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Interferon beta-1b 250mcg (8MU) (BETAFERON®)
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Name Of
The Medicinal Product
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Betaferon 250 microgram/ml, powder and solvent for solution for
injection
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Qualitative
And Quantitative Composition
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Betaferon contains 300 microgram (9.6 million IU) of recombinant
interferon beta-1b per vial.
Recombinant interferon beta-1b* 250 microgram (8.0 million IU) per ml
when reconstituted.
* produced by genetic engineering from a strain of Escherichia coli.
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Therapeutic
indications
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1.
A single clinical event suggestive of multiple sclerosis(MS) (‘Clinically
Isolated Syndrome’)
o Indicated to delay
progression to definite multiples sclerosis
2.
Relapsing forms of Multiple sclerosis
o Indicated for the reduction
of frequency and degree of severity of clinical relapses in ambulatory
patients
3.
Secondary progressive multiple sclerosis with active disease,
evidenced by relapses or pronounced neurological deterioration within the
last two years
o Indicated for the reduction
of frequency and degree of severity of clinical relapses and slowing the
progression of disease
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Age
limitation
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12 years old and above
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Dosage and
administration
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Adults / Children And Adolescent ≥ 12 years old
The
recommended dose is 250 microgram (8.0 million IU), contained in 1 ml of the reconstituted
solution, to be injected subcutaneously every other day (EOD)
Dose
titration recommended at the start of the treatment
Initial:
0.0625 mg (2 million units [0.25 mL]) every other day; gradually increase
dose by 0.0625 mg every 2 weeks to a target dose of 0.25 mg (8 million units
[1 mL]) every other day. The titration period may be adjusted according to
individual tolerability.
No randomised
controlled trials have been conducted in < 18 years old. However, data
from observational studies suggested that the safety profile in adolescents ≥
12 years old receiving 250 mcg Betaferon SC EOD is similar to that seen in
adults.
Only limited
information available on Betaferon use for those below 12. Therefore,
Betaferon should NOT be given to this age group.
Remark: If a dose is missed, administer as
soon as remembered; do not administer on 2 consecutive days.
Time subsequent doses every 48 hours.
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Reconstitution
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To reconstitute lyophilised interferon beta-1b for injection:
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Connect the vial adapter with the attached
needle on the vial.
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Connect the pre-filled syringe with solvent
to the vial adapter and inject the 1.2 ml of the solvent (sodium chloride solution,
5.4 mg/ml (0.54% w/v) into the Betaferon vial.
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Dissolve the powder completely without shaking.
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After reconstitution, draw the required
volume of medicine from the vial into the syringe
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Remove the vial with the vial adapter from
the pre-filled syringe before injection.
Kindly
refer to Pg 58-61 in the following link for graphic and more details:
Kindly
refer to the following Youtube video link:
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Method Of
Administration
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For subcutaneous injection
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Site for injection:
o
Outer surface of the arms
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Abdomen (except 2-inch area around the
navel)
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Buttocks
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Thighs
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For very thin patient, ONLY use the thigh
or outer surface of the arms.
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Rotate injection site.
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Do not inject into area where skin is
bruised, infected or broken.
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Patient should be
well hydrated
Kindly
refer to Pg 58-61 in the following link for graphic and more details:
Kindly
refer to the following Youtube video link:
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Adverse
reactions
(based on physical product leaflet)
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Very common
≥ 1 in 10
users
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Common
≥ 1 in 100
users
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Uncommon
≥ 1 in 1000
users
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Unknown
frequency
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ž Lymphocytopenia
ž Neutropenia
ž Headache
ž Insomnia
ž Incoordination
ž Abdominal pain
ž Raised ALT > 5X
baseline
ž Rash / Skin disorder
ž Myalgia / Hypertonia
ž Urinary urgency
ž Injection site reaction
ž Flu-like symptoms
ž Pain
ž Fever / Chills
ž Peripheral oodema
ž Asthenia (physical
weakness)
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ž Lymphadenopathy
ž Hypertension
ž Dyspneoa
ž Raised AST > 5x baseline
ž Impotence
ž Menorrhagia
ž Injection site necrosis
ž Chest pain
ž Malaise
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ž Nephrotic syndrome
ž Glomerulo-sclerosis
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ž Anaemia
ž Thrombocytopenia
ž Leukopenia
ž Thrombotic
microangiopathy
ž Anaphylaxis
ž Capillary leak syndrome
ž Thyroid disorder
ž Blood triglyceride
increase
ž Weight increase /
decrease
ž Anorexia
ž Bronchospasm
ž Tachycardia
ž Palpitation
ž Vasodilatation
ž Pulmonary arterial
hypertension
ž Raised GGT
ž Blood bilirubin increased
ž Psychiatric adverse
events
ž Confusion / Anxiety
ž Emotional liability
ž Arthralgia
ž Menstrual disorder
ž Menorrhagia
ž Sweating
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Special
warnings / Precautions for use
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Anaphylaxis
/ hypersensitivity
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Discontinue
use
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Drug-induced
lupus erythematosus
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Discontinue
use
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Flu-like
symptoms
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Analgesics and/or antipyretics on treatment days.
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Improvement in symptoms occurs over time.
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Hepatotoxicity
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Use with caution in
patients with concurrent exposure to other hepatotoxic drugs. Monitor liver
function tests as clinically necessary. Consider discontinuation if serum
transaminase levels increase significantly or are associated with clinical
symptoms (eg, jaundice).
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Injection
site reactions
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Reversible / Irreversible necrosis may occur with continued
therapy; reactions generally arise within the first 4 months of therapy,
but have occurred ≥1 year after initiation
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Tend to improve over time.
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Patient and/or caregiver
competency in injection technique should be confirmed and periodically
re-evaluated.
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Do not inject into
affected area until completely healed
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If multiple lesions
occur, discontinue use until they are fully healed.
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Leukopenia
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Recommend routine monitoring of complete blood counts with
differentials.
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Dose reduction may be required.
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(Severe)
Psychiatric adverse events
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e.g. psychosis, mania, depression, suicidal behavior/ideation
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Avoid use in severe psychiatric disorders
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Use with caution in patients with a history of depression
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Those exhibiting symptoms of depression should be closely monitored
and discontinuation of therapy should be considered.
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Thrombotic
microangiopathy
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e.g. Thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic
syndrome (HUS) (some fatal; some occur few years after therapy)
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Monitor for new onset
hypertension / thrombocytopenia / impaired renal function
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Consider discontinuation of therapy and prompt treatment if
confirmed TTP/HUS.
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Cardiovascular
disease
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Use with caution in
patients with preexisting cardiovascular disease.
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Rare cases of new-onset cardiomyopathy and/or HF have been
reported.
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If HF worsens in the absence of another etiology, consider
discontinuation of therapy.
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American Heart Association 2016: Interferon may cause reversible
direct myocardial toxicity or exacerbate underlying myocardial dysfunction
(strength: moderate/major)
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Thyroid
dysfunction
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Thyroid abnormalities may develop with use
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May worsen pre-existing thyroid conditions.
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Monitor thyroid function
tests
every 6 months or as clinically necessary.
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Others: Bone marrow
suppression, pancreatitis, nephritic syndrome, seizure disorder
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Contraindications
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Patients with a history of hypersensitivity to natural or recombinant
interferon beta, human albumin or to any of the excipients
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Canadian labeling: Additional contraindication (not in US labeling): Pregnancy,
decompensated liver disease (Betaseron, Extavia); current severe depression
and/or suicidal ideation (Extavia)
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Monitoring
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Baseline: Thyroid function test, thyroglubulin, anti-thyroglobulin
antibody, TSH receptor antibody, thyroid peroxidise antibody
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Baseline: GAD antibody, anti-islet cell antibody, fasting C-peptide
level, fasting plasma glucose
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Liver function tests
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Full blood count with differentials
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Adverse drug reactions / Side effects:
v Neuropsychiatric side
effects
v Nephrotic syndrome: early
signs or symptoms, e.g. oedema, proteinuria and impaired renal function
v Thrombotic microangiopathy:
new onset hypertension, thrombocytopenia, or impaired renal function
v Others: Flu-like symptoms,
allergic or anaphylactic reactions, injection-site reactions, worsening of
cardiac symptoms (in HF patients); and for sign/symptoms of depression
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Drug
interactions
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No interaction studies have been performed
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Interferons have been reported
to reduce the activity of hepatic
cytochrome P450-dependent enzymes in humans and animals. Caution should
be exercised when Betaferon is administered in combination with medicinal
products that have a narrow therapeutic index and are largely dependent on
the hepatic cytochrome P450 system for clearance
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Pregnancy
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Contraindicated.
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No long-term studies have been conducted.
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Data from pregnancy registries and post-marketing experience (mostly
during 1st trimester) suggest that frequencies of miscarriages and
congenital abnormalities in their children were comparable to estimated
background risk in the general population.
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Spontaneous abortions have been reported in MS subjects in controlled
clinical trials, with incidence rates not exceeding those in general
population.
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Reproduction studies with rhesus monkeys revealed maternal toxicity
and an increased rate of abortion, resulting in prenatal mortality. No
malformations have been observed in the surviving animals.
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Women of
Child-bearing Potential
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Consultation recommended regarding the need for appropriate contraception
measures.
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Lactation
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Betaferon can be used during breast-feeding.
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Unknown if excreted into breastmilk.
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Limited information available on the transfer of interferon beta-1b
into breast milk, together with the chemical / physiological characteristics
of interferon beta, suggests that levels of interferon beta-1b excreted in
human milk are negligible.
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No harmful effects on the breastfed newborn/infant are anticipated.
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Pharmaceutical
Particulars
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Vial (with
powder for solution for injection): Human albumin, Mannitol
Solvent (sodium
chloride solution 5.4 mg/ml (0.54% w/v): Sodium chloride, Water for injection
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Compatibility
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This
medicinal product must NOT be mixed
with other medicinal products except for the supplied solvent
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Shelf life
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As
packaged for sale
2 years,
starting from the date of sterile filtration of the bulk solution
After reconstitution, immediate use is recommended. However,
the in-use stability has been demonstrated for 3 hours at 2-8 °C.
Special
precaution
Do not store above 25°C.
Do not freeze.
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P/S: Dosing
for COVID-19 in adults [based on most available literature]: 250 mcg EOD x 14 days ( total 7 doses )
References
1.
Product
leaflet: Betaferon 25 mcg/ml Injection (Updated 18 July 2018)
2.
EPAR
Product information : Betaferon [online]
4.
UpToDate
[online]: Drug information: Interferon beta-1b [Accessed 27 Mac 2020]
5.
Hoo
G, et al. Interferon beta-1b (Betaferon) use for COVID-19 (Interim Guide v3.0).
Tan Tock Seng Hospital, 13 Feb 2020.
6.
Hospital
Kuala Lumpur: COVID-19 Drug Summary [Updated 20 Mac 2020]
7.
Sarawak
General Hospital: COVID-19 Treatment & Drug Doses [Updated 23 Mac 2020]
Prepared by Mohd Zulhelmy ; Edited by JCK Ho [30.03.2020]
