Bosentan Sandoz (Bosentan)
Endothelin receptor antagonist for pulmonary arterial hypertension and digital ulcers
Quick Facts about Bosentan Sandoz
Key Takeaways
- Specialist-only medicine: Treatment must be initiated and monitored by a physician experienced in managing pulmonary arterial hypertension
- Mandatory liver monitoring: Monthly blood tests for liver function are required throughout treatment, as hepatotoxicity is a known risk
- Absolutely contraindicated in pregnancy: Bosentan causes birth defects; reliable contraception with a barrier method is essential
- Many drug interactions: Cyclosporine is contraindicated; hormonal contraceptives have reduced efficacy; multiple other drugs require caution
- Gradual dose titration: Start at 62.5 mg twice daily for 4 weeks before increasing to the maintenance dose of 125 mg twice daily
What Is Bosentan Sandoz and What Is It Used For?
Bosentan Sandoz is a prescription medicine containing bosentan, a dual endothelin receptor antagonist (ERA) that blocks endothelin-1 (ET-1), a naturally occurring hormone that causes blood vessels to constrict. By blocking this hormone, Bosentan Sandoz widens the blood vessels in the lungs, reducing pulmonary arterial pressure and improving symptoms.
Endothelin-1 is one of the most potent vasoconstrictors known in human physiology. In patients with pulmonary arterial hypertension, endothelin-1 levels are significantly elevated, contributing to the progressive narrowing and remodeling of pulmonary arteries. Bosentan works by blocking both the ETA and ETB receptors on pulmonary artery smooth muscle cells, thereby preventing the vasoconstrictive and proliferative effects of endothelin-1. This dual receptor blockade distinguishes bosentan from some newer endothelin receptor antagonists that selectively target only the ETA receptor.
Bosentan Sandoz is primarily used to treat pulmonary arterial hypertension (PAH), a serious condition characterized by abnormally high blood pressure in the pulmonary arteries that carry blood from the heart to the lungs. This elevated pressure forces the right side of the heart to work harder, eventually leading to right heart failure if left untreated. PAH significantly limits physical activity and reduces quality of life. Clinical trials, most notably the landmark BREATHE studies published in the New England Journal of Medicine, demonstrated that bosentan improves exercise capacity (measured by 6-minute walk distance), reduces clinical worsening, and improves functional class in PAH patients.
Approved Indications
Bosentan Sandoz is approved for the following indications:
- Pulmonary arterial hypertension (PAH) in adults: For patients with WHO functional class III symptoms (marked limitation of physical activity) to improve exercise capacity and symptoms. Benefits have also been shown in class II patients (slight limitation of physical activity).
- PAH in children aged 1 year and older: Used at weight-based dosing to treat PAH in the pediatric population.
- Digital ulcers in systemic sclerosis: Bosentan Sandoz reduces the number of new digital ulcers (sores on fingers and toes) in adult patients with systemic sclerosis (scleroderma) who have ongoing digital ulcer disease.
Types of PAH Treated
The forms of pulmonary arterial hypertension for which Bosentan Sandoz is used include:
- Idiopathic PAH (previously called primary pulmonary hypertension) — where no identifiable cause is found
- Heritable PAH — inherited forms of the disease, often associated with BMPR2 gene mutations
- PAH associated with systemic sclerosis (scleroderma) — a connective tissue disease with abnormal growth of supportive tissue
- PAH associated with congenital heart defects — where abnormal connections (shunts) between heart chambers cause abnormal blood flow through the heart and lungs
Bosentan blocks the action of endothelin-1, one of the body's most powerful blood vessel-narrowing substances. By preventing endothelin-1 from binding to its receptors (ETA and ETB), bosentan causes the pulmonary arteries to relax and widen, making it easier for the heart to pump blood through the lungs. This lowers pulmonary arterial pressure and improves the supply of oxygen to the body.
What Should You Know Before Taking Bosentan Sandoz?
Before starting Bosentan Sandoz, your doctor must check your liver function, hemoglobin levels, and pregnancy status (for women of childbearing age). Several conditions and medications are contraindicated with bosentan, and careful medical assessment is essential before treatment begins.
Bosentan is a medicine with significant safety considerations that require thorough medical evaluation before treatment and ongoing monitoring throughout therapy. Your prescribing physician should be a specialist experienced in the management of pulmonary arterial hypertension or systemic sclerosis. Understanding the contraindications, warnings, and precautions is critical for safe use of this medication.
Contraindications
You must not take Bosentan Sandoz if any of the following apply:
- Allergy to bosentan or any of the other ingredients in the tablets
- Liver problems: Patients with moderate to severe liver impairment (Child-Pugh class B or C) or with baseline liver aminotransferases (AST/ALT) greater than 3 times the upper limit of normal must not use bosentan
- Pregnancy or potential pregnancy: Bosentan is teratogenic (causes birth defects) and must not be used if you are pregnant or could become pregnant without using reliable contraception
- Concomitant use of cyclosporine A: Cyclosporine significantly increases bosentan plasma levels and is strictly contraindicated
Bosentan Sandoz is known to cause serious birth defects and must never be used during pregnancy. Women of childbearing potential must have a negative pregnancy test before starting treatment, use two forms of contraception (since hormonal contraceptives alone are unreliable with bosentan), and undergo monthly pregnancy testing throughout treatment. If you suspect you may be pregnant, contact your doctor immediately.
Warnings and Precautions
Your doctor will perform several important checks before and during treatment with Bosentan Sandoz:
Liver function monitoring: Bosentan can cause dose-dependent elevations in liver enzymes (aminotransferases). Abnormal liver function tests may occur in more than 1 in 10 patients. Your doctor will order liver function blood tests once a month throughout the entire duration of treatment. An additional test is performed 2 weeks after any dose increase. If liver enzymes rise to more than 3 times the upper limit of normal, the dose may need to be reduced or treatment stopped. Symptoms of liver problems include nausea, vomiting, fever, abdominal pain, jaundice (yellowing of skin or eyes), dark urine, itching, fatigue, or flu-like symptoms. Report any of these to your doctor immediately.
Hemoglobin monitoring: Bosentan can cause a decrease in hemoglobin levels (anemia). Blood tests for anemia are performed monthly during the first 4 months and every 3 months thereafter. In some cases, anemia may be severe enough to require blood transfusion. If your hemoglobin drops significantly, your doctor may need to adjust treatment.
Fluid retention: Bosentan may cause edema (swelling), particularly in the legs and ankles. In patients with pre-existing heart failure, this fluid retention can lead to clinical worsening. If you notice increasing swelling or sudden weight gain, contact your doctor promptly.
Pregnancy and Breastfeeding
Pregnancy: Bosentan Sandoz is absolutely contraindicated in pregnancy due to its teratogenic effects. Women of childbearing potential must use reliable contraception. Because bosentan reduces the effectiveness of hormonal contraceptives (oral pills, injections, implants, and patches), these methods alone are not sufficient. You must also use a barrier method (such as a female condom, diaphragm, or your partner must use a condom). Monthly pregnancy tests are recommended throughout treatment. If you become pregnant while taking bosentan, contact your doctor immediately.
Breastfeeding: Bosentan passes into breast milk. It is recommended that you stop breastfeeding if you are prescribed Bosentan Sandoz, as it is not known whether the drug in breast milk could harm your baby. Discuss this with your doctor.
Male fertility: Bosentan may reduce sperm count in men. It cannot be excluded that this could affect your ability to father a child. If you have concerns about fertility, speak with your doctor.
Driving and Operating Machinery
Bosentan Sandoz has negligible direct effects on the ability to drive or use machines. However, it can cause low blood pressure (hypotension), which may lead to dizziness or blurred vision. If you experience these symptoms, do not drive or operate machinery until they resolve.
Bosentan Sandoz tablets contain less than 1 mmol (23 mg) sodium per tablet and are therefore essentially sodium-free. This is relevant for patients on a controlled sodium diet.
How Does Bosentan Sandoz Interact with Other Drugs?
Bosentan Sandoz has clinically significant interactions with many medications. Cyclosporine A is strictly contraindicated. Several other drugs including glyburide, rifampicin, fluconazole, ketoconazole, and nevirapine are not recommended for concurrent use. Hormonal contraceptives have reduced effectiveness when used with bosentan.
Bosentan is metabolized primarily by the cytochrome P450 enzymes CYP2C9 and CYP3A4, and it also acts as an inducer of CYP3A4, CYP2C9, and possibly CYP2C19. This means bosentan can both be affected by and affect the metabolism of many other drugs. It is critical that you inform your doctor about all medications you are currently taking, including prescription drugs, over-the-counter medications, and herbal supplements. The following interactions are among the most clinically important.
Major Interactions (Contraindicated or Not Recommended)
| Drug | Interaction | Recommendation |
|---|---|---|
| Cyclosporine A | Markedly increases bosentan plasma levels; decreased cyclosporine levels | Contraindicated — must not be used together |
| Glyburide (Glibenclamide) | Increased risk of liver enzyme elevations; decreased glyburide levels | Not recommended — use alternative diabetes medication |
| Rifampicin | Complex interaction; initial increase then decrease in bosentan levels | Not recommended — avoid concurrent use |
| Fluconazole | Significant increase in bosentan plasma concentrations | Not recommended — use alternative antifungal |
| Ketoconazole | Increases bosentan levels through CYP3A4 inhibition | Not recommended — avoid concurrent use |
| Nevirapine | Potential for reduced bosentan and nevirapine levels | Not recommended — use alternative HIV treatment |
Other Important Interactions
| Drug | Effect | Clinical Advice |
|---|---|---|
| Hormonal contraceptives | Bosentan induces CYP enzymes, reducing contraceptive efficacy | Not reliable as sole contraception — add barrier method |
| Sildenafil | Sildenafil levels decrease (~60%); bosentan levels may increase slightly | Monitor; dose adjustment may be needed |
| Tadalafil | Tadalafil levels decrease; bosentan levels may increase | Monitor; dose adjustment may be needed |
| Warfarin | Bosentan may alter warfarin metabolism | Monitor INR closely; dose adjustment may be needed |
| Simvastatin | Reduced simvastatin plasma levels (~50%) | Monitor cholesterol; consider dose adjustment |
| Sirolimus / Tacrolimus | Potential for altered levels of both drugs | Not recommended — close monitoring if unavoidable |
| HIV antiretrovirals | Complex interactions with protease inhibitors | Specialist management required; monitor carefully |
Always tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, including over-the-counter medications, vitamins, and herbal supplements. This is particularly important before starting Bosentan Sandoz, as even seemingly minor medications may interact with bosentan.
What Is the Correct Dosage of Bosentan Sandoz?
Adults start with 62.5 mg twice daily for 4 weeks, then increase to 125 mg twice daily. Children aged 1 year and older receive weight-based dosing at 2 mg/kg twice daily. Treatment must only be initiated by a specialist experienced in managing PAH.
Always take Bosentan Sandoz exactly as your doctor has prescribed. Treatment should only be started and supervised by a doctor experienced in treating pulmonary arterial hypertension or systemic sclerosis. The dose is carefully titrated upward to minimize the risk of liver toxicity and other adverse effects.
Adults
Standard Adult Dosing Regimen
Weeks 1–4 (initiation): 62.5 mg twice daily (morning and evening)
Week 5 onward (maintenance): 125 mg twice daily (morning and evening), depending on your response
Tablets should be swallowed whole with water and may be taken with or without food. Take the tablets at approximately the same times each day.
| Phase | Dose | Frequency | Duration |
|---|---|---|---|
| Initiation | 62.5 mg | Twice daily | First 4 weeks |
| Maintenance | 125 mg | Twice daily | Ongoing |
Children and Adolescents
Bosentan Sandoz is approved for children aged 1 year and older with pulmonary arterial hypertension. The dose is based on body weight. It is not recommended for children with systemic sclerosis and digital ulcers.
Pediatric Dosing (PAH only)
Starting dose: 2 mg/kg body weight twice daily (morning and evening)
Children weighing less than 31 kg may require a lower-strength bosentan formulation (dispersible 32 mg tablets) to achieve the correct dose. Your doctor will calculate the appropriate dose based on your child's weight.
Elderly Patients
No dose adjustment is generally necessary in elderly patients (65 years and older). However, as elderly patients may have reduced liver or kidney function, closer monitoring may be warranted. Your doctor will assess the appropriate dose based on your overall health status.
Missed Dose
If you forget to take a dose of Bosentan Sandoz, take it as soon as you remember. Then continue taking your tablets at the usual times. Do not take a double dose to make up for a missed dose. If it is almost time for your next dose, skip the missed dose and continue with your regular schedule.
Overdose
If you take more Bosentan Sandoz than prescribed, or if a child accidentally ingests the medication, contact your doctor or go to the nearest emergency department immediately. Symptoms of overdose may include severe headache, nausea, vomiting, and a significant drop in blood pressure. Treatment is supportive, as there is no specific antidote for bosentan.
Abruptly stopping Bosentan Sandoz can cause a worsening of your symptoms. Never stop taking the medication without your doctor's guidance. If treatment needs to be discontinued, your doctor will typically reduce the dose gradually over several days.
What Are the Side Effects of Bosentan Sandoz?
The most clinically significant side effects of Bosentan Sandoz are liver toxicity (affecting more than 1 in 10 patients) and anemia (affecting up to 1 in 10 patients). Common side effects include headache, edema, and flushing. Monthly blood monitoring is essential to detect these problems early.
Like all medicines, Bosentan Sandoz can cause side effects, although not everyone experiences them. It is important to understand the potential adverse effects so that you can recognize symptoms early and report them to your healthcare provider. The most serious side effects relate to liver function and blood counts, which is why regular monitoring is mandatory.
Signs that your liver may not be functioning properly include: nausea, vomiting, fever, abdominal pain, jaundice (yellowing of skin or whites of the eyes), dark-colored urine, itching, lethargy or unusual fatigue, and flu-like symptoms (muscle and joint pain with fever). Tell your doctor immediately if you experience any of these symptoms.
Very Common
- Abnormal liver function (elevated liver enzymes)
- Headache
- Edema (swelling of legs, ankles, or other signs of fluid retention)
Common
- Anemia (low hemoglobin) — may sometimes require blood transfusion
- Flushing (sudden reddening of the face or skin)
- Hypersensitivity reactions (skin inflammation, itching, rash)
- Gastroesophageal reflux disease (acid reflux, heartburn)
- Diarrhea
- Syncope (fainting, brief loss of consciousness)
- Palpitations (rapid or irregular heartbeat)
- Hypotension (low blood pressure)
- Nasal congestion
Uncommon
- Thrombocytopenia (low platelet count)
- Neutropenia / leukopenia (low white blood cell count)
- Elevated liver enzymes with hepatitis (liver inflammation), potentially including worsening of underlying hepatitis and/or jaundice
Rare
- Anaphylaxis (severe generalized allergic reaction)
- Angioedema (swelling, usually around the eyes, lips, tongue, or throat)
- Liver cirrhosis (scarring of the liver)
- Liver failure (serious impairment of liver function)
Blurred vision has also been reported at an unknown frequency (cannot be estimated from available data).
Side effects in children: Children treated with bosentan have the same reported side effects as adults. No additional or different side effects have been identified in the pediatric population.
If you experience any side effects, including those not listed above, tell your doctor or pharmacist. You can also report side effects directly to your national medicines regulatory authority. By reporting side effects, you help provide more information on the safety of this medicine.
How Should You Store Bosentan Sandoz?
Store Bosentan Sandoz out of the sight and reach of children. No special storage conditions are required. Do not use after the expiry date printed on the packaging.
Proper storage of medications is important to ensure they remain effective and safe throughout their shelf life. Follow these guidelines for Bosentan Sandoz:
- Keep out of the sight and reach of children — store in a secure location
- Check the expiry date — do not use after the date marked "EXP" on the carton and blister pack. The expiry date refers to the last day of the stated month.
- No special storage conditions — Bosentan Sandoz does not require any particular temperature or humidity conditions
- Keep in original packaging — protect the tablets in their blister pack until use
- Proper disposal — do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to properly discard medicines no longer in use. This helps protect the environment.
What Does Bosentan Sandoz Contain?
Each Bosentan Sandoz 62.5 mg tablet contains 62.5 mg of bosentan (equivalent to 64.541 mg bosentan monohydrate). Each 125 mg tablet contains 125 mg bosentan (equivalent to 129.082 mg bosentan monohydrate). The tablets are light orange, film-coated, and available in packs of 14, 56, or 112 tablets.
Active Ingredient
The active substance is bosentan (as monohydrate). The monohydrate form is the chemical form used in the tablet manufacturing process, and the stated dose (62.5 mg or 125 mg) refers to the amount of bosentan base.
Inactive Ingredients (Excipients)
Tablet core: Maize starch, pregelatinised maize starch, sodium starch glycolate type A, povidone K30, poloxamer 188, colloidal anhydrous silica, glycerol dibehenate, and magnesium stearate.
Film coating: Opadry orange 21K23007, containing hypromellose, titanium dioxide (E 171), ethylcellulose, triacetin (E 1518), talc (E 553b), yellow iron oxide (E 172), red iron oxide (E 172), and black iron oxide (E 172).
Tablet Appearance
- 62.5 mg tablets: Light orange, round, biconvex, film-coated, 6 mm diameter
- 125 mg tablets: Light orange, oval, biconvex, film-coated, 11 mm long and 5 mm wide
The tablets are packaged in PVC/PVDC/aluminum blister packs inside a cardboard carton. Available pack sizes are 14, 56, or 112 tablets. Not all pack sizes may be marketed in all countries.
Frequently Asked Questions
Medical References
This article is based on the following international medical guidelines, regulatory documents, and peer-reviewed research:
- European Medicines Agency (EMA). Summary of Product Characteristics: Bosentan. Available at: EMA - Tracleer (Bosentan). Updated 2024.
- Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal. 2022;43(38):3618-3731. doi:10.1093/eurheartj/ehac237
- Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension (BREATHE-1). New England Journal of Medicine. 2002;346(12):896-903. doi:10.1056/NEJMoa012212
- British National Formulary (BNF). Bosentan Drug Monograph. Updated 2024.
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd List, 2023.
- Matucci-Cerinic M, Denton CP, Furst DE, et al. Bosentan treatment of digital ulcers related to systemic sclerosis (RAPIDS-2). Annals of the Rheumatic Diseases. 2011;70(1):32-38. doi:10.1136/ard.2010.130658
- Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal. 2016;37(1):67-119.
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