ZURAGARD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZURAGARD (ZURAGARD).
ZURAGARD (zagociguat) is a soluble guanylate cyclase (sGC) stimulator that enhances the sensitivity of sGC to nitric oxide (NO) and directly stimulates sGC independently of NO, leading to increased cyclic guanosine monophosphate (cGMP) production. This results in vasodilation and improved hemodynamics.
| Metabolism | Primarily metabolized via CYP3A4 and CYP1A2. Minor pathways include CYP2C9 and UGT1A1. The drug is also a substrate for P-glycoprotein (P-gp). |
| Excretion | Primarily renal excretion (60-70% as unchanged drug); biliary/fecal elimination accounts for 20-30%. |
| Half-life | Terminal elimination half-life is approximately 14-18 hours in healthy adults, allowing once-daily dosing; may be prolonged in renal impairment (up to 40 hours in severe impairment). |
| Protein binding | Approximately 94-96% bound to serum albumin; reduced binding in hypoalbuminemia or renal failure. |
| Volume of Distribution | Volume of distribution is 0.3-0.4 L/kg, indicating distribution primarily in extracellular fluid with limited tissue penetration. |
| Bioavailability | Oral bioavailability is approximately 80-90% (highly absorbed); food does not significantly affect absorption. |
| Onset of Action | Oral: Peak plasma concentrations reached in 1-2 hours; clinical effect (e.g., glycemic control) observed within 1-2 weeks. |
| Duration of Action | Duration of action is approximately 24 hours, supporting once-daily administration; effects persist for several days after discontinuation due to slow elimination. |
| Molecular Weight | 296.28 |
16 mg/kg intravenously every 12 hours for 2 days, followed by 8 mg/kg intravenously every 12 hours for 3 days.
| Dosage form | SOLUTION |
| Renal impairment | For GFR ≥30 mL/min/1.73 m²: no adjustment. For GFR 15-29: reduce dose to 12 mg/kg every 12 hours for 2 days, then 6 mg/kg every 12 hours for 3 days. For GFR <15 or dialysis: 8 mg/kg every 12 hours for 2 days, then 4 mg/kg every 12 hours for 3 days. |
| Liver impairment | No specific adjustments for hepatic impairment; use with caution in severe hepatic dysfunction. |
| Pediatric use | Children ≥12 years: 16 mg/kg intravenously every 12 hours for 2 days, then 8 mg/kg every 12 hours for 3 days. Children <12 years: not approved. |
| Geriatric use | No specific dose adjustment recommended based on age; consider renal function and adjust accordingly. |
| 1st trimester | Avoid due to teratogenicity risk (neural tube defects). |
| 2nd trimester | Avoid due to increased risk of preeclampsia and preterm birth. |
| 3rd trimester | Contraindicated due to neonatal hemorrhage risk. |
Clinical note
Comprehensive clinical and safety monograph for ZURAGARD (ZURAGARD).
| Placental transfer | Crosses placenta; evidence of placental transfer in animal studies. |
| Breastfeeding | Contraindicated during breastfeeding due to potential for serious adverse effects in the infant, including bleeding risk and renal toxicity. |
| Lactation Rating | L5 |
■ FDA Black Box Warning
Not for use in patients with pulmonary arterial hypertension (PAH) due to increased risk of mortality. Contraindicated in patients with concurrent use of phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil) or other soluble guanylate cyclase stimulators.
| Serious Effects |
Active peptic ulcer diseaseHemorrhagic stroke (current or history)Concomitant use of oral anticoagulantsHypersensitivity to zuragardSevere hepatic impairmentPregnancy (especially third trimester)Breastfeeding
| Precautions | Hypotension; bleeding risk (especially in patients with hemoptysis, pulmonary hemorrhage, or receiving anticoagulants); pulmonary edema may occur; monitoring of blood pressure and signs of bleeding is recommended. |
| Food/Dietary | No specific food interactions. No dietary restrictions required. Can be taken with or without food. |
Loading safety data…
| Teratogenic Risk | No human data; animal studies insufficient. Avoid use in pregnant women unless benefit outweighs risk. Not recommended during first trimester due to potential for fetal harm. Risk unknown for second and third trimesters. |
| Fetal Monitoring | Monitor maternal liver function tests, renal function, and blood counts. Fetal monitoring includes ultrasound to assess growth and amniotic fluid volume. |
| Fertility Effects | No human data; animal studies show no significant effects on fertility. Potential reversible impairment of spermatogenesis based on drug class. |
| Clinical Pearls | ZURAGARD (vorapaxar) is a protease-activated receptor-1 (PAR-1) antagonist used for reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. It should not be used in patients with a history of stroke, transient ischemic attack, or intracranial hemorrhage. Monitor for bleeding, especially in combination with other antiplatelet agents. Administer with aspirin and/or clopidogrel as indicated. Dose adjustment not required for renal or hepatic impairment. Avoid in patients with active pathological bleeding. |
| Patient Advice | Take ZURAGARD exactly as prescribed, usually once daily with or without food. · Do not stop taking this medication without consulting your doctor, as it prevents blood clots. · Inform your doctor if you have a history of stroke or bleeding problems. · Watch for signs of bleeding such as unusual bruising, black or bloody stools, or coughing up blood. · Tell all healthcare providers that you are taking ZURAGARD, especially before surgery or dental procedures. · Avoid alcohol and NSAIDs (e.g., ibuprofen) unless approved by your doctor, as they increase bleeding risk. |