| Note
: For
the use of registered medical practitioner, hospital
or laboratory only |
|
| INTALFA - Information
for Professionals: |
|
|
|
| Preclinical Pharmacology: |
| Interferon exert their
cellular activities by binding to specific membrane receptors
on the cell surface. These include the induction of certain
enzymes, suppression of cell proliferation, immunomodulating
activities such as enhancement of the phagocytic activity
of macrophages and augmentation of the specific cytotoxicity
of lymphocytes for target cells, and inhibition of virus
replication in virus-infected cells. |
|
|
|
| In
vitro Bioassay: |
| The
biological activity of purified recombinant human Interferon
Alfa 2b was determined by a viral CPER (Cytopathic Effect
Reduction assay) assay. Intas Interferon alfa 2b, reference
standards (NIBSC standard Interferon alfa 2b) and Commercial
standard (INTRON A ®) induce a dose dependent antiviral
activity in the target cell line (WISH). These cells
were then challenged with a known amount of virus
to cause a cytopathic effect. The dilution, at which
the cytopathic effect was reduced by 50 %, is taken as
the end point (ED50). The dose dependent protection of
the WISH cells against the virus is quantified. The potency
is calculated by comparison with Interferon alfa 2b standard
of defined potency from NIBSC, UK. The assay design and
interpretation is according to parallel-line analysis.
In vitro bioassay also forms a test of identity, of the
protein. The in vitro biological activity of Intas Interferon
alfa 2b matches with the specification laid in Ph. Eur
2005 (Not less than 1.4 x108 IU/mg) and also with that
of INTRON A. |
|
|
|
| Animal
Toxicity studies: Acute toxicity |
| studies
were conducted in rats and mice by administering I.M.
and S.C. single doses of 12 mcg/kg of IPL-P02 (r-interferon
alfa-2b). The animals were observed for mortality, clinical
signs and gross organ examinations. There was no death
or any other adverse effect in the animals at all the
dose levels. In repeat dose subacute toxicity studies
in rats and mice a dose of 10 mcg/kg, 30 mcg/kg, and
100 mcg/kg was administered for a period of 28 days by
SC and IM routes. The animals were examined for body
weight changes, food consumption, hematology, blood chemistry
and histopathological examination of body organs. There
was no abnormality detected in any of the parameters
in both the animals. IPL-P02 was well tolerated in low,
medium and high dose levels in these studies. IPL-P02
(r-Interferon alfa 2b) was also evaluated for local
irritation and allergencity by conducting primary
irritation test in rabbits and allergic contact sensitization
in guinea pigs. The test drug was well tolerated and
there was no evidence of any irritation in the animals. |
|
|
|
| Pharmacokinetics: |
| The mean serum interferon
alfa-2b, recombinant concentrations following intramuscular
and subcutaneous injections were comparable. The maximum
serum concentrations obtained via these routes were approximately
18-116 IU/ml and occurred 3-12 hours after administration.
The elimination half-life of interferon alfa-2b, recombinant
for injection following both intramuscular and subcutaneous
injections was approximately 2-3 hours. Serum concentrations
were below the detection limit by 16 hours after the injections. |
After intravenous administration, serum
interferon alfa-2b, recombinant concentrations peaked
(135-273 IU/ml) by the end of the 30 minute infusion,
then declined at a slightly more rapid rate than after
intramuscular or subcutaneous drug administration, becoming
undetectable 4 hours after the infusion. The elimination
half-life was approximately 2 hours. |
|
|
|
| Effects
of recombinant Interferon alfa-2b in Indian patients: |
| The
efficacy and safety of Recombinant interferon alfa-2b
(IPL-P02) was evaluated in an open label, phase III confirmatory
trial conducted in Indian patients for the treatment
of chronic myeloid leukemia in chronic stable phase,
chronic hepatitis B infection and chronic hepatitis C
infection. |
|
| Interferon alfa-2b
in Chronic Myeloid Leukemia: |
| This multicenter study
enrolled adult patients (n=46) with chronic myeloid leukemia
in chronic stable phase. All patients were Philadelphia
chromosomes positive with adequate liver and kidney function.
Patients were evaluated for complete and partial hematological
and cytogenetic responses after treatment with daily injection
of interferon 5 MIU subcutaneously for 6 months. In
this study, a total of 78.4% patients had shown hematological
response. 24.3% had complete and 54.1% had partial hematological
response. Patients were investigated for Philadelphia chromosomes
by FISH technique and 13.2% had partial cytogenetic response
after treatment with interferon. The hematological and
cytogenetic responses of interferon in this study were
comparable to the earlier clinical studies. 61.7% of total
patients in this study had developed side effects. The
commonest side effect was fever that was reported in 70.2%
of the patients followed by body pain in 46.8% patients
(n=46). The other side effects were cough (29.8%), weakness
(23.4%), thrombocytopenia (14.9%), and pain in legs (14.9%).The
observed adverse effects with interferon in this study
were well within the reported range in other studies. There
was no alteration in liver and kidney function and all
laboratory parameters were unaffected after treatment with
interferon. |
|
| Interferon alfa-2b
in Chronic Hepatitis C Infection: |
| This multicenter study
enrolled adult patients (n=32) with chronic hepatitis C
infection. The patients had anti-HCV in serum and elevated
ALT with liver histology index > 3. Quantitative
RNA was measured by PCR method at the baseline, 4 weeks,
12 weeks and at the end of interferon treatment. Interferon
was administered in a dose of 3 MIU thrice weekly with
concomitant oral ribavirin (1000-1200 mg/day) for a period
of 6 months. Patients were evaluated for virological and
biochemical responses after completion of treatment.70%
patients after 12 weeks and 90% patients after completion
of study had shown virological response (undetectable serum
RNA or more than 2 log decrease) after treatment with interferon
and ribavirin. The biochemical response (normalization
of serum ALT) at 12 weeks and end of therapy was shown
in 68% and 80% patients respectively. There was a significant
(p<0.05) decrease in serum ALT after the treatment.
The mean serum ALT at the baseline was 141.1 IU/L and after
completion of treatment it was decreased to 32.5 IU/L.
The commonly reported adverse events during this study
were fever (40.6%), weakness (37.5%), body ache (21.9%)
and dyspepsia (21.9%). Other reported adverse effects were
vomiting (9.4%), depression (9.4%), loss of appetite (9.4%),
abdominal pain (3.1%), common cold (3.1%), palpitation
(3.1%), hair loss (3.1%), dysuria (3.1%), insomnia (3.1%),
diarrhea (3.1%) cough (6.2%), cervical node swelling (3.1%)
and gastroenteritis (3.1%) The observed adverse effects
with interferon in this study were well within the reported
range in other studies. There was no alteration in liver,
kidney and thyroid function after the treatment. There
was a decrease in mean hemoglobin level that was well within
the reported range in available literature. All other laboratory
parameters were normal at the end of treatment. |
|
| Interferon
alfa-2b in Chronic Hepatitis B Infection: |
| This
multicenter study enrolled adult patients (n=31) with
chronic hepatitis B infection. The patients had HBV DNA
in serum and elevated ALT with liver histology index > 3.
Quantitative DNA was measured by RT-PCR method at the
baseline, and at the end of interferon treatment. Interferon
was administered in a dose of 5 MIU daily subcutaneously
for a period of 16 weeks. Patients were evaluated for
virological and biochemical responses after completion
of treatment. 42% patients after completion of study
had shown virological response (undetectable serum HBV
DNA or more than 2 log decrease) after treatment with
interferon. Both HBeAg positive and HBeAg negative patients
had shown virological response. 37.5% patients with HBeAg
positive and 44.5% patients with HBeAg negative had shown
virological response. A total of 36% patients had shown
biochemical response as their serum ALT was restored
to normal after treatment with interferon. |
The
adverse effects commonly reported during this study were
fever (41.9%), weakness (38.7%), body ache (35.5%) and
anorexia (16.1%). Other reported adverse effects were
gastritis (12.9%), depression (6.4%), headache (6.4%),
nausea (6.4%), constipation (6.4%), confusion (3.2 %),
pain in hypochondrium (3.2%), psychiatric manifestation
(3.2%), thrombocytopenia (3.2 %), diarrhea (3.2%), itching
(3.2%), loss of taste (3.2%) and dryness of mouth (3.2
%), vomiting (3.2%). The observed adverse effects with
interferon in this study were well within the reported
range in other studies. There was no alteration in liver,
kidney and thyroid function after the treatment. The
laboratory parameters were normal at the end of treatment. |
|
|
|
| INDICATIONS
AND USAGE: |
| Interferon
alfa- 2b is indicated for the treatment of Chronic Myelogenous
Leukemia, Hepatitis B and Hepatitis C infection. |
|
|
For
further details and product specifications please contact
us. |
|
