- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral formulations of riociguat.
Chronic thromboembolic pulmonary hypertension: functional grades II and III
Pulmonary arterial hypertension: functional grades II and III
Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Riociguat is indicated for the treatment of adult patients with WHO functional class II to III with:
Persistent or recurrent CTEPH after surgical treatment,
to improve exercise capacity.
Pulmonary arterial hypertension (PAH)
Riociguat, as monotherapy or in combination with endothelin receptor antagonists, is indicated for the treatment of adult patients with pulmonary arterial hypertension (PAH) with WHO functional class II to III to improve exercise capacity.
Efficacy has been shown in a PAH population including aetiologies of idiopathic or heritable PAH or PAH associated with connective tissue disease.
The recommended starting dose is 1mg three times daily for 2 weeks. Tablets should be taken three times daily approximately 6 to 8 hours apart.
Dose should be increased by 500micrograms three times daily every two weeks to a maximum of 2.5mg three times daily, if systolic blood pressure is greater than or equal to 95mmHg and the patient has no signs or symptoms of hypotension. In some PAH patients, an adequate response on the 6 minute walk distance may be reached at a dose of 1.5mg three a day. If systolic blood pressure falls below 95mmHg, the dose should be maintained provided the patient does not show any signs or symptoms of hypotension. If at any time during the up-titration phase systolic blood pressure decreases below 95mmHg and the patient shows signs or symptoms of hypotension the current dose should be decreased by 500micrograms three times daily.
The established individual dose should be maintained unless signs and symptoms of hypotension occur. The maximum total daily dose is 7.5mg (i.e. 2.5mg three times daily).If not tolerated, dose reduction should be considered at any time.
Additional Dosage Information
If a dose is missed, treatment should be continued with the next dose as planned.
If treatment has to be interrupted for 3 days or more, restart treatment at 1mg three times daily for 2 weeks, and continue treatment with the dose titration regimen as described above.
Current smokers should be advised to stop smoking due to a risk of a lower response. Plasma concentrations of riociguat in smokers are reduced compared to non-smokers. A dose increase to the maximum daily dose of 2.5mg three times daily may be required in patients who are smoking or start smoking during treatment.
A dose decrease may be required in patients who stop smoking.
For oral administration. For patients who are unable to swallow whole tablets, the tablets may be crushed and mixed with water or soft foods such as apple sauce immediately prior to use and administered orally.
Children under 18 years
History of severe haemoptysis
Systolic blood pressure < 95 mmHg at initiation
Within 48 hours of discontinuing tadalafil
Pulmonary hypertension associated with idiopathic interstitial pneumonia
Pulmonary hypertension secondary to venous occlusive disorder
Renal impairment - creatinine clearance below 30 ml/minute
Serum bilirubin above 2 times upper limit of normal
Serum transaminases above 3 times upper limit of normal
Severe hepatic impairment
Precautions and Warnings
Females of childbearing potential
Patients over 65 years
Glucose-galactose malabsorption syndrome
Left ventricular outflow obstruction
Moderate hepatic impairment
Renal impairment - creatinine clearance 30-50ml/minute
Advise ability to drive/operate machinery may be affected by side effects
Avoid PDE type 5 inhibitor for 24 hours after discontinuing riociguat
Avoid riociguat within 24 hours of discontinuing sildenafil
Reduced plasma level and efficacy in smokers
Treatment to be initiated and supervised by a specialist
Ensure negative monthly pregnancy tests throughout treatment
Consider veno-occlusive disease if pulmonary oedema occurs
Discontinue if idiopathic interstitial pneumonia occurs
Discontinue if pulmonary oedema occurs
Dose adjustment required if patient starts/stops smoking during therapy
Advise patient not to take St John's wort concurrently
Avoid antacids 1 hour after or 2 hours before dose
Female: Ensure adequate contraception during treatment
Advise patient on giving up smoking
The use of riociguat in forms other than idiopathic or heritable PAH and PAH associated with connective tissue disease, have not been studied therefore are not recommended.
In pulmonary hypertension patients there is increased likelihood for respiratory tract bleeding, particularly among patients receiving anticoagulation therapy. A careful monitoring of patients taking anticoagulants according to common medical practice is recommended.
Riociguat should be avoided in patients who have previously undergone bronchial arterial embolisation. In the case of respiratory tract bleeding, the prescriber should regularly assess the benefit-risk of treatment continuation.
Pregnancy and Lactation
Riociguat is contraindicated in pregnancy.
At the time of writing there is limited data from the use of riociguat in pregnant women.
Animal studies have shown reproductive toxicity and placental transfer.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Riociguat is contraindicated in breastfeeding.
At the time of writing there is limited data on the use of riociguat in breastfeeding women. Due to the potential for serious adverse reactions in nursing infants riociguat should not be used during breastfeeding. A risk to the suckling child cannot be excluded.
Data from animals indicate that riociguat is secreted into breast milk.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Gastroesophageal reflux disease
Last Full Review Date: June 2018
Summary of Product Characteristics: Adempas 0.5mg film-coated tablets. Merck Sharp & Dohme Ltd. Revised March 2018.
Summary of Product Characteristics: Adempas 1.0mg film-coated tablets. Merck Sharp & Dohme Ltd. Revised March 2018.
Summary of Product Characteristics: Adempas 1.5mg film-coated tablets. Merck Sharp & Dohme Ltd. Revised March 2018.
Summary of Product Characteristics: Adempas 2mg film-coated tablets. Merck Sharp & Dohme Ltd. Revised March 2018.
Summary of Product Characteristics: Adempas 2.5mg film-coated tablets. Merck Sharp & Dohme Ltd. Revised March 2018.
MHRA Drug Safety Update August 2016
Available at: https://www.mhra.gov.uk
Last accessed: 11 June 2018
Specialist Pharmacy Service (SPS)
Available at: https://www.sps.nhs.uk/
What are the clinically significant drug interactions with tobacco smoking? Last revised: July 2020
Last accessed: 07 December 2020
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.