Drugs List

Therapeutic Indications

Uses

Treatment of relapsing-remitting multiple sclerosis

Contraindications

Absolute lymphocyte count below 0.5 x 10 to the power of 9/L
Children under 18 years
Severe infection
Breastfeeding
Pregnancy
Progressive multifocal leukoencephalopathy (PML)

Precautions and Warnings

Antibodies to JC virus
Females of childbearing potential
Lymphopenia
Severe gastrointestinal disorder
Severe hepatic impairment
Severe renal impairment

Administration of live vaccines is not recommended
Treatment to be initiated and supervised by a specialist
A recent (within 3 months) MRI should be available prior to treatment
Monitor renal and hepatic function before and during treatment
Perform full blood count before treatment
Evaluate renal function if signs of proximal renal tubulopathy occur
Monitor full blood counts every 3 months
Advise patient that flushing reactions may occur
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report symptoms of infection immediately
Advise patient to seek medical advice if severe flushing occurs
Consider stopping if lymphocytes below 0.5x10 to power 9/L for 6 months
Discontinue if anaphylactoid reaction occurs
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue treatment if patient develops a serious infection
Evaluate risk if lymphocyte count below 0.8x10 to power9/L for 6 months
Advise patient to moderate alcohol intake during treatment
Female: Ensure adequate contraception during treatment
Advise patient to report symptoms of herpes zoster urgently

Prior to initiating treatment with dimethyl fumarate, a recent complete blood count (within 6 months) should be available. Assessments of complete blood counts are also recommended every 3 months and as clinically indicated.

Assessments of renal function (e.g. creatinine, blood urea nitrogen and urinalysis) are recommended prior to treatment initiation, after 3 and 6 months and then every 6 to 12 months thereafter as clinically indicated.

If lymphocyte counts are found to be below the normal range prior to treatment, assessments of the possible causes should be completed prior to the initiation of dimethyl fumarate treatment.

Consider a short course of acetylsalicylic acid in cases of intolerable flushing.

Severe flushing as a result of dimethyl fumarate treatment may indicate hypersensitivity.

If symptoms of neurological dysfunction are present, perform an MRI to evaluate patient to determine if these symptoms are typical for multiple sclerosis or suggestive of progressive multifocal leukoencephalopathy syndrome (PML).

If symptoms suggestive of PML occur, interrupt treatment with dimethyl fumarate and perform appropriate diagnostic evaluations. This includes determination of JCV DNA in cerebrospinal fluid (CSF) by quantitative polymerase chain reaction (PCR) methodology.

Prolonged moderate to severe lymphopenia appears to increase the risk of PML, patients with mild lymphopenia cannot be excluded either. Prior immunosuppressive or immunomodulatory therapy might also contribute to the risk of PML in the setting of lymphopenia.

Pregnancy and Lactation

Pregnancy

Dimethyl fumarate is contraindicated during pregnancy.

The manufacturer does not recommend using dimethyl fumarate during pregnancy. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.

Lactation

Dimethyl fumarate is contraindicated during breastfeeding.

The manufacturer advises that the patient either discontinues dimethyl fumarate or discontinues breastfeeding. The presence of dimethyl fumarate in human breast milk and the effects on exposed infants are unknown.

Side Effects

Abdominal discomfort
Abdominal distension
Abdominal pain
Acute leukaemia
Alanine aminotransferase increased
Albuminuria
Allergic skin reactions
Angioedema
Aspartate aminotransferase increased
Asthenia
Burning sensation
Constipation
Decreased appetite
Diarrhoea
Dizziness
Dyspepsia
Eosinophilia
Erythema
Fanconi syndrome
Fatigue
Feeling hot
Flatulence
Flushing
Gastritis
Gastro-enteritis
Gastrointestinal disorder
Headache
Herpes zoster
Hot flushes
Hypersensitivity reactions
Increases in hepatic enzymes
Ketonuria
Leucopenia
Leukocytosis
Lymphopenia
Nausea
Pancytopenia
Paraesthesia
Progressive multifocal leukoencephalopathy (PML)
Proteinuria
Pruritus
Rash
Renal failure
Serum creatinine increased
Upper abdominal pain
Vomiting
White blood cell count decreased

Presentation

Oral formulations of dimethyl fumarate.

Drugs List

Therapeutic Indications

Uses

Treatment of relapsing-remitting multiple sclerosis

Dosage

Adults

Additional Dosage Information

Contraindications

Absolute lymphocyte count below 0.5 x 10 to the power of 9/L
Children under 18 years
Severe infection
Breastfeeding
Pregnancy
Progressive multifocal leukoencephalopathy (PML)

Precautions and Warnings

Antibodies to JC virus
Females of childbearing potential
Lymphopenia
Severe gastrointestinal disorder
Severe hepatic impairment
Severe renal impairment

Administration of live vaccines is not recommended
Treatment to be initiated and supervised by a specialist
A recent (within 3 months) MRI should be available prior to treatment
Monitor renal and hepatic function before and during treatment
Perform full blood count before treatment
Evaluate renal function if signs of proximal renal tubulopathy occur
Monitor full blood counts every 3 months
Advise patient that flushing reactions may occur
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report symptoms of infection immediately
Advise patient to seek medical advice if severe flushing occurs
Consider stopping if lymphocytes below 0.5x10 to power 9/L for 6 months
Discontinue if anaphylactoid reaction occurs
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue treatment if patient develops a serious infection
Evaluate risk if lymphocyte count below 0.8x10 to power9/L for 6 months
Advise patient to moderate alcohol intake during treatment
Female: Ensure adequate contraception during treatment
Advise patient to report symptoms of herpes zoster urgently

Prior to initiating treatment with dimethyl fumarate, a recent complete blood count (within 6 months) should be available. Assessments of complete blood counts are also recommended every 3 months and as clinically indicated.

Assessments of renal function (e.g. creatinine, blood urea nitrogen and urinalysis) are recommended prior to treatment initiation, after 3 and 6 months and then every 6 to 12 months thereafter as clinically indicated.

If lymphocyte counts are found to be below the normal range prior to treatment, assessments of the possible causes should be completed prior to the initiation of dimethyl fumarate treatment.

Consider a short course of acetylsalicylic acid in cases of intolerable flushing.

Severe flushing as a result of dimethyl fumarate treatment may indicate hypersensitivity.

If symptoms of neurological dysfunction are present, perform an MRI to evaluate patient to determine if these symptoms are typical for multiple sclerosis or suggestive of progressive multifocal leukoencephalopathy syndrome (PML).

If symptoms suggestive of PML occur, interrupt treatment with dimethyl fumarate and perform appropriate diagnostic evaluations. This includes determination of JCV DNA in cerebrospinal fluid (CSF) by quantitative polymerase chain reaction (PCR) methodology.

Prolonged moderate to severe lymphopenia appears to increase the risk of PML, patients with mild lymphopenia cannot be excluded either. Prior immunosuppressive or immunomodulatory therapy might also contribute to the risk of PML in the setting of lymphopenia.

Pregnancy and Lactation

Pregnancy

Dimethyl fumarate is contraindicated during pregnancy.

The manufacturer does not recommend using dimethyl fumarate during pregnancy. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.

Lactation

Dimethyl fumarate is contraindicated during breastfeeding.

The manufacturer advises that the patient either discontinues dimethyl fumarate or discontinues breastfeeding. The presence of dimethyl fumarate in human breast milk and the effects on exposed infants are unknown.

Side Effects

Abdominal discomfort
Abdominal distension
Abdominal pain
Acute leukaemia
Alanine aminotransferase increased
Albuminuria
Allergic skin reactions
Angioedema
Aspartate aminotransferase increased
Asthenia
Burning sensation
Constipation
Decreased appetite
Diarrhoea
Dizziness
Dyspepsia
Eosinophilia
Erythema
Fanconi syndrome
Fatigue
Feeling hot
Flatulence
Flushing
Gastritis
Gastro-enteritis
Gastrointestinal disorder
Headache
Herpes zoster
Hot flushes
Hypersensitivity reactions
Increases in hepatic enzymes
Ketonuria
Leucopenia
Leukocytosis
Lymphopenia
Nausea
Pancytopenia
Paraesthesia
Progressive multifocal leukoencephalopathy (PML)
Proteinuria
Pruritus
Rash
Renal failure
Serum creatinine increased
Upper abdominal pain
Vomiting
White blood cell count decreased

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: November 2019

Reference Sources

Summary of Product Characteristics: Tecfidera 120mg and 240mg gastro-resistant hard capsules. Biogen Idec Ltd. Revised November 2020.

MHRA Drug Safety Update 30 March 2015
Available at: https://www.mhra.gov.uk
Last accessed: 8 April 2015.

MHRA Drug Safety Update 7 January 2021
Available at: https://www.mhra.gov.uk
Last accessed: 15 January 2021.