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. |
| Molecular Weight | 296.15 |
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 | Avoid use during first trimester, especially week 20-30. NSAIDs are associated with increased risk of miscarriage and cardiac defects. |
| 2nd trimester | Use with caution; may be used if benefit outweighs risk. Potential for oligohydramnios and premature ductus arteriosus constriction increases after 20 weeks. |
| 3rd trimester | Contraindicated after 30 weeks (or earlier if risk) due to risk of premature closure of ductus arteriosus and oligohydramnios. |
Clinical note
Comprehensive clinical and safety monograph for ZORVOLEX (ZORVOLEX).
| Placental transfer | NSAIDs, including diclofenac, cross the placenta. Transfer is dependent on molecular weight, protein binding, and lipid solubility. Animal studies show transfer; human data confirm placental passage. |
| Breastfeeding | Zorvolex (diclofenac) is excreted into breast milk in very low amounts. Short-term use is considered compatible with breastfeeding. Monitor infant for potential adverse effects such as gastrointestinal upset or rash. |
■ 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 |
Known hypersensitivity to diclofenac or any componentHistory of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsIn the setting of coronary artery bypass graft (CABG) surgeryAdvanced renal disease or significant renal impairmentPregnancy after 30 weeks gestation (premature closure of ductus arteriosus)
| 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. |
| Food/Dietary | Avoid alcohol as it increases risk of GI bleeding. Taking with food may lessen GI irritation. No specific food restrictions but avoid high-sodium diets if hypertension is a concern. |
Loading safety data…
| Lactation Rating | L2 (Safer) |
| 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. |
| 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. |
| Clinical Pearls | Zorvolex (diclofenac potassium) is a nonsteroidal anti-inflammatory drug (NSAID) with a rapid onset due to its immediate-release formulation. It is indicated for mild to moderate acute pain. Monitor renal function in elderly or dehydrated patients. Avoid in patients with history of GI bleeding or NSAID allergy. Use lowest effective dose for shortest duration. |
| Patient Advice | Take with food or milk to reduce stomach upset. · Do not take with other NSAIDs like ibuprofen or naproxen. · Avoid alcohol while taking this medication. · Report signs of stomach bleeding (black/tarry stools, vomit that looks like coffee grounds). · Seek medical attention if you experience chest pain, weakness, or slurred speech (signs of cardiovascular or stroke risk). · Stay hydrated and avoid prolonged sun exposure (may increase sensitivity). |