Bayer Logo Bayer Logo Bayer Logo Bayer Logo

Prescribing Information          

This medicinal product is subject to additional monitoring.

Adempas® Prescribing Information

Composition

Active Ingredient: 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg riociguat. Excipients: cellulose microcrystalline, crospovidone, hypromellose, magnesium stearate, lactose monohydrate, sodium lauril sulfate, hydroxypropylcellulose, hypromellose, propylene glycol and titanium dioxide (E171), ferric oxide yellow (only in 1 mg, 1.5 mg, 2 mg and 2.5 mg tablets), ferric oxide red (only in 2 mg and 2.5 mg tablets).

 

Indications

Chronic thromboembolic pulmonary hypertension (CTEPH):
Treatment of adult patients with WHO functional class II to III with inoperable CTEPH, or persistent or recurrent CTEPH after surgical treatment to improve exercise capacity.

Pulmonary arterial hypertension (PAH):
In monotherapy or in combination with endothelin receptor antagonists, is indicated for the treatment of adult patients with PAH with WHO functional class II to III to improve exercise capacity. Efficacy has been shown in a PAH population including etiologies of idiopathic or heritable PAH or PAH associated with connective tissue disease

 

Contraindications

Co-administration with PDE 5 inhibitiors (such as sildenafil, tadalafil, vardenafil); severe hepatic impairment (Child Pugh C); hypersensitivity to the active substance or to any of the excipients; pregnancy; co-administration with nitrates or nitric oxide donors (such as amyl nitrite) in any form, including recreational drugs called ‘poppers’; patients with systolic blood pressure below 95 mmHg at treatment initiation; patients with pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP).

 

Warnings and Precautions

In PAH, studies with Adempas have been mainly performed in forms related to idiopathic or heritable PAH and PAH associated with connective tissue disease. The use of Adempas in other forms of PAH not studied is not recommended. In CTEPH, pulmonary endarterectomy is the treatment of choice as it is potentially curative. Therefore, an expert assessment of operability should be done prior to treatment with Adempas.

Pulmonary veno-occlusive disease (PVOD): Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD). Therefore, administration of Adempas to PVOD patients is not recommended. Should signs of pulmonary oedema occur, the possibility of associated PVOD should be considered and treatment with riociguat should be discontinued.

Respiratory tract bleeding: Careful monitoring of patients taking anticoagulants is recommended. The risk of serious and fatal respiratory tract bleeding may be further increased under treatment with Adempas. The use should be avoided in patients with a history of serious hemoptysis or who have previously undergone bronchial arterial embolisation. In case of respiratory tract bleeding, the prescriber should regularly assess the benefit-risk of treatment continuation.

Hypotension: Adempas has vasodilatory properties that may result in lowering of the blood pressure. Before prescribing riociguat, physicians should carefully consider whether patients with certain underlying conditions, could be adversely affected by vasodilatory effects (e.g. patients on antihypertensive therapy or with resting hypotension, hypovolemia, severe left ventricular outflow obstruction or autonomic dysfunction) Adempas must not be used in patients with a systolic blood pressure below 95 mmHg. Patients older than 65 years are at increased risk of hypotension. Therefore, caution should be exercised when administering Adempas in these patients.

Renal impairment: Data in patients with severe renal impairment (creatinine clearance < 30 mL/min) are limited and there are no data for patients on dialysis, therefore Adempas is not recommended in these patients. There is increased Adempas exposure in patients with mild and moderate renal impairment. There is a higher risk of hypotension in these patients particular care should be exercised during individual dose titration.

Hepatic impairment: There is no experience in patients with severe hepatic impairment (Child Pugh C); Adempas is contraindicated in these patients. PK data show that higher Adempas exposure was observed in patients with moderate hepatic impairment (Child Pugh B). Particular care should be exercised during individual dose titration. There is no clinical experience with Adempas in patients with elevated liver aminotransferases (> 3 x Upper Limit of Normal (ULN)) or with elevated direct bilirubin (> 2 x ULN) prior to initiation of treatment; Adempas is not recommended in these patients.

Pregnancy/contraception: Adempas is contraindicated in pregnancy. Therefore, female patients at potential risk of pregnancy must use an effective method of contraception. Monthly pregnancy tests are recommended.

Smokers: Plasma concentrations of Adempas in smokers are reduced compared to non-smokers. Dose adjustment may be necessary in patients who start or stop smoking during treatment with Adempas.

Concomitant use with other medicinal products: The concomitant use of Adempas with strong multi pathway cytochrome P450 (CYP) and P-glycoprotein (P-gp) / breast cancer resistance protein (BCRP) inhibitors such as azole antimycotics (e.g. ketoconazole, itraconazole) or HIV protease inhibitors (e.g. ritonavir) is not recommended, due to the pronounced increase in Adempas exposure. The concomitant use of Adempas with strong CYP1A1 inhibitors, such as the tyrosine kinase inhibitor erlotinib and strong P-glycoprotein (P-gp) / breast cancer resistance protein (BCRP) inhibitors, such as the immuno-suppressive agent cyclosporine A, may increase Adempas exposure. Blood pressure should be monitored and dose reduction of Adempas should be considered.

Pediatric population: The safety and efficacy of Adempas in children and adolescents below 18 years have not been established. The use of Adempas in children and in growing adolescents should be avoided.

Information about excipients: Each 0.5 mg film coated tablet contains 37.8 mg lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

 

Undesirable effects

Very common: headache, dizziness, dyspepsia, peripheral edema, nausea, diarrhea and vomiting.

Common: Gastroenteritis, anemia, palpitation, hypotension, hemoptysis epistaxis, nasal congestion, gastritis, gastro-oesophagus reflux disease, dysphagia, gastrointestinal and abdominal pain, constipation, abdominal distension.

Uncommon: Pulmonary hemorrhage (Serious haemoptysis and pulmonary haemorrhage, including cases with fatal outcome have been observed in patients with CTEPH or PAH treated with Adempas).

Classification for supply: Medicinal product subject to medical prescription.

Date of revision of the underlying SmPC: April 2019

Marketing Authorization Holder: Bayer Pharma AG, D-13342 Berlin, Germany

 

Classification for supply: Medicinal product subject to medical prescription.

 

Date of revision of the underlying Prescribing Information: 27.03.2014

Marketing Authorization Holder: Bayer Pharma AG, D-13342 Berlin, Germany

 
MORE IMPORTANT SAFETY INFORMATION LESS IMPORTANT SAFETY INFORMATION

Adempas can cause serious birth defects if taken during pregnancy.

  • Females must not be pregnant when they start taking Adempas (riociguat) tablets or become pregnant during treatment with Adempas.
  • Females who are able to get pregnant must have a negative pregnancy test before beginning treatment with Adempas, each month during treatment, and 1 month after you stop treatment with Adempas. Talk to your doctor about your menstrual cycle. Your doctor will decide when to do the test.
    • Females who are able to get pregnant are females who:
      • Have entered puberty, even if they have not started their period, have a uterus, and have not gone through menopause (have not had a period for at least 12 months for natural reasons, or have had their ovaries removed).
    • Females who are not able to get pregnant are females who:
      • Have not yet entered puberty, do not have a uterus, or have gone through menopause.

Females who are able to get pregnant must use two acceptable forms of birth control, during Adempas treatment and for one month after stopping Adempas.

  • If you have had a tubal sterilization, have a progesterone implant, or have an IUD (intrauterine device), these methods can be used alone and no other form of birth control is needed.
  • Talk with your doctor or gynecologist (a doctor who specializes in female reproduction) to find out how to prevent pregnancy during treatment with Adempas.
    • 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 tell you to use 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.

Females can only receive Adempas through a restricted program called the Adempas Risk Evaluation and Mitigation Strategies (REMS) program. If you are a female who can become pregnant, you must talk to your doctor, understand the benefits and risks of Adempas, and agree to all of the instructions in the Adempas REMS program. Males can receive Adempas without taking part in the Adempas REMS program.

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.
  • you take:
    • a nitrate medicine to treat high blood pressure or heart disease, such as nitroglycerin, or a medicine called a nitric oxide donor, such as amyl nitrite
    • certain other medicines that contain sildenafil (Revatio or Viagra), tadalafil (Adcirca or Cialis), vardenafil (Levitra or Staxyn), dipyridamole, or theophylline. Revatio and Adcirca are also used to treat PAH
  • you have pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP).

Ask your doctor or pharmacist if you are not sure if you take any of the medicines listed above.

Before you take Adempas, tell your doctor if you:

  • smoke; have recently had serious bleeding from your lungs, or if you have had a medical procedure called bronchial arterial embolization to stop you from coughing up blood; have problems with your heart or blood circulation; have low blood pressure; have liver problems; have kidney problems or are on dialysis; have narrowing of the pulmonary veins, a condition called pulmonary veno-occlusive disease or PVOD; have any other medical conditions.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.
Adempas and other medicines may affect each other causing side effects. Do not start any new medicine until you check with your doctor.

What should I avoid while taking Adempas?

  • Do not get pregnant while taking Adempas. If you miss a menstrual period, or think you might be pregnant, call your doctor right away.
  • It is not known if Adempas passes into your breast milk. You should not breastfeed if you take Adempas. Talk to your doctor about the best way to feed your baby if you take Adempas.
  • Adempas may make you feel dizzy. Do not drive, operate machinery, or do other activities that require mental alertness or coordination until you know how Adempas affects you. Talk with your doctor if you are concerned about when it is safe for you to do these activities.
  • Smoking. Adempas may not work as well if you smoke during treatment. Tell your doctor if you stop smoking or start smoking during treatment with Adempas, because your dose of Adempas may need to be changed.

Adempas can cause serious side effects including:

  • Serious birth defects.
  • Reduced blood pressure. This may cause symptoms of low blood pressure, such as lightheadedness, chest pain, and dizziness especially in people who are dehydrated, have a severe blockage of blood flow out of the heart, or have certain other medical problems. Your doctor will check you for any of these problems.
  • Increased risk of bleeding, including bleeding from the respiratory tract. Tell your doctor right away if you cough up blood during treatment with Adempas.
  • Worsening of symptoms in people with Pulmonary Veno-Occlusive Disease (PVOD). If you have PVOD, treatment with Adempas may cause a build-up of fluid in your lungs (pulmonary edema) which may result in shortness of breath. Your doctor may tell you to stop taking Adempas and switch you to a different medicine.

The most common side effects of Adempas are:

  • Headache; dizziness; indigestion; swelling of your hands, legs, feet, and ankles (peripheral edema); nausea; diarrhea; and vomiting

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Adempas.

Adempas is a prescription medicine used to treat adults with:

  • chronic thromboembolic pulmonary hypertension (CTEPH) (WHO Group 4) 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 (measured by 6-minute walk distance) and can help to improve some of your symptoms.
  • pulmonary arterial hypertension (PAH) (WHO Group 1)
    • PAH is a type of high blood pressure in the arteries of your lungs. Adempas can improve your ability to exercise (measured by 6-minute walk distance), improve some of your symptoms, and help slow down the worsening of your physical condition [this includes death, heart/lung transplant, a surgery to reduce pressure in your lung, hospitalization for worsening of pulmonary hypertension, start of a new PAH-specific treatment, continued decline in your ability to exercise (measured by a 6-minute walk distance) and some of your symptoms].

The Adempas clinical studies included mostly patients with WHO functional class II-III symptoms. It is unknown if Adempas is safe and effective in children.

For important risk and use information please see the full Prescribing Information , including Boxed Warning and Medication Guide .