Adempas Tablets

Name: Adempas Tablets

Indications and Usage for Adempas Tablets

Chronic-Thromboembolic Pulmonary Hypertension

Adempas is indicated for the treatment of adults with persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), (WHO Group 4) after surgical treatment, or inoperable CTEPH, to improve exercise capacity and WHO functional class [see Clinical Studies (14.1)].

Pulmonary Arterial Hypertension

Adempas is indicated for the treatment of adults with pulmonary arterial hypertension (PAH), (WHO Group 1), to improve exercise capacity, WHO functional class and to delay clinical worsening.

Efficacy was shown in patients on Adempas monotherapy or in combination with endothelin receptor antagonists or prostanoids. Studies establishing effectiveness included predominately patients with WHO functional class II–III and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (25%) [see Clinical Studies (14.2)].

Adempas Tablets Dosage and Administration

Recommended Dosage in Adult Patients

The recommended starting dosage is 1 mg taken 3 times a day. For patients who may not tolerate the hypotensive effect of Adempas, consider a starting dose of 0.5 mg taken three times a day. If systolic blood pressure remains greater than 95 mmHg and the patient has no signs or symptoms of hypotension, up-titrate the dose by 0.5 mg taken three times a day. Dose increases should be no sooner than 2 weeks apart. The dose can be increased to the highest tolerated dosage, up to a maximum of 2.5 mg taken three times a day. If at any time, the patient has symptoms of hypotension, decrease the dosage by 0.5 mg taken three times a day.

Crushed Tablets

For patients who are unable to swallow whole tablets, Adempas may be crushed and mixed with water or soft foods (such as applesauce) immediately before administration [see Clinical Pharmacology (12.3)].

Dosage Interruption

If a dose is missed, advise patients to continue with the next regularly scheduled dose.

In case Adempas is interrupted for 3 days or more, re-titrate Adempas.

Pregnancy Testing in Females of Reproductive Potential

Obtain pregnancy tests prior to initiation and monthly during treatment [see Use in Specific Populations (8.6)].

Use in Patients who Smoke

Consider titrating to dosages higher than 2.5 mg three times a day, if tolerated, in patients who smoke. A dose decrease may be required in patients who stop smoking [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)].

Strong CYP and P-gp/BCRP Inhibitors

Consider a starting dose of 0.5 mg, three times a day when initiating Adempas in patients receiving strong cytochrome P450 (CYP) and P-glycoprotein/breast cancer resistance protein (P-gp/BCRP) inhibitors such as azole antimycotics (for example, ketoconazole, itraconazole) or HIV protease inhibitors (for example, ritonavir). Monitor for signs and symptoms of hypotension on initiation and on treatment with strong CYP and P-gp/BCRP inhibitors [see Warnings and Precautions (5.3), Drug Interactions (7.2) and Clinical Pharmacology (12.3)].

2.6 Transitioning to and from Adempas

• Discontinue sildenafil at least 24 hours prior to administering Adempas [see Contraindications (4.3) and Drug Interactions (7)]. • Discontinue tadalafil at least 48 hours prior to administering Adempas [see Contraindications (4.3) and Drug Interactions (7)]. Consider initiating Adempas at a starting dose of 0.5 mg in patients at risk of hypotension [see Dosage and Administration (2.1)]. It is recommended to monitor for signs and symptoms of hypotension on initiation. • Discontinue Adempas at least 24 hours prior to administering a PDE5-inhibitor [see Dosage and Administration (2.1), Contraindications (4.3), and Drug Interactions (7)]. It is recommended to monitor for signs and symptoms of hypotension on initiation.

Contraindications

Pregnancy

Adempas may cause fetal harm when administered to a pregnant woman. Adempas is contraindicated in females who are pregnant. Adempas was consistently shown to have teratogenic effects when administered to animals. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].

Nitrates and Nitric Oxide Donors

Co-administration of Adempas with nitrates or nitric oxide donors (such as amyl nitrite) in any form is contraindicated [see Drug Interactions (7.1) and Clinical Pharmacology (12.2)].

Phosphodiesterase Inhibitors

Concomitant administration of Adempas with specific PDE-5 inhibitors (such as sildenafil, tadalafil, or vardenafil) or nonspecific PDE 5 inhibitors (such as dipyridamole or theophylline) is contraindicated [see Dosage and Administration (2.6), Drug Interactions (7.1) and Clinical Pharmacology (12.2)]. Do not administer within 24 hours of sildenafil. Do not administer 24 hours before or within 48 hours after tadalafil.

4.4 Pulmonary Hypertension Associated with Idiopathic Interstitial Pneumonias (PH-IIP)

Adempas is contraindicated in patients with pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP).

How Supplied/Storage and Handling

How Supplied

Adempas (riociguat) tablets are film-coated, round, and debossed with the “Bayer cross” on one side.

Color

Debossing

Side 2

NDC 50419-xxx-xx

Bottle of 9

Bottle of 90

Blister of 42

0.5 mg

White

0.5 R

250-91

250-01

250-03

1 mg

Pale yellow

1 R

251-91

251-01

251-03

1.5 mg

Yellow-orange

1.5 R

252-91

252-01

252-03

2 mg

Pale orange

2 R

253-91

253-01

253-03

2.5 mg

Red-orange

2.5 R

254-91

254-01

254-03

Storage and Handling

Store at 25°C (77°F); excursions are permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

In Summary

Commonly reported side effects of riociguat include: dyspepsia, gastritis, and headache. See below for a comprehensive list of adverse effects.

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