Adempas riociguat 1 mg Tablet, Film Coated

1 INDICATIONS AND USAGE Adempas is a soluble guanylate cyclase (sGC) stimulator 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. ( 1.1 ) • Pulmonary Arterial Hypertension (PAH) (WHO Group 1) to improve exercise capacity, improve WHO functional class and to delay clinical worsening. ( 1.2 )

1.1Chronic-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) ].

1.2Pulmonary 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) ] .

2 DOSAGE AND ADMINISTRATION • Initiate treatment at 1 mg taken three times a day. ( 2.1 ) • For patients who may not tolerate the hypotensive effect of Adempas, consider a starting dose of 0.5 mg, three times a day. ( 2.1 ) • Increase dosage by 0.5 mg at intervals of no sooner than 2-weeks as tolerated to a maximum of 2.5 mg three times a day.

( 2.1 ) • Tablets may be crushed and mixed with water or soft foods for patients who have difficulty swallowing. ( 2.1 )

2.1Recommended 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) ].

2.2Dosage 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.

2.3Pregnancy Testing in Females of Reproductive Potential Exclude pregnancy before initiating Adempas. [see Contraindications (4.1) , Warning and Precautions (5.1) , Use in Specific Populations (8.3) ].

2.4Use 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) ].

2.5Strong 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 (5.2) , Drug Interactions (7.2) and Clinical Pharmacology (12.3) ].

2.6Transitioning 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) ] . 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) ].

Monitor for signs and symptoms of hypotension on initiation.

3 DOSAGE FORMS AND STRENGTHS Tablets: film-coated, round, bi-convex: • 0.5 mg, white, with "BAYER" cross on one side and "0.5" and "R" on the other side • 1 mg, pale-yellow, with "BAYER" cross on one side and "1" and "R" on the other side • 1.5 mg, yellow-orange, with "BAYER" cross on one side and "1.5" and "R" on the other side • 2 mg, pale orange, with "BAYER" cross on one side and "2" and "R" on the other side • 2.5 mg, red-orange, with "BAYER" cross on one side and "2.5" and "R" on the other side Tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg ( 3 )

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Embryo-Fetal Toxicity Instruct patients on the risk of fetal harm when Adempas is used during pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] . Educate and counsel females of reproductive potential to use effective contraception prior to initiation of treatment with Adempas, during treatment, and for one month after stopping treatment.

Instruct patients to contact their healthcare provider immediately if they suspect they may be pregnant. Educate and counsel females of reproductive potential on the use of emergency contraception in the event of unprotected sex or contraceptive failure. Advise pre-pubertal females to report any changes in their reproductive status immediately to their prescriber.

Lactation Advise women not to breastfeed during treatment with Adempas [see Use in Specific Populations (8.2) ] . Other Risks Associated with Adempas • Inform patients of the contraindication of Adempas with nitrates or nitric oxide donors or PDE-5 inhibitors. • Advise patients about the potential risks/signs of hemoptysis and to report any potential signs of hemoptysis to their physicians. • Instruct patients on the dosing, titration, and maintenance of Adempas. • Advise patients regarding activities that may impact the pharmacology of Adempas (strong multi pathway CYP inhibitors and P-gp/BCRP inhibitors and smoking).

Instruct patients to report all current medications and new medications to their physician. • Advise patients that antacids should not be taken within 1 hour of taking Adempas. • Inform patients that Adempas can cause dizziness, which can affect the ability to drive and use machines [see Adverse Reactions (6.1) ] . Advise patients to be aware of how they react to Adempas before driving or operating machinery, and if needed, consult their physician. Patients should consult their physicians if dizziness gets worse with Adempas.

MEDICATION GUIDE Adempas (a-dem-pahs) (riociguat) tablets Read this Medication Guide before you start taking Adempas and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about your medical condition or your treatment.

What is the most important information I should know about Adempas? • Serious birth defects. Adempas may cause serious birth defects if taken during pregnancy. Females should not be pregnant when they start taking Adempas or become pregnant during treatment with Adempas.

Females who are able to get pregnant should have a negative pregnancy status before beginning treatment with Adempas. Females who are able to get pregnant are females who: Have entered puberty, even if they have not started their period, and Have a uterus, and Have not gone through menopause (have not had a period for at least 12 months for natural reasons, or who have had their ovaries removed) Females who are not able to get pregnant are females who: Have not yet entered puberty, or Do not have a uterus, or Have gone through menopause (have not had a period for at least 12 months for natural reasons, or who have had their ovaries removed) Females who are able to get pregnant should use effective birth control before starting treatment with Adempas, during treatment with Adempas and for 1 month after stopping Adempas because the medicine may still be in the body.

Talk with your doctor or gynecologist (a doctor who specializes in female reproduction) to find out about options for effective forms of birth control that you may use to prevent pregnancy during treatment with Adempas. If you decide that you want to change the form of birth control that you use, talk with your doctor or gynecologist to be sure that you choose another effective form of birth control. Do not have unprotected sex.

Talk to your doctor or pharmacist right away if you have unprotected sex or if you think your birth control has failed. Your doctor may talk with you about using emergency birth control. Tell your doctor right away if you miss a menstrual period or think you may be pregnant for any reason.

If you are the parent or caregiver of a female child who started taking Adempas before reaching puberty, you should check your child regularly to see if she is developing signs of puberty. Tell your doctor right away if you notice that she is developing breast buds or any pubic hair. Your doctor should decide if your child has reached puberty.

Your child may reach puberty before having her first menstrual period. If you are a female who can become pregnant, talk to your doctor to understand the benefits and risks of Adempas. What is Adempas?

Adempas is a prescription medicine used to treat adults with: • chronic thromboembolic pulmonary hypertension (CTEPH) • treated with surgery but who continue to have high pulmonary blood pressure (persistent) or it comes back after surgery (recurrent), or • that cannot be treated with surgery. • CTEPH is a type of high blood pressure in the arteries of your lungs caused by blood clots that narrow or block blood flow. Adempas can improve your ability to exercise and can help to improve some of your symptoms. • pulmonary arterial hypertension (PAH) • PAH is a type of high blood pressure in the arteries of your lungs.

Adempas can improve your ability to exercise, improve some of your symptoms, and help slow down the worsening of your physical condition. • It is unknown if Adempas is safe and effective in children. Who should not take Adempas? Do not take Adempas if: • you are pregnant, plan to become pregnant, or become pregnant during treatment with Adempas .

Adempas can cause serious birth defects. (See the Medication Guide section above called "What is the most important information I should know about Adempas?") • you take : • another medicine called a soluble guanylate cyclase stimulator (sGC). Ask your healthcare provider if you are not sure if you are taki…