This year for Hypertension Awareness Month and World Hypertension Day (May 17), I want to discuss about the role of single pill combination in the management of hypertension.  Single Pill Combination has been consistently recommended in various Hypertension Guidelines to assist with blood pressure control.  However, there is no great resource to guide available options of single pill combination in Ontario.

By combining two medications into a single pill (therefore referred to as single pill combination), it offers various advantages. It can increase efficacy, reduce pill burden, lower dispensing cost and improve patient compliance.  Single pill Combinations used in hypertension may result in using lower doses of each drug that would otherwise be necessary to achieve the same goals with monotherapy.

It does sound very convincing but here are few considerations to bear in mind:

  • Education – It is important to educate patients and caregivers that a single pill combination actually contains two different medications with different pharmacological effects and different side effect profiles. It also means each pill contains two different dosing strength to correspond with the two medications (e.g. Each tablet of Coversyl Plus 8mg/1.25mg contains perindopril 8mg and indapamide 1.25mg)
  • Risk of Error and Confusion at Transition of Care – While in community, it would make things easier to combine two medications into a single pill, it can complicate things when patients are transferred to a hospital where single pill combination isn’t part of the hospital formulary. It may be routine practice to substitute the single pill combination with two active medications. However upon discharge, medication reconciliation may not occur or sometimes the patient isn’t discharged back on the single pill combination. For example, a patient may be stabilized on Caduet which contains both atorvastatin and amlodipine. On discharge, the medication list only specified atorvastatin and amlodipine. The nurse / patient may not recognize it is the same as Caduet and start or continue all these medications.
  • Drug Shortages often occur in single pill combination – Nowadays, any medication can go into drug shortage including single pill combination. According to drugshortagecanada.ca, there is a drug shortage of ramipril/hydrochlorothiazide combination pill and the apo-brand of telmisartan/hydrochorothiazide combination pill has been discontinued by Apotex. When this occurs, the default practice is to substitute with two separate medications, defeating the original purpose to save on drug cost, reduce pill burden and improve patient compliance.
  • Combination Pill with Chlorthalidone? – This isn’t really a consideration but my wish list is to have a combination pill with chlorthalidone instead of hydrochlorothiazide. After all, it is recommended to use a long acting diuretic for blood pressure control based on the ALLHAT trial. Why can’t this be done?

Here are the options for ACE inhibitor / Diuretic Combinations Products listed for coverage in Ontario (as of May 2018):

Coversyl Plus:

  • Peridopril/Indapmide 2mg/0.625mg po daily
  • Peridopril/Indapimide 4mg/1.25mg po daily
  • Peridopril/Indapmide 8mg/2.5mg po daily

AltaceHCTZ:

  • Ramipril/Hydrochlorothiazide 2.5mg/12.5mg po daily
  • Ramipril/Hydrochlorothiazide 5mg/12.5mg po daily
  • Ramipril/Hydrochlorothiazide 5mg/25mg po daily
  • Ramipril/Hydrochlorothiazide 10mg/12.5mg po daily
  • Ramipril/Hydrochlorothiazide 10mg/25mg po daily

Vaseretic

  • Enalapril/Hydrochlorothiazide 5mg/12.5mg po daily
  • Enalapril/hydrochlorothiazide 10mg/25mg po daily

Inhibace Plus

  • Cilazapril/Hydrochlorothiazide 5mg/12.5mg po daily

Zestoretic (Type Z)

  • Lisinopril/Hydrochlorothizide 10mg/12.5mg po daily
  • Lisinopril/Hydrochlorothiazide 20mg/12.5mg po daily
  • Lisinopril/Hydrochlorothiazide 20mg/25mg po daily

Prinzide (Type P)

  • Lisinopril/Hydrochlorothizide 10mg/12.5mg po daily
  • Lisinopril/Hydrochlorothiazide 20mg/12.5mg po daily
  • Lisinopril/Hydrochlorothiazide 20mg/25mg po daily

Accuretic

  • Quinapril/Hydrochlorothiazide 10mg/12.5mg po daily
  • Quinapril/Hydrochlorothiazide 20mg/12.5mg po daily
  • Quinapril/Hydrochlorothiazide 20mg/25mg po daily

Here are the options for ARB Combinations Products listed for coverage in Ontario (as of May 2018):

Olmetec Plus

  • Olmesartan medoxomil/Hydrochlorothiazide 20mg/12.5mg po daily
  • Olmesartan medoxomil/Hydrochlorothiazide 40mg/12.5mg po daily
  • Olmesartan medoxomil/Hydrochlorothiazide 40mg/25mg po daily

Teveten Plus

  • Eprosartan/Hydrochlorothiazide 600mg/12.mg po daily

Hyzaar

  • Losartan/Hydrochlorothiazide 100mg/25mg po daily
  • Losartan/Hydrochlorothiazide 50mg/12.5mg po daily
  • Losartan/Hydrochlorothiazide 100mg/12.5mg po daily

Avalide

  • Irbesartan/Hydrochlorothiazide 150mg/12.5mg po daily
  • Irbesartan/Hydrochlorothiazide 300mg/12.5mg po daily
  • Irbesartan/Hydrochlorothiazide 300mg/25mg po daily

Atacand Plus

  • Candesartan/Hydrochlorothiazide 32mg/12.5mg po daily
  • Candesartan/Hydrochlorothiazide 16mg/12.5mg po daily

Valsartan HCT

  • Valsartan/Hydrochlorothiazide 160mg/12.5mg po daily
  • Valsartan/Hydrochlorothiazide 160mg/25mg po daily
  • Valsartan/Hydrochlorothiazide 80mg/12.5mg po daily
  • Valsartan/Hydrochlorothiazide 320mg/12.5mg po daily
  • Valsartan/Hydrochlorothiazide 320mg/25mg po daily

Micardis Plus

  • Telmisartan/Hydrochlorothiazide 80mg/12.5mg po daily
  • Telmisartan/Hydrochlorothiazide 80mg/25mg po daily

Twynsta

  • Telmisartan/Amlodipine 40mg/5mg po daily
  • Telmisartan/Amlodipine 40mg/10mg po daily
  • Telmisartan/Amlodipine 80mg/5mg po daily
  • Telmisartan/Amlodipine 80mg/10mg po daily

 

In addition to these single pill combinations (usually used in the treatment of hypertension), other cardiac medications are also available as single pill combinations.

Below are few examples:

  • Entresto contains valsartan and sacubitril in the following dosing combinations:
    • 26mg/24mg, 51mg/49mg, 103/97mg
  • Caduet contains amlodipine and atorvastatin in the following dosing combinations:
    • 5mg/10mg, 5mg/20mg, 5mg/40mg, 5mg/80mg,
    • 10mg/10mg, 10mg/20mg, 10mg/40mg, 10mg/80mg)
  • Aldactazide – contains hydrochlorothiazide 25mg & spironolactone 25mg
  • Dyazide – contains hydrochlorothiazide 25mg & triamterone 50mg
  • Moduret – contains hydrochlorothiazide 25mg & amiloride 5mg

In my opinion, these are great options to reduce pill burden, improve compliance and save on dispensing fees. But single pill combination also comes with safety concerns especially when there is lack of awareness or education to patients / caregivers or during transition care where single pill combination may be dispensed in different formats.

Do you have any experience or comments about single pill combination? Thank you for reading my post.

 

 

 

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