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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.
TARGET AGENT(S)
ARB and ARB combinations:
Atacand® (candesartan)a
Atacand HCT® (candesartan/hydrochlorothiazide)a
Avapro® (irbesartan)a
Avalide® (irbesartan/hydrochlorothiazide)a
Azor® (olmesartan/amlodipine)a
Benicar® (olmesartan)a
Benicar HCT® (olmesartan/hydrochlorothiazide)a
Cozaar® (losartan) a
Diovan® (valsartan) a
Diovan HCT® (valsartan/hydrochlorothiazide)a
Edarbi® (azilsartan)
Edarbyclor® (azilsartan/chlorthalidone)
Eprosartan
Exforge® (valsartan/amlodipine)a
Exforge HCT® (valsartan/amlodipine/hydrochlorothiazide)a
Hyzaar® (losartan/hydrochlorothiazide)a
Micardis® (telmisartan)a
Micardis HCT® (telmisartan/hydrochrolothiazide)a
Tribenzor® (olmesartan/amlodipine/hydrochlorothiazide)a
Twynsta® (telmisartan/amlodipine)a
Valsartan oral solution
Renin or Renin Inhibitor combinations:
Tekturna® (aliskiren)a
Tekturna HCT® (aliskiren/hydrochlorothiazide)
a – generic available that is a prerequisite agent for step therapy program
PRIOR AUTHORIZATION CRITERIA FOR APPROVAL
Target Agent(s) will be approved when ONE of the following is met:
- Information has been provided that indicates the patient is currently being treated with the requested agent within the past 90 days.
OR
- The prescriber states the patient is currently being treated with the requested agent within the past 90 days AND is at risk if therapy is changed
OR
- The patient’s medication history includes use of a generic ACEI, generic ACEI combination, generic ARB, generic ARB combination, or generic renin inhibitor product within the past 90 days
OR
- The patient has an intolerance or hypersensitivity to a generic ACEI, generic ACEI combination, generic ARB, generic ARB combination, or generic renin inhibitor product
OR
- The patient has an FDA labeled contraindication to ALL generic ACEIs, generic ACEI combinations, generic ARBs, generic ARB combinations, or generic renin inhibitor products
Length of Approval: 12 months
FDA APPROVED INDICATIONS AND DOSAGE
ARBs and ARB Combinations 1-22, 27
Agent(s) |
Indication(s) |
Dosage |
ARBs and ARB Combinations
|
||
Atacand® (candesartan)a
Tablet |
|
Hypertension (HTN): 2-32 mg, usual starting recommended starting dose is 16 mg once daily. May be given once or twice daily with total daily doses from 8-32 mg. Larger doses do not appear to have greater effects; limited experience with such doses. Pediatric HTN: See package insert Heart Failure (HF): Recommended initial dose is 4 mg daily. Target dose is 32 mg daily as tolerated by the patient |
Atacand HCT® (candesartan/HCTZ)a
Tablet |
|
HTN: Usual recommended starting dose is 16-12.5 mg once daily. Dose ranges from 8 mg to 32 mg of candesartan and 12.5 to 50 mg of HCTZ once to twice daily. Doses larger than 32 mg do not appear to have a greater BP lowering effect. |
Avalide® (irbesartan/HCTZ)a
Tablet |
|
HTN: The usual starting dose is 150/12.5 mg once daily. The dosage can be increased to a maximum of 300/25 mg once daily. |
Avapro® (irbesartan)a
Tablet |
|
HTN: Initially, 150 mg once daily; 75 mg in volume- or salt-depleted patients. Patients requiring further BP reduction may be titrated to a maximum dose of 300 mg once daily. Diabetic Nephropathy: Target dose is 300 mg/day. |
Azor® (olmesartan/ amlodipine)a
Tablet |
|
HTN: The recommended starting dose is 5/20 mg once daily. Titrate as needed up to a maximum of 10/40 mg once daily. |
Benicar® (olmesartan)a
Tablet |
|
HTN: The usual recommended starting dose is 20 mg once daily. Doses more than 40 mg/day do not appear to have greater benefit; twice daily dosing has no advantage over the same dose given once daily. Pediatric HTN: The usual recommended starting dose is 10 mg once daily for patients who weigh 20 to < 35 kg or 20 mg once daily for patients who weigh ≥ 35 kg. May be increased to a maximum of 20 mg once daily for patients who weigh < 35 kg or 40 mg once daily for patients who weigh ≥ 35 kg |
Benicar HCT® (olmesartan/HCTZ)a
Tablet
|
|
HTN: The recommended starting dose in patients whose blood pressure is not adequately controlled with olmesartan monotherapy is 40/12.5 mg. Recommended starting dose for patients whose BP is not adequately controlled with HCT monotherapy or who experience dose-limiting adverse reactions with hydrochlorothiazide is 20/12.5 mg Dose can be titrated up to 40/25 mg if necessary.
|
Cozaar® (losartan)a
Tablet |
|
HTN: The usual starting dose is 50 mg once daily; can be increased to a maximum of 100 mg once daily as needed to control blood pressure. A starting dose of 25 mg is recommended for patients with possible intravascular depletion. Pediatric HTN: The usual recommended starting dose is 0.7 mg/kg once daily (up to 50 mg total). Dosage should be adjusted according to blood pressure response. Doses above 1.4 mg/kg (or in excess of 100 mg) daily have not been studied in pediatric patients. Hypertensive patients with left ventricular hypertrophy (LVH): The usual starting dose is 50 mg once daily. Hydrochlorothiazide (HCTZ) 12.5 mg daily should be added and/or the dose of Cozaar should be increased to 100 mg once daily followed by an increase in HCTZ to 25 mg once daily, based on blood pressure response. Nephropathy in type 2 diabetic patients: The usual starting dose is 50 mg once daily. The dose should be increased to 100 mg once daily based on blood pressure response.
|
Diovan®a, Valsartan oral solution
Tablet, solution |
|
HTN: The recommended starting dose is 80 or 160 mg once daily when used as monotherapy in patients who are not volume depleted. Patients requiring greater reduction may be started at the higher dose. The dose range is 80-320 mg once daily. Pediatric HTN: The usual recommended starting dose is 1 mg/kg once daily (up to 40 mg total). Maximum dose is 4 mg/kg once daily (160 mg). HF: The recommended starting dose is 40 mg twice daily. Up-titrate to 80 mg and 160 mg twice daily or to the highest dose tolerated by the patient. The maximum daily dose administered in clinical trials is 320 mg in divided doses. Post-myocardial infarction: The recommended starting dose is 20 mg twice daily. Patients may be up-titrated to a target maintenance dose of 160 mg twice daily, as tolerated by the patient.
|
Diovan HCT® (valsartan/HCTZ)a
Tablet |
|
HTN: The usual starting dose is valsartan/HCTZ 160/12.5 mg once daily. Titrate to maximum of 320/25 mg once daily. |
Edarbi® (azilsartan)
Tablet |
|
HTN: The recommended dose is 80 mg once daily. Consider starting dose of 40 mg for patients who are treated with high doses of diuretics. |
Edarbyclor® (azilsartan/ chorthalidone)
Tablet |
|
HTN: The recommended starting dose is 40/12.5 mg once daily. The dosage may be increased to 40/25 mg after 2 to 4 weeks as need to achieve blood pressure goals. Doses above 40/25 mg are probably not useful. |
Eprosartan
Tablet |
|
HTN: The usual recommended dose is 600 mg once daily when used in patients not volume depleted. Give once or twice daily with total daily doses range 400-800 mg. There is limited experience with doses beyond 800 mg/day. |
Exforge® (valsartan/ amlodipine)a
Tablet |
|
HTN: Dose once daily. Increase as needed to a maximum dose of 10/320 mg once daily. |
Exforge HCT® (valsartan/ amlodipine/HCTZ)a
Tablet |
Limitation of use: Exforge HCT is not indicated for initial treatment of hypertension |
HTN: Initial dose 5/160 mg once daily. The maximum recommended dose is 10/320/25 mg. |
Hyzaar® (losartan/HCTZ)a
Tablet |
|
HTN: The usual starting dose is losartan/HCTZ 50/12.5 mg once daily. May increase to a maximum of losartan/HCTZ 100/25 once daily. HTN/LVH: In patients whose blood pressure is not adequately controlled on 50 mg losartan once daily, initiate treatment with Hyzaar 50/12.5 mg. If additional blood pressure reduction is needed, increase to 100/12.5 mg, followed by 100/25 mg once daily. |
Micardis® (telmisartan)a
Tablet |
|
HTN: The usual starting dose is 40 mg once daily. Blood pressure response is dose-related over the range of 20 to 80 mg. Cardiovascular risk reduction: The recommended dose is 80 mg once daily. |
Micardis HCT® (telmisartan/HCTZ)a
Tablet |
Limitation of use: Micardis HCT is not indicated for initial therapy |
HTN: Initiate a patient whose blood pressure is not adequately controlled with telmisartan monotherapy 80 mg or HCTZ 25 mg on 80/12.5 mg. Dose can be titrated up to 160/25 mg if necessary. |
Tribenzor® (olmesartan/ amlodipine/HCTZ)a
Tablet
|
Limitation of use: Tribenzor is not indicated for initial therapy |
HTN: Dose once daily. Dosage may be increased after 2 weeks. The maximum recommended dose is 40/10/25 mg. |
Twynsta® (telmisartan/ amlodipine)a
Tablet |
|
HTN: The usual starting dose is 40/5 mg once daily. Patients requiring larger blood pressure reductions may be started on 80/5 mg once daily. The maximum recommended dose is 80/10 mg once daily. |
HCTZ = hydrochlorothiazide
HTN = hypertension
a – generic available
Agent(s) |
Indication(s) |
Dosage |
Renin Inhibitors, Renin Inhibitor Combinations |
||
Tekturna® (aliskiren)a
Tablet |
|
HTN: Recommended starting dose is 150 mg once daily. In patients whose blood pressure is not adequately controlled, dose may be increased to 300 mg daily. Doses above 300 mg did not give an increased BP response.
|
Tekturna HCT® (aliskiren/HCTZ)
Tablet |
|
HTN: The usual recommended starting dose is 150/12.5 mg once daily. The dose may be titrated to a maximum of 300/25 mg. |
HCTZ = hydrochlorothiazide
HTN= hypertension
a - generic available
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, 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] < 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
References
- Atacand prescribing information. AstraZeneca. June 2020.
- Atacand HCT prescribing information. AstraZeneca. May 2020.
- Avalide prescribing information. Bristol-Myers Squibb, Sanofi-Aventis. December 2020.
- Avapro prescribing information. Bristol-Myers Squibb, Sanofi-Aventis. December 2020.
- Azor prescribing information. Daiichi-Sankyo, Inc. October 2020.
- Benicar prescribing information. Daiichi-Sankyo, Inc. October 2019.
- Benicar HCT prescribing information. Daiichi-Sankyo, Inc. May 2020.
- Cozaar prescribing information. Merck & Co., Inc. June 2020.
- Diovan prescribing information. Novartis Pharmaceuticals Corporation. April 2021.
- Diovan HCT prescribing information. Novartis Pharmaceuticals Corporation. August 2020.
- Edarbi prescribing information. Takeda Pharmaceuticals Amerca, Inc. March 2020.
- Edarbyclor prescribing information. Takeda Pharmaceuticals America, Inc. March 2020.
- Eprosartan prescribing information. Mylan Pharmaceuticals, Inc. November 2014.
- Exforge prescribing information. Novartis Pharmaceuticals Corporation. March 2020.
- Exforge HCT prescribing information. Novartis Pharmaceuticals Corporation. February 2021.
- Hyzaar prescribing information. Merck & Co., Inc. August 2020.
- Micardis prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. July 2020.
- Micardis HCT prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. August 2020.
- Tribenzor prescribing information. Daiichi Sankyo, Inc. October 2020.
- Twynsta prescribing information. Boehringer Ingelheim Pharmaceuticals Inc. November 2018.
- Tekturna prescribing information. Novartis Pharmaceuticals Corporation. June 2020.
- Tekturna HCT prescribing information. Novartis Pharmaceuticals Corporation. November 2016.
- 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 Accessed 4/8/2021.
- 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 Accessed 4/8/2021.
- 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/ Accessed 4/22/2020
- 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 1/19/2016. Accessed 4/08/2021.
- Valsartan oral solution prescribing information. Lifsa Drugs, LLC. 04/2022
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.