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Drug overview for OPSUMIT (macitentan):
Generic name: MACITENTAN (MA-si-TEN-tan)
Drug class: PAH Agents- Endothelin Receptor Antagonists
Therapeutic class: Cardiovascular Therapy Agents
Macitentan, an endothelin-receptor antagonist, is a vasodilator.
No enhanced Uses information available for this drug.
Generic name: MACITENTAN (MA-si-TEN-tan)
Drug class: PAH Agents- Endothelin Receptor Antagonists
Therapeutic class: Cardiovascular Therapy Agents
Macitentan, an endothelin-receptor antagonist, is a vasodilator.
No enhanced Uses information available for this drug.
DRUG IMAGES
OPSUMIT 10 MG TABLET
The following indications for OPSUMIT (macitentan) have been approved by the FDA:
Indications:
Pulmonary arterial hypertension
Professional Synonyms:
Hypertensive pulmonary arterial disease
Pulmonary hypertensive arterial disease
Indications:
Pulmonary arterial hypertension
Professional Synonyms:
Hypertensive pulmonary arterial disease
Pulmonary hypertensive arterial disease
The following dosing information is available for OPSUMIT (macitentan):
No enhanced Dosing information available for this drug.
No enhanced Administration information available for this drug.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| OPSUMIT 10 MG TABLET | Maintenance | Adults take 1 tablet (10 mg) by oral route once daily |
No generic dosing information available.
The following drug interaction information is available for OPSUMIT (macitentan):
There are 1 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Sparsentan/Angiotensin II Receptor Blockers; Endothelin Receptor Antagonists; Aliskiren SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Sparsentan is an antagonist of the endothelin type A receptor and the angiotensin II type 1 receptor which are thought to contribute to the pathogenesis of IgA nephropathy.(1) Coadministration with angiotensin II receptor blockers (ARBs), endothelin receptor antagonists (ERAs), or aliskiren may result in additive inhibition of angiotensin. CLINICAL EFFECTS: Concurrent use of sparsentan with ARBs, ERAs, or aliskiren may result in hypotension, syncope, hyperkalemia, and changes in renal function (including renal failure).(1) PREDISPOSING FACTORS: Patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion may be at risk of developing acute kidney injury on sparsentan.(1) Patients with advanced kidney disease or taking concomitant potassium-increasing drugs (e.g., potassium supplements, potassium-sparing diuretics), or using potassium-containing salt substitutes are at increased risk for developing hyperkalemia.(1) PATIENT MANAGEMENT: Do not coadminister sparsentan with ARBs, ERAs, or aliskiren. Prior to initiating treatment with sparsentan, discontinue use of ARBs, ERAs, and aliskiren.(1) DISCUSSION: The US manufacturer of sparsentan states that concomitant use of sparsentan with ARBs, ERAs, or aliskiren is contraindicated.(1) |
FILSPARI |
There are 3 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Macitentan/Strong CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong CYP3A4 inducers may induce the metabolism of macitentan.(1) CYP3A4 is the primary metabolism pathway of macitentan to its less active metabolite.(1,2) CLINICAL EFFECTS: Concurrent use of strong CYP3A4 inducers may decrease systemic levels and effectiveness of macitentan.(1,2) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of macitentan recommends avoiding concurrent use of macitentan and strong CYP3A4 inducers.(2) If concurrent therapy is warranted, monitor closely for loss of efficacy and adjust macitentan dose or dosing interval if needed. Note the onset of induction is gradual; maximal induction may not occur for 2 or more weeks. When concurrent treatment with rifampin is stopped, induction will gradually wane and systemic concentrations of macitentan will gradually increase over 2 or more weeks. Monitor for toxicity and adjust dose as required. DISCUSSION: An interaction study in 10 healthy male subjects evaluated the effect of rifampin on macitentan and active metabolite pharmacokinetics. Although less potent, the active metabolite was evaluated as its longer half-life leads to a 3-fold higher systemic exposure than macitentan. About 40% of macitentan pharmacologic activity is thought due to this metabolite.(2) Subjects received a 30 mg macitentan loading dose followed by 10 mg daily for four more days. Beginning on day 6, rifampin 600 mg and macitentan 10 mg were co-administered daily for 7 days. Macitentan area-under-curve (AUC) and concentration minimum (Cmin) were measured on days 5 and 12. Co-administration decreased macitentan AUC 79% and trough concentration 93%. The AUC and Cmin of the macitentan active metabolite was unchanged and decreased 17% respectively.(1) Strong CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's Wort.(3) |
ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, BRAFTOVI, BUTALB-ACETAMINOPH-CAFF-CODEIN, BUTALBITAL, BUTALBITAL-ACETAMINOPHEN, BUTALBITAL-ACETAMINOPHEN-CAFFE, BUTALBITAL-ASPIRIN-CAFFEINE, CARBAMAZEPINE, CARBAMAZEPINE ER, CARBATROL, CEREBYX, DILANTIN, DILANTIN-125, DONNATAL, EPITOL, EQUETRO, ERLEADA, FIORICET, FIORICET WITH CODEINE, FOSPHENYTOIN SODIUM, LYSODREN, MITOTANE, MYSOLINE, ORKAMBI, PENTOBARBITAL SODIUM, PHENOBARBITAL, PHENOBARBITAL SODIUM, PHENOBARBITAL-BELLADONNA, PHENOBARBITAL-HYOSC-ATROP-SCOP, PHENOHYTRO, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED, PRIFTIN, PRIMIDONE, RIFADIN, RIFAMPIN, SEZABY, TEGRETOL, TEGRETOL XR, TENCON, TIBSOVO, XTANDI |
| Macitentan/Strong CYP3A4 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong inhibitors of CYP3A4 may inhibit the metabolism of macitentan.(1) CLINICAL EFFECTS: Concurrent use of a strong inhibitor of CYP3A4 may result in elevated levels and increased effects of macitentan.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of macitentan states that use of strong inhibitors of CYP3A4 should be avoided. When strong CYP3A4 inhibitors are required (e.g. protease inhibitors in the treatment of HIV), use other treatment options for pulmonary arterial hypertension.(1) The Journal of American College of Cardiology (JACC) states concurrent use of macitentan and nirmatrelvir-ritonavir is not advised. JACC recommends discontinuing macitentan for at least 36 hours before initiation of nirmatrelvir-ritonavir.(2) DISCUSSION: Pretreatment with ketoconazole increased the area-under-curve (AUC) and maximum concentration (Cmax) of macitentan approximately 2.3 and 1.3-fold respectively.(1) Strong inhibitors of CYP3A4 include: adagrasib, boceprevir, ceritinib, clarithromycin, cobicistat, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, levoketoconazole, lonafarnib, lopinavir/ritonavir, mibefradil, mifepristone, nefazodone, nelfinavir, nirmatrelvir/ritonavir, paritaprevir, posaconazole, ribociclib, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, tucatinib, and voriconazole.(3) |
APTIVUS, CLARITHROMYCIN, CLARITHROMYCIN ER, EVOTAZ, GENVOYA, ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KALETRA, KETOCONAZOLE, KISQALI, KORLYM, KRAZATI, LANSOPRAZOL-AMOXICIL-CLARITHRO, LOPINAVIR-RITONAVIR, MIFEPREX, MIFEPRISTONE, NEFAZODONE HCL, NOXAFIL, OMECLAMOX-PAK, PAXLOVID, POSACONAZOLE, PREZCOBIX, RECORLEV, SPORANOX, STRIBILD, SYMTUZA, TOLSURA, TUKYSA, TYBOST, VFEND, VFEND IV, VIRACEPT, VOQUEZNA TRIPLE PAK, VORICONAZOLE, ZOKINVY, ZYDELIG, ZYKADIA |
| Macitentan/Dual Moderate CYP2C9 & CYP3A4 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Dual moderate inhibitors of CYP2C9 and CYP3A4 may inhibit the metabolism of macitentan.(1) CLINICAL EFFECTS: Concurrent use of a dual moderate inhibitor of CYP2C9 and CYP3A4 may result in elevated levels and increased effects of macitentan.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of macitentan states that use of dual moderate inhibitors of CYP2C9 and CYP3A4 should be avoided. Concomitant use of both a moderate CYP3A4 inhibitor and a moderate CYP2C9 inhibit should also be avoided.(1) DISCUSSION: Based on pharmacokinetic (PBPK) modeling, dual moderate inhibitors of CYP2C9 and CYP3A4 such as fluconazole are predicted to increase macitentan exposure by 4-fold.(1) Dual moderate inhibitors of CYP2C9 and CYP3A4 include: amiodarone and fluconazole.(2) |
AMIODARONE HCL, AMIODARONE HCL-D5W, DIFLUCAN, FLUCONAZOLE, FLUCONAZOLE-NACL, NEXTERONE, PACERONE |
There are 1 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Macitentan/Moderate CYP3A4 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Macitentan is primarily metabolized by CYP3A4, with minor contributions from CYP2C8, CYP2C9, and CYP2C19. Moderate inhibitors of CYP3A4 may inhibit the metabolism of macitentan.(1) CLINICAL EFFECTS: Concurrent use of a moderate inhibitor of CYP3A4 may result in elevated levels and increased effects of macitentan, including hepatotoxicity and fluid retention.(1) PREDISPOSING FACTORS: Concomitant use of a moderate CYP2C9 inhibitor increases the magnitude of this interaction and the risk of adverse events. PATIENT MANAGEMENT: The manufacturer of macitentan states that concurrent use of both a moderate CYP2C9 inhibitor and a moderate CYP3A4 inhibitor should be avoided.(1) While the manufacturer does not provide recommendations for concurrent use of a moderate CYP3A4 inhibitor alone, it would be prudent to use caution and monitor for adverse effects. DISCUSSION: Based on pharmacokinetic (PBPK) modeling, dual moderate inhibitors of CYP2C9 and CYP3A4 such as fluconazole are predicted to increase macitentan exposure by 4-fold.(1) Pretreatment with ketoconazole increased the area-under-curve (AUC) and maximum concentration (Cmax) of macitentan by approximately 2.3 and 1.3-fold, respectively.(1) Moderate CYP3A4 inhibitors linked to this monograph include: amprenavir, aprepitant, atazanavir, avacopan, berotralstat, clofazimine, conivaptan, crizotinib, darunavir, diltiazem, dronedarone, duvelisib, erythromycin, fedratinib, fluvoxamine, fosamprenavir, fosnetupitant, imatinib, isavuconazonium, oral lefamulin, lenacapavir, letermovir, netupitant, nilotinib, schisandra, tofisopam, treosulfan, verapamil, and voxelotor.(2) |
AKYNZEO, APONVIE, APREPITANT, ATAZANAVIR SULFATE, CARDIZEM, CARDIZEM CD, CARDIZEM LA, CARTIA XT, CINVANTI, CLOFAZIMINE, CONIVAPTAN-D5W, COPIKTRA, CRESEMBA, DANZITEN, DARUNAVIR, DILT-XR, DILTIAZEM 12HR ER, DILTIAZEM 24HR ER, DILTIAZEM 24HR ER (CD), DILTIAZEM 24HR ER (LA), DILTIAZEM 24HR ER (XR), DILTIAZEM HCL, DILTIAZEM HCL-0.7% NACL, DILTIAZEM HCL-0.9% NACL, DILTIAZEM HCL-NACL, DILTIAZEM-D5W, E.E.S. 200, E.E.S. 400, EMEND, ERY-TAB, ERYPED 200, ERYPED 400, ERYTHROCIN LACTOBIONATE, ERYTHROCIN STEARATE, ERYTHROMYCIN, ERYTHROMYCIN ESTOLATE, ERYTHROMYCIN ETHYLSUCCINATE, ERYTHROMYCIN LACTOBIONATE, EVOTAZ, FLUVOXAMINE MALEATE, FLUVOXAMINE MALEATE ER, FOSAMPRENAVIR CALCIUM, GLEEVEC, GRAFAPEX, IMATINIB MESYLATE, IMKELDI, INREBIC, MATZIM LA, MULTAQ, NILOTINIB HCL, ORLADEYO, PREVYMIS, PREZCOBIX, PREZISTA, REYATAZ, SUNLENCA, SYMTUZA, TASIGNA, TAVNEOS, TIADYLT ER, TIAZAC, TRANDOLAPRIL-VERAPAMIL ER, VAPRISOL-5% DEXTROSE, VERAPAMIL ER, VERAPAMIL ER PM, VERAPAMIL HCL, VERAPAMIL SR, XALKORI, XENLETA |
The following contraindication information is available for OPSUMIT (macitentan):
Drug contraindication overview.
*Pregnancy. *History of hypersensitivity reaction to macitentan or any component.
*Pregnancy. *History of hypersensitivity reaction to macitentan or any component.
There are 2 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Lactation |
| Pregnancy |
There are 3 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Anemia |
| Chronic heart failure |
| Pulmonary veno-occlusive disease |
There are 0 moderate contraindications.
The following adverse reaction information is available for OPSUMIT (macitentan):
Adverse reaction overview.
The most common adverse effects reported with macitentan in clinical trials and occurring at least 3% more frequently with the drug than with placebo include anemia, nasopharyngitis/pharyngitis, bronchitis, headache, influenza, and urinary tract infection.
The most common adverse effects reported with macitentan in clinical trials and occurring at least 3% more frequently with the drug than with placebo include anemia, nasopharyngitis/pharyngitis, bronchitis, headache, influenza, and urinary tract infection.
There are 8 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Anemia |
Abnormal hepatic function tests |
| Rare/Very Rare |
|---|
|
Angioedema Drug-induced hepatitis Heart failure Hepatic failure Hyperbilirubinemia Hypotension |
There are 15 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Bronchitis Headache disorder Influenza Pharyngitis Urinary tract infection |
Acute abdominal pain Back pain Palpitations |
| Rare/Very Rare |
|---|
|
Body fluid retention Edema Flushing Nasal congestion Oligospermia Pruritus of skin Skin rash |
The following precautions are available for OPSUMIT (macitentan):
Safety and efficacy of macitentan have not been established in pediatric patients.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Based on data from animal reproduction studies, macitentan may cause embryofetal toxicity, including birth defects and fetal death, when administered to pregnant females and is contraindicated during pregnancy. Data are limited on use of macitentan in pregnant women. Consider the increased risk of pregnancy-associated maternal and fetal morbidity and mortality in patients with PAH, including spontaneous abortion, intrauterine growth restriction, and premature labor.
It is not known whether macitentan is distributed into human milk. Because of the potential for serious adverse reactions to macitentan in nursing infants, advise women not to breastfeed during treatment with macitentan.
In the principal clinical study of macitentan in patients with PAH, 14% of the patients were 65 years of age or older. No overall differences in safety or efficacy were observed between these geriatric patients and younger individuals.
The following prioritized warning is available for OPSUMIT (macitentan):
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 before starting treatment, during treatment, and for 1 month after the last dose. Ask your doctor which forms of birth control to use while taking this medication. Female patients must take a pregnancy test before starting treatment. If you become pregnant or think you may be pregnant, tell your doctor right away.
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 before starting treatment, during treatment, and for 1 month after the last dose. Ask your doctor which forms of birth control to use while taking this medication. Female patients must take a pregnancy test before starting treatment. If you become pregnant or think you may be pregnant, tell your doctor right away.
The following icd codes are available for OPSUMIT (macitentan)'s list of indications:
| Pulmonary arterial hypertension | |
| I27.0 | Primary pulmonary hypertension |
| I27.21 | Secondary pulmonary arterial hypertension |
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