Version July 2025
Macitentan is contraindicated for use during pregnancy because it may cause fetal harm based on animal data. Therefore, for females of reproductive potential, exclude pregnancy before the start of treatment with macitentan. Advise use of effective contraception before the initiation of treatment, during treatment, and for one month after stopping treatment with macitentan. When pregnancy is detected, discontinue macitentan as soon as possible.
Pulmonary arterial hypertension:
Note: Consult a pulmonary arterial hypertension specialist for all management decisions; choice of therapy is dependent on etiology, risk stratification, and cardiopulmonary comorbidities (Ref).
Oral: 10 mg once daily; maximum 10 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling; however, pharmacokinetic changes were not considered clinically relevant. Canadian labeling does not recommend use in dialysis patients (has not been studied).
US labeling: There are no dosage adjustments provided in the manufacturer’s labeling; however, pharmacokinetic changes were not considered clinically relevant.
Canadian labeling:
Baseline ALT or AST >3x ULN: Initiation of therapy is not recommended.
Mild impairment: Dosage adjustment not necessary.
Moderate to severe impairment: Use is not recommended.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Hematologic & oncologic: Anemia (13%)
Nervous system: Headache (14%)
Respiratory: Bronchitis (12%), nasopharyngitis (≤20%), pharyngitis (≤20%)
1% to 10%:
Genitourinary: Urinary tract infection (9%)
Hepatic: Increased serum transaminases (>8 × ULN: 2%; including increased serum alanine aminotransferase, increased serum aspartate aminotransferase)
Infection: Influenza (6%)
Postmarketing:
Cardiovascular: Edema, flushing, symptomatic hypotension
Endocrine & metabolic: Fluid retention
Hepatic: Hepatic injury (including fulminant hepatitis, hepatic failure) (Tran 2018)
Hypersensitivity: Angioedema, hypersensitivity reaction
Respiratory: Nasal congestion
Hypersensitivity to macitentan or any component of the formulation; pregnancy.
Canadian labeling: Additional contraindications (not in US labeling): breastfeeding.
Concerns related to adverse effects:
• Fluid retention/peripheral edema: Development of peripheral edema due to treatment and/or disease state (pulmonary arterial hypertension) may occur. There have been postmarketing reports of fluid retention requiring treatment (eg, diuretics, fluid management, hospitalization) associated with other endothelin antagonists. Further evaluation may be necessary to determine cause and appropriate treatment or discontinuation of therapy. Use with caution in patients with severe chronic heart failure.
• Hematologic effects: A reduction in hematocrit/hemoglobin has been observed and may occur early in therapy with subsequent stabilization. Decreases in hemoglobin rarely required transfusion. Measure hemoglobin prior to initiating therapy and repeat as clinically appropriate. Use is not recommended in patients with severe anemia.
• Hepatic effects: Increases in serum liver aminotransferases, hepatotoxicity, and liver failure have been reported. Monitor transaminases prior to initiation of therapy and repeat as clinically appropriate. Discontinue treatment in patients who develop elevated transaminases either in combination with symptoms of hepatic injury (eg, anorexia, dark urine, fatigue, fever, itching, jaundice, nausea, right upper quadrant pain, vomiting) or elevated bilirubin (>2 x the upper limit of normal [ULN]). Upon normalization of hepatic enzymes, may consider reinitiation of therapy in patients not experiencing clinical signs of hepatotoxicity.
Disease-related concerns:
• Pulmonary veno-occlusive disease (PVOD): If signs of pulmonary edema occur, consider the possibility of PVOD; discontinue if PVOD is confirmed.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Opsumit: 10 mg [contains soybean lecithin]
No
Tablets (Opsumit Oral)
10 mg (per each): $518.20
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Opsumit: 10 mg [contains soybean lecithin]
Oral: Swallow tablet whole. Do not split, crush, or chew tablets. May be administered with or without food.
Hazardous agent (NIOSH 2024 [table 2]).
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:
Opsumit: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204410s029lbl.pdf#page=20
Pulmonary arterial hypertension: Treatment of pulmonary arterial hypertension (PAH) (WHO Group I) to reduce risks of disease progression and hospitalization
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 CYP2C19 (Minor), CYP2C8 (Minor), CYP2C9 (Minor), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
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.
Amiodarone: May increase serum concentration of Macitentan. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Macitentan. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Macitentan. Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Macitentan. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Macitentan. Risk X: Avoid
Fluconazole: May increase serum concentration of Macitentan. Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Grapefruit Juice: May increase serum concentration of Macitentan. Risk C: Monitor
Sparsentan: May increase adverse/toxic effects of Endothelin Receptor Antagonists. Risk X: Avoid
Exclude pregnancy prior to initiation. 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 macitentan.
Sperm count may be reduced during treatment; fertility may be impaired.
Based on data from animal reproduction studies, macitentan may cause harm if administered during pregnancy.
Outcome data following maternal use of macitentan during pregnancy are limited (Amann 2023). Use is contraindicated in pregnant patients. Discontinue as soon as possible if pregnancy is detected.
Untreated maternal pulmonary arterial hypertension is associated with an increased rate of maternal and fetal morbidity and mortality, including spontaneous abortion, intrauterine growth restriction and premature labor. Patients with pulmonary arterial hypertension (PAH) are encouraged to avoid becoming pregnant (ESC [Regitz-Zagrosek 2018]; ESC/ERS [Humbert 2022]).
It is not known if macitentan is present in human milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.
Monitor for significant peripheral edema and evaluate etiology if it occurs; measure liver enzymes prior to initiation and repeat as clinically appropriate (Canadian labeling recommends monthly monitoring of liver enzymes during the first year of therapy and then as clinically appropriate); monitor for clinical signs and symptoms of liver injury (eg, abdominal pain, anorexia, dark urine, fatigue, fever, itching, jaundice, nausea, vomiting); hemoglobin and hematocrit prior to initiation and repeat as clinically appropriate (Canadian labeling recommends to repeat hemoglobin after first month of therapy and then as clinically appropriate); exclude pregnancy prior to initiating therapy in patients who could become pregnant.
Blocks endothelin (ET)-1 from binding to endothelin receptor subtypes ETA and ETB on vascular endothelium and smooth muscle. Stimulation of these receptors is associated with vasoconstriction, fibrosis, proliferation, hypertrophy, and inflammation.
Distribution: Vss: 50 L (active metabolite: 40 L)
Protein binding, plasma: >99% primarily to albumin
Metabolism: Hepatic via CYP3A4 (major) and CYP2C19 to its active metabolite
Half-life elimination: ~16 hours (active metabolite: ~48 hours)
Time to peak, plasma: 8 hours
Excretion: Urine (~50%); feces (~24%)
