ZORVOLEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZORVOLEX (ZORVOLEX).
ZORVOLEX (diclofenac) is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX) enzymes, primarily COX-2, reducing the synthesis of prostaglandins, which are mediators of inflammation, pain, and fever.
| Metabolism | Primarily hepatic via CYP2C9, with minor contributions from CYP3A4. Undergoes glucuronidation and sulfation. |
| Excretion | Renal excretion of metabolites and conjugates accounts for approximately 50% of the dose, with biliary/fecal elimination of the remainder. Less than 5% is excreted unchanged in urine. |
| Half-life | Terminal elimination half-life of the dual-release formulation is approximately 6-7 hours. Clinical context: Allows twice-daily dosing for sustained analgesic effect. |
| Protein binding | 99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 0.1 L/kg. This low Vd indicates limited extravascular distribution, consistent with high protein binding. |
| Bioavailability | Oral bioavailability is approximately 100% for the immediate-release component and 80% for the extended-release component. Overall, the dual-release formulation provides complete systemic absorption. |
| Onset of Action | Oral administration: Onset of analgesic effect within 30-60 minutes. |
| Duration of Action | Duration of effect is approximately 12 hours, consistent with the dual-release profile. Clinical notes: Administered twice daily. |
50 mg orally every 8 hours or 100 mg orally every 12 hours; maximum 200 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-59 mL/min: reduce dose to 50 mg every 12 hours; GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh class B: 50 mg every 12 hours; Child-Pugh class C: avoid use. |
| Pediatric use | 2 years and older: 1 mg/kg orally every 8 hours; maximum 40 mg/day. |
| Geriatric use | Initial dose 50 mg every 12 hours; maximum 100 mg/day; monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZORVOLEX (ZORVOLEX).
| Breastfeeding | Excretion into breast milk is likely low due to high protein binding. The milk-to-plasma ratio is unknown for Zorvolex (diclofenac); for diclofenac, estimated M/P ratio is 0.005-0.05. Use with caution; limited clinical data suggest minimal risk to infant. Prefer short-term use at lowest effective dose. |
| Teratogenic Risk | First trimester: Risk of spontaneous abortion and congenital malformations, particularly cardiovascular and gastrointestinal defects, based on NSAID class effects. Second trimester: No well-documented human teratogenic effects, but avoid due to potential fetal renal impairment and oligohydramnios. Third trimester: Category D; increased risk of premature closure of ductus arteriosus, fetal renal dysfunction, oligohydramnios, and periventricular hemorrhage. Avoid after 30 weeks gestation. |
■ FDA Black Box Warning
NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. ZORVOLEX is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
| Serious Effects |
History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; perioperative pain in the setting of CABG surgery; known hypersensitivity to diclofenac or any component of the formulation.
| Precautions | Cardiovascular thrombotic events; gastrointestinal bleeding, ulceration, and perforation; hypertension; heart failure; renal toxicity; hepatic effects; anemia; skin reactions including Stevens-Johnson syndrome; anaphylactic reactions; asthma exacerbation; fluid retention; concomitant use with aspirin or other NSAIDs; pregnancy avoidance in third trimester. |
Loading safety data…
| Fetal Monitoring | Monitor for uterine contractions, fetal heart rate, and amniotic fluid index by ultrasound if using after 20 weeks. Assess fetal renal function with amniotic fluid volume monitoring. In third trimester, avoid use; if unavoidable, monitor ductus arteriosus by fetal echocardiography. |
| Fertility Effects | Reversible suppression of female fertility due to inhibition of prostaglandin synthesis affecting ovulation and implantation. May delay ovulation or cause luteal phase dysfunction. Discontinuation restores normal fertility. No male fertility effects reported. |