TRYVIO
Generic: APROCITENTAN
Basic Information
Manufacturer
Idorsia Pharmaceuticals Ltd
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
dfe7a2ee-612c-4aba-834a-d68e6b59a0a6
Indications & Usage
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 )
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 )
Adverse Reactions
6 ADVERSE REACTIONS 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.
( 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.