thereof may be off-patent.

Disadvantages

*There may not be an FDC available with the appropriate drugs and/or in the most appropriate respective strength(s) for a given patient, which can lead to some patients getting too much of an ingredient and others getting too little, as the AAO notes that FDCs "limit clinicians' ability to customize dosing regimens." In such cases an alternative possibility (instead of an FDC) is to use custom-compounded polypills prepared by a compounding pharmacist according to a prescription. (

Pharmaceutical compounding In the field of pharmacy, compounding (performed in compounding pharmacies) is preparation of a custom formulation of a medication to fit a unique need of a patient that cannot be met with commercially available products. This may be done for me ...

is the practice of preparing individualized drug products for individual patients, which can aid with polypharmacy.) *If an

adverse drug reaction An adverse drug reaction (ADR) is a harmful, unintended result caused by taking medication. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs. The meaning of this term ...

occurs from using an FDC, it may be difficult to identify the active ingredient responsible for causing the reaction. This problem might be alleviated by starting the medications individually and monitoring for reactions, and then switching to an FDC when no problems have been observed (assuming of course that it's the active ingredient causing the problem). *Formulation scientists experience challenges in the development stages of multi-drug formulations such as compatibility issues among active ingredients and excipients affecting solubility and dissolution * If one drug is contraindicated for a patient, whole FDC cannot be prescribed.Kennedy Seele, 2020

References

External links

* {{Combined substance use and adulteration Dosage forms fi:Yhdistelmälääkkeet