Drugs List

Therapeutic Indications

Uses

Treatment of relapsing-remitting multiple sclerosis

Contraindications

Children under 10 years
Hypoproteinaemia
Severe infection
Bone marrow aplasia
Breastfeeding
Galactosaemia
Immunodeficiency syndromes
Pregnancy
Renal dialysis
Severe anaemia
Severe hepatic impairment
Severe leucopenia
Severe neutropenia
Severe thrombocytopenia

Precautions and Warnings

Females of childbearing potential
High alcohol intake
Patients over 65 years
Anaemia
Glucose-galactose malabsorption syndrome
Hepatic impairment
Interstitial lung disease
Lactose intolerance
Latent or healed tuberculosis
Leucopenia
Thrombocytopenia

Administration of live vaccines is not recommended
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Contains lactose
Exclude pregnancy prior to initiation of treatment
Monitor blood pressure pre-treatment and periodically thereafter
Monitor serum transaminases (including ALT) before and during therapy
Perform full blood count before treatment
ALT (SGPT) between 2-3 x ULN: monitor LFT weekly
Monitor differential blood count
Advise patient to report any symptoms of interstitial lung disease
Advise patient to report symptoms of infection immediately
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
May give falsely decreased values of ionised calcium
Consider accelerated elimination if discontinued due to adverse effects
Advise patient to seek advice at first indications of pregnancy
Consider withdrawal if psoriasis occurs/worsens
Discontinue if ALT level exceeds 3 times the upper limit of normal
Discontinue if evidence of interstitial lung disease
Discontinue if pancreatitis occurs
Discontinue if peripheral neuropathy occurs
Discontinue if severe haematological reactions including pancytopenia occur
Discontinue if severe skin reaction occurs
Discontinue if signs or symptoms of hepatic injury occur
Discontinue if ulcerative stomatitis occurs
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment

For patients who do not have pre-existing or suspected liver disorders, hepatic enzymes should be assessed at least every 4 weeks during the first 6 months of treatment and regularly thereafter. In patients with pre-existing liver disorders or have clinical signs and symptoms of hepatic dysfunction, hepatic enzymes should be assessed every 2 weeks during the first 6 months of treatment, and at least every 8 weeks thereafter for at least 2 years from initiation of treatment.

For patients testing positive in tuberculosis screening, treat by standard medical practice prior to therapy with teriflunomide.

No waiting period is required when initiating teriflunomide after interferon beta or glatiramer acetate or when starting interferon beta or glatiramer acetate, after teriflunomide.

Caution is required when switching patients from natalizumab to teriflunomide. Due to the long half-life of natalizumab, concomitant exposure could occur for up to 2 to 3 months following discontinuation of natalizumab if teriflunomide was immediately started.

Based on the half-life of fingolimod, a 6 week interval without therapy is needed for clearance from the circulation and a 1 to 2 month period is needed for lymphocytes to return to normal range following discontinuation of fingolimod. Starting teriflunomide during this period may lead to an additive effect on the immune system.

Women of childbearing potential have to use effective contraception during treatment and after treatment as long as teriflunomide plasma concentration is above 0.02 mg/l. During this period women should discuss any plans to stop or change contraception with the treating physician.

For women receiving teriflunomide treatment, who wish to become pregnant, the medicine should be stopped and an accelerated elimination procedure is recommended in order to more rapidly achieve concentration below 0.02 mg/l.

Ionised calcium levels may appear falsely decreased. Consider determining the total albumin adjusted serum calcium concentration.

Pregnancy and Lactation

Pregnancy

Teriflunomide is contraindicated during pregnancy.

Use of teriflunomide during pregnancy is contraindicated by the manufacturer. Teriflunomide may cause serious birth defects when administered during pregnancy. If pregnancy occurs despite using contraception, consider accelerated elimination process. There are limited amount of data from the use of teriflunomide in pregnant women. Studies in animals have shown reproductive toxicity.

Lactation

Teriflunomide is contraindicated during breastfeeding.

Use of teriflunomide during breastfeeding is contraindicated by the manufacturer. Animal studies have shown excretion of teriflunomide in breast milk.

Side Effects

Acne
Allergic reaction
Alopecia
Anaemia
Anxiety
Arthralgia
Asthenia
Bronchitis
Carpal tunnel syndrome
Colitis
Creatine phosphokinase increased
Cystitis
Diarrhoea
Drug rash with eosinophilia and systemic symptoms (DRESS)
Drug-induced liver injury
Dyslipidaemia
Gamma glutamyl transferase (GGT) increased
Gastro-enteritis
Headache
Hepatitis
Hyperaesthesia
Hypersensitivity reactions
Hypertension
Increase in serum ALT/AST
Influenza
Interstitial lung disease
Laryngitis
Menorrhagia
Musculoskeletal pain
Myalgia
Nail disorders
Nausea
Neuralgia
Neutropenia
Opportunistic infections
Oral herpes
Pain
Palpitations
Pancreatitis
Paraesthesia
Peripheral neuropathy
Pharyngitis
Pollakiuria
Psoriasis
Pulmonary hypertension
Rash
Reduced neutrophil count
Sciatica
Sepsis
Severe skin reactions
Sinusitis
Stevens-Johnson syndrome
Stomatitis
Thrombocytopenia
Tinea pedis
Tooth ache
Tooth infection
Toxic epidermal necrolysis
Upper abdominal pain
Upper respiratory tract infection
Urinary tract infections
Vomiting
Weight loss
White blood cell count decreased

Presentation

Oral formulations of teriflunomide.

Drugs List

Therapeutic Indications

Uses

Treatment of relapsing-remitting multiple sclerosis

Dosage

Adults

Children

Contraindications

Children under 10 years
Hypoproteinaemia
Severe infection
Bone marrow aplasia
Breastfeeding
Galactosaemia
Immunodeficiency syndromes
Pregnancy
Renal dialysis
Severe anaemia
Severe hepatic impairment
Severe leucopenia
Severe neutropenia
Severe thrombocytopenia

Precautions and Warnings

Females of childbearing potential
High alcohol intake
Patients over 65 years
Anaemia
Glucose-galactose malabsorption syndrome
Hepatic impairment
Interstitial lung disease
Lactose intolerance
Latent or healed tuberculosis
Leucopenia
Thrombocytopenia

Administration of live vaccines is not recommended
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Contains lactose
Exclude pregnancy prior to initiation of treatment
Monitor blood pressure pre-treatment and periodically thereafter
Monitor serum transaminases (including ALT) before and during therapy
Perform full blood count before treatment
ALT (SGPT) between 2-3 x ULN: monitor LFT weekly
Monitor differential blood count
Advise patient to report any symptoms of interstitial lung disease
Advise patient to report symptoms of infection immediately
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
May give falsely decreased values of ionised calcium
Consider accelerated elimination if discontinued due to adverse effects
Advise patient to seek advice at first indications of pregnancy
Consider withdrawal if psoriasis occurs/worsens
Discontinue if ALT level exceeds 3 times the upper limit of normal
Discontinue if evidence of interstitial lung disease
Discontinue if pancreatitis occurs
Discontinue if peripheral neuropathy occurs
Discontinue if severe haematological reactions including pancytopenia occur
Discontinue if severe skin reaction occurs
Discontinue if signs or symptoms of hepatic injury occur
Discontinue if ulcerative stomatitis occurs
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment

For patients who do not have pre-existing or suspected liver disorders, hepatic enzymes should be assessed at least every 4 weeks during the first 6 months of treatment and regularly thereafter. In patients with pre-existing liver disorders or have clinical signs and symptoms of hepatic dysfunction, hepatic enzymes should be assessed every 2 weeks during the first 6 months of treatment, and at least every 8 weeks thereafter for at least 2 years from initiation of treatment.

For patients testing positive in tuberculosis screening, treat by standard medical practice prior to therapy with teriflunomide.

No waiting period is required when initiating teriflunomide after interferon beta or glatiramer acetate or when starting interferon beta or glatiramer acetate, after teriflunomide.

Caution is required when switching patients from natalizumab to teriflunomide. Due to the long half-life of natalizumab, concomitant exposure could occur for up to 2 to 3 months following discontinuation of natalizumab if teriflunomide was immediately started.

Based on the half-life of fingolimod, a 6 week interval without therapy is needed for clearance from the circulation and a 1 to 2 month period is needed for lymphocytes to return to normal range following discontinuation of fingolimod. Starting teriflunomide during this period may lead to an additive effect on the immune system.

Women of childbearing potential have to use effective contraception during treatment and after treatment as long as teriflunomide plasma concentration is above 0.02 mg/l. During this period women should discuss any plans to stop or change contraception with the treating physician.

For women receiving teriflunomide treatment, who wish to become pregnant, the medicine should be stopped and an accelerated elimination procedure is recommended in order to more rapidly achieve concentration below 0.02 mg/l.

Ionised calcium levels may appear falsely decreased. Consider determining the total albumin adjusted serum calcium concentration.

Pregnancy and Lactation

Pregnancy

Teriflunomide is contraindicated during pregnancy.

Use of teriflunomide during pregnancy is contraindicated by the manufacturer. Teriflunomide may cause serious birth defects when administered during pregnancy. If pregnancy occurs despite using contraception, consider accelerated elimination process. There are limited amount of data from the use of teriflunomide in pregnant women. Studies in animals have shown reproductive toxicity.

Lactation

Teriflunomide is contraindicated during breastfeeding.

Use of teriflunomide during breastfeeding is contraindicated by the manufacturer. Animal studies have shown excretion of teriflunomide in breast milk.

Side Effects

Acne
Allergic reaction
Alopecia
Anaemia
Anxiety
Arthralgia
Asthenia
Bronchitis
Carpal tunnel syndrome
Colitis
Creatine phosphokinase increased
Cystitis
Diarrhoea
Drug rash with eosinophilia and systemic symptoms (DRESS)
Drug-induced liver injury
Dyslipidaemia
Gamma glutamyl transferase (GGT) increased
Gastro-enteritis
Headache
Hepatitis
Hyperaesthesia
Hypersensitivity reactions
Hypertension
Increase in serum ALT/AST
Influenza
Interstitial lung disease
Laryngitis
Menorrhagia
Musculoskeletal pain
Myalgia
Nail disorders
Nausea
Neuralgia
Neutropenia
Opportunistic infections
Oral herpes
Pain
Palpitations
Pancreatitis
Paraesthesia
Peripheral neuropathy
Pharyngitis
Pollakiuria
Psoriasis
Pulmonary hypertension
Rash
Reduced neutrophil count
Sciatica
Sepsis
Severe skin reactions
Sinusitis
Stevens-Johnson syndrome
Stomatitis
Thrombocytopenia
Tinea pedis
Tooth ache
Tooth infection
Toxic epidermal necrolysis
Upper abdominal pain
Upper respiratory tract infection
Urinary tract infections
Vomiting
Weight loss
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: April 2022

Reference Sources

Summary of Product Characteristics: Aubagio 7mg film-coated tablets. Sanofi Genzyme. Revised December 2021.
Summary of Product Characteristics: Aubagio 14mg film-coated tablets. Sanofi Genzyme. Revised December 2021.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 07 April 2022