interferons, alpha

Contraindicated in:

Hypersensitivity to alpha interferons or human serum albumin;
Autoimmune hepatitis;
Hepatic decompensation (Child-Pugh class B and C) before or during therapy;
Pedi: Products containing benzyl alcohol should not be used in neonates.

Use Cautiously in:

Severe cardiovascular, pulmonary, renal, or hepatic disease;
CCr <50 mL/min (do not use combination therapy);
Active infections;
Underyling CNS pathology or psychiatric history;
↓bone marrow reserve or underlying immunosuppression;
Current history of chickenpox, herpes zoster, or herpes labialis (may reactivate or disseminate disease);
Previous or concurrent radiation therapy;
Autoimmune disorders (may ↑ risk of exacerbation);
OB: ↑risk of spontaneous abortion in animal studies; use only if potential maternal benefit justifies potential fetal risk; ribavirin is contraindicated in pregnancy and lactation and in men whose female partners are pregnant;
Rep: Women of reproductive potential;
Pedi: Children <3 yr (safety and effectiveness not established);
Geri: ↑risk of adverse reactions in older adults.

Exercise Extreme Caution in:

History of depression/suicide attempt.

Adv. Reactions/Side Effects ⬆ ⬇

All are more prominent with SUBQ, IV, or IM administration

CV: edema, arrhythmias, chest pain, heart block, ISCHEMIC DISORDERS

Derm: alopecia, dry skin, pruritus, rash, sweating

EENT: nose bleeds, rhinitis, blurred vision

Endo: ↓growth (children), thyroid disorders

GI: ↑liver enzymes, abdominal pain, anorexia, diarrhea, dry mouth, nausea, taste disorder, vomiting, weight loss, COLITIS, flatulence, HEPATOTOXICITY, PANCREATITIS

Hemat: anemia, hemolytic anemia (with ribavirin), leukopenia, thrombocytopenia

Local: injection site reactions

MS: arthralgia, myalgia, leg cramps

Neuro: confusion, depression, dizziness, fatigue, headache, insomnia, irritability, aggression, anxiety, HOMICIDAL IDEATION, paresthesia, SUICIDAL IDEATION/ATTEMPTS

Resp: cough, dyspnea

Misc: chills, fever, flu-like syndrome, AUTOIMMUNE DISORDERS, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), INFECTION

Interactions ⬆ ⬇

Drug-drug:

Additive myelosuppression with other antineoplastic agents or radiation therapy.
↑CNS depression may occur with CNS depressants, including alcohol, antihistamines, sedative/hypnotics, and opioids.
May ↓ metabolism and ↑ blood levels and toxicity of theophylline and methadone.
↑risk of adverse reactions with zidovudine.
Ribavirin↑ risk of hemolytic anemia, especially if CCr <50 mL/min (avoid if possible).
May ↓ effects of immunosuppressant agents.

Availability ⬆ ⬇

Peginterferon Alpha-2a

Solution for injection: 180 mcg/1 mL (vials); 180 mcg/0.5 mL (prefilled syringes)

Interferon Alpha-n3

Solution for injection: 5 million units/mL

Route/Dosage ⬆ ⬇

Peginterferon Alpha-2a

SC (Adults ): Chronic hepatitis C: 180 mcg once weekly for 48 wk for Genotypes 1,4 (24 wk for Genotypes 2,3). Patients with chronic hepatitis C co-infected with HIV: 180 mcg once weekly for 48 wk. Chronic hepatitis B: 180 mcg once weekly for 48 wk.
SC (Children 5–17 yr): Chronic hepatitis C (Genotype 1 or 4): 180 mcg/1.73 m² X BSA once weekly (not to exceed 180 mcg) (with PO ribavirin) for 48 wk (should be used in combination with hepatitis C virus NS3/4A protease inhibitor in patients with genotype 1 infection); Chronic hepatitis C (Genotype 2 or 3): 180 mcg/1.73 m² X BSA once weekly (not to exceed 180 mcg) (with PO ribavirin) for 24 wk.

Renal Impairment

SC (Adults ): CCr 30–50 mL/min: 180 mcg once weekly (with PO ribavirin 200 mg alternating with 400 mg every other day) CCr <30 mL/min (including hemodialysis): 135 mcg once weekly (with PO ribavirin 200 mg once daily).

Interferon Alpha-n3

Intralesional (Adults ): 250,000 units/lesion twice weekly for up to 8 wk; for large lesions, divide dose and inject at several sites.

US Brand Names ⬆ ⬇

peginterferon alpha-2a: Pegasys,

interferon alpha-n3: Alferon N

Action ⬆ ⬇

Interferons are proteins capable of modifying the immune response and have antiproliferative action against tumor cells.
Peginterferon is a "pegylated" formulation of interferon alpha-2a formulated to have a longer duration of action; interferon alpha-n3 is from pooled human leukocytes.
Interferons also have antiviral activity.
Unknown mechanism for melanoma.

Therapeutic effects:

Antiviral and antiproliferative activity.
Decreased progression of hepatic damage (for patients with hepatitis).

Classifications ⬆ ⬇

Therapeutic Classification: immune modifiers

Pharmacologic Classification: interferons

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed (>80%) following IM and SUBQ administration. Minimal systemic absorption follows intralesional administration.

Distribution: Unknown.

Metabolism/Excretion: Filtered by the kidneys and subsequently degraded in the renal tubule.

Half-Life: Peginterferon alpha-2a: 50–160 hr;

Time/Action Profile ⬆ ⬇

(clinical effects)

ROUTE	ONSET	PEAK	DURATION
Interferon alpha-n3	unknown	4–8 wk	unknown (IL)

IL= regression of lesions.

Patient/Family Teaching ⬆ ⬇

Advise patient to take medication as directed. If a dose is missed, administer as soon as remembered if within 2 days; if >2 days, notify health care professional.
Home Care Issues: Instruct patient and family on preparation and correct technique for administration of injection and care and disposal of equipment. Advise patient to read Medication Guide prior to administration and with each prescription refill to check for changes. Explain to patient that brands should not be switched without consulting health care professional; may result in a change of dose.
- Discuss possibility of flu-like reaction 3–6 hr after dose. Acetaminophen may be taken prior to injection and every 3–4 hr afterward as needed to control symptoms.
- Instruct patient to notify health care professional promptly if fever; chills; cough; hoarseness; sore throat; signs of infection; lower back or side pain; painful or difficult urination; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased fatigue; dyspnea; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate gastric bleeding.
- Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide; new or worse depression; new or worse anxiety; feeling very agitated or restless; panic attacks; trouble sleeping; new or worse irritability; acting aggressive; being angry or violent; acting on dangerous impulses; an extreme increase in activity and talking, other unusual changes in behavior or mood occur.
- Instruct patient not to receive any vaccinations without advice of health care professional.
- Emphasize need for periodic lab tests to monitor for side effects.
- Inform patient that peginterferon alpha-2a may not reduce the risk of transmission of HCV to others or prevent cirrhosis, liver failure, or liver cancer.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception and to avoid breastfeeding during therapy. If therapy is combined with ribavirin, advise females of reproductive potential and men with female partners of reproductive potential to use two forms of effective contraception during and for at least 6 mo following conclusion of therapy. Females of reproductive potential and female partners of male patients receiving peginterferon alpha-2a and ribavirin must have a routine pregnancy test performed monthly during therapy and for at least 6 mo following therapy. Men must use a condom. May disrupt menstrual cycle.

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Indications ⬇

Contraind./Precautions ⬆ ⬇