Names and pronunciation
(boh′sen-tan) Tracleer
Source page 181
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Individual generic drug information
Extracted information for bosentan only.
(boh′sen-tan) Tracleer
Source page 181
Func. class.: Vasodilator
Source page 181
Chem. class.: Endothelin receptor antagonist
Source page 181
Do not confuse: Tracleer/Tricor
Source page 181
ACTION: Peripheral vasodilation occurs B via the antagonism of the effect of endothelin on endothelium and vascular smooth muscle
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USES: Pulmonary arterial hyperten- sion with WHO class III, IV symptoms
Source page 181
Unlabeled uses: Septic shock to improve microcirculatory blood flow, functional class II pulmonary arterial hypertension
Source page 181
Extracted information for bosentan only.
CONTRAINDICATIONS: Hyper- sensitivity, CVA, CAD
Source page 181
Black Box Warning: Pregnancy Precautions: Breastfeeding, children, geriatric patients, mitral stenosis, ane- mia, edema, jaundice, hypovolemia, hypotension Black Box Warning: Hepatic disease, requires an experienced clinician, contra- ceptive requirements, pregnancy testing, only those registered with the Tracleer REMS program (866-228-3546) may use this product Black Box Warning: Increase: ALT, AST Decrease: Hb, Hct Black Box Warning: Hepatic toxicity: vom- iting, jaundice; product should be discon- tinued; hepatic studies: AST, ALT, bilirubin; hepatic enzymes may increase; if ALT/AST >3 × and ≤5 × ULN, decrease dose or inter- rupt treatment and monitor AST/ALT q2wk; if bilirubin >2 × ULN or signs of hepatitis or hepatic disease are present, stop treatment Black Box Warning: Experienced cli- nician: must be enrolled in the Tracleer REMS program (866-228-3546) and comply with requirements Black Box Warning: Pregnancy: perform pregnancy testing prior to and during treat- ment in all female patients of childbearing potential, do not use unless a negative se- rum or urine pregnancy test is confirmed during the first 5 days of a normal men- strual period and at least 11 days after the last unprotected sex then monthly; do not use hormonal contraceptive as sole method • Beers: use with caution in older adults; syncope may be exacerbated Black Box Warning: Patient must use nonhormonal contraception during and ≥1 mo after conclusion of treatment and another method, discuss risk of low sperm count, obtain monthly pregnancy test, do not breastfeed • That lab work will be required peri- odically • To take without regard to food; not to take new meds/herbs without prescriber approval; to take in AM or PM HIGH ALERT
Source pages 181, 182, 183
SIDE EFFECTS CNS: Headache, flushing, fatigue, fever CV: Hypotension, chest pain, palpitations, edema of lower limbs, fluid retention GI: Abnormal hepatic function, diarrhea, dyspepsia, hepatotoxicity HEMA: Anemia, leukopenia, neutropenia, lymphopenia, thrombocytopenia INTEG: Pruritus, anaphylaxis, rash, Stevens- Johnson syndrome, toxic epidermal necrolysis MISC: Oligospermia, tumor lysis syn- drome, respiratory infection, arthralgia SYST: Secondary malignancy
Source page 182
INTERACTIONS • Do not coadminister cycloSPORINE with bosentan; bosentan is increased, cy- cloSPORINE is decreased • Do not coadminister glyBURIDE with bosentan; glyBURIDE is decreased sig nificantly, bosentan is also decreased, hepatic enzymes may be increased Increase: bosentan effects—CYP2C9, CYP3A4 inhibitors, avoid using together Increase: bosentan level—ketoconazole, assess for adverse reactions Decrease: effects of warfarin, hormonal contraceptives, statins, use 2 forms of contraception if using with hormonal contraceptives Drug/Lab Test
Source page 182
Extracted information for bosentan only.
DOSAGE AND ROUTES Pulmonary hypertension (pulmonary arterial hypertension WHO Group 1) • Adults/adolescents >40 kg: PO tablet 62.5 mg bid × 4 wk, then increase to 125 mg bid • Adults/adolescents ≤40 kg: PO tablet 62.5 mg bid Persistent pulmonary hypertension of the newborn (PPHN) (unlabeled) • Premature and term neonates ≥34 wk gestation: PO 1 mg/kg/dose bid • Children 21-40 kg (unlabeled): PO tablet 62.5 mg bid • Infants/children 10-20 kg (unlabeled): PO 31.25 mg daily for 4 wk • Infants <10 kg (unlabeled): PO 2 mg/kg/ dose bid, initiate at half of maintenance dose and increase to target dosage after 4 wk • Children 3-12 yr and 25-40 kg: PO tablet for suspension 64 mg bid • Children 3-12 yr and 17-24 kg: PO tablet for suspension 48 mg bid • Children 3-12 yr and 9-16 kg: PO tablet for suspension 32 mg bid • Children 3-12 yr and 4-8 kg: PO tab- let for suspension 16 mg bid Hepatic dose • Adult: PO baseline AST/ALT <3 × ULN no dosage change, monitor LFTs monthly, reduce or interrupt if elevated; AST/ALT >3 and ≤5 × ULN repeat test, if confirmed reduce to 62.5 mg bid or interrupt; moni- tor LFTs q2wk, if interrupted, restart when LFTs <3 × ULN, check LFTs within 3 days; increase in AST/ALT >5 and ≤5 × ULN; during treatment repeat test to confirm, discontinue, monitor LFTs q2wk until LFTs <3 × ULN, restart at starting dose; AST/ ALT >8 × ULN discontinue permanently
Source pages 181, 182
Available forms: Tablets 62.5, 125 mg; tablet for oral suspension 32 mg
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Administer: • Give without regard to meals • Only available through the TAP pro- gram; 866-228-3546 • Use water to disperse tablets for oral suspension • Do not stop product abruptly; taper • Store at room temperature
Source page 182
Extracted information for bosentan only.
Assess: • Serious skin toxicities: angioedema occurring 8-21 days after initiating therapy • B/P, pulse during treatment until stable • Blood studies: Hct, HB after 1 mo, 3 mo, then every 3 mo; may be decreased • Pulmonary hypertension/HF: fluid re- tention, weight gain, increased leg edema; may occur within weeks
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Evaluate: • Therapeutic response: decrease in pulmonary hypertension
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To report jaundice, dark urine, joint pain, fatigue, malaise, bruising, easy bleeding, fluid retention
Source page 183
Extracted information for bosentan only.
PHARMACOKINETICS Metabolized by inducer of CYP2C9, CYP3A4, possibly CYP2C19; metabolized by the liver; terminal half-life 5 hr; steady-state 3-5 days
Source page 182
Filter the extracted dose blocks for this individual drug.
Pulmonary hypertension (pulmonary arterial hypertension WHO Group 1)
• Adults/adolescents >40 kg: PO tablet 62.5 mg bid × 4 wk, then increase to 125 mg bid
Candidate age grouping · source pages 181, 182
Pulmonary hypertension (pulmonary arterial hypertension WHO Group 1)
• Adults/adolescents ≤40 kg: PO tablet 62.5 mg bid Persistent pulmonary hypertension of the newborn (PPHN) (unlabeled)
Candidate age grouping · source pages 181, 182
Pulmonary hypertension (pulmonary arterial hypertension WHO Group 1)
• Premature and term neonates ≥34 wk gestation: PO 1 mg/kg/dose bid
Candidate age grouping · source pages 181, 182
Pulmonary hypertension (pulmonary arterial hypertension WHO Group 1)
• Children 21-40 kg (unlabeled): PO tablet 62.5 mg bid
Candidate age grouping · source pages 181, 182
Pulmonary hypertension (pulmonary arterial hypertension WHO Group 1)
• Infants/children 10-20 kg (unlabeled): PO 31.25 mg daily for 4 wk
Candidate age grouping · source pages 181, 182
Pulmonary hypertension (pulmonary arterial hypertension WHO Group 1)
• Infants <10 kg (unlabeled): PO 2 mg/kg/ dose bid, initiate at half of maintenance dose and increase to target dosage after 4 wk
Candidate age grouping · source pages 181, 182
Pulmonary hypertension (pulmonary arterial hypertension WHO Group 1)
• Children 3-12 yr and 25-40 kg: PO tablet for suspension 64 mg bid
Candidate age grouping · source pages 181, 182
Pulmonary hypertension (pulmonary arterial hypertension WHO Group 1)
• Children 3-12 yr and 17-24 kg: PO tablet for suspension 48 mg bid
Candidate age grouping · source pages 181, 182
Pulmonary hypertension (pulmonary arterial hypertension WHO Group 1)
• Children 3-12 yr and 9-16 kg: PO tablet for suspension 32 mg bid
Candidate age grouping · source pages 181, 182
Pulmonary hypertension (pulmonary arterial hypertension WHO Group 1)
• Children 3-12 yr and 4-8 kg: PO tab- let for suspension 16 mg bid Hepatic dose
Candidate age grouping · source pages 181, 182
Pulmonary hypertension (pulmonary arterial hypertension WHO Group 1)
• Adult: PO baseline AST/ALT <3 × ULN no dosage change, monitor LFTs monthly, reduce or interrupt if elevated; AST/ALT >3 and ≤5 × ULN repeat test, if confirmed reduce to 62.5 mg bid or interrupt; moni- tor LFTs q2wk, if interrupted, restart when LFTs <3 × ULN, check LFTs within 3 days; increase in AST/ALT >5 and ≤5 × ULN; during treatment repeat test to confirm, discontinue, monitor LFTs q2wk until LFTs <3 × ULN, restart at starting dose; AST/ ALT >8 × ULN discontinue permanently
Candidate age grouping · source pages 181, 182