Usual Adult Dose for Lupus Nephritis

23.7 mg orally twice a day

Comments:

• The use of this drug in combination with cyclophosphamide is not recommended as safety and efficacy have not been established.
• Use this drug in combination with mycophenolate mofetil (MMF) and corticosteroids.
• Determine an actual baseline estimated glomerular filtration rate (eGFR) prior to initiating treatment.
• Dosage of this drug is based on the patient's eGFR and should be modified accordingly.
• Check blood pressure (BP) at baseline and do not initiate treatment in patients with BP greater than 165/105 mmHg or with hypertensive emergency.
• Treatment discontinuation should be considered if the patient does not experience therapeutic benefit by 24 weeks.
• Safety and efficacy have not been established beyond one year.

Renal Dose Adjustments

Mild or moderate renal dysfunction: No adjustment recommended.
Severe Renal Dysfunction (Estimated glomerular filtration rate 45 mL/min/1.73 m2 or less): Not recommended

• If used in Severe Renal Dysfunction at baseline the recommended starting dose is 15.8 mg twice a day.

Liver Dose Adjustments

Mild or moderate liver dysfunction (Child-Pugh A or B): 15.8 mg twice a day
Severe liver dysfunction (Child-Pugh C): Not recommended

Dose Adjustments

DOSAGE ADJUSTMENTS BASED ON ESTIMATED GLOMERULAR FILTRATION RATE (eGFR):

• If eGFR is less than 60 mL/min/1.73 m2 and reduced from baseline by more than 20% but less than 30%: Reduce dose by 7.9 mg twice a day
• Reassess eGFR within two weeks and if still reduced from baseline by more than 20%: Reduce dose again by 7.9 mg twice a day
• If eGFR is less than 60 mL/min/1.73 m2 and reduced from baseline by 30% or more: Discontinue treatment
• Reassess eGFR within two weeks and if eGFR has returned to 80% or more of baseline: Consider re-initiating treatment at 7.9 mg twice a day
• For patients that had a decrease in dose due to eGFR: Consider increasing the dose by 7.9 mg twice a day for each eGFR measurement that is 80% or more of baseline but do not exceed the starting dose

• Coadministration with mild CYP450 3A4 inhibitors: No adjustment recommended
• Coadministration with moderate CYP450 3A4 inhibitors: Reduce the daily dosage to 15.8 mg in the morning and 7.9 mg in the evening
• Coadministration with strong CYP450 3A4 inhibitors: Contraindicated
• Coadministration with moderate or strong CYP450 3A4 inducers: Avoid use

Precautions

US BOXED WARNING:
MALIGNANCIES AND SERIOUS INFECTIONS:

• Patients treated with this drug or other immunosuppressants are at increased risk for developing serious infections and malignancies that may lead to hospitalization or death.

• Patients concomitantly using strong CYP450 3A inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) because these medications can significantly increase exposure to this drug which may increase the risk of acute and/or chronic nephrotoxicity.
• Patients who have had a known serious or severe hypersensitivity reaction to this drug or any of its excipients.

Dialysis

Hemodialysis: Unknown

Other Comments

Administration Advice:

• Swallow capsules whole; do not open, crush, or divide
• Take capsules on an empty stomach as close to a 12-hour schedule with a minimum of 8 hours between the doses
• If a dose is missed, take it as soon as possible within 4 hours, wait until the next schedule dose if 4 hours have passed.
• Avoid eating or drinking grapefruit juice while taking this drug.

• Store at controlled room temperature.
• Keep in the original packaging until ready to be used.
• Keep the product in the original container.

• Monitor for electrolytes, including potassium levels periodically.
• Monitor for symptoms of neurotoxicity.
• Monitor for the development of infections.
• Monitor blood pressure for hypertension; obtain baseline blood pressure, then every two weeks for the first month, then as clinically indicated.
• Monitor renal function for nephrotoxicity; obtain baseline eGFR and monitor eGFR regularly during treatment.
• Monitor for QTc interval prolongation.

• Read the Patient Information Leaflet (Medication Guide).
• Advise patients to avoid eating grapefruit or drinking grapefruit juice while taking this drug.
• Advise patients to report symptoms of vision changes, delirium, or tremors as this can be signs of neurologic adverse effects.
• Advise patients that this drug may increase the risk of developing lymphomas and other malignancies, particularly of the skin.
• Advise patients to avoid artificial UV light, to wear protective clothing and use a broad-spectrum sunscreen with a high protection factor.
• Advise patients that this drug may increase their risk to infections.
• Advice patients to monitor their blood pressure as this drug can cause hypertension.
• Inform patients that this drug can have toxic effects on the kidney.
• Inform patients that this drug can cause hyperkalemia.
• Advise women not to breastfeed during treatment and for 7 days after the last dose.
• Advise patients that this drug can interfere with usual response to immunization and to avoid live vaccines.