Pulmonary arterial hypertension (PAH)

Active Ingredient: Riociguat

Indication for Riociguat

Population group: only children (1 year - 12 years old) , adolescents (12 years - 18 years old) , adults (18 years old or older)
Therapeutic intent: Curative procedure

Adults

Adempas, as monotherapy or in combination with endothelin receptor antagonists, is indicated for the treatment of adult patients with pulmonary arterial hypertension (PAH) with WHO Functional Class (FC) II to III to improve exercise capacity.

Efficacy has been shown in a PAH population including aetiologies of idiopathic or heritable PAH or PAH associated with connective tissue disease.

Paediatrics

Adempas is indicated for the treatment of PAH in paediatric patients aged less than 18 years of age and body weight ≥50 kg with WHO Functional Class (FC) II to III in combination with endothelin receptor antagonists.

For this indication, competent medicine agencies globally authorize below treatments:

1 mg 3 times daily for 2 weeks and thereafter individual dose titration every two weeks to a maximum of 2.5 mg 3 times daily

For:

Dosage regimens

Oral, 1 milligrams riociguat, 3 times daily, over the duration of 2 weeks. Afterwards, oral, between 1 milligrams riociguat and 2.5 milligrams riociguat, 3 times daily.

Detailed description

Starting dose

The recommended starting dose is 1 mg 3 times daily for 2 weeks. Doses should be taken 3 times daily approximately 6 to 8 hours apart.

Titration

Dose should be increased by 0.5 mg 3 times daily every two weeks to a maximum of 2.5 mg 3 times daily, if systolic blood pressure is ≥95 mmHg and the patient has no signs or symptoms of hypotension. In some PAH patients, an adequate response on the 6-minute walk distance (6MWD) may be reached at a dose of 1.5 mg 3 times a day. If systolic blood pressure falls below 95 mmHg, the dose should be maintained provided the patient does not show any signs or symptoms of hypotension. If at any time during the up-titration phase systolic blood pressure decreases below 95 mmHg and the patient shows signs or symptoms of hypotension the current dose should be decreased by 0.5 mg 3 times daily.

Maintenance dose

The established individual dose should be maintained unless signs and symptoms of hypotension occur.

The maximum total daily dose is 7.5 mg (i.e., 2.5 mg 3 times daily) for adults patients.

If a dose is missed, treatment should be continued with the next dose as planned.

If not tolerated, dose reduction should be considered at any time.

Treatment discontinuation

In case treatment has to be interrupted for 3 days or more, treatment should be restarted with 1 mg 3 times daily for 2 weeks and continued with the dose titration regimen as described above.

Transitioning between phosphodiesterase-5 (PDE5) inhibitors and riociguat

Sildenafil must be discontinued in adults at least 24 hours prior to administration of riociguat.

Tadalafil must be discontinued at least 48 hours in adults prior to administration of riociguat.

Riociguat must be discontinued in adults at least 24 hours prior to administration of a PDE5 inhibitor.

It is recommended to monitor for signs and symptoms of hypotension after any transition.

Dosage considerations

For patients prone to hypotension, as a precautionary measure, switches between fed and fasted riociguat intake are not recommended because of increased peak plasma levels of riociguat in the fasting compared to the fed state.

1 mg 3 times daily for 2 weeks and thereafter individual dose titration every two weeks to a maximum of 2.5 mg 3 times daily

For:

Dosage regimens

In case that patient weight is ≥ 50 kg, oral, 1 milligrams riociguat, 3 times daily, over the duration of 2 weeks. Afterwards, in case that patient weight is ≥ 50 kg, oral, between 1 milligrams riociguat and 2.5 milligrams riociguat, 3 times daily. The maximum allowed total dose is 7.5 milligrams riociguat daily.

Detailed description

Starting dose

The recommended starting dose is 1 mg 3 times daily for 2 weeks. Doses should be taken 3 times daily approximately 6 to 8 hours apart.

Titration

Titration of riociguat dose is to be performed based on the patient’s systolic blood pressure and general tolerability at the discretion of the treating physician/healthcare provider. If systolic blood pressure is ≥90 mmHg for the 6 to <12 years age group or ≥95 mmHg for the 12 to <18 years age group and the patient has no signs or symptoms of hypotension, the dosage should be increased by 0.5 mg every 2 weeks to a maximum dose of 2.5 mg 3 times daily.

If systolic blood pressure falls below these specified levels the dosage should be maintained provided the patient does not show any signs or symptoms of hypotension. If at any time during the up-titration phase systolic blood pressure decreases below the specified levels, or the patient shows signs and symptoms of hypotension the current dose should be decreased by 0.5 mg 3 times daily.

Maintenance dose

The established individual dose should be maintained unless signs and symptoms of hypotension occur.

The maximum total daily dose is 7.5 mg (i.e., 2.5 mg 3 times daily) for paediatric patients with body weight of at least 50 kg.

If a dose is missed, treatment should be continued with the next dose as planned.

If not tolerated, dose reduction should be considered at any time.

Treatment discontinuation

In case treatment has to be interrupted for 3 days or more, treatment should be restarted with 1 mg 3 times daily for 2 weeks and continued with the dose titration regimen as described above.

Transitioning between phosphodiesterase-5 (PDE5) inhibitors and riociguat

Sildenafil must be discontinued in children at least 24 hours prior to administration of riociguat.

Tadalafil must be discontinued at least 72 hours in children prior to administration of riociguat.

Riociguat must be discontinued in children at least 24 hours prior to administration of a PDE5 inhibitor.

It is recommended to monitor for signs and symptoms of hypotension after any transition.

Dosage considerations

For patients prone to hypotension, as a precautionary measure, switches between fed and fasted riociguat intake are not recommended because of increased peak plasma levels of riociguat in the fasting compared to the fed state.

Active ingredient

Riociguat

Riociguat is a stimulator of soluble guanylate cyclase (sGC), an enzyme in the cardiopulmonary system and the receptor for nitric oxide (NO). Riociguat restores the NO-sGC-cGMP pathway and leads to increased generation of cGMP.

Read more about Riociguat

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