CEQUA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CEQUA (CEQUA).
Immunosuppressant; binds to cyclophilin D in mitochondria, inhibiting opening of mitochondrial permeability transition pore (mPTP), which reduces T-lymphocyte activation and cytokine release. Also forms complex with cyclophilin A to inhibit calcineurin, suppressing IL-2 production and T-cell proliferation.
| Metabolism | Hepatic via CYP3A4 and CYP3A5; also undergoes fecal elimination with enterohepatic recirculation. |
| Excretion | Primarily fecal (90%) with minor renal excretion (<1% unchanged drug). Biliary excretion is the major route for elimination of cyclosporine metabolites. |
| Half-life | Terminal elimination half-life is approximately 8.4 hours (range 6-10 hours) in healthy adults; prolonged in hepatic impairment and pediatric patients. |
| Protein binding | 90-98% bound primarily to lipoproteins (HDL, LDL) and to a lesser extent albumin and globulins. |
| Volume of Distribution | 4-8 L/kg, indicating extensive distribution into tissues (e.g., fat, liver, kidneys). |
| Bioavailability | Ophthalmic emulsion: systemic bioavailability is negligible (<0.1%) due to low absorption from the eye. |
| Onset of Action | Ophthalmic emulsion: clinical effect onset within 1 month of twice-daily dosing, with full effect by 3-6 months. |
| Duration of Action | Duration of action persists for the treatment period; continued dosing required to maintain immunosuppressive effect. Withdrawal leads to gradual return of inflammation. |
Instill one drop of 0.09% ophthalmic solution in each eye twice daily, approximately 12 hours apart.
| Dosage form | SOLUTION |
| Renal impairment | No dosage adjustment required for renal impairment. |
| Liver impairment | No dosage adjustment required for hepatic impairment. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. |
| Geriatric use | No specific dosage adjustment recommended; use with caution due to potential for increased systemic exposure. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CEQUA (CEQUA).
| Breastfeeding | Systemic cyclosporine is excreted in human milk. The M/P ratio is approximately 0.3-0.6. However, CEQUA is an ophthalmic formulation with minimal systemic absorption. Unknown whether topically applied cyclosporine is excreted in milk. Use caution, considering the importance of the drug to the mother. Breastfeeding infants should be monitored for potential adverse effects such as immune suppression. |
| Teratogenic Risk | CEQUA (cyclosporine ophthalmic solution) is classified as Pregnancy Category C. Animal studies have shown embryotoxic and fetotoxic effects at doses 0.2-0.8 times the human ocular dose. There are no adequate and well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk to the fetus. First trimester: limited data, theoretical risk of immunosuppression. Second and third trimesters: no specific human data, but systemic cyclosporine is associated with increased risk of prematurity and low birth weight. |
■ FDA Black Box Warning
Increased risk of infection and lymphoproliferative disorders including post-transplant lymphoproliferative disorder (PTLD).
| Serious Effects |
["Hypersensitivity to cyclosporine or any component","Uncontrolled hypertension","Severe renal impairment (except in transplant setting)","Active infections","Concurrent use with PUVA or UVB therapy"]
| Precautions | ["Increased susceptibility to infections","Potential for lymphoproliferative disorders and other malignancies","May cause renal impairment, hypertension, hyperkalemia, and hyperuricemia","Monitor blood cyclosporine levels to avoid toxicity","Avoid concurrent use of live vaccines","Caution with other nephrotoxic drugs"] |
| Food/Dietary | No significant food interactions reported for ophthalmic cyclosporine. However, patients should avoid touching the dropper tip to food surfaces. No dietary restrictions are necessary. |
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| Fetal Monitoring | Monitor maternal blood cyclosporine levels if systemic absorption is suspected (unlikely with ophthalmic use). In pregnant women, monitor for signs of infection (due to immunosuppression), renal function, and blood pressure. Fetal monitoring includes ultrasound for growth restriction and assessment for preterm labor. |
| Fertility Effects | Systemic cyclosporine has been associated with reversible effects on male and female fertility in animal studies, including decreased spermatogenesis and ovarian dysfunction. No data on fertility with ophthalmic cyclosporine. Based on minimal systemic absorption, significant impact on fertility is unlikely. |
| Clinical Pearls | CEQUA (cyclosporine ophthalmic solution 0.09%) is a calcineurin inhibitor immunosuppressant indicated for keratoconjunctivitis sicca (dry eye disease). It increases tear production by inhibiting T-cell activation. Important: CEQUA requires no refrigeration (unlike Restasis), and the vehicle contains no preservatives. Use with caution in patients with active ocular infections; do not administer while wearing contact lenses. Onset of effect may take 2-4 weeks; maximum benefit may require 6 months. Contraindicated in patients with known hypersensitivity to cyclosporine. |
| Patient Advice | CEQUA is a prescription eye drop used to increase tear production in dry eye disease. · Instill one drop in each eye twice daily, about 12 hours apart. · Remove contact lenses before use; wait at least 15 minutes before reinserting. · Do not touch the dropper tip to any surface to avoid contamination. · CEQUA comes in a single-use vial; use immediately after opening and discard any remaining solution. · Temporary blurred vision may occur after instillation; wait until vision clears before driving. · Report any eye pain, vision changes, or signs of infection (redness, discharge) to your doctor. · Store CEQUA at room temperature (20-25°C); do not refrigerate or freeze. · It may take several weeks to notice improvement; continue use as prescribed even if you feel no effect initially. |