INTRON A Redipen Interferon alfa-2b (rbe) 18 million IU/1.2mL injection cartridge

Australia - English - Department of Health (Therapeutic Goods Administration)

Buy It Now

Active ingredient:
Interferon alfa-2b
Available from:
Merck Sharp & Dohme (Australia) Pty Ltd
INN (International Name):
Interferon alfa-2b
Authorization status:
Registered
Authorization number:
66126

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INTRON A

Interferon alfa-2b

Consumer Medicine Information

What is in this leaflet

This leaflet answers some common

questions about INTRON A. It does

not contain all of the available

information.

It does not take the place of talking to

your doctor or pharmacist.

All medicines have risks and

benefits. Your doctor has weighed

the risks of you using INTRON A

against the benefits they expect it

will have for you.

If you have any concerns about

using this medicine, ask your

doctor or pharmacist.

Keep this leaflet with the medicine.

You may want to read it again.

What INTRON A is

used for

INTRON A belongs to a group of

medicines called interferons.

Interferons are a family of naturally

occurring, small protein molecules.

They are produced and secreted by

cells in response to viral infections or

various synthetic and biological

inducers.

Interferons modify the body's

immune system response.

INTRON A is used to treat patients

with the following conditions:

Hairy cell leukaemia

Kaposi's sarcoma in AIDS

Chronic myelogenous leukaemia

Multiple myeloma

Follicular non-Hodgkin's

lymphoma

Malignant melanoma

Chronic hepatitis B

Chronic hepatitis C

Your doctor, however, may prescribe

INTRON A for another purpose.

Before you use

INTRON A

When you must not use it:

Do not use INTRON A if you are

allergic to:

interferon alfa-2b or any of the

ingredients listed at the end of

this leaflet.

Do not use INTRON A if you are

pregnant or breastfeeding unless

your doctor says so. Ask your

doctor about the risks and benefits

involved.

If you are a woman of childbearing

age make sure you do not become

pregnant while using INTRON A.

Do not use INTRON A if

packaging is torn or shows signs of

tampering.

Do not use INTRON A after the

expiry date (EXP) printed on the

pack.

If you use it after the expiry date it

may have no effect at all, or worse,

an unexpected effect.

If you are not sure whether you

should start using INTRON A, talk

to your doctor.

Before you start to use it

You must tell your doctor:

1.

if you are allergic to:

any other medicines or any food,

dyes or preservatives

2.

if you have any of these medical

conditions:

heart disease, high blood pressure

or you have ever had a heart

attack

poor kidney or liver function

advanced liver disease

hepatitis and have been treated

recently with medicines that

suppress the immune system

a history of convulsions or mental

disorder

you have ever been treated for

depression or any other

psychiatric disorder

a history of autoimmune disease

or skin disease (psoriasis)

a history of diabetes, lung disease

or respiratory disease

thyroid disease or blood clotting

disorder

3.

you are taking any other

medicines, including medicines

that you buy without a

prescription from a pharmacy,

supermarket or health food

shop.

Be sure to tell your doctor if

you are taking theophylline for

asthma, as you may need to

take different amounts of your

medicine.

Use in Children

There is limited experience with the

use of INTRON A in children.

INTRON A is not intended for use in

premature infants or neonates.

INTRON A

Effect on Fertility

Fertile women should not use

INTRON A unless effective

contraception is used during

treatment with INTRON A.

INTRON A should be used with

caution in fertile men.

How to use INTRON A

How much to inject

Your doctor has determined the exact

schedule according to your needs.

Your dose may be adjusted by your

doctor during therapy according to

your response.

Do not exceed the recommended

dosage.

How to inject

Your doctor or nurse will tell you

how to give the injection under the

skin if you are injecting this medicine

yourself.

INTRON A can also be injected into

a vein. This would normally be

carried out by your doctor.

How to use INTRON A

INTRON A Injectable Solution is

available in single dose vials or as a

Redipen.

(a) How to use INTRON A

Solution Vials

The solution may be injected directly

under the skin after withdrawal of the

appropriate doses from the vial with

a sterile syringe and needle.

(b) How to use INTRON A

Redipen

INTRON A Redipen is a disposable

self-injectable dosing system.

For detailed instructions on how to

use the INTRON A Redipen, please

read the insert enclosed in the

pack.

The Redipen is designed to deliver 6

doses of INTRON A. Each dose is

0.2 mL in volume. The Redipen can

be adjusted to increase or decrease

the dose, according to your doctor's

instruction.

Needles have been provided for use

with INTRON A Redipen.

You must use a new needle each

time a dose is given.

Make sure the Redipen is at room

temperature (25°C) before

injection. Take the Redipen out of

the refrigerator about half-an-hour

beforehand to allow the solution

contained in the Redipen to reach

room temperature.

Dispose of the needle safely after

each dose and return the Redipen

to the refrigerator immediately.

When to inject

If you are injecting this medicine

yourself, use it at bedtime as

interferons may cause unusual

tiredness and flu-like symptoms.

How long to use it

Do not stop using this medicine

without first checking with your

doctor.

Your doctor will determine when

your treatment should be stopped.

If you forget to use it

If it is almost time for your

injection, skip the injection you

missed and take your next

injection when you are meant to.

Otherwise, use it as soon as you

remember, and then go back to

using it as you would normally.

Do not take a double injection to

make up for the injection that you

missed.

If you have trouble remembering

when to use your medicine, ask your

pharmacist for some hints.

If you use too much

(overdose)

Immediately telephone your doctor

or Poisons Information Centre

(telephone 13 11 26) for advice, or

go to casualty at your nearest

hospital, if you think you or

anyone else may have used too

much INTRON A. Do this even if

there are no signs of discomfort or

poisoning. You may need urgent

medical attention.

Keep telephone numbers for these

places handy.

While you are using

INTRON A

Things you must do

Use INTRON A exactly as your

doctor has prescribed.

Tell all doctors, dentists and

pharmacists who are treating you

that you are using INTRON A.

Tell your doctor immediately if

you become pregnant while you

are using INTRON A.

Things you must not do

INTRON A may cause dizziness

and drowsiness in some people. If

you become drowsy from this

medicine do not drive or use

machinery.

Do not use it to treat any other

complaints unless your doctor says

to.

Do not give this medicine to anyone

else, even if their symptoms seem

similar to yours.

Do not switch to any other brands

of interferon unless advised by

your doctor as your response to

other interferons may be different.

Things to be careful of

Check with your doctor about

drinking alcoholic beverages or

taking sleeping pills, sedatives or

strong painkillers.

Your doctor may want you to

drink extra fluids.

This will help prevent low blood

pressure while you are using

INTRON A.

INTRON A

Check with your doctor if you

think you are developing

symptoms associated with a cold or

other respiratory infection.

While receiving INTRON A, you

may temporarily have a greater risk

of getting an infection.

Check with your doctor

immediately if you notice unusual

bleeding or bruising.

Your blood may temporarily take a

longer time to clot.

Tell your doctor if you notice

any changes in your eyes or

eyesight

worsening psoriasis

psychiatric symptoms,

depression, irritability,

aggressive behaviour

Side effects

Tell your doctor or pharmacist as

soon as possible if you do not feel

well while you are using INTRON

A.

All medicines have side effects.

Sometimes they are serious, most of

the time they are not. You may need

medical treatment if you get some of

the side effects.

Ask your doctor or pharmacist any

questions you may have.

Check with your doctor

immediately if any of the following

side effects occur:

an allergic reaction such as hives

or difficulty in breathing

chest pain or irregular heartbeat

confusion, aggressive behaviour,

suicidal feelings, depression,

trouble sleeping, thinking or

concentrating

numbness or tingling sensation

black or tar-like stools, blood in

stool or urine, painful or difficult

urination

severe nosebleed

fever or chills beginning after a

few weeks of treatment

lower back or side pain

visual disturbances

unusual bruising or bleeding

You may need urgent medical

attention.

Tell your doctor if you notice any

of the following and they worry

you:

flu symptoms including muscle

ache, fever, chills and headache

loss of appetite, taste change or

dry mouth

tiredness, sleepiness or dizziness

feeling sick, vomiting or

diarrhoea

hair loss

increased sweating

irritability

itching

low blood pressure

These side effects may go away as

your body adjusts to the medicine.

Tell your doctor, if they continue

or are severe.

Other side effects not listed above

may also occur in some patients.

Check with your doctor as soon as

possible if you have any problems

while using INTRON A even if you

do not think the problems are

connected with the medicine or the

side effects are not listed in this

leaflet.

Do not be alarmed by this list of

possible side effects. You may not

experience any of them.

After using INTRON A

Storage

Keep INTRON A where children

cannot reach it.

Before use: Store in the

refrigerator (2°C to 8°C). Do not

freeze. Do not leave it in the car.

INTRON A Injectable Solution:

Single Dose Vials

Use once and discard any residue.

INTRON A Redipen:

Return the Redipen to the

refrigerator immediately after use.

If you accidentally leave the Redipen

outside the refrigerator, the solution

will remain stable for a total of 48

hours at room temperature (25°C).

Nevertheless, to reduce the chance of

microbial contamination, you should

try to remember to store the Redipen

in the refrigerator at all times

between use.

Discard the Redipen 14 days after

injecting the first dose.

Disposal

Discard after the last dose is used.

Return any unused medicine to

your pharmacist.

Product description

What it looks like

INTRON A Injectable Solution is a

clear colourless solution.

INTRON A Redipen is a plastic

injector device containing INTRON

A Solution for Injection.

Check that you have the correct

INTRON A Redipen as prescribed

by your doctor.

The INTRON A Redipen Solution

for Injection is available in three

different strengths (with each

Redipen containing 6 doses):

the 18 MIU/pen strength has a

brown push button and brown

colour coding strip (each dose

contains 3 MIU of INTRON A);

# MIU stands for million

international units.

the 30 MIU/pen strength has a

light blue push button and light

blue colour coding strip (each

dose contains 5 MIU of INTRON

the 60 MIU/pen strength has a

pink push button and pink colour

INTRON A

coding strip (each dose contains

10 MIU of INTRON A).

Ingredients

INTRON A Solution for Injection

Each vial contains:

interferon alfa-2b

sodium phosphate dibasic

sodium phosphate monobasic

disodium edetate

sodium chloride

polysorbate 80

water

m-cresol as preservative

INTRON A Redipen

Each INTRON A Redipen contains

the same ingredients as INTRON A

Solution.

Manufacturer

Merck Sharp & Dohme (Australia)

Pty Limited

Level 1, Building A

26 Talavera Road

Macquarie Park, NSW 2113

Australia

Australian Registration

Number

INTRON A Injectable Solution

Single dose vials:

10 MIU/1 mL AUST R 63274

18 MIU/3 mL AUST R 60021

25 MIU/2.5 mL AUST R 60024

INTRON A Redipen

18 MIU/pen AUST R 66126

30 MIU/pen AUST R 66127

60 MIU/pen AUST R 66128

Date of Preparation

05 December 2017

INTRON A

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Page 1 of 16

PRODUCT INFORMATION

INTRON A REDIPEN SOLUTION FOR INJECTION

NAME OF THE MEDICINE

Interferon alfa-2b (rbe)

DESCRIPTION

INTRON A is a sterile, stable formulation of highly purified interferon alfa-2b produced by

recombinant DNA techniques. Recombinant interferon alfa-2b is a water soluble protein with a

molecular weight of approximately 19,300 daltons. It is obtained from a clone of E. coli which

genetically

engineered

plasmid

containing

interferon

alfa-2

gene

from

human

leucocytes. The activity of INTRON A is expressed in terms of International Units (IU). The

specific activity of INTRON A is approximately 2.6 x 10

IU/mg.

INTRON A Redipen is supplied in glass carpoules containing:

18 million IU/pen (6 doses of 3 million IU, 0.2 mL per dose)

30 million IU/pen (6 doses of 5 million IU, 0.2 mL per dose)

60 million IU/pen (6 doses of 10 million IU, 0.2 mL per dose)

Inactive

ingredients:

Sodium

phosphate dibasic,

sodium phosphate

monobasic,

disodium

edetate, sodium chloride, meta cresol, polysorbate 80 and water for injections.

PHARMACOLOGY

Interferons are a family of naturally occurring, small protein molecules produced and secreted

by cells in response to viral infections or various synthetic and biological inducers.

Interferons exert their cellular activities by binding to specific membrane receptors on the cell

surface. Preliminary studies to characterise these membrane receptors and to determine the

subsequent fate of the human interferon-receptor complex have been carried out using

labelled recombinant interferon alfa-2b. Human interferon receptors, as isolated from human

lymphoblastoid (Daudi) cells, appear to be highly asymmetric membrane proteins. They exhibit

selectivity for human but not murine interferons, suggesting species specificity. Studies with

other interferons have demonstrated species specificity.

The results of several studies suggest that, once bound to the cell membrane, the interferon

initiates a complex sequence of intracellular events which include the induction of certain

enzymes. It is thought that this process, at least in part, is responsible for the various cellular

responses

interferons,

including

inhibition

virus

replication

virus-infected

cells,

suppression of cell proliferation and such immunomodulating activities as enhancement of the

phagocytic

activity

macrophages

augmentation

specific

cytotoxicity

lymphocytes for target cells. These activities possibly contribute to the therapeutic effects of

interferons.

Recombinant interferon alfa-2b has exhibited antiproliferative effects in preclinical studies

employing both cell culture systems and human tumour xenografts in animals, and has

demonstrated significant immunomodulatory activity in vitro. Recombinant interferon alfa-2b

also inhibits viral replication in vitro and in vivo.

The antiproliferative activity of recombinant interferon alfa-2b was evaluated in vitro using

mouse and human leukaemia cell lines, and human osteosarcoma, melanoma, and normal

amnion

cells.

antiproliferative

activity

recombinant

interferon

alfa-2b

most

pronounced against human osteosarcoma cells and the human lymphocytic leukaemia cell line

RPMI-8402; growth of both cell lines was inhibited 80-100%. No activity was seen in mouse

Page 2 of 16

leukaemia cells, which again suggests species specificity.

The immunomodulating activity of recombinant interferon alfa-2b was demonstrated in vitro by

augmentation

spontaneous

"natural

killer"

activity

human

lymphocytes,

enhancement of the tumoricidal activity of human monocytes against human tumour cells and

its induction of Class I histocompatibility antigens on the surface of a number of cell types.

These effects appear to be dose-dependent.

Recombinant interferon alfa-2b injected intralesionally (0.2 or 0.8 million IU/day for 7 days)

delayed the development and reduced the volume of human osteosarcoma implants in athymic

mice. The effect was dose-related. Additionally, subcutaneous administration of recombinant

interferon alfa-2b at a dose of 0.2 million IU/day inhibited the growth of implanted human breast

tumour xenografts in athymic mice by about 50% after 23 days. However, intra-peritoneal

administration of recombinant interferon alfa-2b (0.1 - 1 million IU for 9 days) demonstrated no

effect on the growth of human tumour xenografts in athymic mice or on murine leukaemia cells

implanted in BDFI mice.

A human tumour stem cell assay was used to study the effects of recombinant interferon alfa-

in combination

with doxorubicin.

Study results suggested that a schedule-dependent

synergistic effect was exhibited when doxorubicin and recombinant interferon alfa-2b were

combined in the cell lines tested. Antagonistic effects or cell growth enhancement over control

levels were not observed.

Preliminary studies with isolated and perfused rabbit kidneys have shown that the kidney may

be the main site of interferon alfa catabolism.

CLINICAL TRIALS

Kaposi's Sarcoma: In patients with AIDS-related Kaposi's sarcoma, measures of immunologic

competence, commonly characterised by the baseline T4 count or T4/T8 ratio, have been noted

to be highly predictive of the status of AIDS patients and their likelihood of response to INTRON

A treatment. In patients with baseline T4 counts above 400, the overall response rate to

INTRON A can be expected to be as high as 78%. Few patients with baseline T4 counts less

than 200 can be expected to respond to INTRON A.

Chronic hepatitis B: Studies in patients with compensated liver disease and evidence of

chronic hepatitis B virus infection (serum HBsAg positive) and HBV replication (serum HBeAg

positive and serum HBV-DNA positive) have demonstrated that INTRON A therapy can produce

virologic

remission

this

disease

(loss

serum

HBeAg)

normalisation

serum

aminotransferases.

In clinical studies, 39% (15/38) of responding patients lost HBeAg 1 to 6 months following the

end of INTRON A therapy. Virologic response was associated with a reduction in serum ALT to

normal or near normal (

1.5 times the upper limit of normal) in 87% (13/15) of patients

responding to INTRON A therapy at 5 million IU daily. Of responding patients who lost HBsAg,

58% (7/12) did so 1 to 6 months post-treatment.

Chronic hepatitis C: Studies in patients with compensated liver disease and a history of blood or

blood product exposure and/or positive HCV antibody demonstrated that INTRON A therapy

can produce clinically meaningful effects on this disease, manifested by normalisation of

serum ALT and reduction in liver necrosis and degeneration.

A multicentre study comparing treatment of chronic hepatitis C using INTRON A (i) 3 million

IU three times weekly for a duration of 18 months, (ii) 3 million IU three times weekly for 6

months then 1 million IU three times weekly for 12 months and (iii) 3 million IU three times

weekly for 6 months showed that treatment with 3 million IU three times weekly for a duration

of 18 months produced significantly superior histological improvement, virological response and

sustained ALT response than the regimens involving a lower dose or shorter duration of

treatment.

Page 3 of 16

Similarly, an Australian multicentre study evaluated the efficacy of INTRON A (i) 3 million IU

three times weekly for 6 months, (ii) 5 million IU three times weekly for 6 months and (iii) 3

million IU three times weekly for 24 months. Treatment for a

duration

of up

24 months

significantly improved the sustained response in patients who achieved normalisation of ALT

at 24 weeks of therapy compared to the two 6-month treatment regimens.

Sustained ALT

response was associated with virological response and improvement in hepatic inflammation.

This study confirmed that INTRON A 3 million IU three times weekly remains the optimal dose;

increasing the dose to 5 million IU three times weekly did not significantly improve the ALT

response rate or sustained ALT response.

Malignant melanoma: The safety and efficacy of INTRON A was evaluated as adjuvant to

surgical treatment in patients with melanoma who were free of disease (post-surgery) but at

high risk for systemic recurrence. These included patients with lesions of Breslow thickness >4

patients

with

lesions

Breslow

thickness

with

primary

recurrent

nodal

involvement. In a randomised, controlled trial in 280 patients, 143 patients received INTRON A

therapy at 20 million IU/m

intravenously five times per week for 4 weeks (induction phase)

followed by 10 million IU/m

subcutaneously three times per week for 48 weeks (maintenance

phase). INTRON A therapy was begun

56 days after surgical resection. The remaining 137

patients were observed.

INTRON

therapy

produced

significant

increase

relapse-free

overall

survival.

Median time to relapse for the INTRON A treated patients versus observation patients was 1.72

years versus 0.98 years (p=0.01, stratified Log Rank). The estimated 5-year relapse-free

survival rate, using the Kaplan-Meier method, was 37% for INTRON A treated patients versus

26% for observation patients. Median overall survival time for INTRON A treated patients was

3.82 years versus 2.78 years (p=0.047, stratified Log Rank). The estimated 5-year overall

survival rate, using the

Kaplan-Meier

method,

INTRON

treated

patients

versus 37% for observation patients.

The INTRON A dose was modified because of adverse events in 65% (n=93) of the patients.

INTRON A

therapy

discontinued

because

adverse

events

patients

during induction and 18% of the patients during maintenance. The most frequently reported

adverse reaction

fatigue

which

observed

patients.

Other

adverse

reactions that were recorded in >20% of INTRON A treated patients included neutropenia

(92%), fever (81%), myalgia (75%), anorexia (69%), vomiting/nausea (66%), increased SGOT

(63%), headache (62%), chills (54%), depression (40%), diarrhoea (35%), alopecia (29%),

altered taste sensation (24%), dizziness/vertigo (23%), and anaemia (22%).

Adverse reactions classified as severe or life-threatening (ECOG Toxicity Criteria grade 3 or

4) were recorded in 66% and 14% of INTRON A treated patients, respectively. Severe adverse

reactions recorded in >10% of INTRON A treated patients included neutropenia/leucopenia

(26%), fatigue (23%), fever (18%), myalgia (17%), headache (17%), chills (16%), and increased

SGOT (14%). Grade 4 fatigue was recorded in 4% and grade 4 depression was recorded in 2%

of INTRON A treated patients. No other grade 4 adverse event was reported in more than 2

INTRON A treated patients. Lethal hepatotoxicity occurred in 2 INTRON A treated patients

early in the clinical trial. No subsequent lethal hepatotoxicities were observed with adequate

monitoring of liver function tests.

Pharmacokinetics

pharmacokinetics

INTRON

after

single

doses

administered

subcutaneously,

intramuscularly and as a 30-minute intravenous infusion has been studied in healthy male

volunteers. In one study involving 12 subjects, single 5 million IU/m

doses were administered

by the three routes. Serum concentrations of interferon alfa-2b were determined by a radio-

immunoassay

(RIA)

with

detection

limit

IU/mL.

mean

serum

interferon

concentrations

following

subcutaneous

intramuscular

injections

were

comparable.

Maximum serum levels (18-116 IU/mL) occurred at 3 to 12 hours post-injection. The elimination

half-lives of interferon following both injections were 2 to 3 hours. Serum levels were below the

Page 4 of 16

detection limit 16 hours post-injection.

After intravenous administration, serum interferon levels peaked (135-273 IU/mL) at the end of

infusion,

then

declined

slightly

more

rapid

rate

than

after

subcutaneous

intramuscular administration, becoming undetectable 4 hours after the infusion. The elimination

half-life was approximately 2 hours.

In another study also involving 12 subjects, single 10 million IU doses were administered by the

same

three

routes

administration.

Mean

serum

interferon

concentrations

were

again

comparable

following intramuscular

subcutaneous

injections,

with

maximum

serum

levels (150-180 IU/mL) occurring at 6 to 8 hours post-injection. The elimination half-lives

following both injections were 6 to 7 hours. Serum levels were below the detection limit of

25 IU/mL 24 hours post-injection.

As with the other study, after intravenous administration, serum interferon levels peaked (546

IU/mL) at the end of the infusion, then declined rapidly with time, becoming undetectable 4

hours after the infusion.

Urine levels of interferon were below the detection limit following each of the three routes of

administration in both studies.

Interferon

neutralising

factor

assays

were

performed on serum samples of

patients

received INTRON A in Schering-Plough monitored clinical trials. The clinical incidence of

neutralising factors developing in cancer patients treated systemically is 2.9% and in hepatitis

patients, 6.9%. The detected titres are low in almost all cases and have not been regularly

associated with loss of response or any other autoimmune phenomenon.

No development of neutralising antibodies has been demonstrated in patients who received

INTRON

intralesionally

treatment

basal

cell

carcinoma.

Serum

interferon

neutralising factors were detected in 0.8% of patients who received INTRON A intralesionally

for other indications. These titres were low, did not increase during the clinical trials and

demonstrated no clinical sequelae. The significance of the appearance of serum neutralising

factor is not known.

INDICATIONS

Hairy cell leukaemia: INTRON A is indicated for the treatment of hairy cell leukaemia in

splenectomised or non-splenectomised patients.

Kaposi’s sarcoma in AIDS: INTRON A is indicated for the treatment of Kaposi’s sarcoma in

patients with acquired immune deficiency syndrome (AIDS).

Chronic myelogenous leukaemia: INTRON A is indicated for the treatment of Philadelphia

chromosome positive chronic myelogenous leukaemia in the chronic phase.

Multiple

myeloma:

INTRON

indicated

maintenance

control

multiple

myeloma once control has been achieved by chemotherapy. The effect on overall survival

has not as yet been determined.

Follicular non-Hodgkin's lymphoma: INTRON A is indicated as an adjuvant treatment of high

tumour

burden

Stage

IV follicular

non-Hodgkin's lymphoma in conjunction with an

appropriate

chemotherapy

regimen.

controlled

clinical

trials

which

efficacy

demonstrated anthracycline chemotherapy was employed.

Malignant Melanoma: INTRON A is indicated as an adjuvant therapy of malignant melanoma

following surgery in patients who are at high risk of recurrence. The potential benefit to the

patient should be assessed carefully. Although toxicity of the treatment may be substantial, for

most patients, the benefit of therapy outweighed the risk.

Chronic

hepatitis

B:

INTRON

injection

indicated

treatment

adults

with

histologically proven

compensated

chronic

active

hepatitis

Patients

should

serum

Page 5 of 16

HBsAg positive and have evidence of HBV replication (such as serum HBeAg positive) and

raised serum alanine aminotransferase

(ALT)

levels

(>3 times

upper

limit

reference range) for at least 6 months [See Pharmacology for response rate].

Chronic

hepatitis C:

INTRON A

indicated for

the treatment of

histologically

proven

compensated chronic hepatitis due to hepatitis C (HCV antibody positive) in adult patients with

persistently

elevated

serum

alanine

aminotransferase

(ALT).

Studies

these

patients

demonstrate that INTRON A Injection therapy can produce normalisation of

serum ALT,

clearance of serum HCV RNA and improvement in liver histology.

CONTRAINDICATIONS

A history of hypersensitivity to recombinant interferon alfa-2b or any other components of

INTRON A contraindicates its use. Hypersensitivity to other forms of interferon alfa should lead

to extreme caution with the use of INTRON A.

Patients with decompensated liver disease, autoimmune hepatitis or a history of autoimmune

liver disease, and patients who are immunosuppressed transplant recipients should not be

treated with INTRON A for chronic hepatitis. There are reports of worsening liver disease,

including jaundice, hepatic encephalopathy, hepatic failure and death following INTRON A

therapy in such patients.

Patients with severe renal dysfunction or creatinine clearance <50 mL/min must not be treated

with INTRON A injection.

INTRON A is not intended for use in premature infants or neonates.

PRECAUTIONS

Acute,

serious

hypersensitivity

reactions

(e.g.

urticaria,

angioedema,

bronchoconstriction,

anaphylaxis) to INTRON A have been observed rarely during INTRON A therapy. If any such

reaction develops, the drug should be discontinued and appropriate medical therapy instituted

immediately. Transient rashes do not necessitate interruption of treatment.

INTRON A Redipen contains m-cresol as preservative; some patients may experience an

allergic reaction to this ingredient.

Moderate to severe adverse experiences may require modification of the patient's dosage

regimen, or in some cases, termination of INTRON A therapy.

INTRON A should be used cautiously in patients with debilitating medical conditions, such

as those with a history of pulmonary disease (e.g. chronic obstructive pulmonary disease) or

diabetes mellitus prone to ketoacidosis. Caution should be observed also in patients with

coagulation disorder (e.g. thrombophlebitis, pulmonary embolism) or severe myelosuppression.

Administration of INTRON A in combination with other chemotherapeutic agents may lead to

increased risk of toxicity (severity and duration), which may be life-threatening or fatal as a

result of the concomitantly administered drug. The most commonly reported potentially life-

threatening or fatal adverse events include mucositis, diarrhoea, neutropenia, renal impairment

and electrolyte disturbance. Because of the risk of increased toxicity, careful adjustments of

doses are required for INTRON A and for the concomitant chemotherapeutic agents.

While fever may be associated with the flu-like syndrome reported commonly during interferon

therapy, other causes of persistent fever should not be overlooked.

patients

with

liver

disease,

exacerbation of

hepatic

enzyme abnormalities

may occur.

Monitoring of

liver function

tests

is advised.

Hepatotoxicity resulting

in fatality has been

observed rarely. INTRON A increases the risk of hepatic decompensation and death in patients

with cirrhosis. Therefore, any patient developing liver function abnormalities during treatment

with INTRON A should be monitored closely and treatment discontinued if signs and symptoms

Page 6 of 16

progress.

patients

considered

treatment

hepatitis,

a liver

biopsy should be performed to

document diagnosis and extent of disease. Patients with causes of chronic hepatitis other than

chronic hepatitis B or chronic hepatitis C, including autoimmune hepatitis, should be excluded.

Prior to initiation of INTRON A therapy, the physician should establish that the patient has

compensated liver disease. INTRON A should not be used in patients with decompensated liver

disease.

Patients with chronic hepatitis B with evidence of decreasing hepatic synthetic function (e.g.

decreasing albumin or prolongation of prothrombin time), who nevertheless meet the criteria

for therapy, may be at increased risk of clinical decompensation if a flare of aminotransferases

occurs during INTRON A treatment [see Laboratory Tests under Precautions]. In considering

these patients for INTRON A therapy, the potential risks must be evaluated against the potential

benefits of treatment.

Results of two studies indicate that the efficacy of interferon therapy remains uncertain in

chronic active hepatitis B in children or in adults where the presumed route of transmission is

vertical.

Infrequently,

patients treated

for chronic

hepatitis

with

INTRON

developed

thyroid

abnormalities (hypothyroid or hyperthyroid). In clinical trials <1% (4/426) developed thyroid

abnormalities.

abnormalities

were

controlled

conventional

therapy

thyroid

dysfunction. The mechanism by which INTRON A may alter thyroid status is unknown. Prior to

initiation of INTRON

therapy

treatment

chronic

hepatitis C,

serum

thyroid-

stimulating hormone (TSH) levels should be evaluated. Any thyroid abnormality detected at that

time should be treated with conventional therapy. INTRON A treatment may be initiated if TSH

levels can be maintained in the normal range by medication.

Monitor hepatic function with serum bilirubin, ALT (alanine transaminase), AST (aspartate

aminotransferase), alkaline phosphatase and LDH (lactate dehydrogenase) at 2, 8, and 12

weeks following initiation of INTRON A, then every 6 months while receiving INTRON A.

Permanently discontinue INTRON A for evidence of severe (Grade 3) hepatic injury or hepatic

decompensation (Child-Pugh score >6 [class B and C]).

If, during the course of INTRON A therapy, a patient develops symptoms consistent with

possible thyroid dysfunction, TSH levels should be evaluated. In the presence of thyroid

dysfunction, INTRON A treatment may be continued only if TSH levels can be maintained in

the normal range by medication. Discontinuation of INTRON A therapy has not reversed thyroid

dysfunction occurring during treatment.

INTRON A Solution for Injection should not be administered to patients with chronic hepatitis

with decompensated hepatic disease, to patients with autoimmune hepatitis or history of

autoimmune

disease,

immunosuppressed

transplant

recipients

because

INTRON

therapy may lead to worsening of liver disease in these patients.

Hypertriglyceridaemia and aggravation of hypertriglyceridaemia, sometimes severe, have been

observed. Monitoring of lipid levels is, therefore, recommended.

Due to reports of interferon alpha exacerbating pre-existing psoriatic disease and sarcoidosis,

use of INTRON A in patients with psoriasis or sarcoidosis is recommended only if the potential

benefit justifies the potential risk.

Hypotension may occur during INTRON A administration or up to two days post-therapy and

require

supportive

therapy.

Adequate

hydration

should

maintained

patients

undergoing INTRON A therapy since hypotension related to fluid depletion has been seen in

some patients. Fluid replacement to maintain intravascular volume may be necessary.

Patients with a history of cardiac disease (eg. congestive heart failure, myocardial infarction

and/or previous or current arrhythmic disorders), or with AIDS-related Kaposi’s sarcoma, who

require

INTRON

therapy,

should

closely

monitored.

Sometimes

reversible,

Page 7 of 16

cardiomyopathy has been reported rarely in AIDS- related Kaposi’s sarcoma patients treated

with INTRON A. Those patients who have pre-existing cardiac abnormalities and/or are in

advanced stages of cancer, should have electrocardiograms taken prior to and during the

course

treatment.

Cardiac

arrhythmias

(primarily

supraventricular)

occurred

rarely

appeared to be correlated with pre-existing conditions

prior

therapy

with

cardiotoxic

agents. These adverse experiences usually respond to conventional therapy but may require

discontinuation of INTRON A therapy.

Cardiomyopathy was reported in approximately 2% of the AIDS-related Kaposi's sarcoma

patients treated with INTRON A. Cardiomyopathy has also been reported in AIDS patients

not receiving INTRON A therapy. Baseline chest X-rays are suggested and should be repeated

if clinically indicated.

Pulmonary infiltrates, pneumonitis and pneumonia, including fatality, have been observed rarely

in patients treated with interferon alfa including those treated with INTRON A. The aetiology has

not been

defined. Any

patient developing fever, cough, dyspnoea

other

respiratory

symptoms should have a chest X-ray taken. If the chest X-ray shows pulmonary infiltrates or

there

is evidence of pulmonary function impairment, the patient should be monitored closely,

and if appropriate, interferon alfa treatment should be discontinued. While this has been

reported more often in patients with chronic hepatitis C treated with interferon alfa, it has also

been

reported

patients

with

oncologic

diseases

treated

with

interferon

alfa.

Prompt

discontinuation of interferon alfa administration and treatment with corticosteroids appear to

be associated with resolution of pulmonary adverse events. Moreover, these symptoms have

been reported more frequently when shosaikoto, a Chinese herbal medicine, is administered

concomitantly with interferon-alpha.

Patients with a pre-existing psychiatric condition or a history of severe psychiatric disorder

should not be treated with INTRON A.

Treatment with interferons may be associated with exacerbated symptoms of psychiatric disorders

in HCV infected patients with co-occurring psychiatric and substance use disorders. If treatment

with interferons is judged necessary in patients with prior history or existence of psychiatric

condition or with substance use disorders, in order to reach successful adherence to treatment

with interferons, adequate management of psychiatric symptoms and substance use requires

individualized

screening

strategies

frequent

psychiatric

symptom

monitoring.

Early

intervention for re-emergence or development of neuropsychiatric symptoms and substance use is

recommended.

If severe central nervous system (CNS) effects, particularly depression, are observed, INTRON

A therapy should be discontinued. Severe central nervous system (CNS) effects particularly

depression, homicidal ideation, suicidal ideation, suicide or attempted suicide have been observed

in some patients during INTRON A therapy. Other CNS effects including aggressive behavior,

sometimes directed towards others, psychosis including hallucinations, confusion and alterations

of mental status have been observed. These adverse effects have occurred in patients treated

with recommended doses, as well as in patients treated with higher INTRON A doses. More

significant obtundation and coma including cases of encephalopathy, have been observed in

some patients, usually elderly, treated at higher doses. While these effects are generally

reversible, in a few patients full resolution took up to three weeks. Very rarely seizures have

occurred with high doses of INTRON A. If patients develop psychiatric or CNS problems,

including clinical depression, it is recommended that the patients be carefully monitored by the

prescribing physician during treatment and in the 6 month follow-up period. If such symptoms

appear, the potential seriousness of these effects must be borne in mind by the prescribing

physician.

psychiatric

symptoms persist or worsen, or suicidal or homicidal ideation or

aggressive behaviour towards others is identified, it is recommended that treatment with

INTRON

discontinued,

patient

followed

with

psychiatric

intervention

appropriate.

Narcotics,

hypnotics

sedatives

should

administered

with

caution

administered

Page 8 of 16

concomitantly with INTRON A.

Because of reports of exacerbating pre-existing psoriatic disease, INTRON A should be used

in patients with psoriasis only if the potential benefit justifies the potential risk.

The use of INTRON A has been associated with the exacerbation of autoimmune disease,

therefore, when administering INTRON A to patients with a history of, or predisposition to

autoimmune disease, this should be considered.

In patients with AIDS-related Kaposi's Sarcoma, INTRON A therapy should not be used in the

presence of rapidly progressive visceral disease. With the exception of zidovudine, there is a

lack of safety data for the combination of INTRON A with reverse transcriptase inhibitors.

Patients receiving concomitant zidovudine have had a higher incidence of neutropaenia than

that expected with zidovudine alone. The effects of INTRON A when combined with other drugs

used in the treatment of AIDS-related disease are unknown.

Ophthalmologic disorders, including retinal haemorrhage, cotton-wool spots, optic neuritis,

papilloedema, retinal artery or

vein obstruction and serous retinal detachment have been

reported rarely in patients treated with interferon alfa, including INTRON A [see ADVERSE

EFFECTS]. All patients should have a baseline eye examination. Any patient complaining of

ocular symptoms, including loss of visual acuity or visual fields must have a prompt and

complete eye examination. Because these ocular events may occur in conjunction with other

disease states, periodic visual examinations during INTRON A therapy are recommended in

patients with disorders that may be associated with retinopathy, such as diabetes mellitus or

hypertension. Discontinuation of INTRON A should be considered in patients who develop

new or worsening ophthalmological disorders

Preliminary data indicates that interferon alpha therapy may be associated with an increased rate

of kidney graft rejection. Liver graft rejection has also been reported but a causal association with

interferon alfa has not been established.

Effect on Fertility

Interferon may impair fertility. In studies on interferon use in non-human primates, abnormalities of

menstrual

cycle

have

been

observed.

Decreased

serum

oestradiol

progesterone

concentrations have been reported in women treated with human leucocyte interferon. Therefore,

fertile women should not receive INTRON A unless they are using effective contraception during

the treatment period. INTRON A should be used with caution in fertile men.

Use in Pregnancy (Category B3)

Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not

teratogenic in rats or rabbits, nor did it adversely affect pregnancy, foetal development or

reproductive capacity in the offspring of treated rats. Animal studies have also shown that

interferons do not cross the placental barrier.

Interferon has been shown to have abortifacient effects in rhesus monkeys (Macaca mulatta).

Abortion was observed in all dose groups (7.5, 15 and 30 million IU/day IM from Day 20 to Day 80

of gestation), and was statistically significant versus control in the mid- and high-dose groups.

There are no adequate and well controlled studies in pregnant women. INTRON A should be used

during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Use during Lactation

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in

human milk and because of the potential for adverse reactions from INTRON A in nursing infants, a

decision should be made whether to discontinue nursing or to discontinue the drug, taking into

account the importance of the drug to the mother.

Use in Children

Experience in patients below 18 years of age has been limited and in such cases the expected

Page 9 of 16

benefits should be carefully weighed against potential hazards. Results of two studies indicate that

the efficacy of interferon therapy remains uncertain in children with chronic active hepatitis B where

the presumed route of transmission is vertical.

INTERACTIONS WITH OTHERS MEDICINES

Interactions between INTRON A and other drugs have not been fully evaluated. Caution should be

exercised when administering INTRON A in combination with other potentially myelosuppressive

agents.

A synergistic adverse effect on the white blood cell count may occur when INTRON A is

administered concomitantly with zidovudine. Patients receiving the two agents concomitantly have

dose-dependent higher

incidence

of neutropenia

than

expected

when

zidovudine

administered alone.

[See Concomitant Therapy under Dosage and Administration]

Laboratory Tests

The following laboratory tests should be conducted prior to and periodically during INTRON A

treatment for all patients:

Standard haematological tests including complete blood counts (CBC), differential

white blood cell counts and platelet;

Blood chemistry including electrolytes, liver function tests, serum creatinine, serum

protein and TSH

The haematological parameters of the patients should be followed closely as part of the treatment

because a certain degree of myelodepression has been reported in some patients treated with

INTRON A.

Patients with pre-existing thyroid abnormalities may be treated if thyroid stimulating hormone (TSH)

levels can be maintained in the normal range by medication. TSH levels must be within normal

limits upon initiation of INTRON A treatment and TSH testing should be repeated at 3 and 6

months.

Those patients who have pre-existing cardiac abnormalities and/or who are in advanced stages of

cancer should have electrocardiograms taken prior to and during the course of treatment.

Multiple myeloma: Since multiple myeloma may impair renal function, patients should have

renal tests performed periodically.

Malignant melanoma: Liver function and white blood cell (WBC) count and differential should be

monitored

weekly

during

induction

phase

therapy

monthly

during

maintenance phase of therapy.

Chronic hepatitis B: CBC and platelet counts should be evaluated prior to initiation of INTRON

A therapy in order to establish baselines for monitoring potential toxicity. These tests should be

repeated at treatment Weeks 1, 2, 4, 8, 12 and 16. Liver function tests, including serum ALT,

albumin and bilirubin, should be evaluated at

treatment Weeks 1, 2,

12 and 16.

HBeAg, HBsAg and ALT should be evaluated at the end of therapy as well as 3 and 6

months

post therapy, since patients may become virologic responders during the 6 month

period following the end of treatment.

A transient increase in ALT

2 times baseline value (flare) can occur during INTRON A therapy

for chronic hepatitis B. In clinical trials, this flare generally occurred 8 to 12 weeks after initiation

of therapy and was more frequent in responders (63%, 24/38) than in non-responders (27%,

13/48). Elevations in bilirubin

3 mg/dL (51.3

mol/L) occurred infrequently (2%, 2/86) during

therapy.

When ALT flare occurs, in general, INTRON A therapy should be continued unless signs and

symptoms of liver failure are observed. During ALT flare, clinical symptomatology and liver

Page 10 of 16

function tests including ALT, prothrombin time, alkaline phosphatase, albumin and bilirubin

should be monitored at approximately 2-week intervals.

Chronic hepatitis C: Prior to initiation of INTRON A therapy, CBC and platelet counts should

be evaluated in order to establish baselines for monitoring potential toxicity. These tests

should be repeated

Weeks

following

initiation

INTRON

therapy,

monthly thereafter. Serum ALT should be evaluated after 2, 16 and 24 weeks of therapy to

assess response to treatment.

ADVERSE EFFECTS

Adverse reactions of INTRON A are dose-related. Haematological, hepatic, cardiovascular and

neurological toxicities are more common with higher doses.

most

frequently

reported

adverse

reactions

were

flu-like

symptoms,

primarily

fever,

fatigue, headache, myalgia, rigors/chills and malaise, which occurred in almost all patients

treated. These effects

were

reversible

within

hours

interruption

cessation

treatment

were

dose- related. While fever may be related to the flu-like symptoms

commonly reported in patients treated with interferons, other causes of persistent fever should

be excluded.

Other less frequent adverse reactions reported with INTRON A therapy include:

Cardiovascular System

Less common: Hypotension

Rarely

reported:

Tachycardia,

hypertension,

peripheral

ischaemia,

chest

pain,

cardiomyopathy (see below)

Very rarely reported: Palpitations, postural hypotension, bradycardia, cardiac failure, atrial

fibrillation,

arrhythmia,

extrasystole,

angina

pectoris,

thrombophlebitis,

cardiac

ischaemia,

myocardial infarction cerebrovascular haemorrhage, cerebrovascular ischaemia, pericarditis.

Cardiovascular adverse reactions, particularly arrhythmia appeared to be correlated mostly

with pre-existing CVS disease and prior cardiotoxic therapy (see Precautions). Sometimes

reversible, cardiomyopathy has been reported rarely in patients without prior evidence of

cardiac disease.

Central and Peripheral Nervous System (including psychiatric adverse reactions)

Less

common:

Dizziness,

somnolence,

insomnia,

confusion,

impaired

concentration,

depression, irritability, suicidal ideation, suicide attempts, suicide.

Rarely reported: Paraesthesia, impaired consciousness (including cases of encephalopathy, see

PRECAUTIONS),

migraine,

hypo-aesthesia,

nervousness,

anxiety,

seizures,

agitation,

emotional

lability,

flushing,

neuropathy,

peripheral

neuropathy,

polyneuropathy,

psychosis

including hallucinations, aggressive behaviour sometimes directed towards others, vertigo

Very rarely reported: Amnesia, stupor, convulsions, hypertonia, hyperaesthesia, hot flushes,

tremor, coma, extrapyramidal disorder, paresis, speech disorder, syncope, tinnitus, abnormal

coordination,

ataxia,

aphasia,

dysfunction,

abnormal

gait,

hyperkinesia,

dystonia,

paralysis, impotence, personality disorder, abnormal thinking, paroniria, apathy, aggravated

depression, neurosis, feeling of ebriety, dementia

Endocrine System

Rarely reported: Hyperthyroidism, hypothyroidism, diabetes mellitus/hyperglycaemia

Very rarely reported: Gynaecomastia, virilism, aggravation of diabetes, pancreatitis

Gastrointestinal System

Page 11 of 16

Common: Nausea

Less common: Vomiting, diarrhoea

Rarely reported: Abdominal pain, dyspepsia, loose stool, taste perversion, gingival bleeding,

stomatitis, constipation, right upper quadrant (RUQ) pain, glossitis

Very rarely reported: Colitis, eructation, tenesmus, ileus, thirst, melena, increased saliva,

oesophagitis, rectal bleeding after stool, dysphagia, gastrointestinal haemorrhage, gastric ulcer,

gingivitis, gum hyperplasia, rectal haemorrhage, oral leucoplakia, gastrointestinal mucosal

discolouration, abdominal distention, flatulence, tongue discolouration, taste loss, tongue

pigmentation.

Haematological System [See Laboratory Values under Adverse Effects]

Very rarely reported: Haemolytic anaemia, increased gamma globulins, coagulation disorder

Very rarely, alfa interferons, including INTRON A used alone or in combination with Rebetol

may be associated with aplastic anaemia and pure red cell aplasia.

Liver and Biliary System

Rarely reported: Hepatotoxicity including fatality

Very rarely reported: Abnormal hepatic function tests, bilirubinaemia, jaundice,

hepatosplenomegaly, splenomegaly, hepatic encephalopathy

Musculo-Skeletal System

Common: Arthralgia, back pain

Less Common: Musculoskeletal pain.

Rarely reported: Rhabdomyolysis (sometimes serious), myositis

Very rarely reported: Bone pain, muscle weakness, arthritis, arthrosis, myopathy

Reproductive System

Rarely reported: Menstrual disorders eg. menorrhagia, amenorrhoea.

Very rarely reported: Leucorrhoea, uterine bleeding, vaginal haemorrhage,

Resistant Mechanism Disorders

Rarely reported: Resistance mechanism disorders (e.g. altered resistance to infection; these

effects rarely have been life-threatening or fatal), viral infections, conjunctivitis

Very rarely reported: Sty, fungal infections, moniliasis, sepsis

Respiratory System

Rarely reported: Coughing, pharyngitis, dyspnoea, pulmonary infiltrates, pneumonitis,

pneumonia, nasal congestion, sinusitis, rhinitis, respiratory disorder.

Very rarely reported: Hypoxia, stridor, bronchospasm, cyanosis, wheezing, pleural pain,

sneezing, nonproductive coughing, pulmonary embolism, pulmonary oedema, laryngitis,

pulmonary fibrosis

Skin and Appendages

Less common: Alopecia, increased sweating

Rarely reported: Rash (e.g. erythematous and maculopapular), injection site disorders (to

routes of administration other than intralesional), pruritus, dermatitis, dry skin, erythema

Very rarely reported: Urticaria, acne, nail disorders, purpura, peripheral ischaemia, furunculosis,

non-herpetic cold sores, lacrimal gland disorder, photosensitivity, skin discolouration, chloasma,

Page 12 of 16

abnormal hair texture, increased hair growth, skin depigmentation, dermatitis lichenoides,

melanosis, vitiligo, injection site necrosis, toxic epidermal necrolysis, erythema multiforme,

Stevens Johnson syndrome

Urinary System

Rarely reported: Renal insufficiency, renal failure, hyperuricaemia,

Very rarely reported: Micturition disorder, nocturia, polyuria, haematuria, micturition frequency,

cystitis, oliguria, nephrosis, urinary incontinence, nephrotic syndrome.

Visual and Auditory Disorders

Rarely reported: Eye pain, hearing disorder, abnormal/blurred vision, hearing loss, retinal

haemorrhage, retinopathies (including macular oedema), cotton wool spots, and retinal artery or

vein obstruction, loss of visual acuity or visual field, optic neuritis and papilloedema, lacrimal

gland disorder

Very rarely reported: Conjunctivitis, photophobia, diplopia, dry eyes, oculomotor nerve paralysis,

retinal disorder, night blindness, serous retinal detachment, earache, deafness, hyperacusis

General

Common: Anorexia

Less common: Asthenia, dry mouth, flu-like symptoms (unspecified), pain, taste alteration

Rarely reported: Herpes simplex, epistaxis, weight decrease, increased appetite, decreased

libido, weakness, leg cramps, face oedema

Very rarely reported: Dehydration, hypercalcaemia, cachexia, peripheral oedema,

lymphadenopathy, periorbital oedema, malignant hyperpyrexia, transplant rejection, acidosis,

hypertriglyceridaemia sarcoidosis or exacerbation of sarcoidosis, hepatitis B reactivation in

HCV/HBV co-infected patients.

A wide variety of autoimmune and immune-mediated disorders have been reported with alfa

interferons including idiopathic thrombocytopaenic purpura and thrombotic thrombocytopaenic

purpura rheumatoid arthritis, systemic lupus erythematosus, vasculitis, and Vogt-Koyanogi-

Harada syndrome.

Cases of acute hypersensitivity reactions, including anaphylaxis, urticaria, and angioedema

have been reported.

Asthenic conditions (including asthenia, malaise and fatigue), homicidal ideation, dehydration,

palpitations, psoriasis, fungal infection, and bacterial infection (including sepsis), have been

reported.

When INTRON A is used with hydroxyurea, the occurrence of cutaneous vasculitides may be

increased.

Laboratory Values

Clinically significant laboratory abnormalities, most frequently occurring at doses greater than

10 million IU daily, include reduction in granulocyte and white blood cell counts; decreases in

haemoglobin

level

platelet

count;

increases

alkaline

phosphatase,

lactate

dehydrogenase (LDH), serum creatinine, serum urea nitrogen levels and TSH levels. Moderate

and usually reversible reduction in all three blood elements – white blood cells, red blood cells

and platelets, have been reported. Increase in serum ALT/AST levels have been noted as an

abnormality in some non-hepatitis subjects and also in some patients with hepatitis particularly

those with chronic hepatitis B coincident with clearance of viral DNAp.

DOSAGE AND ADMINISTRATION

Parenteral drug products should be inspected visually prior to administration. INTRON A

Page 13 of 16

Redipen contains a solution that is clear and colourless.

INTRON A REDIPEN IS NOT RECOMMENDED FOR INTRALESIONAL ADMINISTRATION.

EACH INTRON A REDIPEN IS FOR AN INDIVIDUAL PATIENT’S USE ONLY.

INTRON

Redipen

contains

pre-filled,

multi-dose

cartridge

subcutaneous

administration.

designed

deliver

fixed

doses

required

using

simple

dial

mechanism. If doses different from those easily measurable with the Redipen are desired,

depending on the dose, the solution vial presentations are available and may be preferred.

The needles provided in the packaging will be used for the INTRON A Redipen only. A new

needle is to be used each time the pen delivers a dose.

During the course of treatment with INTRON A for any indication, if adverse reactions develop,

the dosage should be modified or therapy should be discontinued temporarily until the adverse

reactions abate. If persistent or recurrent intolerance develops following adequate dosage

adjustment, or disease progresses, the treatment with INTRON A should be discontinued.

For maintenance dosage regimens administered subcutaneously,

at the

discretion

physician, the patient may self-administer the dose.

Hairy Cell Leukaemia

The recommended dosage of INTRON A is 2 million IU/m

administered subcutaneously three

times a week (every other day). Higher doses are not recommended. Normalisation of one or

more haematologic variables usually begins within 2 months of therapy. Improvement in all

three haematologic variables (granulocyte count, platelet count and haemoglobin level) may

require 6 months or more. Non-splenectomised patients responded similarly to splenectomised

patients and showed similar demonstrable improvement in transfusion requirements. This

dosage

regimen

should

maintained

unless

disease

progresses

rapidly

severe

intolerance is manifested.

The minimum effective dose of INTRON A has not been established.

Kaposi's Sarcoma

The recommended dosage for INTRON A is 30 million IU/m

administered subcutaneously

three times a week. Alternatively, INTRON A can be administered as an intravenous infusion

in a dose of 50 million IU/m

over a 30-minute period for 5 consecutive days every other week.

minimum

interval

between

treatments

days.

Either

dosage

regimen

should be

maintained

indefinitely

unless

disease

progresses

rapidly

severe

intolerance

manifested.

Chronic Myelogenous Leukaemia

The recommended dosage of INTRON A is 2 to 6 million IU/m

administered subcutaneously

daily. When the white blood cell count is controlled, the dosage may be administered three

times a week (every

other

day).

dosage

regimen

should

maintained

unless

disease progresses rapidly or severe intolerance is manifested.

Multiple Myeloma

The recommended dosage is 3 million IU/m

administered subcutaneously three times a

week. The dosage regimen should be maintained unless the disease progresses rapidly or

severe intolerance is manifested.

Follicular Non-Hodgkin's Lymphoma

The recommended dosage is 3 to 5 million IU administered subcutaneously three times a week

for a duration of up to 18 months. The dosage should be adjusted according to the patient's

response and tolerance of the medication.

Malignant Melanoma

Page 14 of 16

INTRON

Redipen

suitable

only

treatment

phase

involving

subcutaneous

administration.

As induction therapy, INTRON A is administered intravenously at a dose of 20 million IU/m

daily for five days a week over a four-week period. The calculated INTRON A dose is added to

100 mL of saline solution and administered as a 20-minute infusion. As maintenance treatment,

the recommended dose is 10 million IU/m

administered subcutaneously three times a week for

48 weeks.

If severe adverse reactions develop during INTRON A treatment, particularly if granulocytes

decrease to <500/mm

or ALT/AST rises to >5x upper limit of normal, treatment should be

temporarily discontinued until the adverse reactions abate. INTRON A treatment should be

restarted at 50% of the previous dose. If intolerance persists after dose adjustment or if

granulocytes decrease to <250/mm

or ALT/AST rises to >10x upper limit of normal, INTRON

A therapy should be discontinued.

There is no evidence that dose modifications beyond those described will result in maintenance

of clinical benefit. For full clinical benefit, patients should be treated at the recommended doses,

with dose modification for toxicity as described.

Chronic Hepatitis B

Prior to initiation of INTRON A therapy, it is recommended that a liver biopsy be performed to

establish the presence of chronic hepatitis and the extent of liver damage. Patients with causes

of chronic hepatitis other than chronic hepatitis B or chronic hepatitis C should not be treated

with INTRON A. The physician should establish that the patient has compensated liver disease.

The lowest effective dose of INTRON A is 3 million IU administered subcutaneously three times

a week. Patients who do not respond within one month may be treated at doses of 5 million IU

three times a week or up to 10 million IU three times a week or 5 million IU daily. The dosage

may be adjusted according to the patient's tolerance to the medication. With a response, the

selected dosage regimen should be maintained for up to four months unless severe intolerance

develops.

[See Laboratory Tests under Precautions for various tests to be conducted and timing of

these tests.]

Chronic Hepatitis C

Prior to initiation of INTRON A therapy, it is recommended that a liver biopsy be performed to

establish the diagnosis of chronic hepatitis and the extent of liver damage. Patients should

be tested for the presence of antibody to HCV. Patients with causes of chronic hepatitis other

than chronic hepatitis B or chronic hepatitis C should not be treated with INTRON A. The

physician should establish that the patient has compensated liver disease.

The recommended dose is 3 million IU administered subcutaneously three times a week. Most

patients who respond demonstrate improvement in ALT levels within 12 to 16 weeks. In these

patients, therapy should be continued with 3 million IU three times a week for up to 18 months.

patients

fail

respond

after

to 16

weeks

treatment,

INTRON A

Injection should be discontinued.

Current clinical experience in patients who remain on INTRON A Injection for 12 to 18 months

indicates that a higher proportion of patients demonstrated a sustained response after longer

durations of therapy than those who discontinued therapy after six months.

[See Laboratory Tests under Precautions for tests to be conducted and timing of these tests.]

Concomitant Therapy

Paracetamol has been used successfully to alleviate the symptoms of fever and headache

which can occur with INTRON A therapy. The recommended paracetamol dosage is 500 mg to

1g given 30 minutes before administration of INTRON A. The maximum dosage of paracetamol

Page 15 of 16

to be given is 1 g four times daily.

Stability

INTRON A Redipen is stable when stored at 2

to 8

C. Refrigerate. Do not freeze.

Directions for use of Redipen

The Redipen should be at room temperature (15

to 25

C) before administering each dose.

should

removed

from

refrigerator

approximately

minutes

before

administration to allow the injectable solution to reach room temperature.

Each

Redipen

intended

maximum

two-week

period

then

must

discarded. A new needle must be used for each dose. After each use, the needle should be

discarded safely and the Redipen must be returned to the refrigerator immediately. In case the

product is left inadvertently at room temperature, a maximum total of 48 hours (two days) of

exposure to room temperature is permitted over a two-week use period. Nevertheless, to

reduce the risk of microbial contamination, the Redipen should remain stored at 2

to 8

Refer to enclosed package insert for detailed directions on the use of the Redipen injector.

OVERDOSAGE

Most adverse reactions to recombinant interferon alfa-2b listed are dose-related. There is no

specific antidote in the event of overdose. Symptomatic treatment with frequent monitoring of

vital signs and close observation of the patient is indicated.

PRESENTATION AND STORAGE CONDITIONS

INTRON A Redipen is a preloaded, multi-dose disposable injector and is available in the

following strengths as packs of single pens. Each pack also contains 6 needles and 6 swabs.

18 million IU/pen (6 doses of 3 million IU, 0.2 mL per dose)

30 million IU/pen (6 doses of 5 million IU, 0.2 mL per dose)

60 million IU/pen (6 doses of 10 million IU, 0.2 mL per dose)

Store at 2

to 8

C. (Refrigerate. Do not freeze).

NAME AND ADDRESS OF THE SPONSOR

Merck Sharp & Dohme (Australia) Pty Limited

Level 1 – Building A

26 Talavera Road

Macquarie Park NSW 2113

AUSTRALIA

POISON SCHEDULE

Schedule 4 – Prescription Only Medicine

DATE OF FIRST INCLUSION IN THE AUSTRALIAN REGISTER OF THERAPEUTIC

GOODS (ARTG)

19 February 1999

Page 16 of 16

DATE OF MOST RECENT AMENDMENT

05 December 2017

Read the complete document

Public Summary

Summary for ARTG Entry:

66126

INTRON A Redipen Interferon alfa-2b (rbe) 18 million IU/1.2mL injection cartridge

ARTG entry for

Medicine Registered

Sponsor

Merck Sharp & Dohme (Australia) Pty Ltd

Postal Address

North Ryde Post Business Centre,Locked Bag 2234,NORTH RYDE BC, NSW, 1670

Australia

ARTG Start Date

19/02/1999

Product category

Medicine

Status

Active

Approval area

Drug Safety Evaluation Branch

Conditions

Conditions applicable to all therapeutic goods as specified in the document "Standard Conditions Applying to Registered or Listed Therapeutic Goods

Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Conditions applicable to the relevant category and class of therapeutic goods as specified in the document "Standard Conditions Applying to Registered

or Listed Therapeutic Goods Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Products

1. INTRON A Redipen Interferon alfa-2b (rbe) 18 million IU/1.2mL injection cartridge

Product Type

Single Medicine Product

Effective date

11/05/2017

Warnings

See Product Information and Consumer Medicine Information for this product

Standard Indications

Specific Indications

Hairy cell leukaemia: for the treatment of hairy cell leukaemia in splenectomised or non-splenectomised patients. Kaposi's sarcoma in AIDS: for the

treatment of Kaposi's sarcoma in patients with acquired immune deficiency syndrome (AIDS). Chronic myelogenous leukaemia: for the treatment of

Philadelphia chromosome positive chronic myelogenous leukaemia in the chronic phase. Multiple myeloma: for the maintenance of control of multiple

myeloma once control has been achieved by chemotherapy. The effect on overall survival has not as yet been determined. Follicular non-Hodgkin's

lymphoma: as an adjuvant treatment of high tumour burden Stage III or IV follicular non-Hodgkin's lymphoma in conjunction with an appropriate

chemotherapy regimen. In controlled clinical trials in which efficacy was demonstrated, anthracycline chemotherapy was employed. Malignant

melanoma: as an adjuvant therapy of malignant melanoma following surgery in patients who are at high risk of recurrence. The potential benefit to the

patient should be assessed carefully. Although toxicity of the treatment may be substantial, for most patients, the benefit of therapy outweighed the risk.

Chronic hepatitis B: for the treatment of adults with histologically proven compensated chronic active hepatitis B. Patients should be serum HBsAg

positive and have evidence of HBV replication (such as serum HBeAg positive) and raised serum alanine aminotransferase (ALT) levels (>3 times the

upper limit of the reference range) for at least 6 months. [See Pharmacology for response rate]. Chronic hepatitis C: for the treatment of histologically

proven compensated chronic hepatitis due to hepatitis C (HCV antibody positive) in adult patients with persistently elevated serum alanine

aminotransferase (ALT). Studies in these patients demonstrate that Intron A Injection therapy can produce normalisation of serum ALT, clearance of

serum HCV RNA and improvement in liver histology.

Additional Product information

Container information

Type

Material

Life Time

Temperature

Closure

Conditions

Cartridge

Glass

15 Months

Store at 2 to 8

degrees Celsius

Not recorded

Do not Freeze

Refrigerate

Pack Size/Poison information

Pack Size

Poison Schedule

1 pen with 6 needles (30G 0.3 x 8mm)

(S4) Prescription Only Medicine

6 swabs

Not scheduled. Not considered by committee

Components

1. Medicine Component

Dosage Form

Injection, solution

Route of Administration

Subcutaneous

Visual Identification

Clear to opalescent, colourless to light yellow solution, essentially free of

visible particles.

Active Ingredients

Interferon alfa-2b

15 million IU/mL

© Commonwealth of Australia.This work is copyright.You are not permitted to re-transmit, distribute or commercialise the material without obtaining prior

Public Summary

Page 1 of

Produced at 02.11.2017 at 11:33:21 AEDT

This is not an ARTG Certificate document.

The onus is on the reader to verify the current accuracy of the information on the document subsequent to the date shown.

Visit www.tga.gov.au for contact information

written approval from the Commonwealth.Further details can be found at http://www.tga.gov.au/about/website-copyright.htm.

Public Summary

Page 2 of

Produced at 02.11.2017 at 11:33:21 AEDT

This is not an ARTG Certificate document.

The onus is on the reader to verify the current accuracy of the information on the document subsequent to the date shown.

Visit www.tga.gov.au for contact information

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