VERKAZIA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VERKAZIA (VERKAZIA).
CFTR potentiator; increases the open probability of cystic fibrosis transmembrane conductance regulator (CFTR) protein at the cell surface to enhance chloride transport.
| Metabolism | Primarily metabolized by CYP3A4 and CYP3A5. |
| Excretion | Primarily metabolized; renal excretion of unchanged drug is negligible. Less than 5% of a dose is recovered unchanged in urine. Biliary/fecal excretion accounts for the majority of elimination, with approximately 80% of radiolabeled dose recovered in feces over 264 hours. |
| Half-life | Terminal elimination half-life is approximately 51 hours in healthy adults. This supports a dosing interval of twice daily for topical ophthalmic use, as systemic exposure is minimal and accumulation is not clinically relevant. |
| Protein binding | Approximately 53% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | Following intravenous administration, volume of distribution is approximately 1.6 L/kg, suggesting extensive distribution into tissues beyond plasma volume. |
| Bioavailability | Not applicable for systemic routes; ophthalmic administration results in negligible systemic absorption. Plasma concentrations after topical ocular dosing are below the limit of quantitation in most patients. |
| Onset of Action | Topical ophthalmic: Onset of improvement in ocular signs and symptoms is observed within 1 to 4 weeks of initiating treatment, based on clinical trials in vernal keratoconjunctivitis. |
| Duration of Action | Topical ophthalmic: Duration of action persists with continued use; symptoms typically return upon discontinuation. Clinical effect is maintained with twice-daily dosing. |
1 drop in each eye 4 times daily (approximately every 6 hours) during waking hours.
| Dosage form | EMULSION |
| Renal impairment | No dose adjustment is required for renal impairment. |
| Liver impairment | No dose adjustment is required for hepatic impairment. |
| Pediatric use | Approved for children aged 2 years and older: 1 drop in each eye 4 times daily (approximately every 6 hours) during waking hours. No weight-based adjustment necessary as dosing is the same for all pediatric patients ≥2 years. |
| Geriatric use | No specific dose adjustment is recommended; use same as adult dosing. Monitor for adverse reactions as elderly may be more susceptible. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VERKAZIA (VERKAZIA).
| Breastfeeding | Cyclosporine is excreted in human milk following systemic administration. With topical ophthalmic use, systemic absorption is minimal (<0.1 ng/mL), and the expected dose to the infant is negligible. The M/P ratio for systemic cyclosporine is approximately 0.17-1.0. Caution should be exercised when administering VERKAZIA to a nursing woman. |
| Teratogenic Risk | VERKAZIA (cyclosporine ophthalmic emulsion) is not administered systemically; however, cyclosporine is a pregnancy category C drug. For systemically administered cyclosporine, there is an increased risk of premature birth, low birth weight, and intrauterine growth restriction. No adequate and well-controlled studies in pregnant women exist. Use only if potential benefit justifies potential risk to the fetus. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concomitant use with strong CYP3A inducers (e.g., rifampin, St. John's wort)."]
| Precautions | ["Use with CYP3A inducers (e.g., rifampin) may reduce efficacy; avoid coadministration.","Moderate to strong CYP3A inhibitors (e.g., ketoconazole, erythromycin) require dose adjustment.","Monitor transaminases; risk of elevated liver enzymes in some patients.","Not recommended for use with ivacaftor due to increased exposure."] |
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| Fetal Monitoring | No specific monitoring is required due to minimal systemic absorption. If used, monitor for maternal ocular adverse events and fetal growth if systemic exposure is a concern. |
| Fertility Effects | No studies on fertility have been conducted with VERKAZIA. Systemic cyclosporine at high doses has been associated with impaired fertility in animal studies; however, topical ophthalmic use results in negligible systemic exposure and is unlikely to affect fertility. |