Resources
FAQ
Explore commonly asked questions
Find answers to inquiries about getting started, features, data security, integrations, support, customization, and more.
TRYVIO demonstrated a well-tolerated safety profile in patients with uncontrolled BP despite the use of ≥3 antihypertensive medications. Dual ERA activity represents a novel therapeutic approach, targeting the endothelin pathway.1 The balanced antagonism of both ETA and ETB receptors produces less profound fluid retention compared with earlier selective ETA antagonists, while maintaining robust BP reduction.1
In the Phase 3 PRECISION trial involving 724 patients with confirmed uncontrolled BP despite treatment with at least three antihypertensive medications, TRYVIO achieved clinically meaningful SiSBP reduction of 15.3-15.4 mm Hg at Week 4, with sustained effects through 48 weeks of follow-up.2
TRYVIO does not require dose adjustment for age. Of the total number of subjects in the PRECISION study of TRYVIO, 321 (44%) were 65 years and older, whereas 72 (10%) were 75 years and older. Elderly patients demonstrated greater early BP lowering in subgroup analyses. Edema/fluid retention was more common in elderly than younger patients.3
Fluid retention and peripheral edema are among the most common adverse effects associated with TRYVIO, occurring in 9.1% of patients receiving the approved 12.5 mg dose compared with 2.1% of placebo-treated patients during the 4-week double-blind phase of the PRECISION study.1 Older age and chronic kidney disease are established risk factors for edema and fluid retention with TRYVIO.
Hyperkalemia was not identified as a risk factor with TRYVIO. In the PRECISION trial, no treatment-emergent cases of hyperkalemia were reported, and across all treatment groups (aprocitentan 12.5 mg and 25 mg), adverse events occurring in ≥2% or more in any treatment group did not include any instance of hyperkalemia. These results indicate that TRYVIO does not share the hyperkalemia risk profile as RAAS inhibitors.3
BP = blood pressure; ERA = endothelin-1 receptor antagonist; RAAS = renin-angiotensin-aldosterone system; SiSBP = sitting systolic blood pressure.
IMPORTANT SAFETY INFORMATION & INDICATION
- TRYVIO is contraindicated for use during pregnancy because it may cause fetal harm if used by pregnant patients. Therefore in patients who can become pregnant, exclude pregnancy prior to initiation of TRYVIO.
- Advise use of effective contraception before the start of TRYVIO, during treatment and for one month after stopping treatment.
- When pregnancy is detected, discontinue TRYVIO as soon as possible.
CONTRAINDICATIONS
TRYVIO is contraindicated:
- in patients who are pregnant.
- in patients who are hypersensitive to aprocitentan or any of its excipients.
WARNINGS AND PRECAUTIONS
Embryo-Fatal 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 during treatment, and for one month after the final dose of TRYVIO. When pregnancy is detected, discontinue TRYVIO as soon as possible.
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. To reduce the risk of potential serious hepatotoxicity, measure serum aminotransferase levels and total bilirubin prior to initiation of treatment and repeat during treatment periodically and as clinically indicated.
Do not initiate TRYVIO in patients with elevated aminotransferases (>3 × ULN) or moderate to severe hepatic impairment. Advise patients with symptoms suggesting hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, scleral icterus, jaundice, dark urine, fever, or itching) to immediately stop treatment with TRYVIO and seek medical attention.
If sustained, unexplained, clinically relevant aminotransferase elevations occur, or if elevations are accompanied by an increase in bilirubin >2 × ULN, or if clinical symptoms of hepatotoxicity occur, discontinue TRYVIO.
Fluid Retention
Fluid retention and peripheral edema are known effects of ERAs, including TRYVIO. Edema/fluid retention was reported in 9% of TRYVIO-treated patients compared with 18% of patients receiving aprocitentan 25 mg (twice the recommended dose) and 2% on placebo in the clinical trial, requiring additional diuretic use in some patients. Older age and chronic kidney disease are risk factors for edema/fluid retention with TRYVIO. TRYVIO has not been studied in patients with heart failure New York Heart Association stage III–IV, unstable cardiac function, or with NTproBNP ≥500 pg/mL. TRYVIO is not recommended in these patients.
Monitor for signs and symptoms of fluid retention, weight gain, and worsening heart failure. If clinically significant fluid retention develops, treat appropriately, and consider discontinuation of TRYVIO.
Hemoglobin Decrease
Decreases in hemoglobin concentration and hematocrit have occurred following administration of other ERAs and were observed in the clinical trial with TRYVIO. Hemoglobin decreases usually presented early, stabilized thereafter, and were reversible after discontinuation. A decrease in hemoglobin of >2 g/dL from baseline was observed in 7% of patients compared to 1% of placebo patients. A decrease to below 10.0 g/dL was observed in 3% of TRYVIO-treated patients compared to 0 patients taking placebo. Initiation of TRYVIO is not recommended in patients with severe anemia. Measure hemoglobin prior to initiation of treatment and periodically during treatment as clinically indicated.
Decreased Sperm Counts
TRYVIO, like other ERAs, may have an adverse effect on spermatogenesis. Counsel men about potential effects on fertility.
MOST COMMON ADVERSE REACTIONS
The most common adverse reactions (more frequent than placebo and ≥ 2% in TRYVIO-treated patients) are edema/fluid retention and anemia.
USE IN SPECIFIC POPULATIONS
Lactation
There are no data on the presence of aprocitentan in human milk, the effects on the breastfed infant, or the effect on milk production. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with TRYVIO.
Renal Impairment
TRYVIO is not recommended in patients with kidney failure (eGFR <15 mL/min) or on dialysis. Patients with renal impairment are at increased risk of edema/fluid retention.
Hepatic Impairment
TRYVIO is not recommended in patients with moderate and severe hepatic impairment (Child-Pugh class B and C) because these patients may be at increased risk for poor outcomes from hepatotoxicity.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. Please see full Prescribing Information including BOXED Warning and Medication Guide.
INDICATION
TRYVIO is an endothelin receptor antagonist indicated for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs. Lowering blood pressure reduces the risk of fatal and non fatal cardiovascular events, primarily strokes and myocardial infarctions.