Brand Name
Adempas
Generic Name
Riociguat
View Brand Information FDA approval date: October 08, 2013
Classification: Soluble Guanylate Cyclase Stimulator
Form: Tablet
What is Adempas (Riociguat)?
Adempas is a soluble guanylate cyclase stimulator indicated for the treatment of adults with: Persistent/recurrent Chronic Thromboembolic Pulmonary Hypertension after surgical treatment or inoperable CTEPH to improve exercise capacity and WHO functional class.
Approved To Treat
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Brand Information
Adempas (riociguat)
WARNING: EMBRYO-FETAL TOXICITY
Do not administer Adempas to a pregnant female because it may cause fetal harm
Females of reproductive potential: Exclude pregnancy before the start of treatment, monthly during treatment, and 1 month after stopping treatment. To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for one month after
For all female patients, Adempas is available only through a restricted program called the Adempas Risk Evaluation and Mitigation Strategy (REMS) Program
1DOSAGE 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
2ADVERSE REACTIONS
The following serious adverse reactions are discussed elsewhere in the labeling:
- Embryo-Fetal Toxicity
- Hypotension
- Bleeding
2.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety data described below reflect exposure to Adempas in two, randomized, double blind, placebo-controlled trials in patients with inoperable or recurrent/persistent CTEPH (CHEST-1) and treatment naive or pre-treated PAH patients (PATENT-1). The population (Adempas: n = 490; Placebo: n = 214) was between the age of 18 and 80 years
The safety profile of Adempas in patients with inoperable or recurrent/persistent CTEPH (CHEST-1) and treatment naive or pre-treated PAH (PATENT-1) were similar. Therefore, adverse drug reactions (ADRs) identified from the 12 and 16 week placebo-controlled trials for PAH and CTEPH respectively were pooled, and those occurring more frequently on Adempas than placebo (≥3%) are displayed in Table 1 below. Most adverse reactions in Table 1 can be ascribed to the vasodilatory mechanism of action of Adempas.
The overall rates of discontinuation due to an adverse event in the pivotal placebo-controlled trials were 2.9% for Adempas and 5.1% for placebo (pooled data).
Other events that were seen more frequently in Adempas compared to placebo and potentially related to treatment were: palpitations, nasal congestion, epistaxis, dysphagia, abdominal distension and peripheral edema. With longer observation in uncontrolled long-term extension studies the safety profile was similar to that observed in the placebo controlled phase 3 trials.
3OVERDOSAGE
In cases of overdose, blood pressure should be closely monitored and supported as appropriate. Based on extensive plasma protein binding, riociguat is not expected to be dialyzable.
4DESCRIPTION
Adempas (riociguat) is a soluble guanylate cyclase stimulator tablet for oral administration. Riociguat is methyl 4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo [3,4-b]pyridin-3-yl]-5-pyrimidinyl(methyl)carbamate with the following structural formula:
C
Riociguat is a white to yellowish, crystalline, non-hygroscopic substance with a molecular weight of 422.42 g/mol. In solid form it is stable to temperature, light, and humidity.
The solubility at 25°C in water: 4 mg/L, in ethanol: 800 mg/L, in 0.1 HCl (pH 1): 250 mg/L and in buffer (phosphate) pH 7: 3 mg/L. In the pH range of 2 to 4 the solubility showed strong pH-dependency. Solubility increases at lower pH values.
Each round film-coated tablet contains 0.5 mg (1.0, 1.5, 2.0, 2.5 mg) riociguat. The inactive ingredients are cellulose microcrystalline, crospovidone, hypromellose 5cP, lactose monohydrate, magnesium stearate, sodium laurylsulfate, hydroxypropylcellulose, hypromellose 3cP, propylene glycol, and titanium dioxide. Adempas 1, 1.5, 2 and 2.5 mg tablets contain, in addition, ferric oxide yellow. Adempas 2 and 2.5 mg tablets contain, in addition, ferric oxide red.
5PATIENT 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
Adempas REMS Program
For female patients, Adempas is available only through a restricted program called the Adempas REMS Program
Inform female patients (and their guardians, if applicable) of the following important requirements:
- All female patients must sign an enrollment form.
- Advise female patients of reproductive potential that she must comply with the pregnancy testing and contraception requirements
- 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 her prescriber.
Review the Medication Guide and REMS educational materials with female patients.
Lactation
Advise women not to breastfeed during treatment with ADEMPAS
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
6Medication Guide
MEDICATION GUIDE
Adempas (a dem pahs)
(riociguat)
(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 can cause serious birth defects if taken during pregnancy.
- Females must not be pregnant when they start taking Adempas 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 tests, and order the tests for you depending on your menstrual cycle.
- Have entered puberty, even if they have not started their period, and
- Have a uterus, and
Females who are able to get pregnant must use 2 acceptable forms of birth control, during treatment with Adempas and for 1 month after stopping Adempas because the medicine may still be in the body.
- 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.
- 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 acceptable form of birth control.
See the chart below for Acceptable Birth Control Options 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 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.
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.
What is Adempas?
Adempas is a prescription medicine used to treat adults with:
- chronic thromboembolic pulmonary hypertension (CTEPH)
- 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 taking an sGC medicine.
- 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.
What should I tell my doctor before taking Adempas?
Before you take Adempas, tell your doctor if you:
- smoke
- have recently had serious bleeding from your lung, 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.
How should I take Adempas?
Adempas will be provided to you by a certified pharmacy. Your doctor will give you complete details.
- Do not take Adempas within 24 hours of sildenafil. Do not take Adempas 24 hours before or within 48 hours after tadalafil.
- Take Adempas exactly as your doctor tells you. Do not stop taking Adempas or change your dose without talking to your doctor.
- When you begin treatment with Adempas, your blood pressure should be monitored about every 2 weeks to help your doctor decide the correct dose of medicine for you.
- Your doctor may change your dose during treatment, especially when you first start taking Adempas. It is important to tell your doctor if you have any symptoms of low blood pressure during this time, such as dizziness, lightheadedness, or fainting.
- Take Adempas 3 times each day, about 6 to 8 hours apart.
- Take Adempas with or without food.
- Do not take more than a total of 7.5 mg of Adempas in 1 day unless your doctor tells you to.
- If you take a heartburn medicine (antacid) that contains aluminum hydroxide or magnesium hydroxide, do not take it within
- If you take too much Adempas, call your doctor right away or go to the nearest hospital emergency room.
- If you miss a dose, take your next dose of Adempas at the regular time.
- If you miss 3 or more days of treatment with Adempas, call your doctor for instructions before you restart Adempas.
What should I avoid while taking Adempas?
- Do not get pregnant while taking Adempas. (See serious birth defects section of the Medication Guide above called "What is the most important information I should know about 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.
- 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.
What are the possible side effects of Adempas?
Adempas can cause serious side effects including:
- Serious birth defects. (See "What is the most important information I should know about Adempas?")
- Reduced blood pressure. Adempas reduces blood pressure. This may cause symptoms of low blood pressure, such as lightheadedness, chest pain, and dizziness especially in people who are dehydrated, or have a severe blockage of blood flow out of the heart, or have certain other medical problems. Your doctor will check you for 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). This may cause you to feel short 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.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Adempas?
- Store Adempas at room temperature between 59° F to 86° F (15° C to 30° C)
Keep Adempas and all medicines out of the reach of children.
General Information about Adempas
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Adempas for a condition for which it is not prescribed. Do not give Adempas to other people, even if they have the same symptoms that you have. It may harm them.
This Medication Guide summarizes the most important information about Adempas. If you would like more information about Adempas, talk with your doctor. You can ask your doctor or pharmacist for information about Adempas that is written for health professionals. For more information go to www.Adempas-us.com or call 1-888-842-2937.
What are the ingredients in Adempas?
Active ingredient: riociguat
Inactive ingredients: cellulose microcrystalline, crospovidone, hypromellose 5cP, lactose monohydrate, magnesium stearate, sodium laurylsulfate, hydroxypropylcellulose, hypromellose 3cP, propylene glycol, titanium dioxide. Adempas 1 mg, 1.5 mg, 2 mg and 2.5 mg tablets also contain ferric oxide yellow. Adempas 2 mg and 2.5 mg tablets also contain ferric oxide red.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Revised 9 2021
Manufactured for:
Bayer HealthCare Pharmaceuticals Inc.
Manufactured in Germany
©2013 Bayer HealthCare Pharmaceuticals Inc.
7PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
NDC 50419-250-01
Note to Dispencer: Provide a copy of the Adempas Medication Guide included in this carton to each patient and at each refill.
- 90 tablets
8PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
NDC 50419-251-01
Note to Dispencer: Provide a copy of the Adempas Medication Guide included in this cartonto each patient and at each refill.
- 90 tablets
9PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
NDC 50419-252-01
Note to Dispencer: Provide a copy of the Adempas Medication Guide included in this cartonto each patient and at each refill.
- 90 tablets
10PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
NDC 50419-253-01
Note to Dispencer: Provide a copy of the Adempas Medication Guide included in this cartonto each patient and at each refill.
- 90 tablets
11PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
NDC 50419-254-01
Note to Dispencer: Provide a copy of the Adempas Medication Guide included in this cartonto each patient and at each refill.
- 90 tablets
