Farantan

Bosentan Tablet (62.5mg, 125mg)

Introduction

Bosentan is endothelin receptor antagonist that blocks endothelin receptors on endothelium and vascular smooth muscle (stimulation of these receptors is associated with vasoconstriction).
Farantan® tablet _Manufactured by Faran Shimi Pharmaceutical Company_ is available in two dosage strengths, 62.5mg, 125mg. 10 tablets are packed in a blister and 6 blisters are packaged in one box with a leaflet.

Indications

Farantan® is indicated for the treatment of pulmonary artery hypertension (PAH) (WHO Group I) in adults with WHO-FC II, III, or IV symptoms to improve exercise ability and to decrease clinical deterioration; treatment of idiopathic or congenital PAH (WHO Group 1) in pediatric patients ≥3 years to improve pulmonary vascular resistance (PVR), resulting in an improvement in exercise ability.

Important Information

Dosing

• Adults:

<40 kg: Initial and maintenance: 62.5mg twice daily.
≥40 kg: Initial: 62.5mg twice daily; after 4 weeks, may increase to a maximum dose of 125mg twice daily.
Note: When discontinuing treatment, consider a reduction in dosage to 62.5mg twice daily for 3 to 7 days to avoid clinical deterioration, and then stop treatment.

Patient Information for Farantan (Bosentan)

• Pediatrics

Infants and Children <12 years: Initial: 1mg/kg/dose twice daily; increase to a target dose of 2mg/kg/dose twice daily; maximum dose: 125mg/dose.
Children ≥12 years and Adolescents:
>20 to 40kg: Initial: 31.25mg twice daily; increase to a target dose of 62.5mg twice daily.
>40kg: Initial: 62.5mg twice daily; increase to a target dose of 125mg twice daily.

• Renal Impairment:

No dosage adjustment necessary.

• Hepatic Impairment (at treatment initiation):

Mild impairment: No dosage adjustment necessary.
Moderate to Severe impairment: Avoid use.

• Hepatic Impairment (at during treatment): Modification based on transaminase elevation:

Serum bilirubin ≥2 times ULN: Discontinue treatment.
AST/ALT >3 times but ≤5 times ULN: >40 kg: reduce dose to 62.5mg twice daily or interrupt treatment and monitor at least every 2 weeks.
AST/ALT >5 times but ≤8 times ULN: >40 kg: stop treatment. Monitor transaminase levels at least every 2 weeks.
AST/ALT >8 times ULN: Stop treatment and do not reintroduce.

Administration

Administer with or without food.

Major Interactions (Risk X)

Abemaciclib, Antihepaciviral Combination Products, Asunaprevir, Avapritinib, Axitinib, Bedaquiline, Bosutinib, Capmatinib, Cobimetinib, Cyclosporine, Dasabuvir, Deflazacort, Elbasvir, Encorafenib, Entrectinib, Fedratinib, Fluconazole, Glyburide, Grazoprevir, Lemborexant, Letermovir, Lumateperone, Lurbinectedin, Mifepristone, Neratinib, Nisoldipine, Olaparib, Pemigatinib, Pimavanserin, Pretomanid, Ranolazine, Rimegepant, Selpercatinib, Selumetinib, Simeprevir, Sonidegib, Tazemetostat, Ulipristal, Velpatasvir, Venetoclax, Zanubrutinib.

Pregnancy

Farantan® is contraindicated in females who are or may become pregnant.

Breast-Feeding

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended.
• Anticoagulants, axitinib, bosutinib, cabazitaxel, statins, hormonal contraceptives.

Contraindications & Cautions

Contraindications

Hypersensitivity to bosentan or any component of the formulation; concurrent use of cyclosporine or glyburide; women who are or may become pregnant.

Warnings/Precautions

• Fluid retention/peripheral edema: If clinically significant fluid retention develops (with or without weight gain), further evaluation is necessary to determine cause and appropriate treatment or discontinuation of therapy. Use with caution in patients with underlying heart failure due to potential complications from fluid retention.
• Hematologic effects: Monitor hemoglobin prior to treatment initiation, after 1 and 3 months, and every 3 months thereafter. Significant decreases in hemoglobin require further evaluation to determine the cause and specific management.
• Pulmonary veno-occlusive disease: If signs of pulmonary edema occur, consider possibility of pulmonary veno-occlusive disease; may require discontinuation of bosentan.
• Hepatotoxicity: Monitor transaminases at baseline then monthly thereafter.

Side Effects

>10%:
Cardiovascular: Edema (≤11%)
Central nervous system: Headache (15%)
Hepatic: Increased serum ALT (≥3 times ULN: ≤12%; 8 times ULN: ≤2%; dose-related), Increased serum AST (≥3 times ULN: ≤12%; 8 times ULN: ≤2%; dose-related)
Respiratory: Respiratory tract infection (22%)

1% to 10%:
Cardiovascular: Chest pain (5%), syncope (5%), flushing (4%), hypotension (4%), palpitations (4%)
Endocrine & metabolic: Fluid retention (≤2%)
Hematologic & oncologic: Anemia (3%)
Neuromuscular & skeletal: Arthralgia (4%)
Respiratory: Sinusitis (4%)