Letairis (ambrisentan)

WARNING

EMBRYO-FETAL TOXICITY

Do not administer Letairis to a pregnant female because it may cause fetal harm. Letairis is very likely to produce serious birth defects if used by pregnant females, as this effect has been seen consistently when it is administered to animals.

Exclude pregnancy before the initiation of treatment with Letairis. Females of reproductive potential must use acceptable methods of contraception during treatment with Letairis and for one month after treatment. Obtain monthly pregnancy tests during treatment and 1 month after discontinuation of treatment.

Because of the risk of embryo-fetal toxicity, females can only receive Letairis through a restricted program called the Letairis REMS program.

Letairis can cause serious side effects including:

• Swelling all over the body (fluid retention) can happen within weeks after starting Letairis. Tell your doctor right away if you have any unusual weight gain, tiredness, or trouble breathing while taking Letairis. These may be symptoms of a serious health problem. You may need to be treated with medicine or need to go to the hospital.
• Decreased sperm count. Decreased sperm counts have happened in some men taking a medicine that is like Letairis. A decreased sperm count may affect the ability to father a child. Tell your doctor if being able to have children is important to you.
• Low red blood cell levels (anemia) can happen during the first weeks after starting Letairis. If this happens, you may need a blood transfusion. Your doctor will do blood tests to check your red blood cells before starting Letairis. Your doctor may also do these tests during treatment with Letairis.

The most common side effects of Letairis include:

• swelling of hands, legs, ankles and feet (peripheral edema)
• stuffy nose (nasal congestion)
• inflamed nasal passages (sinusitis)
• hot flashes or getting red in the face (flushing)

Some medicines that are like Letairis can cause liver problems. Tell your doctor if you get any of these symptoms of a liver problem while taking Letairis:

• loss of appetite
• nausea or vomiting
• fever
• achiness
• generally do not feel well
• pain in the upper right stomach (abdominal) area
• yellowing of your skin or the whites of your eyes
• dark urine
• itching

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of Letairis. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Adult Dosage

Initiate treatment at 5 mg once daily, with or without tadalafil 20 mg once daily. At 4-week intervals, either the dose of Letairis or tadalafil can be increased, as needed and tolerated, to Letairis 10 mg or tadalafil 40 mg.

Do not split, crush, or chew tablets.

Pregnancy Testing In Females Of Reproductive Potential

Initiate treatment with Letairis in females of reproductive potential only after a negative pregnancy test. Obtain monthly pregnancy tests during treatment.

Multiple dose coadministration of ambrisentan and cyclosporine resulted in an approximately 2-fold increase in ambrisentan exposure in healthy volunteers; therefore, limit the dose of ambrisentan to 5 mg once daily when coadministered with cyclosporine.

• Letairis may cause fetal harm when administered to a pregnant woman and is contraindicated during pregnancy.
• If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential hazard to a fetus.
• It is not known whether ambrisentan is present in human milk. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from Letairis, a decision should be made whether to discontinue nursing or discontinue Letairis, taking into account the importance of the drug to the mother.