Macitentan Bioglan
Endothelin receptor antagonist for pulmonary arterial hypertension
Quick facts about Macitentan Bioglan
Key takeaways about Macitentan Bioglan
- Treats pulmonary arterial hypertension: Macitentan blocks endothelin receptors to lower blood pressure in the lungs and reduce disease progression
- Proven efficacy in SERAPHIN trial: Demonstrated a 45% reduction in morbidity and mortality events compared to placebo over long-term treatment
- Strictly contraindicated in pregnancy: Macitentan causes birth defects – women of childbearing potential must use two reliable contraceptive methods
- Monitor for anaemia: Haemoglobin levels should be checked before and during treatment as decreases are common
- Once-daily dosing: Take one 10 mg tablet daily, with or without food, at the same time each day
What Is Macitentan Bioglan and What Is It Used For?
Macitentan Bioglan contains the active substance macitentan, a dual endothelin receptor antagonist (ERA) approved for the long-term treatment of pulmonary arterial hypertension (PAH) in adults with WHO Functional Class II to III symptoms. It reduces disease progression, decreases hospitalisations, and improves exercise capacity.
Pulmonary arterial hypertension is a serious and progressive condition characterised by abnormally high blood pressure in the arteries that supply the lungs. In PAH, the walls of the pulmonary arteries become thickened and stiff, which increases resistance to blood flow and places a significant strain on the right side of the heart. Over time, this can lead to right heart failure if left untreated. The condition affects approximately 15–50 people per million in the general population and is more common in women than in men.
Endothelin-1 (ET-1) is a potent vasoconstrictor and pro-proliferative peptide that plays a central role in the pathogenesis of PAH. Patients with PAH have elevated levels of ET-1, which acts through two receptor subtypes: endothelin receptor type A (ETA) and endothelin receptor type B (ETB). Activation of these receptors causes constriction and remodelling of the pulmonary vasculature. Macitentan blocks both ETA and ETB receptors, providing dual receptor antagonism that counteracts the harmful effects of excessive endothelin-1 signalling.
What distinguishes macitentan from earlier endothelin receptor antagonists such as bosentan is its tissue-targeting properties. Macitentan was specifically designed to have a high affinity for endothelin receptors and sustained receptor binding, meaning it remains active at the receptor site for a longer duration. This pharmacological profile was developed to improve efficacy and tolerability compared to previous generation ERAs.
The efficacy of macitentan was established in the landmark SERAPHIN trial (Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome), a large-scale, double-blind, placebo-controlled study involving 742 patients with symptomatic PAH. The trial 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). This included reductions in disease worsening, initiation of intravenous or subcutaneous prostanoid therapy, lung transplantation, atrial septostomy, and death from any cause.
Macitentan blocks both ETA and ETB endothelin receptors in the pulmonary arterial smooth muscle cells. By blocking these receptors, it prevents endothelin-1 from causing vasoconstriction (narrowing of blood vessels) and cellular proliferation (abnormal cell growth) in the lung arteries. This leads to reduced pulmonary arterial pressure, decreased vascular resistance, and improved blood flow through the lungs, ultimately reducing the workload on the right side of the heart.
What Should You Know Before Taking Macitentan Bioglan?
Before starting Macitentan Bioglan, your doctor must confirm you are not pregnant, check your liver function and haemoglobin levels, and ensure you are not taking contraindicated medicines. This medicine must only be prescribed by physicians experienced in treating PAH.
Macitentan Bioglan is a specialist medicine that requires careful medical assessment before initiation. Because PAH is a serious condition and macitentan carries specific risks, treatment should only be started and supervised by a physician experienced in the management of pulmonary arterial hypertension. A thorough evaluation of your medical history, current medications, and baseline laboratory values is essential before beginning therapy.
Contraindications
You must not take Macitentan Bioglan if any of the following apply to you:
- Pregnancy or planning to become pregnant: Macitentan is teratogenic and can cause severe birth defects. Women of childbearing potential must have a negative pregnancy test before starting treatment
- Breastfeeding: It is not known whether macitentan passes into breast milk; breastfeeding must be stopped during treatment
- Severe liver impairment: Patients with severe hepatic impairment (Child-Pugh class C) or clinically significant elevated liver aminotransferases (>3 times the upper limit of normal) must not use this medicine
- Hypersensitivity: Known allergy to macitentan or any of the excipients
- Concomitant use of strong CYP3A4 inhibitors: Medicines such as ketoconazole, itraconazole, ritonavir, and clarithromycin significantly increase macitentan levels and are contraindicated
Warnings and Precautions
Several important warnings apply to patients taking macitentan. Liver function should be assessed before starting treatment, as endothelin receptor antagonists as a class have been associated with hepatotoxicity. While macitentan has shown a more favourable hepatic safety profile than bosentan in clinical trials, periodic monitoring of liver enzymes is still recommended, particularly in patients with pre-existing liver conditions.
Haemoglobin and haematocrit levels should be measured before initiating treatment and periodically during therapy. Decreases in haemoglobin concentration have been observed in clinical trials with macitentan, and the development of anaemia may necessitate dose adjustments of other medications, blood transfusion, or in rare cases, discontinuation of macitentan. Patients should report symptoms such as unusual tiredness, pallor, or shortness of breath that is worse than usual.
Fluid retention and oedema are potential effects of endothelin receptor antagonists. Patients should monitor for signs of fluid overload, including unexpected weight gain, swelling of the ankles or legs, and increasing breathlessness. If clinically significant fluid retention develops, treatment should be evaluated.
Macitentan causes birth defects and must not be used during pregnancy. Women of childbearing potential must use two reliable methods of contraception during treatment and for one month after stopping treatment. Monthly pregnancy tests are required. If you become pregnant or suspect pregnancy while taking this medicine, stop taking it immediately and contact your doctor.
Pregnancy and Breastfeeding
Macitentan is classified as Category X for pregnancy risk, the highest risk category, indicating that it is strictly contraindicated in pregnancy due to evidence of foetal harm. Animal studies have demonstrated teratogenic effects including cardiovascular and mandibular abnormalities. No adequate studies have been conducted in pregnant women, but the risk is considered too great to permit use under any circumstances during pregnancy.
Women of childbearing potential must meet the following requirements before and during treatment with Macitentan Bioglan:
- A negative pregnancy test must be obtained before starting treatment
- Pregnancy testing must be repeated monthly during treatment
- Two reliable methods of contraception must be used simultaneously (e.g. hormonal contraceptive plus barrier method)
- Contraception must continue for at least one month after discontinuation of macitentan
- If hormonal contraception is used, note that macitentan does not affect the efficacy of hormonal contraceptives at clinically relevant concentrations
It is not known whether macitentan or its metabolites are excreted in human breast milk. Because of the potential for serious adverse effects in nursing infants, breastfeeding is contraindicated during treatment with macitentan.
How Does Macitentan Bioglan Interact with Other Drugs?
Macitentan is metabolised primarily by CYP3A4 and, to a lesser extent, CYP2C9. Strong CYP3A4 inhibitors significantly increase macitentan exposure and are contraindicated. Strong CYP3A4 inducers substantially decrease macitentan levels and should be avoided. Several other drug interactions require monitoring.
Understanding drug interactions is essential for the safe and effective use of Macitentan Bioglan. The medicine is metabolised in the liver mainly by the cytochrome P450 enzyme CYP3A4, with minor contributions from CYP2C8, CYP2C9, and CYP2C19. Its active metabolite, ACT-132577, is also pharmacologically active and contributes to the overall therapeutic effect. Therefore, any drug that significantly alters CYP3A4 activity can affect the blood levels of both macitentan and its active metabolite.
Macitentan is neither an inhibitor nor an inducer of CYP enzymes at clinically relevant concentrations, which means it is unlikely to affect the metabolism of other drugs via these pathways. However, macitentan inhibits hepatic uptake transporters (OATP1B1 and OATP1B3) at high concentrations, which could potentially affect the disposition of certain drugs that are substrates of these transporters.
Major Interactions
| Drug / Drug Class | Effect | Recommendation |
|---|---|---|
| Ketoconazole, itraconazole (strong CYP3A4 inhibitors) | Approximately 2-fold increase in macitentan exposure | Contraindicated – do not use together |
| Ritonavir, cobicistat (HIV protease inhibitor boosters) | Significant increase in macitentan and active metabolite levels | Contraindicated – do not use together |
| Rifampicin (strong CYP3A4 inducer) | Approximately 79% decrease in active metabolite exposure | Avoid – significantly reduces efficacy |
| Carbamazepine, phenytoin, phenobarbital (anticonvulsants, CYP3A4 inducers) | Substantially decreased macitentan and metabolite levels | Avoid – use alternative anticonvulsants |
| St John’s Wort (Hypericum perforatum) | Potent CYP3A4 inducer that reduces macitentan levels | Avoid – do not use during treatment |
Minor Interactions
| Drug / Drug Class | Effect | Recommendation |
|---|---|---|
| Sildenafil, tadalafil (PDE-5 inhibitors) | No clinically significant pharmacokinetic interaction | Can be used together – commonly combined in PAH treatment |
| Warfarin (anticoagulant) | No clinically significant effect on INR; macitentan does not inhibit CYP2C9 | No dose adjustment needed – routine INR monitoring sufficient |
| Hormonal contraceptives | Macitentan does not affect hormonal contraceptive efficacy | Safe to use together – hormonal methods remain effective |
| Moderate CYP3A4 inhibitors (e.g. fluconazole, erythromycin) | May moderately increase macitentan levels | Use with caution – monitor for adverse effects |
What Is the Correct Dosage of Macitentan Bioglan?
The recommended dose of Macitentan Bioglan is 10 mg taken orally once daily, with or without food. The tablet should be swallowed whole and taken at approximately the same time each day. No dose titration is required. Treatment should be initiated and monitored by a physician experienced in PAH management.
Macitentan Bioglan is available in a single strength of 10 mg film-coated tablets. The dosing regimen is straightforward: one tablet once daily, which can be taken with or without food. Unlike some other PAH therapies, macitentan does not require gradual dose titration – the treatment dose of 10 mg is started from the first day. The tablet should be swallowed whole with water and should not be crushed, broken, or chewed, as this may alter the drug’s release characteristics.
Adults
Standard adult dosage
Dose: 10 mg once daily
Administration: Oral, with or without food
Timing: Take at the same time each day
Duration: Long-term treatment – continue for as long as the prescribing physician deems beneficial
No dose adjustment is required for patients with mild to moderate hepatic impairment. However, there is no clinical experience with macitentan in patients with severe hepatic impairment (Child-Pugh class C), and use in these patients is contraindicated. No dose adjustment is required based on renal function, though caution is advised in patients on dialysis due to limited data.
Children
Paediatric use
Macitentan Bioglan is not recommended for use in children and adolescents under 18 years of age. The safety and efficacy of macitentan have not been established in paediatric patients. Clinical trials have primarily included adult populations, and extrapolation of dosing from adults to children is not appropriate due to differences in drug metabolism, body composition, and disease characteristics in younger patients.
Elderly
Elderly patients (65 years and older)
No dose adjustment is required in elderly patients based on age alone. In the SERAPHIN trial, approximately 14% of enrolled patients were aged 65 years and older. No overall differences in safety or efficacy were observed between older and younger patients. However, as with all medicines, elderly patients may be more susceptible to adverse effects due to age-related changes in organ function, and clinical monitoring should be individualised.
Missed Dose
If you forget to take a dose of Macitentan Bioglan, take it as soon as you remember on the same day. If it is almost time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a forgotten dose. Taking two tablets at once may increase the risk of side effects without providing additional therapeutic benefit. If you frequently forget doses, discuss strategies with your doctor or pharmacist, such as setting a daily alarm.
Overdose
There is limited clinical experience with macitentan overdose. In healthy volunteers, single doses up to 600 mg have been administered without specific dose-limiting adverse events. In the event of overdose, standard supportive measures should be taken as required. Macitentan and its active metabolite are highly bound to plasma proteins, so haemodialysis is unlikely to be effective in removing the drug from the body. Symptoms of overdose may include headache, nausea, and vomiting. Hypotension may also occur. If overdose is suspected, contact a poison control centre or emergency medical services immediately.
What Are the Side Effects of Macitentan Bioglan?
The most frequently reported side effects of Macitentan Bioglan include anaemia, headache, nasopharyngitis, bronchitis, and urinary tract infections. Anaemia is the most clinically significant side effect and requires regular monitoring of haemoglobin levels. Most side effects are mild to moderate in severity.
Like all medicines, Macitentan Bioglan can cause side effects, although not everybody gets them. The safety profile of macitentan has been well characterised through clinical trials, most notably the SERAPHIN study involving 742 patients treated for a median duration of approximately 2 years. Understanding the frequency and nature of potential side effects helps patients and healthcare providers make informed treatment decisions and recognise adverse events early.
The side effects are categorised below according to their frequency of occurrence, based on the following convention: very common (may affect more than 1 in 10 people), common (may affect up to 1 in 10 people), uncommon (may affect up to 1 in 100 people), and rare (may affect up to 1 in 1,000 people).
Very Common
- Anaemia (decreased haemoglobin) – reported in approximately 13% of patients in the SERAPHIN trial; haemoglobin decreases of >1 g/dL were common and clinically significant decreases (<10 g/dL) occurred in some patients
- Nasopharyngitis (common cold symptoms) – nasal congestion, sore throat, runny nose
- Bronchitis – infection of the airways with cough, mucus production, and sometimes fever
Common
- Headache – often mild and may resolve with continued treatment
- Urinary tract infection – burning sensation during urination, increased frequency of urination
- Pharyngitis – sore throat and inflammation
- Influenza – flu-like symptoms including fever, body aches, fatigue
- Oedema / fluid retention – swelling of the ankles, legs, or other areas
- Hypotension – low blood pressure, which may cause dizziness or lightheadedness
- Nasal congestion – blocked or stuffy nose
Uncommon
- Elevated liver aminotransferases – increased levels of liver enzymes (ALT/AST), usually mild and reversible
- Leukopenia – decreased white blood cell count
- Thrombocytopenia – decreased platelet count
- Hypersensitivity reactions – rash, pruritus (itching), or angioedema (swelling)
Rare
- Hepatotoxicity – clinically significant liver injury; although rare with macitentan, any signs of liver problems (unexplained nausea, vomiting, right upper abdominal pain, jaundice, unusual fatigue, dark urine) should be reported immediately
- Severe allergic reactions – anaphylaxis or severe angioedema requiring emergency treatment
It is important to note that PAH itself causes many symptoms that overlap with the side effects of macitentan, including breathlessness, oedema, and fatigue. Your healthcare team will help distinguish between disease-related symptoms and medication side effects. If you experience any unexpected symptoms or if known side effects become severe, contact your prescribing physician.
Contact your doctor or seek emergency medical care immediately if you experience signs of severe allergic reaction (difficulty breathing, swelling of the face or throat), signs of liver problems (unexplained nausea, dark urine, yellowing of the skin or eyes), or signs of severe anaemia (extreme tiredness, very pale skin, fast heartbeat, shortness of breath at rest).
How Should You Store Macitentan Bioglan?
Store Macitentan Bioglan tablets below 30°C in the original packaging to protect from moisture. Keep out of the sight and reach of children. Do not use after the expiry date printed on the packaging.
Proper storage of Macitentan Bioglan is essential to ensure the medicine remains effective and safe throughout its shelf life. The film-coated tablets should be stored at a temperature not exceeding 30°C (86°F). They should be kept in the original blister packaging until immediately before use, as this protects the tablets from moisture and light exposure.
Do not store Macitentan Bioglan in the bathroom, near a sink, or in other humid locations, as moisture can degrade the tablet’s film coating and potentially alter the drug’s bioavailability. Similarly, avoid storing the tablets in direct sunlight or near heat sources such as radiators or car glove compartments, particularly during summer months.
The expiry date refers to the last day of the stated month. Do not use Macitentan Bioglan after the expiry date printed on the carton and blister pack. Expired medicines should not be used, as their chemical composition may have changed, leading to reduced efficacy or potential safety concerns.
Do not dispose of unused or expired Macitentan Bioglan tablets in household waste or down the drain. Return them to your pharmacist or local medicine take-back programme for safe disposal. This helps protect the environment and prevents accidental ingestion by others, particularly children or vulnerable individuals.
Keep this medicine out of the sight and reach of children. Because macitentan is teratogenic, particular care should be taken to ensure that women who may be pregnant do not handle broken or crushed tablets. If accidental exposure occurs, wash the affected area with soap and water.
What Does Macitentan Bioglan Contain?
Each Macitentan Bioglan film-coated tablet contains 10 mg of the active substance macitentan, along with several inactive ingredients (excipients) that form the tablet core and coating.
The active substance in Macitentan Bioglan is macitentan. Each film-coated tablet contains exactly 10 mg of macitentan as the active ingredient responsible for the therapeutic effect.
The inactive ingredients (excipients) in Macitentan Bioglan tablets serve various pharmaceutical functions, including ensuring tablet stability, providing the appropriate release profile, and forming the protective film coating. The typical excipients found in macitentan film-coated tablets include:
- Tablet core: Lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, povidone, magnesium stearate, polysorbate 80
- Film coating: Polyvinyl alcohol, titanium dioxide (E171), talc, lecithin (soya), xanthan gum
Patients with known allergies to soya or peanuts should inform their healthcare provider, as the film coating contains soya lecithin. Similarly, patients with lactose intolerance should be aware that the tablet core contains lactose monohydrate. The amount of lactose per tablet is generally small, but patients with severe lactose intolerance or rare hereditary conditions of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should discuss this with their prescribing physician.
Macitentan Bioglan tablets are round, biconvex, white to off-white film-coated tablets. They are supplied in blister packs, typically containing 28 or 30 tablets per carton, corresponding to approximately one month of treatment. The tablet packaging is designed to protect the contents from environmental degradation and facilitate adherence to the once-daily dosing regimen.
Frequently Asked Questions About Macitentan Bioglan
References
This article is based on the following peer-reviewed sources and international medical 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. EMA/CHMP, last updated 2024.
- U.S. Food and Drug Administration (FDA). Opsumit (macitentan) – Prescribing Information. Reference ID: current approved labelling.
- 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
- 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
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: WHO; 2023.
- British National Formulary (BNF). Macitentan. NICE Evidence Services. Last reviewed 2024.
About the Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians in pulmonology, cardiology, and clinical pharmacology. Our editorial process follows the GRADE evidence framework and adheres to international guidelines from the ESC, ERS, EMA, and WHO.
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