Interferon Alfa 2b

Dosage Forms & Strengths

injectable solution

• 6 million International Units/mL (3.8mL vial)
• 10 million International Units/mL (3.2mL vial)

multidose pen; 6 doses each

• 22.5 million International Units/1.5mL
• 37.5 million International Units/1.5mL
• 75 million International Units/1.5mL

powder for injection

• 10 million International Units/vial
• 18 million International Units/vial
• 50 million International Units/vial

Hairy Cell Leukemia

2 million Units/m² IM/SC 3 times/wk for up to 6 mo 

If severe adverse reaction (ADR) develop: reduce dose by 50% or temporarily withhold, THEN

Resume at 50% after ADRs abate: 1 million Units/m² IM/SC 3 times/wk

If severe ADRs persist discontinue permanently

Discontinue Intron A for progressive disease or failure to respond after 6 mo of treatment

Malignant Melanoma

Induction 20 million Units/m² IV over 20 min, 5 days/wk for 4 wk 

Maintenance dose: 10 million Units/m² SC 3 times/wk for 48 wk

Withhold treatment if ANC <500/mm³ or ALT/AST >5 times upper limit of normal (ULN); re-start at 50% previous dose

Permanently discontinue if the following is observed

• Toxicity does not abate after withholding
• Severe ADRs recur in patients receiving reduced doses
• ANC <250/mm³ or ALT/AST >10x ULN

Follicular Lymphoma

5 million units 3 times/week for up to 18 mo in conjunction with anthracycline-containing combination chemotherapy in patients >18 years old

See Mfr's prescribing packet for additional chemo dosing information

Condylomata Acuminata

1 million units injected into each lesion 3 times/week qODay for 3week

May repeat course if unsatisfactory results 12-16 wk after initial treatment

Max 5 lesions/single course of treatment

Do not use the 18 or 50 million Units powder for injection

Do not use the 18 million Units multidose Intron A solution for injection

Do not use multidose pens

AIDS-related Kaposi's Sarcoma

30 million Units/m² IM/SC 3 times/wk for 16 wk 

Dose reduction frequently required: See Mfr's PI

Chronic Hepatitis C

3 million units IM/SC 3 times/wk for16 wk

If ALT normalized after 16 wk, continue treatment for 18-24 mo

If ALT not normalized or high levels of HCV RNA after 16 wk, consider discontinuing treatment

Acute Hepatitis C

5 million Units SC/IM qd for 4 wk, then 3 times/wk for 20 wk

If severe adverse reactions develop reduce dose by 50% or temporarily withhold until adverse reactions abate

If intolerance persists discontinue permanently

Chronic Hepatitis B

30-35 million Units SC/IM per wk, either as 5 million Units qDay or 10 millon Units 3 times/wk for 16 wk

Reduce 50%: WBC <1.5 x 10^9/L; Granulocyte <0.75 x 10^9/L; platelets <50 x 10^9/L

Discontinue permanently: WBC < 1.0 x 10^9/L; Granulocyte <0.5 x 10^9/L; platelet < 25 x 10^9/L

If severe adverse reactions develop reduce dose by 50% or temporarily withhold until adverse reaction abate

If intolerance persists discontinue permanently

Other Information

Monitor: LFTs, CBC, platelets, Hgb, Electrolytes, TSH

See also combo with ribavirin

Dosage Forms & Strengths

injectable solution

• 6 million International Units/mL (3.8mL vial)
• 10 million International Units/mL (3.2mL vial)

multidose pen; 6 doses each

• 22.5 million International Units/1.5mL
• 37.5 million International Units/1.5mL
• 75 million International Units/1.5mL

powder for injection

• 10 million International Units/vial
• 18 million International Units/vial
• 50 million International Units/vial

Chronic Hepatitis B

3 million Units/m² IM/SC 3 times/wk for 1 wk; increase to 6 million U/m² 3 times/wk SC for 16-24 wk; not to exceed 10 million Units/dose 3 times/wk 

Dose adjustments: See manufacturer's package insert

Interferon alfa-2b can cause serious side effects that:

• may cause death, or
• may worsen certain serious diseases that you may already have.

Tell your healthcare provider right away if you have any of the symptoms listed below while taking interferon alfa-2b. If symptoms get worse, or become severe and continue, your healthcare provider may tell you to stop taking interferon alfa-2b permanently. In many, but not all people, these symptoms go away after they stop taking interferon alfa-2b.

• low blood pressure
• fast heart rate or abnormal heart beats
• trouble breathing or chest pain
• heart attacks or heart muscle problems (cardiomyopathy)

• irritability (getting upset easily)
• depression (feeling low, feeling bad about yourself, or feeling hopeless)
• aggressive behavior
• thoughts of hurting yourself or others, or suicide
• former drug addicts may fall back into drug addiction or overdose

If you have these symptoms, your healthcare provider should carefully monitor you during treatment with interferon alfa-2b and for 6 months after your last dose.

• fever
• chills
• bloody diarrhea
• burning or pain with urination
• urinating often
• coughing up mucus (phlegm) that is discolored (for example yellow or pink)

While taking interferon alfa-2b, you should see a healthcare provider regularly for check-ups and blood tests to make sure that your treatment is working and to check for side effects.

Do not take interferon alfa-2b if you:

• had a serious allergic reaction to another alpha interferon product or are allergic to any of the ingredients in interferon alfa-2b. Ask your healthcare provider if you are not sure.
• have certain types of hepatitis (autoimmune hepatitis)
• have certain other liver problems

Talk to your healthcare provider before taking interferon alfa-2b if you have any of these conditions.

Tell your healthcare provider if you are pregnant or plan to become pregnant. It is not known if interferon alfa-2b will harm your unborn baby. You should use effective birth control during treatment with interferon alfa-2b. Talk to your healthcare provider about birth control choices for you during treatment with interferon alfa-2b. Tell your healthcare provider if you become pregnant during treatment with interferon alfa-2b.

You should not use interferon alfa-2b if you are allergic to it, or if you have:

• autoimmune hepatitis, or severe liver problems from causes other than hepatitis B or C.

You should not use the combination of interferon alfa-2b and ribavirin if you have:

• severe kidney disease;

• a blood cell disorder such as thalassemia or sickle cell anemia;

• an allergy to interferons or ribavirin;

• if you are pregnant; or

• if you are a man and your sexual partner is pregnant.

To make sure interferon alfa-2b is safe for you, tell your doctor if you have ever had

• cirrhosis or liver problems other than hepatitis;

• depression, mental illness, thoughts about hurting yourself or someone else;

• drug or alcohol addiction;

• heart disease, high blood pressure, heart attack or stroke;

• a blood clot in your lung;

• a bleeding or blood clotting disorder;

• eye problems;

• asthma, COPD, or other breathing disorder;

• diabetes, or a thyroid disorder;

• a weak immune system, low blood cell counts;

• colitis or other intestinal disorder;

• kidney disease; or

• an organ transplant.

Interferon alfa-2b can harm an unborn baby or cause a miscarriage. Do not use interferon alfa-2b with ribavirin (Rebetol) if you are pregnant. The combination of these medicines can cause birth defects. Use 2 forms of effective birth control to prevent pregnancy while you are using this drug combination and for at least 6 months after your last dose.

If a man fathers a child while using interferon alfa-2b and ribavirin, the baby may have birth defects. Use a condom to prevent pregnancy during your treatment. Continue using condoms for at least 6 months after you stop using this drug combination.

Tell your doctor right away if a pregnancy occurs while either the mother or the father is using interferon alfa-2b and ribavirin.

It is not known whether interferon alfa-2b passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Interferon alfa-2b with ribavirin can affect growth in children. Talk with your doctor if you think your child is not growing at a normal rate while using this medicine.

The powder form of interferon alfa-2b is made from human plasma (part of the blood) which may contain viruses and other infectious agents. Donated plasma is tested and treated to reduce the risk of it containing infectious agents, but there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended. If your doctor changes your brand, strength, or type of interferon, your dosage needs may change. Do not change your doses or medication schedule without your doctor's advice.

Interferon alfa-2b is given as an injection into a vein, into a muscle, under the skin, or directly into a genital wart. You may be shown how to use the medicine at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of needles, IV tubing, and other items used.

The powder form of interferon alfa-2b must be mixed with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medicine. Do not use if the medicine has changed colors or has particles in it. Call your pharmacist for new medicine.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Interferon alfa-2b can lower blood cells that help your body fight infections and help your blood to clot. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often. Your heart, lung, and liver function may also need to be checked.

Store this medicine in the refrigerator. Do not freeze. After mixing the powder with a diluent, store this mixture in the refrigerator and use it within 24 hours.

Each single-use vial (bottle) of this medicine is for one use only. Throw it away after one use, even if there is still medicine left inside. Throw away any leftover medicine in a multi-dose vial 30 days after the first use.

• Intron A

Binds to a specific receptor on the cell wall to initiate intracellular activity; multiple effects can be detected including induction of gene transcription. Inhibits cellular growth, alters the state of cellular differentiation, interferes with oncogene expression, alters cell surface antigen expression, increases phagocytic activity of macrophages, and augments cytotoxicity of lymphocytes for target cells

Distribution

Vd: 31 L; but has been noted to be much greater (370 to 720 L) in leukemia patients receiving continuous infusion IFN; IFN does not penetrate the CSF

Metabolism

Primarily renal, filtered and absorbed at the renal tubule

Time to Peak

Serum: IM, SubQ: ~3 to 12 hours; IV: By the end of a 30-minute infusion

Half-Life Elimination

IV: ~2 hours; IM, SubQ: ~2 to 3 hours

Consider premedication with acetaminophen prior to administration to reduce the incidence of some adverse reactions. Not all dosage forms and strengths are appropriate for all indications; refer to product labeling for details. Interferon alfa-2b at doses ≥10 million units/m2 is associated with a moderate emetic potential; antiemetics may be recommended to prevent nausea and vomiting.

Hairy cell leukemia: IM, SubQ: 2 million units/m2 3 times weekly for up to 6 months (may continue treatment with sustained treatment response); discontinue for disease progression or failure to respond after 6 months

Lymphoma (follicular): SubQ: 5 million units 3 times weekly for up to 18 months

Malignant melanoma: Induction: 20 million units/m2 IV for 5 consecutive days per week for 4 weeks, followed by maintenance dosing of 10 million units/m2 SubQ 3 times weekly for 48 weeks

AIDS-related Kaposi sarcoma: IM, SubQ: 30 million units/m2 3 times weekly; continue until disease progression or until maximal response has been achieved after 16 weeks

Chronic hepatitis B: IM, SubQ: 5 million units daily or 10 million units 3 times weekly for 16 weeks

Chronic hepatitis C: IM, SubQ: 3 million units 3 times weekly. In patients with normalization of ALT at 16 weeks, continue treatment (if tolerated) for 18-24 months; consider discontinuation if normalization does not occur at 16 weeks. Note: May be used in combination therapy with ribavirin in previously untreated patients or in patients who relapse following alpha interferon therapy.

Condyloma acuminata: Intralesionally: 1 million units/lesion (maximum: 5 lesions per treatment) 3 times weekly (on alternate days) for 3 weeks. May administer a second course at 12-16 weeks.

Consider premedication with acetaminophen prior to administration to reduce the incidence of some adverse reactions. Not all dosage forms and strengths are appropriate for all indications; refer to product labeling for details.

Note: The following dosing may also be used in infants in the setting of HIV-exposure/-infection (CDC 2009).

Chronic hepatitis B (including HIV coinfection): SubQ: Children and Adolescents 1 to 17 years: 3 million units/m2 3 times weekly for 1 week, followed by 6 million units/m2 3 times weekly (maximum: 10 million units per dose); total duration of therapy 16 to 24 weeks (treat for 24 weeks in HIV-exposure/-infection)

Chronic hepatitis C with HIV coinfection: IM, SubQ: Children and Adolescents 1 to 17 years: 3 to 5 million units/m2 3 times weekly (maximum: 3 million units per dose) with ribavirin for 48 weeks, regardless of HCV genotype (CDC 2009)

Renal impairment at treatment initiation: Combination therapy with ribavirin (hepatitis C) is contraindicated in patients with CrCl <50 mL/minute; use combination therapy with ribavirin (hepatitis C) with caution in patients with impaired renal function and CrCl ≥50 mL/minute.

Renal toxicity during treatment: Indication-specific adjustments: Lymphoma (follicular): Serum creatinine >2 mg/dL: Permanently discontinue.

Hematologic toxicity (also refer to indication specified adjustments below): ANC <500/mm3 or platelets <25,000/mm3: Discontinue treatment.

Hypersensitivity reaction (acute, serious), ophthalmic disorders (new or worsening), thyroid abnormality development (which cannot be normalized with medication), signs or symptoms of liver failure: Discontinue treatment.

Liver function abnormality, pulmonary infiltrate development, evidence of pulmonary function impairment, or autoimmune disorder development, triglycerides >1,000 mg/dL: Monitor closely and discontinue if appropriate. Permanently discontinue for severe (grade 3) hepatic injury or hepatic decompensation (Child-Pugh class B and C [score >6]).

Neuropsychiatric disorders (during treatment):

Clinical depression or other psychiatric problem: Monitor closely during and for 6 months after treatment.

Severe depression or other psychiatric disorder: Discontinue treatment.

Persistent or worsening psychiatric symptoms, suicidal ideation, aggression towards others: Discontinue treatment and follow with appropriate psychiatric intervention.

Manufacturer-recommended adjustments, listed according to indication:

Lymphoma (follicular):

Neutrophils >1000/mm3 to <1,500/mm3: Reduce dose by 50%; may re-escalate to starting dose when neutrophils return to >1,500/mm3

Severe toxicity (neutrophils <1000/mm3 or platelets <50,000/mm3): Temporarily withhold.

AST >5 times ULN or serum creatinine >2 mg/dL: Permanently discontinue.

Hairy cell leukemia:

Platelet count <50,000/mm3: Do not administer intramuscularly (administer SubQ instead).

Severe toxicity: Reduce dose by 50% or temporarily withhold and resume with 50% dose reduction; permanently discontinue if persistent or recurrent severe toxicity is noted.

Chronic hepatitis B:

WBC <1,500/mm3, granulocytes <750/mm3, or platelet count <50,000/mm3, or other laboratory abnormality or severe adverse reaction: Reduce dose by 50%; may re-escalate to starting dose upon resolution of hematologic toxicity. Discontinue for persistent intolerance.

WBC <1,000/mm3, granulocytes <500/mm3, or platelet count <25,000/mm3: Permanently discontinue

Chronic hepatitis C: Severe toxicity: Reduce dose by 50% or temporarily withhold until subsides; permanently discontinue for persistent toxicities after dosage reduction.

AIDS-related Kaposi sarcoma: Severe toxicity: Reduce dose by 50% or temporarily withhold; may resume at reduced dose with toxicity resolution; permanently discontinue for persistent/recurrent toxicities.

Malignant melanoma (induction and maintenance):

Severe toxicity including neutrophils >250/mm3 to <500/mm3 or ALT/AST >5 to 10 times ULN: Temporarily withhold; resume with a 50% dose reduction when adverse reaction abates.

Neutrophils <250/mm3, ALT/AST >10 times ULN, or severe/persistent adverse reactions: Permanently discontinue.

Store intact vials under refrigeration at 2°C to 8°C (36°F to 46°F); do not freeze. After reconstitution of powder for injection, product should be used immediately, but may be stored under refrigeration for ≤24 hours.

3 million international units IM or subcutaneously 3 times a week

Duration of Therapy:
Combination therapy with ribavirin:
-Interferon alpha-naive patients: 24 to 48 weeks
-Retreatment in patients relapsing after nonpegylated interferon monotherapy: 24 weeks

Monotherapy: 72 to 96 weeks

Comments:
-In patients tolerating therapy with ALT normalization at 16 weeks of treatment, monotherapy should be extended to 18 to 24 months to improve sustained response rate.
-Patients whose ALTs have not normalized or high levels of HCV-RNA persist after 16 weeks of monotherapy rarely achieve sustained response with extended treatment; should consider discontinuing therapy in such patients
-When used with ribavirin, patients with renal dysfunction and/or those older than 50 years should be carefully monitored for anemia.
-The manufacturer product information for ribavirin capsules/oral solution should be consulted.
-Duration of combination therapy should be individualized for interferon alpha-naive patients depending on baseline disease characteristics, response to therapy, and tolerability of regimen.
-Virologic response should be assessed after 24 weeks of combination therapy; discontinuation of combination therapy should be considered in any interferon alpha-naive patient whose HCV-RNA levels remain detectable after 24 weeks of therapy.
-Studies established that this drug can have clinically meaningful effects on this disease, shown by serum ALT normalization and reduced liver necrosis and degeneration.
-Liver biopsy is recommended to establish diagnosis of chronic hepatitis; patients should be tested for antibody to HCV.
-Confirmation that the patient has compensated liver disease is recommended before starting this drug.
-The following should be considered before therapy (patient entrance criteria for compensated liver disease in clinical studies): No history of hepatic encephalopathy, variceal bleeding, ascites, or other clinical signs of decompensation; bilirubin up to 2 mg/dL; albumin stable and within normal limits; prothrombin time prolonged less than 3 seconds; WBC at least 3000/mm3; platelets at least 70,000/mm3; serum creatinine normal/near normal
-Before starting therapy, CBC and platelet counts should be evaluated to establish baselines (for monitoring potential toxicity); these tests should be repeated at 1 and 2 weeks after starting therapy, and monthly thereafter.
-Serum ALT should be measured about every 3 months (to assess response to therapy).
-Thyroid-stimulating hormone (TSH) should be within normal limits when starting therapy; TSH testing should be repeated at 3 and 6 months.

Uses: For the treatment of chronic hepatitis C in patients with compensated liver disease who have history of blood or blood-product exposure and/or are HCV antibody positive; in combination with ribavirin, for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with alpha interferon therapy and in patients who relapsed after alpha interferon therapy