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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 

10-01-2024            

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)

FDA Indication(s)

Notes

Ref#

Atacand®

(candesartan)*

Tablet
  • Treatment of hypertension in adults and children 1 to less than 17 years of age
  • Treatment of heart failure (NYHA class II-IV)

ARBs and ARB Combinations  

*generic available

1

Atacand HCT®

(candesartan/hydrochlorothiazide)*

Tablet
  • Treatment of hypertension

ARBs and ARB Combinations

*generic available

2

Avalide®

(irbesartan/hydrochlorothiazide)*

Tablet
  • Treatment of hypertension:
    • In patients not adequately controlled with monotherapy
    • As initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals

ARBs and ARB Combinations

*generic available

3

Avapro® 

(irbesartan)*

Tablet
  • Treatment of hypertension
  • Treatment of diabetic nephropathy in hypertensive patients with type 2 diabetes, an elevated serum creatinine and proteinuria

ARBs and ARB Combinations

*generic available

4

Azor®

(olmesartan/amlodipine)*

Tablet
  • Treatment of hypertension, alone or with other antihypertensive agents
  • May also be used as initial therapy in patients likely to need multiple antihypertensive agents to achieve their blood pressure goals

ARBs and ARB Combinations

*generic available

5

Benicar®

(olmesartan)*

Tablet
  • Treatment of hypertension in adult and pediatric patients six years of age and older, alone or with other antihypertensive agents

ARBs and ARB Combinations

*generic available

6

Benicar HCT®

(olmesartan/hydrochlorothiazide)*

Tablet
  • Treatment of hypertension

ARBs and ARB Combinations

*generic available

7

Cozaar®

(losartan)*

Tablet
  • Treatment of hypertension in adults and pediatric patients 6 years of age and older
  • To reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy
  • Treatment of diabetic nephropathy with an elevated serum creatine and proteinuria in patients with type 2 diabetes and a history of hypertension

ARBs and ARB Combinations  

 *generic available

8

Diovan®, Valsartan oral solution

Tablet*

Solution
  • Treatment of hypertension in adults and pediatric patients one year of age and older
  • Treatment of heart failure (NYHA class II-IV)
  • Post-myocardial infarction in clinically stable patients with left ventricular failure or left ventricular dysfunction

ARBs and ARB Combinations

*generic available

9, 27

Diovan HCT®

(valsartan/hydrochlorothiazide)*

Tablet
  • Treatment of hypertension in patients not adequately controlled with monotherapy, or as initial therapy in patients likely to need multiple drugs to achieve their BP goals.

ARBs and ARB Combinations

*generic available

10

Edarbi®

(azilsartan)

Tablet
  • Treatment of hypertension

ARBs and ARB Combinations

 

11

Edarbyclor®

(azilsartan/chlorthalidone)

Tablet
  • Treatment of hypertension in patients not adequately controlled with monotherapy or as initial therapy in patients likely to need multiple drugs to help achieve blood pressure goals

ARBs and ARB Combinations

12

Exforge®

(valsartan/amlodipine)*

Tablet
  • Treatment of hypertension in patients not adequately controlled with monotherapy or as initial therapy in patients likely to need multiple drugs to achieve blood pressure goals

ARBs and ARB Combinations

*generic available

14

Exforge HCT®

(valsartan/amlodipine/hydrochlorothiazide)*

Tablet
  • Treatment of hypertension

Limitation of use: Exforge HCT is not indicated for initial treatment of hypertension

ARBs and ARB Combinations

*generic available

15

Hyzaar®

(losartan/hydrochlorothiazide)*

Tablet
  • Treatment of hypertension
  • Reduction in the risk of stroke in patients with hypertension and left ventricular hypertrophy

ARBs and ARB Combinations

*generic available

16

Micardis®

(telmisartan)*

Tablet
  • Treatment of hypertension
  • Cardiovascular risk reduction in patients unable to take angiotensin-converting enzyme (ACE) inhibitors

ARBs and ARB Combinations

*generic available

17

Micardis HCT®

(telmisartan/hydrochlorothiazide)*

Tablet
  • Treatment of hypertension

Limitation of use: Micardis HCT is not indicated for initial therapy

ARBs and ARB Combinations

*generic available

18

Tekturna®

(aliskiren)*

Tablet
  • Treatment of hypertension in adults and in pediatric patients weighing 50 kg or greater who are at least 6 years of age

Renin Inhibitors, Renin Inhibitor Combinations

*generic available

21

Tekturna HCT®

(aliskiren/hydrochlorothiazide)

Tablet
  • Treatment of hypertension in patients not adequately controlled with monotherapy
  • As initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals

Renin Inhibitors, Renin Inhibitor Combinations

22

Tribenzor®

(olmesartan/amlodipine/hydrochlorothiazide)*

Tablet
  • Treatment of hypertension

Limitation of use: Tribenzor is not indicated for initial therapy

ARBs and ARB Combinations

*generic available

19

Telmisartan/Amlodipine*

Tablet
  • Treatment of hypertension
  • Initial therapy in patients likely to need multiple antihypertensive agents to achieve their blood pressure goals

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 Cardiology/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 boxed 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. July 2023.

7

Benicar HCT prescribing information. Cosette Pharmaceuticals, Inc. July 2023.

8

Cozaar prescribing information. Organon LLC. June 2022.

9

Diovan prescribing information. Novartis Pharmaceuticals Corporation. July 2023.

10

Diovan HCT prescribing information. Novartis Pharmaceuticals Corporation. July 2023.

11

Edarbi prescribing information. Azurity Pharmaceuticals America, Inc. January 2024.

12

Edarbyclor prescribing information. Azurity Pharmaceuticals America, Inc. January 2024.

13

Reference no longer used

14

Exforge prescribing information. Novartis Pharmaceuticals Corporation. July 2023.

15

Exforge HCT prescribing information. Novartis Pharmaceuticals Corporation. July 2023.

16

Hyzaar prescribing information. Organon LLC, Inc. March 2023.

17

Micardis prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. December 2022.

18

Micardis HCT prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. June 2023.

19

Tribenzor prescribing information. Cosette Pharmaceuticals, Inc. July 2023.

20

Telmisartan and Amlodipine prescribing information. Mylan Pharmaceuticals Inc. November 2018.

21

Tekturna prescribing information. LXO US. March 2024.

22

Tekturna HCT prescribing information. Noden Pharma INC. November 2022.

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

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Targeted MSC

Available MSC

Final Age Limit

Preferred Status

1-Step

telmisartan-amlodipine tab

40-10 MG ; 40-5 MG ; 80-10 MG ; 80-5 MG

M ; N ; O

N ; Y

Atacand

candesartan cilexetil tab

16 MG ; 32 MG ; 4 MG ; 8 MG

M ; N ; O

O ; Y

Atacand hct

candesartan cilexetil-hydrochlorothiazide tab

16-12.5 MG ; 32-12.5 MG ; 32-25 MG

M ; N ; O

O ; Y

Avalide

irbesartan-hydrochlorothiazide tab

150-12.5 MG ; 300-12.5 MG

M ; N ; O

O ; Y

Avapro

irbesartan tab

150 MG ; 300 MG ; 75 MG

M ; N ; O

O ; Y

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

20 MG ; 40 MG ; 5 MG

M ; N ; O

O ; Y

Benicar hct

olmesartan medoxomil-hydrochlorothiazide tab

20-12.5 MG ; 40-12.5 MG ; 40-25 MG

M ; N ; O

O ; Y

Cozaar

losartan potassium tab

100 MG ; 25 MG ; 50 MG

M ; N ; O

O ; Y

Diovan

valsartan oral soln  ; valsartan tab

160 MG ; 320 MG ; 4 MG/ML ; 40 MG ; 80 MG

M ; N ; O

M ; O ; Y

Diovan hct

valsartan-hydrochlorothiazide tab

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

Exforge

amlodipine besylate-valsartan tab

10-160 MG ; 10-320 MG ; 5-160 MG ; 5-320 MG

M ; N ; O

O ; Y

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

M ; N ; O

O ; Y

Hyzaar

losartan potassium & hydrochlorothiazide tab

100-12.5 MG ; 100-25 MG ; 50-12.5 MG

M ; N ; O

O ; Y

Micardis

telmisartan tab

20 MG ; 40 MG ; 80 MG

M ; N ; O

O ; Y

Micardis hct

telmisartan-hydrochlorothiazide tab

40-12.5 MG ; 80-12.5 MG ; 80-25 MG

M ; N ; O

O ; Y

Tekturna

aliskiren fumarate tab

150 MG ; 300 MG

M ; N ; O

O ; Y

Tekturna hct

aliskiren-hydrochlorothiazide tab

150-12.5 MG ; 150-25 MG ; 300-12.5 MG ; 300-25 MG

M ; N ; O

N

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

CLIENT SUMMARY – STEP THERAPY

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Client Formulary

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

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

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

STEP THERAPY CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

1-Step

TARGET AGENT(S)

PREREQUISITE AGENT(S)

Atacand (candesartan) tablet*
Atacand HCT
(candesartan/hydrochlorothiazide) tablet*
Avapro (irbesartan) tablet*
Avalide (irbesartan/hydrochlorothiazide) tablet*
Azor (olmesartan/amlodipine) tablet*
Benicar (olmesartan) tablet*
Benicar HCT  (olmesartan/hydrochlorothiazide) tablet*
Cozaar (losartan) tablet*
Diovan tablet*, Valsartan oral suspension^
Diovan HCT (valsartan/hydrochlorothiazide) tablet*
Edarbi (azilsartan) tablet
Edarbyclor (azilsartan/chlorthalidone) tablet
Exforge (valsartan/amlodipine) tablet*
Exforge HCT (valsartan/amlodipine/hydrochlorothiazide) tablet*
Hyzaar (losartan/hydrochlorothiazide) tablet*
Micardis (telmisartan) tablet*
Micardis HCT (telmisartan/hydrochrolothiazide) tablet*
Tekturna (aliskiren) tablet*
Tekturna HCT (aliskiren/HCTZ) tablet
Tribenzor (olmesartan/amlodipine/hydrochlorothiazide) tablet*
Telmisartan/Amlodipine tablet*

Any generic ACEI or ACEI combination
OR
any generic ARB or ARB combination
OR
any generic renin inhibitor or generic renin inhibitor combination

* 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:

  1. The requested agent is eligible for continuation of therapy AND ONE of the following:

Agents Eligible for Continuation of Therapy

All target agents are eligible for continuation of therapy
  1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
  2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
  3. The patient has a medication history of use in the past 90 days, intolerance, or hypersensitivity to a prerequisite agent OR
  4. The patient has an FDA labeled contraindication to ALL prerequisite agents

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 _ ARBs_Renin_Inhibitors_and_Combinations_ST _ProgSum_ 10-01-2024