Version July 2025
Aprocitentan 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 aprocitentan. Advise use of effective contraception before the start of aprocitentan, during treatment and for one month after stopping treatment. When pregnancy is detected, discontinue aprocitentan as soon as possible.
Hypertension: Oral: 12.5 mg once daily.
Missed doses: If a dose is missed, skip the missed dose and take the next dose at the regular time. Do not take 2 doses on the same day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function: Oral:
eGFR ≥15 mL/minute: No dosage adjustment necessary.
eGFR <15 mL/minute: Use not recommended.
Dialysis: Use not recommended.
Hepatic impairment prior to treatment initiation:
Baseline ALT or AST >3 × ULN: Initiation of therapy is not recommended.
Child-Turcotte-Pugh class A: Oral:No dosage adjustment necessary.
Child-Turcotte-Pugh class B and C: Oral: Use not recommended.
Hepatotoxicity during treatment: Discontinue treatment in patients who develop symptoms of hepatic injury (eg, anorexia, dark urine, fatigue, fever, itching, jaundice, nausea, right upper quadrant pain, vomiting) or who experience sustained, clinically relevant aminotransferase elevations, or if aminotransferase elevations are accompanied by elevated bilirubin (>2 × ULN).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
1% to 10%:
Cardiovascular: Edema (≤9%; including peripheral edema)
Endocrine & metabolic: Fluid retention (≤9%)
Hematologic & oncologic: Anemia (4%)
<1%: Hypersensitivity: Hypersensitivity reaction (including allergic angioedema)
Frequency not defined: Hepatic: Hepatotoxicity, increased serum transaminases (including increased serum alanine aminotransferase, increased serum aspartate aminotransferase)
Hypersensitivity to aprocitentan or any component of the formulation; pregnancy.
Concerns related to adverse effects:
• Fluid retention/peripheral edema: Development of fluid retention and peripheral edema may occur. Risk factors include older age and chronic kidney disease. Use is not recommended in patients with heart failure New York Heart Association class III to IV, unstable cardiac function, or N-terminal prohormone brain natriuretic peptide ≥500 pg/mL.
• Hematologic effects: A reduction in hematocrit/Hb may occur early in therapy with subsequent stabilization. Use is not recommended in patients with severe anemia.
• Hepatic effects: Increases in serum liver aminotransferases and hepatotoxicity have been reported.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Tryvio: 12.5 mg
No
Tablets (Tryvio Oral)
12.5 mg (per each): $31.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Tryvio is available through Walgreens Specialty Pharmacy. Additional information is available at https://www.tryviohcp.com/ or (888) 347-3416.
Oral: Swallow tablet whole. May be administered with or without food.
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Aprocitentan may cause teratogenicity and has a structural and/or toxicity profile similar to existing hazardous agents.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Tryvio: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217686s000lbl.pdf#page=18
Hypertension: May be used in patients whose BP is not adequately controlled on other antihypertensive medications.
Apresoline, aprepitant.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (contraindicated in pregnancy) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
Substrate of UGT1A1, UGT2B7;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification
Amphetamines: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Atazanavir: May increase serum concentration of UGT1A1 Substrates. Management: Do not use UGT1A1 substrates for which small increases in exposure can cause serious adverse effects together with atazanavir, and use caution with any UGT1A1 substrate, even when small changes in exposure are less likely to cause serious adverse effects. Risk D: Consider Therapy Modification
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Belumosudil: May increase serum concentration of UGT1A1 Substrates. Management: Avoid coadministration of belumosudil with substrates of UGT1A1 for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the UGT1A1 substrate may be required. Risk D: Consider Therapy Modification
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Brigatinib: May decrease antihypertensive effects of Antihypertensive Agents. Brigatinib may increase bradycardic effects of Antihypertensive Agents. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
Dexmethylphenidate: May decrease therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor
Flunarizine: May increase therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Herbal Products with Blood Pressure Increasing Effects: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Indoramin: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Isocarboxazid: May increase antihypertensive effects of Antihypertensive Agents. Risk X: Avoid
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Loop Diuretics: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
Methylphenidate: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Mitapivat: May decrease serum concentration of UGT1A1 Substrates. Risk C: Monitor
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Obinutuzumab: May increase hypotensive effects of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider Therapy Modification
Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Perazine: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Prazosin: Antihypertensive Agents may increase hypotensive effects of Prazosin. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Sparsentan: May increase adverse/toxic effects of Endothelin Receptor Antagonists. Risk X: Avoid
Terazosin: Antihypertensive Agents may increase hypotensive effects of Terazosin. Risk C: Monitor
Urapidil: Antihypertensive Agents may increase hypotensive effects of Urapidil. Risk C: Monitor
Evaluate pregnancy status prior to use. Pregnancy tests should be conducted prior to therapy in patients who could become pregnant. Conduct additional pregnancy testing if the onset of menses is delayed or if pregnancy is suspected during treatment.
Patients who could become pregnant should use effective contraception prior to starting treatment, during therapy, and for 1 month after the last dose of aprocitentan.
Aprocitentan may decrease spermatogenesis; it is not known if this is reversible once aprocitentan is discontinued.
Based on data from animal reproduction studies with other endothelin receptor antagonists, in utero exposure to aprocitentan may cause fetal harm including embryo-fetal toxicity, birth defects, and fetal death.
Aprocitentan is contraindicated in patients who are pregnant; discontinue as soon as possible if pregnancy occurs during treatment.
It is not known if aprocitentan is present in human milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.
Exclude pregnancy prior to initiating therapy in patients who could become pregnant; signs and symptoms of liver injury (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, scleral icterus, jaundice, dark urine, fever, or itching); ALT/AST (baseline, repeat as clinically indicated); total bilirubin (baseline; repeat as clinically indicated); Hb (baseline, as clinically indicated); fluid retention, weight gain, worsening heart failure).
Blocks endothelin (ET)-1 from binding to endothelin receptor subtypes ETA and ETB. Stimulation of these receptors is associated with vasoconstriction, fibrosis, cell proliferation, hypertrophy, and inflammation.
Distribution: Vd: ~20 L.
Protein binding: >99%, primarily to albumin.
Metabolism: Hepatic by UGT1A1- and UGT2B7-mediated N-glucosidation and non-enzymatic hydrolysis.
Half-life elimination: ~41 hours.
Time to peak: 4 to 5 hours.
Excretion: Urine: ~52% (0.2% as unchanged drug); feces: 25% (6.8% as unchanged drug).
