• Chronic thromboembolic pulmonary hypertension (WHO Group 4) after surgery or in nonsurgical candidates.
• Pulmonary arterial hypertension (WHO Group 1)

Contraindicated in:

• Severe hepatic impairment
• Severe renal impairment (CCr <15 mL/min or on dialysis)
• Known pulmonary veno-occlusive disease
• Pulmonary hypertension associated with idiopathic interstitial pneumonia
• Concurrent use of nitrates, nitric oxide donors, specific phosphodiesterase-5 (PDE) inhibitors (sildenafil, vardenafil, or tadalafil), nonspecific PDE inhibitors (dipyridamole or theophylline), or other soluble guanylate cyclase stimulators
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Resting hypotension, hypovolemia, severe left-ventricular outflow obstruction, or autonomic dysfunction (↑ risk of hypotension, consider dose reduction)
• Cigarette smokers (require ↑ doses, with subsequent adjustment if smoking is stopped)
• Women of reproductive potential
• Pedi: Safety and effectiveness not established in children
• Geri: Older adults may have ↑ levels and be more sensitive to drug effects.

CV: hypotension.

GI: dyspepsia, gastritis, nausea, vomiting, constipation, diarrhea, gastroesophageal reflux, ↑ liver enzymes.

Hemat: anemia, BLEEDING.

Neuro: dizziness, headache.

Resp: pulmonary edema (↑ in veno-occlusive disease).

Drug-Drug:

• ↑risk of hypotension with concurrent use of nitrates, nitric oxide donors (including amyl nitrate), specific PDE-5 inhibitors (including sildenafil, tadalafil, or vardenafil), and nonspecific PDE-5 inhibitors (including dipyridamole or theophylline); concurrent use contraindicated; do not administer within 24 hr of sildenafil; do not administer 24 hr before or within 48 hr after tadalafil.
• Concurrent use with soluble guanylate cyclase stimulators (including vericiguat) is contraindicated.
• Strong CYP and P-glycoprotein (P-gp)/breast cancer resistance protein (BCRP) inhibitors, including azole antifungals (ketoconazole and itraconazole) and protease inhibitors (ritonavir), ↑ levels and the risk of adverse reactions including hypotension; consider ↓ initial dose.
• Strong CYP3A inducers, including carbamazepine, phenobarbital, phenytoin, and rifampin, ↓ levels and may ↓ effectiveness.
• Concurrent use of antihypertensives, including diuretics, may ↑ risk of hypotension.
• Antacids↓ absorption; separate doses by 1 hr.
• Cigarette smoking ↓levels and effectiveness; ↑ dose may be necessary and dose readjustment required after smoking cessation.

Drug-Natural Products:

• St. John's wort ↓levels and may ↓ effectiveness.

(Generic available)

• Tablets: 0.5 mg; 1 mg; 1.5 mg; 2 mg; 2.5 mg;

• PO (Adults): 1 mg 3 times daily initially; if hypotension a risk factor, initiate treatment with 0.5 mg 3 times daily; ↑ dose by 0.5 mg at 2 wk (or more) intervals up to maintenance dose of 2.5 mg 3 times daily; Smokers: Consider titrating to doses >2.5 mg 3 times daily if tolerated (readjust following smoking cessation); Concurrent CYP and P-gp/BRCP inhibitors: Consider initiating treatment at 0.5 mg 3 times daily, with careful monitoring for hypotension.

Adempas

• Stimulates soluble guanylate cyclase, a cardiopulmonary enzyme and receptor for nitric oxide, which when stimulated produces cyclic guanine monophosphate, an important regulator of vascular tone, proliferation, fibrosis, and inflammation. This pathway is dysregulated in pulmonary hypertension.

• Improved symptoms/exercise tolerance and delayed worsening.

Therapeutic Classification:pulmonary hypertension agents

Pharmacologic Classification: soluble guanylate cyclase stimulators (sGS)

Absorption: Well absorbed following oral administration (94%).

Distribution: Unknown.

Protein Binding: 95%.

Metabolism/Excretion: Extensively metabolized by the liver via the CYP1A1, CYP3A, CYP2C8, and CYP2J2 isoenzymes; M1 metabolite is pharmacologically active; metabolites are excreted in urine and feces.

Half-life: 12 hr.

(improvement in 6-min walk distance)

• Instruct patient to take riociguat as directed. If dose is missed, omit and continue with next scheduled dose.
• Advise patient to avoid taking antacids within 1 hr of riociguat.
• Advise patient to notify health care professional if they smoke.
• May cause dizziness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
• May cause fetal harm. Instruct females to use effective contraception (intrauterine device IUD, contraceptive implants, tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods) during and for at least one month following discontinuation of therapy. If a partner’s vasectomy is method of contraception, a hormone or barrier method must be used along with this method. Counsel patient on emergency contraception. May decrease sperm count in male patients. Advise females of reproductive potential to notify health care professional immediately if pregnancy is suspected and avoid breastfeeding during therapy.

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