VOYXACT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VOYXACT (VOYXACT).
GABAA receptor positive allosteric modulator; a neuroactive steroid that potentiates GABAergic inhibition.
| Metabolism | Primarily via CYP3A4 and CYP3A5; also undergoes aldo-keto reductase (AKR1C1, AKR1C2, AKR1C3) metabolism. |
| Excretion | Primarily hepatic metabolism via CYP3A4, with 53% of the dose excreted in feces (mainly as metabolites) and 27% in urine (mostly as metabolites); less than 1% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life approximately 37 hours (range 24-51 hours), supporting once-daily dosing with steady-state achieved in 5-8 days. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution 9-12 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability approximately 90% with minimal food effect. |
| Onset of Action | Oral administration: clinical improvement observed within 2-4 weeks, with maximal effect at 8-12 weeks. |
| Duration of Action | Sustained over 24 hours with once-daily dosing; steady-state conditions maintained with regular administration. |
| Molecular Weight | 384.5 |
Adults: 200 mg orally once daily with food.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), reduce dose to 100 mg once daily. For end-stage renal disease (ESRD) not on dialysis, use is not recommended. |
| Liver impairment | Child-Pugh A: No dose adjustment. Child-Pugh B: Reduce dose to 100 mg once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients under 18 years of age. |
| Geriatric use | No specific dose adjustment is recommended based on age alone, but monitor renal function and consider renal adjustment criteria if CrCl <30 mL/min. |
| 1st trimester | Avoid use due to potential teratogenicity. Animal studies show skeletal and visceral malformations at clinically relevant doses. |
| 2nd trimester | Avoid use; risk of fetal nephrotoxicity and oligohydramnios. If essential, monitor amniotic fluid index. |
| 3rd trimester | Avoid use; risk of neonatal nephrotoxicity, hyperkalemia, and respiratory distress. If used, monitor neonate closely. |
Clinical note
Comprehensive clinical and safety monograph for VOYXACT (VOYXACT).
| Placental transfer | VOYXACT crosses the placenta extensively. Studies demonstrate umbilical cord plasma concentrations approximately 50-70% of maternal plasma levels at steady state. |
| Breastfeeding | VOYXACT is excreted in human milk at low concentrations. Due to potential for serious adverse reactions in nursing infants, including nephrotoxicity and hyperkalemia, breastfeeding is not recommended during therapy and for 30 days after last dose. |
■ FDA Black Box Warning
None.
| Common Effects | Nausea Vomiting Stomach pain Indigestion Heartburn Loss of appetite Diarrhea |
| Serious Effects |
Anuria (present or history of)Severe renal impairment (eGFR < 15 mL/min/1.73 m²)Hyperkalemia > 5.5 mEq/L at initiationKnown hypersensitivity to VOYXACT or any componentConcurrent use with potassium-sparing diureticsConcurrent use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole)
| Precautions | Somnolence/sedation, Suicidal thoughts and behaviors, Risk of CNS depression with alcohol or other CNS depressants, Hypersensitivity reactions including angioedema |
| Food/Dietary | No significant food interactions. Grapefruit juice may increase vorapaxar exposure due to CYP3A4 inhibition; avoid excessive grapefruit juice consumption. St. John's wort may reduce vorapaxar efficacy; avoid concurrent use. |
Loading safety data…
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | Category X: Contraindicated in pregnancy. First trimester: high risk of major congenital malformations (neural tube defects, craniofacial anomalies, cardiac defects). Second/third trimester: risk of fetal growth restriction, oligohydramnios, neonatal renal impairment. |
| Fetal Monitoring | Maternal: renal function, hepatic function, blood pressure. Fetal: ultrasound for malformations, growth scans, amniotic fluid index. |
| Fertility Effects | May impair fertility in females (oligomenorrhea) and males (spermatogenesis disruption). Effects are reversible upon discontinuation. |
| Clinical Pearls | VOYXACT (vorapaxar) is a protease-activated receptor-1 (PAR-1) antagonist that inhibits thrombin-induced platelet aggregation. It is indicated for reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or peripheral arterial disease. Avoid use in patients with a history of stroke, transient ischemic attack, or intracranial hemorrhage due to increased bleeding risk. Monitor for bleeding, especially in patients also taking antiplatelet agents, anticoagulants, NSAIDs, or SSRIs. The drug is metabolized by CYP3A4; avoid strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) and inducers (e.g., rifampin, St. John's wort). No dose adjustment for renal impairment. |
| Patient Advice | Take VOYXACT exactly as prescribed, usually once daily with or without food. · Do not stop taking this medication without consulting your doctor, as it may increase your risk of heart attack or stroke. · Inform all healthcare providers that you are taking VOYXACT, especially before any surgery or dental procedure due to increased bleeding risk. · Report any unusual bleeding, bruising, blood in urine or stool, or prolonged bleeding from cuts immediately. · Avoid taking other medications that increase bleeding risk such as aspirin, NSAIDs (e.g., ibuprofen, naproxen), blood thinners (e.g., warfarin), or SSRIs without your doctor's approval. · Seek emergency medical attention if you experience sudden severe headache, vision changes, weakness on one side of the body, or difficulty speaking, which may indicate a stroke. · Store at room temperature away from moisture and heat. |