Uptravi

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

You may take selexipag with or without food.

Do not crush, chew, or break a selexipag tablet. Swallow it whole.

You should not stop taking selexipag without your doctor's advice. Stopping suddenly may make your condition worse.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if your next dose is less than 6 hours away. Do not take extra medicine to make up the missed dose.

If you miss doses or forget to take selexipag for 3 or more days, call your doctor before taking another dose. You may need to restart the medicine at a lower dose than you took before.

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.

• Actelion Pharmaceuticals US, Inc.

Serious side effects have been reported with Uptravi including the following:

Pulmonary Veno-Occlusive Disease (PVOD). Uptravi can cause a condition where you have abnormal fluid buildup in your lungs. If this condition develops, you may need to discontinue Uptravi. Tell your doctor if you have any of the following signs or symptoms:

• coughing up blood
• you have a hard time breathing when lying flat
• gurgling or wheezing sounds when breathing
• shortness of breath
• fainting

Do not take Uptravi if you are allergic to Uptravi or to any of its ingredients.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• gemfibrozil.

This list is not complete. Other drugs may interact with selexipag, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Package Insert).1

Inform patients what to do if they miss a dose. 1

Inform patients not to split, crush, or chew tablets. 1

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Loose stools (diarrhea).
• Jaw pain.
• Upset stomach or throwing up.
• Muscle or joint pain.
• Pain in arms or legs.
• Flushing.
• Not hungry.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Uptravi, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Uptravi. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Uptravi (selexipag).

Review Date: October 4, 2017

Pulmonary Arterial Hypertension

Uptravi is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.

Effectiveness was established in a long-term study in PAH patients with WHO Functional Class II-III symptoms.

Patients had idiopathic and heritable PAH (58%), PAH associated with connective tissue disease (29%), PAH associated with congenital heart disease with repaired shunts (10%) [see Clinical Studies (14.1)].

Pregnancy

Risk Summary

There are no adequate and well-controlled studies with Uptravi in pregnant women. Animal reproduction studies performed with selexipag showed no clinically relevant effects on embryofetal development and survival. A slight reduction in maternal as well as in fetal body weight was observed when pregnant rats were administered selexipag during organogenesis at a dose producing an exposure approximately 47 times that in humans at the maximum recommended human dose. No adverse developmental outcomes were observed with oral administration of selexipag to pregnant rabbits during organogenesis at exposures up to 50 times the human exposure at the maximum recommended human dose.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Animal Data

Pregnant rats were treated with selexipag using oral doses of 2, 6, and 20 mg/kg/day (up to 47 times the exposure at the maximum recommended human dose of 1600 mcg twice daily on an area under the curve [AUC] basis) during the period of organogenesis (gestation days 7 to 17). Selexipag did not cause adverse developmental effects to the fetus in this study. A slight reduction in fetal body weight was observed in parallel with a slight reduction in maternal body weight at the high dose.

Pregnant rabbits were treated with selexipag using oral doses of 3, 10, and 30 mg/kg (up to 50 times the exposure to the active metabolite at the maximum recommended human dose of 1600 mcg twice daily on an AUC basis) during the period of organogenesis (gestation days 6 to 18). Selexipag did not cause adverse developmental effects to the fetus in this study.

Lactation

It is not known if Uptravi is present in human milk. Selexipag or its metabolites were present in the milk of rats. Because many drugs are present in the human milk and because of the potential for serious adverse reactions in nursing infants, discontinue nursing or discontinue Uptravi.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Of the 1368 subjects in clinical studies of Uptravi 248 subjects were 65 years of age and older, while 19 were 75 and older. No overall differences were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity cannot be ruled out.

Patients with Hepatic Impairment

No adjustment to the dosing regimen is needed in patients with mild hepatic impairment (Child-Pugh class A).

A once-daily regimen is recommended in patients with moderate hepatic impairment (Child-Pugh class B) due to the increased exposure to selexipag and its active metabolite. There is no experience with Uptravi in patients with severe hepatic impairment (Child-Pugh class C). Avoid use of Uptravi in patients with severe hepatic impairment [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].

Patients with Renal Impairment

No adjustment to the dosing regimen is needed in patients with estimated glomerular filtration rate > 15 mL/min/1.73 m2.

There is no clinical experience with Uptravi in patients undergoing dialysis or in patients with glomerular filtration rates < 15 mL/min/1.73 m2 [see Clinical Pharmacology (12.3)].

NDC 66215-602-06

Uptravi®
selexipag
tablets

200 mcg

Rx only
60 tablets

NDC 66215-610-06

Uptravi®
selexipag
tablets

1000 mcg

Rx only
60 tablets

NDC 66215-628-20

TITRATION PACK

Uptravi®
selexipag
tablets

200 mcg

Rx only
140 tablets

Uptravi®
selexipag
tablets

800 mcg

Rx only
60 tablets

Take Uptravi exactly as prescribed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

You may take Uptravi with or without food.

Do not crush, chew, or break a Uptravi tablet. Swallow it whole.

You should not stop taking Uptravi without your doctor's advice. Stopping suddenly may make your condition worse.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Store at room temperature away from moisture and heat.

Applies to selexipag: oral tablet

General

The most frequently reported side effects included headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, and flushing.[Ref]

Nervous system

Very common (10% or more): Headache (up to 65%)
Frequency not reported: Burning sensation[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (up to 42%), nausea (up to 34%), vomiting (up to 18%)
Common (1% to 10%): Abdominal pain, dyspepsia, abdominal discomfort
Frequency not reported: Ascites[Ref]

Musculoskeletal

Very common (10% or more): Jaw pain (26%), pain in extremity (up to 17%), myalgia (up to 16%), arthralgia (up to 11%)
Common (1% to 10%): Musculoskeletal pain, neck pain
Frequency not reported: Bone pain[Ref]

Cardiovascular

Very common (10% or more): Flushing (up to 12%), sinus tachycardia (up to 11.3%)
Common (1% to 10%): Hypotension
Frequency not reported: Hot flush[Ref]

Dermatologic

Very common (10% or more): Rash (11%)
Common (1% to 10%): Urticaria, erythema[Ref]

Respiratory

Very common (10% or more): Nasopharyngitis (13%)
Common (1% to 10%): Nasal congestion
Frequency not reported: Pulmonary veno-occlusive disease[Ref]

Endocrine

Common (1% to 10%): Hyperthyroidism, thyroid stimulating hormone decreased[Ref]

Hematologic

Common (1% to 10%): Anemia, hemoglobin decreased[Ref]

Metabolic

Common (1% to 10%): Appetite decreased[Ref]

Ocular

Common (1% to 10%): Eye pain, retinal disorder[Ref]

Oncologic

Common (1% to 10%): Malignancy[Ref]

Other

Common (1% to 10%): Asthenia, pyrexia, pain, influenza, weight decreased[Ref]

Renal

Frequency not reported: Acute renal failure

Some side effects of Uptravi may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.