Names and pronunciation
(am-bri-sen′tan) Letairis, Volibris
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Drug reference
(am-bri-sen′tan) Letairis, Volibris
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Func. class.: Antihypertensive
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ACTION: Endothelin-A receptor antag- onist; endothelin-A is a vasoconstrictor
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USES: Pulmonary arterial hyperten- A sion, alone or in combination with other antihypertensives in WHO class II (sig- nificant exertion), III (mild exertion)
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CONTRAINDICATIONS: Breast- feeding, hypersensitivity, idiopathic pul- monary fibrosis (IPF)
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Black Box Warning: Pregnancy Precautions: Children, females, geriat- ric patients, hepatitis, anemia, heart fail- ure, jaundice, peripheral edema, hepatic disease, pulmonary disease Black Box Warning: Only those facilities enrolled in the LEAP program (866-664- 5327) may administer this product • Store in tight container at room tem- perature Black Box Warning: Assess pregnancy status before giving this product and monthly and 1 mo after concluding ther- apy; pregnancy • Hepatotoxicity: nausea, vomiting, ab- dominal pain/cramping, jaundice, an- orexia, itching • Beers: use in older adults cautiously; may exacerbate syncope Black Box Warning: To notify if pregnancy is planned or suspected (if pregnant, product will need to be discontinued, preg- nancy test done monthly); to use 2 contra- ception methods while taking this product and for 1 mo after concluding therapy • Not to use OTC products, including herbs, supplements, unless approved by prescriber • To take tablet whole; not to crush, chew • To report to prescriber immediately: dizziness, faintness, chest pain, palpita- tions, uneven or rapid heart rate, head- ache, edema, weight gain • To report hepatic dysfunction: nau- sea/vomiting, anorexia, fatigue, jaundice, right upper quadrant abdominal pain, itching, fever, malaise
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SIDE EFFECTS CNS: Headache, fever, flushing, fatigue CV: Orthostatic hypotension, hypoten- sion, peripheral edema, palpitations EENT: Sinusitis, rhinitis GI: Abdominal pain, constipation, anorexia, hepatotoxicity GU: Decreased sperm counts HEMA: Anemia INTEG: Rash, angioedema RESP: Pharyngitis, dyspnea, pulmonary edema, veno-occlusive disease (VOD)
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INTERACTIONS • Possibly increase ambrisentan: cimeti- dine, clopidogrel, efavirenz, felbamate, FLUoxetine, modafinil, OXcarbazepine, ticlopidine Increase: hypotension—other antihyper- tensives, diuretics, MAOIs Increase: ambrisentan—CYP3A4 inhibi- tors (amprenavir, aprepitant, atazanavir, clarithromycin, conivaptan, cycloSPORINE, dalfopristin, danazol, darunavir, erythro- mycin, estradiol, imatinib, itraconazole, ketoconazole, nefazodone, nelfinavir, qui- nupristin, ritonavir, RU-486, saquinavir, tamoxifen, telithromycin, troleandomycin, zafirlukast); CYP2C19/CYP3A4 (chloram- phenicol, delavirdine, fluconazole, fluvox- aMINE, isoniazid, voriconazole) Decrease: ambrisentan—CYP3A4 induc- ers (carBAMazepine, PHENobarbital, phe- nytoin, rifAMPin) Decrease: ambrisentan absorption—meflo- quine, niCARdipine, propafenone, quiNI- Dine, ranolazine, tacrolimus, testosterone Drug/Herb • Need for ambrisentan dosage change: St. John’s wort, ephedra (ma huang) Drug/Food • Avoid use with grapefruit products Drug/Lab Test Increase: LFTs, bilirubin Decrease: Hct, HB
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DOSAGE AND ROUTES • Adult: PO 5 mg/day; may increase q4wk to max 10 mg/day if needed Hepatic dose • Adult: PO Discontinue if AST/ALT >5× ULN, or if elevations are accompanied by bilirubin >2× ULN, or other signs of liver dysfunction
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Available forms: Tablets 5, 10 mg
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Administer: • Do not break, crush, chew tablets • Daily with a full glass of water without regard to food • Do not discontinue abruptly
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Assess: • Pulmonary status: improvement in breathing, ability to exercise; pulmonary edema that may indicate veno-occlusive disease • Blood studies: CBC with differential; Hct, HB may be decreased • Liver function tests: AST, ALT, bilirubin
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Evaluate: • Therapeutic response: decrease in B/P; decreased shortness of breath
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • The importance of complying with dosage schedule even if feeling better • The importance of follow-up with labs • That sperm count may be decreased
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PHARMACOKINETICS Rapidly absorbed, peak 2 hr, protein binding 99%, metabolized by CYP3A4, CYP2C19, UGTa, terminal half-life 15 hr, effective half-life 9 hr
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• Adult: PO 5 mg/day; may increase q4wk to max 10 mg/day if needed Hepatic dose
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• Adult: PO Discontinue if AST/ALT >5× ULN, or if elevations are accompanied by bilirubin >2× ULN, or other signs of liver dysfunction
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