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Indications and Dosage
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.
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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. |
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Hepatic Impairment
Severe (Child Pugh C): Contraindicated.
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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).
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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.
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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). |
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Patient Counseling Information
This drug may cause drowsiness and dizziness, if affected, do not drive of operate machinery.
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Monitoring Parameters
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.
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Overdosage
Symptoms: Pronounced hypotension. Management: Supportive treatment.
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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). |
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Food Interaction
Decreased serum concentration with St. John’s wort.
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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. |
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Chemical Structure
 Source: National Center for Biotechnology Information. PubChem Database. Riociguat, CID=11304743, https://pubchem.ncbi.nlm.nih.gov/compound/Riociguat (accessed on Jan. 23, 2020) |
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Storage
Store at 25°C.
Follow applicable procedures for receiving, handling, administration, and disposal. Wear gloves during receiving, unpacking, and placing in storage. |
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MIMS Class
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ATC Classification
C02KX05 - riociguat ; Belongs to the class of other antihypertensives. Used in the treatment of pulmonary arterial hypertension.
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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.
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