Adempas

Name: Adempas

How should this medicine be used?

Riociguat comes as a tablet to take by mouth. It is usually taken with or without food 3 times a day. Take riociguat at around the same time(s) every day and space your doses about 6 to 8 hours apart. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take riociguat exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

If you cannot swallow the tablet whole, you can crush the tablet and mix the contents with a small amount of water or a soft food such as applesauce. Swallow the mixture right after you mix it.

Your doctor may start you on a low dose of riociguat and gradually increase your dose, not more than once every 2 weeks. Your doctor may decrease your dose if you experience side effects.

What should I discuss with my healthcare provider before taking riociguat?

You should not use riociguat if you are allergic to it, or if you are pregnant or might become pregnant during treatment.

Some medicines can interact with riociguat and should not be used at the same time. Your doctor may need to change your treatment plan if you use any of the following drugs:

  • dipyridamole;

  • theophylline;

  • erectile dysfunction medicine such as sildenafil, tadalafil, or vardenafil;

  • a nitrate drug for chest pain or heart problems (amyl nitrite, nitroglycerin, and others); or

  • other medicines to treat PAH (Adcirca or Revatio).

To make sure riociguat is safe for you, tell your doctor if you have:

  • heart disease;

  • blood circulation problems;

  • low blood pressure;

  • a condition called pulmonary veno-occlusive disease (PVOD);

  • a recent history of coughing up blood or bleeding from your lung;

  • liver disease;

  • kidney disease (or if you are on dialysis);

  • if you smoke; or

  • if you are dehydrated.

Do not use riociguat if you are pregnant. It could harm the unborn baby or cause birth defects. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 1 month after your treatment ends. Tell your doctor right away if you miss a menstrual period or think you may have become pregnant during treatment.

You will need to have a negative pregnancy test before starting this treatment. You will also be re-tested every month during your treatment, and 1 month after you stop taking this medicine.

Even if you are not planning a pregnancy, you are considered able to become pregnant if:

  • you have entered puberty (even if you have not yet started having periods);

  • you have never had a hysterectomy or had your ovaries removed; or

  • you have not gone through menopause (you have never gone 12 months in a row without a menstrual period).

While taking riociguat you must use a highly effective form of birth control, or two methods together.

  • A tubal ligation alone is an effective birth control method.

  • An intrauterine device (IUD) or birth control implant alone are also effective birth control methods.

  • If you use birth control pills, injections, skin patches, or vaginal rings, you must use a back-up barrier form of birth control, such as a condom or diaphragm or cervical cap. Always use a spermicide gel or insert together with a barrier form of birth control.

  • If you use only a barrier method, you must use a second barrier method as a back-up. For example, use a diaphragm or cervical cap in addition to a condom, plus a spermicide gel or insert.

  • If your sexual partner has had a vasectomy, you must still use a second method of birth control--either a barrier method or a hormonal form (birth control pills, injections, skin patch, or vaginal ring).

Riociguat comes with patient instructions about acceptable forms of birth control to use while taking this medicine. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

If you are the parent or caregiver of a female child taking this medication, talk to the child's doctor once you notice any signs of puberty (breast development or pubic hair), even if menstrual periods have not yet begun.

It is not known whether riociguat passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Uses for Adempas

Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Management of CTEPH (WHO group 4 pulmonary hypertension) to improve exercise capacity and NYHA/WHO functional class in patients with inoperable disease or persistent/recurrent pulmonary hypertension after surgery (i.e., pulmonary endarterectomy).1 2 20

Standard treatment for patients with CTEPH is pulmonary endarterectomy.2 7 8 9 Because such surgery is potentially curative, an experienced clinician should assess patients to determine suitability for surgery before medical therapy is considered.2 8 9 12 13 20

Has been designated an orphan drug by FDA for treatment of CTEPH.4

Pulmonary Arterial Hypertension (PAH)

Management of PAH (WHO group 1 pulmonary hypertension) to improve exercise capacity and NYHA/WHO functional class and to delay clinical worsening.1 3

Efficacy established principally in patients with NYHA/WHO functional class II or III PAH (idiopathic, heritable, or associated with connective tissue diseases) receiving the drug as monotherapy or in combination with an endothelin-receptor antagonist or a prostanoid.1 3

Recommended as one of several treatment options for initial management of PAH in patients with NYHA/WHO functional class II, III, or IV symptoms who are not candidates for calcium-channel blocker therapy or in whom such therapy failed.40 Individualize choice of therapy; consider factors such as disease severity, route of administration, potential adverse effects and costs of treatment, clinician experience, and patient preference.27 38 40

In patients with inadequate response to initial monotherapy, may consider combination therapy with a prostanoid or endothelin-receptor antagonist (added sequentially);40 however, concomitant use of riociguat and phosphodiesterase (PDE) type 5 inhibitors is contraindicated.1 40 (See Cardiovascular Effects under Cautions.) By targeting different pathophysiologic pathways of the disease, such combination therapy may provide additive and/or synergistic benefits.24 25 29 40

Has been designated an orphan drug by FDA for treatment of PAH.4

Adempas Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration; peak plasma concentrations attained in approximately 0.5–1.5 hours.1 7 15 Plasma concentrations of the active M-1 metabolite are about 50% of those of the parent drug.1

Food

Food does not affect absorption.1

Distribution

Plasma Protein Binding

Approximately 95%.1

Elimination

Metabolism

Principally undergoes hepatic metabolism by CYP1A1, 3A, 2C8, and 2J2.1 Converted to major active M-1 metabolite by CYP1A1, then further metabolized to inactive N-glucuronide conjugate.1

Elimination Route

Following oral administration of radiolabeled dose, approximately 40 and 53% of total radioactivity recovered in urine and feces, respectively.1

Half-life

Elimination half-life about 7 hours in healthy individuals and 12 hours in patients with pulmonary hypertension.1 15 16

Special Populations

In geriatric patients, systemic exposure to riociguat may be increased.1

In patients with mild to moderate hepatic impairment (Child-Pugh class A or B), systemic exposure to riociguat may be increased.1

In patients with renal impairment, systemic exposure to riociguat may be increased.1

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).1

Adempas Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common
  • Confusion
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • nosebleeds
  • unusual tiredness or weakness
Less common
  • Abdominal or stomach pain or swelling
  • bloating or swelling of the face, arms, hands, lower legs, or feet
  • bloody or black, tarry stools
  • bruising or purple areas on the skin
  • coughing or spitting up blood
  • decreased alertness
  • fast, irregular, pounding, or racing heartbeat or pulse
  • heavy non-menstrual vaginal bleeding
  • rapid weight gain
  • troubled breathing with exertion
  • vomiting of blood or material that looks like coffee grounds

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Diarrhea
  • headache
  • heartburn or indigestion
  • nausea or vomiting
  • stuffy nose
Less common
  • Difficulty having a bowel movement (stool)

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Dizziness or passing out.
  • A heartbeat that does not feel normal.
  • Trouble swallowing.
  • Swelling of belly.
  • Swelling in the arms or legs.
  • Chest pain.
  • Pale skin.
  • Feeling very tired or weak.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine (Adempas) is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Review Date: October 4, 2017

Important information

Adempas is available to women only under a special program from a certified pharmacy. You will need to have a negative pregnancy test before starting this treatment.

Adempas can cause birth defects. Do not use if you are pregnant. Avoid getting pregnant while taking Adempas and for at least 1 month after your last dose. Do not have unprotected sex.

Tell your doctor about all your current medicines and any you start or stop using. Many drugs can interact with riociguat, and some drugs should not be used together.

How should I take Adempas?

Take Adempas exactly as prescribed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Adempas is usually taken 3 times per day. Space your doses 6 to 8 hours apart.

You may take rhis medicine with or without food.

You may need frequent medical tests to help your doctor determine how long to treat you with Adempas.

Store at room temperature away from moisture and heat.

Renal Dose Adjustments

CrCl less than 15 mL/min: Safety and efficacy have not been established.

Dose Adjustments

CrCl less than 15 mL/min: Safety and efficacy have not been established.

Riociguat Pregnancy Warnings

Animal studies have revealed evidence of teratogenicity, embryotoxicity, placental transfer, and reproductive toxicity. There are no controlled data in human pregnancy. AU TGA pregnancy category X: Drugs which have such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy. US FDA pregnancy category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

Use is contraindicated. AU TGA pregnancy category: X US FDA pregnancy category: X Comments: -A negative pregnancy test must be obtained prior to initiation, monthly during treatment, and for 1 month after discontinuation. -Adequate methods of contraception must be used during treatment and for 1 month after discontinuing treatment. -Patients may choose one highly effective form of contraception (e.g., intrauterine device, contraceptive implants, tubal sterilization) or a combination of methods (e.g., hormone method with barrier method or 2 barrier methods); if a partner's vasectomy is the chosen method, a hormone or barrier method must also be used concurrently. -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 harm to the fetus.

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