Bosentan

Bosentan is a prescription medicine used to treat the symptoms of pulmonary arterial hypertension (PAH).

• Bosentan is available under the following different brand names: Tracleer

Adult and pediatric dosage

Tablet, film-coated

• 62.5mg
• 125 mg

Tablet, for oral suspension

• 32 mg

Pulmonary Arterial Hypertension (PAH)

Adult dosage

• Weightless than 40 kg: Maintain dose at 62.5 mg orally every 12 hours
• Weight more than 40 kg: 62.5 mg orally every 12 hours for 4 weeks and then increased to a maintenance dosage of 125 mg orally every 12 hours
• Discontinuation of treatment: Consider a reduction in dosage to 62.5 mg orally every 12 hours for 3-7 days

Pediatric dosage

• Children below 3 years: Safety and efficacy not established
• Children between 3 to 12 years: 
  • Weighing between 4-8 kg: Maintain dose at 16 mg orally every 12 hours
  • Weighing between 8-16 kg: Maintain dose at 32 mg orally every 12 hours
  • Weighing between 16-24 kg: Maintain dose at 48 mg orally every 12 hours
  • Weighing between 24-40 kg: Maintain dose at 64 mg orally every 12 hours
• Children above 12 years: 
  • Weighing less than 40 kg: Maintain dose at 62.5mg orally every 12 hours
  • Weighing more than 40 kg: 62.5mg orally every 12 hours initially for 4 weeks, then increase to maintenance dose 125 mg orally every 12 hours

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Bosentan include:

• headache,
• joint pain,
• low blood pressure,
• fainting,
• flushing (warmth, redness, or tingly feeling),
• irregular heartbeats,
• stuffy nose,
• sinus pain,
• sneezing, and
• sore throat.

Serious side effects of Bosentan include:

• hives,
• difficulty breathing,
• swelling of face, lips, tongue, or throat,
• skin rash,
• fever,
• swollen glands,
• muscle aches,
• severe weakness,
• unusual bruising,
• yellowing of skin or eyes (jaundice),
• swelling in legs and ankles with or without weight gain,
• lightheadedness,
• pale skin,
• unusual tiredness,
• shortness of breath,
• cold hands and feet,
• nausea,
• vomiting,
• upper stomach pain,
• dark urine,
• anxiety,
• sweating,
• pale skin,
• wheezing,
• gasping for breath,
• cough with foamy mucus,
• chest pain, and
• fast or uneven heart rate.

Rare side effects of Bosentan include:

• none 

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Bosentan has severe interactions with the following drugs:
  • artemether/lumefantrine
  • cariprazine
  • cobimetinib
  • cyclosporine
  • dienogest/estradiol valerate
  • doravirine
  • elvitegravir/cobicistat/emtricitabine/tenofovir DF
  • fostemsavir
  • glyburide
  • isavuconazonium sulfate
  • lonafarnib
  • lorlatinib
  • lumacaftor/ivacaftor
  • lumefantrine
  • naloxegol
  • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
  • panobinostat
  • praziquantel
  • regorafenib
  • roflumilast
  • vandetanib
• Bosentan has serious interactions with at least 123 other drugs.
• Bosentan has moderate interactions with at least 236 other drugs.
• Bosentan has minor interactions with at least 132 other drugs. 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• Hypersensitivity
• Pregnancy
• Concomitant cyclosporine or glyburide use

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Bosentan?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Bosentan?”

Cautions

• Hypersensitivity of bosentan; observed reactions include Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), anaphylaxis, rash, and angioedema
• Monitor LFTs; avoid use if ALT or AST more than 3 times ULN or bilirubin more than 2 times ULN (see Black Box Warnings and Dosage Modifications)
• Pulmonary edema may occur; if signs/symptoms arise, consider possibly associated with pulmonary venoocclusive disease and whether treatment should be discontinued
• Embryo-fetal toxicity reported; see Black Box Warnings and Pregnancy
• Decreased sperm counts have been observed; preclinical data also suggest bosentan and other endothelin receptor antagonists, may hurt spermatogenesis
• A dose-related decrease in hemoglobin and hematocrit may occur with treatment; it is recommended that hemoglobin concentrations be checked after 1, 3 months, and every 3 months thereafter; if a marked decrease in hemoglobin concentration occurs, further evaluation should be undertaken to determine the cause and need for specific treatment

Fluid retention

• Peripheral edema is a known clinical consequence of PAH, worsening PAH, and is also a known effect of bosentan and other endothelin receptor antagonists
• In clinical trials with bosentan, combined adverse events of fluid retention or edema were reported
• Patients required intervention with a diuretic, fluid management, or hospitalization for decompensating heart failure
• If clinically significant fluid retention develops, with or without associated weight gain, further evaluation should be undertaken to determine whether treatment-related or possible underlying heart failure and consider the need for treatment or discontinuation of bosentan
• Monitor hemoglobin levels after 1, 3 months of treatment, then every 3 months thereafter

Drug interactions overview

• Bosentan is metabolized by CYP2C9 and CYP3A; inhibition of these enzymes may increase the plasma concentration of bosentan
• Concomitant administration of a CYP2C9 inhibitor (eg, fluconazole, amiodarone), a strong CYP3A inhibitor (eg, ketoconazole, itraconazole), or a moderate CYP3A inhibitor (eg, amprenavir, erythromycin, fluconazole, diltiazem) will likely lead to large increases in plasma concentrations of bosentan
• Coadministration of such combinations of a CYP2C9 inhibitor plus a strong or moderate CYP3A inhibitor with bosentan is not recommended
• Bosentan is an inducer of CYP3A and CYP2C9; plasma concentrations of drugs metabolized by these two isozymes will be decreased when coadministered bosentan
• Reduces efficacy of hormonal contraceptives

Pregnancy and Lactation

• Based on animal data, bosentan may cause fetal harm, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy; see Contraindications and Black Box Warnings
• Advise pregnant women of the potential risk to a fetus
• The patient should contact her physician immediately for pregnancy testing if the onset of menses is delayed or pregnancy is suspected
• If the pregnancy test is positive, the physician and patient must discuss the risks to her, the pregnancy, and the fetus
• Based on findings in animals, bosentan may impair fertility in males of reproductive potential; It is unknown whether effects on fertility would be reversible

Contraception

• Advise the use of at least 2 reliable methods of contraception (unless tubal sterilization or Copper T 380A IUD or LNG 20 IUD inserted, in which case no other contraception is required)

Lactation

• There are no data on the presence of bosentan in human milk, the effects on the breastfed infant, or the effect on milk production
• Because of the potential for serious adverse reactions, such as fluid retention and hepatotoxicity, in breastfed infants from bosentan, advise women not to breastfeed during treatment with bosentan