Usual Adult Dose for Histiocytosis

• Initial dose: 1 mg/kg IV over 1 hour 2 times a week (every 3 to 4 days)
• Doses after the initial dose may be increased stepwise to 10 mg/kg based on clinical and laboratory criteria (see Dose Adjustments).
• Duration of therapy: Until hematopoietic stem cell transplantation (HSCT) is performed or unacceptable toxicity; discontinue when a patient no longer requires treatment of HLH.

Premedication/Concomitant Medication:

• For patients who are not receiving baseline dexamethasone: Begin dexamethasone at a daily dose of at least 5 to 10 mg/m2 the day before initiation of this drug.
• For patients who were receiving baseline dexamethasone: They may continue their regular dose provided the dose is at least 5 mg/m2.
• Dexamethasone can be tapered according to the judgment of the physician.

Comments:

• Test for latent TB using the purified protein derivative (PPD) or IFNy release assay and evaluate patients for TB risk factors.
• Administer TB prophylaxis to patients at risk, or known to have a positive PPD test result, or positive IFNy release assay.
• Administer prophylaxis for herpes zoster, Pneumocystis jirovecii, and fungal infections prior to therapy initiation.
• During therapy monitor for TB, adenovirus, EBV, and CMV every 2 weeks and as clinically indicated.

Use: For the treatment of primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease or intolerance with conventional HLH therapy

Usual Pediatric Dose for Histiocytosis

• Initial dose: 1 mg/kg IV over 1 hour 2 times a week (every 3 to 4 days)
• Doses after the initial dose may be increased stepwise to 10 mg/kg based on clinical and laboratory criteria (see Dose Adjustments).
• Duration of therapy: Until hematopoietic stem cell transplantation (HSCT) is performed or unacceptable toxicity; discontinue when a patient no longer requires treatment of HLH.

Premedication/Concomitant Medication:

• For patients who are not receiving baseline dexamethasone: Begin dexamethasone at a daily dose of at least 5 to 10 mg/m2 the day before initiation of this drug.
• For patients who were receiving baseline dexamethasone: They may continue their regular dose provided the dose is at least 5 mg/m2.
• Dexamethasone can be tapered according to the judgment of the physician.

Comments:

• Test for latent TB using the purified protein derivative (PPD) or IFNy release assay and evaluate patients for TB risk factors.
• Administer TB prophylaxis to patients at risk, or known to have a positive PPD test result, or positive IFNy release assay.
• Administer prophylaxis for herpes zoster, Pneumocystis jirovecii, and fungal infections prior to therapy initiation.
• During therapy monitor for TB, adenovirus, EBV, and CMV every 2 weeks and as clinically indicated.

Use: For the treatment of pediatric (newborn and older) patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease or intolerance with conventional HLH therapy

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

No adjustment recommended.

Dose Adjustments

Dose Modification Based on Response:

• Day 1: Starting dose of 1 IV mg/kg
• Increase dose to 3 mg/kg IV on Day 3 for unsatisfactory improvement
• Increase dose to 6 mg/kg IV on Day 6 onwards for unsatisfactory improvement
• Increase dose to 10 mg/kg IV from Day 9 onwards

NOTE: UNSATISFACTORY IMPROVEMENT ON DAY 3 AND DAY 6 IS DEFINED AS ASSESSED BY A HEALTHCARE PROVIDER AND AT LEAST ONE OF THE FOLLOWING:
FEVER: Persistent or recurring
PLATELET COUNT:

• If baseline is less than 50,000/mm3 and no improvement to greater than 50,000/mm3
• If baseline is greater than 50,000/mm3 and less than 30% improvement
• If baseline is greater than 100,000/mm3 and decrease to less than 100,000/mm3

NEUTROPHIL COUNT:

• If baseline is less than 500/mm3 and no improvement to greater than 500/mm3
• If baseline is greater than 500 to 1000/mm3 and decrease to less than 500/mm3 -If baseline is 1000 to 1500/mm3 and decrease to less than 1000/ mm3

FERRITIN (ng/mL):

• If baseline is 3000 ng/mL or greater and less than 20% decrease
• If baseline is less than 3000 ng/mL and any increase to greater tahn 3000 ng/mL SPLENOMEGALY: Any worsening

COAGULOPATHY (both D-Dimer and Fibrinogen must apply):

• D-Dimer: If abnormal at baseline and no improvement
• Fibrinogen (mg/dL): If baseline levels 100 mg/dL or less and no improvement
• If baseline levels greater than 100 mg/dL) and any decrease to less than 100 mg/dL

NOTE: UNSATISFACTORY IMPROVEMENT ON DAY 9 IS DEFINED AS:

• Assessment by a healthcare provider that based on initial signs of response, a further increase in the dose can be of benefit.

Precautions

CONTRAINDICATIONS:

• None

Consult WARNINGS section for additional precautions.

Dialysis

No adjustment recommended.

Other Comments

Administration advice:

• Administer diluted solution IV over 1 hour through an IV line containing a sterile, non-pyrogenic, low-protein binding 0.2 micron in-line filter.
• Do not infuse this drug concomitantly with other agents and do not add any other product to the infusion bag or syringe.

Storage requirements:

• Store in a refrigerator at 2C to 8C (36F to 46F) in original carton to protect from light.
• Store the diluted solution in a refrigerator at 2C to 8C (36F to 46F) for no more than 4 hours from the time of dilution.
• If refrigerated, allow the diluted solution to come to room temperature prior to administration.
• Do not freeze or shake.
• Do not store any unused portion of the solution for reuse.
• Any unused product or waste material should be disposed of in accordance with local requirements.

General:

• This product contains no preservative.

Monitoring:

• Infusion-related reactions
• Infections

Patient advice:

• Report any signs of infection to your healthcare provider.
• Do not receive live or live attenuated vaccines during therapy.
• This drug may cause infusion-related reactions (e.g., drug eruption, pyrexia, rash, erythema, hyperhidrosis).