Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1175
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Roferon-A (Injection, Solution)
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Roferon-A recommended dosing regimens are different
for each of the following indications as described below. Note: Parenteral
drug products should be inspected visually for particulate matter
and discoloration before administration, whenever solution and container
permit. Roferon-A is administered subcutaneously.<br/>Chronic Hepatitis C: The recommended dosage of Roferon-A for the treatment
of chronic hepatitis C is 3 MIU three times a week (tiw) administered
subcutaneously for 12 months (48 to 52 weeks). As an alternative,
patients may be treated with an induction dose of 6 MIU tiw for the
first 3 months (12 weeks) followed by 3 MIU tiw for 9 months (36 weeks).
Normalization of serum ALT generally occurs within afew weeks after
initiation of treatment in responders. Approximately 90% of patients
who respond to Roferon-A do so within the first 3 months of treatment;
however, patients responding to Roferon-A with a reduction in ALT
should complete 12 months of treatment. Patients who have no response
to Roferon-A within the first 3 months of therapy are not likely to
respond with continued treatment; treatment discontinuation should
be considered in these patients. Patients who
tolerate and partially or completely respond to therapy with Roferon-A
but relapse following its discontinuation may be re-treated. Re-treatment
with either 3 MIU tiw or with 6 MIU tiw for 6 to 12 months may be
considered. Please see ADVERSE
REACTIONS regarding the increased frequency of adverse
reactions associated with treatment with higher doses. Temporary dose reduction by 50% is recommended in patients
who do not tolerate the prescribed dose. If adverse events resolve,
treatment with the original prescribed dose can be re-initiated. In
patients who cannot tolerate the reduced dose, cessation of therapy,
at least temporarily, is recommended.<br/>Chronic Myelogenous Leukemia: For patients with Ph-positive CML in chronic phase:
Prior to initiation of therapy, a diagnosis of Philadelphia chromosome
positive CML in chronic phase by the appropriate peripheral blood,
bone marrow and other diagnostic testing should be made. Monitoring
of hematologic parameters should be done regularly (e.g., monthly).
Since significant cytogenetic changes are not readily apparent until
after hematologic response has occurred, and usually not until several
months of therapy have elapsed, cytogenetic monitoring may be performed
at less frequent intervals. Achievement of complete cytogenetic response
has been observed up to 2 years following the start of Roferon-A treatment. The recommended initial dose of Roferon-A is 9 MIU daily
administered as a subcutaneous injection. Based on clinical experience,short-term tolerance may be improved by gradually increasing
the dose of Roferon-A over the first week of administration from 3
MIU daily for 3 days to 6 MIU daily for 3 days to the target dose
of 9 MIU daily for the duration of the treatment period. The optimal dose and duration of therapy have not yet
been determined. Even though the median time to achieve a complete
hematologic response was 5 months in study MI400, hematologic responses
have been observed up to 18 months after treatment start. Treatment
should be continued until disease progression. If severe side effects
occur, a treatment interruption or a reduction in either the dose
or the frequency of injections may benecessary to achieve the individual
maximally tolerated dose . Limited data are available on the use of Roferon-A in
children with CML. In one report of 15 children with Ph-positive,
adult-type CML doses between 2.5 to 5 MIU/m/day given
intramuscularly were tolerated.In another study, severe
adverse effects including deaths were noted in children with previously
untreated, Ph-negative, juvenile CML, who received interferon doses
of 30 MIU/m/day.<br/>Hairy Cell Leukemia: Prior to initiation of therapy, tests should be performed
to quantitate peripheral blood hemoglobin, platelets, granulocytes
and hairy cells and bone marrow hairy cells. These parameters should
be monitored periodically (e.g., monthly) during treatment to determine
whether response to treatment has occurred. If a patient does not
respond within 6 months, treatment should be discontinued. If a response
to treatment does occur, treatment should be continued until no further
improvement is observed and these laboratory parameters have been
stable for about 3 months. Patients with hairy cell leukemia have
been treated for up to 24 consecutive months. The optimal duration
oftreatment for this disease has not been determined. The induction dose of Roferon-A is 3 MIU daily for 16
to 24 weeks, administered as a subcutaneous injection. The recommended
maintenance dose is 3 MIU, tiw. Dose reduction by one-half or withholding
of individual doses may be needed when severe adverse reactions occur.
The use of doses higher than 3 MIU is not recommended in hairy cell
leukemia.
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| dailymed-instance:descripti... |
Roferon-A (Interferon alfa-2a, recombinant) is a
sterile protein product for use by injection. Roferon-A is manufactured
by recombinant DNA technology that employs a genetically engineered Escherichia coli bacterium containing
DNA that codes for the human protein. Interferon alfa-2a, recombinant
is a highly purified protein containing 165 amino acids, and it has
an approximate molecular weight of 19,000 daltons. Fermentation is
carried out in a defined nutrient medium containing the antibiotic
tetracycline hydrochloride, 5 mg/L. However, the presence of the antibiotic
is not detectable in the final product. Roferon-Ais supplied in prefilled
syringes. Each glass syringe barrel contains 0.5 mL of product. In
addition, there is a needle, which is��inch in length.<br/>Single Use Prefilled Syringes: 3 million IU (11.1 mcg/0.5
mL) Roferon-A per syringe���The solution is colorless
and each 0.5 mL contains 3 MIU of Interferon alfa-2a, recombinant,
3.605 mg sodium chloride, 0.1 mg polysorbate 80, 5 mg benzyl alcohol
as a preservative and 0.385 mg ammonium acetate. 6 million IU (22.2 mcg/0.5 mL) Roferon-A
per syringe���The solution is colorless and each
0.5 mL contains 6 MIU of Interferon alfa-2a, recombinant, 3.605 mg
sodium chloride, 0.1 mg polysorbate 80, 5 mg benzyl alcohol as a preservative
and 0.385 mg ammonium acetate. 9 million IU (33.3 mcg/0.5 mL) Roferon-A per syringe���The solution is colorless and each 0.5 mL contains 9 MIU
of Interferon alfa-2a, recombinant, 3.605 mg sodium chloride, 0.1
mg polysorbate 80, 5 mg benzyl alcohol as a preservative and 0.385
mg ammonium acetate. The route of administration
is by subcutaneous injection.
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The mechanism by which Interferon alfa-2a, recombinant,
or any other interferon, exerts antitumor or antiviral activity is
not clearly understood. However, it is believed that direct antiproliferative
action against tumor cells, inhibition of virus replication and modulation
of the host immune response play important roles in antitumor and
antiviral activity. The biological activities
of Interferon alfa-2a, recombinant are species-restricted, i.e., they
are expressed in a very limited number of species other than humans.
As a consequence, preclinical evaluation of Interferon alfa-2a, recombinant
has involved in vitro experiments with human cells and some in vivo
experiments.Using human cells in culture, Interferon
alfa-2a, recombinant has been shown to have antiproliferative and
immunomodulatory activities that are very similar to those of the
mixture of interferon alfa subtypes produced by human leukocytes.
In vivo, Interferon alfa-2a, recombinant has been shown to inhibit
the growth of several human tumors growing in immunocompromised (nude)
mice. Because of its species-restricted activity, it has not been
possible to demonstrate antitumor activity in immunologically intact
syngeneic tumor model systems, where effects on the host immunesystem
would be observable. However, such antitumor activity has been repeatedly
demonstrated with, for example, mouse interferon-alfa in transplantable
mouse tumor systems. The clinical significance of these findings is
unknown. The metabolism of Interferon alfa-2a,
recombinant is consistent with that of alpha-interferons in general.
Alpha-interferons are totally filtered through the glomeruli and undergo
rapid proteolytic degradation during tubular reabsorption, rendering
a negligible reappearance of intact alfa interferon in the systemic
circulation. Small amounts of radiolabeled Interferon alfa-2a, recombinant
appear in the urine of isolated rat kidneys, suggesting near complete
reabsorption of Interferon alfa-2a, recombinant catabolites. Liver
metabolism and subsequent biliary excretion are considered minor pathways
of elimination for alfa interferons. The serum
concentrations of Interferon alfa-2a, recombinant reflected a large
intersubject variation in both healthy volunteers and patients with
disseminated cancer. In healthy people, Interferon
alfa-2a, recombinant exhibited an elimination half-life of 3.7 to
8.5 hours (mean 5.1 hours), volume of distribution at steady-state
of 0.223 to 0.748 L/kg (mean 0.400 L/kg) and a total body clearance
of 2.14 to 3.62 mL/min/kg (mean 2.79 mL/min/kg) after a 36 MIU (2.2��10pg) intravenous infusion. After intramuscular and subcutaneous
administrations of 36 MIU, peak serum concentrations ranged from 1500
to 2580 pg/mL (mean 2020 pg/mL) at a mean time to peak of 3.8 hours
and from 1250 to 2320 pg/mL (mean 1730 pg/mL) at a mean time to peak
of 7.3 hours, respectively. The apparent fraction of the dose absorbed
after intramuscular injection was greater than 80%. The pharmacokinetics of Interferon alfa-2a, recombinant after single
intramuscular doses to patients with disseminated cancer were similar
to those found in healthy volunteers. Dose proportional increases
in serum concentrations were observed after single doses up to 198
MIU. There were no changes in the distribution or elimination of Interferon
alfa-2a, recombinant during twice daily (0.5 to 36 MIU), once daily
(1 to 54 MIU), or three times weekly (1 to 136 MIU) dosing regimens
up to 28 days of dosing. Multiple intramuscular doses of Interferon
alfa-2a, recombinant resulted in an accumulation of two to four times
the single dose serum concentrations. There is no pharmacokinetic
information in patients with chronichepatitis C, hairy cell leukemia,
and chronic myelogenous leukemia. Serum neutralizing
activity, determined by a highly sensitive enzyme immunoassay, and
a neutralization bioassay, was detected in approximately 25% of all
patients who received Roferon-A.Antibodies to human leukocyte
interferon may occur spontaneously in certain clinical conditions
(cancer, systemic lupus erythematosus, herpes zoster) in patients
who have never received exogenous interferon.The significance
of the appearance of serum neutralizing activity is not known.<br/>Clinical Studies: Studies have shown that Roferon-A can normalize serum
ALT, improve liver histology and reduce viral load in patients with
chronic hepatitis C. Other studies have shown that Roferon-A can produce
clinically meaningful tumor regression or disease stabilization in
patients with hairy cell leukemia.In Ph-positive Chronic
Myelogenous Leukemia, Roferon-A supplemented with intermittent chemotherapy
has been shown to prolong overall survival and to delay disease progression
compared to patients treated with chemotherapy alone.In
addition, Roferon-A has been shown to produce sustained complete cytogenetic
responses in a small subset of patients with CML in chronic phase.
The activity of Roferon-A in Ph-negative CML has not been determined.<br/>Effects On Chronic Hepatitis
C: The safety and efficacy of Roferon-A was evaluated
in multiple clinical trials involving over 2000 patients 18 years
of age or older with hepatitis, with or without cirrhosis, who had
elevated serum alanine aminotransferase (ALT) levels and tested positive
for antibody to hepatitis C. Roferon-A was given three times a week
(tiw) by subcutaneous (SC) or intramuscular (IM) injection in a variety
of dosing regimens, including dose escalation and de-escalation regimens.
Normalization of serum ALT was defined in all studies as two consecutive
normal serum ALT values at least 21 days apart. A sustained response
(SR) was defined as normalization of ALT both at the end of treatment
and at the end of at least 6 months of treatment-free follow-up. In trials in which Roferon-A was administered for 6 months,
6 MIU, 3 MIU, and 1 MIU were directly compared. Six MIU was associated
with higher SR rates but greater toxicity . In studies in which the same dose of Roferon-A was administered
for 6 or 12 months, the longer duration was associated with higher
SR rates and adverse events were no more severe or frequent in the
second 6 months than in the first 6 months. Based on these data, the
recommended regimens are 3 MIU for 12 months or 6 MIU for the first
3 months followed by 3 MIU for the next 9 months . There are no direct comparisons of these two regimens. Younger patients (e.g., less than 35 years of age) and
patients without cirrhosis on liver biopsy were more likely to respond
completely to Roferon-A than those patients greater than 35 years
of age or patients with cirrhosis on liver biopsy. In the two studies in which Roferon-A was administered subcutaneously
three times weekly for 12 months, 20/173 (12%) patients experienced
a sustained response to therapy (see Table
1). Of these patients, 15/173 (9%) maintained this sustained
response during continuous follow-up for up to four years. Patients
who have ALT normalization but who fail to have a sustained response
following an initial course of therapy may benefit from retreatment
with higher doses of Roferon-A . A subset of patients had liver
biopsies performed both before and after treatment with Roferon-A.
An improvement in liver histology as assessed by Knodell Histology
Activity Index was generally observed. A retrospective
subgroup analysis of 317 patients from two studies suggested a correlation
between improvement in liver histology, durable serum ALT response
rates, and decreased viral load as measured by the polymerase chain
reaction (PCR).<br/>Effects on Ph-Positive Chronic
Myelogenous Leukemia (CML): Roferon-A was evaluated in two trials of patients
with chronic phase CML. Study DM84-38 was a single center phase II
study conducted at the MD Anderson Cancer Center, which enrolled 91
patients, 81% were previously treated, 82% were Ph positive, and 63%
received Roferon-A within 1 year of diagnosis. Study MI400 was a multicenter
randomized phase III study conducted in Italy by the Italian Cooperative
Study Group on CML in 335 patients; 226 Roferon-A and 109 chemotherapy.
Patients with Ph-positive, newly diagnosed or minimally treated CML
were randomized (ratio 2:1) to either Roferon-A or conventional chemotherapy
with either hydroxyurea or busulfan. In study DM84-38, patients started
Roferon-A at 9 MIU/day, whereas in study MI400, it was progressively
escalated from 3 to 9 MIU/day over the first month. In both trials,
dose escalation for insufficient hematologic response, and dose attenuation
or interruption for toxicity was permitted. No formal guidelines for
dose attenuation were given in the chemotherapy arm of study MI400.
In addition, in the Roferon-A arm, the MI400 protocol allowed the
addition of intermittent single agent chemotherapy for insufficient
hematologic response to Roferon-A alone. In this trial, 44% of the
Roferon-A treated patients also received intermittent single agent
chemotherapy at some time during the study. The two studies were analyzed according to uniform response criteria.
For hematologic response: complete response (WBC<9��10/L, normalization of the differential with no immature forms
in the peripheral blood, disappearance of splenomegaly), partial response
(>50% decrease from baseline of WBC to<20%��10/L). For cytogenetic response: complete response (0% Ph-positive
metaphases), partial response (1% to 34% Ph-positive metaphases). In study DM84-38, the median survival from initiation
of Roferon-A was 47 months. In study MI400, the median survival for
the patients on the interferon arm was 69 months, which was significantly
better than the 55 months seen in the chemotherapy control group (48
patients in study MI400 proceeded to BMT and in study DM84-38, 15
patients proceeded to BMT). Roferon-A treatment significantly delayed
disease progression to blastic phase as evidenced by a median time
to disease progression of 69 months to 46 months with chemotherapy. By multivariate analysis of prognostic factors associated
with all 335 patients entered into the randomized study, treatment
with Roferon-A (with or without intermittent additional chemotherapy;
p=0.006), Sokal index(p=0.006) and WBC (p=0.023) were
the three variables associated with an improved survival, independent
of other baseline characteristics (Karnofsky performance status and
hemoglobin being the other factors entered into the model). In study MI400, overall hematologic responses, [complete
responses (CR) and partial responses (PR)], were observed in approximately
60% of patients treated with Roferon-A (40% CR, 20% PR), compared
to 70% with chemotherapy (30% CR, 40% PR). The median time to reach
a complete hematologic response was 5 months in the Roferon-A arm
and 4 months in the chemotherapy arm. The overall cytogenetic response
rate (CR+PR), in patients receiving Roferon-A, was 10% and 12% in
studies MI400 and DM84-38, respectively, according to the intent-to-treat
principle. In contrast, only 2% of the patients in the chemotherapy
arm of study MI400 achieved a cytogenetic response (with no complete
responses). Cytogenetic responses were observed only in patients who
had complete hematologic responses. In study DM84-38, hematologic
and cytogenetic response rates were higher in the subset of patients
treated with Roferon-A within 1 year of diagnosis (76% and 17%, respectively)
compared to the subset initiating Roferon-A therapy more than 1 year
from diagnosis (29% and 4%, respectively). In an exploratory analysis,
patients who achieved a cytogenetic response lived longer than those
who did not. Severe adverse events were observed
in 66% and 31% of patients on study DM84-38 and MI400, respectively.
Dose reduction and temporary cessation of therapy was required frequently.
Permanent cessation of Roferon-A, due to intolerable side effects,
was required in 15% and 23% of patients on studies DM84-38 and MI400,
respectively . Limited data are available on the use of Roferon-A in
children with Ph-positive, adult-type CML. A published report on 15
children with CML suggests a safety profile similar to that seen in
adult CML; clinical responses were also observed(see DOSAGE
AND ADMINISTRATION).<br/>Effects on Hairy Cell Leukemia: A multicenter US phase II study (N2752) enrolled
218 patients; 75 were evaluable for efficacy in a preliminary analysis;
218 patients were evaluable for safety. Patients were to receive a
starting dose of Roferon-A up to 6 MIU/m/day, for an induction
period of 4 to 6 months. Responding patients were to receive 12 months
maintenance therapy. During the first 1 to 2
months of treatment of patients with hairy cell leukemia, significant
depression of hematopoiesis was likely to occur. Subsequently, there
was improvement in circulating blood cell counts. Of the 75 patients
who were evaluable for efficacy following at least 16 weeks of therapy,
46 (61%) achieved complete or partial response. Twenty-one patients
(28%) had a minor remission, 8 (11%) remained stable, and none had
worsening of disease. All patients who achieved either a complete
or partial response had complete or partial normalization of all peripheral
blood elements including hemoglobin level, white blood cell, neutrophil,
monocyte and platelet counts with a concomitant decrease in peripheral
blood and bone marrow hairy cells. Responding patients also exhibited
a marked reduction in red blood cell and platelet transfusion requirements,
a decrease in infectious episodes and improvement in performance status.
The probability of survival for 2 years in patients receiving Roferon-A
(94%) was statistically increased compared to a historical control
group (75%).
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Single Use Prefilled Syringes: (for subcutaneous administration) 3 million IU Roferon-A per syringe���Each 0.5 mL contains 3 MIU of Interferon alfa-2a, recombinant,
3.605 mg sodium chloride, 0.1 mg polysorbate 80, 5 mg benzyl alcohol
as a preservative and 0.385 mg ammonium acetate. Boxes of 1 (NDC 0004-2015-09);
Boxes of 6 (NDC 0004-2015-07). 6 million IU Roferon-A per syringe���Each 0.5 mL contains 6 MIU of Interferon alfa-2a, recombinant, 3.605
mg sodium chloride, 0.1 mg polysorbate 80, 5 mg benzyl alcohol as
a preservative and 0.385 mg ammonium acetate. Boxes of 1 (NDC 0004-2016-09);
Boxes of 6 (NDC 0004-2016-07). 9 million IU Roferon-A per syringe���Each 0.5 mL contains 9 MIU of Interferon alfa-2a, recombinant, 3.605
mg sodium chloride, 0.1 mg polysorbate 80, 5 mg benzyl alcohol as
a preservative and 0.385 mg ammonium acetate. Boxes of 1 (NDC 0004-2017-09);
Boxes of 6 (NDC 0004-2017-07).<br/>Storage: The prefilled syringe should be stored in the refrigerator
at 36��to 46��F (2��to 8��C). Do not freeze or shake. Protect Roferon-A
from light during storage.
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Alpha-interferons, including Interferon alfa-2a,
cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune,
ischemic, and infectious disorders. Patients should be monitored closely
with periodic clinical and laboratory evaluations. Patients with persistently
severe or worsening signs or symptoms of these conditions should be
withdrawn from therapy. In many, but not all cases, these disorders
resolve after stopping Interferon alfa-2a therapy .
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There are no reports of overdosage, but repeated
large doses of interferon can be associated with profound lethargy,
fatigue, prostration, and coma. Such patients should be hospitalized
for observation and appropriate supportive treatment given.
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interferon alfa-2a
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Roferon-A (Injection, Solution)
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Depressive illness and suicidal behavior, including
suicidal ideation, suicide attempt, and suicides, have been reported
in association with the use of alfa-interferon products. The incidence
of reported depression has varied substantially among trials, possibly
related to the underlying disease, dose, duration of therapy and degree
of monitoring, but has been reported to be 15% or higher .<br/>For Patients With Chronic
Hepatitis C: The most frequent adverse experiences were reported
to be possibly or probably related to therapy with 3 MIU tiw Roferon-A,
were mostly mild to moderate in severity and manageable without the
need for discontinuation of therapy. A relative increase in the incidence,
severity and seriousness of adverse events was observed in patients
receiving doses above 3 MIU tiw. Adverse reactions
associated with the 3 MIU dose include: Flu-like
Symptoms: Fatigue (58%), myalgia/arthralgia (51%), flu-like symptoms
(33%), fever (28%), chills (23%), asthenia (6%), sweating (5%), leg
cramps (3%) and malaise (1%). Central and Peripheral
Nervous System: Headache (52%), dizziness (13%), paresthesia (7%),
confusion (7%), concentration impaired (4%) and change in taste or
smell (3%). Gastrointestinal: Nausea/vomiting
(33%), diarrhea (20%), anorexia (14%), abdominal pain (12%), flatulence
(3%), liver pain (3%), digestion impaired (2%) and gingival bleeding
(2%). Psychiatric: Depression (16%), irritability
(15%), insomnia (14%), anxiety (5%) and behavior disturbances (3%). Pulmonary and Cardiovascular: Dryness or inflammation
of oropharynx (6%), epistaxis (4%), rhinitis (3%), arrhythmia (1%)
and sinusitis (<1%). Skin: Injection site
reaction (29%), partial alopecia (19%), rash (8%), dry skin or pruritus
(7%), hematoma (1%), psoriasis (<1%), cutaneous eruptions (<1%),
eczema (<1%) and seborrhea (<1%). Other:
Conjunctivitis (4%), menstrual irregularity (2%) and visual acuity
decreased (<1%). Patients receiving 6 MIU
tiw experienced a higher incidence of severe psychiatric events (9%)
than those receiving 3 MIU tiw (6%) in two large US studies. In addition,
more patients withdrew from these studies when receiving 6 MIU tiw
(11%) than when receiving 3 MIU tiw (7%). Up to half of patients receiving
3 MIU or 6 MIU tiw withdrawing from the study experienced depression
or other psychiatric adverse events. At higher doses anxiety, sleep
disorders, and irritability were observed more frequently. An increased
incidence of fatigue, myalgia/arthralgia, headache, fever, chills,
alopecia, sleep disturbances and dry skin or pruritus was also generally
observed during treatment with higher doses of Roferon-A. Generally there were fewer adverse events reported in
the second 6 months of treatment than in the first 6 months for patients
treated with 3 MIU tiw. Patients tolerant of initial therapy with
Roferon-A generally tolerate re-treatment at the same dose, but tend
to experience more adverse reactions at higher doses. Infrequent adverse events (>1% but<3% incidence) included: cold
feeling, cough, muscle cramps, diaphoresis, dyspnea, eye pain, reactivation
of herpes simplex, lethargy, edema, sexual dysfunction, shaking, skin
lesions, stomatitis, tooth disorder, urinary tract infection, weakness
in extremities. Triglyceride levels were not
evaluated in the clinical trials. However, hypertriglyceridemia has
been reported postmarketing in patients receiving Roferon-A therapy
for chronic hepatitis C.<br/>For Patients With Chronic
Myelogenous Leukemia: For patients with chronic myelogenous leukemia, the
percentage of adverse events, whether related to drug therapy or not,
experienced by patients treated with rIFN��-2a is given below.
Severe adverse events were observed in 66% and 31% of patients on
study DM84-38 and MI400, respectively. Dose reduction and temporary
cessation of therapy were required frequently. Permanent cessation
of Roferon-A, due to intolerable side effects, was required in 15%
and 23% of patients on studies DM84-38 and MI400, respectively. Flu-like Symptoms: Fever (92%), asthenia or fatigue (88%),
myalgia (68%), chills (63%), arthralgia/bone pain (47%) and headache
(44%). Gastrointestinal: Anorexia (48%), nausea/vomiting
(37%) and diarrhea (37%). Central and Peripheral
Nervous System: Headache (44%), depression (28%), decreased mental
status (16%), dizziness (11%), sleep disturbances (11%), paresthesia
(8%), involuntary movements (7%) and visual disturbance (6%). Pulmonary and Cardiovascular: Coughing (19%), dyspnea
(8%) and dysrhythmia (7%). Skin: Hair changes
(including alopecia) (18%), skin rash (18%), sweating (15%), dry skin
(7%) and pruritus (7%). Uncommon adverse events
(<4%) reported in clinical studies included chest pain, syncope,
hypotension, impotence, alterations in taste or hearing, confusion,
seizures, memory loss, disturbances of libido, bruising and coagulopathy.
Miscellaneous adverse events that were rarely observed included Coombs'
positive hemolytic anemia, aplastic anemia, hypothyroidism, cardiomyopathy,
hypertriglyceridemia and bronchospasm.<br/>For Patients With Hairy Cell
Leukemia: Constitutional (100%): Fever (92%), fatigue (86%),
headache (64%), chills (64%), weight loss (33%), dizziness (21%) and
flu-like symptoms (16%). Integumentary (79%):
Skin rash (44%), diaphoresis (22%), partial alopecia (17%), dry skin
(17%) and pruritus (13%). Musculoskeletal (73%):
Myalgia (71%), joint or bone pain (25%) and arthritis or polyarthritis
(5%). Gastrointestinal (69%): Anorexia (43%),
nausea/vomiting (39%) and diarrhea (34%). Head
and Neck (45%): Throat irritation (21%), rhinorrhea (12%) and sinusitis
(11%). Pulmonary (40%): Coughing (16%), dyspnea
(12%) and pneumonia (11%). Central Nervous System
(39%): Dizziness (21%), depression (16%), sleep disturbance (10%),
decreased mental status (10%), anxiety (6%), lethargy (6%), visual
disturbance (6%) and confusion (5%). Cardiovascular
(39%): Chest pain (11%), edema (11%) and hypertension (11%). Pain (34%): Pain (24%) and pain in back (16%). Peripheral Nervous System (23%): Paresthesia (12%) and
numbness (12%). Rarely (<5%), central nervous
system effects including gait disturbance, nervousness, syncope and
vertigo, as well as cardiac adverse events including murmur, thrombophlebitis
and hypotension were reported. Adverse experiences that occurred rarely,
and may have been related to underlying disease, included ecchymosis,
epistaxis, bleeding gums and petechiae. Urticaria and inflammation
at the site of injection were also rarely observed.<br/>In Other Investigational Studies
of Roferon-A: The following infrequent adverse events have been
reported with the investigational use of Roferon-A. Gastrointestinal: Pancreatitis, colitis, gastrointestinal hemorrhage,
stomatitis (<5%); constipation (<3%); hepatitis, abdominal fullness,
hypermotility, excessive salivation, gastric distress (<1%). Cardiovascular: Palpitations (<3%); myocardial infarction,
congestive heart failure, ischemic retinopathy, Raynaud's phenomenon,
hot flashes (<1%). Pulmonary: Pneumonitis,
some cases responded to interferon cessation and corticosteroid therapy
(<5%); chest congestion (<3%); tachypnea (<1%). Central Nervous System and Psychiatric: Stroke, coma,
encephalopathy, transient ischemic attacks, dysphasia, hallucinations,
gait disturbance, psychomotor retardation, apathy, sedation, irritability,
hyperactivity, claustrophobia, loss of libido, ataxia, neuropathy,
poor coordination, dysarthria, aphasia, aphonia, amnesia (<1%). Autoimmune Disease: Vasculitis, arthritis, hemolytic anemia
and lupus erythematosus syndrome (<3%). Other:
Thyroid dysfunction including hypothyroidism and hyperthyroidism,
diabetes requiring insulin therapy in some patients (<5%); anaphylactic
reactions, eye irritation, earache, cyanosis, flushing of skin (<1%).<br/>Abnormal Laboratory Test Values: The percentage of patients with chronic hepatitis
C, hairy cell leukemia, and with chronic myelogenous leukemia who
experienced a significant abnormal laboratory test value (NCI or WHO grades III or IV) at least
once during their treatment with Roferon-A is shown in Table 2: Elevated triglyceride levels have been observed
in patients receiving interferon therapy, including Roferon-A.<br/>Chronic Hepatitis C: The incidence of neutropenia (WHO grades III or IV) was over twice
as high in those treated with 6 MIU tiw (21%) as those treated with
3 MIU tiw (10%).<br/>Chronic Myelogenous Leukemia: In the two clinical studies, a severe or life-threatening
anemia was seen in up to 15% of patients. A severe or life-threatening
leukopenia and thrombocytopenia were observed in up to 20% and 27%
of patients, respectively. Changes were usually reversible when therapy
was discontinued. One case of aplastic anemia and one case of Coombs'
positive hemolytic anemia were seen in 310 patients treated with rIFN��-2a
in clinical studies. Severe cytopenias led to discontinuation of therapy
in 4% of all Roferon-A treated patients. Transient
increases in liver transaminases or alkaline phosphatase of any intensity
were seen in up to 50% of patients during treatment with Roferon-A.
Only 5% of patients had a severe or life-threatening increase in SGOT.
In the clinical studies, such abnormalities required termination of
therapy in less than 1% of patients.<br/>Hairy Cell Leukemia: Increases in serum phosphorus (���1.6 mmol/L)
and serum uric acid (���9.1 mg/dL) were observed in 9% and 10%
of patients, respectively. The increase in serum uric acid is likely
to be related to the underlying disease. Decreases in serum calcium
(���1.9 mmol/L) and serum phosphorus (���0.9 mmol/L) were
seen in 28% and 22% of patients, respectively.<br/>Postmarketing: Central and Peripheral Nervous System: Somnolence,
hearing impairment, hearing loss. Vision: Retinopathy
including retinal hemorrhages and cotton-wool spots, papilledema,
retinal artery and vein thrombosis and optic neuropathy. Skin: Injection site necrosis. Blood:
Idiopathic thrombocytopenic purpura, cyanosis. Renal and Urinary System: Increased blood urea and serum creatinine,
decreased renal function and acute renal failure. Endocrine: Hyperglycemia. Immune System Disorder:
Sarcoidosis. Respiratory: Pulmonary edema. Metabolic and Nutritional: Cases of hypertriglyceridemia/hyperlipidemia
have been reported including some occurring in association with pancreatitis.
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| dailymed-instance:indicatio... |
Roferon-A is indicated for the treatment of chronic
hepatitis C and hairy cell leukemia in patients 18 years of age or
older. In addition, it is indicated for chronic phase, Philadelphia
chromosome (Ph) positive chronic myelogenous leukemia (CML) patients
who are minimally pretreated (within 1 year of diagnosis).<br/>For Patients With Chronic
Hepatitis C: Roferon-A is indicated for use in patients with chronic
hepatitis C diagnosed by HCV antibody and/or a history of exposure
to hepatitis C who have compensated liver disease and are 18 years
of age or older. A liver biopsy and a serum test for the presence
of antibody to HCV should be performed to establish the diagnosis
of chronic hepatitis C. Other causes of hepatitis, including hepatitis
B, should be excluded prior to therapy with Roferon-A.
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| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Roferon-A
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