Adempas

Name: Adempas

Adempas Interactions

Do not have unprotected sex while taking riociguat. You must use birth control to prevent pregnancy during treatment and for at least 30 days after you stop taking this medicine.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Smoking can make riociguat less effective. Tell your doctor if you start or stop smoking while you are taking this medicine. Your dose needs may need to be changed

Avoid taking an antacid within 1 hour before or after you take riociguat. Some antacids can make it harder for your body to absorb riociguat.

Other drugs may interact with riociguat, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Adempas Dosage

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.

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

You may take riociguat with or without food.

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

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Call your doctor if you miss your doses for 3 days in a row or longer.

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Riociguat side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using riociguat and call your doctor at once if you have:

  • a light-headed feeling, like you might pass out;

  • abnormal vaginal bleeding, or any other unusual bleeding;

  • vomiting or coughing up bright red blood, or vomit that looks like coffee grounds;

  • low red blood cells (anemia)--pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or

  • new lung problems--anxiety, sweating, pale skin, severe shortness of breath, wheezing, gasping for breath, cough with foamy mucus, chest pain, fast or uneven heart rate.

Common side effects may include:

  • dizziness;

  • headache;

  • heartburn, upset stomach, nausea, vomiting;

  • diarrhea, constipation; or

  • swelling in your hands, legs, or feet.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Adempas Dosage and Administration

General

    Restricted Distribution Program
  • Distribution of riociguat to female patients is restricted; available only through the Adempas REMS program.1 5 (See Boxed Warning and also see REMS.)

  • All female patients (regardless of childbearing potential), clinicians, and pharmacies must enroll in the program in order to receive, prescribe, and dispense the drug, respectively; in addition, females of childbearing potential must comply with pregnancy testing and contraception requirements.1 Male patients do not need to enroll.1 Additional information available at or 855-423-3672.1

Administration

Oral Administration

Administer orally without regard to meals.1

If a dose is missed, take next dose at the regularly scheduled time; if treatment is interrupted for ≥3 days, retitrate dosage.1

Dosage

Adults

CTEPH Oral

Initially, 1 mg 3 times daily (doses approximately 6–8 hours apart); consider reduced initial dosage of 0.5 mg 3 times daily in patients who may not tolerate the hypotensive effects of the drug.1 41

Adjust dosage based on response and tolerance.1 In patients without manifestations of hypotension and in whom systolic BP >95 mm Hg, may titrate dosage up to maximum of 2.5 mg 3 times daily.1 Adjust dosage in increments of 0.5 mg 3 times daily at intervals of at least 2 weeks.1 If symptoms of hypotension occur at any time, reduce dosage by 0.5 mg 3 times daily.1

In patients receiving concomitant therapy with potent inhibitors of CYP and P-glycoprotein (P-gp)/breast cancer resistance protein (BCRP), consider reduced initial dosage of 0.5 mg 3 times daily.1 Monitor for hypotension upon initiation of and during such concomitant therapy.1 (See Drugs Affecting Hepatic Microsomal Enzymes and Efflux Transport Systems under Interactions.)

PAH Oral

Initially, 1 mg 3 times daily (doses approximately 6–8 hours apart).1 41

Consider reduced initial dosage of 0.5 mg 3 times daily in patients who may not tolerate the hypotensive effects of the drug.1

Adjust dosage based on response and tolerance.1 In patients without manifestations of hypotension and in whom systolic BP >95 mm Hg, may titrate dosage up to maximum of 2.5 mg 3 times daily.1 Adjust dosage in increments of 0.5 mg 3 times daily at intervals of at least 2 weeks.1 If symptoms of hypotension occur at any time, reduce dosage by 0.5 mg 3 times daily.1

In patients receiving concomitant therapy with potent inhibitors of CYP and P-gp/BCRP, consider reduced initial dosage of 0.5 mg 3 times daily.1 Monitor for hypotension upon initiation of and during such concomitant therapy.1 (See Drugs Affecting Hepatic Microsomal Enzymes and Efflux Transport Systems under Interactions.)

Prescribing Limits

Adults

CTEPH Oral

Maximum recommended dosage 2.5 mg 3 times daily; consider higher dosages in patients who smoke.1

PAH Oral

Maximum recommended dosage 2.5 mg 3 times daily; consider higher dosages in patients who smoke.1

Special Populations

Smokers

Smoking can reduce plasma concentrations of riociguat; may consider titration to maximum dosages >2.5 mg 3 times daily in patients who smoke.1 6 19 (See Specific Drugs under Interactions.) Such dosage recommendations based on pharmacokinetic modeling; safety and efficacy not established in smokers.1 Dosage reduction may be required in patients who stop smoking.1 19

Hepatic Impairment

No specific dosage recommendations at this time.1

Renal Impairment

No specific dosage recommendations at this time.1

Geriatric Patients

Dosage adjustments based solely on age not necessary.1

Cautions for Adempas

Contraindications

  • Pregnancy.1

  • Concomitant therapy with nitrates or nitric oxide donors in any form (e.g., amyl nitrite, nitroglycerin).1

  • Concomitant therapy with PDE inhibitors, including specific PDE type 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil) and nonspecific PDE inhibitors (e.g., dipyridamole, theophylline).1

Warnings/Precautions

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity and embryotoxicity demonstrated in animals.1 (See Boxed Warning and also see Restricted Distribution Program under Dosage and Administration.)

Exclude pregnancy prior to initiation of therapy; perform monthly pregnancy tests during therapy and at 1 month following discontinuance of therapy.1

Females of childbearing potential must use acceptable methods of contraception during and for 1 month following cessation of therapy.1 (See Advice to Patients.)

If riociguat is used during pregnancy or patient becomes pregnant during therapy, apprise of potential fetal hazard.1

Cardiovascular Effects

Risk of hypotension.1 Consider potential for symptomatic hypotension or ischemia in patients with predisposing risk factors (e.g., hypovolemia, severe left-ventricular outflow obstruction, resting hypotension, autonomic dysfunction, concomitant use of antihypertensive agents or drugs that can increase exposure to riociguat).1 (See Interactions.)

Concomitant use of nitrates, nitric oxide donors, or phosphodiesterase inhibitors can potentiate hypotensive effects of riociguat.1 (See Contraindications under Cautions.)

If manifestations of hypotension occur at any time, reduce dosage.1 (See Dosage under Dosage and Administration.)

Bleeding

Bleeding (e.g., hemoptysis, vaginal bleeding, catheter site bleeding, subdural hematoma, hematemesis, intra-abdominal bleeding) reported, including at least 1 death.1

Pulmonary Effects

If acute pulmonary edema occurs, consider possibility of pulmonary veno-occlusive disease; if confirmed, discontinue riociguat.1

Specific Populations

Pregnancy

Category X.1 (See Fetal/Neonatal Morbidity and Mortality and also Contraindications, under Cautions.)

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in pediatric patients.1

Geriatric Use

No overall differences in safety or efficacy relative to younger patients.1

Hepatic Impairment

Safety and efficacy not established in patients with severe hepatic impairment (Child-Pugh class C).1

Renal Impairment

Safety and efficacy not established in patients with severe renal impairment (Clcr<15 mL/minute) or in those undergoing dialysis.1

Common Adverse Effects

Headache,1 2 3 dyspepsia/gastritis,1 2 3 dizziness,1 2 3 nausea,1 2 3 diarrhea,1 2 3 hypotension,1 2 3 vomiting,1 2 anemia,1 3 GERD,1 3 constipation.1 2

Advice to Patients

  • Risk of fetal harm; importance of advising females of childbearing potential to avoid pregnancy and to use acceptable methods of contraception during and for 1 month following discontinuance of riociguat therapy.1 41 Acceptable methods of contraception include one highly effective form of contraception (intrauterine device [IUD], progesterone implant, or tubal sterilization) or a combination of methods (either one hormonal and one barrier method or 2 barrier methods where one form is the male condom).1 41 Acceptable hormonal methods of contraception include estrogen-progestin combination oral contraceptives or transdermal contraceptive systems, vaginal ring, and progesterone injections.1 41 Acceptable barrier methods include male condoms, diaphragms with spermicide, and cervical caps with spermicide.1 41 Even if the partner has had a vasectomy, an additional hormonal or barrier method must be used.1 41

  • Advise females to inform their clinician immediately if a menstrual period is missed or pregnancy is suspected; clinicians should provide counseling on the use of emergency contraception in the event of unprotected sexual intercourse or contraceptive failure.1 Apprise patient of potential risk to fetus if pregnancy occurs.1

  • Importance of monthly pregnancy testing.1

  • Importance of all female patients (regardless of childbearing potential) enrolling in the Adempas REMS program and complying with contraceptive and pregnancy testing requirements.1 Importance of monitoring reproductive status of prepubertal females and immediately reporting changes to clinician.1 41

  • Risk of hemoptysis; importance of advising patients to report any potential manifestations of hemoptysis to their clinician.1 41

  • Importance of advising patients that smoking during riociguat therapy may decrease concentrations of the drug and reduce efficacy; importance of informing clinician if smoking is started or stopped during riociguat therapy as riociguat dosage adjustment may be needed.1 41

  • Importance of advising patients to not take antacids within 1 hour of riociguat administration and to avoid use of nitrates, nitric oxide donors, and PDE inhibitors while undergoing riociguat therapy.1 41

  • Risk of dizziness; importance of advising patients to avoid driving or operating machinery until effects of the drug on the individual are known and to consult their clinician, if necessary.1 41

  • Importance of taking riociguat as prescribed and of not discontinuing therapy or altering dosage without consulting a clinician.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., azole antifungal agents, HIV protease inhibitors) and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Before Using Adempas

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of riociguat in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of riociguat in the elderly. However, elderly patients may be more sensitive to the effects of this medicine than younger adults, which may require caution in patients receiving riociguat.

Pregnancy

Pregnancy Category Explanation
All Trimesters X Studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. This drug should not be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Aminophylline
  • Amyl Nitrite
  • Avanafil
  • Caffeine
  • Cobicistat
  • Dipyridamole
  • Dyphylline
  • Erythrityl Tetranitrate
  • Isosorbide Dinitrate
  • Isosorbide Mononitrate
  • Lopinavir
  • Nelfinavir
  • Nitric Oxide
  • Nitroglycerin
  • Papaverine
  • Pentaerythritol Tetranitrate
  • Pentoxifylline
  • Propatyl Nitrate
  • Ritonavir
  • Saquinavir
  • Sildenafil
  • Tadalafil
  • Telaprevir
  • Theophylline
  • Vardenafil

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Clarithromycin
  • Eliglustat
  • Idelalisib

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Bleeding problems—Use with caution. May make this condition worse.
  • Heart or blood circulation problems, severe or
  • Hypotension (low blood pressure) or
  • Hypovolemia (low blood volume)—Use with caution. May increase risk for more serious side effects.
  • Kidney disease that is severe, or on dialysis, or
  • Liver disease that is severe, or
  • Pulmonary veno-occlusive disease (lung problem)—Use is not recommended.
  • Pulmonary hypertension caused by idiopathic interstitial pneumonia—Should not be used in patients with this condition.

Precautions While Using Adempas

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and to check for unwanted effects. Blood tests may be needed to check for unwanted effects. Your blood pressure should be checked by your doctor every 2 weeks while taking this medicine.

Using this medicine while you are pregnant can cause very serious birth defects. Use 2 forms of effective birth control to keep from getting pregnant while you are using this medicine and for at least 1 month after you stop taking the medicine. The most effective forms of birth control are hormone birth control pills, patches, shots, vaginal rings, or implants, or a vasectomy (for men). One of these forms of birth control should be combined with a condom, a diaphragm, or a cervical cap. If a woman has had a tubal ligation or has an IUD, she does not need to use a second form of birth control. If you think you have become pregnant while using this medicine, tell your doctor right away.

If you are a woman who can get pregnant, you must have a negative pregnancy test before you will be allowed to take this medicine. You will also be required to have a pregnancy test every month during your treatment and 1 month after stopping therapy. If you miss a period while you are using this medicine, tell your doctor right away.

Do not use this medicine together with a nitrate medicine (such as nitroglycerin) or nitric oxide donor (such as amyl nitrite). Do not use this medicine together with dipyridamole, theophylline, or medicine for impotence (eg, sildenafil, tadalafil, vardenafil). Using these medicines together may cause hypotension (low blood pressure).

This medicine could lower your blood pressure and cause you to feel dizzy or lightheaded. Avoid driving, using machines, or doing anything else that could be dangerous until you know how this medicine affects you. If you feel dizzy, lie or sit down so you do not faint.

Pulmonary edema may occur with this medicine. Check with your doctor right away if you have chest pain, difficult, fast, or noisy breathing, sometimes with wheezing, blue lips and fingernails, pale skin, increased sweating, coughing that sometimes produces a pink frothy sputum, or shortness of breath.

Tell your doctor if you are smoking before taking this medicine.

Do not take other medicines unless thy have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

What are some things I need to know or do while I take Adempas?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine (Adempas) affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Very bad and sometimes deadly bleeding problems have happened with this medicine. Talk with the doctor.
  • If you start or stop smoking, talk with your doctor. How much drug you take may need to be changed.
  • Have your blood pressure checked often. Talk with your doctor.
  • Do not take this medicine (Adempas) within 24 hours of taking sildenafil. Do not take this medicine within 24 hours before or 48 hours after taking tadalafil.
  • If you are a woman and you miss a period, have unprotected sex, or think that your birth control has not worked, call your doctor right away.

How do I store and/or throw out Adempas?

  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Call your doctor if you miss your doses for 3 days in a row or longer.

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.

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