Pulmoten Tablet

Pulmoten Tablet is used for: Pulmonary Arterial Hypertension (PAH)

Oral Pulmonary hypertension Indicated to improve exercise ability and decrease worsening of PAH; effectiveness shown in NYHA II-IV, idiopathic or heritable PAH, connective tissue diseases that result in PAH, and PAH associated with congenital heart disease with left-to-right shunts Adult: >12 yr <40 kg: Initial and maintenance dose is 62.5 mg bid; >40 kg: Initially, 62.5 mg bid for 4 wk, then increased to a maintenance dose of 125 mg bid. Discontinuation of treatment: Consider a reduction in dosage to 62.5 mg PO q12hr for 3-7 days

Pulmonary Arterial Hypertension (PAH) Indicated in children and adolescents aged >3 years with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR) <3 years: Safety and efficacy not established 3 to >12 years >4-8 kg: Maintain dose at 16 mg bid >8-16 kg: Maintain dose at 32 mg bid >16-24 kg: Maintain dose at 48 mg bid >24-40 kg: Maintain dose at 64 mg bid >12 years <40 kg: Maintain dose at 62.5mg bid >40 kg: 62.5mg bid initially for 4 weeks, then increase to maintenance dose 125 mg bid

Renal impairment: No dosage adjustment needed in renal impairment or dialysis patients.

Bosentan should be administered in the morning and evening with or without food.

Hypersensitivity Pregnancy Concomitant cyclosporine or glyburide use

Hepatotoxicity and teratogenicity. Elevations of AST or ALT associated with Bosentan are dose-dependent, occur both early and late in treatment, usually progress slowly, are typically asymptomatic, and usually have been reversible after treatment interruption or cessation. Aminotransferase elevations also may reverse spontaneously while continuing treatment with Bosentan. Liver aminotransferase levels must be measured prior to initiation of treatment and then monthly and therapy adjusted accordingly. Discontinue Bosentan if liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin>2 Based on animal data, Bosentan is likely to cause major birth defects if used during pregnancy Must exclude pregnancy before and during treatment To prevent pregnancy, females of reproductive potential must use two reliable forms of contraception during treatment and for one month after stopping Bosentan. Hypersensitivity of bosentan; observed reactions include Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), anaphylaxis, rash, and angioedema 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 have an adverse effect on spermatogenesis 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 cause and need for specific treatment MONITORING PARAMETERS Monitor hemoglobin before and during treatment (monthly for first 4 months, then every 3 months thereafter ). Monitor liver function before treatment, at monthly intervals during treatment, and 2 weeks after dose increase (reduce dose or suspend treatment if liver enzymes raised significantly)—discontinue if symptoms of liver impairment.

Pregnancy Based on animal data, bosentan may cause fetal harm, including birth defects and fetal death, when administered to pregnant females and is contraindicated during pregnancy Advise pregnant females of potential fetal risk Pregnancy testing Verify the pregnancy status of females of reproductive potential before initiating bosentan, monthly during treatment, and 1 month after stopping treatment If onset of menses delayed or pregnancy is suspected, the patient should contact her physician immediately for pregnancy testing If pregnancy test is positive, the physician and patient must discuss the risks to her, the pregnancy, and the fetus Contraception Bosentan reduces serum levels of estrogen and progestin in oral contraceptives Hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable when coadministered with bosentan Use additional methods of nonhormonal contraception and do not rely on hormonal contraception alone when taking bosentan Throughout treatment and for 1 month after stopping bosentan, females of reproductive potential must use 2 reliable methods of contraception unless the patient has an intrauterine device (IUD) or tubal sterilization, in which case no other contraception is needed Animal studies Oral administration to pregnant rats at 2-times the maximum recommended human dose (MRHD) on a mg/m2 basis caused teratogenic effects in rats, including malformations of the head, mouth, face, and large blood vessels Infertility Males of reproductive potential Based on findings in animals, decreased sperm counts observed in males receiving bosentan that may impair fertility Unknown whether effects on fertility would be reversible Lactation Data from a case report describe the presence of bosentan in human milk; there is insufficient information about effects of this drug on the breastfed infant and no information on effects on milk production Owing to potential for serious adverse reactions (eg, fluid retention, hepatotoxicity) in breastfed infants from therapy, advise women not to breastfeed during treatment

Increased bosentan levels w/ CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, diltiazem), CYP2C9 inhibitors (e.g. amiodarone, fluconazole), tacrolimus. Rifampicin initially increases but subsequently decreases bosentan concentration. May decrease plasma levels of warfarin, statins (e.g. simvastatin, lovastatin), hormonal contraceptives, sildenafil, tadalafil. Potentially Fatal: Increased risk of hepatotoxicity may occur w/ glibenclamide. Ciclosporin markedly increases bosentan concentration. Contraindicated (22) artemether/lumefantrine cariprazine cobimetinib cyclosporine dienogest/estradiol valerate doravirine elvitegravir/cobicistat/emtricitabine/tenofovir DF fostemsavir glyburide isavuconazonium sulfate lonafarnib lorlatinib lumacaftor/ivacaftor lumefantrine mavacamten naloxegol ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) panobinostat regorafenib roflumilast sparsentan vandetanib

Side effects of Bosentan : >10% Hgb decreased; >1 g/dL (57%),Inhibition of spermatogenesis (25%),Headache (16-22%),Nasopharyngitis (11%),Transaminses increased (12%),Respiratory tract infection (22%),Increased transaminases (12%) 1-10% Edema, lower limb (5-8%),Flushing (7-9%),Hypotension (7%),Hepatic abnormalities (4%),Palpitations (4%),Anemia (3%),Dyspepsia (4%),Edema, general (4%),Fatigue (2%),Pruritus (4%) <1% Hyperbilirubinemia,Vasculitis,Jaundice,Leukopenia,Thrombocytopenia,Leukocytoplastic

Competitive antagonist of endothelin-1; blocks endothelin receptors on vascular endothelium and smooth muscle resulting in inhibition of vasoconstriction

Pulmoten 62.5mg Tablet manufactured by UniMed UniHealth Pharmaceuticals Ltd.. Its generic name is Bosentan. Pulmoten is availble in Bangladesh. Farmaco BD drug index information on Pulmoten Tablet is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.