Polypill

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A polypill or single pill combination (SPC) 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 "multiple", referring to the multiplicity of distinct drugs in a given "pill". In precise usage, a pill is a polypill if it contains at least 4 drugs (meaning that fixed-dose combinations of 2 or 3 drugs are not polypills). An occasional synonym is combopill. A polypill is commonly targets treatment or prevention of chronic conditions. [1]

Contents

Polypills may be aimed to be consumed by healthy people as a means of preventive medicine, 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 prevention, [2] [3] 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) for those diagnosed with cardiovascular disease. Fixed-dose combination (FDC) products today are also common for treating other diseases, such as tuberculosis and HIV/AIDS.

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. [4] In 2001, a World Health Organization 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” [5] 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 Organization Annual Report outlined the substantial potential public health impact and cost-effectiveness of scaling up access to combination cardiovascular treatment [6] 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. [7]

Treating diabetes and metabolic syndrome

Polypills have been proposed for managing diabetes (and potentially for pre-diabetes). [8]

Diabetes - particularly Type II diabetes - 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 and thiazide diuretics). A polypill for diabetes could include a statin (to reduce LDL cholesterol and for their anti-inflammatory properties), an ACE inhibitor (for blood pressure control and to protect the kidneys), aspirin (for antiplatelet and anti-inflammatory properties), and metformin (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. 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). [9] [10] [11] 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 and Law had first proposed using a combination of well-known and inexpensive medications in one pill for protection against cardiovascular disease. [3] They presented a statistical model which suggested widespread use of such a polypill could reduce mortality due to heart disease and strokes 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 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). [3]

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, 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 [12] [13] in Iran by the support of Execution of Imam Khomeini's Order 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. [14] [15]

Certain "cardiovascular polypills" are currently available in India and have been extensively studied there (see Polycap and PolyIran, for examples). Also, cardiologists in Spain are developing a polypill for secondary cardiovascular prevention. [16]

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. [17]

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, 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, such as hydrochlorothiazide, a beta-blocker such as atenolol, and an ACE inhibitor such as lisinopril; and these could be combined with a statin such as simvastatin, aspirin at a dose of 75 mg, and folic acid, which has been shown to reduce the level of homocysteine in the blood, which is another risk factor for heart disease.

Related Research Articles

<span class="mw-page-title-main">Aspirin</span> Medication

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 include Kawasaki disease, pericarditis, and rheumatic fever.

<span class="mw-page-title-main">Coronary artery disease</span> Reduction of blood flow to the heart

Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic plaque in the arteries of the heart. It is the most common of the cardiovascular diseases. Types include stable angina, unstable angina, and myocardial infarction.

<span class="mw-page-title-main">Statin</span> Class of drugs used to lower cholesterol levels

Statins are a class of medications that reduce illness and mortality in people who are at high risk of cardiovascular disease. They are the most commonly prescribed cholesterol-lowering drugs, and are also known as HMG-CoA reductase inhibitors.

An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effective in the arterial circulation where classical Vitamin K antagonist anticoagulants have minimal effect.

<span class="mw-page-title-main">Cardiovascular disease</span> Class of diseases that involve the heart or blood vessels

Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, arrhythmia, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, thromboembolic disease, and venous thrombosis.

<span class="mw-page-title-main">Hydrochlorothiazide</span> Diuretic medication

Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension 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 those with a high calcium level in the urine. Hydrochlorothiazide is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness. Hydrochlorothiazide is a thiazide medication which inhibits reabsorption of sodium and chloride ions from the distal convoluted tubules of the kidneys, causing a natriuresis. This initially increases urine volume and lowers blood volume. It is believed to reduce peripheral vascular resistance.

<span class="mw-page-title-main">Atorvastatin</span> Cholesterol-lowering medication

Atorvastatin is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth.

<span class="mw-page-title-main">Simvastatin</span> Lipid-lowering medication

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 problems in those at high risk. It is taken by mouth.

<span class="mw-page-title-main">Rosuvastatin</span> Statin medication

Rosuvastatin, sold under the brand name Crestor among others, is a statin medication, used to prevent cardiovascular disease in those at high risk and treat abnormal lipids. It is recommended to be used together with dietary changes, exercise, and weight loss. It is taken orally.

<span class="mw-page-title-main">Indapamide</span> Thiazide diuretic drug

Indapamide is a thiazide-like diuretic drug used in the treatment of hypertension, as well as decompensated heart failure. Combination preparations with perindopril are available. The thiazide-like diuretics reduce risk of major cardiovascular events and heart failure in hypertensive patients compared with hydrochlorothiazide with a comparable incidence of adverse events. Both thiazide diuretics and thiazide-like diuretics are effective in reducing risk of stroke. Both drug classes appear to have comparable rates of adverse effects as other antihypertensives such as angiotensin II receptor blockers and dihydropyridine calcium channel blockers and lesser prevalence of side-effects when compared to ACE-inhibitors and non-dihydropyridine calcium channel blockers.

<span class="mw-page-title-main">Polypharmacy</span> Use of five or more medications daily

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 definition and the term has also been used in the context of when a person is prescribed 2 or more medications at the same time. Polypharmacy may be the consequence of having multiple long-term conditions, also known as multimorbidity and is more common in people who are older. In some cases, an excessive number of medications at the same time is worrisome, especially for people who are older with many chronic health conditions, because this increases the risk of an adverse event in that population. In many cases, polypharmacy cannot be avoided, but 'appropriate polypharmacy' practices are encouraged to decrease the risk of adverse effects. Appropriate polypharmacy is defined as the practice of prescribing for a person who has multiple conditions or complex health needs by ensuring that medications prescribed are optimized and follow 'best evidence' practices.

<span class="mw-page-title-main">Valsartan</span> Angiotensin II receptor antagonist

Valsartan, sold under the brand name Diovan among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth.

<span class="mw-page-title-main">Fenofibrate</span> Drug of the fibrate class, mainly used to reduce cholesterol levels

Fenofibrate, is an oral medication of the fibrate class used to treat abnormal blood lipid levels. It is less commonly used compared than statins because it treats a different type of cholesterol abnormality to statins. While statins have strong evidence for reducing heart disease and death, there is evidence to suggest that fenofibrate also reduces the risk of heart disease and death. However, this seems only to apply to specific populations of people with elevated triglyceride levels and reduced high-density lipoprotein (HDL) cholesterol. Its use is recommended together with dietary changes.

<span class="mw-page-title-main">Perindopril</span> High blood pressure medication

Perindopril is a medication used to treat high blood pressure, heart failure, or stable coronary artery disease.

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 an FDC product, although the latter is more precise if in fact referring to a mass-produced product having a predetermined combination of drugs and respective dosages. 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. When a combination drug product is a "pill", then it may also be a kind of "polypill" or combopill.

<span class="mw-page-title-main">Ethyl eicosapentaenoic acid</span> Medication

Ethyl eicosapentaenoic acid, sold under the brand name Vascepa among others, is a medication used to treat dyslipidemia and hypertriglyceridemia. It is used in combination with changes in diet in adults with hypertriglyceridemia ≥ 150 mg/dL. Further, it is often required to be used with a statin.

Polycap is a specific five-in-one fixed dose combination polypill created by Cadila Pharmaceuticals Limited of Ahmedabad, India that combines moderate levels of five different medications in a single, one-a-day pill aimed at reducing/preventing heart attacks and strokes.

QRISK3 is a prediction algorithm for cardiovascular disease (CVD) that uses traditional risk factors together with body mass index, ethnicity, measures of deprivation, family history, chronic kidney disease, rheumatoid arthritis, atrial fibrillation, diabetes mellitus, and antihypertensive treatment.

<span class="mw-page-title-main">Dulaglutide</span> Diabetes medication

Dulaglutide, sold under the brand name Trulicity among others, is a medication used for the treatment of type 2 diabetes in combination with diet and exercise. It is also approved in the United States for the reduction of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. It is a once-weekly injection.

Bempedoic acid, sold under the brand name Nexletol among others, is a medication for the treatment of hypercholesterolemia.

References

  1. ↑ "WHO | Polypill holds promise for people with chronic disease". Archived from the original on November 1, 2013.
  2. ↑ "Polypill".
  3. 1 2 3 Wald NJ, Law MR (June 2003). "A strategy to reduce cardiovascular disease by more than 80%". BMJ. 326 (7404): 1419. doi:10.1136/bmj.326.7404.1419. PMC   162259 . PMID   12829553.
  4. ↑ Yusuf S; Islam S; Chow CK; Rangarajan S; Dagenais G; Diaz R; et al. (2011). "Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE Study): a prospective epidemiological survey". Lancet. 378 (9798): 1231–43. doi:10.1016/S0140-6736(11)61215-4. PMID   21872920.
  5. ↑ World Health Organization(2002) Secondary prevention of non-communicable disease in low and middleincome countries through community-based and health service interventions. World Health Organization - Wellcome Trust meeting report 1–3 August 2001, Geneva. http://www.who.int/cardiovascular_diseases/media/en/615.pdf
  6. ↑ World Health Organization(2002) The World Health Report 2002. Reducing risks, promoting healthy life.;WHO, editor. Geneva: WHO.
  7. ↑ Yusuf S (2002). "Two decades ofprogress in preventing vascular disease". Lancet. 360 (9326): 2–3. doi:10.1016/s0140-6736(02)09358-3. PMID   12114031. S2CID   33042777.
  8. ↑ Kuehn BM (July 2006). ""Polypill" could slash diabetes risks". JAMA. 296 (4): 377–80. doi:10.1001/jama.296.4.377. PMID   16868284.
  9. ↑ Sandler, Niklas; Määttänen, Anni; Ihalainen, Petri; Kronberg, Leif; Meierjohann, Axel; Viitala, Tapani; Peltonen, Jouko (Aug 2011). "Inkjet printing of drug substances and use of porous substrates-towards individualized dosing". J Pharm Sci. 100 (8): 3386–95. doi:10.1002/jps.22526. PMID   21360709.
  10. ↑ Elele, Ezinwa; Shen, Yueyang; Khusid, Boris (2010). "Electrodeless electrohydrodynamic printing of personalized medicines". Applied Physics Letters. 97 (23): 233501. Bibcode:2010ApPhL..97w3501E. doi:10.1063/1.3524512.
  11. ↑ Elele, Ezinwa; Shen, Yueyang; Susarla, Ramana; Khusid, Boris; Keyvan, Golshid; Michniak-Kohn, Bozena (Jul 2012). "Electrodeless electrohydrodynamic drop-on-demand encapsulation of drugs into porous polymer films for fabrication of personalized dosage units". Journal of Pharmaceutical Sciences. 101 (7): 2523–2533. doi:10.1002/jps.23165. PMID   22527973.
  12. ↑ "بازتاب دستاورد جدید ستاد اجرایی فرمان امام در تولید دارویی برای سکته قلبی و مغزی". Isna. Retrieved 23 August 2019.
  13. ↑ "تولید داروی پلی پیل و کاهش 50درصدی سکته قلبی و مغزی". فارس.
  14. ↑ Gallagher, James (2019-08-23). "Four-in-one pill prevents third of heart problems". BBC News. Retrieved 23 August 2019.
  15. ↑ McNeil Jr., Donald G. (2019-08-22). "This Daily Pill Cut Heart Attacks by Half. Why Isn't Everyone Getting It?". The New York Times. Retrieved 22 August 2019.
  16. ↑ Sanz G, Fuster V (February 2009). "Fixed-dose combination therapy and secondary cardiovascular prevention: rationale, selection of drugs and target population". Nat Clin Pract Cardiovasc Med. 6 (2): 101–10. doi:10.1038/ncpcardio1419. PMID   19104519. S2CID   205339553.
  17. ↑ Law MR, Wald NJ (June 2002). "Risk factor thresholds: their existence under scrutiny". BMJ. 324 (7353): 1570–6. doi:10.1136/bmj.324.7353.1570. PMC   1123506 . PMID   12089098.

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