- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral formulations of cladribine.
Treatment of relapsing-remitting multiple sclerosis
Treatment of adult patients with highly active relapsing multiple sclerosis (MS).
Due to the complexity and specialist nature of dosage regimens for the treatment of multiple sclerosis, specific dosing information on this agent is not included, and only a broad outline of the treatment protocol is given. When using this agent specialist literature and national guidelines should be consulted.
Treatment with oral cladribine is administered as 2 treatment courses over 2 years, with a recommended dosage of 1.75mg per kilogram per year, and a recommended cumulative dose of 3.5mg per kilogram of bodyweight over 2 years. A single treatment course consists of one treatment week at the beginning of the first month, and one treatment week at the beginning of the second month, of the respective treatment year. If clinically necessary, the treatment course of year 2 can be delayed for 6 months.
Additional Dosage Information
Before treatment cycle
Lymphocyte count below normal range at the start of treatment year 1: Withhold initiation of oral cladribine therapy.
Lymphocyte count below 0.8 x 10 to the power of 9 per litre at the start of treatment year 2: Delay year 2 treatment cycle, up to a duration of 6 months, to allow for recovery of lymphocytes. If lymphocyte count has not recovered after 6 months, discontinue oral cladribine.
During treatment cycle
Lymphocyte count below 0.5 x 10 to the power of 9 per litre: The patient should be actively monitored for signs and symptoms of infection. If signs of infections occur, initiate anti-infective treatment as clinically necessary, and consider interruption or delay of oral cladribine treatment until infection resolves.
Lymphocyte count below 0.2 x 10 to the power of 9 per litre: The patient should be actively monitored for signs and symptoms of infection. If signs of infections occur, initiate anti-infective treatment as clinically necessary, and consider interruption or delay of oral cladribine treatment until infection resolves. In addition, prophylactic treatment of herpes should be considered.
Avoid other medicines 3 hours before or after cladribine dose during treatment period.
Children under 18 years
Hepatic impairment - Child-Pugh score greater than 6
Hereditary fructose intolerance
Positive HIV status
Renal impairment - creatinine clearance below 60ml/minute
Precautions and Warnings
Patients over 65 years
Weight below 40kg
History of drug induced hepatic impairment
History of hepatic disorder
Administration of live vaccines is not recommended
Before initiating screen all patients for viral hepatitis
Prior to starting therapy screen for latent tuberculosis
Treat and control infections prior to commencing therapy
Treatment to be initiated and supervised by a specialist
Varicella vaccination recommended for antibody-negative patients
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Advise patient to avoid other oral medicines 3 hours before or after dose
Consult local policy on the safe use of oral anti-cancer drugs
Patients who require blood transfusion should only receive irradiated blood
Staff: Not to be handled by pregnant staff
A recent (within 3 months) MRI should be available prior to treatment
Monitor lymphocyte count before and regularly during treatment
Perform liver function tests before commencing therapy and during therapy
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient/carer to contact GP immediately if signs of liver disorder
Reactivation of latent chronic infections may occur
Risk of developing opportunistic infections
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Suspend if drug induced liver injury is suspected
Advise patient not to take St John's wort concurrently
Female: Oral contraception may not be adequate during treatment
Female: Use barrier contraception during and for 1 month after treatment
Male & female: Contraception required during & for 6 months after treatment
Lymphocyte count should be determined before initiating each treatment cycle, as well as 2 months and 6 months after the start of each treatment cycle.
Varicella vaccination is recommended for antibody-negative patients before initiating treatment. Initiation of treatment cycle should then be delayed by 4 to 6 weeks to allow for vaccination effect to occur.
The potential for an additive immunosuppressive effect should be considered in patients treated with other immunomodulatory/immunosuppressive medicinal products before or after treatment with cladribine.
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported following use of parenteral cladribine, including cases 6 months to several years after treatment had finished. Advise patients on the signs and symptoms of PML including the potential for delayed presentation. Consider PML as a potential diagnosis if patients present with new or worsening neurological, cognitive or behavioural signs or symptoms. If PML is diagnosed, permanently discontinue treatment.
Prior to treatment assess patient history of underlying liver disorders or episodes of liver injury. Similarly, liver function tests including serum aminotransferase, alkaline phosphatase and total bilirubin levels should be assessed before initiating treatment.
Monitor liver function tests before each treatment course in years 1 and 2 and when clinically necessary.
Pregnancy and Lactation
Cladribine is contraindicated in pregnancy.
There are no data for the use of cladribine in pregnant women. Animal studies have shown reproductive toxicity.
It is not known if cladribine crosses the human placenta, but it's molecular weight, terminal half-life and low plasma protein binding suggest the drug will cross the placental barrier.
Similar drugs that also work by inhibiting DNA synthesis are known human teratogens.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Cladribine is contraindicated during breastfeeding.
There is no published evidence of cladribine use during breastfeeding. Because of the potential for adverse reactions in a nursing infant, the manufacturer contraindicates the use of clofarabine during breastfeeding, and for 1 week after the last dose.
The molecular weight, terminal half-life and low plasma protein binding of cladribine suggests that it will be excreted into breast milk, but the effect of exposure on the bread-fed infant is still unknown.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Decrease in haemoglobin and haematocrit
Drug-induced liver injury
Reduced neutrophil count
Reduced platelet count
Reduction in blood count
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 ).
Last Full Review Date: February 2018
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Summary of Product Characteristics: MAVENCLAD 10mg tablets. Merck Serono europe limited. Revised March 2022.
MHRA Drug Safety Update December 2017
Available at: https://www.mhra.gov.uk
Last accessed: 14 March 2018
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
Cladribine Last revised: 11 April 2017
Last accessed: 07 February 2018
MHRA Drug Safety Update March2022
Available at: https://www.mhra.gov.uk
Last accessed: 05 April 2022
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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