Tryvio
Aprocitentan · Tablet, Film Coated · Oral
Uses
1 INDICATIONS AND USAGE 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. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes. There are no controlled trials demonstrating reduction of risk of these events with TRYVIO. Control of high BP should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve BP goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is BP reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher BPs, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from BP reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower BP goal. 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. ( 1 )
Dosage and administration
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) ] .
Dosage forms and strengths
(aprocitentan) tablets are available as: 12.5 mg: yellow to orange round, film-coated tablet, debossed with "AN" on one side and plain on the other side. Tablets: 12.5 mg ( 3 )
Contraindications
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) ] .
Warnings and precautions
5 WARNINGS AND PRECAUTIONS 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. There were no reports of patients with ALT and/or AST >3 × ULN and total bilirubin >2 × ULN or cases of liver failure observed in TRYVIO-treated patients in the clinical trials. 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. 5.3 Fluid Retention Fluid retention and peripheral edema are known effects of ERAs, including TRYVIO [see Adverse Reactions (6.1) ] . 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. 5.4 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 [see Adverse Reactions (6.1) ] . 5.5 Decreased Sperm Counts TRYVIO, like other ERAs, may have an adverse effect on spermatogenesis. Counsel men about potential effects on fertility [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1) ] .
Side effects
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. Table 1 Adverse reactions reported with a frequency of ≥2% in TRYVIO-treated patients and greater (≥1%) than in placebo-treated patients during the initial 4-week double-blind placebo-controlled treatment (part 1) Adverse Reaction 12.5 mg N = 243 % Placebo N = 242 % Edema/fluid retention 9.1 2.1 Anemia 3.7 0 Hypersensitivity Reactions During the initial 4-week double-blind placebo-controlled treatment period (part 1), 0.8% of patients experienced an adverse reaction of hypersensitivity (i.e., rash, erythema, allergic edema) on TRYVIO compared to no reports in patients treated with placebo. One patient experienced allergic dermatitis requiring hospitalization while receiving aprocitentan 25 mg. Laboratory Tests Initiation of TRYVIO may cause an initial small decrease in estimated glomerular filtration rate (eGFR) that occurs within the first 6 weeks of starting therapy and then stabilizes. In the initial 4-week double-blind treatment period, TRYVIO 12.5 mg caused a mean decrease of about 0.8 g/dL in hemoglobin compared to no change in the placebo patients.
Use in specific populations
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. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In embryo-fetal development toxicity studies in pregnant rats and rabbits given macitentan (for which aprocitentan is a major metabolite) during the period of major organogenesis, cardiovascular and mandibular arch fusion malformations were observed at all doses studied. The lowest doses in rats and rabbits produced aprocitentan exposures that were equivalent to and 15-fold, respectively, the clinical exposures at the maximum recommended human dose (MRHD) based on area under the curve (AUC). In pre- and post-natal development studies, female rats given macitentan (for which aprocitentan is a major metabolite) from late pregnancy through lactation showed reduced pup survival and impairment of the male fertility of the offspring at all doses. The lowest dose produced aprocitentan exposures approximately 2-fold the clinical exposures at the MRHD based on AUC. 8.2 Lactation Risk Summary There are no data on the presence of aprocitentan in human milk, the effects on the breastfed infant, or the effect on milk production. In rats, aprocitentan was excreted into milk during lactation (see Data ). When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with TRYVIO. Data A single 14 C-radiolabeled macitentan dose of 3 mg/kg was given orally to lactating Wistar rats. Aprocitentan was consistently observed in milk samples across all collection times after oral administration. 8.3 Females and Males of Reproductive Potential Based on data from animal reproductive toxicity studies with other ERAs, TRYVIO can cause fetal harm, including birth defects and fetal death, when administered to a pregnant patient and is contraindicated during pregnancy [see Contraindications (4.1) , Use in Specific Populations (8.1) ] . Pregnancy Testing Verify that patients who can become pregnant, are not pregnant prior to initiating TRYVIO. The patient should contact their physician immediately if onset of menses is delayed or pregnancy is suspected. If the pregnancy test is positive, the physician and patient should discuss the risks to the patient, the pregnancy, and the fetus [see Warnings and Precautions (5.1) , Dosage and Administration (2.2) , Contraindications (4.1) ] . Contraception Patients using TRYVIO who can become pregnant should use effective contraception prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with TRYVIO to prevent pregnancy [see Warnings and Precautions (5.1) ] . Infertility Other ERAs have shown an adverse effect on spermatogenesis in humans and/or animals. TRYVIO, like other ERAs, may impair fertility in males of reproductive potential. It is not known whether effects on fertility would be reversible [see Warnings and Precautions (5.5) , Nonclinical Toxicology (13.1) ]. 8.4 Pediatric Use The safety and efficacy of TRYVIO in pediatric patients have not been established. 8.5 Geriatric Use Of the total number of subjects in the PRECISION study of TRYVIO, 321 (44%) were 65 years and older, while 72 (10%) were 75 years and older. Edema/fluid retention was more common in these patients than younger patients [see Warnings and Precautions (5.3) ] . No dose adjustment is required in patients over the age of 65 years [see Clinical Pharmacology (12.3) ] . 8.6 Renal Impairment TRYVIO is not recommended in patients with kidney failure (eGFR <15 mL/min) or on dialysis. The effect of kidney failure (eGFR <15 mL/min) or dialysis on aprocitentan pharmacokinetics is unknown [see Clinical Pharmacology (12.3) ] . Patients with renal impairment are at increased risk of edema/fluid retention [see Warnings and Precautions (5.3) ] . No dose adjustment is required in patients with mild to severe renal impairment (eGFR ≥15 mL/min). 8.7 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. No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh class A) [see Clinical Pharmacology (12.3) ] .
Pregnancy
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. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In embryo-fetal development toxicity studies in pregnant rats and rabbits given macitentan (for which aprocitentan is a major metabolite) during the period of major organogenesis, cardiovascular and mandibular arch fusion malformations were observed at all doses studied. The lowest doses in rats and rabbits produced aprocitentan exposures that were equivalent to and 15-fold, respectively, the clinical exposures at the maximum recommended human dose (MRHD) based on area under the curve (AUC). In pre- and post-natal development studies, female rats given macitentan (for which aprocitentan is a major metabolite) from late pregnancy through lactation showed reduced pup survival and impairment of the male fertility of the offspring at all doses. The lowest dose produced aprocitentan exposures approximately 2-fold the clinical exposures at the MRHD based on AUC.
Pediatric use
8.4 Pediatric Use The safety and efficacy of TRYVIO in pediatric patients have not been established.
Geriatric use
8.5 Geriatric Use Of the total number of subjects in the PRECISION study of TRYVIO, 321 (44%) were 65 years and older, while 72 (10%) were 75 years and older. Edema/fluid retention was more common in these patients than younger patients [see Warnings and Precautions (5.3) ] . No dose adjustment is required in patients over the age of 65 years [see Clinical Pharmacology (12.3) ] .
Overdosage
10 OVERDOSAGE 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).
Description
(aprocitentan) is an endothelin receptor antagonist. The chemical name of aprocitentan is N-[5-(4-bromophenyl)-6- [2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-sulfamide. It has a molecular formula of C 16 H 14 Br 2 N 6 O 4 S and a molecular weight of 546.2 g/mol. The structural formula is: Aprocitentan is a white to off-white powder that is insoluble in water. TRYVIO is available as film-coated 12.5 mg strength tablets for oral administration. The inactive ingredients in TRYVIO are croscarmellose sodium, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. The film coating contains the following inactive ingredients: hydroxypropyl cellulose, iron oxide black, iron oxide red, iron oxide yellow, polyvinyl alcohol, silica colloidal hydrated, talc, titanium dioxide, and triethyl citrate. Chemical Structure
Mechanism of action
12.1 Mechanism of Action 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. In hypertension, ET-1 can cause endothelial dysfunction, vascular hypertrophy and remodeling, sympathetic activation, and increased aldosterone synthesis.
How supplied
16.1 How Supplied TRYVIO tablets are available as: 12.5 mg: yellow to orange round, film-coated tablet, debossed with "AN" on one side and plain on the other side. – NDC 80491-8012-8, each blister contains 10 tablets – NDC 80491-8012-3, each bottle contains 30 tablets and has a child-resistant closure 16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] . Store in the original package. Dispense to patient in original container only. Replace cap securely each time after opening. Do not discard desiccant. Protect from light and moisture.
Storage
16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] . Store in the original package. Dispense to patient in original container only. Replace cap securely each time after opening. Do not discard desiccant. Protect from light and moisture.
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Embryo-Fetal Toxicity Counsel patients who can become pregnant to use effective methods of contraception before treatment with TRYVIO, during treatment with TRYVIO, and for one month after treatment discontinuation. Patients who can become pregnant should have a negative pregnancy test prior to initiation of TRYVIO, [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1 , 8.3) ] . Patients should be instructed to contact their healthcare provider if they suspect they may be pregnant. Patients should seek additional contraceptive advice from a gynecologist or similar expert as needed. Educate and counsel patients who can become pregnant on the use of emergency contraception in the event of unprotected sex or contraceptive failure. Advise pre-pubertal females and/or their guardian(s) to report any changes in their reproductive status immediately to their prescriber. Lactation Advise females not to breastfeed during treatment with TRYVIO [see Use in Specific Populations (8.2) ] . Hepatotoxicity Educate patients on signs of hepatotoxicity. Advise patients that they should contact their healthcare provider if they have unexplained nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching. Fluid Retention Educate patients on signs of fluid retention. Advise patients that they should contact their healthcare provider if they have unusual weight increase or swelling of the ankles or legs.
Label text from the FDA structured product label by Idorsia Pharmaceuticals Ltd (revised Aug 14, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Aprocitentan in 2 products
Tryvio NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 46014-8012 | Aprocitentan 12.5 mg/1 Capsule | Excella GmbH & Co. KG | DRUG FOR FURTHER PROCESSING |
| 80491-8012 | Aprocitentan 12.5 mg/1 Tablet, Film Coated | Idorsia Pharmaceuticals Ltd | NDA |
Frequently asked questions
What is Tryvio used for?
1 INDICATIONS AND USAGE 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. These benefits have been seen in controlled trials…
What are the side effects of Tryvio?
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… See the full label for the complete list.
Who makes Tryvio?
Tryvio is listed by 2 labelers in the FDA NDC directory, including Excella GmbH & Co. KG, Idorsia Pharmaceuticals Ltd.