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tion including complete lymphadenectomy. Interferon alpha-n3: Treatment of
condylomata acuminata (intralesional).
INTERFERONS, ALPHA
Action
(in-ter-feer-onz)
peginterferon alpha-2a
Interferons are proteins capable of modifying the immune response and have antiproliferative action against tumor cells. Interferon alpha-2b is produced by recombinant DNA techniques, peginterferon is a “pegylated” formulation of interferon alpha2b 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: Antineoplastic, antiviral, and antiproliferative
activity. Decreased progression of hepatic damage (for patients with hepatitis). Improved relapse-free survival (for melanoma).
Pegasys
interferon alpha-2b (recombinant)
Intron A
peginterferon alpha-2b (pegylated)
Pegintron, Sylatron
Pharmacokinetics
Absorption: Not absorbed orally. Well absorbed (⬎80%) following IM and subcut
interferon alpha-n3 (human)
Alferon N
Classification
Therapeutic: immune modifiers
Pharmacologic: interferons
Pregnancy Category C
administration. Minimal systemic absorption follows intralesional administration.
Distribution: Unknown.
Metabolism and Excretion: Filtered by the kidneys and subsequently degraded
in the renal tubule; peginterferon alpha-2b— 30% renally excreted.
Half-life: Peginterferon alpha-2a— 50– 160 hr; interferon alpha-2b— 2– 3
hr; peginterferon alpha-2b— 40 hr.
TIME/ACTION PROFILE (clinical effects)
Indications
Peginterferon alpha-2a: Treatment of: Chronic hepatitis C (alone or with ribavirin), Chronic hepatitis B. Interferon alpha-2b Treatment of: Hairy cell leukemia,
Malignant melanoma, AIDS-related Kaposi’s sarcoma, Condylomata acuminata (intralesional), Chronic hepatitis B, Chronic hepatitis C (with oral ribavirin) which has
relapsed following previous treatment with interferon alone, Follicular non-Hodgkin’s lymphoma. Peginterferon alpha– 2b (Pegintron) Treatment of: Chronic
hepatitis C in patients ⱖ18 yr who have compensated liver disease and HCV genotype
1 infection (in combination with ribavirin and approved hepatitis C virus [HCV] NS3/
4A protease inhibitor), Chronic hepatitis C in patients with compensated liver disease
who have HCV genotypes 2 or 3, are 3– 17 years old, or have HCV genotype 1 and are
unable to take a HCV NS3/4A protease inhibitor (in combination with ribavirin),
Chronic hepatitis C in previously untreated patients who have compensated liver disease and contraindications to or significant intolerances to ribavirin (as monotherapy). Peginterferon alpha– 2b (Sylatron) Adjuvant treatment of melanoma with
microscopic or gross nodal involvement within 84 days of definitive surgical resec⫽ Canadian drug name.
⫽ Genetic Implication.
ROUTE
ONSET
PEAK
DURATION
Interferon alpha-2b IM, 1–3 mo
unknown
unknown (CR)
subcut
Interferon alpha-2b IM, unknown
3–5 days
3–5 days (BC)
subcut
Interferon alpha-2b IM, 2 wk
unknown
unknown (LFT)
subcut
Interferon alpha-2b and unknown
4–8 wk
unknown (IL)
n3
Peginterferon alpha-2b unknown
6 mos or more
unknown
subcut
BC ⫽ effects on platelet counts; CR ⫽ clinical response; IL⫽ regression of lesions; LFT ⫽ effects
on liver function in patients with hepatitis
Contraindications/Precautions
Contraindicated in: Hypersensitivity to alpha interferons or human serum albumin; Autoimmune hepatitis; Hepatic decompensation (Child-Pugh class B and C) be-
CAPITALS indicate life-threatening, underlines indicate most frequent.
Strikethrough ⫽ Discontinued.
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fore or during therapy; Pedi: Products containing benzyl alcohol should not be used
in neonates.
Use Cautiously in: Severe cardiovascular, pulmonary, renal, or hepatic disease;
Active infections; Underyling CNS pathology or psychiatric history;pbone 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 (mayqrisk of exacerbation); OB:q
risk of spontaneous abortion in animal studies; use only if potential fetal risks are
outweighed by potential maternal benefit; women with childbearing potential should
be advised of potential risk to fetus; Lactation: Usually compatible with breast feeding (AAP); Pedi: Children ⬍3 yr (⬍18 yr for Sylatron) (safety not established); Geri:
qrisk of adverse reactions.
Exercise Extreme Caution in: History of depression/suicide attempt.
Adverse Reactions/Side Effects
All are more prominent with subcut, IV, or IM administration CNS: NEUROPSYCHIATRIC DISORDERS, SUICIDAL IDEATION, confusion, depression, dizziness, fatigue, headache, insomnia, irritability, anxiety. EENT: blurred vision, nose bleeds, rhinitis. CV:
ISCHEMIC DISORDERS, edema, arrhythmias, chest pain, heart block. GI: COLITIS, PANCREATITIS, anorexia, abdominal pain, diarrhea, dry mouth,qliver enzymes, nausea,
taste disorder, vomiting, weight loss, drug-induced hepatitis, flatulence. Derm: alopecia, dry skin, pruritus, rash, sweating. Endo:pgrowth (children), thyroid disorders. Hemat: LEUKOPENIA, THROMBOCYTOPENIA, anemia, hemolytic anemia (with ribavirin). MS: arthralgia, myalgia, leg cramps. Neuro: paresthesia. Resp: cough,
dyspnea. Local: injection site reactions. Misc: AUTOIMMUNE DISORDERS, INFECTIOUS
DISORDERS, allergic reactions including ANAPHYLAXIS, chills, fever, flu-like syndrome.
Interactions
Drug-Drug: Additive myelosuppression with other antineoplastic agents or radiation therapy.qCNS depression may occur with CNS depressants, including
alcohol, antihistamines, sedative/hypnotics, and opioids. Maypmetabolism
andqblood levels and toxicity of theophylline and methadone.qrisk of adverse
reactions with zidovudine. Ribavirinqrisk of hemolytic anemia, especially if CCr
⬍50 mL/min (avoid if possible). Maypeffects of immunosuppressant agents.
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Route/Dosage
Peginterferon Alpha-2a
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Subcut (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.
Subcut (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
Subcut (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-2b
IV (Adults): Malignant melanoma (induction)— 20 million units/m2 for 5 days
of each week for 4 wk initially, followed by subcut maintenance dosing.
IM, Subcut (Adults): Hairy cell leukemia— 2 million units/m2 IM or subcut 3
times weekly for up to 6 mo. Malignant melanoma (maintenance)— 10 million
units/m2 subcut 3 times weekly for 48 wk, following initial IV dosing. AIDS-related
Kaposi’s sarcoma— 30 million units/m2 IM or subcut 3 times weekly until disease
progression or maximum response has been achieved after 16 wk. Chronic hepatitis C— 3 million units IM or subcut 3 times weekly. If normalization of ALT occurs
after 16 wk of therapy, continue treatment for total of 18– 24 mo. If normalization of
ALT does not occur after 16 wk of therapy, may consider discontinuing treatment.
Chronic hepatitis B— 5 million units/day IM or subcut or 10 million units IM or
subcut 3 times weekly for 16 wk. Follicular non-Hodgkin’s lymphoma— 5 million
units subcut 3 times weekly for up to 18 mo (to be used following completion of anthracycline-containing chemotherapy).
Subcut (Children ⬎ 3 yr): Chronic hepatitis B— 3 million units/m2 3 times
weekly for the first week of therapy then increase to 6 million units/m2 3 times weekly
(not to exceed 10 million units/dose) for 16 to 24 weeks.
IL (Adults): Condylomata acuminata— 1 million units/lesion 3 times weekly for
3 wk; treat only 5 lesions per course. An additional course of treatment may be initiated at 12– 16 wk.
䉷 2015 F.A. Davis Company
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INTERFERONS, ALPHA
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Peginterferon Alpha-2b
Monotherapy
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Subcut (Adults): 137– 160 kg— 150 mcg once weekly for 1 yr. 107– 136 kg—
120 mcg once weekly for 1 yr. 89– 106 kg— 96 mcg once weekly for 1 yr. 73– 88
kg— 80 mcg once weekly for 1 year. 57– 72 kg— 64 mcg once weekly for 1 yr. 46–
56 kg— 50 mcg once weekly for 1 yr. 37– 45 kg— 40 mcg once weekly for 1 yr.
●
Combination Therapy (Duration of therapy is 48 wk for viral genotype 1 or if previously failed therapy; 24 wk for viral genotypes 2
and 3)
●
Subcut (Adults): ⬎105kg— 1.5 mcg/kg once weekly based on actual body weight.
86– 105 kg— 150 mcg once weekly. 76– 85 kg— 120 mcg once weekly. 61– 75
kg— 96 mcg once weekly. 51– 60 kg— 80 mcg once weekly. 40– 50 kg— 64 mcg
once weekly. ⬍40 kg— 50 mcg once weekly.
Subcut (Children 3– 17 yr): 60 mcg/m2 once weekly.
Melanoma
Subcut (Adults): 6 mcg/kg/week for 8 doses, then 3 mcg/kg/week for up to 5 yr.
Interferon Alpha-n3
IL (Adults): 250,000 units/lesion twice weekly for up to 8 wk; for large lesions, divide dose and inject at several sites.
NURSING IMPLICATIONS
Assessment
● Assess for signs of neuropsychiatric disorders (irritability, anxiety, de-
pression, suicidal ideation, aggressive behavior). For patients taking interferon alfa 2a or peginterferon alpha 2b, if depression is mild, visit
weekly by phone or in person. If depression is moderate, decrease interferon alfa
2a dose to 135 mcg or to 90 mcg if needed or peginterferon alpha 2b to 40 mcg/
m2/wk , then to 20 mcg/m2/wk, if needed; see in office at least every other week.
Consider psychiatric counseling. If symptoms improve and are stable for 4 wks,
⫽ Canadian drug name.
⫽ Genetic Implication.
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may return to regular visit schedule and may increase dose. If depression is severe, obtain psychiatric consultation and discontinue interferon alfa 2a or peginterferon alpha 2b permanently.
Monitor for signs of infection (vital signs, WBC) during therapy. Discontinue drug therapy in cases of severe infection, and antibiotic therapy instituted.
Assess for cardiovascular disorders (pulse, BP, chest pain). An ECG
should be performed before and periodically during the course of therapy in patients with a history of cardiovascular disease.
Assess for signs of colitis (abdominal pain, bloody diarrhea, fever) and
pancreatitis (nausea, vomiting, abdominal pain) during therapy. Discontinue therapy if these occur; may be fatal. Colitis usually resolves
within 1– 3 wk of discontinuation.
Assess for development of flu-like syndrome (fever, chills, myalgia, headache).
Symptoms often appear suddenly 3– 6 hr after therapy. Symptoms tend to decrease, even with continued therapy. Acetaminophen may be used for control of
these symptoms.
Monitor for bone marrow depression. Assess for bleeding (bleeding gums; bruising; petechiae; guaiac stools, urine, and emesis) and avoid IM injections and rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for
10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
May cause nausea and vomiting. Antiemetics may be used prophylactically. Monitor intake and output, daily weight, and appetite. Adjust diet as tolerated for anorexia. Encourage fluid intake of at least 2 L/day.
Assess pulmonary status (lung sounds, respirations) periodically during therapy.
Perform a baseline eye exam in all patients prior to initiation of therapy. Eye exams
should be performed periodically during therapy in patients with pre-existing diabetic or hypertensive retinopathy. Discontinue therapy if patients develop new or
worsening eye disorders.
Assess for signs of thyroid dysfunction, as hypothyroidism or hyperthyroidism may
occur. Discontinue therapy if the patient’s thyroid function cannot be controlled
with medications (e.g., thyroid hormone supplementation, antithyroid medications).
Kaposi’s Sarcoma: Monitor number, size, and character of lesions prior to and
throughout therapy.
Lab Test Considerations: Systemic: Monitor for CBC and differential
prior to and periodically during therapy. May cause leukopenia, neutro-
CAPITALS indicate life-threatening, underlines indicate most frequent.
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● Reconstitute 10-, 18-, and 50-million-unit vials with 1 mL of diluent provided by
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penia, thrombocytopenia, decreased hemoglobin and hematocrit, and
hemolytic anemia. The nadirs of leukopenia and thrombocytopenia occur in 3–
5 days, with recovery 3– 5 days after withdrawal of interferon alpha-2b For malignant melanoma, if granulocyte count ⬎250/mm3 but ⬍500/mm3, discontinue
interferon alpha-2b until platelet or granulocyte counts return to normal or
baseline levels, then reinstitute at 50% of dose. If granulocyte count ⬍250/mm3
with interferon alpha-2b, discontinue permanently. For follicular non-Hodgkin’s
lymphoma, if granulocyte count ⬍1000/mm3 or platelet count ⬍50,000/mm3, discontinue interferon alpha-2b. Peginterferon alpha-2b should be discontinued if
granulocyte count ⬍1000/mm3 or platelet count ⬍50,000/mm3. Peginterferon
alpha-2a should be discontinued if ANC⬍500/mm3 or platelet count ⬍25,000/
mm3 and then may be restarted at a lower dose if the ANC ⬎1000/mm3.
Platelet count should be ⱖ90,000 cells/mm3 and ANC ⱖ1500 cells/mm3 prior to
initiation of peginterferon therapy. Commonly causesphemoglobin, hematocrit,
WBC, ANC, lymphocytes and platelet counts within first 2 wk of therapy.
Monitor liver function tests (AST, ALT, LDH, bilirubin, alkaline phosphatase), triglycerides, and renal function tests (BUN, creatinine, uric acid, urinalysis) prior
to and periodically during therapy. CCr should be ⬎50 mL/min prior to initiation
of peginterferon therapy. Peginterferon alpha-2a should be discontinued if liver
function diminishes.
Monitor TSH at baseline and if patients develop symptoms consistent with hypothyroidism or hyperthyroidism.
Hairy Cell Leukemia: Monitor number of peripheral blood hairy cells and bone
marrow hairy cells prior to and during therapy.
manufacturer (sterile water for injection). Agitate gently. Solution may be colorless to light yellow. Solution should be used immediately; stable for up to 24 hr if
refrigerated.
● The solution for injection vials do not require reconstitution prior to use and may
be used for IM, subcut, or intralesional administration.
● The solution for injection in multidose pens are for subcut use only. Only the needles provided in the package should be used with the pen. A new needle should be
used with each dose. Follow instructions in Medication Guide for use of multidose pens.
● IL: Reconstitute 10-million-unit vial with 1 mL of diluent provided by manufacturer (sterile water for injection). Use a TB syringe with 25– 30-gauge needle to
administer. Each 0.1-mL dose is injected into the center of the base of the wart using the intradermal injection approach. As many as 5 lesions can be treated at one
time.
IV Administration
● Intermittent Infusion: (For Malignant Melanoma). Diluent: Add 1 mL of dil-
uent provided by manufacturer (sterile water for injection) to vial. Further dilute
appropriate dose in 100 mL of 0.9% NaCl. Solution should be used immediately;
stable for 24 hr if refrigerated. The solution for injection vials are not recommended for IV administration. Concentration: Final concentration of infusion
should not be less than 10 million units/100 mL. Rate: Infuse over 20 min.
Peginterferon Alpha–2a
● Vials and pre-filled syringes should be stored in refrigerator. Do not administer
solution that is cloudy or contains a precipitate.
Potential Nursing Diagnoses
● Follow instructions in Medication Guide for use of pre-filled syringes.
Risk for injury (Side Effects)
Risk for infection (Side Effects)
Peginterferon Alpha–2b
Implementation
for injection). Administer immediately; stable for 24 hr if refrigerated. Solution
should be clear and colorless. Discard unused solution.
● For PEG Intron Redipen— To reconstitute the drug, hold the Redipen upright
(dose button down) and press 2 halves of pen together until a click is heard. Gently invert the pen to mix the solution (do not shake). Solution should be clear and
colorless. Follow instructions in Medication Guide for RediPen use. Dispose of
RediPen and other materials in puncture-resistant container.
● Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask
while handling medication. Discard equipment in specially designated containers.
Interferon Alpha-2b
● IM, Subcut: Subcut route is preferred for patients with a platelet count ⬍50,000/
mm3.
● Reconstitute vial with 0.7 mL of diluent provided by manufacturer (sterile water
䉷 2015 F.A. Davis Company
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INTERFERONS, ALPHA
●
●
Interferon Alpha-n3
●
● Vials should be refrigerated.
Patient/Family Teaching
● Advise patient to take medication as directed. If a dose is missed, omit dose and
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return to the regular schedule. Notify health care professional if more than 1 dose
is missed.
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.
Review side effects with patient. Interferon may be temporarily discontinued or
dose decreased by 50% if serious side effects occur.
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;
⫽ Canadian drug name.
⫽ Genetic Implication.
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being angry or violent; acting on dangerous impulses; an extreme increase in activity and talking, other unusual changes in behavior or
mood occur.
Discuss with patient the possibility of hair loss. Explore coping strategies.
Explain to patient that fertility may be impaired and that contraception is needed
during treatment to prevent potential harm to the fetus.
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.
Evaluation/Desired Outcomes
● Normalized blood parameters (hemoglobin, neutrophils, platelets, monocytes,
●
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and bone marrow and peripheral hairy cells) in hairy cell leukemia. Response
may not be seen for 6 mo with interferon alpha-2b.
Decrease in the size and number of lesions in Kaposi’s sarcoma. Therapy may be
required for 6 mo before full response is seen. Therapy is continued until disease
progresses or a maximum response has been achieved after 4 mo of therapy.
Increase in time to relapse and overall survival in patients with malignant melanoma.
Disappearance of or decrease in size and number of genital warts. Condylomata
acuminata usually respond in 4– 8 wk. A second course of therapy may be required if genital warts persist and laboratory values remain in acceptable limits.
Decrease in symptoms and improvement in liver function tests andpprogression
of hepatic damage in patients with hepatitis B or hepatitis C infection. Discontinue
Peginterferon alpha-2atherapy if patient fails to demonstrate at least a 2 log10 reduction from baseline in HCV RNA titer by 12 weeks of therapy or undetectable
HCV RNA after 24 weeks of therapy.
Why was this drug prescribed for your patient?
CAPITALS indicate life-threatening, underlines indicate most frequent.
Strikethrough ⫽ Discontinued.
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