A polypill is a type of
drug combination consisting of a single drug product in pill form (i.e.,
tablet
Tablet may refer to:
Medicine
* Tablet (pharmacy), a mixture of pharmacological substances pressed into a small cake or bar, colloquially called a "pill"
Computing
* Tablet computer, a mobile computer that is primarily operated by touching the s ...
or
capsule) and thus ''combines'' multiple
medication
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...
s (that is, more than one
active pharmaceutical ingredient
An active ingredient is any ingredient that provides biological activity, 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 h ...
). The prefix "poly" means "multiple", referring to the multiplicity of distinct drugs in a given "pill". In precise
usage
The usage of a language is the ways in which its written and spoken variations are routinely employed by its speakers; that is, it refers to "the collective habits of a language's native speakers", as opposed to idealized models of how a language ...
, a pill is a polypill if it contains at least 4 drugs (meaning that
fixed-dose combinations
A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC prod ...
of 2 or 3 drugs are not polypills). An occasional synonym is ''combopill''. A polypill is commonly targets treatment or prevention of
chronic condition
A chronic condition is a health condition or disease that is persistent or otherwise long-lasting in its effects or a disease that comes with time. The term ''chronic'' is often applied when the course of the disease lasts for more than three mo ...
s.
Polypills may be aimed to be consumed by healthy people as a means of
preventive medicine
Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
, and/or treating actual pathophysiological condition(s), the former typically involving lower dosages than the latter. Polypills can reduce the number of
tablets or
capsules (generally
orally administered) that need to be taken, which in turn may facilitate handling and administration of pharmaceuticals as well as alleviate patient pill-burden. Sometimes the multiple drugs in a given polypill might all be aimed at a single underlying condition (or, group of related conditions), partly because this expands the pool of potential patients for whom a given combination of drugs/dosages might be appropriate (particularly in the case of mass-produced polypills, i.e. FDCs). The term polypill was first coined in the context of
cardiovascular disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
prevention,
but has since gained broader acceptance, including now for combinatorial drug products that existed before the term was actually coined (as the bare term without any modifiers is now quite generic).
In addition to the noted fixed-dose types of polypills, polypills can also be custom-made for specific patients through a process called
pharmacy compounding. Physicians in most jurisdictions have wide discretion to prescribe customized drug products containing unique drug-dosage combinations (and/or formulations thereof) specifically for individual patients, which certain pharmacies can then sometimes produce for such patients.
For treatment or management of disease
Polypills are a useful therapeutic tool for those afflicted with various diseases/conditions, by consolidating multiple medications into a single product and thereby simplifying medication administration for healthcare personnel as well as alleviating pill-burden for patients.
HIV, mental-health, transplant, and certain other patient groups are known for especially high pill-burdens (whether temporary or indefinite). Also, elderly patients in particular are likely to require several medications on a daily basis for managing multiple conditions, and they are also particularly susceptible to difficulties remembering or keeping track of their regimen.
Origin of multi-drug pill usage
Combinatorial drug products were proposed for ''treating'' diagnosed conditions long before they were proposed for preventive medicine, including "aspolol" (a combination of aspirin and
atenolol
Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of mi ...
) for those diagnosed with cardiovascular disease. Fixed-dose combination (FDC) products today are also common for treating other diseases, such as
tuberculosis
Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
and
HIV/AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
.
Developments in polypill usage for disease therapy
Treating cardiovascular disease
One of the first recommended roles of a polypill was as a means of providing recommended medications to people with heart disease, stroke and other forms of cardiovascular disease. Most cardiovascular disease patients do not receive recommended medications long-term: the proportion of cardiovascular disease patients ''not ''receiving a statin, aspirin and blood pressure lowering medication long-term ranges from about 50% in high income countries to over 90% in low income countries. In 2001, a World Health Organisation and The Wellcome Trust meeting of experts to discuss interventions for non-communicable diseases noted “the use of a single pill could well encourage patients to adhere to treatment as well as seriously reduce the cost of the drugs” A programme of research was outlined, including stability and bio-availability testing followed by assessment of short-term effects on blood pressure, cholesterol, platelet aggregation, safety and side effects. In 2002, the World Health Organisation Annual Report outlined the substantial potential public health impact and cost-effectiveness of scaling up access to combination cardiovascular treatment and an editorial in ''The Lancet'' noted that a four component combination pill would reduce cardiovascular risk by about 75% among people with vascular disease.
Treating diabetes and metabolic syndrome
Polypills have been proposed for managing
diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
(and potentially for
pre-diabetes
Prediabetes is a component of the metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesit ...
).
Diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
- particularly
Type II diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...
- is a major cause of morbidity and mortality. Diabetes also contributes substantially to cardiovascular risk, yet some ingredients appropriate for a cardiovascular polypill may not be advisable for patients with diabetes (such as
beta-blockers
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack (secondary prevention). They are al ...
and
thiazide diuretics
Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The first ...
). A polypill for diabetes could include a
statin
Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs.
Low- ...
(to reduce
LDL cholesterol
Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...
and for their
anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...
properties), an
ACE inhibitor
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...
(for blood pressure control and to protect the
kidneys
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
),
aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
(for anti
platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
and anti-inflammatory properties), and
metformin
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...
(a medication for diabetes that is also associated with weight loss).
Role of compounding pharmacy
As noted, not all polypills are mass-produced fixed-dose (FDC) drug products. Physicians in many countries have wide discretion to prescribe customized drug products containing unique drug-dosage combinations and/or formulations thereof specifically for individual patients, which can then be custom-produced in a
compounding pharmacy
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 ...
. Some kinds or compositions of polypills or similar drug products are more amenable to custom-compounding than others, and most retail pharmacies no longer offer compounding services at all (although hospital pharmacies still commonly compound ''intravenous'' medications). While fewer pharmacists are trained and experienced in the relevant skills anymore, especially regarding oral dosage forms, such compounding pharmacies nevertheless can be found and utilized via mail-order (if not available locally) with sufficient notice and planning. Generally, if a customized drug product is produced for a specific patient in response to a prescription specifying said patient's drug(s)/dosage(s), it is ''not'' subject to regulatory approval (e.g., FDA in the US) but is instead regulated under the practice of pharmacy (governed at the state-level in the US).
Technologies are under development to facilitate production of customized polypills, such as for example by the use of ink-jet printing mechanisms to precisely deposit selected drug substance(s) onto sheets which can then be inserted into capsules (enabling "individualized dosing and automated fabrication of medicines containing multiple drugs," in addition to custom single-drug products). Similar technology can also be used to print tablets, more directly. Ink-jet or fluid-jet approaches require each drug substance to be dissolved in a liquid solvent, but they can be particularly conducive to custom formulation with various possible excipients (in addition to custom drug/dose selections).
For preventive medicine
Origin of preventive medicine applications
Wald
WALD (1080 kHz) is an AM radio station licensed to Johnsonville, South Carolina. The station is part of the Worship and Word Network and is owned by Glory Communications, Inc., based in St. Stephen, South Carolina. It carries an Urban Gosp ...
and
Law
Law is a set of rules that are created and are enforceable by social or governmental institutions to regulate behavior,Robertson, ''Crimes against humanity'', 90. with its precise definition a matter of longstanding debate. It has been vario ...
had first proposed using a combination of well-known and inexpensive medications in one pill for protection against cardiovascular disease.
They presented a
statistical model
A statistical model is a mathematical model that embodies a set of statistical assumptions concerning the generation of Sample (statistics), sample data (and similar data from a larger Statistical population, population). A statistical model repres ...
which suggested widespread use of such a polypill could reduce mortality due to
heart disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...
and
stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
s by up to 80%, while the drugs and their respective interactions are already fairly well known and understood due to many years of being prescribed together (via separate pills). They proposed combining six medications already established in treating
cardiovascular disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
and associated conditions, providing these in a single pill to people in Western countries aged 55 years or more as a preventive measure (albeit in lower doses than when used for treatment).
Developments of preventive medicine applications
Any physician could currently prescribe all the components of many proposed polypills separately for their patients, whether therapeutically or preventively. And since the ingredients of many possible polypills are off
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 ...
, it can be cheap to commercialize, although FDC products with novel combinations or formulations can sometimes themselves be patented. Of course, for any FDC product, the potential market for a given combination of drugs/dosages would need to be sufficiently large to justify the clinical trials and other expenses associated with mass-producing a new drug.
Producing countries
The polypill, drugs to lower blood pressure, is produced in
Iran
Iran, officially the Islamic Republic of Iran, and also called Persia, is a country located in Western Asia. It is bordered by Iraq and Turkey to the west, by Azerbaijan and Armenia to the northwest, by the Caspian Sea and Turkmeni ...
by the support of
Execution of Imam Khomeini's Order
The Execution of Imam Khomeini's Order (EIKO) ( fa, ستاد اجرایی فرمان امام, ''Setâd-e Ejrây-ye Farmân-e Emâm''), also known as the Executive Headquarters of Imam's Directive or simply Setad, is a parastatal organization in ...
was designed 14 years ag and called "PolyIran". According to the study was conducted by doctors from Tehran University, the University of Birmingham in Britain and other institutions and published by The Lancet, it worked quite well in a new study, slashing the rate of heart attacks by more than half among those who regularly took the pills. The pill in the study, which involved the participation of 6,800 rural villagers aged 50 to 75 in Iran, contained a cholesterol-lowering statin, two blood-pressure drugs and a low-dose aspirin.
Certain "cardiovascular polypills" are currently available in
India
India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
and have been extensively studied there (see
Polycap and
PolyIran, for examples). Also, cardiologists in Spain are developing a polypill for secondary cardiovascular prevention.
Preventive use rationale: Treatment of population risk
Some preventive-use advocates propose that everyone over a given age (e.g., 55) should take such medications for preventive health, irrespective of individual risk factor levels. The idea is that most people in western countries are at high overall risk, thus lowering risk factor levels will provide broad benefit. This approach emphasizes the perspective that risk factors are continuous, and rigid dichotomies such as "hypertension" and "no hypertension" may be over-simplified and can be viewed instead as continuums of inter-connected factors.
In this paradigm, doctors would in effect be treating population risk rather than individual risk factor thresholds as is current mainstream practice. So, if everyone were given a relevant kind of polypill, the average blood pressure and cholesterol levels in the population would fall, thus reducing overall population risk. Perhaps ironically, this is in a sense going in the ''opposite'' direction from
personalized medicine
Personalized medicine, also referred to as precision medicine, is a medical model that separates people into different groups—with medical decisions, practices, interventions and/or products being tailored to the individual patient based on the ...
, since mass-produced or fixed-dose-combination polypills are in some tension with the goals of personalized medicine, due to the "fixed" nature of the "dose combinations." Proponents of this population-focused approach contend that the advantages of drug consolidation can outweigh any reduction in personalization of drug and/or dose selection. Also, depending on the demographic distribution and market size, there may be room for some different alternative versions of certain general FDCs to be manufactured with differences in their respective dosages and/or drugs. A widely distributed polypill could contain three blood pressure medications at low dose: a
diuretic
A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...
, such as
hydrochlorothiazide
Hydrochlorothiazide is a diuretic medication often used to treat high blood pressure and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in tho ...
, a
beta-blocker
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack (secondary prevention). They are al ...
such as
atenolol
Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of mi ...
, and an
ACE inhibitor
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...
such as
lisinopril
Lisinopril is a medication of the angiotensin-converting enzyme (ACE) inhibitor and is used to treat high blood pressure, heart failure, and after heart attacks. For high blood pressure it is usually a first-line treatment. It is also used to ...
; and these could be combined with a
statin
Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs.
Low- ...
such as
simvastatin
Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of heart ...
,
aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
at a dose of 75 mg, and
folic acid
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
, which has been shown to reduce the level of homocysteine in the blood, which is another risk factor for heart disease.
References
Selected publications
*
*
"Tests start on pill that could lengthen millions of lives: Tablet aims to cut heart attack and stroke risk: Four-in-one drug could be sold for just $1 a month" Sarah Boseley, health editor ''The Guardian'', Monday September 29 2008.*
*
*Gorman, Rachael Moeller. "The Polypill" ''Proto'', Winter 2007
External links
The Polypill - Proto Magazine - Massachusetts General Hospital
{{Combined substance use and adulteration
Combination drugs