temporary classcalcineurin 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.
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)
|PO||unknown||1–4 hr||12 hr|
- Severe hypersensitivity
- Concurrent use of strong CYP3A4 inhibitors;
- Severe hepatic impairment;
- OB: Pregnancy (formulation contains alcohol; also used with mycophenolate, which can cause fetal harm)
- Lactation: Lactation.
Use Cautiously in:
- Bradycardia, electrolyte disorders (hypokalemia, hypomagnesemia), QT interval prolongation, or concurrent use of QT interval prolonging medications
- eGFR ≤45 mL/min/1.73 m2 (↓ dose in severe renal impairment)
- Mild or moderate hepatic impairment (↓ dose recommended)
- Rep: Women of reproductive potential and men with female partners of reproductive potential (used with mycophenolate which can cause fetal harm)
- Pedi: Safety and effectiveness not established in children
- Geri: Initiate therapy with lower dose in older adults due to age-related ↓ in renal and hepatic function.
Adverse Reactions/Side Effects
CV: hypertension, QT interval prolongation
Derm: alopecia, hypertrichosis
F and E: hyperkalemia
GI: diarrhea, abdominal pain, dyspepsia, gingivitis, mouth ulceration
Hemat: anemia, pure red cell aplasia
Neuro: POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), SEIZURES, headache, attention disturbance, delirium, dizziness, fatigue, mental status changes, paresthesia, tremor
Misc: INFECTION , MALIGNANCY (including lymphoma and skin cancer)
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Strong CYP3A4 inhibitors, including clarithromycin, itraconazole, and ketoconazole may significantly ↑ levels and risk of acute and/or chronic nephrotoxicity; concurrent use contraindicated.
- Moderate CYP3A4 inhibitors, including diltiazem, fluconazole, and verapamil may ↑ levels and risk of toxicity; ↓ voclosporin dosage.
- Strong CYP3A4 inducers, including rifampin, or moderate CYP3A4 inducers, including efavirenz , may ↓ levels and effectiveness; avoid concurrent use.
- May ↑ levels and risk of toxicity of P-glycoprotein substrates, including digoxin.
- Aminoglycosides, amphotericin B, cisplatin, or NSAIDs may ↑ risk of nephrotoxicity.
- ACE inhibitors, aldosterone receptor antagonists, angiotensin receptor blockers, and potassium-sparing diuretics may ↑ risk of hyperkalemia.
- Concurrent use with QT interval prolonging medications may ↑ risk of QT interval prolongation.
- Vaccinations may be less effective if given concurrently with voclosporin; avoid administration of live attenuated vaccines.
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.
PO (Adults): Severe renal impairment– 15.8 mg twice daily.
PO (Adults): Mild or moderate hepatic impairment– 15.8 mg twice daily.
Capsules: 7.9 mg
- Monitor BP at baseline, every 2 wk for first month, and periodically during therapy. Do not begin therapy in patients with BP >165/105 mmHg or with hypertensive emergency; discontinue therapy if BP increases to >165/105 mmHg or hypertensive emergency occurs.
- 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.
- Monitor serum potassium periodically during therapy.
- PO Administer on an empty stomach every 12 hr, with a minimum of 8 hr between doses. DNC: Swallow capsule whole; do not open, crush, or chew.
- Instruct patient to take as directed. Take missed doses with 4 hr after missing dose. If >4 hr since last dose, omit dose and take next scheduled dose at regular time. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
- Advise patient to avoid eating grapefruit or drinking grapefruit juice during therapy.
- 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 avoid live virus vaccines during therapy.
- 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.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during therapy and avoid breastfeeding during and for at least 7 days after last dose. Advise patient to notify health care professional if pregnancy is suspected.
Reduction in urine protein-to-creatinine ratio and improvement/stabilization of renal function. If no therapeutic benefit in 24 wk, consider discontinuation of voclosporin.
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