Adempas

Name: Adempas

What other information should I know?

Keep all appointments with your doctor. Your doctor will check your blood pressure regularly during your treatment with riociguat.

Do not let anyone else take your medication.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Interactions for Adempas

Metabolized by CYP1A1, 3A, 2C8, and 2J2.1 Both drug and active metabolite are potent inhibitors of CYP1A1.19

Substrate of P-gp and BCRP.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

CYP3A4 inhibitors or inducers: Potential pharmacokinetic interaction (increased or decreased riociguat concentrations, respectively); caution is advised and dosage adjustments may be necessary.1 19

CYP1A1 inhibitors or inducers: Potential pharmacokinetic interaction (increased or decreased riociguat concentrations, respectively); caution is advised and dosage adjustments may be necessary.1 19

CYP1A1 substrates: Clinically important interactions are possible.19

Drugs Affecting Efflux Transport Systems

Pharmacokinetic interactions possible with inhibitors or inducers of P-gp and BCRP.1 19 (See Specific Drugs under Interactions.)

Drugs Affecting Hepatic Microsomal Enzymes and Efflux Transport Systems

Concomitant use of potent inhibitors of both CYP and P-gp/BRCP is expected to substantially increase exposure to riociguat and, thus, risk of hypotension.1 Dosage adjustments may be required.1 (See Dosage and Administration: Dosage.)

Specific Drugs

Drug

Interaction

Comments

Antacids (aluminum hydroxide and magnesium hydroxide)

Possible reduced absorption and bioavailability of riociguat1 19

Do not administer antacids within 1 hour of taking riociguat1 19

Antihypertensive agents

Possible additive hypotensive effects1

Aspirin

No substantial pharmacokinetic or pharmacodynamic (bleeding time or platelet aggregation) interactions observed1

No dosage adjustments necessary1

Azole antifungals (e.g., itraconzole, ketoconazole)

Increased exposure to riociguat and risk of hypotension1

Concomitant use not recommended; however, if necessary, consider reduced initial dosage of riociguat and monitor for hypotension1

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Potential decreased plasma concentrations of riociguat1

Use concomitantly with caution19

Bosentan

Potential decrease in plasma riociguat concentrations; however, efficacy of combination not likely to be affected1 19

No dosage adjustments necessary1

Clarithromycin

Increased systemic exposure to riociguat and its major active metabolite; no substantial change in peak plasma concentrations of riociguat1

Use concomitantly with caution; no dosage adjustments necessary1 19

Cyclosporine

Potential increased exposure to riociguat19

Use concomitantly with caution19

H2-receptor antagonists (e.g., ranitidine)

Potential decreased bioavailability of riociguat due to increased gastric pH induced by H2-receptor antagonists1 19

Ranitidine: Slightly reduced peak plasma concentrations and systemic exposure of riociguat19

HIV protease inhibitors (e.g., ritonavir)

Increased exposure to riociguat and risk of hypotension1

Concomitant use not recommended; however, if necessary, consider reduced initial dosage of riociguat and monitor for hypotension1

Midazolam

Pharmacokinetics of midazolam not altered1

Nitrates and nitric oxide donors (e.g., nitroglycerin, amyl nitrate)

Possible additive hypotensive effects; syncope also reported1

Concomitant use contraindicated1

Proton-pump inhibitors (e.g., omeprazole)

Potential decreased bioavailability of riociguat due to increased gastric pH induced by proton-pump inhibitors1 19

Omeprazole: Modest decrease in peak plasma concentrations and systemic exposure of riociguat1 19

No dosage adjustments necessary1 19

PDE inhibitors, including specific PDE type 5 inhibitors (sildenafil, tadalafil) and nonspecific PDE inhibitors (e.g., dipyridamole, theophylline)

Possible additive hypotensive effects1

Concomitant use contraindicated1

Rifampin

Possible decreased plasma concentrations of riociguat1

Use concomitantly with caution19

Smoking

Decreased plasma concentrations of riociguat by approximately 50–60%1

Consider increasing dosage to >2.5 mg 3 times daily if necessary1

St. John's wort

Possible decreased plasma concentrations of riociguat1

Use concomitantly with caution19

Tyrosine kinase inhibitors (e.g., erlotinib, gefitinib)

Clinically important CYP1A1-mediated interactions possible19

Use concomitantly with caution19

Warfarin

No substantial change in pharmacodynamics (e.g., PT) or pharmacokinetics of warfarin; increased peak plasma concentrations of riociguat, but not clinically important1 14

No dosage adjustments necessary1 14

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Distribution of riociguat is restricted.1 (See Restricted Distribution Program under Dosage and Administration.)

Riociguat

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

0.5 mg

Adempas

Bayer

1 mg

Adempas

Bayer

1.5 mg

Adempas

Bayer

2 mg

Adempas

Bayer

2.5 mg

Adempas

Bayer

Commonly used brand name(s)

In the U.S.

  • Adempas

Available Dosage Forms:

  • Tablet

Therapeutic Class: Cardiovascular Agent

Uses of Adempas

  • It is used to treat high blood pressure in the lungs.

What do I need to tell my doctor BEFORE I take Adempas?

  • If you have an allergy to riociguat or any other part of this medicine.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have a health problem called pulmonary veno-occlusive disease (PVOD).
  • If you have pneumonia.
  • If you are taking any of these drugs: Amyl nitrate, avanafil, dipyridamole, a nitrate drug like nitroglycerin, sildenafil, tadalafil, theophylline, or vardenafil.
  • If you are breast-feeding. Do not breast-feed while you take this medicine (Adempas).

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine (Adempas) with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Pregnancy & Lactation

Pregnancy Category: X; Contraindicated in pregnancy due to consistent teratogenic effects shown in animal studies

Females of reproductive potential must have a negative pregnancy test before initiation, monthly during, and 1 month after discontinuation of treatment; contraception must also be used during and for 1 month after treatment (see Boxed Warning)

If pregnancy suspected, contact healthcare provider immediately

Lactation: Unknown if distributed in human breast milk; due to potential for serious adverse effects in infants and studies showing distribution into milk of rats, do not recommend nursing during treatment

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

What is Adempas?

Adempas (riociguat) lowers blood pressure in your lungs, helping your heart pump blood more efficiently.

Adempas is used to treat chronic thromboembolic pulmonary hypertension (CTEPH) in people who cannot be treated with surgery, or in people who have undergone surgery but still have symptoms. Riociguat can treat certain symptoms of CTEPH and can improve your ability to exercise.

Adempas is used to treat pulmonary arterial hypertension (PAH). Riociguat can improve your ability to exercise and help prevent PAH from getting worse.

Adempas is available to women only under a special program from a certified pharmacy. You must be registered in the program and understand the risks and benefits of taking this medication.

Before taking this medicine

You should not use Adempas if you are allergic to riociguat, or if:

  • you are pregnant or might become pregnant during treatment; or

  • you have PAH related to a condition called idiopathic interstitial pneumonias (PH-IIP).

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 Viagra, Cialis, Levitra, and others;

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

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

Do not take Adempas within 24 hours before or after taking sildenafil (Revatio, Viagra), or within 24 hours before or 48 hours after taking tadalafil (Adcirca, Cialis).

To make sure Adempas 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 Adempas 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. Do not have unprotected sex.

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 Adempas, girls and women who are able to get pregnant must use highly effective 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).

Adempas 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.

Adempas dosing information

Usual Adult Dose for Pulmonary Hypertension:

Initial dose: 1 mg orally 3 times a day
Maximum dose: 2.5 mg orally 3 times a day

Comments:
-For patients who cannot tolerate the hypotensive effect, consider a starting dose of 0.5 mg orally 3 times a day. If systolic blood pressure remains greater than 95 mmHg and the patient has no signs of hypotension, the dose may be titrated up by 0.5 mg orally 3 times a day.
-Dose increases should be no more frequent than every 2 weeks.

Use(s):
-Persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) (WHO group 4) after surgical treatment or inoperable CTEPH to improve exercise capacity and WHO functional class.
-As monotherapy or in combination with endothelin receptor antagonists or prostanoids to treat pulmonary arterial hypertension (PAH) (WHO group 1) to improve exercise capacity, improve WHO functional class and to delay clinical worsening.

For Healthcare Professionals

Applies to riociguat: oral tablet

General

The most frequently reported side effects were headache, dyspepsia/gastritis, dizziness, nausea, diarrhea, hypotension, vomiting, anemia, gastroesophageal reflux, and constipation.[Ref]

Cardiovascular

Very common (10% or more): Peripheral edema (up to 17.3%), hypotension (up to 10%)
Common (1% to 10%): Palpitation, chest pain, chest discomfort[Ref]

Nervous system

Very common (10% or more): Headache (up to 27%), dizziness (up to 20%)[Ref]

Gastrointestinal

Very common (10% or more): Dyspepsia (up to 21%), gastritis (21%), nausea (up to 14.1%), diarrhea (up to 12%), vomiting (up to 10.2%)
Common (1% to 10%): Gastroesophageal reflux disease, constipation, gastroenteritis, gastrointestinal/abdominal pain, dysphagia, abdominal distention[Ref]

Hematologic

Very common (10% or more): Hemoglobin decreased (24.1%), hematocrit decreased (13.3%)
Common (1% to 10%): Anemia[Ref]

Respiratory

Very common (10% or more): Nasopharyngitis (11.8%)
Common (1% to 10%): Dyspnea, cough, nasal congestion, epistaxis, hemoptysis
Frequency not reported: Pulmonary hemorrhage[Ref]

Musculoskeletal

Common (1% to 10%): Pain in extremity[Ref]

Other

Common (1% to 10%): Fatigue[Ref]

Some side effects of Adempas may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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