USA AND CANADA
USA AND CANADA
List of Related Indications:
- Pulmonary hypertension
List Of Drugs:
- Riociguat - Adempas- @- (Oct 2013)-Anti-hypertensives
Indication Type Description:
Dosages/ Overdosage Etc
Pregnancy and lactation
Strong CYP and P-gp/BCRP inhibitors: For patients receiving strong CYP
and P-gp/BCRP inhibitors, consider a starting dose of 0.5 mg three times a
day. Monitor for hypotension.
Antacids: Separate administration by at least 1 hour.
Adempas (riociguat) tablets, for oral use
Initial U.S. Approval: 2013
WARNING: EMBRYO-FETAL TOXICITY
See full prescribing information for complete boxed warning
Do not administer Adempas to a pregnant female because it may
cause fetal harm. (4.1, 5.1, 8.1)
Females of reproductive potential: Exclude pregnancy before start
of treatment, monthly during treatment, and 1 month after
treatment discontinuation. Prevent pregnancy during treatment and
for one month after treatment discontinuation by use of acceptable
methods of contraception. (2.3, 5.1, 5.2, 8.6)
For females, Adempas is available only through a restricted
program called the Adempas REMS Program. (5.1, 5.2)
RECENT MAJOR CHANGES
Phosphodieterase (PDE) Inhibitors (4.3) (5/2014)
Drug Name- Adempas
Active Ingredient - Riociguat
To treat adults with two forms of pulmonary hypertension
Approved by FDA on 8-10-2013 (Ref- FDA approved List- 2013)
Adverse reactions occurring more frequently (.3%) on Adempas compared to
placebo are headache, dyspepsia/gastritis, dizziness, nausea, diarrhea,
hypotension, vomiting, anemia, gastroesophageal reflux, and constipation.
. Use with nitrates or nitric oxide donors in any form
. Use with PDE inhibitors
WARNINGS AND PRECAUTIONS
- Pulmonary edema in patients with pulmonary veno-occlusive disease. If
confirmed, discontinue treatment
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
Adempas is a soluble guanylate cyclase (sGC) stimulator indicated for the
treatment of adults with:
Persistent/recurrent Chronic Thromboembolic Pulmonary Hypertension
(CTEPH) (WHO Group 4) after surgical treatment or inoperable CTEPH to
improve exercise capacity and WHO functional class.
Pulmonary Arterial Hypertension (PAH) (WHO Group 1) to improve
exercise capacity, improve WHO functional class and to delay clinical
DOSAGE AND ADMINISTRATION
Initiate treatment at 1 mg taken three times a day.
For patients who may not tolerate the hypotensive effect of Adempas,
consider a starting dose of 0.5 mg, three times a day.
Increase dosage by 0.5 mg at intervals of no sooner than 2-weeks as
tolerated to a maximum of 2.5 mg three times a day.
DOSAGE FORMS AND STRENGTHS
Tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg
PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Medication Guide). Embryo-Fetal Toxicity
Instruct patients on the risk of fetal harm when Adempas is used during pregnancy
Instruct females of reproductive potential to use effective contraception and to
contact her physician immediately if they suspect they may be pregnant.
Female patients must enroll in the Adempas REMS Program.
Adempas REMS Program
For female patients, Adempas is available only through a restricted program
called the Adempas REMS
Male patients are not enrolled in the Adempas REMS Program.
Inform female patients (and their guardians, if applicable) of the following
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
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. Other Risks Associated
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.
1. Mechanism of Action
Riociguat is a stimulator of soluble guanylate cyclase (sGC), an enzyme in the
cardiopulmonary system and the receptor for nitric oxide (NO).
When NO binds to sGC, the enzyme catalyzes synthesis of the signaling
molecule cyclic guanosine monophosphate (cGMP). Intracellular cGMP
plays an important role in regulating processes that influence vascular tone,
proliferation, fibrosis and inflamm
Riociguat pharmacokinetics are dose proportional from 0.5 to 2.5 mg. Inter-individual
variability of riociguat exposure (AUC) across all doses is approximately 60%,
and within-subject variability is approximately 30%.
Absorption and distribution
The absolute bioavailability of riociguat is about 94%. Peak plasma riociguat
concentrations were observed within 1.5 hours after tablet intake.
Food does not affect the bioavailability of riociguat.
Pregnancy and lactation:
Pregnancy Category X
Adempas may cause fetal harm when administered to a pregnant woman and is
contraindicated during pregnancy. Adempas was teratogenic and embryotoxic
in rats at doses with exposures to unbound drug that were approximately
8 times and 2 times, respectively, the human exposure. .
If Adempas is used in pregnancy, or if the patient becomes pregnant while taking
this drug, apprise the patient of the potential hazard to the fetus
2. Nursing Mothers
It is not known if Adempas is present in human milk. Riociguat or its metabolites
were present in the milk of rats. Because many drugs are present in human milk
and because of the potential for serious adverse reactions in nursing infants from
riociguat, discontinue nursing or Adempas.
Safety and effectiveness of Adempas in pediatric patients have not been
4. Geriatric Use
Of the total number of subjects in clinical studies of Adempas, 23% were 65 and over,
and 6% were 75 and over
. No overall differences in safety or effectiveness were observed between these
subjects and younger subjects, and other reported clinical experience has not
identified differences in responses between the elderly and younger patients,
but greater sensitivity of some older individuals cannot be ruled out.
Elderly patients showed a higher exposure to Adempas [see Clinical Pharmacology (12.3)].