REMS restricted

Riociguat

ADEMPAS

Open Riociguat in the interactive console ↗

Pronunciation: rye-oe-SIG-yoo-at

Riociguat ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Riociguat ballicule

What it isSoluble guanylate cyclase stimulator; pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Why this oneThe only approved medical therapy for inoperable CTEPH.

What limits itEmbryo-fetal toxicity under a REMS, and combining it with a PDE5 inhibitor or nitrate causes severe hypotension. Hemoptysis.

Riociguat molecular structure (skeletal formula) — Molecular structure: Riociguat

FDA-approved for

pulmonary hypertension (2013)

Classes and tags

Clinical profile

Therapeutic safety burden3 / 4

Overdose danger1 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk4 / 4

Legacy pregnancy categoryX

Defining liabilityGenerally tolerated at therapeutic doses; clinically important risks are agent-specific and increase with interactions or organ impairment.

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Embryo-fetal toxicity: contraindicated in pregnancy; exclude pregnancy and use effective contraception.

FDA dosing	Population	Start	Target	Max
Pulmonary arterial hypertension (PAH) & chronic thromboembolic pulmonary hypertension (CTEPH)	Adults	1 mg TID (0.5 mg TID if at risk of hypotension)	up-titrate by 0.5 mg TID as tolerated	2.5 mg TID

Titration Increase by 0.5 mg no sooner than every 2 weeks

Renal Not recommended if CrCl <15 mL/min or on dialysis

Hepatic Not recommended in severe (Child-Pugh C) hepatic impairment

Instructions

May crush and mix with water or soft food (e.g., applesauce) if unable to swallow whole
If interrupted for 3 days or more, re-titrate
Smokers may require doses >2.5 mg TID; a dose decrease may be needed on smoking cessation
Start 0.5 mg TID with strong CYP and P-gp/BCRP inhibitors (e.g., azole antifungals, HIV protease inhibitors)
Separate from PDE5 inhibitors: stop sildenafil >=24 h and tadalafil >=48 h before starting; stop Adempas >=24 h before a PDE5 inhibitor

Available strengths

tab 0.5, 1, 1.5, 2, 2.5 mg

Contraindications

Pregnancy
Concomitant nitrates or nitric oxide donors (e.g., amyl nitrite) in any form
Concomitant PDE inhibitors (specific PDE-5 such as sildenafil, tadalafil, vardenafil; nonspecific such as dipyridamole, theophylline)
Concomitant other soluble guanylate cyclase (sGC) stimulators
Pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP)

Cautions

Symptomatic hypotension (reduces blood pressure)
Bleeding, including serious hemoptysis
Pulmonary veno-occlusive disease - discontinue if pulmonary edema occurs

Adverse reactions

Headache
Dyspepsia/gastritis
Dizziness
Nausea
Diarrhea
Hypotension
Vomiting
Anemia
GERD
Constipation

Pregnancy Contraindicated; may cause fetal harm based on animal data.

Lactation Advise not to breastfeed during treatment.

Cost

Riociguat (ADEMPAS)

Strength		#/mo	CostPlus
0.5 mg	tab	90 TID	not offered
1 mg	tab	90 TID	not offered
1.5 mg	tab	90 TID	not offered
2 mg	tab	90 TID	not offered
2.5 mg	tab	90 TID	not offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Riociguat is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

Generic entry2022

Open Riociguat in the interactive console ↗

Self-check

Riociguat: Which CTEPH population has its approved medical therapy?
Inoperable CTEPH.
Riociguat: Why avoid PDE5 inhibitors or nitrates with it?
Severe hypotension.