Aprocitentan

Aprocitentan is an ERA that inhibits the binding of endothelin (ET)-1 to ET A and ET B receptors. ET-1, via its receptors (ET A and ET B ), mediates a variety of deleterious effects such as vasoconstriction, fibrosis, cell proliferation, and inflammation.

• TRYVIO, in combination with other antihypertensive drugs, is indicated for the treatment of hypertension, to lower blood pressure (BP) in adult patients who are not adequately controlled on other drugs. Lowering BP reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.ICD-10: I10

• Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 ) 4.1 Pregnancy Use of TRYVIO is contraindicated in patients who are pregnant [see Dosage and Administration (2.2) , Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] . 4.2 Hypersensitivity TRYVIO is contraindicated in patients who are hypersensitive to aprocitentan or any of its excipients [see Adverse Reactions (6.1) ] .contraindicated

The recommended dosage of TRYVIO is 12.5 mg orally once daily, with or without food. ( 2.1 ) 2.1 Recommended Dosage The recommended dosage of TRYVIO is 12.5 mg orally once daily. Swallow tablets whole. TRYVIO may be taken with or without food. If a dose is missed, skip the missed dose and take the next dose at the regular time. Do not take two doses on the same day. 2.2 Pregnancy Testing in Females of Reproductive Potential Exclude pregnancy before initiating treatment with TRYVIO in females of reproductive potential [see Boxed Warning, Contraindications (4.1) , Warnings and Precautions (5.1) , Use in Specific Populations (8.3) ] .

ERAs cause hepatotoxicity and liver failure. Measure serum aminotransferase levels and total bilirubin prior to initiation of treatment and repeat periodically during treatment and as clinically indicated. ( 5.2 ) Fluid retention may require intervention ( 5.3 ) Decreases in hemoglobin ( 5.4 ) Decreased sperm counts ( 5.5 ) 5.1 Embryo-Fetal Toxicity Based on data from animal reproduction studies with endothelin receptor antagonists (ERAs), TRYVIO may cause fetal harm when administered during pregnancy and is contraindicated for use in patients who are pregnant. The available human data for endothelin receptor antagonists do not establish the presence or absence of fetal harm related to the use of TRYVIO. Counsel patients who can become pregnant about the potential risk to a fetus. Obtain a pregnancy test prior to initiation of treatment with TRYVIO. Advise patients who can become pregnant to use effective contraception prior to initiation of treatment with TRYVIO, during treatment, and for one month after the final dose of TRYVIO. When pregnancy is detected, discontinue TRYVIO as soon as possible [see Dosage and Administration (2.2) , Contraindications (4.1) , Use in Specific Populations (8.1 , 8.3) ] . 5.2 Hepatotoxicity Elevations of aminotransferases and hepatotoxicity are known effects of ERAs, including TRYVIO. Elevations in alanine transaminase (ALT) or aspartate aminotransferase (AST) of greater than 5-fold upper limit of normal (ULN) were observed rarely in patients treated with aprocitentan in the clinical trial, including cases with positive rechallenge.

Clinically significant adverse reactions that appear in other sections of the labeling include: Embryo-fetal toxicity [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Fluid retention [see Warnings and Precautions (5.3) ] Hemoglobin decrease [see Warnings and Precautions (5.4) ] Decreased sperm counts [see Warnings and Precautions (5.5) ] Most common adverse reactions (more frequent than placebo and ≥ 2% in TRYVIO-treated patients) are edema/fluid retention and anemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Idorsia Pharmaceuticals Ltd at 1-833-400-9611 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of TRYVIO was evaluated in a placebo-controlled phase 3 clinical study (PRECISION, NCT03541174) in adults with uncontrolled BP (systolic blood pressure [SBP] ≥140 mmHg) despite the use of at least three antihypertensive medications. In this study, 724 patients received any dose of aprocitentan, with 633 patients treated for at least 26 weeks, 192 patients for at least 47 weeks, and 99 patients for at least 48 weeks. The most frequently reported adverse reactions to TRYVIO during the 4-week double-blind placebo-controlled treatment period (part 1) of the PRECISION study are presented in Table 1.

Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on animal reproduction studies with other ERAs, TRYVIO can cause embryo-fetal toxicity, including birth defects and fetal death when administered to a pregnant patient and is contraindicated during pregnancy [see Contraindications (4.1) ] . Available data from post-marketing reports and published literature over decades of use with endothelin receptor antagonists in the same class as TRYVIO have not identified an increased risk of fetal harm; however, these data are limited. Methodological limitations of these post-marketing reports and published literature include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and missing data. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal endothelin receptor antagonist use. Administration of macitentan, where approximately ≥50% of total exposure was to aprocitentan, was teratogenic in rats and rabbits at all doses tested (see Data ). Available data from reports of pregnancy in clinical trials with TRYVIO are insufficient to rule out a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Advise pregnant patients of the potential risk to a fetus.

Metabolism

The aprocitentan mean (%CV) C max is approximately 1.3 mcg/mL (19) following a single 25 mg dose (twice the recommended dose). The mean (%CV) aprocitentan AUC to the dosing interval (AUC 0-tau ) is approximately 23 mcg⸱h/mL (17) following a single 25 mg dose.

TRYVIO has been administered as a single dose of up to 600 mg, and as multiple doses of up to 100 mg daily, to healthy subjects (48 and 8 times the recommended dose, respectively). Adverse events of headache, nasal congestion, nausea, and upper respiratory tract infection were observed. In the event of an overdose, standard supportive measures should be taken, as required. Dialysis is unlikely to be effective because aprocitentan is highly protein-bound. Consult a Certified Poison Control Center for the most up-to-date information on the management of overdosage (1-800-222-1222 or www.poison.org).

• Mar 19, 2024NDANDA217686Idorsia

1. 1Weight Increased214%
2. 2Anaemia17.1%
3. 3Aortic Valve Replacement17.1%
4. 4Arthralgia17.1%
5. 5Asthenia17.1%
6. 6Atrial Fibrillation17.1%
7. 7Blood Sodium Decreased17.1%
8. 8Blood Urine17.1%
9. 9Breast Cancer17.1%
10. 10Cardiac Failure17.1%
11. 11Cardiogenic Shock17.1%
12. 12Catheter Site Pain17.1%
13. 13Chest Pain17.1%
14. 14Cough17.1%
15. 15Discomfort17.1%

The 10 most recently updated of 14 ClinicalTrials.gov registrations naming Aprocitentan as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study Evaluating Aprocitentan Tablets(SYH9108) for the Treatment of Resistant Hypertension
  Not yet recruiting · Phase 3 · Interventional · 382 enrolled · CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
  NCT07635914updated 2026-06-09
• A Drug-drug Interaction Trial in Healthy Female Participants to Investigate the Effect of Aprocitentan on Combined Hormonal Contraceptives
  Completed · Phase 1 · Interventional · 19 enrolled · Idorsia Pharmaceuticals Ltd.
  NCT06799884updated 2025-03-11
• A Research Study to Show the Effect of Aprocitentan in the Treatment of Difficult to Control (Resistant) High Blood Pressure (Hypertension) and Find Out More About Its Safety
  Completed · Phase 3 · Interventional · 730 enrolled · Idorsia Pharmaceuticals Ltd.
  NCT03541174updated 2023-03-21
• A Study in Healthy Male Subjects to Investigate Whether Administration of ACT-132577 Can Affect Rosuvastatin's Fate in the Body (Amount and Time of Presence in the Blood)
  Completed · Phase 1 · Interventional · 20 enrolled · Idorsia Pharmaceuticals Ltd.
  NCT03245229updated 2022-11-29
• A Study to Evaluate ACT-132577 in Healthy Male Subjects
  Completed · Phase 1 · Interventional · 6 enrolled · Idorsia Pharmaceuticals Ltd.
  NCT03100591updated 2022-11-29
• Clinical Study to Assess Body Fluid Homeostasis After Administration of ACT-132577 in Healthy Subjects
  Completed · Phase 1 · Interventional · 24 enrolled · Idorsia Pharmaceuticals Ltd.
  NCT02708004updated 2022-11-29
• A Study to Investigate the Effect of ACT-132577 on the Pharmacokinetics of Midazolam and 1-hydroxy Midazolam in Healthy Male Subjects
  Completed · Phase 1 · Interventional · 20 enrolled · Idorsia Pharmaceuticals Ltd.
  NCT02841761updated 2022-11-29
• A Study to Evaluate How Aprocitentan is Safe and How it is Absorbed and Broken Down in the Body of Japanese and Caucasian Subjects
  Completed · Phase 1 · Interventional · 20 enrolled · Idorsia Pharmaceuticals Ltd.
  NCT03586570updated 2022-11-23
• A Study to Evaluate ACT-132577 in Healthy Subjects and in People With Severe Kidney Disease
  Completed · Phase 1 · Interventional · 16 enrolled · Idorsia Pharmaceuticals Ltd.
  NCT03165071updated 2022-11-23
• The Effect of Hepatic Impairment on Aprocitentan Pharmacokinetics
  Completed · Phase 1 · Interventional · 17 enrolled · Idorsia Pharmaceuticals Ltd.
  NCT04252495updated 2022-11-23

Frequently asked questions

How does Aprocitentan work?

Aprocitentan is an ERA that inhibits the binding of endothelin (ET)-1 to ET A and ET B receptors. ET-1, via its receptors (ET A and ET B ), mediates a variety of deleterious effects such as vasoconstriction, fibrosis, cell proliferation, and inflammation.

What is Aprocitentan used for?

According to FDA labeling, Aprocitentan carries indications including: TRYVIO, in combination with other antihypertensive drugs, is indicated for the treatment of hypertension, to lower blood pressure (BP) in adult patients who are not adequately controlled on other drugs. Lowering BP reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Aprocitentan?

Aprocitentan is classified as Other antihypertensives, Endothelin Receptor Antagonist, Endothelin Receptor Antagonists, Decreased Blood Pressure.

What are the brand names for Aprocitentan?

Aprocitentan is marketed under brand names including Tryvio.

What are the contraindications for Aprocitentan?

Aprocitentan labeling lists contraindications including: Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 ) 4.1 Pregnancy Use of TRYVIO is contraindicated in patients who are pregnant [see Dosage and Administration (2.2) , Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] . 4.2 Hypersensitivity TRYVIO is contraindicated in patients who are hypersensitive to aprocitentan or any of its excipients [see Adverse Reactions (6.1) ] .. Always consult the full prescribing information and a clinician.