APROCITENTAN TAB

Clinical Criteria Summary

Resistant or pseudoresistant hypertension due to nonadherence, suboptimal antihypertensive therapy, or secondary causes including primary aldosteronism
Recent cerebrovascular or cardiovascular event (e.g., transient ischemic attack, stroke, myocardial infarction in the past 6 months)
Clinically significant unstable cardiac disease (e.g., uncontrolled symptomatic arrhythmias, current decompensated heart failure, baseline class III or IV heart failure, or class II heart failure with relevant mitral valve insufficiency or aortic stenosis)
Severe renal impairment with eGFR less than 15 ml/min or on dialysis
ALT (alanine transferase) or AST (aspartate transferase) elevations of greater than 3 times the upper limit of normal, or moderate to severe hepatic impairment (Child-Pugh class B and C)
Baseline severe anemia (e.g., hemoglobin less than 10 g/dL)
Treatment with another endothelin receptor antagonist (ERA)
Known pregnancy
Lactating

Provider is a VA or VA Community Care cardiology or nephrology specialist or other locally designated provider
Resistant hypertension defined as inadequate control of blood pressure with documented adherence and the use of maximally tolerated doses of triple therapy and spironolactone (if appropriate)
Medication profile reviewed to eliminate or minimize the concurrent use of drugs that elevate blood pressure (e.g., NSAIDs)
Lifestyle modifications on how to reduce blood pressure have been discussed with patient and documented (e.g., diet, alcohol consumption, exercise)
Baseline evaluation of labs including serum transaminases, bilirubin, hemoglobin, and NT-proBNP (or BNP)

For females who can become pregnant: Pregnancy must be excluded prior to receiving aprocitentan
For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for one month after stopping treatment
For males of reproductive potential: Counseling provided on the potential risk of aprocitentan to adversely affect spermatogenesis and impair fertility

Secondary causes of resistant hypertension workup should include plasma renin activity and serum aldosterone to calculate aldosterone/renin ratio
Triple therapy must include a diuretic (thiazide-type), calcium channel blocker, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (beta-blocker may also be used for patients with another compelling indication)
Spironolactone (or eplerenone if spironolactone is not tolerated) should be considered as a fourth line agent in patients when appropriate (e.g., in patients without contraindications, prior intolerance, severe renal impairment, high potassium)
Aprocitentan is associated with risk of fluid retention, edema, and worsening of heart failure, especially in patients with cardiovascular risk factors
Patients with renal artery stenosis may be predisposed to fluid retention/pulmonary edema; alternate therapies should be considered in these patients

Indicated for treatment of hypertension in combination with other antihypertensive agents when blood pressure is inadequately controlled on other agents
Indicated as add-on treatment for resistant hypertension (defined as blood pressure above goal on maximally tolerated doses of triple therapy: a diuretic, calcium channel blocker, and ACE inhibitor or angiotensin II receptor blocker)

12.5 mg oral tablet dosed orally once daily; only the 12.5 mg dose is FDA approved

Appropriate for patients with uncontrolled hypertension despite treatment with three or more antihypertensive agents from different drug classes and SBP ≥140 mmHg
Not recommended in patients with eGFR <15 ml/min/1.73 m2 or on dialysis
Not recommended in patients with moderate to severe hepatic impairment (Child-Pugh class B and C)
Not recommended in patients with NYHA stage III or IV heart failure, unstable cardiac function, or NTproBNP ≥500 pg/mL

Contraindicated in pregnancy due to risk of embryo-fetal toxicity and fetal death
Contraindicated in hypersensitivity
Associated with hepatotoxicity; discontinue if symptoms suggestive of hepatotoxicity occur or if transaminases are elevated with bilirubin >2 times ULN
Associated with fluid retention/edema; monitor for worsening heart failure
Associated with decreased hemoglobin and anemia

Obtain baseline serum aminotransferase levels and total bilirubin prior to initiation; monitor periodically during treatment
Do not initiate if AST or ALT >3 times ULN
Obtain baseline hemoglobin prior to initiation; monitor periodically during treatment
Monitor for signs and symptoms of fluid retention, weight gain, and worsening heart failure
Females who can become pregnant must have monthly negative pregnancy tests during treatment and one month after discontinuation

Requires a multidisciplinary approach to hypertension management prior to initiation
Requires ambulatory blood pressure monitoring and confirmation of medication adherence before adding a fourth agent
Pharmacologic and lifestyle factors exacerbating blood pressure (e.g., NSAIDs, alcohol consumption, obstructive sleep apnea, obesity, physical inactivity) must be addressed
Secondary and pseudoresistant hypertension should be considered; evaluation of medication adherence and reinforcement of nonpharmacologic interventions are required before adding a fourth agent
Professional guidelines recommend considering spironolactone as a fourth-line agent when appropriate (or eplerenone if spironolactone is not tolerated)

Only available through the TRYVIO REMS program due to embryo-fetal toxicity risk
Requires prescriber enrollment, training, and certification, and pharmacy certification