Pronunciation:

am-bri-SEN-tan

Brand Names:

• Letairis

Dosage Forms:

• Tablet

Warnings:

Embryo-fetal toxicityDo not administer ambrisentan to a pregnant female because it may cause fetal harm. Ambrisentan 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 ambrisentan. Females of reproductive potential must use acceptable methods of contraception during treatment with ambrisentan and for one month after treatment. Obtain monthly pregnancy tests during treatment and 1 month after discontinuation of treatment.Because of the risks of embryo-fetal toxicity, for all female patients, ambrisentan is only available through a restricted program under a Risk Evaluation and Mitigation (REMS) called the Ambrisentan REMS .

Classifications:

Therapeutic—

Antihypertensive

Pharmacologic—

Endothelin Receptor Antagonist

Uses of This Medicine:

Ambrisentan is used to treat symptoms of pulmonary arterial hypertension, which is high blood pressure in the main artery that carries blood from the right side of the heart (the ventricle) to the lungs, to improve your ability to exercise and slow down the worsening of your condition. It is also used together with tadalafil to decrease the risk of disease progression and hospitalization, and to improve exercise ability. When the small blood vessels in the lungs become more resistant to blood flow, the right ventricle must work harder to pump enough blood through the lungs. Ambrisentan works by relaxing these blood vessels and increasing the supply of blood to the lungs, which reduces the workload of the heart.

This medicine is available only through a special restricted distribution program called the Letairis® REMS (Risk Evaluation and Mitigation Strategy) Program.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of ambrisentan in the pediatric population. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of ambrisentan in the elderly. However, elderly patients are more likely to have peripheral edema (swelling in the arms or legs), which may require caution in patients receiving ambrisentan.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Sparsentan

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Azathioprine
• Cyclosporine
• Levoketoconazole
• Mercaptopurine
• Methotrexate
• Simeprevir

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia (low red blood cells) or
• Heart failure or
• Liver disease, mild—Use with caution. May make these conditions worse.

• Idiopathic pulmonary fibrosis (IPF), including IPF patients with pulmonary hypertension—Should not be used in patients with this condition.

• Liver disease, moderate or severe—Use is not recommended in patients with this condition.

Proper Use of This Medicine:

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. Also, do not stop taking this medicine without checking first with your doctor.

It is very important that you understand the requirements of the Letairis® REMS program, and become familiar with the Letairis® Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions. You might be asked to sign a form to show that you understand the information.

Swallow the tablet whole. Do not crush, break, or chew it. You may take this medicine with or without food.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For pulmonary arterial hypertension:
    • Adults—At first, 5 milligrams (mg) once a day. Your doctor may increase your dose to 10 mg once a day, as needed.
    • Children—Use and dose must be determined by your doctor.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can cause very serious birth defects. Use a highly effective birth control or 2 forms of effective birth control to keep from getting pregnant while you are using this medicine (even if the medicine is temporarily stopped), and for at least 1 month after your last dose. The most effective forms of birth control are hormone birth control pills, patches, shots, vaginal rings, or implants, or a vasectomy (for men). One of these forms of birth control should be combined with a condom, a diaphragm, or a cervical cap. If a partner’s vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method. If you think you have become pregnant while using this medicine, tell your doctor right away.

If you are a woman who can get pregnant, you must have a negative pregnancy test before you will be allowed to take this medicine. You will also be required to have a pregnancy test every month during your treatment and for 1 month after treatment with this medicine. If you miss a period while you are using this medicine, tell your doctor right away.

This medicine may cause fluid retention (edema) in some patients. Check with your doctor right away if you are gaining weight rapidly, have swelling in your hands, ankles, feet, or all over the body, or if you have trouble breathing while you are using this medicine.

Check with your doctor right away if you start to have nausea, vomiting, fever, dark urine or pale stools, a loss of appetite, stomach pain, or yellow eyes or skin. These could be signs of liver injury.

This medicine may decrease the amount of sperm men make, which may affect their ability to have children. If you plan to have children, talk with your doctor before using this medicine.

Pulmonary edema (swelling in the lungs) may occur with this medicine. Check with your doctor right away if you have chest pain, difficult, fast, or noisy breathing, blue lips and fingernails, pale skin, increased sweating, or coughing that sometimes produces a pink frothy sputum.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Bloating or swelling of the face, arms, hands, lower legs, or feet

rapid weight gain

tingling of the hands or feet

unusual weight gain or loss

Less common

Cough

fast, irregular, pounding, or racing heartbeat or pulse

fever

headache

muscle aches

pain or tenderness around the eyes and cheekbones

sore throat

stuffy or runny nose

tightness of the chest

trouble breathing

unusual tiredness or weakness

Incidence not known

Chest pain

clay colored stools

dark urine

decrease in the amount of urine

decreased appetite

dilated neck veins

extreme tiredness or weakness

irregular breathing

large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals

loss of appetite

nausea

noisy, rattling breathing

pale skin

skin rash, itching

stomach pain or tenderness

troubled breathing at rest

troubled breathing with exertion

vomiting

yellow skin or eyes

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

Blurred vision

confusion

dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position

sweating

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

Difficulty having a bowel movement

feeling of warmth

redness of the face, neck, arms, and occasionally, upper chest

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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