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Angiotensin II Receptor Antagonists (ARBs), Renin Inhibitors, and Combinations Step Therapy Program Summary
Policy Number: PH-1027
This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx, and Health Insurance Marketplace formularies.
POLICY REVIEW CYCLE
Effective Date |
Date of Origin |
10/1/2023 |
|
FDA APPROVED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Atacand® (candesartan) |
|
ARBs and ARB Combinations *- generic available |
1 |
Atacand HCT® (candesartan/HCTZ) |
|
ARBs and ARB Combinations HCTZ = hydrochlorothiazide * - generic available |
2 |
Avalide® (irbesartan/HCTZ) |
|
ARBs and ARB Combinations HCTZ = hydrochlorothiazide * - generic available |
3 |
Avapro® (irbesartan) Tablet* |
|
ARBs and ARB Combinations * - generic available |
4 |
Azor® (olmesartan/amlodipine) Tablet* |
|
ARBs and ARB Combinations * - generic available |
5 |
Benicar® (olmesartan) Tablet* |
|
ARBs and ARB Combinations * - generic available |
6 |
Benicar HCT® (olmesartan/HCTZ) Tablet* |
|
ARBs and ARB Combinations HCTZ = hydrochlorothiazide * - generic available |
7 |
Cozaar® (losartan) Tablet* |
|
ARBs and ARB Combinations * - generic available |
8 |
Diovan®, Valsartan oral solution |
|
ARBs and ARB Combinations * - generic available |
9, 27 |
Diovan HCT® (valsartan/HCTZ) Tablet* |
|
ARBs and ARB Combinations HCTZ = hydrochlorothiazide * - generic available |
10 |
Edarbi® (azilsartan) Tablet |
|
ARBs and ARB Combinations
|
11 |
Edarbyclor® (azilsartan/chlorthalidone) Tablet |
|
ARBs and ARB Combinations |
12 |
Exforge® (valsartan/amlodipine) Tablet* |
|
ARBs and ARB Combinations * - generic available |
14 |
Exforge HCT® (valsartan/amlodipine/HCTZ) Tablet* |
Limitation of use: Exforge HCT is not indicated for initial treatment of hypertension |
ARBs and ARB Combinations HCTZ = hydrochlorothiazide * - generic available |
15 |
Hyzaar® (losartan/HCTZ) Tablet* |
|
ARBs and ARB Combinations HCTZ = hydrochlorothiazide * - generic available |
16 |
Micardis® (telmisartan) Tablet* |
|
ARBs and ARB Combinations * - generic available |
17 |
Micardis HCT® (telmisartan/HCTZ) Tablet* |
Limitation of use: Micardis HCT is not indicated for initial therapy |
ARBs and ARB Combinations HCTZ = hydrochlorothiazide * - generic available |
18 |
Tekturna® (aliskiren) Tablet* |
|
Renin Inhibitors, Renin Inhibitor Combinations * - generic available |
21 |
Tekturna HCT® (aliskiren/HCTZ) Tablet |
|
Renin Inhibitors, Renin Inhibitor Combinations HCTZ = hydrochlorothiazide |
22 |
Tribenzor® (olmesartan/amlodipine/HCTZ) Tablet* |
Limitation of use: Tribenzor is not indicated for initial therapy |
ARBs and ARB Combinations HCTZ = hydrochlorothiazide * - generic available |
19 |
Twynsta® (telmisartan/amlodipine) Tablet* |
|
ARBs and ARB Combinations * - generic available |
20 |
See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm
CLINICAL RATIONALE
ACEIs & ARBs |
Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin II Receptor Blockers (ARBs) are recommended as a first-line pharmacotherapy options for adults with hypertension (HTN), for adults with hypertension and comorbid stable ischemic heart disease (SIHD), and heart failure with reduced ejection fraction (HFrEF). In adults with hypertension and heart failure with preserved ejection fraction (HFpEF), ACEI and ARBs are to be added once diuretics have managed volume overload. ACEIs are first-line options for adults with hypertension and chronic kidney disease (CKD). ARBs are a reasonable alternative if the patient is intolerant of ACEIs. For adults who experience a stroke or transient ischemic attack (TIA) and are hypertensive, once stabilized, thiazide diuretics, ACEIs, ACEi and thiazide combinations, and ARBs are useful. In adults with hypertension and diabetes mellitus, ACEIs and ARBs are among first-line options. If albuminuria is present, ACEis or ARBs may be considered due to their best efficacy among the drug classes on urinary albumin excretion. Treatment of adults with hypertension with an ARB can be useful for prevention of recurrence of atrial fibrillation. The American College of Cariology/American Heart Association Task Force on Clinical Practice Guidelines did not differentiate ACEIs or ARBs within their pharmacological classes.(23) Pediatric guidelines state that pharmacologic treatment of hypertension in children and adolescents should be initiated with an ACEI, ARB, long-acting calcium channel blocker, or a thiazide diuretic. In children with hypertension and CKD, proteinuria, or diabetes mellitus, an ACEI or ARB is recommended as the initial antihypertensive agent unless there is an absolute contraindication.(24) |
Direct Renin Inhibitors |
Aliskiren decreases plasma renin activity (PRA), a different mechanism than ACEIs and ARBS. Studies have shown aliskiren to be as effective as other antihypertensive drugs. It is unclear whether the PRA decrease provided by aliskiren has an impact on clinical outcomes and cardiovascular endpoints.(25) |
Safety |
In patients with hypertension undergoing major surgery, discontinuation of ACEIs or ARBs perioperatively may be considered.(23)
The FDA added a contraindication against the use of aliskiren with ARBs or ACEIs in patients with diabetes because of the risk of renal impairment, hypotension, and hyperkalemia. A warning was added to avoid use of aliskiren with ARBs or ACEIs in patients with moderate to severe renal impairment (i.e., where glomerular filtration rate [GFR] les than 60 mL/min). The FDA stated that Valturna (a combination containing aliskiren and valsartan) should not be used in patients with diabetes and Valturna was removed from the market in July 2012.(26)
All ARBs and Renin Inhibitors have a black box warning concerning fetal toxicity. When pregnancy is detected, the agent should be discontinued. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.(1-22, 27) |
REFERENCES
Number |
Reference |
1 |
Atacand prescribing information. AstraZeneca. June 2020. |
2 |
Atacand HCT prescribing information. AstraZeneca. May 2020. |
3 |
Avalide prescribing information. Bristol-Myers Squibb, Sanofi-Aventis. September 2021. |
4 |
Avapro prescribing information. Bristol-Myers Squibb, Sanofi-Aventis. September 2021. |
5 |
Azor prescribing information. Cosette Pharmaceuticals, Inc. February 2022. |
6 |
Benicar prescribing information. Cosette Pharmaceuticals, Inc. February 2022. |
7 |
Benicar HCT prescribing information. Cosette Pharmaceuticals, Inc. February 2022. |
8 |
Cozaar prescribing information. Organon LLC. October 2021. |
9 |
Diovan prescribing information. Novartis Pharmaceuticals Corporation. April 2021. |
10 |
Diovan HCT prescribing information. Novartis Pharmaceuticals Corporation. August 2020. |
11 |
Edarbi prescribing information. Takeda Pharmaceuticals America, Inc. March 2020. |
12 |
Edarbyclor prescribing information. Takeda Pharmaceuticals America, Inc. March 2020. |
13 |
|
14 |
Exforge prescribing information. Novartis Pharmaceuticals Corporation. April 2021. |
15 |
Exforge HCT prescribing information. Novartis Pharmaceuticals Corporation. February 2021. |
16 |
Hyzaar prescribing information. Organon LLC, Inc. June 2021. |
17 |
Micardis prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. December 2022. |
18 |
Micardis HCT prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. December 2022. |
19 |
Tribenzor prescribing information. Daiichi Sankyo, Inc. October 2020. |
20 |
Twynsta prescribing information. Boehringer Ingelheim Pharmaceuticals Inc. November 2018. |
21 |
Tekturna prescribing information. Noden Pharma. March 2021. |
22 |
Tekturna HCT prescribing information. Noden Pharma. September 2020. |
23 |
2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Journal of the American College of Cardiology. 71(19): e127-e248. May 2018. http://www.onlinejacc.org/content/71/19/e127?_ga=2.237976455.681665904.1587569918-1112583575.1587569918. |
24 |
Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;140(3):e20171904 September 2017. https://pediatrics.aappublications.org/content/140/3/e20171904. |
25 |
Sen S, Ufuktepe B, et al. “Renin inhibitors in diabetes and hypertension: an update”. EXCLI Journal 2014; 13: 1111-1119. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464353/. |
26 |
FDA. FDA Drug Safety Communication: New Warning and Contraindication for blood pressure medicines containing aliskiren (Tekturna). https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-new-warning-and-contraindication-blood-pressure-medicines-containing Content current as of 6/24/2021. |
27 |
Valsartan oral solution prescribing information. Lifsa Drugs, LLC. April 2022 |
POLICY AGENT SUMMARY STEP THERAPY
Agent Names |
Strength |
Targeted MSC |
Available MSC |
Final Age Limit |
Preferred Status |
1-Step |
|||||
ATACAND*candesartan cilexetil tab ; CANDESARTAN*candesartan cilexetil tab |
16 MG ; 32 MG ; 4 MG ; 8 MG |
M ; N ; O |
O ; Y |
|
|
ATACAND*candesartan cilexetil-hydrochlorothiazide tab ; CANDESARTAN*candesartan cilexetil-hydrochlorothiazide tab |
16-12.5 MG ; 32-12.5 MG ; 32-25 MG |
M ; N ; O |
O ; Y |
|
|
AVALIDE*irbesartan-hydrochlorothiazide tab ; IRBESARTAN/HYDROCHLOROTHI*irbesartan-hydrochlorothiazide tab |
150-12.5 MG ; 300-12.5 MG |
M ; N ; O |
O ; Y |
|
|
AVAPRO*irbesartan tab ; IRBESARTAN*irbesartan tab |
150 MG ; 300 MG ; 75 MG |
M ; N ; O |
O ; Y |
|
|
AMLODIPINE/OLMESARTAN*amlodipine besylate-olmesartan medoxomil tab ; AZOR*amlodipine besylate-olmesartan medoxomil tab |
10-20 MG ; 10-40 MG ; 5-20 MG ; 5-40 MG |
M ; N ; O |
O ; Y |
|
|
BENICAR*olmesartan medoxomil tab ; OLMESARTAN*olmesartan medoxomil tab |
20 MG ; 40 MG ; 5 MG |
M ; N ; O |
O ; Y |
|
|
BENICAR*olmesartan medoxomil-hydrochlorothiazide tab ; OLMESARTAN*olmesartan medoxomil-hydrochlorothiazide tab |
20-12.5 MG ; 40-12.5 MG ; 40-25 MG |
M ; N ; O |
O ; Y |
|
|
COZAAR*losartan potassium tab ; LOSARTAN*losartan potassium tab |
100 MG ; 25 MG ; 50 MG |
M ; N ; O |
O ; Y |
|
|
DIOVAN*valsartan tab ; VALSARTAN*valsartan oral soln ; VALSARTAN*valsartan tab |
160 MG ; 320 MG ; 4 MG/ML ; 40 MG ; 80 MG |
M ; N ; O |
N ; O ; Y |
|
|
DIOVAN*valsartan-hydrochlorothiazide tab ; VALSARTAN/HYDROCHLOROTHIA*valsartan-hydrochlorothiazide tab |
0 ; 160-12.5 MG ; 160-25 MG ; 320-12.5 MG ; 320-25 MG ; 80-12.5 MG |
M ; N ; O |
O ; Y |
|
|
EDARBI*azilsartan medoxomil tab |
40 MG ; 80 MG |
M ; N ; O |
N |
|
|
EDARBYCLOR*azilsartan medoxomil-chlorthalidone tab |
40-12.5 MG ; 40-25 MG |
M ; N ; O |
N |
|
|
AMLODIPINE*amlodipine besylate-valsartan tab ; EXFORGE*amlodipine besylate-valsartan tab |
10-160 MG ; 10-320 MG ; 5-160 MG ; 5-320 MG |
M ; N ; O |
O ; Y |
|
|
AMLODIPINE/VALSARTAN/HYDR*amlodipine-valsartan-hydrochlorothiazide tab ; EXFORGE*amlodipine-valsartan-hydrochlorothiazide tab |
10-160-12.5 MG ; 10-160-25 MG ; 10-320-25 MG ; 5-160-12.5 MG ; 5-160-25 MG |
M ; N ; O |
O ; Y |
|
|
HYZAAR*losartan potassium & hydrochlorothiazide tab ; LOSARTAN*losartan potassium & hydrochlorothiazide tab |
100-12.5 MG ; 100-25 MG ; 50-12.5 MG |
M ; N ; O |
O ; Y |
|
|
MICARDIS*telmisartan tab ; TELMISARTAN*telmisartan tab |
20 MG ; 40 MG ; 80 MG |
M ; N ; O |
O ; Y |
|
|
MICARDIS*telmisartan-hydrochlorothiazide tab ; TELMISARTAN/HYDROCHLOROTH*telmisartan-hydrochlorothiazide tab |
40-12.5 MG ; 80-12.5 MG ; 80-25 MG |
M ; N ; O |
O ; Y |
|
|
ALISKIREN*aliskiren fumarate tab ; TEKTURNA*aliskiren fumarate tab |
150 MG ; 300 MG |
M ; N ; O |
O ; Y |
|
|
TEKTURNA*aliskiren-hydrochlorothiazide tab |
150-12.5 MG ; 150-25 MG ; 300-12.5 MG ; 300-25 MG |
M ; N ; O |
N |
|
|
OLMESARTAN*olmesartan-amlodipine-hydrochlorothiazide tab ; TRIBENZOR*olmesartan-amlodipine-hydrochlorothiazide tab |
20-5-12.5 MG ; 40-10-12.5 MG ; 40-10-25 MG ; 40-5-12.5 MG ; 40-5-25 MG |
M ; N ; O |
O ; Y |
|
|
TELMISARTAN/AMLODIPINE*telmisartan-amlodipine tab ; TWYNSTA*telmisartan-amlodipine tab |
40-10 MG ; 40-5 MG ; 80-10 MG ; 80-5 MG |
M ; N ; O |
N ; O ; Y |
|
|
CLIENT SUMMARY – STEP THERAPY
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Atacand |
candesartan cilexetil tab |
16 MG ; 32 MG ; 4 MG ; 8 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Atacand hct |
candesartan cilexetil-hydrochlorothiazide tab |
16-12.5 MG ; 32-12.5 MG ; 32-25 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Avalide |
irbesartan-hydrochlorothiazide tab |
150-12.5 MG ; 300-12.5 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Avapro |
irbesartan tab |
150 MG ; 300 MG ; 75 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Azor |
amlodipine besylate-olmesartan medoxomil tab |
10-20 MG ; 10-40 MG ; 5-20 MG ; 5-40 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Benicar |
olmesartan medoxomil tab |
20 MG ; 40 MG ; 5 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Benicar hct |
olmesartan medoxomil-hydrochlorothiazide tab |
20-12.5 MG ; 40-12.5 MG ; 40-25 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Cozaar |
losartan potassium tab |
100 MG ; 25 MG ; 50 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Diovan |
valsartan oral soln ; valsartan tab |
160 MG ; 320 MG ; 4 MG/ML ; 40 MG ; 80 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Diovan hct |
valsartan-hydrochlorothiazide tab |
0 ; 160-12.5 MG ; 160-25 MG ; 320-12.5 MG ; 320-25 MG ; 80-12.5 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Edarbi |
azilsartan medoxomil tab |
40 MG ; 80 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Edarbyclor |
azilsartan medoxomil-chlorthalidone tab |
40-12.5 MG ; 40-25 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Exforge |
amlodipine besylate-valsartan tab |
10-160 MG ; 10-320 MG ; 5-160 MG ; 5-320 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Exforge hct |
amlodipine-valsartan-hydrochlorothiazide tab |
10-160-12.5 MG ; 10-160-25 MG ; 10-320-25 MG ; 5-160-12.5 MG ; 5-160-25 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Hyzaar |
losartan potassium & hydrochlorothiazide tab |
100-12.5 MG ; 100-25 MG ; 50-12.5 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Micardis |
telmisartan tab |
20 MG ; 40 MG ; 80 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Micardis hct |
telmisartan-hydrochlorothiazide tab |
40-12.5 MG ; 80-12.5 MG ; 80-25 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Tekturna |
aliskiren fumarate tab |
150 MG ; 300 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Tekturna hct |
aliskiren-hydrochlorothiazide tab |
150-12.5 MG ; 150-25 MG ; 300-12.5 MG ; 300-25 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Tribenzor |
olmesartan-amlodipine-hydrochlorothiazide tab |
20-5-12.5 MG ; 40-10-12.5 MG ; 40-10-25 MG ; 40-5-12.5 MG ; 40-5-25 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Twynsta |
telmisartan-amlodipine tab |
40-10 MG ; 40-5 MG ; 80-10 MG ; 80-5 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
STEP THERAPY CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
||||||
1-Step |
* Available as generic; included as a prerequisite in the step therapy program ^ Branded generic products available; targeted in the step therapy program Target Agent(s) will be approved when ONE of the following is met:
Length of Approval: 12 months |
This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.
Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.
Commercial _ PS _ Angiotensin II Receptor Antagonists (ARBs), Renin Inhibitors, and Combinations Step Therapy _ProgSum_ 10/1/2023