Usual Adult Dose for Chronic Myelogenous Leukemia

Oral Capsules (i.e., Hydrea): Individualize treatment based on tumor type, disease state, response to treatment, patient risk factors, and current clinical practice standards

Comments:

• As monotherapy or in conjunction with other antitumor agents or radiation therapy to treat neoplastic diseases.
• Prophylactic administration of folic acid is recommended.
• Blood counts should be monitored at least once a week during therapy.
• Severe anemia should be corrected before initiating therapy.

Uses:

• For the treatment of resistant chronic myeloid leukemia (CML).
• For the treatment of locally advanced squamous cell carcinomas of the head and neck (excluding lip), in combination with concurrent chemoradiation.

Usual Adult Dose for Head and Neck Cancer

Oral Capsules (i.e., Hydrea): Individualize treatment based on tumor type, disease state, response to treatment, patient risk factors, and current clinical practice standards

Comments:

• As monotherapy or in conjunction with other antitumor agents or radiation therapy to treat neoplastic diseases.
• Prophylactic administration of folic acid is recommended.
• Blood counts should be monitored at least once a week during therapy.
• Severe anemia should be corrected before initiating therapy.

Uses:

• For the treatment of resistant chronic myeloid leukemia (CML).
• For the treatment of locally advanced squamous cell carcinomas of the head and neck (excluding lip), in combination with concurrent chemoradiation.

Usual Adult Dose for Sickle Cell Anemia

Oral Tablets (i.e., Siklos):

• Initial dose: 15 mg/kg orally once a day
• Increase 5 mg/kg/day every 8 weeks or if a painful crisis occurs; increase only if blood counts are in an acceptable range
• Maximum dose: 35 mg/kg/day

BLOOD COUNTS IN THE ACCEPTABLE RANGE:

• Neutrophils greater than or equal to 2000 cells/mm3
• Platelets greater than or equal to 80,000/mm3
• Hemoglobin greater than 5.3 g/dL
• Reticulocytes greater than or equal to 80,000/mm3 if the hemoglobin concentration is less than 9 g/dL

Oral Capsules (i.e., Droxia):

• Initial dose: 15 mg/kg orally once a day
• Increase 5 mg/kg/day every 12 weeks; increase only if blood counts are in an acceptable range
• Maximum dose: 35 mg/kg/day

BLOOD COUNTS IN THE ACCEPTABLE RANGE:

• Neutrophils greater than or equal to 2500 cells/mm3
• Platelets greater than or equal to 95,000/mm3
• Hemoglobin greater than 5.3 g/dL
• Reticulocytes greater than or equal to 95,000/mm3 if the hemoglobin concentration is less than 9 g/dL

Comments:

• Dosage is based on the actual or ideal patient weight, whichever is less.
• Blood counts should be monitored every 2 weeks.
• Tablets may be spilt or quartered along score lines, tablet doses can be rounded to the nearest 50 mg or 100 mg strength based on clinical judgement; capsules should be swallowed whole and should not be opened or chewed.
• Prophylactic administration of folic acid is recommended.

Use: To reduce the frequency of painful crises and to reduce the need for blood transfusions in patients with sickle cell anemia with recurrent moderate to severe painful crises.

Usual Pediatric Dose for Sickle Cell Anemia

Oral Tablets (i.e., Siklos):

• Initial dose: 20 mg/kg orally once a day
• Increase 5 mg/kg/day every 8 weeks or if a painful crisis occurs; increase only if blood counts are in an acceptable range
• Maximum dose: 35 mg/kg/day

BLOOD COUNTS IN THE ACCEPTABLE RANGE:

• Neutrophils greater than or equal to 2000 cells/mm3
• Platelets greater than or equal to 80,000/mm3
• Hemoglobin greater than 5.3 g/dL
• Reticulocytes greater than or equal to 80,000/mm3 if the hemoglobin concentration is less than 9 g/dL

Comments:

• Dosage is based on the actual or ideal patient weight, whichever is less.
• Blood counts should be monitored every 2 weeks.
• Tablets may be spilt or quartered along score lines, tablet doses can be rounded to the nearest 50 mg or 100 mg strength based on clinical judgement.
• Prophylactic administration of folic acid is recommended.

Use: To reduce the frequency of painful crises and to reduce the need for blood transfusions in pediatric patients 2 years or older with sickle cell anemia with recurrent moderate to severe painful crises.

Renal Dose Adjustments

CrCl less than 60 mL/min or ESRD: Reduce dose by 50%

Liver Dose Adjustments

Data not available; however, caution is recommended.

Dose Adjustments

SICKLE CELL ANEMIA:

• Treatment for Sickle Cell Anemia should be interrupted if blood counts are in the toxic range:

TOXIC RANGE

• Neutrophils less than 2000 cells/mm3 (younger patients with lower baseline counts may safely tolerate absolute neutrophil counts down to 1250/mm3)
• Platelets less than 80,000/mm3
• Hemoglobin less than 4.5 g/dL
• Reticulocytes less than 80,000/mm3 if the hemoglobin concentration is less than 9 g/dL

Dosing After Hematologic Recovery:

• Upon recovery, reduce from dose associated with hematologic toxicity:
• Tablets: Reduce by 5 mg/kg/day; may titrate up or down every 8 weeks in 5 mg/kg/day increments
• Capsules: Reduce by 2.5 mg/kg/day; may titrate up or down every 12 weeks in 2.5 mg/kg/day increments
• Patients should be at a stable dose with no hematologic toxicity for 24 weeks.
• Permanently discontinue if the patient develops hematologic toxicity twice.

NEOPLASTIC DISEASES:

• Myelosuppression: Provide supportive care and modify dose or discontinue therapy as needed.
• If cutaneous vasculitic ulcers occur, institute treatment and discontinue this drug.

Precautions

US BOXED WARNINGS: MYELOSUPPRESSION and MALIGNANCIES

• Myelosuppression: May cause severe myelosuppression, monitor blood counts at baseline and throughout treatment; interrupt treatment and reduce dose as necessary
• Malignancies: This drug is carcinogenic; advise sun protection and monitor patients for malignancies

CONTRAINDICATIONS:

• Hypersensitivity to the active substance or any product ingredients

Safety and efficacy have not been established for use of the capsule formulation in patients younger than 18 years.
Safety and efficacy for use of the tablet formulation for treating sickle cell anemia have not been established in pediatric patients younger than 2 years.

Consult WARNINGS section for additional precautions.

Dialysis

ESRD: Dose should be reduced 50%; on dialysis days, administer following dialysis

Other Comments

Administration advice: Take orally once a day.

Oral Capsules:

• Swallow whole; do not open, break, or chew because this drug is cytotoxic

Oral Tablets:

• The 100 mg tablets have 1 score line and can be split into 2 parts (each 50 mg); the 1000 mg tablets have 3 score lines and can be split into 4 parts (each 250 mg); calculate the rounded doses to the nearest 50 mg or 100 mg strength based on clinical judgment
• Tablet breaking instructions are provided in the instructions for use handout and should be reviewed with each prescription.

General:

• This is a cytotoxic drug; special handling and disposal procedures should be followed.
• Different products are labeled for specific indications; the manufacturer product information should be consulted prior to using a product.

Monitoring:

• Monitor blood counts weekly (neoplastic diseases) or every 2 weeks (sickle cell anemia)
• Monitor efficacy of sickle cell anemia by obtaining hemoglobin (HbF) levels every 3 to 4 months; an increase in HbF of at least 2-fold over baseline is desired
• Monitor for malignancies, pulmonary toxicities

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling (Medication Guide and Instructions for Use).
• Patients should be advised to promptly report signs and symptoms of infection or bleeding.
• Patients should be advised to use sun protection.
• Patients should discuss vaccinations with their healthcare provider.
• Both male and females of reproductive potential should be advised to use contraception during and after treatment.