Pronunciation:
voe-kloe-spor-in
Trade Name(s)
Ther. Class.
Pharm. Class.
calcineurin inhibitors
Active lupus nephritis (in combination with corticosteroids and mycophenolate).
Inhibits calcineurin, which results in immunosuppressant effects through inhibition of lymphocyte proliferation, T-cell cytokine production, and expression of T-cell activation surface antigens.
Therapeutic Effect(s):
Reduction in urine protein-to-creatinine ratio and improvement/stabilization of renal function.
Absorption: Rapidly absorbed following oral administration; fatty meals reduce rate and extent of absorption.
Distribution: Extensively distributed to extravascular tissues.
Protein Binding: 97%.
Metabolism and Excretion: Primarily metabolized in the liver via the CYP3A4 isoenzyme. Primarily excreted in feces (93%; 5% as unchanged drug), with 2% being excreted in urine.
Half-life: 30 hr.
TIME/ACTION PROFILE (whole blood concentrations)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
PO | unknown | 1–4 hr | 12 hr |
Contraindicated in:
Use Cautiously in:
CV: hypertension, QT interval prolongation
Derm: alopecia, hypertrichosis
F and E: hyperkalemia
GI: diarrhea, abdominal pain, dyspepsia, gingivitis, mouth ulceration
GU: nephrotoxicity
Hemat: anemia, pure red cell aplasia
Metabolic: anorexia
Neuro: headache, attention disturbance, delirium, dizziness, fatigue, mental status changes, paresthesia, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), SEIZURES, tremor
Resp: cough
Misc: INFECTION , MALIGNANCY (including lymphoma and skin cancer)
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Drug-Drug
Strong CYP3A4 inhibitors, including clarithromycin, itraconazole, and ketoconazole may significantly ↑ levels and risk of acute and/or chronic nephrotoxicity; concurrent use contraindicated.
Drug-Food:
Grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent use.
PO (Adults): 23.7 mg twice daily. Concurrent use of moderate CYP3A4 inhibitor: 15.8 mg in the morning and 7.9 mg in the evening.
Renal Impairment
PO (Adults): Severe renal impairment: 15.8 mg twice daily.
Hepatic Impairment
PO (Adults): Mild or moderate hepatic impairment: 15.8 mg twice daily.
Capsules: 7.9 mg
Examine patient for changes in skin periodically during therapy due to increased risk of malignancy.
Monitor for signs and symptoms of infection (fever; chills; sore throat; cough or flu-lie symptoms; muscle aches; warm, red, or painful areas of skin). Use lowest dose needed to maintain response.
Monitor for signs and symptoms of posterior reversible encephalopathy syndrome (PRES) (headache, seizure, lethargy, hypertension, confusion, blindness, and other visual and neurologic disturbances) during therapy. Confirm diagnosis of PRES with magnetic resonance imaging (MRI). Discontinue voclosporin if PRES develops during therapy.
Lab Test Considerations:
Determine baseline glomerular filtration rate (eGFR) before starting therapy. Voclosporin is not recommended in patients with a baseline eGFR ≤45 mL/min/1.73 m2 unless the benefit exceeds the risk; may increased risk for acute and/or chronic nephrotoxicity. Assess eGFR every 2 wk for first month, and every 4 wk thereafter. If eGFR <60 mL/min/1.73 m2 and reduced from baseline by >20% and <30%, decrease dose by 7.9 mg twice a day. Reassess eGFR within 2 wk; if eGFR is still reduced from baseline by >20%, reduce dose again by 7.9 mg twice a day. If eGFR <60 mL/min/1.73 m2 and reduced from baseline by ≥30%, discontinue voclosporin. Reassess eGFR within 2 wk; consider re-initiating voclosporin at a lower dose (7.9 mg twice a day) only if eGFR has returned to ≥80% of baseline. For patients that had a decrease in dose due to eGFR, consider increasing dose by 7.9 mg twice a day for each eGFR measurement that is ≥80% of baseline; do not exceed the starting dose.
Caution patient of risk of malignancies. Advise patient to avoid or limit sun exposure and to avoid artificial UV light (tanning beds, sun lamps) by wearing protective clothing and using a broad spectrum sunscreen with a high protection factor (≥SPF 30).
Advise patient to notify health care professional promptly if signs and symptoms of infection or nervous system problems (confusion, numbness and tingling, seizures, changes in alertness, headache, vision changes, muscle tremors) occur.
Reduction in urine protein-to-creatinine ratio and improvement/stabilization of renal function. If no therapeutic benefit in 24 wk, consider discontinuation of voclosporin.