ZIFERON.INFO
 

ZIFERON®

Pharmacologic Category

Interferon

Dosing: Adult

Note: Gradual dose-titration, analgesics, and/or antipyretics may help decrease flu-like symptoms on treatment days.

Multiple sclerosis (relapsing): Initial: 0.0625 mg (2 million units [0.25 mL]) every other day; gradually increase dose by 0.0625 every 2 weeks

Target dose: 0.25 mg (8 million units [1 mL]) every other day

Multiple sclerosis (secondary-progressive): Initial: 0.125 mg (4 million units [0.5 mL]) every other day for 2 weeks

Target dose: 0.25 mg (8 million units [1 mL]) every other day

Dosing: Pediatric

Not recommended in children <18 years of age

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment available

Dosing: Hepatic Impairment

No dosage adjustment available

Dosage Forms

Injection, powder for reconstitution:

Ziferon®: 0.3 mg [~9.6 million units] [contains albumin (human); supplied with diluent]

Administration

Withdraw dose of reconstituted solution from the vial into a sterile syringe and inject the solution subcutaneously; sites for self-injection include outer surface of the arms, abdomen, hips, and thighs. Rotate SubQ injection site. Patient should be well hydrated.

Use

Treatment of relapsing forms of multiple sclerosis (MS); treatment of first clinical episode with MRI features consistent with MS

Adverse Reactions

Note: Flu-like syndrome (including at least two of the following - headache, fever, chills, malaise, diaphoresis, and myalgia) are reported in the majority of patients (60%) and decrease over time (average duration ~1 week).

       >10%:

Cardiovascular: Peripheral edema (15%), chest pain (11%)

Central nervous system: Headache (57%), fever (36%), pain (51%), chills (25%), dizziness (24%), insomnia (24%)

Dermatologic: Rash (24%), skin disorder (12%)

Endocrine & metabolic: Metrorrhagia (11%)

Gastrointestinal: Nausea (27%), diarrhea (19%), abdominal pain (19%), constipation (20%), dyspepsia (14%)

Genitourinary: Urinary urgency (13%)

Hematologic: Lymphopenia (88%), neutropenia (14%), leukopenia (14%)

Local: Injection site reaction (85%), inflammation (53%), pain (18%)

Neuromuscular & skeletal: Weakness (61%), myalgia (27%), hypertonia (50%), myasthenia (46%), arthralgia (31%), incoordination (21%)

Miscellaneous: Flu-like syndrome (decreases over treatment course; 60%), neutralizing antibodies (≤45%; significance not known)

        1%   to 10%:

Cardiovascular: Palpitation (4%), vasodilation (8%), hypertension (7%), tachycardia (4%), peripheral vascular disorder (6%)

Central nervous system: Anxiety (10%), malaise (8%), nervousness (7%)

Dermatologic: Alopecia (4%)

Endocrine & metabolic: Menorrhagia (8%), dysmenorrhea (7%)

Gastrointestinal: Weight gain (7%)

Genitourinary: Impotence (9%), pelvic pain (6%), cystitis (8%), urinary frequency (7%), prostatic disorder (3%)

Hematologic: Lymphadenopathy (8%)

Hepatic: ALT increased >5x baseline (10%), AST increased >5x baseline (3%)

Local: Injection site necrosis (4% to 5%), edema (3%), mass (2%)

Neuromuscular & skeletal: Leg cramps (4%)

Respiratory: Dyspnea (7%)

Miscellaneous: Diaphoresis (8%), hypersensitivity (3%)

<1% (Limited to important or life-threatening): Anorexia, apnea, arrhythmia, ataxia, autoimmune hepatitis, bronchospasm, capillary leak syndrome (in patients with pre-existing monoclonal gammopathy) , cardiac arrest, cardiomegaly, cardiomyopathy, cerebral hemorrhage, coma, confusion, delirium, depersonalization, depression, DVT, emotional lability, erythema nodosum, ethanol intolerance, exfoliative dermatitis, gamma GT increase, GI hemorrhage, hallucinations, heart failure, hematemesis, hepatic failure, hepatitis, hyperthyroidism, hyperuricemia, hypocalcemia, mania, MI, pancreatitis, paresthesia, pericardial effusion, photosensitivity, pneumonia, pruritus, psychosis, pulmonary embolism, rash, seizure, sepsis, shock, skin discoloration, suicidal ideation, syncope, SIADH, thrombocytopenia, thyroid dysfunction, triglyceride increased, urinary tract infection, urosepsis, urticaria, vasculitis, vaginal hemorrhage, vomiting, weight loss

Contraindications

Hypersensitivity to E. coli-derived products, natural or recombinant interferon beta, albumin human or any other component of the formulation, pregnancy

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis: Has been reported rarely with use.

• Flu-like symptoms: Associated with a high incidence of flu-like adverse effects; use of analgesics and/or antipyretics on treatment days may be helpful. Improvement in symptoms occurs over time.

• Hepatotoxicity: Has been reported with beta interferons, including rare reports of hepatitis (autoimmune) and hepatic failure requiring transplant; use with caution in patients with hepatic impairment.

• Hyper-/hypothyroidism: Thyroid dysfunction has rarely been reported with use.

• Infection: Increased risk of infection.

• Injection site reactions: Severe injection site reactions (necrosis) may occur, which may or may not heal with continued therapy; patient and/or caregiver competency in injection technique should be confirmed and periodically re-evaluated.

• Leukopenia: Routine monitoring is recommended; dose reduction may be required.

• Neuropsychiatric disorders: Interferons have been associated with severe psychiatric adverse events (psychosis, mania, depression, suicidal behavior/ideation) in patients with and without previous psychiatric symptoms, avoid use in severe psychiatric disorders and use caution in patients with a history of depression; patients exhibiting symptoms of depression should be closely monitored and discontinuation of therapy should be considered.

Disease-related concerns:

• Bone marrow suppression: Use with caution in patients with bone marrow suppression.

• Cardiovascular disease: Use with caution in patients with pre-existing cardiovascular disease, including angina, HF, and/or arrythmia. Rare cases of new-onset cardiomyopathy and/or HF have been reported.

• Respiratory disease: Use with caution in patients with respiratory disease.

• Renal impairment: Use with caution in patients with renal impairment.

• Seizure disorder: Use with caution in patients with a history of seizure disorder.

Dosage form specific issues:

• Albumin: Contains albumin, which may carry a remote risk of transmitting Creutzfeldt-Jakob or other viral diseases.

Metabolism/Transport Effects

None known.

Drug Interactions

Theophylline Derivatives: Interferons may decrease the metabolism of Theophylline Derivatives.

Zidovudine: Interferons may enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine.

Pregnancy Risk Factor

Category C

Pregnancy Implications

A dose-related abortifacient activity was reported in Rhesus monkeys. There are no adequate and well-controlled studies in pregnant women. Treatment should be discontinued if a woman becomes pregnant, or plans to become pregnant during therapy.

Lactation

Excretion in breast milk unknown/not recommended

Breast-Feeding Considerations

Because its use has not been evaluated during lactation, breast-feeding is not recommended.

Monitoring Parameters

Complete blood chemistries (including platelet count) and liver function tests are recommended at 1, 3, and 6 months following initiation of therapy and periodically thereafter. Thyroid function should be assessed every 6 months in patients with history of thyroid dysfunction. Baseline pregnancy test.

Mechanism of Action

Interferon beta-1b differs from naturally occurring human protein by a single amino acid substitution and the lack of carbohydrate side chains; mechanism in the treatment of MS is unknown; however, immunomodulatory effects attributed to interferon beta-1b include enhancement of suppressor T cell activity, reduction of proinflammatory cytokines, down-regulation of antigen presentation, and reduced trafficking of lymphocytes into the central nervous system. Improves MRI lesions, decreases relapse rate, and disease severity in patients with secondary progressive MS.

Pharmacodynamics/Kinetics

Limited data due to small doses used

        Half-life elimination: 8 minutes to 4.3 hours

        Time to peak, serum: 1-8 hours