Selexipag

Dosage Forms & Strengths

tablet

• 200mcg
• 400mcg
• 600mcg
• 800mcg
• 1000mcg
• 1200mcg
• 1400mcg
• 1600mcg

Pulmonary Arterial Hypertension

Indicated for pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH

Starting dose: 200 mcg PO BID

Increase dose by increments of 200 mcg BID, usually at weekly intervals, to the highest tolerated dose; not to exceed 1600 mcg BID

If a patient reaches a dose that cannot be tolerated, the dose should be reduced to the previous tolerated dose

Also see Administration section

Dosage Modifications

Renal impairment: No dosage adjustment required

Hepatic impairment

• Mild (Child-Pugh A): No dosage adjustment required
• Moderate (Child-Pugh B): Starting dose is 200 mcg qDay; increase by increments of 200 mcg/day at weekly intervals, as tolerated
• Severe (Child-Pugh C): Avoid use

Dosage Considerations

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

Patients had idiopathic and heritable PAH (58%), PAH associated with connective-tissue disease (29%), or PAH associated with congenital heart disease with repaired shunts (10%)

Safety and efficacy not established

Pregnancy

No adequate and well-controlled studies with selexipag exist in pregnant women

Animal studies

• 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 ~47 times that in humans at the maximum recommended human dose

Lactation

Unknown if distributed in human breast 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 selexipag

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.

Selexipag lowers blood pressure in your lungs by dilating (widening) blood vessels that supply blood to the lungs.

Selexipag is used to treat pulmonary arterial hypertension (PAH). Selexipag helps keep your condition from getting worse and helps lower your risk of needing to be hospitalized for PAH.

Selexipag may also be used for purposes not listed in this medication guide.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

You should not use selexipag if you are allergic to it.

To make sure selexipag is safe for you, tell your doctor if you have:

• a condition called pulmonary veno-occlusive disease (narrowing of the veins that carry blood from the lungs to the heart);
• liver disease;
• a thyroid disorder; or
• kidney disease (or if you are on dialysis).

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether selexipag passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take medications that block the enzyme CYP2C8 such as gemfibrozil (Lopid), fluvoxamine (Luvox), ketoconazole (Nizoral), trimethoprim (Bactrim, Septra)

This is not a complete list of selexipag drug interactions. Ask your doctor or pharmacist for more information.

• Store selexipag tablets at room temperature.
• Keep this and all medications out of the reach of children.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

You should not use selexipag if you are allergic to it.

To make sure selexipag is safe for you, tell your doctor if you have:

• a condition called pulmonary veno-occlusive disease (narrowing of the veins that carry blood from the lungs to the heart);

• liver disease;

• a thyroid disorder; or

• kidney disease (or if you are on dialysis).

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether selexipag passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Usual Adult Dose for Pulmonary Hypertension:

Initial dose: 200 mcg orally twice a day
Maintenance dose: Increase in increments of 200 mcg orally twice a day at weekly intervals to the highest tolerated dose
Maximum dose: 1600 mcg orally twice a day

Comment:
-If the patient reaches a dose that is not well tolerated, reduce to a previously tolerated dose.

Use: For the treatment of pulmonary arterial hypertension (PAH) to delay disease progression and reduce the risk of hospitalization for PAH

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 selexipag, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to selexipag 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.

Pediatric

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

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of selexipag in the elderly.

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.

Interactions with 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 selexipag, 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 selexipag 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.

• Abiraterone Acetate
• Apixaban
• Argatroban
• Bivalirudin
• Citalopram
• Dabigatran Etexilate
• Danaparoid
• Desirudin
• Edoxaban
• Escitalopram
• Fluoxetine
• Fluvoxamine
• Fondaparinux
• Gemfibrozil
• Heparin
• Lepirudin
• Paroxetine
• Phenindione
• Phenprocoumon
• Protein C
• Rivaroxaban
• Sertraline
• Vilazodone
• Vortioxetine

Interactions with Food/Tobacco/Alcohol

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 selexipag. Make sure you tell your doctor if you have any other medical problems, especially:

• Liver disease, moderate—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

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

• Pulmonary venoocclusive disease (narrowing of the veins in the lungs)—Use with caution. May make this condition worse.

• If you have an allergy to selexipag or any part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have liver disease.
• If you are taking gemfibrozil.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with selexipag.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Uptravi: 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1000 mcg, 1200 mcg, 1400 mcg, 1600 mcg

Tablet Therapy Pack, Oral:

Uptravi: 200 mcg (140s) and 800 mcg (60s) (200 ea)

• Prostacyclin
• Prostacyclin IP Receptor Agonist
• Vasodilator

A 40% to 70% increase in exposure to selexipag and its active metabolite was observed in severe renal impairment (estimated glomerular filtration rate ≥15 to <30 mL/minute/1.73 m2).

Pulmonary arterial hypertension: Oral: Initial: 200 mcg twice daily; increase by 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose (maximum dose: 1,600 mcg twice daily). If a dose is not tolerated, reduce dose to previously tolerated dose.

Missed dose: If dose is missed, take dose as soon as possible unless the next dose is within the next 6 hours. If ≥3 days of treatment are missed, restart at a lower dose and then retitrate.

Oral: Administer with or without food; tolerability may be improved when taken with food. Swallow tablets whole; do not split, crush, or chew.