Drugs List

Therapeutic Indications

Uses

Combination therapy for multiple myeloma pts ineligible for high dose chemo
Combination treatment of multiple myeloma in patients over 65

In combination with melphalan and prednisone as first line treatment of patients with untreated multiple myeloma who are 65 years and over or ineligible for high dose chemotherapy.

Unlicensed Uses

Inflammatory bowel disease
Leprosy

Multibacillary leprosy

Administration

It is recommended that thalidomide is taken as a single dose at bedtime to reduce the impact of somnolence.

Contraindications

Children under 18 years
Patients not compliant with Pregnancy Prevention Programme
Breastfeeding
Pregnancy

Precautions and Warnings

Females of childbearing potential
Patients over 75 years
Predisposition to venous thromboembolism
Risk factors for cardiovascular disorder
Dehydration
History of hepatitis B
Peripheral neuropathy
Pulmonary hypertension
Severe hepatic impairment
Severe renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Before initiating screen all patients for hepatitis B infection
Consider use of anticoagulant prophylaxis if at risk of thromboembolism
Female: Do not exceed 4 weeks treatment on one prescription
Hepatitis B: Refer prior to initiation to liver disease specialist
Maintain adequate hydration of patient prior / during treatment
Male: Do not exceed 12 weeks of treatment on one prescription
Staff & patients: Must comply with Pregnancy Prevention Programme
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor differential WBC count before and during therapy
Monitor platelets before starting and during treatment
Pre-treatment neurological examination recommended
Consider PTLD or PML if new or worsening neurological symptoms occur
Evaluate patients with respiratory symptoms for pulmonary hypertension
Exclude pregnancy before issuing each prescription
Monitor closely patient at risk of cardiovascular disorders
Monitor for symptoms of peripheral neuropathy
Monitor for syncope and bradycardia
Monitor hepatic function
Monitor neurological function
Monitor patients at risk for signs & symptoms of venous thromboembolism
Monitor patients for development of second primary malignancies
Monitor patients for signs of tumour lysis syndrome
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report signs of neuropathy
Reactivation of hepatitis B may occur in chronic carriers
Reactivation of herpes zoster may occur
Discontinue if angioedema occurs
Discontinue if grade 3 or higher neuropathy occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if severe skin reaction occurs
Suspend treatment or reduce dose if peripheral neuropathy occurs
Patient should avoid alcohol as effect may be potentiated
Female: Contraception required during and for 1 month after treatment
Female: Contraception required for 1 month before initiation of treatment
Male: Contraception required for partners if patient unable to use condoms
Male: Use of condoms required during and for 1 week after treatment
Advise patient of risk of bleeding
Patients must not donate blood during or for 1 week after treatment
Patients must not donate semen during or for 1 week after treatment

Pregnancy Prevention Programme
Thalidomide is a powerful human teratogen, inducing a high frequency of severe and life-threatening birth defects. Thalidomide must never be used by women who are pregnant or by women who could become pregnant unless all the conditions of the manufacturers Pregnancy Prevention Programme (PPP) are met. The conditions of the PPP must be fulfilled for all male and female patients. Refer to the manufacturers documentation for full details and requirements for the PPP.

Only prescribers and pharmacies registered with the programme are allowed to prescribe and dispense the product. Prescriber, patient and dispensing pharmacist must each comply fully with the PPP.

The PPP outlines specific criteria for determination of child bearing potential, required testing, suitable contraception, specific patient counselling, prescribing and dispensing requirements.

The prescriber must ensure that: The patient complies with the conditions of the PPP. The patient confirms that they understand the conditions of the PPP.

Cardiovascular disorders
Closely monitor patients with cardiovascular risk factors (e.g. prior thrombosis) action should be taken to minimise modifiable risk factors such as smoking hypertension and hyperlipidaemia.

There is an increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) with thalidomide treatment. The risk appears to be greatest during the first 5 months of therapy, therefore thromboprophylaxis is strongly recommended for the first 5 months of treatment especially in patients with other thrombotic risk factors. History of thromboembolic events and concomitant hormone replacement therapy or erythropoietic agents may also increase thromboembolic risk. In particular, a haemoglobin concentration of 12 g/dl should lead to discontinuation of erythropoietic agents.

Posterior Reversible Encephalopathy Syndrome (PRES) also known as Reversible Posterior Leucoencephalopathy Syndrome (RPLS)
Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.

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

Contraindicated during pregnancy.

Thalidomide is a powerful human teratogen, inducing a high frequency of severe and live-threatening birth defects such as: ectromelia (amelia, phocomelia, hemimelia) of the upper and/or lower extremities, microtia with abnormality of the external acoustic meatus (blind or absent), middle and internal ear lesions (less frequent), ocular lesions (anophthalmia, microphthalmia), congenital heart disease, renal abnormalities. Other less frequent abnormalities have also been described. Further abnormalities and problems, including effects on the CNS, may develop in later life.

Refer to the manufacturers documentation for requirements and responsibilities under the Pregnancy Prevention Programme in the event of pregnancy.

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 14-17 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 ).

Lactation

Contraindicated during breastfeeding.

It is not known if thalidomide is excreted in human milk. However, the molecular weight is low enough that excretion into milk is likely. The effects on a nursing infant from exposure to thalidomide and its metabolites in breast milk are unknown.

Animal studies have shown thalidomide to be excreted into breast milk.

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

Side Effects

Acute myeloid leukaemia
Amenorrhoea
Anaemia
Angioedema
Anxiety
Asthenia
Atrial fibrillation
Atrioventricular block
Blurred vision
Bradycardia
Bronchitis
Bronchopneumopathy
Cardiac failure
Cerebrovascular accident
Confusion
Constipation
Convulsions
Deafness
Deep vein thrombosis (DVT)
Depression
Dizziness
Dry mouth
Dry skin
Dysaesthesia
Dyspepsia
Dyspnoea
Fatigue
Febrile neutropenia
Foetal defects
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Hearing loss
Hepatic impairment
Hypersensitivity reactions
Hypotension
Hypothyroidism
Impaired co-ordination
Interstitial lung disease
Intestinal obstruction
Leucopenia
Lymphopenia
Malaise
Mood changes
Myelodysplastic syndrome
Myocardial infarction
Nausea
Neutropenia
Orthostatic hypotension
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral neuropathy
Peripheral oedema
Peritonitis
Pneumonia
Posterior reversible encephalopathy syndrome (PRES)
Progressive multifocal leukoencephalopathy (PML)
Pulmonary embolism
Pulmonary hypertension
Pyrexia
Rash
Reactivation of hepatitis B
Reactivation of herpes zoster
Renal failure
Sedation
Sepsis
Septic shock
Severe cutaneous skin eruptions
Sexual dysfunction
Skin reactions
Somnolence
Stevens-Johnson syndrome
Syncope
Teratogenic effects
Thrombocytopenia
Thromboembolic disorders
Toxic epidermal necrolysis
Transient ischaemic attack
Tremor
Tumour lysis syndrome
Urticaria
Vertigo
Vomiting
Worsening of Parkinson's disease

Presentation

Thalidomide oral formulations

Drugs List

Therapeutic Indications

Uses

Combination therapy for multiple myeloma pts ineligible for high dose chemo
Combination treatment of multiple myeloma in patients over 65

In combination with melphalan and prednisone as first line treatment of patients with untreated multiple myeloma who are 65 years and over or ineligible for high dose chemotherapy.

Unlicensed Uses

Inflammatory bowel disease
Leprosy

Multibacillary leprosy

Dosage

Thalidomide is supplied only under a special risk management programme. Prescriber, patient and dispensing pharmacist must each comply with the programme.

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

Adults

Elderly

Additional Dosage Information

Administration

It is recommended that thalidomide is taken as a single dose at bedtime to reduce the impact of somnolence.

Contraindications

Children under 18 years
Patients not compliant with Pregnancy Prevention Programme
Breastfeeding
Pregnancy

Precautions and Warnings

Females of childbearing potential
Patients over 75 years
Predisposition to venous thromboembolism
Risk factors for cardiovascular disorder
Dehydration
History of hepatitis B
Peripheral neuropathy
Pulmonary hypertension
Severe hepatic impairment
Severe renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Before initiating screen all patients for hepatitis B infection
Consider use of anticoagulant prophylaxis if at risk of thromboembolism
Female: Do not exceed 4 weeks treatment on one prescription
Hepatitis B: Refer prior to initiation to liver disease specialist
Maintain adequate hydration of patient prior / during treatment
Male: Do not exceed 12 weeks of treatment on one prescription
Staff & patients: Must comply with Pregnancy Prevention Programme
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor differential WBC count before and during therapy
Monitor platelets before starting and during treatment
Pre-treatment neurological examination recommended
Consider PTLD or PML if new or worsening neurological symptoms occur
Evaluate patients with respiratory symptoms for pulmonary hypertension
Exclude pregnancy before issuing each prescription
Monitor closely patient at risk of cardiovascular disorders
Monitor for symptoms of peripheral neuropathy
Monitor for syncope and bradycardia
Monitor hepatic function
Monitor neurological function
Monitor patients at risk for signs & symptoms of venous thromboembolism
Monitor patients for development of second primary malignancies
Monitor patients for signs of tumour lysis syndrome
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report signs of neuropathy
Reactivation of hepatitis B may occur in chronic carriers
Reactivation of herpes zoster may occur
Discontinue if angioedema occurs
Discontinue if grade 3 or higher neuropathy occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if severe skin reaction occurs
Suspend treatment or reduce dose if peripheral neuropathy occurs
Patient should avoid alcohol as effect may be potentiated
Female: Contraception required during and for 1 month after treatment
Female: Contraception required for 1 month before initiation of treatment
Male: Contraception required for partners if patient unable to use condoms
Male: Use of condoms required during and for 1 week after treatment
Advise patient of risk of bleeding
Patients must not donate blood during or for 1 week after treatment
Patients must not donate semen during or for 1 week after treatment

Pregnancy Prevention Programme
Thalidomide is a powerful human teratogen, inducing a high frequency of severe and life-threatening birth defects. Thalidomide must never be used by women who are pregnant or by women who could become pregnant unless all the conditions of the manufacturers Pregnancy Prevention Programme (PPP) are met. The conditions of the PPP must be fulfilled for all male and female patients. Refer to the manufacturers documentation for full details and requirements for the PPP.

Only prescribers and pharmacies registered with the programme are allowed to prescribe and dispense the product. Prescriber, patient and dispensing pharmacist must each comply fully with the PPP.

The PPP outlines specific criteria for determination of child bearing potential, required testing, suitable contraception, specific patient counselling, prescribing and dispensing requirements.

The prescriber must ensure that: The patient complies with the conditions of the PPP. The patient confirms that they understand the conditions of the PPP.

Cardiovascular disorders
Closely monitor patients with cardiovascular risk factors (e.g. prior thrombosis) action should be taken to minimise modifiable risk factors such as smoking hypertension and hyperlipidaemia.

There is an increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) with thalidomide treatment. The risk appears to be greatest during the first 5 months of therapy, therefore thromboprophylaxis is strongly recommended for the first 5 months of treatment especially in patients with other thrombotic risk factors. History of thromboembolic events and concomitant hormone replacement therapy or erythropoietic agents may also increase thromboembolic risk. In particular, a haemoglobin concentration of 12 g/dl should lead to discontinuation of erythropoietic agents.

Posterior Reversible Encephalopathy Syndrome (PRES) also known as Reversible Posterior Leucoencephalopathy Syndrome (RPLS)
Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.

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

Contraindicated during pregnancy.

Thalidomide is a powerful human teratogen, inducing a high frequency of severe and live-threatening birth defects such as: ectromelia (amelia, phocomelia, hemimelia) of the upper and/or lower extremities, microtia with abnormality of the external acoustic meatus (blind or absent), middle and internal ear lesions (less frequent), ocular lesions (anophthalmia, microphthalmia), congenital heart disease, renal abnormalities. Other less frequent abnormalities have also been described. Further abnormalities and problems, including effects on the CNS, may develop in later life.

Refer to the manufacturers documentation for requirements and responsibilities under the Pregnancy Prevention Programme in the event of pregnancy.

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 14-17 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 ).

Lactation

Contraindicated during breastfeeding.

It is not known if thalidomide is excreted in human milk. However, the molecular weight is low enough that excretion into milk is likely. The effects on a nursing infant from exposure to thalidomide and its metabolites in breast milk are unknown.

Animal studies have shown thalidomide to be excreted into breast milk.

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

Side Effects

Acute myeloid leukaemia
Amenorrhoea
Anaemia
Angioedema
Anxiety
Asthenia
Atrial fibrillation
Atrioventricular block
Blurred vision
Bradycardia
Bronchitis
Bronchopneumopathy
Cardiac failure
Cerebrovascular accident
Confusion
Constipation
Convulsions
Deafness
Deep vein thrombosis (DVT)
Depression
Dizziness
Dry mouth
Dry skin
Dysaesthesia
Dyspepsia
Dyspnoea
Fatigue
Febrile neutropenia
Foetal defects
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Hearing loss
Hepatic impairment
Hypersensitivity reactions
Hypotension
Hypothyroidism
Impaired co-ordination
Interstitial lung disease
Intestinal obstruction
Leucopenia
Lymphopenia
Malaise
Mood changes
Myelodysplastic syndrome
Myocardial infarction
Nausea
Neutropenia
Orthostatic hypotension
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral neuropathy
Peripheral oedema
Peritonitis
Pneumonia
Posterior reversible encephalopathy syndrome (PRES)
Progressive multifocal leukoencephalopathy (PML)
Pulmonary embolism
Pulmonary hypertension
Pyrexia
Rash
Reactivation of hepatitis B
Reactivation of herpes zoster
Renal failure
Sedation
Sepsis
Septic shock
Severe cutaneous skin eruptions
Sexual dysfunction
Skin reactions
Somnolence
Stevens-Johnson syndrome
Syncope
Teratogenic effects
Thrombocytopenia
Thromboembolic disorders
Toxic epidermal necrolysis
Transient ischaemic attack
Tremor
Tumour lysis syndrome
Urticaria
Vertigo
Vomiting
Worsening of Parkinson's disease

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: December 2015

Reference Sources

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 7 December 2015.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

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: Thalidomide Celgene 50mg hard capsules. Celgene Ltd. Revised July 2021.

MHRA Drug Safety Updates Thalidomide
Available at: https://www.gov.uk/drug-safety-update
Last accessed: 7 December 2015

MHRA Drug Safety Update May 2020
Available at: https://www.mhra.gov.uk
Last accessed: 17 June 2020