Bosentan

Bosentan tablets are indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1):

• in adults to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with WHO Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%)
  [see Clinical Studies (14.1)]
  .
• in pediatric patients aged 3 years and older with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR), which is expected to result in an improvement in exercise ability.

• Patients older than 12 years of age: initiate at 62.5 mg orally twice daily; for patients weighing greater than 40 kg, increase to 125 mg orally twice daily after 4 weeks. (
  2.2 Recommended Dosage

  Administer bosentan tablets orally following the dosing recommendations in Table 1. Doses above 125 mg twice daily did not appear to confer additional benefit sufficient to offset the increased risk of hepatotoxicity.

  Table 1: Dosing Recommendations

  	Initial 4 weeks	Maintenance (after 4 weeks)
  Patients > 12 years of age and > 40 kg	62.5 mg twice daily	125 mg twice daily
  Patients > 12 years of age and < 40 kg	62.5 mg twice daily	62.5 mg twice daily
  Patients ≤ 12 years of age
  ≥ 4-8 kg	16 mg twice daily	16 mg twice daily
  ˃ 8-16 kg	32 mg twice daily	32 mg twice daily
  ˃ 16-24 kg	48 mg twice daily	48 mg twice daily
  ˃ 24-40 kg	64 mg twice daily	64 mg twice daily
  )
• Patients 12 years of age and younger: dosage is based on weight, see Table 1 (
  2.2 Recommended Dosage

  Administer bosentan tablets orally following the dosing recommendations in Table 1. Doses above 125 mg twice daily did not appear to confer additional benefit sufficient to offset the increased risk of hepatotoxicity.

  Table 1: Dosing Recommendations

  	Initial 4 weeks	Maintenance (after 4 weeks)
  Patients > 12 years of age and > 40 kg	62.5 mg twice daily	125 mg twice daily
  Patients > 12 years of age and < 40 kg	62.5 mg twice daily	62.5 mg twice daily
  Patients ≤ 12 years of age
  ≥ 4-8 kg	16 mg twice daily	16 mg twice daily
  ˃ 8-16 kg	32 mg twice daily	32 mg twice daily
  ˃ 16-24 kg	48 mg twice daily	48 mg twice daily
  ˃ 24-40 kg	64 mg twice daily	64 mg twice daily
  ).
• Reduce the dose and closely monitor patients developing aminotransferase elevations more than 3 × Upper Limit of Normal (ULN). (
  2.1 Required Monitoring

  Healthcare professionals who prescribe bosentan tablets must enroll in the Bosentan REMS Program and must comply with the required monitoring to minimize the risks associated with bosentan tablets

  [see

  Warnings and Precautions (5.3)].

  Obtain a pregnancy test in females of reproductive potential prior to bosentan tablets treatment, monthly during treatment and one month after stopping bosentan tablets. Initiate treatment with bosentan tablets in females of reproductive potential only after a negative pregnancy test

  [see Boxed Warning

  ,

  Contraindications (4.1), Warnings and Precautions (5.3)

  ,

  Use in Specific Populations (8.1, 8.3)]

  .

  Measure liver aminotransferase levels prior to initiation of treatment and then monthly

  [see Warnings and Precautions (5.1)]

  .
  )

Bosentan tablets are available as

Bosentan tablets,

Bosentan tablets,

• Nursing mothers: Choose breastfeeding or bosentan. (
  8.2 Lactation

  Risk Summary

  Data from a case report describe the presence of bosentan in human milk. There is insufficient information about the effects of bosentan on the breastfed infant and no information on the effects of bosentan 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.
  )