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. |
| Molecular Weight | 541.6 |
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 | No adequate human data; limited animal studies do not indicate fetal risk. Use only if clearly needed. |
| 2nd trimester | No adequate human data; limited animal studies do not indicate fetal risk. Use only if clearly needed. |
| 3rd trimester | No adequate human data; limited animal studies do not indicate fetal risk. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for VERKAZIA (VERKAZIA).
| Placental transfer | Predicted to cross placenta due to MW < 1500 Da; no human data. |
| Breastfeeding | Unknown if distributed in human milk; consider risk vs benefit. Caution advised due to potential for infant exposure. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to active substance or excipients
| 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. |
| Food/Dietary | There are no significant food interactions with ophthalmic cyclosporine. However, if VEKZIA is used systemically, avoid grapefruit and grapefruit juice as they may increase cyclosporine levels. For ophthalmic use, no dietary restrictions are necessary. |
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| L3 |
| 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. |
| 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. |
| Clinical Pearls |
| Verkaizia (cyclosporine ophthalmic emulsion) 0.05% is indicated for dry eye disease. Administer as one drop in each eye twice daily, approximately 12 hours apart. Shake vial vigorously before each use. Contraindicated in patients with active ocular infections. Monitor for conjunctival hyperemia, burning, or stinging. Not for use during contact lens wear; remove lenses before instillation and wait 15 minutes before reinsertion. May take 3-6 months for full effect. |
| Patient Advice | Shake the vial vigorously before each use. · Instill one drop in each eye twice daily, about 12 hours apart. · Remove contact lenses before using and wait 15 minutes before reinserting. · Avoid touching the tip of the vial to your eye or any surface to prevent contamination. · Do not use while wearing contact lenses. · Temporary blurred vision may occur immediately after instillation; wait until vision clears before driving or operating machinery. · It may take up to 6 months to feel the full benefit of the medication. · Report any eye pain, vision changes, or persistent redness to your healthcare provider. |