Editing Polypill (section)

==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.<ref>{{cite journal |author1=Yusuf S |author2=Islam S |author3=Chow CK |author4=Rangarajan S |author5=Dagenais G |author6=Diaz R | year = 2011 | title = 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 | journal = Lancet | volume = 378 | issue = 9798| pages = 1231–43 | pmid = 21872920 | doi=10.1016/S0140-6736(11)61215-4|display-authors=etal}}</ref> 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”<ref>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</ref> 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<ref>World Health Organization(2002) The World Health Report 2002. Reducing risks, promoting healthy life.;WHO, editor. Geneva: WHO. [https://web.archive.org/web/20021202073217/http://www.who.int/whr/2002/en/]</ref> 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.<ref>{{cite journal | author = Yusuf S | year = 2002 | title = Two decades ofprogress in preventing vascular disease | journal = Lancet | volume = 360 | issue = 9326| pages = 2–3 | doi=10.1016/s0140-6736(02)09358-3 | pmid=12114031| s2cid = 33042777 }}</ref>

====Treating diabetes and metabolic syndrome====

Polypills have been proposed for managing [[diabetes]] (and potentially for [[pre-diabetes]]).<ref>{{cite journal |author=Kuehn BM |title="Polypill" could slash diabetes risks |journal=JAMA |volume=296 |issue=4 |pages=377–80 |date=July 2006 |pmid=16868284 |doi=10.1001/jama.296.4.377}}</ref>

[[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 anti[[platelet]] 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).<ref>{{cite journal |pmid=21360709 | doi=10.1002/jps.22526 | volume=100 | issue=8 | title=Inkjet printing of drug substances and use of porous substrates-towards individualized dosing. | date=Aug 2011 | journal=J Pharm Sci | pages=3386–95| last1=Sandler | first1=Niklas | last2=Määttänen | first2=Anni | last3=Ihalainen | first3=Petri | last4=Kronberg | first4=Leif | last5=Meierjohann | first5=Axel | last6=Viitala | first6=Tapani | last7=Peltonen | first7=Jouko }}</ref><ref>{{cite journal|doi=10.1063/1.3524512|title=Electrodeless electrohydrodynamic printing of personalized medicines|journal=Applied Physics Letters|volume=97|issue=23|pages=233501|year=2010|last1=Elele|first1=Ezinwa|last2=Shen|first2=Yueyang|last3=Khusid|first3=Boris|bibcode=2010ApPhL..97w3501E}}</ref><ref>{{cite journal | doi = 10.1002/jps.23165 | volume=101 | issue=7 | title=Electrodeless electrohydrodynamic drop-on-demand encapsulation of drugs into porous polymer films for fabrication of personalized dosage units | journal=Journal of Pharmaceutical Sciences | pages=2523–2533 | pmid=22527973 | date=Jul 2012| last1=Elele | first1=Ezinwa | last2=Shen | first2=Yueyang | last3=Susarla | first3=Ramana | last4=Khusid | first4=Boris | last5=Keyvan | first5=Golshid | last6=Michniak-Kohn | first6=Bozena }}</ref> 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).