Macitentan Sandoz
Endothelin Receptor Antagonist for Pulmonary Arterial Hypertension
Macitentan Sandoz is a prescription medication containing the active ingredient macitentan, a dual endothelin receptor antagonist (ERA) used for the long-term treatment of pulmonary arterial hypertension (PAH) in adults. It works by blocking the vasoconstrictor endothelin-1 in the pulmonary vasculature, reducing pulmonary vascular resistance and slowing disease progression. This guide covers everything you need to know about Macitentan Sandoz, including uses, dosage, side effects, drug interactions, and important safety information.
Quick Facts
Key Takeaways
- Macitentan Sandoz is a dual endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH) in adults with WHO Functional Class II-III symptoms.
- The SERAPHIN trial demonstrated that macitentan 10 mg significantly reduced morbidity and mortality events by 45% compared to placebo over a median follow-up of 115 weeks.
- Macitentan is strictly contraindicated in pregnancy due to the risk of serious birth defects; a pregnancy prevention program is mandatory for women of childbearing potential.
- Common side effects include nasopharyngitis, headache, and anemia. Hemoglobin levels should be monitored regularly during treatment.
- Macitentan is often used in combination with PDE5 inhibitors and/or prostacyclin pathway agents as part of current guideline-directed combination therapy for PAH.
What Is Macitentan Sandoz and What Is It Used For?
Macitentan Sandoz contains the active substance macitentan, which belongs to a class of medicines known as endothelin receptor antagonists (ERAs). Pulmonary arterial hypertension is a serious and progressive condition characterized by abnormally high blood pressure in the arteries of the lungs. This elevated pressure forces the right side of the heart to work harder than normal, eventually leading to right heart failure if left untreated. PAH affects an estimated 15 to 50 people per million worldwide, and without treatment, median survival historically ranged from only 2.8 years after diagnosis.
Endothelin-1 (ET-1) is one of the most potent vasoconstrictors known in human physiology. In patients with PAH, endothelin-1 levels are significantly elevated, contributing to both vasoconstriction (narrowing of blood vessels) and pathological vascular remodeling, in which the walls of the pulmonary arteries become thickened and stiff. Macitentan works by blocking both subtypes of the endothelin receptor—ETA and ETB—thereby counteracting the harmful effects of endothelin-1 on the pulmonary vasculature.
What distinguishes macitentan from earlier ERAs, such as bosentan, is its superior pharmacological profile. Macitentan was specifically designed to have high lipophilicity and sustained receptor binding, which translates into better tissue penetration within the pulmonary vascular wall. This means the drug can reach and bind to endothelin receptors deep within diseased tissue, not just those accessible from the bloodstream. The active metabolite of macitentan (ACT-132577) is also pharmacologically active and has a long half-life of approximately 48 hours, contributing to the sustained therapeutic effect.
Macitentan Sandoz is specifically approved for the long-term treatment of PAH in adult patients classified as WHO Functional Class II (mild limitation of physical activity) or Functional Class III (marked limitation of physical activity). The drug has been studied both as monotherapy and in combination with other PAH-targeted therapies, including phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil and tadalafil. Current international guidelines from the European Society of Cardiology (ESC) and European Respiratory Society (ERS) recommend initial combination therapy for most PAH patients, making macitentan a cornerstone of modern PAH treatment strategies.
The landmark SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome) trial, published in the New England Journal of Medicine in 2013, was the largest and longest randomized controlled trial in PAH history. This event-driven trial enrolled 742 patients across 151 centers in 39 countries and demonstrated that macitentan 10 mg reduced the composite endpoint of morbidity and mortality by 45% compared to placebo (hazard ratio 0.55; 97.5% CI, 0.39–0.76; p < 0.001). Importantly, these benefits were observed both in treatment-naive patients and in those already receiving background PAH therapy, supporting its use in combination treatment strategies.
What Should You Know Before Taking Macitentan Sandoz?
Contraindications
There are several situations in which Macitentan Sandoz must not be used. Identifying these contraindications before starting treatment is essential to prevent serious adverse outcomes.
- Pregnancy: Macitentan is classified as pregnancy category X. Animal studies have demonstrated severe birth defects (teratogenicity) at clinically relevant doses. Macitentan must never be initiated in a woman who is pregnant, and pregnancy must be excluded before starting treatment.
- Hypersensitivity: Do not use macitentan if you have a known allergy to macitentan or any of the excipients in the formulation.
- Severe hepatic impairment: Macitentan is contraindicated in patients with severe liver disease (Child-Pugh class C) because the drug is extensively metabolized by the liver. Patients with moderate hepatic impairment should be carefully evaluated, and the drug is not recommended in this population unless the potential benefit outweighs the risk.
- Baseline liver transaminases: Do not start treatment if alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels are greater than 3 times the upper limit of normal at baseline.
Warnings and Precautions
Several important warnings apply to the use of macitentan. Your prescribing physician should be a specialist with experience in managing pulmonary arterial hypertension, as this medication requires careful monitoring and management.
Hepatotoxicity: While macitentan has a more favorable hepatic safety profile than older ERAs such as bosentan (which required monthly liver function monitoring), liver injury remains a theoretical concern with all ERAs. Liver function tests (ALT, AST, bilirubin) should be obtained at baseline and monitored periodically during treatment. If clinically significant elevations occur (more than 3 times the upper limit of normal accompanied by symptoms or elevated bilirubin), treatment should be discontinued.
Anemia and hemoglobin decrease: Endothelin receptor antagonists as a class are associated with dose-dependent decreases in hemoglobin. In the SERAPHIN trial, a decrease in hemoglobin to below 10 g/dL was reported in approximately 8.7% of patients receiving macitentan 10 mg compared to 3.4% with placebo. Hemoglobin and hematocrit should be measured at baseline, after 1 month and 3 months of treatment, and periodically thereafter. Macitentan is not recommended for patients with severe anemia that has not been adequately treated.
Fluid retention and edema: ERAs can cause fluid retention, which may manifest as peripheral edema, weight gain, or worsening heart failure symptoms. Patients should report sudden weight gain or new swelling to their healthcare provider. In patients with underlying pulmonary veno-occlusive disease (PVOD), vasodilators including ERAs may cause severe pulmonary edema, and macitentan should be discontinued if signs of PVOD develop.
Decreased sperm count: In animal studies and clinical experience with the ERA drug class, decreased spermatogenesis has been observed. While the clinical significance is uncertain, male patients should be informed of this potential effect on fertility.
Macitentan Sandoz causes serious birth defects and is strictly contraindicated during pregnancy. All women of childbearing potential must have a negative pregnancy test before starting treatment, use two reliable methods of contraception during treatment, and undergo monthly pregnancy testing. Contraception must continue for one month after stopping macitentan. If pregnancy occurs during treatment, stop the drug immediately and consult your doctor.
Pregnancy and Breastfeeding
Macitentan is absolutely contraindicated during pregnancy. Endothelin receptor antagonists as a class are potent teratogens, meaning they can cause severe developmental abnormalities in the fetus. In preclinical studies, macitentan caused malformations of the head, face, mouth, and major blood vessels at all doses tested. There is no safe dose of macitentan during pregnancy.
A robust pregnancy prevention program is a mandatory requirement for prescribing macitentan to women of childbearing potential. This program includes: pregnancy testing prior to initiation and monthly thereafter; use of at least two reliable methods of contraception (or one highly effective method such as an intrauterine device or implant plus a barrier method); and continued contraception for one month after discontinuation. Healthcare providers who prescribe macitentan must ensure that patients understand these requirements before treatment begins.
It is not known whether macitentan or its metabolites are excreted in human breast milk. In animal studies, macitentan and its active metabolite were found in breast milk. Due to the potential for serious adverse effects in the nursing infant, breastfeeding is not recommended during treatment with macitentan.
How Does Macitentan Sandoz Interact with Other Drugs?
Understanding drug interactions is essential for safe and effective use of Macitentan Sandoz. Macitentan undergoes extensive hepatic metabolism, primarily through the cytochrome P450 enzyme CYP3A4 (with minor contribution from CYP2C19). This means that medications which strongly inhibit or induce CYP3A4 can significantly alter the blood levels and clinical effects of macitentan.
Unlike bosentan, macitentan does not significantly induce or inhibit CYP enzymes, which gives it a more favorable drug interaction profile overall. Macitentan does not affect the metabolism of sildenafil, warfarin, or oral contraceptives to a clinically meaningful degree. This is an important practical advantage, as PAH patients frequently take multiple medications concurrently.
Major Interactions
| Interacting Drug | Effect | Clinical Significance | Recommendation |
|---|---|---|---|
| Ketoconazole (strong CYP3A4 inhibitor) | Approximately 2-fold increase in macitentan exposure | High – increased risk of side effects | Avoid concomitant use |
| Ritonavir (strong CYP3A4 inhibitor) | Significant increase in macitentan and metabolite levels | High – increased risk of adverse events | Avoid concomitant use |
| Rifampicin (strong CYP3A4 inducer) | Approximately 79% decrease in macitentan exposure | High – loss of therapeutic efficacy | Avoid concomitant use |
| St. John’s Wort (strong CYP3A4 inducer) | Significant decrease in macitentan levels | High – reduced efficacy | Avoid concomitant use |
| Carbamazepine / Phenytoin (strong CYP3A4 inducers) | Significant decrease in macitentan levels | High – reduced efficacy | Avoid concomitant use |
Minor Interactions and Safe Combinations
Several commonly prescribed medications have been studied in combination with macitentan and show no clinically significant interactions. This is particularly relevant because PAH patients typically require multiple medications.
| Drug / Drug Class | Interaction Status | Notes |
|---|---|---|
| Sildenafil (PDE5 inhibitor) | No clinically significant interaction | Frequently used in combination for PAH |
| Tadalafil (PDE5 inhibitor) | No clinically significant interaction | Common combination therapy partner |
| Warfarin (anticoagulant) | No significant effect on INR | Routine INR monitoring still recommended |
| Hormonal contraceptives | No significant interaction | Unlike bosentan, macitentan does not reduce contraceptive efficacy |
| Cyclosporine A (immunosuppressant) | Mild increase in macitentan levels (not clinically relevant at steady-state) | No dose adjustment needed |
Current ESC/ERS guidelines recommend initial combination therapy for newly diagnosed PAH patients at intermediate or high risk. Macitentan plus a PDE5 inhibitor (typically tadalafil) is one of the most commonly used upfront combinations. The SERAPHIN trial confirmed the benefit of macitentan even when added on top of existing PAH therapy, supporting its role in sequential combination strategies.
What Is the Correct Dosage of Macitentan Sandoz?
Macitentan Sandoz has a straightforward dosing regimen. The approved dose is 10 mg once daily, taken by mouth. The film-coated tablet should be swallowed whole and should not be crushed, chewed, or broken. Macitentan can be taken with or without food, as food does not significantly affect its absorption. It is recommended to take the medication at approximately the same time each day to maintain consistent blood levels.
Adults
Standard Adult Dose
Dose: 10 mg once daily, taken orally
Form: Film-coated tablet, swallowed whole
Timing: Once daily, with or without food
Duration: Long-term treatment; continue as long as clinically beneficial
The 10 mg dose was the dose that demonstrated a statistically significant reduction in the primary composite endpoint of morbidity and mortality in the SERAPHIN trial. A lower dose of 3 mg was also studied but did not reach significance on the primary endpoint, which is why only the 10 mg dose is recommended for clinical use.
Children
Pediatric Population
The safety and efficacy of macitentan in children and adolescents below the age of 18 years have not been established. No data are available. Macitentan is therefore not recommended for use in the pediatric population. Clinical studies evaluating macitentan in pediatric PAH patients are ongoing.
Elderly
Patients Aged 65 and Over
No dose adjustment is required for elderly patients. Clinical experience in patients over 75 years of age is limited. In the SERAPHIN trial, approximately 14% of enrolled patients were aged 65 or older, and no clinically relevant differences in safety or efficacy were observed in this subgroup. However, as with all medications in older adults, careful monitoring is advised due to the higher prevalence of comorbidities and concurrent medication use.
Missed Dose
If you forget to take Macitentan Sandoz, take the missed dose as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose entirely and continue with your regular dosing schedule. Do not take two doses at the same time or take an extra dose to make up for the one you missed. If you have difficulty remembering your medication, discuss strategies such as using a pill organizer or daily alarm with your healthcare provider.
Overdose
Macitentan has been administered at doses up to 600 mg in clinical studies in healthy volunteers. The most commonly reported adverse events at supratherapeutic doses include headache, nausea, and vomiting. In the event of an overdose, standard supportive measures should be taken. Due to its high protein binding (greater than 99%), macitentan is unlikely to be significantly removed by dialysis. There is no specific antidote for macitentan overdose. Contact your local poison control center or seek immediate medical attention if an overdose is suspected.
Renal impairment: No dose adjustment is necessary in patients with renal impairment, including those on dialysis, as renal elimination is a minor pathway for macitentan.
Hepatic impairment: Macitentan is contraindicated in severe hepatic impairment (Child-Pugh C). It is not recommended in moderate hepatic impairment (Child-Pugh B). No dose adjustment is needed for mild hepatic impairment (Child-Pugh A).
What Are the Side Effects of Macitentan Sandoz?
Like all medicines, Macitentan Sandoz can cause side effects, although not everybody experiences them. The safety profile of macitentan has been well characterized through the SERAPHIN trial and post-marketing surveillance. Understanding the frequency and nature of potential side effects helps patients and healthcare providers make informed treatment decisions and enables early recognition of complications.
The side effect profile of macitentan is generally considered favorable compared to older ERAs. Notably, macitentan does not cause the dose-dependent liver transaminase elevations that were a major concern with bosentan (which required mandatory monthly liver function monitoring). However, as with all ERAs, hemoglobin decreases are a recognized class effect that requires monitoring.
Side effects are classified below according to their frequency, based on data from clinical trials involving over 900 patients treated with macitentan.
Very Common
Affects more than 1 in 10 patients
- Nasopharyngitis (common cold symptoms, sore throat, runny nose)
- Headache
- Anemia (low hemoglobin / red blood cell count)
Common
Affects 1 in 10 to 1 in 100 patients
- Bronchitis (chest infection)
- Urinary tract infection
- Influenza (flu)
- Pharyngitis (sore throat)
- Peripheral edema (swelling of the ankles, feet, or legs)
- Hypotension (low blood pressure)
- Nasal congestion
Uncommon
Affects 1 in 100 to 1 in 1,000 patients
- Hypersensitivity reactions (rash, pruritus)
- Elevated liver transaminases (ALT/AST)
- Leukopenia (low white blood cell count)
- Flushing
Rare
Affects fewer than 1 in 1,000 patients
- Severe hepatotoxicity (serious liver injury with jaundice)
- Angioedema (severe allergic swelling of the face, lips, or throat)
- Severe anemia requiring blood transfusion
Anemia in detail: In the SERAPHIN trial, the mean decrease in hemoglobin from baseline to month 18 was approximately 1 g/dL in the macitentan 10 mg group compared to 0.2 g/dL in the placebo group. A hemoglobin decrease to below 10 g/dL was observed in 8.7% of patients on macitentan 10 mg versus 3.4% on placebo. Most cases of anemia were mild to moderate and did not require discontinuation of therapy. However, in rare cases, blood transfusions were needed.
Liver safety: One of the significant advantages of macitentan over bosentan is its improved liver safety profile. In the SERAPHIN trial, elevated liver transaminases (>3 times the upper limit of normal) occurred at a similar rate in the macitentan and placebo groups (3.4% vs. 4.5%, respectively), suggesting that macitentan does not cause significant dose-dependent hepatotoxicity. Nevertheless, baseline and periodic liver function monitoring remains prudent clinical practice.
When to seek urgent medical attention: Contact your doctor or seek emergency care immediately if you experience signs of a severe allergic reaction (difficulty breathing, swelling of the face or throat), unexplained jaundice (yellowing of the skin or eyes), severe fatigue or shortness of breath that may indicate worsening anemia, or sudden weight gain with swelling that could indicate fluid retention or disease progression.
How Should You Store Macitentan Sandoz?
Proper storage of Macitentan Sandoz is important to ensure the medication retains its efficacy and safety throughout its shelf life. Film-coated tablets should be stored in their original blister packaging until ready for use. This protects the tablets from light and moisture, which can degrade the active ingredient over time.
Store the medication at room temperature, generally below 30°C (86°F). Do not refrigerate or freeze the tablets. Avoid storing the medication in bathrooms or other humid environments, as moisture can affect the integrity of the film coating. Keep the medication in a secure location out of the sight and reach of children and pets, as accidental ingestion could be harmful.
Do not use Macitentan Sandoz after the expiry date stated on the carton and blister pack. The expiry date refers to the last day of that month. Do not dispose of medicines via wastewater or household waste. Ask your pharmacist about the proper disposal of medicines you no longer need, in accordance with local regulations. Proper disposal helps protect the environment.
What Does Macitentan Sandoz Contain?
Understanding the full composition of your medication is important, particularly if you have known allergies or intolerances to specific pharmaceutical ingredients. Each film-coated tablet of Macitentan Sandoz contains:
Active substance: Macitentan 10 mg
Tablet core excipients: The inactive ingredients in the tablet core typically include lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, povidone, magnesium stearate, and poloxamer. These excipients serve various pharmaceutical functions including binding, disintegration, flow, and lubrication during the tablet manufacturing process.
Film coating: The tablet is film-coated using a blend that typically contains polyvinyl alcohol, titanium dioxide (E171), macrogol/polyethylene glycol, talc, and lecithin. The film coating serves to protect the tablet core, improve swallowability, and give the tablet its characteristic appearance. The film-coated tablets are typically round, biconvex, and white to off-white in color.
Patients with lactose intolerance: Macitentan Sandoz tablets contain lactose monohydrate. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medication. The quantity of lactose per tablet is generally small, but patients with severe galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
Sodium content: This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, meaning it is essentially sodium-free. This is relevant for patients on sodium-restricted diets.
Frequently Asked Questions About Macitentan Sandoz
Macitentan Sandoz is used for the long-term treatment of pulmonary arterial hypertension (PAH) in adults with WHO Functional Class II to III. It is an endothelin receptor antagonist that works by blocking the effects of endothelin-1, a substance that causes the blood vessels in the lungs to narrow. By reducing pulmonary vascular resistance, macitentan helps improve exercise capacity and slows disease progression. It is often used as part of combination therapy with other PAH medications.
No. Macitentan Sandoz is strictly contraindicated during pregnancy as it can cause serious birth defects. All women of childbearing potential must use reliable contraception during treatment and for one month after stopping. Monthly pregnancy tests are required. A pregnancy prevention program must be followed as directed by your healthcare provider. If you suspect you may be pregnant, stop the medication immediately and contact your doctor.
The most common side effects include nasopharyngitis (common cold symptoms), headache, and anemia. Bronchitis, urinary tract infections, and peripheral edema are also commonly reported. Anemia is a class effect of endothelin receptor antagonists and requires regular monitoring of hemoglobin levels. Most side effects are mild to moderate. Serious side effects such as severe liver injury are rare. Always report any unusual symptoms to your healthcare provider.
Macitentan is a dual endothelin receptor antagonist (ERA) with superior tissue penetration and sustained receptor binding compared to older ERAs such as bosentan. The landmark SERAPHIN trial demonstrated that macitentan 10 mg significantly reduced morbidity and mortality in PAH patients. Unlike bosentan, macitentan does not require routine monthly liver function monitoring and does not reduce the efficacy of hormonal contraceptives. It is often used as part of combination therapy with PDE5 inhibitors and/or prostacyclin pathway agents.
Yes. Current ESC/ERS guidelines recommend combination therapy for PAH. Macitentan is frequently used together with PDE5 inhibitors such as sildenafil or tadalafil, and/or prostacyclin pathway agents such as selexipag, treprostinil, or epoprostenol. The SERAPHIN trial included patients already on background PAH therapy, and macitentan showed benefit in both treatment-naive and pre-treated patients. Your doctor will determine the best combination based on your disease severity and risk profile.
Macitentan reaches steady-state plasma levels within approximately 3 days. However, clinical improvements in exercise capacity, symptoms, and hemodynamic parameters typically develop gradually over weeks to months. In the SERAPHIN trial, benefits were assessed over a long-term follow-up period with a median of 115 weeks. Patients should not expect immediate symptomatic relief. Your doctor will monitor your progress through regular assessments including 6-minute walk tests, echocardiography, NT-proBNP levels, and symptom evaluation.
References
This article is based on the following peer-reviewed sources and international guidelines:
- Pulido T, Adzerikho I, Channick RN, et al. Macitentan and Morbidity and Mortality in Pulmonary Arterial Hypertension. N Engl J Med. 2013;369(9):809-818. doi:10.1056/NEJMoa1215010
- Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension. Eur Heart J. 2022;43(38):3618-3731. doi:10.1093/eurheartj/ehac237
- European Medicines Agency. Opsumit (macitentan) – Summary of Product Characteristics. EMA/2025. Available at: www.ema.europa.eu
- U.S. Food and Drug Administration. Opsumit (macitentan) – Prescribing Information. FDA/2024. Available at: www.accessdata.fda.gov
- Klinger JR, Elliott CG, Levine DJ, et al. Therapy for Pulmonary Arterial Hypertension in Adults: Update of the CHEST Guideline and Expert Panel Report. Chest. 2019;155(3):565-586. doi:10.1016/j.chest.2018.11.030
- Galiè N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019;53(1):1801889. doi:10.1183/13993003.01889-2018
- World Health Organization. WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: WHO; 2023.
- Sidharta PN, van Giersbergen PL, Halabi A, Dingemanse J. Macitentan: entry-into-humans study with a new endothelin receptor antagonist. Eur J Clin Pharmacol. 2011;67(10):977-984. doi:10.1007/s00228-011-1043-2
Editorial Team
This article has been written and reviewed by qualified medical professionals with expertise in pulmonary medicine and clinical pharmacology.
iMedic Medical Editorial Team
Lead Authors
Board-certified specialists in pulmonology, cardiology, and clinical pharmacology with extensive experience in pulmonary hypertension management.
iMedic Medical Review Board
Independent Reviewers
Independent panel of medical experts who verify clinical accuracy against current ESC/ERS, EMA, and FDA guidelines using the GRADE evidence framework.
Evidence standard: All claims in this article are supported by Level 1A evidence from randomized controlled trials and international clinical guidelines. This content is updated regularly to reflect the latest medical evidence and prescribing information.
Conflict of interest statement: iMedic receives no funding from pharmaceutical companies. All content is editorially independent.