UPTRAVI FILM-COATED TABLETS 1000MCG [SIN15287P]

Product Info

UPTRAVI FILM-COATED TABLETS 1000MCG

[SIN15287P]

INDICATIONS

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%).

DOSAGE AND ADMINISTRATION
Treatment should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension (PAH).

Selexipag can be used in combination therapy in patients insufficiently controlled with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE 5) inhibitor, or as monotherapy in patients who are not candidates for these therapies.

Method of administration

The film-coated tablets are to be taken orally in the morning and in the evening. UPTRAVI® should be taken consistently with or without food. Tolerability may be improved when taken with food.

The tablets should not be split, crushed or chewed, and are to be swallowed with some water.

Dosage
Individualised dose titration

The goal is to reach the individually appropriate dose for each patient (the individualised maintenance dose).

The recommended starting dose of UPTRAVI® is 200 micrograms given twice daily, approximately 12 hours apart. The dose is increased in increments of 200 micrograms given twice daily, usually at weekly intervals, until adverse pharmacological effects that cannot be tolerated or medically managed are experienced, or until a maximum dose of 1600 micrograms twice daily is reached. At the beginning of treatment and at each up-titration step it is recommended to take the first dose in the evening. During dose titration, it is recommended not to discontinue treatment in the event of expected pharmacological side effects since they are usually transient or manageable with symptomatic treatment (see ADVERSE EFFECTS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). If a patient reaches a dose that cannot be tolerated the dose should be reduced to the previous dose level.

Individualised maintenance dose

The highest tolerated dose reached during dose titration should be maintained. If the therapy is less tolerated at a given dose over time, symptomatic treatment or a dose reduction to the next lower dose should be considered. PAH patients have variable degrees of IP receptor expression. Differences in maintenance dose of selexipag between individuals may be related to differences in IP receptor expression levels.

Interruptions and discontinuations

If a dose of medication is missed, it should be taken as soon as possible. The missed dose should not be taken if it is almost time for the next scheduled dose (within approximately 6 hours).

If treatment is missed for 3 days or more, UPTRAVI® should be re-started at a lower dose and then titrated.

Dosage adjustment in elderly patients
Elderly (≥ 65 years)
No adjustment to the dosing regimen is needed in elderly patients.

Dosage adjustment in patients with hepatic impairment
No adjustment to the dosing regimen is needed in patients with mild hepatic impairment (i.e., 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. Avoid use of UPTRAVI® in patients with severe hepatic impairment (Child-Pugh class C, see CONTRAINDICATIONS).

Dosage adjustment in patients with renal impairment
No adjustment to the dosing regimen is needed in patients with mild or moderate renal impairment.

No change in starting dose is required in patients with severe renal impairment. Dose titration in these patients should be done with caution.

Dosage adjustment with co-administration of moderate CYP2C8 inhibitors
When co-administered with moderate CYP2C8 inhibitors (e.g., clopidogrel, deferasirox and teriflunomide), reduce the dosing of UPTRAVI® to once daily. Revert to twice daily dosing frequency of UPTRAVI® when co-administration of moderate CYP2C8 inhibitor is stopped (see INTERACTIONS WITH OTHER MEDICINES, in-vivo studies Inhibitors of CYP2C8 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

CONTRAINDICATIONS

UPTRAVI® is contraindicated in patients with:

• known hypersensitivity to the active substance selexipag or to any of the excipients listed in DESCRIPTION – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

• Severe hepatic impairment (Child-Pugh class C).

• Severe coronary heart disease or unstable angina.

• Myocardial infarction within the last 6 months.

• Decompensated cardiac failure if not under close medical supervision.

• Severe arrhythmias.

• Cerebrovascular events (e.g., transient ischaemic attack, stroke) within the last 3 months.

• Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension.

• Concomitant use of strong inhibitors of CYP2C8 (e.g., gemfibrozil).