Macitentan Teva: Uses, Dosage & Side Effects
Dual Endothelin Receptor Antagonist for Pulmonary Arterial Hypertension
Macitentan Teva is a prescription medicine containing the active ingredient macitentan, a dual endothelin receptor antagonist (ERA) used to treat pulmonary arterial hypertension (PAH). Available as a 10 mg film-coated tablet, it works by blocking the effects of endothelin-1, a naturally occurring substance that causes blood vessels in the lungs to narrow. This comprehensive guide covers dosage, side effects, drug interactions, and important safety information based on the latest international guidelines.
Quick Facts
Key Takeaways
- Macitentan Teva is specifically indicated for the long-term treatment of pulmonary arterial hypertension (PAH) in adults with WHO Functional Class II-III symptoms.
- It works as a dual endothelin receptor antagonist (ETA and ETB), reducing pulmonary vascular resistance and improving exercise capacity.
- The standard dose is one 10 mg tablet taken once daily, with or without food, and it must not be split, crushed, or chewed.
- Macitentan is absolutely contraindicated in pregnancy due to teratogenic risk, and women of childbearing potential require reliable contraception and monthly pregnancy testing.
- Regular monitoring of liver function and haemoglobin levels is essential throughout treatment, as macitentan may cause hepatotoxicity and anaemia.
What Is Macitentan Teva and What Is It Used For?
Macitentan Teva contains the active substance macitentan, which belongs to a class of medicines known as endothelin receptor antagonists (ERAs). It is specifically designed to treat pulmonary arterial hypertension, a serious and progressive condition characterised by abnormally high blood pressure in the arteries that supply the lungs. PAH causes the walls of these arteries to thicken and stiffen, forcing the right side of the heart to work harder to pump blood through the lungs, which can ultimately lead to right heart failure if left untreated.
The role of endothelin-1 in PAH is central to understanding how macitentan works. Endothelin-1 is a potent vasoconstrictor peptide produced by endothelial cells that line blood vessels. In patients with PAH, endothelin-1 levels are significantly elevated, contributing to vasoconstriction (narrowing of blood vessels), smooth muscle cell proliferation, fibrosis, and inflammation in the pulmonary vasculature. By blocking both ETA and ETB endothelin receptors, macitentan counteracts these pathological effects, leading to vasodilation and reduced vascular remodelling in the lungs.
Macitentan was specifically engineered to have enhanced tissue penetration and sustained receptor binding compared to earlier ERAs. This pharmacological profile was validated in the landmark SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome) trial, a pivotal phase III randomised, double-blind, placebo-controlled study involving 742 patients across 39 countries. The trial demonstrated that macitentan 10 mg significantly 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).
Macitentan Teva is approved for use in adults with PAH classified as WHO Functional Class II (mild limitation of physical activity) or Class III (marked limitation of physical activity). It can be used as monotherapy in treatment-naive patients or as add-on therapy to existing PAH treatments, including phosphodiesterase type 5 (PDE-5) inhibitors such as sildenafil or tadalafil, and inhaled or subcutaneous prostacyclin analogues. The decision to initiate macitentan therapy should be made by a physician experienced in the management of PAH.
Unlike some older endothelin receptor antagonists, macitentan has a favourable hepatic safety profile and does not require routine monthly liver function monitoring mandated by regulatory agencies, although periodic monitoring is still recommended by most clinical guidelines. The European Society of Cardiology (ESC) and European Respiratory Society (ERS) jointly recommend ERAs, including macitentan, as first-line therapy for PAH in combination with a PDE-5 inhibitor for patients presenting in WHO Functional Class II or III.
What Should You Know Before Taking Macitentan Teva?
Contraindications
Macitentan Teva must not be used in patients who have a known hypersensitivity to macitentan or any of the excipients in the formulation. It is absolutely contraindicated in pregnancy due to its teratogenic potential, meaning it can cause serious harm to an unborn baby, including severe birth defects. Animal studies have demonstrated embryo-fetal toxicity, including cardiovascular and mandibular arch malformations, at clinically relevant doses.
Patients with severe hepatic impairment (Child-Pugh Class C) must not take macitentan, as the drug undergoes extensive hepatic metabolism primarily through the cytochrome P450 system (CYP3A4 and, to a lesser extent, CYP2C19). Pre-existing significant elevation of hepatic aminotransferases (ALT or AST greater than 3 times the upper limit of normal) also constitutes a contraindication. Baseline liver function tests must be performed before initiating therapy.
Macitentan Teva is classified as a teratogen. It must never be taken during pregnancy. Women of childbearing potential must have a negative pregnancy test before starting treatment, use two reliable methods of contraception during treatment, and continue contraception for one month after discontinuation. Monthly pregnancy testing is strongly recommended throughout treatment.
Warnings and Precautions
Liver function should be assessed before initiating macitentan and should be monitored periodically during treatment. If clinically relevant, unexplained hepatic aminotransferase elevations occur (ALT or AST greater than 3 times the upper limit of normal), or if elevations are accompanied by symptoms of liver injury such as jaundice, nausea, vomiting, fever, abdominal pain, or unusual fatigue, treatment should be discontinued and not restarted until aminotransferases have normalised.
Haemoglobin concentration should be measured before starting treatment, at regular intervals during treatment (typically every 3 months), and as clinically indicated. Macitentan has been associated with a decrease in haemoglobin levels and the development of anaemia. In the SERAPHIN trial, a decrease in haemoglobin to below 10 g/dL was reported in 8.7% of patients receiving macitentan 10 mg compared with 3.4% in the placebo group. The mechanism is related to the endothelin receptor system's role in erythropoiesis and fluid retention.
Fluid retention may occur in some patients, particularly at the initiation of therapy. Patients should be monitored for signs of fluid overload, including peripheral oedema and weight gain. If clinically significant fluid retention develops that does not respond to standard diuretic therapy, the possibility that it may be related to macitentan should be considered.
Pulmonary veno-occlusive disease (PVOD) is a rare but serious condition that may present similarly to PAH. If signs of pulmonary oedema occur during macitentan treatment, PVOD should be considered. If PVOD is confirmed, treatment with macitentan should be discontinued, as vasodilator therapy can worsen the cardiovascular status of patients with this condition.
Pregnancy and Breastfeeding
As described above, macitentan is a known teratogen and is absolutely contraindicated in pregnancy. The pregnancy prevention programme for macitentan requires that women of childbearing potential must use reliable contraception. Effective contraception should be initiated before starting treatment, maintained during treatment, and continued for at least one month after stopping macitentan to allow for complete drug elimination from the body.
It is not known whether macitentan or its active metabolite ACT-132577 is excreted in human breast milk. In animal studies, macitentan and its metabolites were detected in milk. Due to the potential for serious adverse effects in nursing infants, breastfeeding is not recommended during treatment with macitentan. The decision to discontinue breastfeeding or discontinue the drug should take into account the importance of the drug to the mother's health.
For male patients, available evidence does not suggest that macitentan affects male fertility. However, animal studies have shown effects on the male reproductive system, including testicular tubular atrophy at high doses. Patients concerned about fertility should discuss this with their treating physician.
How Does Macitentan Teva Interact with Other Drugs?
Drug-drug interactions with macitentan are primarily driven by its metabolism through the cytochrome P450 system, particularly CYP3A4 and, to a lesser extent, CYP2C19. Macitentan is converted to its active metabolite ACT-132577, which also contributes to the pharmacological effect. Understanding these interactions is critical for patient safety, as concomitant use of certain medicines can significantly alter macitentan plasma concentrations.
Unlike bosentan, another endothelin receptor antagonist, macitentan has not been shown to be a significant inducer of CYP enzymes or drug transporters at therapeutic concentrations. However, in vitro studies suggest that macitentan and its metabolite may inhibit organic anion transporting polypeptide (OATP) 1B1 and 1B3, although the clinical significance of this finding is not fully established.
Major Interactions
| Interacting Drug | Effect | Clinical Recommendation |
|---|---|---|
| Ketoconazole (strong CYP3A4 inhibitor) | Approximately 2-fold increase in macitentan exposure | Avoid concomitant use |
| Itraconazole (strong CYP3A4 inhibitor) | Significantly increased macitentan exposure | Avoid concomitant use |
| Ritonavir, Nelfinavir (HIV protease inhibitors) | Strong CYP3A4 inhibition increases macitentan levels | Avoid concomitant use |
| Rifampicin (strong CYP3A4 inducer) | Approximately 79% decrease in macitentan exposure | Avoid concomitant use |
| Carbamazepine, Phenytoin (strong CYP3A4 inducers) | Significant decrease in macitentan exposure | Avoid concomitant use |
| St John's Wort (CYP3A4 inducer) | Potentially significant decrease in macitentan exposure | Avoid concomitant use |
Minor Interactions
| Interacting Drug | Effect | Clinical Recommendation |
|---|---|---|
| Fluconazole (moderate CYP3A4 inhibitor) | Moderate increase in macitentan exposure | Use with caution; monitor for adverse effects |
| Erythromycin, Clarithromycin | Moderate CYP3A4 inhibition | Monitor closely; consider alternatives |
| Warfarin | No clinically significant pharmacokinetic interaction demonstrated | No dose adjustment needed; monitor INR as routine |
| Sildenafil (PDE-5 inhibitor) | No clinically significant pharmacokinetic interaction | Can be used in combination for PAH treatment |
| Cyclosporine A | Increased macitentan exposure (via OATP inhibition) | Monitor closely; may require dose adjustment consideration |
Patients should always inform their doctor about all medications they are currently taking, including over-the-counter medicines, herbal products, and dietary supplements. Grapefruit and grapefruit juice should be consumed with caution, as they are moderate CYP3A4 inhibitors and may modestly increase macitentan plasma levels, although no formal interaction study has been conducted.
Macitentan can be safely combined with PDE-5 inhibitors (sildenafil, tadalafil) and prostacyclin analogues as part of combination PAH therapy. Pharmacokinetic studies have shown no clinically relevant interactions between macitentan and sildenafil, making this a well-established therapeutic combination in current PAH management guidelines.
What Is the Correct Dosage of Macitentan Teva?
Adults
Standard Adult Dosage
The approved dose of macitentan is 10 mg once daily, taken orally at approximately the same time each day. The tablet can be taken with or without food. No dose titration is required. The 10 mg dose was established in the SERAPHIN trial as the dose that provides the optimal balance between efficacy and safety.
Treatment should be initiated by a physician experienced in the treatment of pulmonary arterial hypertension. The duration of treatment is long-term, as PAH is a chronic progressive disease. In the SERAPHIN trial, the median duration of treatment was approximately 115 weeks (over 2 years), with patients showing sustained benefits over this period.
No dose adjustment is required for patients with mild to moderate hepatic impairment (Child-Pugh Class A or B), although caution is advised and liver function should be monitored more frequently in these patients. Macitentan is contraindicated in severe hepatic impairment (Child-Pugh Class C). Similarly, no dose adjustment is needed for patients with renal impairment, including those with severe renal insufficiency (creatinine clearance 15-29 mL/min), as renal clearance is not a significant elimination pathway for macitentan.
Children
Paediatric Use
The safety and efficacy of macitentan in children and adolescents under 18 years of age have not been established. No data are available in this age group. Therefore, macitentan is not recommended for use in paediatric patients. Clinical trials in the paediatric PAH population are ongoing, and future guidance may provide specific dosing recommendations for this group.
Elderly
Elderly Patients (≥65 years)
No dose adjustment is required for elderly patients based on age alone. In the SERAPHIN trial, a sufficient number of patients aged 65 years and older were included, and no overall differences in safety or effectiveness were observed between these patients and younger adults. However, as with all medications in elderly patients, careful clinical monitoring is recommended due to the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
Missed Dose
If a dose of Macitentan Teva is missed, it should be taken as soon as the patient remembers, unless it is almost time for the next scheduled dose. In that case, the missed dose should be skipped and the next dose taken at the regular time. Patients should never take a double dose to make up for a missed dose. Maintaining a consistent daily dosing schedule is important for optimal therapeutic effect.
Overdose
In the event of an overdose, standard supportive measures should be implemented. Macitentan is highly bound to plasma proteins (>99%), so it is unlikely to be removed by dialysis. The most likely symptoms of overdose are expected to be an extension of the known pharmacological effects, including headache, nasal congestion, and hypotension. In clinical studies, single doses of up to 600 mg were administered to healthy volunteers without significant safety concerns, although hypotension and headache were more common at higher doses.
When switching from bosentan or ambrisentan to macitentan, treatment with macitentan can generally be started the day after the previous ERA is discontinued. However, there may be clinical circumstances where overlap or a washout period is preferred. The transition should always be supervised by a specialist experienced in PAH management.
What Are the Side Effects of Macitentan Teva?
Like all medicines, Macitentan Teva can cause side effects, although not everybody gets them. The safety profile of macitentan has been extensively characterised in the SERAPHIN trial and in post-marketing surveillance. Understanding the frequency and nature of side effects is important for patients and healthcare providers to enable early recognition and appropriate management.
The side effects listed below are based on data from the SERAPHIN clinical trial (742 patients) and post-marketing experience. They are categorised according to the standard frequency classification used in medical practice.
Very Common (affects more than 1 in 10 patients)
>10% incidence
- Anaemia / decreased haemoglobin – Haemoglobin decrease below 10 g/dL reported in approximately 8.7% of patients on 10 mg; decreases of any magnitude are very common
- Nasopharyngitis (inflammation of the nose and throat / common cold symptoms)
- Bronchitis (inflammation of the bronchial tubes)
Common (affects 1 to 10 in 100 patients)
1–10% incidence
- Headache – one of the most frequently reported symptoms at treatment initiation
- Pharyngitis (sore throat)
- Urinary tract infection
- Influenza (flu-like symptoms)
- Oedema / fluid retention – peripheral swelling, particularly in the legs and ankles
- Hypotension (low blood pressure)
- Nasal congestion
Uncommon (affects 1 to 10 in 1,000 patients)
0.1–1% incidence
- Hepatotoxicity – elevated liver enzymes (ALT/AST), potentially leading to liver injury
- Leukopenia (decreased white blood cell count)
- Thrombocytopenia (decreased platelet count)
- Hypersensitivity reactions including rash, pruritus, and angioedema
- Flushing
Rare (affects fewer than 1 in 1,000 patients)
<0.1% incidence
- Severe hepatic injury – including cases of autoimmune hepatitis reported post-marketing
- Anaphylactic reactions
- Severe anaemia requiring blood transfusion
The most clinically significant side effect is anaemia. In the SERAPHIN trial, the mean haemoglobin decrease from baseline was approximately 1 g/dL at month 6 in the macitentan 10 mg group. This effect was generally stable over time and rarely required treatment discontinuation. However, in some patients, the decrease can be more pronounced, and regular haemoglobin monitoring is essential. If a patient develops symptomatic anaemia or haemoglobin falls below 8 g/dL, further investigation and management, including possible blood transfusion, should be considered.
Infections, particularly of the upper respiratory tract and urinary tract, were reported more frequently in patients taking macitentan compared to placebo. The mechanism behind this observation is not fully understood but may be related to the immune-modulating effects of endothelin receptor blockade. Patients should be counselled to report any signs of infection promptly.
Contact your doctor or seek emergency care immediately if you experience: yellowing of the skin or eyes (jaundice), dark urine, severe fatigue, persistent nausea or vomiting, unexplained right upper abdominal pain, severe shortness of breath not typical of your PAH, signs of severe allergic reaction (facial swelling, difficulty breathing, widespread rash), or signs of significant anaemia (extreme fatigue, pale skin, rapid heartbeat, dizziness).
Long-term safety data from the SERAPHIN trial and open-label extension studies have been reassuring, with no new safety signals emerging over extended treatment periods. The overall rate of treatment discontinuation due to adverse events was comparable between macitentan and placebo groups in the SERAPHIN trial, suggesting that the medication is generally well tolerated when used appropriately with regular monitoring.
How Should You Store Macitentan Teva?
Macitentan Teva film-coated tablets should be stored at a temperature not exceeding 30°C (86°F). The tablets should be kept in the original blister packaging until the time of use to protect them from moisture. There are no special requirements for refrigeration or freezing; in fact, freezing the tablets is not recommended as it may affect the integrity of the film coating.
As with all medicines, Macitentan Teva should be kept out of the reach and sight of children. Given that macitentan is a teratogenic substance, extra care should be taken to ensure that the medicine is stored securely, particularly in households where women of childbearing potential may be present. Accidental ingestion by a pregnant woman could pose a serious risk to the foetus.
Do not use Macitentan Teva after the expiry date (EXP) stated on the carton and blister. The expiry date refers to the last day of that month. Unused or expired tablets should not be disposed of via household waste or wastewater. Patients should ask their pharmacist how to dispose of medicines they no longer use, in accordance with local regulations. Proper disposal helps protect the environment.
If you notice any visible damage to the tablets, such as discolouration, cracking, or a broken film coating, do not take the medicine and consult your pharmacist for a replacement. The tablets should appear as white to off-white, round, biconvex film-coated tablets.
What Does Macitentan Teva Contain?
The active substance in Macitentan Teva is macitentan. Each film-coated tablet contains 10 mg of macitentan. Macitentan is a synthetic compound with the chemical name N-[5-(4-bromophenyl)-6-(2-(5-bromopyrimidin-2-yloxy)ethoxy)pyrimidin-4-yl]-N'-propylaminosulfonamide. It has a molecular weight of 588.27 g/mol and is practically insoluble in water.
The inactive ingredients (excipients) in the tablet core typically include microcrystalline cellulose, which serves as a bulking agent and binder; lactose monohydrate, used as a diluent; sodium starch glycolate, which acts as a disintegrant to help the tablet break apart in the gastrointestinal tract; magnesium stearate, a lubricant that prevents the tablet from sticking to manufacturing equipment; and poloxamer 188, a surfactant that improves drug dissolution.
The film coating contains substances such as polyvinyl alcohol, titanium dioxide (for white colour), talc, and lecithin (soya). These coating materials protect the tablet from moisture, mask any unpleasant taste, and make the tablet easier to swallow. Patients with known allergies to soya or peanuts should be aware that the film coating may contain soya lecithin, although the amount is extremely small and severe allergic reactions to this component are very rare.
Macitentan Teva tablets do not contain gluten, sugar (sucrose), or any animal-derived ingredients other than lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicine due to the lactose content. If you have any concerns about the ingredients, consult your pharmacist or prescribing physician before starting treatment.
Frequently Asked Questions About Macitentan Teva
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/NEJMoa1213917. (SERAPHIN Trial)
- European Medicines Agency (EMA). Opsumit (macitentan) Summary of Product Characteristics. Last updated 2024. Available at: ema.europa.eu.
- U.S. Food and Drug Administration (FDA). Opsumit (macitentan) Prescribing Information. Reference ID: 4848623. Available at: accessdata.fda.gov.
- 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.
- 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.
- British National Formulary (BNF). Macitentan. National Institute for Health and Care Excellence (NICE). Available at: bnf.nice.org.uk.
- World Health Organization (WHO). WHO Model List of Essential Medicines - 23rd List, 2023. Geneva: WHO; 2023.
- Sitbon O, Gomberg-Maitland M, Granton J, et al. Clinical trial design and new therapies for pulmonary arterial hypertension. Eur Respir J. 2019;53(1):1801908. doi:10.1183/13993003.01908-2018.
Editorial Team
This article has been written and reviewed by qualified medical professionals to ensure accuracy and adherence to current clinical guidelines.
iMedic Medical Editorial Team — specialists in pulmonary medicine, clinical pharmacology, and pharmaceutical sciences with documented academic and clinical experience.
iMedic Medical Review Board — independent panel of board-certified physicians who verify all content against current international guidelines (ESC/ERS, EMA, FDA, WHO).
Evidence Framework: All medical claims in this article are supported by Level 1A evidence (systematic reviews and randomised controlled trials) following the GRADE methodology. This article follows the editorial standards described on our Editorial Standards page.