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interferon alfa-2b
Drug Monograph
Drug Name | Mechanism of Action and Pharmacokinetics | Indications and Status | Adverse Effects | Dosing | Administration
Guidelines | Special Precautions | Interactions | Recommended Clinical Monitoring | Supplementary Public Funding |
References | Disclaimer A - Drug Name
interferon alfa-2b
SYNONYM(S): IFN alpha-2B
COMMON TRADE NAME(S): Intron A® (Merck)
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B - Mechanism of Action and Pharmacokinetics
Interferons are a group of naturally occurring proteins that have a broad range of activities that are
antiviral, antiproliferative, cytostatic, immunomodulatory, differentiating, and inhibitory of cellular
genes, including oncogenes. Interferons can act directly on tumour cells as well as effector cells
such as NK cells, T cells, and macrophages.
Absorption
Bioavailability
Oral: No, degraded by enzymes.
Distribution
Metabolism
Elimination
Large glycoprotein with poor interstitial penetration. 80% absorbed after IM or
SC injection. Pharmacokinetics linear but large intersubject variation.
Cross blood brain barrier?
Trace
PPB
no information found
Catabolized by proteolysis in renal tubular cells during reabsorption
Active metabolites
no
Inactive metabolites
yes
Disposition described by two-compartment model.
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Urine
no
Half-life
2 to 3 hours
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C - Indications and Status
Health Canada Approvals:
Basal cell carcinoma (intralesional)
Chronic myelogenous leukemia (CML)
Hairy cell leukemia
Kaposi’s sarcoma (patients with AIDS) - in patients ≥ 18 years
Multiple myeloma (maintenance)
Non-Hodgkin’s lymphoma (combination)
Malignant melanoma (adjuvant) - in patients ≥ 18 years
Condylomata acuminata (intralesional)
Other Uses:
Chronic Myelomonocytic Leukemia (CMML)
Renal cell carcinoma
Cutaneous T-cell lymphoma (CTCL)
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D - Adverse Effects
Emetogenic Potential: Minimal Extravasation Potential: None
ORGAN SITE
SIDE EFFECT* (%)
ONSET**
Auditory
Hearing impaired (rare)
E
Cardiovascular
Arrhythmia
E
Arterial thromboembolism
E
Cardiomyopathy (2%) (AIDS patients; reversible)
E
Chest pain (rare)
E
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Heart failure (rare)
E
Hypertension (rare)
I
Hypotension
I
Pulmonary hypertension
E
Venous thromboembolism
E
Dental
Dental disorder (or periodontal disorder, in combination with E
ribavirin)
Dermatological
Alopecia
E
Dry skin (rare)
E
Hirsutism (rare)
E
Hyperhidrosis
E
Nail disorder (rare)
E
Other (exacerbation of psoriasis, herpes labialis)
E
Photosensitivity (rare)
E
Rash (pruritus; transient)
E
Stevens-Johnson syndrome (very rare)
E
Urticaria (rare)
E
Abdominal pain (rare)
E
Anorexia (common)
E
Colitis (rare)
E
Constipation (rare)
E
Diarrhea (common)
E
Dry mouth
E
Dyspepsia (rare)
E
GI hemorrhage (rare)
E
GI ulcer (gastric - rare)
E
Mucositis (rare)
E
Nausea (and vomiting; common)
I E
Weight changes (rare)
E
Edema (rare)
E
Flu-like symptoms (very common)
I E
Bone marrow hypocellular (aplastic anemia - rare)
E
Hemolysis (rare)
E
Hemorrhage (rare)
E
Gastrointestinal
General
Hematological
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Myelosuppression (transient)
E
↑ LFTs (especially > 10 MU daily, transient; may be severe)
E
Pancreatitis (rare)
E
Hypersensitivity
Anaphylaxis (rare)
I
Immune
Autoimmune disorder (vasculitis, hemolysis, hyperthyroidism, E
hypothyroidism, lupus, sarcoidosis - rare)
Hepatobiliary
Other (allograft rejection)
E
Infection
Infection (atypical)
E D
Injection site
Injection site reaction (common)
I
Metabolic /
Endocrine
Abnormal electrolyte(s) (↑ / ↓ Calcium)
E
Hyperglycemia (rare)
E
Hyperuricemia (rare)
E
↑ LDH
E
↑ Triglycerides
E
Muscle weakness (generalized - rare)
E
Rhabdomyolysis (rare)
E
Anxiety (rare)
E
Ataxia (rare)
E
Confusion (dose-related, reversible)
E
Depression (dose-related, reversible; may be severe)
E
Dizziness (common)
E
Dysgeusia
E
Headache (common)
E
Neuropathy (rare)
E
Psychosis (dose-related, reversible)
E
Seizure (rare, high dose)
E
Sleep disorder (rare)
E
Suicidal ideation (rare)
E
Vertigo
E
Conjunctivitis (rare)
E
Optic nerve disorder (rare)
E
Photophobia (rare)
E
Musculoskeletal
Nervous System
Ophthalmic
Retinopathy (retinal vein/artery occlusion, retinal detachment; E
rare)
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Renal
Reproductive and
breast disorders
Respiratory
Urinary
Creatinine increased (may be severe)
E
Nephritis
E
Proteinuria
E
Gynecomastia (rare)
E
Irregular menstruation (rare)
E
Asthma (exacerbation)
E
Cough (and dyspnea; rare)
E
Lung infiltrate (rare)
E
Pneumonitis (rare)
E
Cystitis (rare)
E
Hematuria (rare)
E
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies, isolated data or anecdotal reports.
Dose-limiting side effects are underlined.
** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)
The most common adverse effect is flu-like syndrome consisting of fever, chills, fatigue, myalgias,
anorexia and headache. These effects are transient, dose-related and reversible within 72 hours of
cessation of treatment. Acetaminophen 500-1000 mg (max 4g/d) 30 minutes before administration
of interferon and q4h after alleviates the flu-like symptoms. Chills and rigors can be managed with
meperidine 50 mg IV or chlorpromazine 25-50 mg IM before dose. Tolerance to the flu-like
syndrome develops over several months on continued dosing. The significance of developing neutralizing antibodies to interferon remains controversial. The
incidence of antibody formation to interferon alpha is approximately 0-10% but may be as high as
38% in patients with renal cell cancer. Elevation in liver function tests occur frequently, especially at doses greater than 10 MU daily, but
generally decrease despite continued treatment, and return to pre-existing levels within two weeks
following cessation of treatment. Severe toxicity and liver failure can occur rarely.
CNS toxicity is dose-related and generally reversible, but resolution may take up to three weeks.
Emotional and/or psychiatric problems have been reported. At doses ≥100 MU, marked lethargy,
confusion, dysphagia and overall mental and motor slowing occurs. Rarely, seizures have occurred
at high doses. Suicidal ideation and aggressive behaviour have been reported; interferon should be
discontinued.
Cardiovascular adverse events, especially arrhythmias, are correlated with pre-existing cardiac
dysfunction and prior cardiotoxic therapy. Hypotension may occur during, or up to two days after,
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interferon therapy. Patients should be adequately hydrated during therapy.
Adverse reactions to the intralesional administration of interferon are common (80%, severe 9%);
most are mild to moderate in severity, are transient and rapidly reversible usually within 24 hours.
The most common reactions are flu-like symptoms, and local reactions such as pruritus,
paresthesia, swelling or pain. Low WBC and/or platelet counts and elevated LFTs have also been
observed with intralesional administration.
Because the toxicity of high-dose interferon can be severely debilitating in patients with AIDSrelated Kaposi's sarcoma, it is advisable to escalate dose levels slowly in 3 MU/m2 increments
over several weeks and to immediately reduce doses by 50% when serious toxicity is encountered.
Treatment should be discontinued if patient develops symptoms of colitis. It has been observed
within 12 weeks of starting Interferon-alfa treatment, and will usually resolve within 1 to 3 weeks after
discontinuation.
Ophthalmic disorders (retinopathy, retinal hemorrhages, retinal vein or artery occlusion, serious
retinal detachment, cotton wool spots and loss of visual acuity) have occurred rarely with interferon
treatment. Patients with disorders associated with retinopathy (i.e. diabetes) should have periodic
visual examinations.
Fatal pneumonitis may occur and the incidence is higher when used in combination with Chinese
herbal agents (i.e. sho-saiko-to). Interferon should be discontinued immediately and pneumonitis to
be investigated and treated appropriately (i.e. with steroids).
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E - Dosing
Refer to protocol by which patient is being treated. Note: 1 MU = 1 million units = 1 million IU (international units) = 1 megaunit. Acetaminophen
should be administered 30 minutes before interferon.
Adults:
Hairy cell leukemia: 2 MU/m2 SC three times a week* (*every other day) Kaposi’s sarcoma: 30 MU/m2 SC/IM three times a week*. Titrate to tolerability ± progression.
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CML: 4 – 5 MU/m2 SC daily (range: 0.5 to 10 MU/m2), then three times a week* when WBC
controlled. Myeloma: 3 MU/m2 SC three times a week*
NHL: 5 MU SC three times a week*. When used in combination, dose of cytotoxics may
require modification including increase in cycle length
Melanoma: Induction: 20 MU/m2 IV 5 days/week for 4 weeks
Maintenance: 10 MU/m2 SC three times a week* for 48 weeks
Intralesionally for Basal cell carcinoma:
Lesions < 2 cm2: 1.5 MU three times a week* x 3 weeks (maximum of 3 lesions/time)
Lesions 2-10 cm2: 0.5 MU/cm2 of lesion (range 1.5 MU – 5 MU) three times a week* for
3 weeks (maximum of 1 lesion at one time) Dosage with Toxicity:
Doses should be held or reduced (50%) for severe toxicity. Consider permanent
discontinuation if recurs.
Dosage with myelosuppression: Reduce dose or hold dose for significant myelosuppression.
(Continued on next page)
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Toxicity
Action
Dose (% of previous
dose)
Colitis, pancreatitis
Pulmonary infiltrates/
Pulmonary function
impairment
Discontinue
Not applicable
May continue treatment; treat
symptomatically
Continue if TSH normalized
after medication
No change
Ischemic disease
Autoimmune disorders
New or worsening
ophthalmological disorders
Severe depression, suicidal
behaviour, psychosis,
hallucinations, aggressive
behaviour
Severe hypersensitivity
reaction Severe exacerbation of preexisting neuropsychiatric,
autoimmune, ischemic or
infective conditions.
Transient rashes
Thyroid dysfunction
No change
Dosage with Hepatic Impairment:
Do not use in patients with autoimmune hepatitis.
LFTs (AST and/or ALT)
Action
Dose (% of previous
dose)
5 – 10 x ULN
Hold until recovery
50%
> 10 x ULN
Discontinue
Not applicable
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Dosage with Renal Impairment:
Caution if CrCl < 50 mL/min. Contraindicated in combination therapy with ribavirin in patients
with CrCl < 50 mL/min.
Dosage in the elderly:
Use with caution. The elderly may be more susceptible to toxicity.
Children:
Safety and efficacy not established. Formulations containing benzyl alcohol are
contraindicated in infants/neonates.
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F - Administration Guidelines
Subcutaneous self-administration (or administered by home caregiver); drug available by retail
prescription.
IV administration (ready-to-use solution): Mix in 50 mL bag of NS; infuse over 20 minutes. Final concentration must be ≥ 0.3 mg/mL.
May give acetaminophen 500mg-1000mg 30 min prior to administration to alleviate flu-like
symptoms.
Avoid IM use with thrombocytopenia
Do not administer with other drugs
For intralesional administration, must use 10 MU lyophilized vials to ensure isotonic solution
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G - Special Precautions
Contraindications:
patients who have a hypersensitivity to this drug or any of its components or other interferon
preparations
patients with pre-existing neuropsychiatric, autoimmune, ischemic or infectious conditions;
interferon may exacerbate these conditions (may be fatal)
avoid preparations containing benzyl alcohol as a preservative in patients with hypersensitivity
to benzyl alcohol and in neonates/infants
avoid in patients with rapidly progressive visceral Kaposi's sarcoma
avoid in combination with ribavirin in patients with CrCl < 50 ml/min
Other Warnings/Precautions:
interferon may cause CNS depression and may interfere with the ability to drive or operate
machinery
patients with a history of seizures, neurological, cardiac, autoimmune disorders or pre-existing
myelosuppresion
patients with psoriatic disease, sarcoidosis, debilitating medical conditions, allografts, and in
patients with HIV-related Kaposi's sarcoma
use live vaccines with caution (possible reduced response)
Other Drug Properties:
Carcinogenicity: Unknown
Pregnancy and Lactation:
Mutagenicity: Unlikely
Abortifacient effects: Documented in animals
Interferon is not recommended for use in pregnancy. Adequate contraception should be used
by both sexes during treatment, and for at least 6 months after the last dose.
Fertility effects: Probable
Excretion into breast milk: Documented in animals
Breastfeeding is not recommended.
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H - Interactions
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AGENT
EFFECT
CNS depressants ↑ CNS depression
Live vaccines
MECHANISM
Additive
Lack of response to vaccine ↓ antibody response
MANAGEMENT
Caution
Avoid
Phenobarbital and ↑ serum levels of
drugs metabolized phenobarbital
by CYP450 (i.e.
cimetidine,
warfarin,
diazepam)
IFN inhibits metabolism Monitor for toxicity of
phenobarbital
Steroidal and
nonsteroidal antiinflammatory
drugs
Potential for reduced
efficacy of interferon
Interference with
Avoid
immune mechanism of
action
Theophylline
↑ theophylline levels
↓ metabolism
Monitor levels
Shosaikoto
(Chinese herb)
↑ incidence of pneumonitis
Unknown
Avoid concomitant use
Vidarabine
↑ neurotoxicity
Unknown
Caution
Zidovudine
↑ hematologic and hepatic
toxicity
Possibly Additive
Caution
Telbivudine
↑ peripheral neuropathy
Unknown
Avoid
Antineoplastic
agents
↑ risk of toxicity (severity and Additive or synergistic
duration)
Caution; dose
adjustment required for
interferon alfa and
antineoplastic agents
Aldesleukin
Hypersensitivity reactions,
Unknown
development of autoimmune
disease and inflammatory
disorders, myocardial injury
Caution
Ribavirin
Aplastic anemia, pure red
cell aplasia reported (very
rare)
Avoid in CrCl < 50
ml/min
Unknown
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I - Recommended Clinical Monitoring
Treating physicians may decide to monitor more or less frequently for individual patients but should
always consider recommendations from the product monograph.
Recommended Clinical Monitoring
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Monitor Type
Monitor Frequency
Thyroid function tests
Baseline and regular
Liver function tests
Baseline and regular
Renal function tests and electrolytes
Baseline and regular
CBC
Baseline and intermittent; regular if
high dose
Ophthalmologic evaluation
Baseline
Clinical toxicity assessment of flu-like symptoms,
ophthalmic, psychiatric, endocrine, cardiovascular,
pulmonary, autoimmune and GI adverse effects
At each visit
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events)
version
Suggested Clinical Monitoring
Monitor Type
Monitor Frequency
ECG, in patients with pre-existing cardiac disease or
advanced cancer
Baseline and regular
Blood glucose in diabetic patients.
Baseline and regular
Triglyceride levels
Baseline and regular
Ophthalmoscopy
regular
Calcium
Baseline and regular
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J - Supplementary Public Funding
New Drug Funding Program (NDFP Website)
Interferon - Melanoma
ODB Limited Use (ODB Formulary)
For hairy cell leukemia and Kaposi's Sarcoma
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K - References
Product Monograph: Intron A® (Inteferon alfa-2b). Schering-Plough Canada, Inc. March 24, 2011.
Cancer Drug Manual (the Manual), revised December 2013, British Columbia Cancer Agency
(BCCA)
Interferon alfa: e-Drugdex, Micromedex Healthcare Series.
McEvoy GK, editor. AHFS Drug Information 2009. Bethesda: American Society of Health-System
Pharmacists, p. 1108-31.
Memorial Sloan Kettering Cancer Centre: About Herbs - Sho-saiko-to.
August 2016 edited indications
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L - Disclaimer
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public
funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management
information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare
providers and is to be used for informational purposes only. The information is not intended to cover all possible uses,
directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate
that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is
not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All
uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information
provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management
information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of
last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly
evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended
that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom
management information (for patients), are intended for patients. Patients should always consult with their healthcare
provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is
provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory
or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
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information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO
and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and
expenses) arising from such person’s use of the information in the Formulary.
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