Usual Adult Dose for Polycythemia Vera

For Patients NOT Receiving Hydroxyurea:
Initial dose: 100 mcg subcutaneously every 2 weeks

• Increase the dose in increments of 50 mcg every 2 weeks until the hematologic parameters stabilize

Maximum dose: 500 mcg subcutaneously every 2 weeks

For Patients TRANSITIONING from Hydroxyurea:
Initial dose: 50 mcg subcutaneously every 2 weeks in combination with hydroxyurea

• Gradually taper off hydroxyurea in weeks 3 through 12 by reducing total biweekly dose by 20% to 40% every 2 weeks while increasing this drug in increments of 50 mcg every 2 weeks until the hematologic parameters stabilize; discontinue hydroxyurea by week 13

Maximum dose: 500 mcg subcutaneously every 2 weeks

Stabilized Hematologic Parameters:

• Hematocrit less than 45%
• Platelets less than 400 x 10(9)/L
• Leukocytes less than 10 x 10(9)/L

Maintenance dose:

• Maintain 2-week dosing interval with hematological stability for at least 1 year
• After 1 year of hematological stability on a stable dose, the dosing interval may be expanded to every 4 weeks

Comments:

• Patients should be monitored closely; complete blood counts (CBC) should be obtained every 2 weeks during titration and every 3 to 6 months during maintenance phase, and as clinically indicated.
• Phlebotomy may be necessary as rescue treatment to normalize blood hyperviscosity,

Use: For the treatment of polycythemia vera.

Renal Dose Adjustments

eGFR 30 mL/min: No adjustment recommended
eGFR less than 30 mL/min: Avoid use

Discontinue therapy if severe renal impairment develops during treatment

Liver Dose Adjustments

Mild hepatic impairment: No adjustment recommended
Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment: Use is contraindicated

See Dose Adjustments for dose modifications due to elevated hepatic transaminases

Dose Adjustments

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:

• If there is insufficient efficacy at the decreased dose following dose modification, consider increasing dose to the next higher dose level after recovery to grade 1 toxicity

HEPATIC:

• Liver enzyme elevations ABOVE BASELINE with concomitant bilirubin elevation or other evidence of hepatic decompensation: Interrupt until recovery; restart at 50 mcg lower than interrupted dose. If interrupted dose is 50 mcg, hold until recovery; consider permanent discontinuation if toxicity persists after 4-dose modifications
• Liver enzyme elevations GREATER THAN 5 to 20 x ULN (upper limit of normal): Decrease dose by 50 mcg and if toxicity does not improve, continue decreasing at biweekly intervals until transaminases (ALT and AST) recover to less than 3 x ULN if baseline was normal (or 3 x baseline if baseline was abnormal), and gamma-glutamyltransferase (GGT) recovers to less than 2.5 x ULN if baseline was normal (or 2.5 x baseline if baseline was abnormal). If the interrupted dose is 50 mcg, refrain from treatment until recovery
• Liver enzyme elevations GREATER THAN 20 x ULN: Interrupt treatment until ALT and AST recover to less than 3 x ULN if baseline was normal (or 1.5 x baseline if baseline was abnormal), and GGT recovers to less than 2.5 x ULN if baseline was normal (or 2 x baseline if baseline was abnormal). Consider permanent discontinuation if toxicity persists after 4 dose-modifications.

HEMATOLOGIC:

• ANEMIA: For Hb less than 8 g/dL: Decrease dose by 50 mcg, if toxicity does not improve, continue decreasing at bi-weekly intervals until recovery to 10 g/dL; Interrupt therapy if Hb levels are life threatening, or urgent intervention is needed until recovery to greater than 10 g/dL
• THROMBOCYTOPENIA: For platelet count less than 50,000/mm3 but at 25,000/mm3 or greater: Decrease dose by 50 mcg, if toxicity does not improve, continue decreasing at bi-weekly intervals until recovery to greater than 75,000 mm3; interrupt therapy if platelet count is less than 25,000/mm3 until recovery to 75,000/mm3
• LEUKOPENIA: For WBCs less than 2000/mm3 but at 1000/mm3 or greater: Decrease dose by 50 mcg, if toxicity does not improve, continue decreasing at biweekly intervals until recovery to greater than 3000/mm3; interrupt therapy if WBC is less than 1000/mm3 until recovery to 3000/mm3

Consider permanent discontinuation if cytopenia persists after 4 dose modifications.

DEPRESSION:

• MILD, without suicidal ideation: Consider psychiatric consultation if persists greater than 8 weeks
• MODERATE, without suicidal ideation: Consider dose reduction and psychiatric consultation
• SEVERE, or any severity with suicidal ideation: Discontinue therapy, recommend psychiatric consultation

Precautions

US BOXED WARNING: RISK OF SERIOUS DISORDERS

• Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders.
• Patients should be monitored closely with periodic clinical and laboratory evaluations.
• Therapy should be withdrawn for persistently severe or worsening signs or symptoms of these conditions; most cases resolved after stopping therapy.

CONTRAINDICATIONS:

• Hypersensitivity to interferons including interferon alfa-2b or any product ingredients
• Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt
• Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment
• History or presence of active serious or untreated autoimmune disease
• Immunosuppressed transplant recipients

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• For subcutaneous administration into lower stomach (abdomen) or top of thighs
• Rotate injection sites; do not inject into skin that is irritated, red, bruised, infected, or scarred
• Self-administration should be reserved for patients who have received training on storage, preparation, and administration

Storage requirements:

• Store refrigerated 36F to 46F (2C to 8C) in the original carton to protect from light; do not freeze

Reconstitution/preparation techniques:

• Patients should be instructed to follow the enclosed Instructions for Use

Monitoring:

• CBC at baseline and every 2 weeks during titration, then at least every 3 to 6 months, and as clinically indicated
• Monitor serum triglycerides at baseline and intermittently during therapy
• Monitor liver function tests at baseline and during therapy; if AST/ALT/GGT elevations occur, monitor weekly until resolution
• Monitor serum creatinine at baseline and during therapy
• Monitor for neuropsychiatric, autoimmune, ischemic, and infections disorders

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling (Medication Guide and Instructions for Use).
• Patients/caregivers should be advised to promptly report any unusual changes in mood or behavior, new onset or worsening of depression, or the emergence of suicidal thoughts or behavior.
• Patients/caregivers should be advised to report any symptoms of diabetes, thyroid dysfunction, cardiovascular toxicity, fatigue, fever, easy bruising, or frequent nose bleeds.
• Patients should be advised to maintain good oral hygiene and to have regular dental examinations.
• Patients should be advised to refrain from engaging in operating heavy or potentially dangerous machinery until they know how this drug will affect them; if they experience dizziness, somnolence, or hallucinations, they should not drive or use heavy machinery.
• Women should be advised to use an effective method of contraception and avoid breastfeeding while taking this drug and for at least 8 weeks after their last dose.