macitentan 10 mg Tablet, Film Coated, 30-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Endothelin Receptor Antagonist class.
Where does this data come from?
🏭 Manufacturer & labeler
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🩺 Clinical
Macitentan is used to manage the symptoms of pulmonary arterial hypertension (PAH; high blood pressure in the blood vessels that carry blood to the lungs). Macitentan is in a class of medications called endothelin receptor antagonists. It works by stopping the action of endothelin, a natural substance that causes blood vessels to narrow.
Read the full MedlinePlus article ↗- Macitentan (brand name Opsumit) is used to treat pulmonary arterial hypertension — PAH for short — which is a condition where the blood pressure in the arteries going to your lungs...
- You take one tablet by mouth once a day. The good news is you can take it with or without food — it doesn't matter if you've just eaten a big meal or nothing at all. Try to take it...
- The most common side effects are things like a stuffy or sore throat, bronchitis, headaches, flu-like symptoms, urinary tract infections, and low red blood cell counts (anemia), wh...
- What side effects should I watch out for?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Macitentan — tap one for details:
Macitentan may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
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Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII 532B59J990
Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
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UNII U725QWY32X
Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach so the medicine can be absorbed.
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UNII 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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UNII 5856J3G2A2
A starch-based powder made from potatoes and processed with sodium. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the medicine can be absorbed.
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UNII 1DI56QDM62
A natural fatty substance from soybeans that helps mix oil and water-based ingredients together. It acts as an emulsifier and lubricant in medicines to improve texture and help the product break down properly in your body.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
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UNII TTV12P4NEE
Xanthan gum is a thickening and stabilizing ingredient made from fermented corn or other sugars. It's added to medicines to improve texture, prevent separation of liquids and solids, and help the product stay consistent.
11 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Macitentan 10 mg 00378-0606-93 | Mylan | 30 tablets | — | AB | FDA listed | — |
| macitentan 10 mg 00480-0915-56 | Teva | 30 tablets | — | AB | FDA listed | — |
| macitentan 10 mgthis 00781-8135-31 | Sandoz | 30 tablets | — | AB | FDA listed | — |
| Macitentan 10 mg 13668-0542-05 | Torrent | 500 tablets | — | AB | FDA listed | — |
| Macitentan 10 mg 42385-0907-15 | Laurus | 15 tablets | — | AB | FDA listed | — |
| Macitentan 10 mg 46708-0373-30 | Alembic | 30 tablets | — | AB | FDA listed | — |
| Macitentan 10 mg 47335-0070-15 | Sun | 3 tablets | — | AB | FDA listed | — |
| Macitentan 10 mg 59651-0147-30 | Aurobindo | 30 tablets | — | AB | FDA listed | — |
| macitentan 10 mg 60505-4644-03 | Apotex | 30 tablets | — | AB | FDA listed | — |
| Macitentan 10 mg 62332-0373-30 | Alembic | 30 tablets | — | AB | FDA listed | — |
| Opsumit 10 mg 66215-0501-15 | Actelion | 15 tablets | — | AB | FDA listed | — |
| Macitentan 10 mg 69238-1327-03 | Amneal | 30 tablets | — | AB | FDA listed | — |
| Macitentan 10 mg 70710-1166-03 | Zydus | 30 tablets | — | AB | FDA listed | — |
| Macitentan 10 mg 82293-0041-10 | Novugen | 15 tablets | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00781-8135-31 You're viewing this | 30 TABLET, FILM COATED in 1 BOTTLE (0781-8135-31) | 2026-06-05 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: EMBRYO-FETAL TOXICITY Macitentan is contraindicated for use during pregnancy because it may cause fetal harm based on animal data [see Contraindications (4.1) , Warnings and Precautions (5.1 ), Use in Specific Populations (8.1) ]. 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 [see Dosage and Administration (2.2) , Use in Specific Populations (8.3) ].
When pregnancy is detected, discontinue macitentan as soon as possible [see Warnings and Precautions (5.1) ]. WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. Based on animal data, macitentan may cause fetal harm if used during pregnancy ( 4.1 , 5.1 , 8.1 ).
Females of reproductive potential: exclude pregnancy before start of treatment. Prevent pregnancy prior to initiation of treatment, during treatment and for one month after treatment by using effective methods of contraception ( 2.2 , 8.3 ). When pregnancy is detected, discontinue macitentan as soon as possible ( 5.1 ).
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Macitentan tablets are an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adults to reduce the risks of disease progression and hospitalization for PAH ( 1.1 ).
1.1Pulmonary Arterial Hypertension Macitentan tablets are an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adults to reduce the risks of disease progression and hospitalization for PAH. Effectiveness was established in a long-term study in PAH patients with predominantly WHO Functional Class II-III symptoms treated for an average of 2 years. Patients had idiopathic and heritable PAH (57%), PAH caused by connective tissue disorders (31%), and PAH caused by congenital heart disease with repaired shunts (8%) [ see Clinical Studies (14.1)].
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION 10 mg once daily. Doses higher than 10 mg once daily have not been studied in patients with PAH and are not recommended ( 2.1 ).
2.1Recommended Dosage The recommended dosage of macitentan tablets are 10 mg once daily for oral administration. Doses higher than 10 mg once daily have not been studied in patients with PAH and are not recommended.
2.2Pregnancy Testing in Females of Reproductive Potential Exclude pregnancy before initiating treatment with macitentan tablets in females of reproductive potential [see Boxed Warning, Contraindications (4.1) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.3) ].
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablets: 10 mg, bi-convex film-coated, round, white, and debossed with "M" on one side and "10" on other side. Tablet: 10 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 )
4.1Pregnancy Macitentan may cause fetal harm when administered to a pregnant woman. Macitentan is contraindicated in females who are pregnant. Macitentan was consistently shown to have teratogenic effects when administered to animals. If macitentan is used during pregnancy, advise the patient of the potential risk to a fetus [ see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].
4.2Hypersensitivity Macitentan is contraindicated in patients with a history of a hypersensitivity reaction to macitentan or any component of the product [ see Adverse Reactions (6.2 )].
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS ERAs cause hepatotoxicity and liver failure. Obtain baseline liver enzymes and monitor as clinically indicated ( 5.2) . Fluid retention may require intervention ( 5.3 ). Decreases in hemoglobin ( 5.4 ). Pulmonary edema in patients with pulmonary veno-occlusive disease. If confirmed, discontinue treatment ( 5.5 ). Decreases in sperm count have been observed in patients taking ERAs ( 5.6 ). .
5.1Embryo-fetal Toxicity Based on data from animal reproduction studies, macitentan may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. The available human data for ERAs do not establish the presence or absence of major birth defects related to the use of macitentan. Advise patients who can become pregnant of the potential risk to a fetus.
Obtain a pregnancy test prior to initiation of therapy with macitentan. Advise patients who can become pregnant to use effective contraceptive methods prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with macitentan. When pregnancy is detected, discontinue use as soon as possible [see Dosage and Administration (2.2) , Contraindications (4.1) , and Use in Specific Populations (8.1 , 8.3) ].
5.2Hepatotoxicity ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure. The incidence of elevated aminotransferases in the study of macitentan in PAH is shown in Table 1. Table 1: Incidence of Elevated Aminotransferases in the SERAPHIN Study Macitentan 1 0 mg ( N=242 ) Placebo (N =2 4 9 ) >3 x ULN 3.4% 4.5% >8 x ULN 2.1% 0.4% In the placebo-controlled study of macitentan, discontinuations for hepatic adverse events were 3.3% in the macitentan 10 mg group vs.
1.6% for placebo. Obtain liver enzyme tests prior to initiation of macitentan and repeat during treatment as clinically indicated [ see Adverse Reactions (6.2)]. 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 macitentan. Consider re-initiation of macitentan when hepatic enzyme levels normalize in patients who have not experienced clinical symptoms of hepatotoxicity.
5.3Fluid Retention Peripheral edema and fluid retention are known clinical consequences of PAH and known effects of ERAs. In the placebo-controlled study of macitentan in PAH, the incidence of edema was 21.9% in the macitentan 10 mg group and 20.5% in the placebo group. Patients with underlying left ventricular dysfunction may be at particular risk for developing significant fluid retention after initiation of ERA treatment.
In a small study of macitentan in patients with pulmonary hypertension because of left ventricular dysfunction, more patients in the macitentan group developed significant fluid retention and had more hospitalizations because of worsening heart failure compared to those randomized to placebo. Postmarketing cases of edema and fluid retention occurring within weeks of starting macitentan, some requiring intervention with a diuretic or hospitalization for decompensated heart failure, have been reported [ see Adverse Reactions (6.2 )].
Monitor for signs of fluid retention after macitentan initiation. If clinically significant fluid retention develops, evaluate the patient to determine the cause, such as macitentan or underlying heart failure, and the possible need to discontinue macitentan.
5.4Hemoglobin Decrease Decreases in hemoglobin concentration and hematocrit have occurred following administration of other ERAs and were observed in clinical studies with macitentan. These decreases occurred early and stabilized thereafter. In the placebo-controlled study of macitentan in PAH, macitentan 10 mg caused a mean decrease in…
🤒 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 )] • Decrease in Hemoglobin [see Warnings and Precautions (5.4 )] Most common adverse reactions (more frequent than placebo by ≥3%) are anemia, nasopharyngitis/pharyngitis, bronchitis, headache, influenza, and urinary tract infection ( 6.1 ).
To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in 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 clinical practice. Safety data for macitentan were obtained primarily from one placebo-controlled clinical study in 742 patients with PAH (SERAPHIN study) [ see Clinical Studies (14.1 )]. The exposure to macitentan in this trial was up to 3.6 years with a median exposure of about 2 years (N=542 for 1 year; N=429 for 2 years; and N=98 for more than 3 years).
The overall incidence of treatment discontinuations because of adverse events was similar across macitentan 10 mg and placebo treatment groups (approximately 11%). Table 2 presents adverse reactions more frequent on macitentan than on placebo by ≥3%. Table 2: Adverse Reactions Adverse Reactio n Macitentan 10 mg (N=242) (%) Placebo (N=249) (%) Anemia 13 3 Nasopharyngitis/pharyngitis 20 13 Bronchitis 12 6 Headache 14 9 Influenza 6 2 Urinary tract infection 9 6
6.2Postmarketing Experience The following adverse reactions have been identified during post-approval use of macitentan. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune system disorders : hypersensitivity reactions (angioedema, pruritus and rash) Vascular disorders: flushing Respiratory, thoracic and mediastinal disorders : nasal congestion Gastrointestinal disorders : Elevations of liver aminotransferases (ALT, AST) and liver injury have been reported with macitentan use; in most cases alternative causes could be identified (heart failure, hepatic congestion, autoimmune hepatitis).
Endothelin receptor antagonists have been associated with elevations of aminotransferases, hepatotoxicity, and cases of liver failure [ see Warnings and Precautions (5.2) ]. 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 [ see Warnings and Precautions (5.3) ] .
Cardiac disorders: symptomatic hypotension
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS • Strong CYP3A4 inducers (rifampin) reduce exposure to macitentan: avoid co-administration with macitentan ( 7.1 , 12.3 ). • Strong CYP3A4 inhibitors (ketoconazole, ritonavir) increase exposure to macitentan: avoid co-administration with macitentan ( 7.2 , 12.3 ). • Moderate dual CYP3A4 and CYP2C9 inhibitors (fluconazole, amiodarone) or use of combined CYP3A4 and CYP2C9 inhibitors may increase exposure to macitentan: avoid co-administration with macitentan ( 7.3, 12.3 ).
7.1Strong CYP3A4 Inducers Strong inducers of CYP3A4 such as rifampin significantly reduce macitentan exposure. Concomitant use of macitentan with strong CYP3A4 inducers should be avoided [ see Clinical Pharmacology (12.3)].
7.2Strong CYP3A4 Inhibitors Concomitant use of strong CYP3A4 inhibitors like ketoconazole approximately double macitentan exposure. Many HIV drugs like ritonavir are strong inhibitors of CYP3A4. Avoid concomitant use of macitentan with strong CYP3A4 inhibitors [ see Clinical Pharmacology (12.3)]. Use other PAH treatment options when strong CYP3A4 inhibitors are needed as part of HIV treatment [ see Clinical Pharmacology (12.3)].
7.3Moderate 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) modeling. Avoid concomitant use of macitentan with moderate dual inhibitors of CYP3A4 and CYP2C9 (such as fluconazole and amiodarone) [ see Clinical Pharmacology (12.3) ] . Concomitant treatment of both a moderate CYP3A4 inhibitor and moderate CYP2C9 inhibitor with macitentan should also be avoided [ see Clinical Pharmacology (12.3) ] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 )
8.1Pregnancy Risk Summary Based on data from animal reproduction studies, macitentan 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 the mother and the fetus associated with pulmonary arterial hypertension in pregnancy [see Clinical Considerations]. Available data from postmarketing reports and published literature over decades of use with ERAs in the same class as macitentan have not identified an increased risk of major birth defects; however, these data are limited.
Methodological limitations of these postmarketing reports and published literature include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and missing data. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal ERA use. Macitentan was teratogenic in rabbits and rats at all doses tested.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the risk to a fetus [ see Contraindications (4.1) ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryo/Fetal Risk In patients with pulmonary arterial hypertension, pregnancy is associated with an increased rate of maternal and fetal morbidity and mortality, including spontaneous abortion, intrauterine growth restriction and premature labor. Data Animal Data In both rabbits and rats, there were cardiovascular and mandibular arch fusion abnormalities.
Administration of macitentan to female rats from late pregnancy through lactation caused reduced pup survival and impairment of the male fertility of the offspring at all dose levels tested.
8.2Lactation Risk Summary There are no data on the presence of macitentan in human milk, the effects on the breastfed infant, or the effect on milk production. Because of the potential for serious adverse reactions in breastfed infants from macitentan advise women not to breastfeed during treatment with macitentan.
8.3Females and Males of Reproductive Potential Based on data from animal reproductive toxicity studies, macitentan can cause fetal harm, including birth defects and fetal death, when administered to a pregnant patient and is contraindicated during pregnancy [see Contraindications (4.1) , and U se in Specific Populations (8.1) ]. Pregnancy Testing Verify that patients who can become pregnant are not pregnant prior to initiating macitentan. The patient should contact their physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected.
If the pregnancy test is positive, the physician and patient should discuss the risks to the pregnancy, and the fetus. Contraception Patients who can become pregnant who are using macitentan should use an effective method of contraception prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with macitentan to prevent pregnancy [see Warnings and Precautions (5.1) ]. Infertility Based on findings in animals, macitentan may impair fertility in males of reproductive potential.
It is not known whether effects on fertility would be reversible [ see Warnings and Precautions (5.6) , Adverse Reactions (6.1) , and Nonclinical Toxicology (13.1) ].
8.4Pediatric Use The safety and effectiveness of macitentan in pediatric patients have not been established for the treatment of PAH. Pediatric information descri…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on data from animal reproduction studies, macitentan 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 the mother and the fetus associated with pulmonary arterial hypertension in pregnancy [see Clinical Considerations]. Available data from postmarketing reports and published literature over decades of use with ERAs in the same class as macitentan have not identified an increased risk of major birth defects; however, these data are limited.
Methodological limitations of these postmarketing reports and published literature include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and missing data. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal ERA use. Macitentan was teratogenic in rabbits and rats at all doses tested.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the risk to a fetus [ see Contraindications (4.1) ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryo/Fetal Risk In patients with pulmonary arterial hypertension, pregnancy is associated with an increased rate of maternal and fetal morbidity and mortality, including spontaneous abortion, intrauterine growth restriction and premature labor. Data Animal Data In both rabbits and rats, there were cardiovascular and mandibular arch fusion abnormalities.
Administration of macitentan to female rats from late pregnancy through lactation caused reduced pup survival and impairment of the male fertility of the offspring at all dose levels tested.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of macitentan in pediatric patients have not been established for the treatment of PAH. Pediatric information describing a clinical study in which efficacy was not demonstrated is approved for Actelion Pharmaceuticals US, Inc.’s Opsumit (macitentan) tablets. However, due to Actelion Pharmaceuticals US, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the total number of subjects in the clinical study of macitentan for PAH, 14% were 65 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.
🆘 Overdosage ▾
10 OVERDOSAGE Macitentan has been administered as a single dose of up to and including 600 mg to healthy subjects (60 times the approved dosage). Adverse reactions of headache, nausea and vomiting were observed. In the event of an overdose, standard supportive measures should be taken, as required. Dialysis is unlikely to be effective because macitentan is highly protein-bound.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Endothelin (ET)-1 and its receptors (ET A and ET B ) mediate a variety of deleterious effects, such as vasoconstriction, fibrosis, proliferation, hypertrophy, and inflammation. In disease conditions such as PAH, the local ET system is upregulated and is involved in vascular hypertrophy and in organ damage. Macitentan is an endothelin receptor antagonist that inhibits the binding of ET-1 to both ET A and ET B receptors.
Macitentan displays high affinity and sustained occupancy of the ET receptors in human pulmonary arterial smooth muscle cells. One of the metabolites of macitentan is also pharmacologically active at the ET receptors and is estimated to be about 20% as potent as the parent drug in vitro. The clinical impact of dual endothelin blockage is unknown.
12.2Pharmacodynamics Pulmonary Hemodynamics The clinical efficacy study in patients with pulmonary arterial hypertension assessed hemodynamic parameters in a subset of patients after 6 months of treatment. Patients treated with macitentan 10 mg (N=57) achieved a median reduction of 37% (95% CI 22 to 49) in pulmonary vascular resistance and an increase of
0.6L/min/m 2 (95% CI 0.3 to 0.9) in cardiac index compared to placebo (N=67). Cardiac Electrophysiology In a randomized, placebo-controlled four-way crossover study with a positive control in healthy subjects, repeated doses of macitentan 10 and 30 mg (3 times the recommended dosage) had no significant effect on the QTc interval.
12.3Pharmacokinetics The pharmacokinetics of macitentan and its active metabolite have been studied primarily in healthy subjects. The pharmacokinetics of macitentan are dose proportional over a range from 1 mg to 30 mg after once daily administration. A cross study comparison shows that the exposures to macitentan and its active metabolite in patients with PAH are similar to those observed in healthy subjects.
Absorption and Distribution The maximum plasma concentration of macitentan is achieved about 8 hours after oral administration. The absolute bioavailability after oral administration is not known. In a study in healthy subjects, the exposure to macitentan and its active metabolite were unchanged after a high fat breakfast.
Macitentan may therefore be taken with or without food. Macitentan and its active metabolite are highly bound to plasma proteins (>99%), primarily to albumin and to a lesser extent to alpha-1-acid glycoprotein. The apparent volumes of distribution (Vss/F) of macitentan and its active metabolite were about 50 L and 40 L respectively in healthy subjects.
Metabolism and Elimination Following oral administration, the apparent elimination half-lives of macitentan and its active metabolite are approximately 16 hours and 48 hours, respectively. Macitentan is metabolized primarily by oxidative depropylation of the sulfamide to form the pharmacologically active metabolite. This reaction is dependent on the cytochrome P450 (CYP) system, mainly CYP3A4 with minor contributions of CYP2C8, CYP2C9, and CYP2C19.
At steady state in PAH patients, the systemic exposure to the active metabolite is 3-times the exposure to macitentan and is expected to contribute approximately 40% of the total pharmacologic activity. In a study in healthy subjects with radiolabeled macitentan, approximately 50% of radioactive drug material was eliminated in urine but none was in the form of unchanged drug or the active metabolite. About 24% of the radioactive drug material was recovered from feces.
Special Populations There are no clinically relevant effects of age, sex, or race on the pharmacokinetics of macitentan and its active metabolite. Renal Impairment Exposure to macitentan and its active metabolite in patients with severe renal impairment (CrCl 15 to 29 mL/min) compared to healthy subjects was increased by 30% and 60%, respectively. This increase is not considered clinically relevant.
Hepatic Impairment Exposure to macitentan was decreased by 21%…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Endothelin (ET)-1 and its receptors (ET A and ET B ) mediate a variety of deleterious effects, such as vasoconstriction, fibrosis, proliferation, hypertrophy, and inflammation. In disease conditions such as PAH, the local ET system is upregulated and is involved in vascular hypertrophy and in organ damage. Macitentan is an endothelin receptor antagonist that inhibits the binding of ET-1 to both ET A and ET B receptors.
Macitentan displays high affinity and sustained occupancy of the ET receptors in human pulmonary arterial smooth muscle cells. One of the metabolites of macitentan is also pharmacologically active at the ET receptors and is estimated to be about 20% as potent as the parent drug in vitro. The clinical impact of dual endothelin blockage is unknown.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Macitentan tablets are 10 mg white colored, round shaped, biconvex, film-coated tablets, debossed with "M" on one side and "10" on other side and supplied as follows: 30 tablets white high-density polyethylene bottle (NDC 0781-8135-31) Store at 20ºC to 25ºC (68ºF to 77ºF). Excursions are permitted between 15°C and 30°C (59°F and 86°F). [See USP Controlled Room Temperature]. Keep out of reach of children.
📋 Description ▾
11 DESCRIPTION Macitentan tablet is an endothelin receptor antagonist. The chemical name of macitentan is N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-propylsulfamide. It has a molecular formula of C 19 H 20 Br 2 N 6 O 4 S and a molecular weight of 588.27.
Macitentan is achiral and has the following structural formula: Macitentan is a crystalline powder that is insoluble in water. In the solid state macitentan is very stable, is not hygroscopic, and is not light sensitive. Macitentan tablets are available as a 10 mg film-coated tablet for once daily oral administration.
The tablets include the following inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone K 30, sodium starch glycolate Type A and sodium lauryl sulfate. The tablets are film-coated with a coating material containing polyvinyl alcohol, soya lecithin, talc, titanium dioxide, and xanthan gum. structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patient to read FDA-approved patient labeling (Medication Guide). Embryo-Fetal Toxicity Counsel female patients of reproductive potential about the need to use effective methods of contraception prior to initiation of treatment with macitentan, during treatment and for one month after treatment discontinuation. Females of reproductive potential should have a negative pregnancy test prior to treatment with macitentan [see Contraindications (4.1), and Use in Specific Populations (8.1 , 8.3) ].
Patients should be instructed to contact their physician if they suspect they may be pregnant. Patients should seek additional contraceptive advice from a gynecologist or similar expert as needed. Educate and counsel females of reproductive potential on the use of emergency contraception in the event of unprotected sex or contraceptive failure.
Advise pre-pubertal females to report any changes in their reproductive status immediately to her prescriber. Review the Medication Guide with female patients. Lactation Advise women not to breastfeed during treatment with macitentan [ see Use in Specific Populations (8.2) ] .
Hepatotoxicity Some members of this pharmacological class are hepatotoxic. Educate patients on signs of hepatotoxicity. Advise patients that they should contact their doctor if they have unexplained nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching [see Warnings and Precautions (5.2) ] .
Fluid Retention Educate patients on signs of fluid retention. Advise patients that they should contact their doctor if they have unusual weight increase or swelling of the ankles or legs [see Warnings and Precautions (5.3) ] . Manufactured by: MSN Laboratories Private Limited Telangana 509228, India for Sandoz Inc., Princeton, NJ 08540 The brands listed are the registered trademarks of their respective owners and are not trademarks of Sandoz Inc.