Adult Dosing

Pulmonary arterial hypertension

• Start 5 mg PO qd
• May increase to 10 mg PO qd
• Max: 10 mg/day
• Refer package insert for modifications based on AST/ALT evaluation

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment of pulmonary arterial hypertension (WHO Group I) in patients with WHO Class II - III symptoms, to improve exercise ability and decrease the rate of clinical worsening

• Hypersensitivity to ambrisentan or any component of the product
• Pregnancy
• AST or ALT> 3x ULN at baseline
• Idiopathic pulmonary fibrosis

• To minimize hepatic injury and fetal exposure, ambrisentan is prescribed only through Letairis Education and Access Program (LEAP). Prescribers/pharmacies must be registered and activated with the program. Letairis may be dispensed only to patients who are enrolled in and meet all conditions of LEAP
• Elevations of AST/ALT of at least three times ULN have occured in patients receiving ambrisentan. Aminotransferase elevations >3 x ULN have occured in 0.8% of patients in 12-week trials and in 2.8% of patients including long-term open-label trials of upto one year. This may be accompanied with elevated bilirubin. Measure baseline and monthly AST/ALT; check bilirubin if AST/ALT elevation. Avoid use if baseline AST/ALT >3x ULN since monitoring hepatic injury may be more difficult. If AST/ALT elevations occur with clinical symptoms of hepatic injury or increases in bilirubin 2x ULN, discontinue therapy. There is no experience with treatment re-introduction
• Use is contraindicated during pregnancy due to major birth defect risks. Exclude pregnancy prior to starting therapy. During therapy and for 4wks after D/C, women of child bearing potential must use 2 reliable forms of contraception unless they have a tubal sterilization or Copper T 380A IUD or LNG 20 IUS inserted. Hormonal contraceptives should not be sole method as they may not be effective. Obtain monthly pregnancy tests

Renal Dose Adjustment

• Mild/Moderate impairment: No dose adjustments
• Severe impairment: Dose adjustments not defined

Hepatic Dose Adjustment

• Mild impairment: Use with caution, consider decreasing dose
• Moderate/Severe impairment: Avoid use

• Do not use in pre-existing hepatic impairment (moderate/severe). AST/ALT elevations of > 3x ULN have occured. Measure liver transaminases at baseline, then qmo. If elevated ALT/AST occurs, reduce dosage accordingly
• Fluid retention may occur within weeks after starting therapy. Treat appropriately with a diuretic/fluid management or hospitalization for decompensating heart failure
• Dose related decreases in hemoglobin and hematocrit have occured within the first few weeks of therapy. Monitor Hb at baseline, at 1 month, then q3 periodically
• Serious birth defects were seen consistently when ambrisentan was administered to animals, use is contraindicated in pregnancy
• Perform pregnancy test at baseline, then every month. Women must use two acceptable methods of contraception unless they have had a tubal sterilization or choose to use a Copper T 380A IUD or LNg 20 IUS, in which case no additional contraception is needed

Cautions: Use cautiously in

• Hepatic impairment, mild to moderate
• Hx of liver disease
• Use of hepatotoxic drugs
• CHF
• Decreased hemoglobin
• Fluid retention
• Elderly patients

Pregnancy Category:X

Breastfeeding: Safety unknown. Because of the potential for possible serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

• CV: Palpitations
• CNS: Headache
• DERM: Flushing
• EENT: Nasal congestion, nasopharyngitis, sinusitis
• GI: Constipation, abdominal pain, hepatotoxicity
• RESP: Dyspnea
• MISC: Birth defects, peripheral edema, decreased sperm count, hypersensitivity, anemia

• Endothelin receptor antagonist; has selective affinity for endothelial receptors. Blocks endothelin receptors ETA and ETB present in the vascular endothelium and smooth muscles. It has greater affinity for the A subtype, the receptor which causes vasoconstriction, and thereby improves symptoms of pulmonary artery hypertension
• Metabolized by liver; CYP450: CYP2C19 and 3A4 substrate; UGT: 1A3S, 1A9S, 2B7S substrate
• Non renal excretion
• Half-life: 9 hrs

US Trade Name(s)

• Letairis

US Availability

Letairis

• TABS: 5, 10 mg

Canadian Trade Name(s)

• Volibris

Canadian Availability

Volibris

• TABS: 5, 10 mg

UK Trade Name(s)

• Volibris

UK Availability

Volibris

• TABS: 5, 10 mg

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Cardiovascular

Pulmonary Hypertension Agents

Pulmonary

Pulmonary Hypertension Agents

Endothelin Antagonists

Drug Name: Letairis 10 MG Oral Tablet

Ingredient(s): Ambrisentan

Imprint: GSI;10

Color(s): Red

Shape: Oval

Size (mm): 10.00

Score: 1

Inactive Ingredient(s): N/A

Drug Label Author:
Gilead Sciences, Inc.

DEA Schedule:
Non-Scheduled

Drug Name: Letairis 5 MG Oral Tablet

Ingredient(s): Ambrisentan

Imprint: GSI;5

Color(s): Pink

Shape: Square

Size (mm): 7.00

Score: 1

Inactive Ingredient(s): N/A

Drug Label Author:
Gilead Sciences, Inc.

DEA Schedule:
Non-Scheduled