ambrisentan (Rx)

Brand and Other Names:Letairis
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 5mg
  • 10mg

Pulmonary Arterial Hypertension

Indicated for treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability and delay clinical worsening or in combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability

Initiate treatment at 5 mg PO qDay, with or without tadalafil 20 mg PO qDay

At 4-week intervals, either ambrisentan or tadalafil dose can be increased, as needed and tolerated, not to exceed ambrisentan 10 mg/day or tadalafil 40 mg/day

Dosage Modifications

Coadministration with cyclosporine: Limit ambrisentan to 5 mg/day

Renal impairment

  • Mild-to-moderate: No dosage adjustment required
  • Severe: Not studied
  • Hemodialysis: Not studied

Hepatic impairment

  • Pre-existing
    • Mild: No information available
    • Moderate-to-severe: Not recommended
  • Elevated LFTs after initiating
    • LFTs >5x ULN: Discontinue
    • LFTs increased and accompanied by bilirubin >2x ULN (or signs/symptoms of liver dysfunction): Discontinue

Dosing Considerations

Studies establishing effectiveness included predominantly patients with WHO functional Class II–III symptoms and etiologies of idiopathic or heritable PAH (60%) or PAH associated with connective tissue diseases (34%)

Initiate treatment with ambrisentan in females of reproductive potential only after a negative pregnancy test; obtain monthly pregnancy tests during treatment

Safety and efficacy not established

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Interactions

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              Serious - Use Alternative (7)

              • apalutamide

                apalutamide will decrease the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP2C19 inducer, with drugs that are CYP2C19 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered.

                apalutamide will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

              • cyclosporine

                cyclosporine will increase the level or effect of ambrisentan by Other (see comment). Avoid or Use Alternate Drug. may increase plasma concentrations of OATP substrates

              • idelalisib

                idelalisib will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

              • lasmiditan

                lasmiditan increases effects of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

              • lonafarnib

                lonafarnib will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Lonafarnib may increase the AUC and peak concentration of CYP2C19 substrates. If coadministration unavoidable, monitor for adverse reactions and reduce the CYP2C19 substrate dose in accordance with its approved product labeling.

              • sotorasib

                sotorasib will decrease the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

              • tepotinib

                tepotinib will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

              Monitor Closely (35)

              • apalutamide

                apalutamide will decrease the level or effect of ambrisentan by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces OATP1B1 and may decrease systemic exposure of drugs that are OATP1B1 substrates.

              • bazedoxifene/conjugated estrogens

                ambrisentan will increase the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

                ambrisentan will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              • berotralstat

                berotralstat will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

              • cannabidiol

                cannabidiol will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

              • cenobamate

                cenobamate will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider a dose reduction of CYP2C19 substrates, as clinically appropriate, when used concomitantly with cenobamate.

              • conjugated estrogens

                ambrisentan will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

                ambrisentan will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              • conjugated estrogens, vaginal

                ambrisentan will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

                ambrisentan will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              • crofelemer

                crofelemer increases levels of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

              • cyclosporine

                cyclosporine will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. 2-fold increase in ambrisentan exposure; limit ambrisentan dose to 5 mg/day when coadministered with cyclosporine

              • dabrafenib

                dabrafenib will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              • elagolix

                elagolix will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak CYP2C19 inhibitor. Caution with sensitive CYP2C19 substrates.

                elagolix will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              • eliglustat

                eliglustat increases levels of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.

              • elvitegravir/cobicistat/emtricitabine/tenofovir DF

                elvitegravir/cobicistat/emtricitabine/tenofovir DF increases effects of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

              • eslicarbazepine acetate

                eslicarbazepine acetate will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              • etonogestrel

                ambrisentan will increase the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • fedratinib

                fedratinib will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

              • fexinidazole

                fexinidazole will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              • fostamatinib

                fostamatinib will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp substrates. Monitor for toxicities of the P-gp substrate drug that may require dosage reduction when given concurrently with fostamatinib.

              • fostemsavir

                fostemsavir will increase the level or effect of ambrisentan by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits OATP1B1/3 transporter. If possible, avoid coadministration or modify dose of OATP1B1/3 substrates coadministered with fostemsavir.

              • glecaprevir/pibrentasvir

                glecaprevir/pibrentasvir will increase the level or effect of ambrisentan by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

                glecaprevir/pibrentasvir will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

              • iloperidone

                iloperidone increases levels of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

              • istradefylline

                istradefylline will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

              • ivacaftor

                ivacaftor increases levels of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              • letermovir

                letermovir increases levels of ambrisentan by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

              • lumacaftor/ivacaftor

                lumacaftor/ivacaftor, ambrisentan. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

              • mitotane

                mitotane decreases levels of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

              • ponatinib

                ponatinib increases levels of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              • rifampin

                rifampin will decrease the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

                rifampin will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration was associated with a transient 2-fold increase in ambrisentan AUC; however, by day 7, rifampin had no clinically important effect on ambrisentan. Use with caution.

              • rucaparib

                rucaparib will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP2C19 substrates, if clinically indicated.

              • sarecycline

                sarecycline will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

              • sofosbuvir/velpatasvir

                sofosbuvir/velpatasvir increases levels of ambrisentan by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

              • stiripentol

                stiripentol will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of CYP2C19 substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

                stiripentol will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

              • tecovirimat

                tecovirimat will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Monitor for adverse effects if coadministered with sensitive substrates of these enzymes.

              • triclabendazole

                triclabendazole will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. If plasma concentrations of the CYP2C19 substrates are elevated during triclabendazole, recheck plasma concentration of the CYP2C19 substrates after discontinuation of triclabendazole.

              • tucatinib

                tucatinib will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

              Minor (42)

              • amiodarone

                amiodarone will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

              • atazanavir

                atazanavir will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • bosentan

                bosentan will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • carbamazepine

                carbamazepine will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • clarithromycin

                clarithromycin will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

                clarithromycin will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

              • dexamethasone

                dexamethasone will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • dronedarone

                dronedarone will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

              • efavirenz

                efavirenz will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • erythromycin base

                erythromycin base will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

              • erythromycin ethylsuccinate

                erythromycin ethylsuccinate will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

              • erythromycin lactobionate

                erythromycin lactobionate will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

              • erythromycin stearate

                erythromycin stearate will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

              • esomeprazole

                esomeprazole will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

              • fluconazole

                fluconazole will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

              • fosphenytoin

                fosphenytoin will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • indinavir

                indinavir will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • isoniazid

                isoniazid will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

                isoniazid will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • itraconazole

                itraconazole will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • ketoconazole

                ketoconazole will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

                ketoconazole will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

              • modafinil

                modafinil will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

                modafinil will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • nefazodone

                nefazodone will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • nelfinavir

                nelfinavir will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • nevirapine

                nevirapine will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • nicardipine

                nicardipine will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

              • omeprazole

                omeprazole will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

              • pentobarbital

                pentobarbital will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • phenobarbital

                phenobarbital will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • phenytoin

                phenytoin will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • posaconazole

                posaconazole will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • primidone

                primidone will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • quinidine

                quinidine will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

              • ranolazine

                ranolazine will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

              • ribociclib

                ribociclib will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • rifabutin

                rifabutin will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • rifapentine

                rifapentine will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • shepherd's purse

                shepherd's purse, ambrisentan. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

              • simvastatin

                simvastatin will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

              • St John's Wort

                St John's Wort will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • tolvaptan

                tolvaptan will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

              • verapamil

                verapamil will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

              • voclosporin

                voclosporin will increase the level or effect of ambrisentan by Other (see comment). Minor/Significance Unknown. Information suggests voclosporin (an OATP1B1 inhibitor) may increase in the concentration of OATP1B1 substrates is possible. Monitor for adverse reactions of OATP1B1 substrates when coadministered with voclosporin.

              • voriconazole

                voriconazole will increase the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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              Adverse Effects

              >10%

              Peripheral edema (17%)

              Headache (15%)

              1-10%

              Nasal congestion (6%)

              Palpitations (5%)

              Constipation (4%)

              Dyspnea (4%)

              Flushing (4%)

              Abdominal pain (3%)

              Nasopharyngitis (3%)

              Sinusitis (3%)

              Postmarketing Reports

              Anemia

              Dizziness

              Fatigue

              Fluid retention

              Heart failure (associated with fluid retention)

              Nausea

              Vomiting

              Increased liver aminotransferases (ALT, AST)

              Hypersensitivity (eg, angioedema, rash)

              Symptomatic hypotension

              Hepatotoxicity

              Liver failure

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              Warnings

              Black Box Warnings

              Embryo-fetal toxicity

              • Do not administer ambrisentan to a pregnant female because it may cause fetal harm
              • Females of reproductive potential: Exclude pregnancy before starting treatment, monthly during treatment, and 1 month after stopping treatment
              • Prevent pregnancy during treatment and for 1 month after stopping treatment by using acceptable methods of contraception
              • For all female patients, Letairis is available only through a restricted program called the Letairis Risk Evaluation and Mitigation Strategy (REMS)

              Contraindications

              Pregnancy

              Idiopathic pulmonary fibrosis

              Cautions

              Fetal harm when administered during pregnancy and is contraindicated for use in females who are pregnant (see Pregnancy and Black Box Warnings)

              Caution with hepatic impairment; may be associated with rare cases of hepatic cirrhosis with prolonged use; not recommended in patients with moderate-to-severe hepatic impairment

              Discontinue in patients with elevated aminotransferases >5x ULN, or if elevations are accompanied by bilirubin >2X ULN, or signs/symptoms of liver dysfunction

              Reports of decreased hemoglobin concentrations from baseline that persisted for up to 4 yr of treatment; these decreases were observed within first few weeks of treatment, and stabilized thereafter; the cause of the decrease in hemoglobin is unknown, but it does not appear to result from hemorrhage or hemolysis; measure hemoglobin prior to initiation of therapy, at one month, and periodically thereafter; initiation of therapy is not recommended for patients with clinically significant anemia; if a clinically significant decrease in hemoglobin is observed and other causes have been excluded, consider discontinuing therapy

              Coadministration with cyclosporine or CYP3A4 or CYP2C19 inhibitors

              Peripheral edema is known class effect of endothelin receptor antagonists, and also a clinical consequence of pulmonary arterial hypertension (PAH) and worsening PAH; fluid retention in patients with pulmonary hypertension, occurring within weeks of initiating therapy reported; if clinically significant fluid retention develops, with or without associated weight gain, further evaluate to determine cause, such as ambrisentan or underlying heart failure, possible need for specific treatment or discontinuation of therapy

              Risk of fluid retention and peripheral edema; more common in combination with tadalafil, than with ambrisentan or tadalafil alone

              Decreased sperm counts observed in human and animal studies with another endothelin receptor antagonist and in animal fertility studies with ambrisentan; therapy may have an adverse effect on spermatogenesis; counsel patients about potential effects on fertility

              Development of acute pulmonary edema during therapy initiation may occur; if patient develops acute pulmonary edema during initiation of therapy with vasodilating agents such as ambrisentan, the possibility of pulmonary veno-occlusive disease should be considered, and if confirmed therapy should be discontinued.

              Restricted Distribution Program

              • Because of risk of birth defects, available only through restricted distribution program called the Ambrisentan REMS, by calling 1-888-417-3172; only prescribers and pharmacies certified with Ambrisentan REMS may prescribe and distribute ambrisentan or the brand Letairis
              • Requirements of the REMS program include the following:
                • Prescribers must be certified with the program by enrolling and completing training
                • All females, regardless of reproductive potential, must enroll in the Ambrisentan REMS program prior to initiating treatment
                • Male patients are not enrolled in the REMS
                • Females of reproductive potential must comply with the pregnancy testing and contraception requirements
                • Pharmacies that dispense ambrisentan must be certified with the program and must dispense to female patients who are authorized to receive ambrisentan
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              Pregnancy & Lactation

              Pregnancy

              Based on data from animal reproduction studies, fetal harm may occur when administered to a pregnant woman and is contraindicated during pregnancy

              There are limited data on use in pregnant women

              Advise patient of the potential hazard to a fetus

              Animal data

              • In animal reproduction studies, ambrisentan was teratogenic in rats and rabbits at doses which resulted in exposures of 3.5 and 1.7 times, respectively, the human dose of 10 mg/day

              Contraception

              • Female patients of reproductive potential must use acceptable methods of contraception during treatment and for 1 month after stopping treatment
              • Patients should choose one highly effective form of contraception (intrauterine device [IUD], contraceptive implant, or tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods)
              • If a partner’s vasectomy is one method of contraception, a hormone or barrier method must be used along with this method
              • Counsel patients on pregnancy planning and prevention, including emergency contraception, or designate counseling by another healthcare provider trained in contraceptive counseling

              Infertility

              • Males: Based on findings and preclinical data, endothelin receptor antagonists have an adverse effect on spermatogenesis; counsel patients about the potential effects on fertility

              Lactation

              Unknown whether present in human milk

              Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              High affinity endothelin (ETa) receptor subtype antagonist, resulting in inhibition of vasoconstriction

              Two receptor subtypes, ETA and ETB, mediate the effects of ET-1 in the vascular smooth muscle and endothelium

              Primary actions of ETA are vasoconstriction and cell proliferation, while the predominant actions of ETB are vasodilation, antiproliferation, and ET-1 clearance

              Absorption

              Peak Plasma Time: 2 hr

              Distribution

              Protein Bound: 99%

              Metabolism

              Substrate of hepatic CYP3A4, CYP2C19, UGTs (1A9S, 2B7S, and 1A3S)

              Elimination

              Half-life: 15 hr

              Excretion: Predominantly nonrenal

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              Administration

              Oral Administration

              Administer with or without food

              Swallow whole, do not split, crush, or chew tablets

              Storage

              Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F)

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              Images

              BRAND FORM. UNIT PRICE PILL IMAGE
              ambrisentan oral
              -
              10 mg tablet
              ambrisentan oral
              -
              10 mg tablet
              ambrisentan oral
              -
              5 mg tablet
              ambrisentan oral
              -
              5 mg tablet
              ambrisentan oral
              -
              10 mg tablet
              ambrisentan oral
              -
              5 mg tablet
              ambrisentan oral
              -
              10 mg tablet
              ambrisentan oral
              -
              5 mg tablet
              ambrisentan oral
              -
              10 mg tablet
              ambrisentan oral
              -
              5 mg tablet
              Letairis oral
              -
              10 mg tablet
              Letairis oral
              -
              5 mg tablet

              Copyright © 2010 First DataBank, Inc.

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              Patient Handout

              Patient Education
              ambrisentan oral

              AMBRISENTAN - ORAL

              (AM-bri-SEN-tan)

              COMMON BRAND NAME(S): Letairis

              WARNING: This medication must not be used during pregnancy because it can harm an unborn baby. See also Precautions section.For female patients to receive this medication, all doctors, pharmacists, and female patients must agree to, understand, and carefully follow the requirements of the Ambrisentan Shared System or PS-Ambrisentan Shared System REMS Programs. These requirements apply in the United States. If you live in Canada or any other country, consult your doctor and pharmacist for your country's regulations. Consult your doctor or pharmacist for more details about these programs and about the risks and benefits of using this medication.

              USES: Ambrisentan is used to treat high blood pressure in the lungs (pulmonary arterial hypertension). This condition is thought to be caused by increased levels of a certain natural substance (endothelin-1). This medication blocks the effects of endothelin-1, thereby helping to decrease the blood pressure in the lungs, slow the worsening of symptoms, and improve your ability to exercise.

              HOW TO USE: This drug is controlled through a special program. A program worker will call you each month to make sure that you have gotten a pregnancy test if you are a woman who may become pregnant. See also Warning and Precautions sections.Read the Medication Guide provided by your pharmacist before you start using ambrisentan and each time you get a refill. If you have any questions, consult your doctor or pharmacist.Take this medication by mouth with or without food, usually once daily or as directed by your doctor. Do not crush, chew, or break the tablets.The dosage is based on your medical condition, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.Do not stop taking this medication without consulting your doctor. Some conditions may become worse when the drug is suddenly stopped. Your dose may need to be gradually decreased.Women who are pregnant or who may become pregnant should not handle the tablets or breathe the dust from this medication.Tell your doctor if your condition persists or worsens.

              SIDE EFFECTS: Stuffy nose, runny nose, or flushing may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: fast heartbeat, extreme tiredness, swelling ankles/feet, sudden/unexplained weight gain.Other medications that are like ambrisentan may rarely cause very serious liver problems. Tell your doctor right away if you develop symptoms of liver disease, including: persistent nausea/vomiting, loss of appetite, severe stomach/abdominal pain, dark urine, yellowing eyes/skin.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

              PRECAUTIONS: Before taking ambrisentan, tell your doctor or pharmacist if you are allergic to it; or to other endothelin receptor blockers (e.g., bosentan); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, certain lung conditions (pulmonary fibrosis), anemia.Older adults may be at greater risk for swelling ankles/feet while using this drug.This medication can affect fertility in males. Ask your doctor for more details.This medication must not be used during pregnancy. It may harm an unborn baby. If you are planning pregnancy, become pregnant, or think you may be pregnant, tell your doctor right away. Women who may become pregnant must have a negative pregnancy test before starting this medication, once a month while taking it, and for 1 month after stopping the medication. Consult your doctor for more details and to discuss reliable forms of birth control. Unless otherwise directed by your doctor, it is recommended that at least 2 reliable forms of birth control (e.g., birth control pills, condoms) be used while taking this medication and for 1 month after stopping the medication. Birth control should still be used, even if your partner had a vasectomy.It is not known whether this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this medication is not recommended. Consult your doctor before breast-feeding.

              DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

              OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe dizziness.

              NOTES: Do not share this medication with others.Laboratory and/or medical tests (such as liver function test, monthly pregnancy test, hemoglobin level) will be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

              MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

              STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

              Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

              IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

              To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

              Adding plans allows you to:

              • View the formulary and any restrictions for each plan.
              • Manage and view all your plans together – even plans in different states.
              • Compare formulary status to other drugs in the same class.
              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.