macitentan (Rx)

Brand and Other Names:Opsumit

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 10mg

Pulmonary Arterial Hypertension

Indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to reduce the risks of disease progression and hospitalization

10 mg PO qDay

Higher doses have not been studied and are not recommended

Dosage Modifications

Renal impairment

  • Severe (CrCl 15-29 mL/min): No dosage modification needed
  • Systemic exposure to macitentan and its active metabolite were increased by 30% and 60% respectively (not considered clinically relevant)

Hepatic impairment

  • Mild, moderate, or severe (Child-Pugh Class A, B, and C): No dosage modification needed
  • System exposure decreased by 21%, 34%, and 6% and exposure to the active metabolite was decreased by 20%, 25%, and 25% in subjects with mild, moderate, or severe hepatic impairment respectively (not considered clinically relevant)

Dosing Considerations

Obtain pregnancy test in females of reproductive potential before initiating, monthly during treatment, and 1 month after discontinuing; initiate in females of reproductive potential only after a negative pregnancy test

Measure hemoglobin before initiating treatment and repeat during treatment as clinically indicated

Orphan Designations

Fixed dose combination of macitentan and tadalafil for treatment of pulmonary arterial hypertension

Fontan-palliated patients

Chronic thromboembolic pulmonary hypertension (CTEPH)

Orphan sponsor

  • Actelion Clinical Research, Inc; 1820 Chapel Avenue West, Suite 300; Cherry Hill, New Jersey 08002

Safety and efficacy not established

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Interactions

Interaction Checker

and macitentan

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     activity indicator 
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    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Contraindicated (1)

            • sparsentan

              sparsentan, macitentan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of endothelin antagonists with sparsentan is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (eg, acute renal failure).

            Serious - Use Alternative (47)

            • apalutamide

              apalutamide will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • atazanavir

              atazanavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • bosentan

              bosentan will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • carbamazepine

              carbamazepine will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • clarithromycin

              clarithromycin will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • conivaptan

              conivaptan will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • dabrafenib

              dabrafenib will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • darunavir

              darunavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • dexamethasone

              dexamethasone will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • efavirenz

              efavirenz will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • enzalutamide

              enzalutamide will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • etravirine

              etravirine will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • fexinidazole

              fexinidazole will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fosamprenavir

              fosamprenavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • fosphenytoin

              fosphenytoin will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • idelalisib

              idelalisib will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • imatinib

              imatinib will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • indinavir

              indinavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • isoniazid

              isoniazid will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • itraconazole

              itraconazole will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • ivosidenib

              ivosidenib will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • ketoconazole

              ketoconazole will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • levoketoconazole

              levoketoconazole will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • lopinavir

              lopinavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • nafcillin

              nafcillin will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • nefazodone

              nefazodone will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • nelfinavir

              nelfinavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • nevirapine

              nevirapine will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • nicardipine

              nicardipine will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • pentobarbital

              pentobarbital will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • phenobarbital

              phenobarbital will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • phenytoin

              phenytoin will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • posaconazole

              posaconazole will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • primidone

              primidone will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • quinidine

              quinidine will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • rifabutin

              rifabutin will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • rifampin

              rifampin will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • rifapentine

              rifapentine will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

            • ritonavir

              ritonavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • saquinavir

              saquinavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • tipranavir

              tipranavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • tucatinib

              tucatinib will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • voriconazole

              voriconazole will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • voxelotor

              voxelotor will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            Monitor Closely (12)

            • cenobamate

              cenobamate will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • duvelisib

              duvelisib will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

            • elagolix

              elagolix decreases levels of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • encorafenib

              encorafenib, macitentan. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • fedratinib

              fedratinib will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • istradefylline

              istradefylline will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • lenacapavir

              lenacapavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

            • mitotane

              mitotane decreases levels of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • rucaparib

              rucaparib will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • stiripentol

              stiripentol, macitentan. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

            • tazemetostat

              tazemetostat will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            Minor (2)

            • nirmatrelvir/ritonavir

              nirmatrelvir/ritonavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Macitentan is metabolized mainly by CYP3A4, but is not a substrate of OATPs. The magnitude of interaction is expected to be low. No dosage adjustment required.

            • sildenafil

              macitentan increases levels of sildenafil by unspecified interaction mechanism. Minor/Significance Unknown. Systemic exposure of steady-state sildenafil (20 mg TID) increased by 15% during coadministration of macitentan (10 mg/day); this change is not considered clinically relevant.

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            Adverse Effects

            >10%

            Nasopharyngitis (20%)

            Headache (14%)

            Anemia (13%)

            Bronchitis (12%)

            1-10%

            Urinary tract infection (9%)

            Hemoglobin <10 g/dL (8.7%)

            Influenza (6%)

            Elevated aminotransferases >3 x ULN (3.4%)

            Elevated aminotransferases >8 x ULN (2.1%)

            Postmarketing Reports

            Immune system disorders: Hypersensitivity reactions (angioedema, pruritus and rash)

            Respiratory, thoracic and mediastinal disorders: Nasal congestion

            Gastrointestinal disorders: Elevations of liver aminotransferases (ALT, AST) and liver injury have been reported; in most cases alternative causes could be identified (heart failure, hepatic congestion, autoimmune hepatitis); ERAs have been associated with elevations of aminotransferases, hepatotoxicity, and cases of liver failure

            General disorders and administration site conditions: Edema/fluid retention; cases of edema and fluid retention occurred within weeks of starting macitentan, some requiring intervention with a diuretic, fluid management, or hospitalization for decompensated heart failure

            Cardiac disorders: Symptomatic hypotension

            Vascular disorders: Flushing

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            Warnings

            Black Box Warnings

            Pregnancy contraindication

            • Do not administer to pregnant women because it may cause fetal harm
            • Females of reproductive potential: Exclude pregnancy before starting treatment, monthly during treatment, and 1 month after stopping treatment
            • Prevent pregnancy during treatment and for 1 month after stopping treatment by using acceptable methods of contraception (see Pregnancy)

            Restricted distribution program

            • Because of risks of birth defects, available only through restricted distribution program called the Opsumit REMS program
            • May be dispensed only to patients enrolled in and meet all conditions of the REMS program
            • All females, regardless of reproductive potential, must enroll in the OPSUMIT REMS Program before initiating; male patients are not enrolled in the REMS
            • Females of reproductive potential must comply with the pregnancy testing and contraception requirements
            • Prescribers must be certified with the program by enrolling and completing training
            • Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive macitentan

            Contraindications

            History of hypersensitivity reaction to drug or excipients

            Pregnancy; consistently shown to have teratogenic effects in animal studies

            Cautions

            If pulmonary edema occurs, consider the possibility of associated pulmonary veno-occlusive disease, and if confirmed, discontinue drug

            Decreases in hemoglobin concentration and hematocrit reported; decreases in hemoglobin seldom require transfusion; initiation of therapy is not recommended in patients with severe anemia; measure hemoglobin prior to initiation of treatment and repeat during treatment as clinically indicated

            Hepatotoxicity

            • Other endothelin receptor antagonists (ERAs) have been associated with elevated liver aminotransferases, hepatotoxicity, and liver failure
            • Obtain liver enzymes tests before initiating and repeat as clinically warranted
            • Discontinue if aminotransferase elevations are accompanied by clinical symptoms of hepatoxicity
            • Advise patients to report symptoms suggesting hepatic injury (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching)
            • If clinically relevant aminotransferase elevations occur, or if elevations are accompanied by an increase in bilirubin >2 x ULN, or by clinical symptoms of hepatotoxicity, discontinue therapy
            • Consider re-initiation of therapy when hepatic enzyme levels normalize in patients who have not experienced clinical symptoms of hepatotoxicity

            Fluid retention

            • Patients with underlying left ventricular dysfunction may be at particular risk for developing significant fluid retention after initiation of ERA treatment
            • Postmarketing cases of edema and fluid retention occurring within weeks of starting therapy, some requiring intervention with a diuretic or hospitalization for decompensated heart failure, reported
            • Monitor for signs of fluid retention after initiating therapy; if clinically significant fluid retention develops, evaluate patient to determine the cause, such as the therapy being administered or underlying heart failure, and the possible need to discontinue therapy

            Drug interaction overview

            • Macitentan is a CYP3A4 substrate
            • Strong CYP3A4 inducers significantly reduce macitentan systemic exposure; avoid coadministration
            • Avoid coadministration with strong CYP3A4 inhibitors, as macitentan systemic exposure is ~doubled; use other PAH treat option when CYP3A4 inhibitors are needed as part of HIV treatment
            • Moderate dual or combined CYP3A4 and CYP2C9 inhibitors
              • Concomitant use of moderate dual inhibitors of CYP3A4 and CYP2C9 such as fluconazole is predicted to increase macitentan exposure approximately 4-fold based on physiologically based pharmacokinetic (PBPK) modelling; avoid concomitant use of drug with moderate dual inhibitors of CYP3A4 and CYP2C9 (such as fluconazole and amiodarone)
              • Concomitant treatment of both a moderate CYP3A4 inhibitor and moderate CYP2C9 inhibitor with macitentan should also be avoided
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            Pregnancy & Lactation

            Pregnancy

            Based on data from animal reproduction studies, therapy may cause embryo-fetal toxicity, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy; there are risks to mother and fetus associated with pulmonary arterial hypertension in pregnancy; there are limited data on use in pregnant women; the drug was teratogenic in rabbits and rats at all doses tested; if drug is used during pregnancy, or if patient becomes pregnant while taking this drug, advise the patient of risk to a fetus

            In patients with pulmonary arterial hypertension, pregnancy is associated with increased rate of maternal and fetal morbidity and mortality, including spontaneous abortion, intrauterine growth restriction and premature labor

            Pregnancy testing

            • Verify pregnancy status of females of reproductive potential prior to initiating therapy, monthly during treatment and one month after stopping treatment; the patient should contact her physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected; if pregnancy test is positive, the physician and patient must discuss risks to her, the pregnancy, and fetus

            Contraception

            • Female patients of reproductive potential must use acceptable methods of contraception during treatment and for 1 month after stopping
            • Patients may choose 1 highly effective form of contraception (intrauterine devices [IUD], contraceptive implants, or tubal sterilization) or a combination of methods (hormone method with a barrier method or 2 barrier methods)
            • If a partner’s vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method

            Infertility

            • Based on findings in animals, drug may impair fertility in males of reproductive potential; not known whether effects on fertility would be reversible
            • Therapy may have an adverse effect on spermatogenesis; counsel men about potential effects on fertility

            Lactation

            There are no data on presence of macitentan in human milk, effects on breastfed infant, or on milk production; because of potential for serious adverse reactions in breastfed infants advise women not to breastfeed during treatment

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Endothelin receptor antagonist (ERA); prevents binding of endothelin (ET)-1 to both ET-A and ET-B receptors with high affinity to ET receptors in pulmonary arterial smooth muscle cells; active metabolite 20% as potent as parent compound

            Absorption

            Peak plasma time: 8 hr

            Absolute bioavailability: Unknown

            Distribution

            Protein bound: >99%; mainly to albumin and to a lesser extent alpha-1-glycoprotein

            Vd: 50 L; 40 L (active metabolite)

            Metabolism

            Metabolized by liver: Mainly by CYP3A4, minor amount by CYP2C19; primarily metabolized by oxidative depropylation of the sulfamide to form active metabolite

            Active metabolite: At steady state, systemic exposure of active metabolite is 3-times the exposure of macitentan; active metabolite thought to contribute approximately 40% of total pharmacologic activity

            Elimination

            Half-life: 16 hr; 48 hr (active metabolite)

            Excretion: 50% urine; 24% feces

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            Administration

            Oral Administration

            May take with or without food

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Opsumit oral
            -
            10 mg tablet
            Opsumit oral
            -
            10 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            macitentan oral

            MACITENTAN - ORAL

            (MA-si-TEN-tan)

            COMMON BRAND NAME(S): Opsumit

            WARNING: Macitentan must not be used during pregnancy. It may harm an unborn baby. It is important to prevent pregnancy while taking this medication and for 1 month after treatment. Female patients must use reliable birth control during treatment and for 1 month after the end of treatment. Ask your doctor which forms of birth control to use while taking this medication. Female patients must take a pregnancy test before starting treatment, monthly during treatment, and 1 month after stopping treatment. If you become pregnant or think you may be pregnant, tell your doctor right away.For female patients to receive this medication in the United States, they must understand, agree to, and carefully follow the requirements of the Macitentan REMS Program. If you are a female patient that lives in Canada or any other country, consult your doctor and pharmacist for your country's regulations.

            USES: Macitentan is used to treat high blood pressure in the lungs (pulmonary arterial hypertension). This condition is thought to be caused by increased levels of a certain natural substance (endothelin-1). This medication blocks the effects of endothelin-1, which helps decrease the blood pressure in the lungs, and reduces the risk of worsening of symptoms and hospital stays due to the disease.

            HOW TO USE: Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start taking macitentan and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with or without food as directed by your doctor, usually once daily. Swallow the tablet whole. Do not split, crush, or chew the tablet.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.Tell your doctor if your condition does not improve or if it worsens.

            SIDE EFFECTS: Runny nose, sore throat, cough, headache, chills, or body aches may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: signs of low red blood cell count (such as unusual tiredness, rapid breathing, pale skin, shortness of breath, fast heartbeat), unusual weight gain, new or worsening swelling of the hands/ankles/feet.Macitentan may rarely cause serious liver disease. Tell your doctor right away if you have any symptoms of liver disease, including: nausea/vomiting that doesn't stop, loss of appetite, dark urine, stomach/abdominal pain, yellowing eyes/skin.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking macitentan, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: anemia, other lung conditions (such as pulmonary veno-occlusive disease).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).This medication can affect fertility in males. Ask your doctor for more details.This medication must not be used during pregnancy. It may harm an unborn baby. See also Warning section.Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.A product that may interact with this drug is: sparsentan.Other medications can affect the removal of macitentan from your body, which may affect how macitentan works. Examples include amiodarone, azole antifungals (such as fluconazole, ketoconazole), cobicistat, macrolide antibiotics (such as clarithromycin), rifamycins (such as rifampin), ritonavir, among others.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

            NOTES: Do not share this medication with others.Lab tests (such as liver function, pregnancy tests, hemoglobin) should be done before you start taking this medication and while you are taking it. Keep all medical and lab appointments. Consult your doctor for more details.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised March 2023. Copyright(c) 2023 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.