Drugs List

Therapeutic Indications

Uses

Single severe demyelinating event with active inflammatory process
Treatment of relapsing-remitting multiple sclerosis

Treatment of ambulatory patients with relapsing multiple sclerosis without evidence of continuous progression between relapses. Interferon slows the progression of disability and decreases the frequency of relapses.

Treatment of patients who have experienced a single demyelinating event with an active inflammatory process if it is severe enough to warrant treatment with intravenous corticosteroids, if alternative diagnoses have been excluded and if the patient is determined to be at high risk of developing multiple sclerosis.

Interferon beta-1a has not been shown to be efficacious in patients with progressive multiple sclerosis and should be discontinued in those who develop secondary progressive multiple sclerosis.

Administration

For intramuscular or subcutaneous injection depending on the brand used.

The manufacturer of the 30 microgram intramuscular pre-filled pen recommends administration to the upper outer thigh.

To minimise the risk of injection site necrosis, the site of injection should be varied with each dose, an aseptic technique should be used and the procedure for self administration should be reviewed periodically if injection site reactions have occurred.

Contraindications

Children under 2 years
Suicidal ideation
Decompensated liver disease
Severe depression

Precautions and Warnings

Children aged 12 to 18 years
Elevated serum transaminases - greater than 2.5 times upper limit of normal
Cardiac disorder
Depression
Epileptic disorder
History of alcohol abuse
History of cardiac disorder
History of depression
History of hepatic disorder
History of seizures
Pregnancy
Severe hepatic impairment
Severe myelosuppression
Severe renal impairment
Thyroid dysfunction

Advise ability to drive/operate machinery may be affected by side effects
Not all available brands are licensed for all age groups
Not all available brands are licensed for all routes of administration
Premedication with antipyretic recommended
Treatment to be initiated and supervised by a specialist
Some presentations may contain benzyl alcohol
Different brands of this product are not interchangeable
Advise patient to report injection site reactions where the skin breaks
Record name and batch number of administered product
Rotate injection site to minimise the risk of necrosis
Monitor full blood count and differential WBC before and during therapy
Monitor hepatic function before treatment and regularly during treatment
Monitor renal function before treatment and regularly during treatment
Monitor thyroid function at baseline and where clinically indicated
Monitor cardiac function in patients with cardiac disease
Monitor for signs of nephrotic syndrome
Monitor patient for signs and symptoms of depression
Monitor serum biochemistry regularly
Monitor thyroid function regularly if history of dysfunction
Reduce dose if ALT levels rise above 5 times the upper limit of normal
Review self injection technique periodically, especially if reactions occur
Advise patient to report any new or worsening depression/suicidal ideation
Advise patient to report symptoms of thrombotic microangiopathy
Advise patients/carers to seek medical advice if changes in behaviour/mood
Consider discontinuing if depression develops
Consider discontinuing treatment if nephrotic syndrome occurs
Discontinue if jaundice or other clinical symptoms of hepatic injury
Neutralising antibodies may develop that decrease clinical efficacy
Discontinue at first signs of thrombotic microangiopathy
Discontinue if multiple injection site lesions present until healing occurs
Discontinue in patients who develop progressive multiple sclerosis
Female: Ensure adequate contraception during treatment

Nephrotic syndrome with differing underlying nephropathies have been reported during treatment with interferon beta products, at varying points during and for several years following treatment. Monitoring for the early signs of nephrotic syndrome e.g. oedema, proteinuria and impaired renal function is recommended.

Thrombotic microangiopathy (TMA)
Cases of TMA have been reported and may occur several weeks to years after commencing treatment. Cases may manifest as thrombocytopenic purpura or haemolytic uraemic syndrome. Early symptoms include thrombocytopenia, new onset hypertension, fever and central nervous system symptoms and impaired renal function. If such symptoms develop testing of blood platelet levels, serum lactate dehydrogenase (LDH), blood films and renal function should be carried out. Interferon beta-1a should be discontinued if TMA is diagnosed and immediate treatment is required (consider plasma exchange).

All patients should be clinically evaluated after two years of treatment and longer term treatment should be decided on an individual basis.

One manufacturer recommends monitoring liver enzymes, complete and differential blood cell and platelet counts prior to, at months 1, 3, 6 and periodically thereafter.

Thyroid function should be monitored at baseline and if abnormal every 6 to 12 months after initiating treatment. If baseline tests are normal thyroid function should be monitored only if clinical findings of thyroid dysfunction develop.

Pregnancy and Lactation

Pregnancy

Use interferon beta-1a with caution during pregnancy.

The manufacturer states that the use of interferon beta-1a during pregnancy may be considered if clinically required. Human data suggests no increased risk of major congenital abnormalities during the first trimester due to interferon beta-1a. Experience during the second than third trimester is very limited.

Animal studies have shown interferon beta may possibly increase the risk of spontaneous abortion and low birth weight when administered in the first trimester. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot be evaluated based on the currently available data, but does not currently suggest an increase.

Lactation

Interferon beta-1a is considered safe for use during breastfeeding.

The manufacturer states that interferon beta-1a can be used during breastfeeding. It is suggested that the levels of interferon beta-1a secreted into human breast milk is negligible.

Schaefer suggests that due to the large molecular weight of interferon beta it is not excreted into human milk.

LactMed reported no adverse effects in partially breastfed infants when breastfeeding mothers received interferon beta-1a. Therefore, no special precautions appear to be necessary while using interferon beta-1a.

Side Effects

Abnormal liver function tests
Abscess formation (injection site)
Alopecia
Anaemia
Anaphylactic reaction
Angioedema
Anorexia
Antibody formation
Anxiety
Arrhythmias
Arthralgia
Arthritis
Asthenia
Autoimmune hepatitis
Back pain
Cardiomyopathy
Cellulitis (injection site)
Chest pain
Chills
Confusion
Congestive cardiac failure
Contusion
Cotton wool spots
Cutaneous lupus erythematosus
Decrease in haematocrit
Depression (with risk of suicide)
Diarrhoea
Dizziness
Dyspnoea
Elevated serum potassium
Emotional lability
Erythema
Erythema multiforme
Exacerbation of psoriasis
Extremity pain
Fatigue
Fever
Flushing
Haemolytic uraemic syndrome
Headache
Hepatic failure
Hepatitis
Hypersensitivity reactions
Hyperthyroidism
Hypertonia
Hypoesthesia
Hypothyroidism
Increase in blood urea nitrogen
Influenza-like syndrome
Insomnia
Jaundice
Leucopenia
Local reaction at injection site
Lymphopenia
Maculopapular rash
Malaise
Menorrhagia
Metrorrhagia
Migraine
Muscle weakness
Muscular cramps
Myalgia
Nausea
Neck pain
Necrosis (injection site)
Nephrotic syndrome
Neurological effects
Neutropenia
Night sweats
Pain
Palpitations
Pancytopenia
Panniculitis
Paraesthesia
Personality change
Pruritus
Psychosis
Pulmonary artery hypertension
Rash
Retinopathy
Rhinorrhoea
Rigors
Seizures
Spasticity
Stevens-Johnson syndrome
Stiffness
Sweating
Syncope
Systemic lupus erythematosus
Tachycardia
Thrombocytopenia
Thromboembolism
Thrombotic microangiopathy
Thrombotic thrombocytopenic purpura
Urticaria
Vasodilatation
Visual disturbances
Vomiting
Weight changes

Presentation

Injections of interferon beta-1a.

These products have been produced by recombinant technology using Chinese Hamster Ovary (CHO) cell lines.

Drugs List

Therapeutic Indications

Uses

Single severe demyelinating event with active inflammatory process
Treatment of relapsing-remitting multiple sclerosis

Treatment of ambulatory patients with relapsing multiple sclerosis without evidence of continuous progression between relapses. Interferon slows the progression of disability and decreases the frequency of relapses.

Treatment of patients who have experienced a single demyelinating event with an active inflammatory process if it is severe enough to warrant treatment with intravenous corticosteroids, if alternative diagnoses have been excluded and if the patient is determined to be at high risk of developing multiple sclerosis.

Interferon beta-1a has not been shown to be efficacious in patients with progressive multiple sclerosis and should be discontinued in those who develop secondary progressive multiple sclerosis.

Dosage

Adults

Administration

For intramuscular or subcutaneous injection depending on the brand used.

The manufacturer of the 30 microgram intramuscular pre-filled pen recommends administration to the upper outer thigh.

To minimise the risk of injection site necrosis, the site of injection should be varied with each dose, an aseptic technique should be used and the procedure for self administration should be reviewed periodically if injection site reactions have occurred.

Contraindications

Children under 2 years
Suicidal ideation
Decompensated liver disease
Severe depression

Precautions and Warnings

Children aged 12 to 18 years
Elevated serum transaminases - greater than 2.5 times upper limit of normal
Cardiac disorder
Depression
Epileptic disorder
History of alcohol abuse
History of cardiac disorder
History of depression
History of hepatic disorder
History of seizures
Pregnancy
Severe hepatic impairment
Severe myelosuppression
Severe renal impairment
Thyroid dysfunction

Advise ability to drive/operate machinery may be affected by side effects
Not all available brands are licensed for all age groups
Not all available brands are licensed for all routes of administration
Premedication with antipyretic recommended
Treatment to be initiated and supervised by a specialist
Some presentations may contain benzyl alcohol
Different brands of this product are not interchangeable
Advise patient to report injection site reactions where the skin breaks
Record name and batch number of administered product
Rotate injection site to minimise the risk of necrosis
Monitor full blood count and differential WBC before and during therapy
Monitor hepatic function before treatment and regularly during treatment
Monitor renal function before treatment and regularly during treatment
Monitor thyroid function at baseline and where clinically indicated
Monitor cardiac function in patients with cardiac disease
Monitor for signs of nephrotic syndrome
Monitor patient for signs and symptoms of depression
Monitor serum biochemistry regularly
Monitor thyroid function regularly if history of dysfunction
Reduce dose if ALT levels rise above 5 times the upper limit of normal
Review self injection technique periodically, especially if reactions occur
Advise patient to report any new or worsening depression/suicidal ideation
Advise patient to report symptoms of thrombotic microangiopathy
Advise patients/carers to seek medical advice if changes in behaviour/mood
Consider discontinuing if depression develops
Consider discontinuing treatment if nephrotic syndrome occurs
Discontinue if jaundice or other clinical symptoms of hepatic injury
Neutralising antibodies may develop that decrease clinical efficacy
Discontinue at first signs of thrombotic microangiopathy
Discontinue if multiple injection site lesions present until healing occurs
Discontinue in patients who develop progressive multiple sclerosis
Female: Ensure adequate contraception during treatment

Nephrotic syndrome with differing underlying nephropathies have been reported during treatment with interferon beta products, at varying points during and for several years following treatment. Monitoring for the early signs of nephrotic syndrome e.g. oedema, proteinuria and impaired renal function is recommended.

Thrombotic microangiopathy (TMA)
Cases of TMA have been reported and may occur several weeks to years after commencing treatment. Cases may manifest as thrombocytopenic purpura or haemolytic uraemic syndrome. Early symptoms include thrombocytopenia, new onset hypertension, fever and central nervous system symptoms and impaired renal function. If such symptoms develop testing of blood platelet levels, serum lactate dehydrogenase (LDH), blood films and renal function should be carried out. Interferon beta-1a should be discontinued if TMA is diagnosed and immediate treatment is required (consider plasma exchange).

All patients should be clinically evaluated after two years of treatment and longer term treatment should be decided on an individual basis.

One manufacturer recommends monitoring liver enzymes, complete and differential blood cell and platelet counts prior to, at months 1, 3, 6 and periodically thereafter.

Thyroid function should be monitored at baseline and if abnormal every 6 to 12 months after initiating treatment. If baseline tests are normal thyroid function should be monitored only if clinical findings of thyroid dysfunction develop.

Pregnancy and Lactation

Pregnancy

Use interferon beta-1a with caution during pregnancy.

The manufacturer states that the use of interferon beta-1a during pregnancy may be considered if clinically required. Human data suggests no increased risk of major congenital abnormalities during the first trimester due to interferon beta-1a. Experience during the second than third trimester is very limited.

Animal studies have shown interferon beta may possibly increase the risk of spontaneous abortion and low birth weight when administered in the first trimester. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot be evaluated based on the currently available data, but does not currently suggest an increase.

Lactation

Interferon beta-1a is considered safe for use during breastfeeding.

The manufacturer states that interferon beta-1a can be used during breastfeeding. It is suggested that the levels of interferon beta-1a secreted into human breast milk is negligible.

Schaefer suggests that due to the large molecular weight of interferon beta it is not excreted into human milk.

LactMed reported no adverse effects in partially breastfed infants when breastfeeding mothers received interferon beta-1a. Therefore, no special precautions appear to be necessary while using interferon beta-1a.

Side Effects

Abnormal liver function tests
Abscess formation (injection site)
Alopecia
Anaemia
Anaphylactic reaction
Angioedema
Anorexia
Antibody formation
Anxiety
Arrhythmias
Arthralgia
Arthritis
Asthenia
Autoimmune hepatitis
Back pain
Cardiomyopathy
Cellulitis (injection site)
Chest pain
Chills
Confusion
Congestive cardiac failure
Contusion
Cotton wool spots
Cutaneous lupus erythematosus
Decrease in haematocrit
Depression (with risk of suicide)
Diarrhoea
Dizziness
Dyspnoea
Elevated serum potassium
Emotional lability
Erythema
Erythema multiforme
Exacerbation of psoriasis
Extremity pain
Fatigue
Fever
Flushing
Haemolytic uraemic syndrome
Headache
Hepatic failure
Hepatitis
Hypersensitivity reactions
Hyperthyroidism
Hypertonia
Hypoesthesia
Hypothyroidism
Increase in blood urea nitrogen
Influenza-like syndrome
Insomnia
Jaundice
Leucopenia
Local reaction at injection site
Lymphopenia
Maculopapular rash
Malaise
Menorrhagia
Metrorrhagia
Migraine
Muscle weakness
Muscular cramps
Myalgia
Nausea
Neck pain
Necrosis (injection site)
Nephrotic syndrome
Neurological effects
Neutropenia
Night sweats
Pain
Palpitations
Pancytopenia
Panniculitis
Paraesthesia
Personality change
Pruritus
Psychosis
Pulmonary artery hypertension
Rash
Retinopathy
Rhinorrhoea
Rigors
Seizures
Spasticity
Stevens-Johnson syndrome
Stiffness
Sweating
Syncope
Systemic lupus erythematosus
Tachycardia
Thrombocytopenia
Thromboembolism
Thrombotic microangiopathy
Thrombotic thrombocytopenic purpura
Urticaria
Vasodilatation
Visual disturbances
Vomiting
Weight changes

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: April 2020

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Summary of Product Characteristics: AVONEX 30micrograms/ 0.5ml solution for injection. Biogen Idec Ltd. Revised September 2019.

Summary of Product Characteristics: AVONEX 30micrograms/ 0.5ml solution for injection in pre-filled pen. Biogen Idec Ltd. Revised September 2019.

Summary of Product Characteristics: Rebif solution for injection in pre-filled syringes. Merck Serono. Revised January 2020.

Summary of Product Characteristics: Rebif solution for injection in cartridges. Merck Serono. Revised January 2020.

Summary of Product Characteristics: Rebif solution for injection in pre-filled pens. Merck Serono. Revised January 2020.

MHRA Drug Safety Update December 2013
Available at: https://www.mhra.gov.uk
Last accessed: 6 October 2015.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 7 April 2020

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Interferon Beta. Last revised: 31 October 2018
Last accessed: 07 November 2019.