Drugs List

Therapeutic Indications

Uses

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:
Inoperable CTEPH
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.

Administration

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.

Contraindications

Children under 18 years
History of severe haemoptysis
Systolic blood pressure < 95 mmHg at initiation
Within 48 hours of discontinuing tadalafil
Breastfeeding
Galactosaemia
Pregnancy
Pulmonary hypertension associated with idiopathic interstitial pneumonia
Pulmonary hypertension secondary to venous occlusive disorder
Renal dialysis
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
Tobacco smoking
Autonomic dysfunction
Glucose-galactose malabsorption syndrome
Hypotension
Hypovolaemia
Lactose intolerance
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
Contains lactose
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

Pregnancy

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 ).

Lactation

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

Side Effects

Abdominal distension
Abdominal pain
Anaemia
Constipation
Diarrhoea
Dizziness
Dyspepsia
Dysphagia
Epistaxis
Gastritis
Gastro-enteritis
Gastro-intestinal pain
Gastroesophageal reflux disease
Haemoptysis
Headache
Hypotension
Nasal congestion
Nausea
Palpitations
Peripheral oedema
Pulmonary haemorrhage
Vomiting

Presentation

Oral formulations of riociguat.

Drugs List

Therapeutic Indications

Uses

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:
Inoperable CTEPH
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.

Dosage

Adults

Additional Dosage Information

Administration

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.

Contraindications

Children under 18 years
History of severe haemoptysis
Systolic blood pressure < 95 mmHg at initiation
Within 48 hours of discontinuing tadalafil
Breastfeeding
Galactosaemia
Pregnancy
Pulmonary hypertension associated with idiopathic interstitial pneumonia
Pulmonary hypertension secondary to venous occlusive disorder
Renal dialysis
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
Tobacco smoking
Autonomic dysfunction
Glucose-galactose malabsorption syndrome
Hypotension
Hypovolaemia
Lactose intolerance
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
Contains lactose
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

Pregnancy

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 ).

Lactation

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

Side Effects

Abdominal distension
Abdominal pain
Anaemia
Constipation
Diarrhoea
Dizziness
Dyspepsia
Dysphagia
Epistaxis
Gastritis
Gastro-enteritis
Gastro-intestinal pain
Gastroesophageal reflux disease
Haemoptysis
Headache
Hypotension
Nasal congestion
Nausea
Palpitations
Peripheral oedema
Pulmonary haemorrhage
Vomiting

Further Information

Last Full Review Date: June 2018

Reference Sources

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