Macitentan Zentiva: Uses, Dosage & Side Effects
A dual endothelin receptor antagonist for the long-term treatment of pulmonary arterial hypertension (PAH) in adults, WHO Functional Class II to III
Macitentan Zentiva is a prescription medication containing macitentan, a dual endothelin receptor antagonist (ERA) used for the long-term treatment of pulmonary arterial hypertension (PAH) in adults classified as WHO Functional Class II or III. Macitentan Zentiva is a generic version of Opsumit, containing the same active ingredient at the same strength (10 mg). It works by blocking the effects of endothelin-1, a powerful vasoconstrictor that is overproduced in the lungs of PAH patients. In the landmark SERAPHIN trial, macitentan significantly reduced the composite endpoint of morbidity and mortality, including disease progression, hospitalization for worsening PAH, lung transplantation, and death. The medication is taken once daily as a film-coated tablet and is typically prescribed by specialists experienced in treating pulmonary hypertension.
Quick Facts: Macitentan Zentiva
Key Takeaways
- Macitentan Zentiva contains macitentan 10 mg, a dual endothelin receptor antagonist (ERA) that blocks both ETA and ETB receptors to reduce pulmonary vascular resistance and slow disease progression in pulmonary arterial hypertension (PAH).
- The SERAPHIN trial demonstrated that macitentan 10 mg reduced the risk of the composite morbidity/mortality endpoint by 45% compared with placebo, including reductions in disease worsening events and hospitalizations.
- Macitentan is teratogenic and absolutely contraindicated during pregnancy. Women of childbearing potential must use reliable contraception and undergo monthly pregnancy testing throughout treatment.
- Common side effects include anemia (decreased hemoglobin), nasopharyngitis, bronchitis, headache, and urinary tract infections. Regular blood monitoring of liver enzymes and hemoglobin is required.
- Macitentan can be used as monotherapy or in combination with other PAH-specific therapies such as phosphodiesterase type 5 inhibitors (sildenafil, tadalafil) or prostacyclin pathway agents, in line with current ESC/ERS treatment guidelines.
What Is Macitentan Zentiva and What Is It Used For?
Macitentan Zentiva is a generic formulation of macitentan manufactured by Zentiva, containing the same active ingredient and dosage strength (10 mg) as the original brand product Opsumit. As a generic medication approved by the European Medicines Agency (EMA), Macitentan Zentiva has been demonstrated to be bioequivalent to the originator product, meaning it delivers the same amount of active drug to the bloodstream at the same rate. This ensures that patients receive the same therapeutic benefit regardless of whether they take the branded or generic formulation.
Pulmonary arterial hypertension (PAH) is a rare, progressive, and life-threatening condition characterized by abnormally elevated blood pressure within the pulmonary arteries – the blood vessels that carry blood from the right side of the heart to the lungs. In healthy individuals, pulmonary arterial pressure at rest is typically around 14 mmHg (mean). In PAH, the mean pulmonary arterial pressure exceeds 20 mmHg at rest, as defined by the 2022 ESC/ERS guidelines. This elevated pressure is driven by a combination of vasoconstriction (narrowing of blood vessels), structural remodeling of the pulmonary artery walls (thickening and stiffening), in situ thrombosis (blood clot formation within the vessels), and endothelial dysfunction. Over time, the right ventricle of the heart must work progressively harder to pump blood through these narrowed, stiff pulmonary vessels. If untreated, this eventually leads to right heart failure and death.
The endothelin system plays a central role in the pathogenesis of PAH. Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor known, and its levels are markedly elevated in the plasma and lung tissue of patients with PAH. ET-1 exerts its effects through two receptor subtypes: ETA receptors, which are found predominantly on pulmonary artery smooth muscle cells and mediate vasoconstriction and cell proliferation; and ETB receptors, found on both endothelial cells (where they promote vasodilation via nitric oxide and prostacyclin release) and smooth muscle cells (where they also mediate vasoconstriction). In PAH, the balance of ET-1 signaling is disrupted, with a net effect of sustained vasoconstriction, vascular remodeling, inflammation, and fibrosis.
Macitentan is a dual endothelin receptor antagonist, meaning it blocks both ETA and ETB receptors. This distinguishes it from selective ERA agents that target only one receptor subtype. By blocking both receptor subtypes, macitentan comprehensively inhibits the deleterious effects of endothelin-1 in the pulmonary vasculature. Macitentan was specifically designed to have sustained receptor binding and high tissue penetration, optimizing its pharmacological activity at the site of disease. It has a significantly higher affinity for the endothelin receptors and slower receptor dissociation rate compared with earlier-generation ERAs such as bosentan, which translates into more sustained pharmacological blockade.
The clinical efficacy of macitentan was established in the landmark SERAPHIN trial (Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome), the largest and longest randomized controlled trial ever conducted in PAH at the time of its publication in 2013. This event-driven, double-blind, placebo-controlled trial enrolled 742 patients with PAH across 151 centers in 39 countries. Patients were randomized to receive macitentan 3 mg, macitentan 10 mg, or placebo, and were followed for a median of 115 weeks (approximately 2.2 years). The primary endpoint was a composite of disease worsening or death from any cause, where disease worsening was defined as a decrease in 6-minute walk distance of at least 15% from baseline plus worsening of WHO functional class, or need for additional PAH-specific therapy, or hospitalization for worsening PAH, or lung or heart-lung transplantation, or atrial septostomy.
The results were striking: macitentan 10 mg reduced the risk of the composite primary endpoint by 45% compared with placebo (hazard ratio 0.55; 97.5% CI, 0.39 to 0.76; p<0.001). This benefit was driven primarily by reductions in disease worsening events and hospitalizations for PAH. The effect was consistent across subgroups, including patients already receiving background PAH therapy (approximately 64% of enrolled patients were on a phosphodiesterase type 5 inhibitor). Macitentan 10 mg also significantly improved exercise capacity, with a treatment effect of +22 meters in 6-minute walk distance compared with placebo at month 6.
PAH severity is classified using the WHO functional classification system, which ranges from Class I (no limitation of physical activity) to Class IV (inability to perform any physical activity without symptoms; right heart failure at rest). Macitentan is indicated for patients in Class II (slight limitation; comfortable at rest but ordinary activity causes symptoms) and Class III (marked limitation; comfortable at rest but less than ordinary activity causes symptoms). Treatment aims to improve or maintain functional class and prevent progression to more advanced disease.
What Should You Know Before Taking Macitentan Zentiva?
Contraindications
Macitentan Zentiva must not be used in certain situations where the risks clearly outweigh any potential benefits. The most critical contraindication is pregnancy. Macitentan belongs to the class of endothelin receptor antagonists, all of which have demonstrated teratogenic effects (the ability to cause birth defects) in animal studies. Specifically, macitentan caused birth defects in rabbits and rats at doses lower than the human therapeutic dose, including cardiovascular and mandibular arch abnormalities. For this reason, macitentan is classified as Pregnancy Category X, meaning it is absolutely contraindicated during pregnancy.
Other contraindications include hypersensitivity to macitentan or any of the excipients in the tablet, severe hepatic impairment (Child-Pugh Class C) with or without cirrhosis, baseline values of liver aminotransferases (AST and/or ALT) greater than 3 times the upper limit of normal, and women of childbearing potential who are not using reliable contraception. Patients with pre-existing severe anemia should be carefully evaluated before initiating treatment, as macitentan can further decrease hemoglobin levels.
Warnings and Precautions
Hepatotoxicity: Endothelin receptor antagonists as a class have been associated with liver injury. While macitentan demonstrated a lower rate of liver enzyme elevations in the SERAPHIN trial compared with earlier ERAs (notably bosentan), liver function monitoring remains important. Liver aminotransferases (ALT, AST) and bilirubin should be measured before starting treatment. If clinically significant elevations occur during treatment (greater than 3 times the upper limit of normal), treatment should be interrupted and the patient reassessed. Macitentan should not be restarted if liver enzyme elevations are accompanied by signs or symptoms of liver injury or if elevations of bilirubin greater than 2 times the upper limit of normal are present.
Anemia and decreased hemoglobin: Macitentan causes a decrease in hemoglobin concentration, which is a well-recognized class effect of endothelin receptor antagonists. In the SERAPHIN trial, a decrease in hemoglobin to below 10 g/dL was observed in 8.7% of patients receiving macitentan 10 mg compared with 3.4% of patients receiving placebo. The mechanism is multifactorial and includes hemodilution (increased plasma volume) and possible inhibition of erythropoiesis. Hemoglobin should be measured before treatment initiation, at month 1, month 3, and periodically thereafter. If a clinically significant decrease in hemoglobin occurs, further investigation should be undertaken to determine the cause and consider whether treatment should be continued.
Pulmonary veno-occlusive disease (PVOD): Cases of pulmonary edema have been reported with vasodilators (including ERAs) in patients with pulmonary veno-occlusive disease. If signs of pulmonary edema occur in a patient being treated for PAH, the possibility of PVOD should be considered and macitentan should be discontinued.
Fluid retention: ERAs can cause fluid retention, which may present as peripheral edema or weight gain. If clinically significant fluid retention develops, investigation should include assessment for possible underlying right heart failure or right ventricular decompensation, and appropriate management should be initiated.
Pregnancy and Breastfeeding
Macitentan must NOT be used during pregnancy. It can cause serious birth defects. Women of childbearing potential must have a negative pregnancy test before starting treatment, use reliable contraception throughout treatment, and undergo monthly pregnancy testing. If pregnancy is suspected while taking macitentan, the drug must be stopped immediately and the patient should seek urgent medical advice. Reliable contraception must continue for at least one month after stopping treatment.
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 the milk of lactating rats. Because of the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment with macitentan. The decision to discontinue breastfeeding or discontinue treatment should be made taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.
Fertility: In male patients, macitentan may affect spermatogenesis. In animal studies, testicular tubular atrophy was observed at exposures approximately 4 to 25 times the human exposure. In the SERAPHIN trial, no cases of male infertility were reported, but the sample size was insufficient to detect rare events. Male patients should be informed about this potential risk and may consider sperm preservation before starting treatment.
How Does Macitentan Zentiva Interact with Other Drugs?
Macitentan is extensively metabolized in the liver, primarily by cytochrome P450 3A4 (CYP3A4) and, to a lesser extent, by CYP2C19. Its major active metabolite, ACT-132577, is also formed via CYP3A4. Therefore, drugs that significantly inhibit or induce CYP3A4 can alter the plasma levels of macitentan and its active metabolite, potentially affecting both efficacy and safety. Unlike the earlier ERA bosentan, macitentan does not induce CYP enzymes and does not require dose adjustments of co-administered drugs that are CYP substrates (such as sildenafil or warfarin).
Major Interactions
| Drug / Class | Effect on Macitentan | Clinical Recommendation |
|---|---|---|
| Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin) | Approximately 2-fold increase in macitentan exposure (AUC); active metabolite exposure approximately doubled | Avoid concomitant use. If unavoidable, monitor closely for adverse effects. |
| Strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, St. John’s wort) | Significantly reduced macitentan and active metabolite plasma levels (rifampicin reduces AUC by approximately 79%) | Concomitant use is not recommended. Efficacy may be significantly compromised. |
| Moderate CYP3A4 inhibitors (fluconazole, erythromycin, ciprofloxacin) | Moderate increase in macitentan exposure (exact magnitude varies) | Use with caution. Monitor for increased side effects. |
Minor Interactions and Combinations
| Drug / Class | Interaction | Dose Adjustment |
|---|---|---|
| Sildenafil (PDE5 inhibitor) | No clinically significant pharmacokinetic interaction | None required |
| Tadalafil (PDE5 inhibitor) | No clinically significant pharmacokinetic interaction | None required |
| Warfarin (anticoagulant) | No effect on INR or warfarin pharmacokinetics (unlike bosentan) | None required |
| Hormonal contraceptives | No significant interaction (unlike bosentan, which reduces efficacy of hormonal contraceptives) | None required |
| Prostacyclin pathway agents (epoprostenol, treprostinil, iloprost, selexipag) | No pharmacokinetic interaction; additive therapeutic effects expected | None required |
An important advantage of macitentan over the earlier-generation ERA bosentan is its lack of CYP enzyme induction. Bosentan induces CYP3A4 and CYP2C9, which reduces the plasma levels of many co-administered drugs including sildenafil, warfarin, and hormonal contraceptives, requiring dose adjustments and additional monitoring. Macitentan does not share this property, making it easier to combine with other medications commonly used in PAH management and in patients with comorbidities.
Current ESC/ERS guidelines (2022) recommend initial combination therapy for most treatment-naive PAH patients at intermediate or high risk. Macitentan is frequently combined with a phosphodiesterase type 5 inhibitor (such as tadalafil) as a first-line dual combination. In the SERAPHIN trial, approximately 64% of patients were receiving background PDE5 inhibitor therapy, and macitentan demonstrated consistent benefits in this subgroup. Triple combination therapy adding a prostacyclin pathway agent may be considered for patients who remain at intermediate or high risk despite dual therapy.
What Is the Correct Dosage of Macitentan Zentiva?
Adults
Standard Adult Dose
10 mg orally once daily, with or without food. No dose titration is needed. The tablet should be swallowed whole (not crushed, broken, or chewed) with a glass of water. It may be taken at any time of day but should be taken at approximately the same time each day to maintain consistent plasma levels. Treatment is intended for long-term use and should not be discontinued abruptly without medical supervision.
The 10 mg once-daily dose was established in the SERAPHIN trial as the optimal therapeutic dose. In the trial, both 3 mg and 10 mg doses were evaluated. While both doses showed superiority over placebo, the 10 mg dose demonstrated a larger and more consistent treatment effect (45% risk reduction vs. 30% for 3 mg). Therefore, 10 mg is the only recommended dose in clinical practice. No dose reduction to 3 mg is currently approved for maintenance therapy.
Macitentan can be taken with or without food, as food does not significantly affect its bioavailability. After oral administration, macitentan is well absorbed with peak plasma concentrations reached in approximately 8 hours. Steady-state plasma concentrations of macitentan are reached within approximately 3 days, while the active metabolite ACT-132577 reaches steady state within approximately 7 days due to its longer half-life (approximately 48 hours).
Children
Pediatric Use
The safety and efficacy of macitentan in children and adolescents below 18 years of age have not been established. No data are available. Use in the pediatric population is not currently recommended. The ongoing TOMORROW study is investigating macitentan pharmacokinetics and safety in pediatric patients with PAH, but results are not yet available to support a dosing recommendation.
Elderly
Elderly Patients (≥65 years)
No dose adjustment is required in elderly patients. In the SERAPHIN trial, approximately 14% of patients were aged 65 years or older. Analysis of this subgroup showed consistent efficacy and safety compared with younger patients. However, greater susceptibility to adverse effects cannot be excluded in the elderly population, particularly regarding anemia and hepatic function. Regular monitoring is recommended.
Hepatic and Renal Impairment
Dose Adjustments for Organ Impairment
Hepatic impairment: No dose adjustment is necessary for patients with mild or moderate hepatic impairment (Child-Pugh Class A or B). However, macitentan is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C) due to lack of clinical data and the potential for significantly increased drug exposure. Patients with baseline liver aminotransferases (AST and/or ALT) greater than 3 times the upper limit of normal should not initiate macitentan.
Renal impairment: No dose adjustment is necessary for patients with renal impairment, including those with an estimated GFR as low as 15 mL/min/1.73 m². Macitentan and its active metabolite are not significantly removed by dialysis, but there is limited experience in patients receiving dialysis.
Missed Dose
If you miss a dose of Macitentan Zentiva, take it as soon as you remember on the same day. If it is almost time for your next dose, skip the missed dose and take your next dose at the regular scheduled time. Do not take a double dose to make up for a missed one. If you have any concerns about missed doses, consult your doctor or pharmacist. Consistent daily dosing is important for maintaining therapeutic plasma levels and optimal disease control.
Overdose
There is limited experience with macitentan overdose in humans. In clinical trials, single doses up to 600 mg were administered to healthy volunteers. The most likely symptoms of overdose would be headache, nausea, and vomiting, consistent with the known pharmacological effects and side effect profile of the drug. Hypotension may also occur. There is no specific antidote for macitentan. In case of overdose, standard supportive measures should be employed. Macitentan is highly protein-bound (greater than 99%) and is unlikely to be removed by hemodialysis. If overdose occurs, contact your local poison control center or emergency department immediately.
What Are the Side Effects of Macitentan Zentiva?
The safety profile of macitentan has been extensively characterized in the SERAPHIN trial and in post-marketing surveillance. The most commonly reported adverse reactions reflect both the pharmacological effects of endothelin receptor blockade and the underlying disease burden in PAH patients. Below, side effects are categorized by frequency according to the internationally standardized system used in pharmaceutical reporting.
Very Common
- Anemia / decreased hemoglobin (13.2% vs. 3.4% placebo)
- Nasopharyngitis (common cold) (13.6%)
- Bronchitis (11.6%)
Common
- Headache
- Urinary tract infection
- Influenza
- Pharyngitis (sore throat)
- Hypotension (low blood pressure)
- Nasal congestion
- Edema (fluid retention / swelling)
- Elevated liver aminotransferases (ALT/AST)
Uncommon
- Hepatotoxicity (clinically significant liver injury)
- Allergic reactions (rash, pruritus)
- Leukopenia (decreased white blood cell count)
- Flushing
Rare
- Severe hepatic injury with jaundice
- Angioedema
- Severe anemia requiring blood transfusion
The most clinically important side effect of macitentan is anemia. In the SERAPHIN trial, hemoglobin decreased by a mean of approximately 1 g/dL during the first few months of treatment and then stabilized. A hemoglobin level below 10 g/dL was observed in 8.7% of patients receiving macitentan 10 mg compared with 3.4% of placebo patients. The mechanism involves both hemodilution (fluid retention causing a relative decrease in red blood cell concentration) and a possible direct effect on erythropoiesis. Severe anemia requiring red blood cell transfusion occurred in approximately 4.3% of patients on macitentan 10 mg versus 0.4% on placebo. Patients with pre-existing anemia, particularly those also receiving anticoagulant or antiplatelet therapy, should be monitored closely.
Hepatotoxicity is a recognized class effect of ERAs. However, macitentan has demonstrated a more favorable hepatic safety profile compared with the first-generation ERA bosentan, which was associated with dose-dependent liver aminotransferase elevations in up to 11% of patients. In the SERAPHIN trial, the incidence of liver aminotransferase elevations greater than 3 times the upper limit of normal was 3.4% in the macitentan 10 mg group compared with 4.5% in the placebo group, suggesting no increased hepatic risk attributable to macitentan. Nevertheless, liver function should be monitored before initiation and during treatment, particularly in the first few months.
Respiratory tract infections (nasopharyngitis, bronchitis, pharyngitis, influenza) were reported more frequently in macitentan-treated patients than in placebo patients. This may be related to immunomodulatory effects of endothelin receptor blockade, as ETB receptors are involved in immune cell function. These infections were generally mild to moderate and did not typically require treatment discontinuation.
Seek urgent medical attention if you experience: unexplained shortness of breath or worsening breathlessness, signs of severe anemia (extreme fatigue, pale skin, rapid heartbeat, dizziness), yellowing of the skin or eyes (jaundice), dark urine, persistent nausea or vomiting, severe swelling in the legs or ankles, or signs of allergic reaction (rash, facial swelling, difficulty breathing). If you miss your period or suspect you may be pregnant, stop taking macitentan immediately and contact your doctor.
How Should You Store Macitentan Zentiva?
Macitentan Zentiva film-coated tablets should be stored at temperatures not exceeding 30°C (86°F). The tablets should be kept in their original blister packaging or bottle until the time of use in order to protect them from moisture. Do not remove the tablets from the blister pack until you are ready to take your dose. The medication does not require refrigeration under normal storage conditions.
The expiry date (EXP) printed on the outer carton and blister foil refers to the last day of the indicated month. Do not use Macitentan Zentiva after this date. If you notice any visible changes in the appearance of the tablets (such as discoloration, crumbling, or unusual odor), do not take them and consult your pharmacist.
As with all medications, keep Macitentan Zentiva out of the reach and sight of children. Given the teratogenic potential of macitentan, special care should be taken to ensure that the medication is stored securely and that it cannot be accidentally accessed by women who may be pregnant. Unused or expired medication should not be disposed of via wastewater or household waste. Return any unused tablets to your pharmacy for safe disposal in accordance with local regulations. This helps protect the environment and prevents accidental exposure.
What Does Macitentan Zentiva Contain?
The active substance is macitentan. Each film-coated tablet contains exactly 10 mg of macitentan. Macitentan is chemically described as N-[5-(4-bromophenyl)-6-(2-(5-bromopyrimidin-2-yloxy)ethoxy)pyrimidin-4-yl]-N′-propylsulfamide, with a molecular formula of C19H20Br2N6O4S and a molecular weight of 588.27 g/mol. It is a white to off-white crystalline powder that is practically insoluble in water.
The tablet core contains the following inactive ingredients (excipients): lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, povidone, magnesium stearate, and polysorbate 80. The film coating typically contains hypromellose, titanium dioxide (E171), talc, propylene glycol, and soya lecithin. These excipients are standard pharmaceutical ingredients used to ensure the tablet has appropriate physical characteristics, stability, and bioavailability. Patients with known allergies to soya or peanut should be aware of the soya lecithin content and discuss this with their doctor or pharmacist before use.
Macitentan Zentiva tablets are typically white to off-white, round, biconvex film-coated tablets that may be debossed with identifying markings depending on the specific manufacturer’s presentation. The tablets are supplied in PVC/PVDC-aluminium blister packs or HDPE bottles with child-resistant closures, in pack sizes that vary by market.
Frequently Asked Questions About Macitentan Zentiva
Macitentan Zentiva is a generic version of Opsumit, manufactured by Zentiva. Both products contain the same active ingredient (macitentan 10 mg) and are bioequivalent, meaning they deliver the same amount of drug to the bloodstream at the same rate. Generic medications must meet the same rigorous quality, safety, and efficacy standards as the original brand-name product, as regulated by the European Medicines Agency (EMA). The main differences may be in the inactive ingredients (excipients), the appearance of the tablet, and the price. Generic medications typically cost less than their branded equivalents, which can improve access to treatment for patients with PAH.
There is no specific pharmacokinetic interaction between macitentan and alcohol. However, both macitentan and alcohol can lower blood pressure, so combining them may increase the risk of hypotension (low blood pressure), causing dizziness, lightheadedness, or fainting. Additionally, alcohol can affect liver function, and since liver monitoring is important during macitentan treatment, excessive alcohol consumption should be avoided. It is advisable to discuss your alcohol intake with your doctor, who can provide personalized guidance based on your overall health status and PAH severity.
Macitentan Zentiva is intended for long-term treatment of PAH. Pulmonary arterial hypertension is a chronic, progressive condition, and the benefits of macitentan are maintained through continuous therapy. In the SERAPHIN trial, patients were treated for a median of over 2 years. Stopping treatment abruptly can lead to a rebound increase in pulmonary artery pressure and clinical deterioration. You should never stop taking macitentan without consulting your specialist, even if you feel well. Your doctor will regularly assess your response to treatment and adjust your overall PAH management plan accordingly.
Macitentan may have a minor influence on the ability to drive and use machines. Some patients may experience side effects such as headache, dizziness, or hypotension, which could impair their ability to drive or operate machinery safely. If you experience any of these effects, avoid driving or operating machinery until you know how macitentan affects you. Additionally, PAH itself can cause fatigue and exercise limitation that may affect driving ability. Discuss with your doctor whether it is safe for you to drive while being treated for PAH.
No, macitentan does not cure PAH. Currently, there is no cure for pulmonary arterial hypertension (except lung transplantation in select cases). Macitentan is a disease-modifying treatment that slows disease progression, reduces the risk of hospitalization and clinical worsening events, improves exercise capacity, and can enhance quality of life. It works by targeting one of the key pathological pathways (the endothelin pathway) driving the disease. PAH management typically involves combination therapy targeting multiple pathways, along with supportive measures such as diuretics, oxygen therapy, and supervised exercise rehabilitation. The goal of treatment is to achieve and maintain a low-risk status as defined by current ESC/ERS guidelines.
If you accidentally take an extra tablet, contact your doctor or pharmacist for advice. A single double dose is unlikely to cause serious harm based on clinical trial data where higher doses were administered to healthy volunteers. However, you may experience an increase in side effects such as headache, nausea, or a temporary drop in blood pressure. Do not take any additional doses and resume your regular dosing schedule the next day. If you feel unwell or experience concerning symptoms (severe dizziness, fainting, or difficulty breathing), seek immediate medical attention. Keep track of your doses to prevent accidental double dosing – a daily pill organizer may help.
References
- European Medicines Agency (EMA). Opsumit (macitentan) – Summary of Product Characteristics. Last updated 2025. Available at: EMA Opsumit EPAR.
- U.S. Food and Drug Administration (FDA). Opsumit (macitentan) – Prescribing Information. Actelion Pharmaceuticals (Janssen). Revised 2024.
- 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.
- 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.
- Sidharta PN, van Giersbergen PLM, Dingemanse J. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Macitentan, an Endothelin Receptor Antagonist, in an Ascending Multiple-Dose Study in Healthy Subjects. J Clin Pharmacol. 2013;53(11):1131–1138.
- World Health Organization (WHO). Pulmonary Hypertension. WHO Classification of Pulmonary Hypertension. 2024.
- British National Formulary (BNF). Macitentan. National Institute for Health and Care Excellence (NICE). 2025.
- Rubin LJ, Galiè N, Grimminger F, et al. Riociguat for the Treatment of Pulmonary Arterial Hypertension: A Long-Term Extension Study (PATENT-2). Eur Respir J. 2015;45(5):1303–1313.
- Sitbon O, Channick R, Chin KM, et al. Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2015;373(26):2522–2533. doi:10.1056/NEJMoa1503184.
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