Riociguat


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Pulmonary arterial hypertension; Chronic thromboembolic pulmonary hypertension Dosage is individualised based on patient’s response and tolerance: Initial: 0.5-1 mg tid for 2 weeks, increase in increments of 1.5 mg daily at 2 weeks interval. Max dose: 2.5 mg tid.
Dosage Details
Oral
Chronic thromboembolic pulmonary hypertension, Pulmonary arterial hypertension
Adult: Dosage is individualised based on patient’s response and tolerance: Initially, 0.5-1 mg tid, approximately 6-8 hours apart for 2 weeks. Increase dose in increments of 1.5 mg daily at 2 weeks interval up to Max 2.5 mg tid if systolic blood pressure ≥95 mmHg and no hypotension. Decrease dose by 0.5 mg tid if hypotension occurs. If treatment is interrupted for ≥3 days, retitrate from the initial dose.
Special Patient Group
Current smokers: Increase dose up to Max 2.5 mg tid.
Patients taking strong CYP and P-gp/BRCP inhibitors (e.g. azole antifungals or protease inhibitors): Initially, 0.5 mg tid.
Hepatic Impairment
Severe (Child Pugh C): Contraindicated.
Contraindications
Pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP). Severe hepatic impairment (Child Pugh C). Pregnancy and lactation. Concomitant use with nitrates or nitric acid donors, phosphodiesterase (PDE-5) inhibitors (e.g. sildenafil, tadanafil, vardenafil).
Special Precautions
Patient with pulmonary veno-occlusive disease (PVOD), systolic blood pressure <95 mm Hg, hypovolaemia, severe left-ventricular outflow obstruction, autonomic dysfunction, history of serious haemoptysis or bronchial arterial embolization surgery. Smokers. Renal and mild to moderate hepatic impairment.
Adverse Reactions
Significant: Hypotension, pulmonary oedema.
Blood and lymphatic system disorders: Anaemia.
Cardiac disorders: Palpitations.
Gastrointestinal disorders: Dyspepsia, nausea, diarrhoea, vomiting, gastroenteritis, gastritis, GERD, dysphagia, abdominal pain, constipation, abdominal distention.
General disorders and administration site conditions: Peripheral oedema.
Nervous system disorders: Headache, dizziness.
Respiratory, thoracic and mediastinal disorders: Epistaxis, nasal congestion.
Potentially Fatal: Serious bleeding (e.g. haemoptysis, pulmonary haemorrhage).
Patient Counseling Information
This drug may cause drowsiness and dizziness, if affected, do not drive of operate machinery.
MonitoringParameters
Monitor blood pressure; perform pregnancy test prior to and throughout treatment duration; screen for smoking. Monitor signs and symptoms of hypotension, bleeding, and pulmonary oedema.
Overdosage
Symptoms: Pronounced hypotension. Management: Supportive treatment.
Drug Interactions
Decreased serum concentration with antacids, PPI, CYP3A4 inducers (e.g. phenytoin, rifampicin). Increased plasma concentration with CYP1A1 (e.g. erlotinib), CYP3A4 inhibitors (e.g. clarithromycin), potent P-gp/BCRP inhibitors (e.g. ciclosporin, azole antifungals, protease inhibitors).
Potentially Fatal: Enhanced hypotensive effect with amyl nitrate, nitroglycerin, PDE-5 inhibitors (e.g. sildenafil, tadanafil, vardenafil).
Food Interaction
Decreased serum concentration with St. John’s wort.
Action
Description: Riociguat is a soluble guanylate cyclase(sGC) stimulator. It sensitise sGC to endogenous nitric oxide (NO) by stabilising the NO-sGC binding and directly stimulates sGC independent of NO, leading to increased cyclic guanosine monophosphate (cGMP) generation, thereby producing vasodilation and reducing pulmonary artery pressure.
Pharmacokinetics:
Absorption: Rapidly absorbed from the gastrointestinal tract. Absolute bioavailability: Approx 94%. Time to peak plasma concentration: Approx 1.5 hours.
Distribution: Volume of distribution: Approx 30 L. Plasma protein binding: Approx 95% mainly to serum albumin and α1-acid glycoprotein.
Metabolism: Metabolised by CYP1A1, 3A4, 2C8, 2J2 enzymes to an active metabolite, M1, then further metabolised to an inactive metabolite, N-glucuronide.
Excretion: Via faeces (approx 53%); urine (approx 40%). Elimination half-life: Approx 7 hours.
Chemical Structure

Chemical Structure Image
Riociguat

Source: National Center for Biotechnology Information. PubChem Database. Riociguat, CID=11304743, https://pubchem.ncbi.nlm.nih.gov/compound/Riociguat (accessed on Jan. 23, 2020)

Storage
Store at 25°C.
Follow applicable procedures for receiving, handling, administration, and disposal. Wear gloves during receiving, unpacking, and placing in storage.
ATC Classification
C02KX05 - riociguat ; Belongs to the class of other antihypertensives. Used in the treatment of pulmonary arterial hypertension.
References
Adempas Tablet, Film-Coated (Bayer HealthCare Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 02/03/2018.

Anon. Riociguat. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/03/2018.

Buckingham R (ed). Riociguat. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/03/2018.

Joint Formulary Committee. Riociguat. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/03/2018.

McEvoy GK, Snow EK, Miller J et al (eds). Riociguat. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 02/03/2018.

Disclaimer: This information is independently developed by MIMS based on Riociguat from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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