Drugs List

Therapeutic Indications

Uses

Treatment of relapsing-remitting multiple sclerosis

Treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with highly active disease despite a full and adequate course of treatment with at least 1 other disease-modifying treatment or in patients with rapidly worsening disease with at least 2 disabling relapses in a year and with one or more gadolinium enhancing lesions on brain MRI or a significant increase in T2-lesion load compared to a recent MRI scan.

Administration

For intravenous infusion.

Administered by intravenous infusion over approximately 4 hours. If acute infusion reaction persist, the administration time may be extended.

Contraindications

Autoimmune disease
Children under 18 years
Severe infection
Breastfeeding
Coagulopathy
History of angina
History of arterial dissection
History of cerebrovascular accident
History of myocardial infarction
Positive HIV status
Pregnancy
Uncontrolled hypertension

Precautions and Warnings

History of autoimmune disorder
Patients over 55 years
Hepatic impairment
Hepatitis B
Hepatitis C
History of thyroid disorder
Malignant neoplasm
Renal impairment

Administration of live vaccines is not recommended
Antibodies may develop and increase risk of autoimmune mediated disorders
Consider screening at risk patients for hepatitis B and/or C virus
If ITP is suspected perform complete blood count immediately
ITP and/or nephropathies require prompt treatment
Advise ability to drive/operate machinery may be affected by side effects
Consider pre-medication with antihistamines and/or antipyretics
Ensure relevant vaccinations administered at least 6 weeks before treatment
Monitor patient during and for 2 hours post administration
Premedicate for herpes infection from day 1 until, 1 month after treatment
Premedicate with corticosteroids prior to admin on 1st 3 days of course
Prior to starting therapy rule out active tuberculosis
Prior to starting therapy screen for latent tuberculosis
Treatment to be initiated and supervised by a specialist
Varicella vaccination recommended for antibody-negative patients
Administration carried out in centres with intensive care facilities
Dilute and use as an infusion
Reducing the infusion rate may minimise severity of infusion reactions
Resuscitation facilities must be immediately available
Monitor blood pressure pre-treatment and periodically thereafter
Monitor CBC with differential prior to & monthly until 4 years after
Monitor creatinine prior to & monthly until 4 years after treatment
Monitor hepatic function before treatment and regularly during treatment
Monitor thyroid function prior to & 3 monthly until 4 years after treatment
Perform liver function tests prior to and monthly until 4 years after
Perform urinalysis with microscopy prior to & monthly until 4 years after
Autoimmune disorders can occur many months after initiation of treatment
Consider additional monitoring if significant changes in vital signs occur
Human papilloma virus (HPV) screening recommended annually
If hepatic impairment symptoms occur monitor LFT & consider discontinuation
Monitor coagulation values
Monitor for acquired haemophilia
Monitor patient for infusion-associated reactions (IARs)
Monitor patients for signs of adverse cardiovascular effects
Monitor platelet count immediately after dose on days 3+5 of 1st cycle
Monitor vital signs and ECG every day during infusion
Advise on the need to report unusual bleeding
Advise patient to consult Doctor if spontaneous bruising occurs
Advise patient to report any chest pain
Advise patient to report breathlessness or cough immediately
Advise patient to report signs and symptoms of nephropathy
Advise patient to report signs of haemophagocytic lymphohistiocytosis (HLH)
Advise patient to report symptoms of cholelithiasis and cholecystitis
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Consider discontinuing therapy if significant changes in vital signs occur
Risk of developing opportunistic infections
Consider discontinuing if severe infusion reactions occur
Discontinue if headache assoc with weakness/numbness one side/part occurs
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Female: Contraception required during and for 4 months after treatment
Breastfeeding: Do not breastfeed during & for 4 months after treatment
Advise patient to seek medical advice if delayed adverse event(s) occurs
Avoid foods w/ high risk of listeria 2 weeks prior to 1 mth post treatment
Remind patient of importance of carrying Alert Card with them at all times

Complete blood count (CBC) results should be monitored for cytopenias. If a cytopenia is confirmed, appropriate medical intervention should be promptly initiated, including referral to a specialist.

Progressive Multifocal Leukoencephalopathy Syndrome (PML)
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with this agent. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. If PML is diagnosed, treatment should be permanently discontinued.

Pregnancy and Lactation

Pregnancy

Alemtuzumab is contraindicated during pregnancy.

The manufacturer recommends that alemtuzumab should only be administered during pregnancy if the potential benefit justifies the potential risk to the foetus.

There is limited data for the use of alemtuzumab in pregnant women. Human IgG is known to cross the placental barrier; alemtuzumab may cross the placental barrier and thus potentially cause foetal harm.

Lactation

Alemtuzumab is contraindicated during breastfeeding.

The manufacturer recommends that breastfeeding should be discontinued during treatment and for at least 4 months following alemtuzumab therapy.

It is unknown if alemtuzumab is excreted in human breast milk. However, it was detected in the milk and offspring in animals, therefore the risk to the breastfed child cannot be excluded.

Side Effects

Abdominal pain
Acne
Alopecia
Antibody formation
Arthralgia
Asthenia
Autoimmune hepatitis
Blistering
Blood pressure changes
Candidiasis
Cardiac arrhythmias
Cervicocephalic arterial dissection
Chills
Cholecystitis
Conjunctivitis
Constipation
Contusion
Cough
Cytokine release syndrome
Cytomegalovirus infection
Decrease in haematocrit
Diarrhoea
Dizziness
Dysgeusia
Dyspepsia
Dysphagia
Dyspnoea
Ear infection
Ecchymosis
Epistaxis
Epstein-Barr virus
Extremity pain
Fatigue
Flushing
Gastroesophageal reflux disease
Gingival bleeding
Goitre
Goodpasture's syndrome
Graves' disease
Haematuria
Haemolytic anaemia
Haemophagocytic lymphohistiocytosis
Headache
Herpes infections
Hiccups
Hyperaesthesia
Hyperhidrosis
Hypersensitivity reactions including anaphylaxis
Hypoaesthesia
Idiopathic thrombocytopenic purpura (ITP)
Increased susceptibility to infection
Increases in hepatic enzymes
Influenza-like symptoms
Infusion-related symptoms
Insomnia
Leucopenia
Leukocytosis
Listeriosis
Lymphadenopathy
Lymphopenia
Malaise
Migraine
Muscle spasm and pain of back and chest
Muscle weakness
Myalgia
Myocardial infarction
Nausea
Nephropathy
Night sweats
Onychomycosis
Oropharyngeal pain
Pancytopenia
Paraesthesia
Peripheral oedema
Pneumonitis
Progressive multifocal leukoencephalopathy (PML)
Proteinuria
Psychiatric disorders
Pulmonary alveolar haemorrhage
Pyrexia
Reproductive disorders
Respiratory tract infection
Sensory disturbances
Serum creatinine increased
Stomatitis
Stroke
Throat irritation
Throat tightness
Thrombocytopenia
Thyroid abnormalities
Thyroiditis
Tooth infection
Tremor
Tuberculosis
Urinary tract infections
Urticaria
Vomiting
Weight loss

Presentation

Infusions containing alemtuzumab.

Drugs List

Therapeutic Indications

Uses

Treatment of relapsing-remitting multiple sclerosis

Treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with highly active disease despite a full and adequate course of treatment with at least 1 other disease-modifying treatment or in patients with rapidly worsening disease with at least 2 disabling relapses in a year and with one or more gadolinium enhancing lesions on brain MRI or a significant increase in T2-lesion load compared to a recent MRI scan.

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local protocols for the relevant indication should be consulted.

Adults

Additional Dosage Information

Administration

For intravenous infusion.

Administered by intravenous infusion over approximately 4 hours. If acute infusion reaction persist, the administration time may be extended.

Contraindications

Autoimmune disease
Children under 18 years
Severe infection
Breastfeeding
Coagulopathy
History of angina
History of arterial dissection
History of cerebrovascular accident
History of myocardial infarction
Positive HIV status
Pregnancy
Uncontrolled hypertension

Precautions and Warnings

History of autoimmune disorder
Patients over 55 years
Hepatic impairment
Hepatitis B
Hepatitis C
History of thyroid disorder
Malignant neoplasm
Renal impairment

Administration of live vaccines is not recommended
Antibodies may develop and increase risk of autoimmune mediated disorders
Consider screening at risk patients for hepatitis B and/or C virus
If ITP is suspected perform complete blood count immediately
ITP and/or nephropathies require prompt treatment
Advise ability to drive/operate machinery may be affected by side effects
Consider pre-medication with antihistamines and/or antipyretics
Ensure relevant vaccinations administered at least 6 weeks before treatment
Monitor patient during and for 2 hours post administration
Premedicate for herpes infection from day 1 until, 1 month after treatment
Premedicate with corticosteroids prior to admin on 1st 3 days of course
Prior to starting therapy rule out active tuberculosis
Prior to starting therapy screen for latent tuberculosis
Treatment to be initiated and supervised by a specialist
Varicella vaccination recommended for antibody-negative patients
Administration carried out in centres with intensive care facilities
Dilute and use as an infusion
Reducing the infusion rate may minimise severity of infusion reactions
Resuscitation facilities must be immediately available
Monitor blood pressure pre-treatment and periodically thereafter
Monitor CBC with differential prior to & monthly until 4 years after
Monitor creatinine prior to & monthly until 4 years after treatment
Monitor hepatic function before treatment and regularly during treatment
Monitor thyroid function prior to & 3 monthly until 4 years after treatment
Perform liver function tests prior to and monthly until 4 years after
Perform urinalysis with microscopy prior to & monthly until 4 years after
Autoimmune disorders can occur many months after initiation of treatment
Consider additional monitoring if significant changes in vital signs occur
Human papilloma virus (HPV) screening recommended annually
If hepatic impairment symptoms occur monitor LFT & consider discontinuation
Monitor coagulation values
Monitor for acquired haemophilia
Monitor patient for infusion-associated reactions (IARs)
Monitor patients for signs of adverse cardiovascular effects
Monitor platelet count immediately after dose on days 3+5 of 1st cycle
Monitor vital signs and ECG every day during infusion
Advise on the need to report unusual bleeding
Advise patient to consult Doctor if spontaneous bruising occurs
Advise patient to report any chest pain
Advise patient to report breathlessness or cough immediately
Advise patient to report signs and symptoms of nephropathy
Advise patient to report signs of haemophagocytic lymphohistiocytosis (HLH)
Advise patient to report symptoms of cholelithiasis and cholecystitis
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Consider discontinuing therapy if significant changes in vital signs occur
Risk of developing opportunistic infections
Consider discontinuing if severe infusion reactions occur
Discontinue if headache assoc with weakness/numbness one side/part occurs
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Female: Contraception required during and for 4 months after treatment
Breastfeeding: Do not breastfeed during & for 4 months after treatment
Advise patient to seek medical advice if delayed adverse event(s) occurs
Avoid foods w/ high risk of listeria 2 weeks prior to 1 mth post treatment
Remind patient of importance of carrying Alert Card with them at all times

Complete blood count (CBC) results should be monitored for cytopenias. If a cytopenia is confirmed, appropriate medical intervention should be promptly initiated, including referral to a specialist.

Progressive Multifocal Leukoencephalopathy Syndrome (PML)
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with this agent. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. If PML is diagnosed, treatment should be permanently discontinued.

Pregnancy and Lactation

Pregnancy

Alemtuzumab is contraindicated during pregnancy.

The manufacturer recommends that alemtuzumab should only be administered during pregnancy if the potential benefit justifies the potential risk to the foetus.

There is limited data for the use of alemtuzumab in pregnant women. Human IgG is known to cross the placental barrier; alemtuzumab may cross the placental barrier and thus potentially cause foetal harm.

Lactation

Alemtuzumab is contraindicated during breastfeeding.

The manufacturer recommends that breastfeeding should be discontinued during treatment and for at least 4 months following alemtuzumab therapy.

It is unknown if alemtuzumab is excreted in human breast milk. However, it was detected in the milk and offspring in animals, therefore the risk to the breastfed child cannot be excluded.

Side Effects

Abdominal pain
Acne
Alopecia
Antibody formation
Arthralgia
Asthenia
Autoimmune hepatitis
Blistering
Blood pressure changes
Candidiasis
Cardiac arrhythmias
Cervicocephalic arterial dissection
Chills
Cholecystitis
Conjunctivitis
Constipation
Contusion
Cough
Cytokine release syndrome
Cytomegalovirus infection
Decrease in haematocrit
Diarrhoea
Dizziness
Dysgeusia
Dyspepsia
Dysphagia
Dyspnoea
Ear infection
Ecchymosis
Epistaxis
Epstein-Barr virus
Extremity pain
Fatigue
Flushing
Gastroesophageal reflux disease
Gingival bleeding
Goitre
Goodpasture's syndrome
Graves' disease
Haematuria
Haemolytic anaemia
Haemophagocytic lymphohistiocytosis
Headache
Herpes infections
Hiccups
Hyperaesthesia
Hyperhidrosis
Hypersensitivity reactions including anaphylaxis
Hypoaesthesia
Idiopathic thrombocytopenic purpura (ITP)
Increased susceptibility to infection
Increases in hepatic enzymes
Influenza-like symptoms
Infusion-related symptoms
Insomnia
Leucopenia
Leukocytosis
Listeriosis
Lymphadenopathy
Lymphopenia
Malaise
Migraine
Muscle spasm and pain of back and chest
Muscle weakness
Myalgia
Myocardial infarction
Nausea
Nephropathy
Night sweats
Onychomycosis
Oropharyngeal pain
Pancytopenia
Paraesthesia
Peripheral oedema
Pneumonitis
Progressive multifocal leukoencephalopathy (PML)
Proteinuria
Psychiatric disorders
Pulmonary alveolar haemorrhage
Pyrexia
Reproductive disorders
Respiratory tract infection
Sensory disturbances
Serum creatinine increased
Stomatitis
Stroke
Throat irritation
Throat tightness
Thrombocytopenia
Thyroid abnormalities
Thyroiditis
Tooth infection
Tremor
Tuberculosis
Urinary tract infections
Urticaria
Vomiting
Weight loss

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: July 2019

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.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

EMA 15 November 2019: Measures to minimise risk of serious side effects of multiple sclerosis medicine Lemtrada
Available at: https://www.ema.europa.eu/en/documents/referral/lemtrada-article-20-procedure-measures-minimise-risk-serious-side-effects-multiple-sclerosis_en.pdf
Last accessed: 13 January 2020

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. Accessed on 15 July 2019.

MHRA Drug Safety Update May 2019
Available at: https://www.gov.uk/drug-safety-update/lemtrada-alemtuzumab-and-serious-cardiovascular-and-immune-mediated-adverse-reactions-new-restrictions-to-use-and-strengthened-monitoring-requirements
Last accessed: 19 July 2019

MHRA Drug Safety Update February 2020
Available at: https://www.gov.uk/drug-safety-update/lemtrada-alemtuzumab-updated-restrictions-and-strengthened-monitoring-requirements-following-review-of-serious-cardiovascular-and-immune-mediated-reactions
Last accessed: 10 March 2020

Summary of Product Characteristics: Lemtrada 12mg/1.2ml concentrate for solution for infusion. Sanofi Genzyme. Revised September 2020.

The Renal Drug Handbook. 4th edition. (2014) ed. Ashley, C and Dunleavy, A. Radcliffe Publishing Ltd, London.