Approved Drug Label (PDF)
4
Contraindications
(additions
underlined)
PEGINTRON
is contraindicated in patients with:
known hypersensitivity reactions, such as urticaria,
angioedema, bronchoconstriction,
anaphylaxis, Stevens-Johnson syndrome, and toxic epidermal necrolysis to
interferon alpha or any other component of the product
autoimmune
hepatitis
hepatic
decompensation (Child-Pugh score greater than 6 [class B and C]) in
cirrhotic CHC patients before or during treatment
If
PEGINTRON is administered with ribavirin, the contraindications to ribavirin
also apply to this combination regimen. Refer to the ribavirin prescribing
information for a list of contraindications for ribavirin. PEGINTRON
combination treatment with ribavirin is contraindicated in women who are or may
become pregnant and men whose female partners are pregnant. Advise pregnant
women about the potential risk to a fetus.
5
Warnings and Precautions
(The following subsections revised or added, please refer to label)
5.1 Risks Associated with Ribavirin Combination
Treatment
5.2 Neuropsychiatric Events
5.3 Cardiovascular Events
5.4 Endocrine Disorders
5.5 Ophthalmologic Disorders
5.6 Cerebrovascular Disorders
5.7 Bone Marrow Toxicity
5.8 Autoimmune Disorders
5.9 Pancreatitis
5.10 Colitis
5.11 Pulmonary Disorders
5.12 Hepatic Failure
5.13 Patients with Renal Insufficiency
5.14 Hypersensitivity
5.15 Laboratory Tests
5.16 Dental and Periodontal Disorders
5.17 Triglycerides
5.18 Impact on Growth — Pediatric Use
5.19 Peripheral Neuropathy
6
Adverse Reactions
6.1 Clinical Trials Experience
(extensive
additions and revisions, please refer to label)
6.2 Immunogenicity
(additions
underlined)
As
with all therapeutic proteins, there is potential for immunogenicity. Approximately
2% of subjects receiving PEGINTRON (32/1759) or INTRON A (11/728) with or without
REBETOL developed low-titer (less
than or equal to 160) neutralizing antibodies to PEGINTRON or INTRON A.
The clinical and pathological significance of the appearance of serum-neutralizing antibodies is unknown.
…
6.3 Postmarketing Experience
(additions
underlined)
...
Cardiac
Disorders
Palpitations, pericarditis
Ear and
Labyrinth Disorders
Hearing loss, vertigo, hearing
impairment
Endocrine
Disorders
Diabetic ketoacidosis, diabetes
Eye Disorders
Vogt-Koyanagi-Harada syndrome, serous
retinal detachment
Gastrointestinal
Disorders
Aphthous stomatitis, tongue pigmentation
General
Disorders and Administration Site Conditions
Asthenic conditions (including asthenia,
malaise, fatigue)
Immune System
Disorders
Cases of acute hypersensitivity
reactions (including anaphylaxis, angioedema, urticaria); Stevens-Johnson
syndrome, toxic epidermal necrolysis, systemic lupus erythematosus, erythema
multiforme
Infections and Infestations
Bacterial infection including sepsis,
Hepatitis B virus reactivation in HCV/HBV co-infected patients
Metabolism and
Nutrition Disorders
Dehydration,
hypertriglyceridemia
Musculoskeletal
and Connective Tissue Disorders
Rhabdomyolysis, myositis
Nervous System
Disorders
Seizures, memory loss, peripheral
neuropathy, paraesthesia, migraine headache
Psychiatric
Disorders
Homicidal ideation
Respiratory,
Thoracic, and Mediastinal Disorders
Pulmonary hypertension, pulmonary
fibrosis
Renal and Urinary
Disorders
Renal failure, renal insufficiency
…
7
Drug Interactions
7.1 Drugs Metabolized by Cytochrome P-450
(new
subsection added)
Peginterferon
alfa-2b inhibits CYP1A2 and CYP2D6 activity. Drugs with a narrow therapeutic
range metabolized by CYP1A2 (caffeine) or CYP2D6 (thioridazine) should be
administered with caution when coadministered withPEGINTRON (Table 11).
Table
11: Established and Other Potentially Significant Drug Interactions:
Alterations in Dose or Regimen May Be Recommended Based on Drug Interaction
Studies or Predicted Interaction
(please
refer to label to view table 11)
7.2 Use with Ribavirin (Nucleoside Analogues)
(new
subsection added)
Hepatic
decompensation (some fatal) has occurred in cirrhotic HIV/HCV co-infected
patients receiving combination antiretroviral therapy for HIV and interferon
alpha and ribavirin. Adding treatment with alpha interferons alone or in
combination with ribavirin may increase the risk in this patient subset.
Patients receiving interferon with ribavirin and nucleoside reverse
transcriptase inhibitors (NRTIs) should be closely monitored for treatment-
associated toxicities, especially hepatic decompensation and anemia.
Discontinuation of NRTIs should be considered as medically appropriate [see labeling for individual NRTI product].
Dose reduction or discontinuation of interferon, ribavirin, or both should also
be considered if worsening clinical toxicities are observed, including hepatic
decompensation (e.g., Child-Pugh greater than 6).
Stavudine,
Lamivudine, and Zidovudine
In vitro studies have
shown ribavirin can reduce the phosphorylation of pyrimidine nucleoside
analogues such as stavudine, lamivudine, and zidovudine. In a trial with
another pegylated interferon alpha, no evidence of a pharmacokinetic or pharmacodynamic
(e.g., loss of HIV/HCV virologic suppression) interaction was seen when
ribavirin was co-administered with zidovudine, lamivudine, or stavudine in
HIV/HCV co-infected subjects [see
Clinical Pharmacology (12.3)].
HIV/HCV
co-infected subjects who were administered zidovudine in combination with
pegylated interferon alpha and ribavirin developed severe neutropenia (ANC less
than 500) and severe anemia (hemoglobin less than 8 g/dL) more frequently than
similar subjects not receiving zidovudine (see
Table 11).
Didanosine
Co-administration
of ribavirin and didanosine is not recommended. Reports of fatal hepatic
failure, as well as peripheral neuropathy, pancreatitis, and symptomatic
hyperlactatemia/lactic acidosis have been reported in clinical trials.
8
Use in Specific Populations
8.1 Pregnancy
(additions
underlined)
Risk
Summary
PEGINTRON
may be used in combination with ribavirin. If PEGINTRON is administered with
ribavirin, the combination regimen is contraindicated in pregnant women and men
whose female partners are pregnant because ribavirin may cause birth defects
and death of the unborn child. Refer to the ribavirin prescribing information
for more information on use during pregnancy.
on findings from animal studies, PEGINTRON can
cause fetal harm when administered to a pregnant woman. Available human data with PEGINTRON use in pregnant women are
insufficient to identify a drug-associated
risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.
In animal reproduction studies, administration of interferon to rhesus
monkeys beginning from the onset of organogenesis resulted in increased
abortion and premature infant death (see
Data). Advise pregnant women of the potential risk to a fetus.
The
estimated background risk of major birth defects and miscarriage for the
indicated population is unknown. All pregnancies have a background risk of
birth defect, loss, or other adverse outcomes. In the U.S.
general population, the estimated background risk of major birth defects and
miscarriage is 2-4% and 15-20%, respectively.
Data
Animal Data
In
an embryo-fetal development study, rhesus monkeys received nonpegylated
interferon alfa-2b daily by intramuscular injection during and past the
period of organogenesis (Gestation Days 20-80). Nonpegylated interferon
alfa-2b was abortifacient at 15 and 30 million international units (IU)/kg
(estimated human equivalent of 5 and 10 million IU/kg, based on body surface
area).
8.2 Lactation
(additions
underlined)
Risk
Summary
PEGINTRON
may be used in combination with ribavirin. If PEGINTRON is administered with
ribavirin, breastfeeding is not recommended because of the potential for
serious adverse reactions from ribavirin in the breastfed infant.
…
8.3 Females and Males of Reproductive Potential
(additions
underlined)
PEGINTRON
may be used in combination with ribavirin. If PEGINTRON is administered with
ribavirin, the information for ribavirin regarding pregnancy testing,
contraception, and infertility also applies to this combination regimen. Refer
to ribavirin prescribing information for additional information.
…
Infertility
Females
Based
on animal fertility studies conducted in female cynomolgus monkeys,
PEGINTRON may impair human fertility. These effects were shown to be
reversible.
8.4 Pediatric Use
(additions
underlined)
Safety
and effectiveness of PEGINTRON in pediatric patients below the age of 3
years have not been established.
Long-term
follow-up data in pediatric subjects indicates that PEGINTRON in combination
with ribavirin may induce a growth inhibition that results in reduced height in
some patients.
8.5 Geriatric Use
(additions
underlined)
In
general, younger patients tend to respond better than older patients to
interferon-based therapies. Clinical trials of PEGINTRON alone or in combination
with ribavirin did not include sufficient numbers of subjects aged 65 and
over to determine whether they respond differently than younger subjects.Treatment
with alpha interferons, including PEGINTRON, is associated with neuropsychiatric,
cardiac, pulmonary, GI, and systemic (flu-like) adverse effects. Because these
adverse reactions may be more severe in the elderly, caution should be
exercised in the use of PEGINTRON in
this population. This drug is known to be substantially excreted by the
kidney. Because elderly patients are more likely to have decreased renal
function, the risk of toxic reactions to this drug may be greater in
patients with impaired renal function.
When using PEGINTRON/ribavirin therapy, refer also to the ribavirin
labeling.
8.6 Organ Transplant Recipients
(new
subsection added)
The
safety and efficacy of PEGINTRON alone or in combination with ribavirin for the
treatment of hepatitis C in liver or other organ transplant recipients have not
been studied. In a small (n=16) single-center, uncontrolled case experience,
renal failure in renal allograft recipients receiving interferon alpha and
ribavirin combination therapy was more frequent than expected from the center’s
previous experience with renal allograft recipients not receiving combination
therapy. The relationship of the renal failure to renal allograft rejection is
not clear.
8.7 HIV or HBV Co-infection
(new
subsection added)
The
safety and efficacy of PEGINTRON/ribavirin for the treatment of patients with
HCV co-infected with HIV or HBV have not been established.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
(revised
to be consistent with the prescribing information, please refer to label)
PATIENT COUNSELING INFORMATION
(extensive
additions, please refer to label)
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