Adult Dosing

Pulmonary Hypertension

• Initial dose: 1 mg PO tid. consider 0.5 mg PO tid for patients who are unable to tolerate the hypotensive effect of riociguat
• If systolic blood pressure >95 mmHg and no symptoms of hypotension: up-titrate dose by 0.5 mg PO tid with dose increases no sooner than 2 weeks apart to highest tolerated dose. Max: 2.5 mg PO tid
• If symptoms of hypotension occur, decrease dose by 0.5 mg PO tid

Note:

• If a dose is missed, continue with next regularly scheduled dose or if interrupted for 3 days, re-titrate riociguat
• Get pregnancy tests done before initiation and monthly during treatment
• Titrate dosages higher than 2.5 mg PO tid, if tolerated, in patients who smoke. Consider dose decrease in patients who stop smoking
• Consider dose of 0.5 mg tid when coadministrating with strong CYP and P-gp/BCRP inhibitors

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) (WHO Group 4) after surgical treatment or inoperable CTEPH to improve exercise capacity and WHO functional class
• Pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity, improve WHO functional class and to delay clinical worsening

• Pregnancy
• Nitrates and nitric oxide donors
• Phosphodiesterase inhibitors
• Hypersensitivity to any of the ingredients of the product

• Therapy may cause fetal harm and is contraindicated in pregnant female
• Exclude pregnancy prior to treatment, monthly during treatment, and 1 month after stopping treatment. Prevent pregnancy during treatment and for one month after stopping treatment by using acceptable methods of contraception
• For all female patients, therapy is available ONLY through a restricted program called the Adempas Risk Evaluation and Mitigation Strategy (REMS) Program

Renal Dose Adjustment

• Renal impairment: Not recommended in creatinine clearance <15mL/min o on dialysis.

Hepatic Dose Adjustment

• Hepatic impairment:Not recommended in patients with severe (Child Pugh C) hepatic impairment

Smokers

• Dosage higher than 2.5 mg TID, if tolerated. Dose decrease may be needed if patient quits smoking

See Supplemental Patient Information

• Therapy may cause fetal harm and is contraindicated in pregnant female. Exclude pregnancy prior to treatment, monthly during treatment, and 1 month after stopping treatment. Prevent pregnancy during treatment and for one month after stopping treatment by using acceptable methods of contraception. For all female patients, therapy is available only through a restricted program called the Adempas Risk Evaluation and Mitigation Strategy (REMS) Program [FDA Black Box Warning]
• Therapy may reduces blood pressure. Consider the potential for symptomatic hypotension or ischemia in patients with hypovolemia, severe left ventricular outflow obstruction, resting hypotension, autonomic dysfunction, or concomitant treatment with antihypertensives or strong CYP and P-gp/BCRP inhibitors
• Serious bleeding was reported including hemoptysis, vaginal bleeding, catheter site hemorrhage, subdural hematoma, hematemesis, and intra-abdominal hemorrhage in patient receiving riociguat
• Pulmonary vasodilators may exacerbate cardiovascular status of patients with pulmonary veno-occlusive disease; avoid use in these patients and discontinue if signs of pulmonary edema is reported

Supplemental Patient Information

• Advise patients that antacids should not be taken within 1 hour of taking riociguat
• Inform patients that therapy can cause dizziness, which can affect the ability to drive and use machines

Adempas interacts with :

	Dilatrate-SR
	Imdur ER
	Ismo
	IsoDitrate
	Isordil
	Isordil Titradose
	Isosorbide Dinitrate
	Isosorbide Mononitrate
	Minitran
	Monoket
	Nitro-Bid
	Nitro-Dur
	Nitrogard
	Nitroglycerin
	Nitrolingual
	Nitromist
	Nitrostat
	Rectiv

Pregnancy Category:X

Breastfeeding: Riociguat or its metabolites were present in the milk of rats. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from riociguat, discontinue nursing or drug

• CNS: Headache, dizziness
• GI: Dyspepsia and gastritis, nausea, diarrhea, vomiting, gastroesophageal reflux disease, constipation, dysphagia, abdominal distension
• HEMA: Bleeding, anemia
• CV: Hypotension, palpitations
• REPRODUCTIVE: Embryo-fetal toxicity
• EENT: Nasal congestion, epistaxis
• MISC: Peripheral edema

• Soluble guanylate cyclase (sGC) stimulator: It sensitizes sGC to endogenous nitric oxide (NO) by stabilizing the NO-sGC binding. Riociguat also act by stimulating the NO-sGC-cGMP pathway and leads to increased generation of cGMP with subsequent vasodilation
• Absolute bioavailability is 94%
• Metabolized by liver; CYP450: 1A1, 3A, 2C8 2J2
• Excreted in urine (40%) and feces (53%)
• Half-life: 12 hr (patients with PAH); 7 hr (healthy individuals)

US Trade Name(s)

• Adempas

US Availability

Adempas

• TABS: 0.5, 1, 1.5, 2, 2.5 mg

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Cardiovascular

Pulmonary Hypertension Agents

Soluble Guanylate Cyclase (sGC) Stimulator