Adult: As treatment for persistent or recurrent cases after surgical treatment or for inoperable cases to improve exercise capacity: Individualise dosing according to patient's response and tolerance. Usual dose: Initially, 1 mg tid (approx 6-8 hours apart) for 2 weeks. Consider an initial dose of 0.5 mg tid for patients who are at higher risk of hypotension. If systolic blood pressure remains ≥95 mmHg and no signs or symptoms of hypotension are present, increase the dose by 0.5 mg tid every 2 weeks up to a Max of 2.5 mg tid. If signs or symptoms of hypotension occur during therapy, decrease the dose by 0.5 mg tid. Re-titrate from the initial dose if treatment is interrupted for ≥3 days. Recommendations may vary among countries and between individual products (refer to specific product guidelines).
Oral Pulmonary arterial hypertension
Adult: As monotherapy or in combination with endothelin receptor antagonists: Individualise dosing according to patient's response and tolerance. Usual dose: Initially, 1 mg tid (approx 6-8 hours apart) for 2 weeks. Consider an initial dose of 0.5 mg tid for patients who are at higher risk of hypotension. If systolic blood pressure remains ≥95 mmHg and no signs or symptoms of hypotension are present, increase the dose by 0.5 mg tid every 2 weeks up to a Max of 2.5 mg tid. If signs or symptoms of hypotension occur during therapy, decrease the dose by 0.5 mg tid. Re-titrate from the initial dose if treatment is interrupted for ≥3 days. Recommendations may vary among countries and between individual products (refer to specific product guidelines).
What are the brands available for Riociguat in Singapore?
Adempas
Special Patient Group
Patients concurrently receiving strong multi-pathway CYP and P-gp/BCRP inhibitors such as azole antimycotics (e.g. ketoconazole, itraconazole) or HIV protease inhibitors (e.g. ritonavir): Initially, 0.5 mg tid.
Patients who started or stopped smoking during riociguat treatment: Dosing adjustment may be required.
Hepatic Impairment
Severe (Child-Pugh class C): Contraindicated.
Contraindications
Pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP). Severe hepatic impairment (Child-Pugh class C). Pregnancy and lactation. Concurrent use with phosphodiesterase (PDE) inhibitors, nitrates or nitric oxide donors (e.g. amyl nitrite), and other soluble guanylate cyclase (sGC) stimulators.
Special Precautions
Patient with pulmonary veno-occlusive disease (PVOD); increased risk for ischaemia or symptomatic hypotension (e.g. hypovolaemia, resting hypotension, severe left ventricular outflow obstruction, autonomic dysfunction). Avoid use in patients with history of serious haemoptysis or those previously managed with bronchial arterial embolisation. Concurrent use with strong multi-pathway CYP and P-gp/BCRP inhibitors. Smoking (including cessation). Renal and moderate hepatic impairment. Elderly.
Adverse Reactions
Significant: Hypotension. Blood and lymphatic system disorders: Anaemia. Cardiac disorders: Palpitations. Gastrointestinal disorders: Nausea, vomiting, dyspepsia, diarrhoea, constipation, gastroenteritis, gastritis, GERD, dysphagia, abdominal distension, gastrointestinal and abdominal pain. General disorders and administration site conditions: Peripheral oedema. Nervous system disorders: Headache, dizziness. Respiratory, thoracic and mediastinal disorders: Nasal congestion, epistaxis. Potentially Fatal: Serious bleeding (including haemoptysis or pulmonary haemorrhage).
PO: Z (Embryo-foetal mortality and malformations were observed in animal studies. Contraindicated during
pregnancy.)
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery. Women of childbearing potential must use proven birth control methods during therapy and for 1 month after stopping the treatment.
Monitoring Parameters
Evaluate pregnancy status in women of childbearing potential before treatment initiation, monthly during therapy, and 1 month after discontinuation of treatment. Monitor blood pressure. Assess for signs and symptoms of hypotension, significant peripheral oedema, pulmonary oedema, and bleeding.
Drug Interactions
Increased risk of respiratory tract bleeding with anticoagulants. Concomitant use with strong multi-pathway CYP and P-gp/BCRP inhibitors such as azole antimycotics (e.g. ketoconazole, posaconazole, itraconazole), ciclosporin or HIV protease inhibitors (e.g. ritonavir), and with strong CYP1A1 inhibitors such as tyrosine kinase inhibitors (e.g. erlotinib) may increase riociguat exposure which may cause hypotension. Lower oral bioavailability with drugs that increase gastric pH (e.g. antacids containing Al hydroxide or Mg hydroxide). Decreased plasma concentrations with bosentan and strong CYP3A4 inducers (e.g. phenytoin, carbamazepine, phenobarbital). May enhance the adverse effects of other sGC stimulators (e.g. vericiguat). Potentially Fatal: Concurrent use with PDE inhibitors, including specific PDE-5 inhibitors (e.g. vardenafil, tadalafil, sildenafil) or nonspecific PDE inhibitors (e.g. theophylline, dipyridamole), and nitrates or nitric oxide donors (e.g. amyl nitrite) may result in additive hypotensive effects.
Food Interaction
Decreased plasma concentration with St. John's wort.
Action
Description: Mechanism of Action: Riociguat is a stimulator of soluble guanylate cyclase (sGC), a receptor for nitric oxide (NO) and an enzyme present in the cardiopulmonary system. It enhances the sensitivity of sGC to endogenous NO by stabilising the NO-sGC binding and also directly stimulates sGC independently of NO. Riociguat restores the NO-sGC-cyclic guanosine monophosphate (cGMP) pathway, resulting in increased cGMP generation and subsequent vasodilation. Pharmacokinetics: Absorption: Bioavailability: Approx 94%. Time to peak plasma concentration: Approx 1-1.5 hours. Distribution: Plasma protein binding: Approx 95%, mainly to serum albumin and α1-acid glycoprotein. Metabolism: Metabolised by CYP1A1, CYP3A4, CYP2C8, and CYP2J2 into M1 (major active metabolite) which is further metabolised into inactive N-glucuronide. Excretion: Via faeces (approx 53%); urine (approx 40%). Elimination half-life: Approx 7 hours.
Chemical Structure
Riociguat Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 11304743, Riociguat. https://pubchem.ncbi.nlm.nih.gov/compound/Riociguat. Accessed Sept. 25, 2024.
Storage
Store between 15-30°C. Follow applicable procedures for receiving, handling, administration, and disposal.
C02KX05 - riociguat ; Belongs to the class of other antihypertensives. Used in the treatment of pulmonary arterial hypertension.
References
Adempas 2.5 mg Film-Coated Tablets (Bayer plc). MHRA. https://products.mhra.gov.uk. Accessed 04/09/2024.Adempas Film-coated Tablet (Bayer Co. [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 04/09/2024.Adempas Tablet, Film Coated (Bayer Healthcare Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 04/09/2024.Anon. Riociguat. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 05/09/2024.Brayfield A, Cadart C (eds). Riociguat. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/09/2024.Joint Formulary Committee. Riociguat. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/09/2024.Riociguat. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 05/09/2024.
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