Drugs List

Therapeutic Indications

Uses

Follicular non-Hodgkin's lymphoma
Mantle cell lymphoma (MCL)
Myeloma - multiple
Transfusion-dependent anaemia due to myelodysplastic syndrome

Treatment of adult patients with newly diagnosed multiple myeloma who have undergone autologous stem cell transplantation.

Treatment of previously untreated multiple myeloma in combination with dexamethasone, or bortezomib and dexamethasone, or melphalan and prednisone in patients not eligible for transplant.

Treatment of multiple myeloma in combination with dexamethasone in patients who have received at least one prior therapy.

Treatment of transfusion dependent anaemia due to low or intermediate -1 risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.

Treatment of adult patients with relapsed or refractory mantle cell lymphoma.

Treatment of adult patients with previously treated follicular lymphoma (Grade 1-3a) in combination with rituximab.

Dosage

Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent is not included.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.

Contraindications

Children under 18 years
Patients not compliant with Pregnancy Prevention Programme
Patients not registered with Pregnancy Prevention Programme
ANC below 0.5x10 to power of 9/L at baseline - if treating MDS
ANC below 1x10 to power of 9/L at baseline - if treating multiple myeloma
ANC below 1x10 to power of 9/L at baseline- if treating follicular lymphoma
Breastfeeding
Galactosaemia
Platelet count below 25x10 to power of 9/L at baseline- if treating MDS
Platelet count below 50 x 10 to power of 9/L at baseline - if treating FL
Platelet count below 50x10 to power of 9/L at baseline- if treating myeloma
Pregnancy

Precautions and Warnings

Females of childbearing potential
History of herpes zoster infection
Patients over 75 years
Predisposition to infection
Predisposition to thromboembolic disease
Risk factors for cardiovascular disorder
Dehydration
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of hepatitis B
Lactose intolerance
Renal impairment - creatinine clearance below 50ml/minute
Thrombosis
Thyroid dysfunction

Reduce dose in patients with 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
Do not initiate if history of severe rash associated with thalidomide
Evaluate patient for cardiopulmonary disease before and during treatment
Female: Do not exceed 4 weeks treatment on one prescription
Maintain adequate hydration of patient prior / during treatment
May be increased risk of skin cancer
Premedicate with a hypouricaemic agent
Staff & patients: Must comply with Pregnancy Prevention Programme
Treatment to be initiated and supervised by a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor hepatic function before treatment and regularly during treatment
Monitor renal function before treatment and regularly during treatment
Monitor thyroid function prior to and periodically during treatment
Elderly: Monitor renal function and consider dose modification
Exclude pregnancy before issuing each prescription
Monitor closely patient at risk of cardiovascular disorders
Monitor for signs of tumour flare reaction
Monitor full blood count regularly
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
Monitor patients with high tumour burden closely during therapy
Monitor visual status
Advise patient to report signs of neuropathy
Advise patient to report symptoms of infection immediately
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Advise patients to report any signs of dyspnoea, chest pain or ankle oedema
Consider treatment with blood growth factors if severe cytopenias develop
Discontinue treatment if DRESS is suspected
Discontinue treatment if Stevens-Johnson Syndrome suspected
Discontinue treatment if toxic epidermal necrolysis is suspected
Reactivation of hepatitis B may occur in chronic carriers
Reactivation of herpes zoster may occur
Consider suspending treatment if grade 2 or 3 skin reaction occurs
Discontinue if angioedema occurs
Discontinue if grade 4 skin reaction occurs
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if serious allergic or anaphylactic reaction occurs
Interrupt treatment and/or reduce dose for any grade 3 toxicity
MDS: Discontinue if no minor erythroid response within 4 months
MDS: Suspend therapy if platelet count falls below 25 x 10 to power of 9/L
MM: Suspend therapy if platelet count falls below 25 x 10 to power of 9/L
Suspend therapy if neutrophils fall below 0.5 x 10 to the power of 9 / L
Suspend treatment if thromboembolic events occur
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 advised if partner pregnant or may become pregnant
Male: Use of condoms required during and for 1 week after treatment
Advise patients to report skin rash
Patients must not donate blood during or for 1 week after treatment

Cases of hyperthyroidism and hypothyroidism have been reported, control of co-morbid conditions influencing thyroid function is recommended prior to treatment.

Cases of viral reactivation have been reported following treatment with lenalidomide, particularly in patients previously infected with hepatitis B or herpes zoster. Cases of hepatitis B reactivation have been reported and in some cases progressed to hepatic failure requiring antiviral treatment and discontinuation of lenalidomide. Reactivation of herpes zoster led in some cases to disseminated herpes zoster, meningitis herpes zoster or ophthalmic herpes zoster and patients in these cases needed to discontinue the treatment with lenalidomide.

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 lenalidomide treatment. The use of other erythropoietic agents including hormone replacement therapy should be used with caution. A haemoglobin concentration of 12g/dl should lead to discontinuation of erythropoietic agents.

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 Prevention Programme
Lenalidomide is structurally related to thalidomide. Thalidomide is a powerful human teratogen, inducing a high frequency of severe and life-threatening birth defects. Lenalidomide 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.

Neutropenia and thrombocytopenia
A complete blood count, including white blood cell count with differential count, platelet count, haemoglobin and haematocrit should be performed at baseline and every week for the first 8 weeks of lenalidomide and monthly thereafter.

In mantle cell lymphoma patients, complete blood count should be monitored every 2 weeks in cycles 3 and 4, and then at the start of each subsequent treatment cycle.

In follicular lymphoma patients, complete blood count should be monitored weekly for the first 3 weeks of cycle 1, every 2 weeks during cycles 2 to 4 and then at the start of each subsequent treatment cycle.

Pregnancy and Lactation

Pregnancy

Lenalidomide is contraindicated during pregnancy.

The manufacturer states that lenalidomide is contraindicated during pregnancy. There have been no reports of human pregnancies exposed to lenalidomide but as it is an analogue of thalidomide which is a known human teratogen that causes life-threatening birth defects, the teratogenic effect of lenalidomide can be expected. Animal studies in have shown teratogenicity similar to thalidomide. Refer to the manufacturers documentation for requirements and responsibilities under the Pregnancy Prevention Programme in the event of pregnancy.

Lactation

Lenalidomide is contraindicated during breastfeeding.

The manufacturer states that breastfeeding should be discontinued during therapy with lenalidomide. Animal studies have shown thalidomide, an analogue of lenalidomide, to be excreted into breast milk. It is not known if lenalidomide 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 lenalidomide and its metabolites in breast milk are unknown.

Side Effects

Abdominal pain
Abnormal liver function tests
Anaemia
Anaphylactic reaction
Angioedema
Arrhythmias
Asthenia
Ataxia
Blindness
Blood pressure changes
Blurred vision
Bronchitis
Cataracts
Cerebral ischaemia
Cerebrovascular accident
Coagulation disorders
Congestive cardiac failure
Constipation
Deafness
Decreased appetite
Deep vein thrombosis (DVT)
Dehydration
Depression
Diabetes mellitus
Diarrhoea
Dizziness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dysaesthesia
Dysgeusia
Dysphagia
Dyspnoea
Electrolyte disturbances
Erectile dysfunction
Fanconi syndrome
Fatigue
Febrile neutropenia
Gastro-intestinal symptoms
Haematuria
Haemolysis
Haemolytic anaemia
Haemorrhage
Headache
Hepatic failure
Hepatotoxicity
Herpes zoster
Hyperglycaemia
Hyperhidrosis
Hypersensitivity reactions
Increased susceptibility to infection
Influenza
Influenza-like syndrome
Insomnia
Intracranial bleeding
Ischaemia
Joint swelling
Leucopenia
Loss of balance
Loss of libido
Lymphopenia
Micturition disorders
Muscle spasm
Myocardial infarction
Nasopharyngitis
Neuralgia
Neutropenia
Oedema
Pancytopenia
Paraesthesia
Peripheral neuropathy
Pharyngitis
Photosensitivity
Pneumonia
Progressive multifocal leukoencephalopathy (PML)
Pruritus
Pulmonary embolism
Pulmonary hypertension
Pyrexia
Rash
Reduced visual acuity
Renal failure
Renal tubular necrosis
Respiratory distress
Respiratory tract infection
Second primary malignancies
Sepsis
Sinusitis
Skin discolouration
Stevens-Johnson syndrome
Stomatitis
Syncope
Thrombocytopenia
Thyroid abnormalities
Tinnitus
Toxic epidermal necrolysis
Transient ischaemic attack
Tremor
Tumour lysis syndrome
Vasculitis
Vomiting
Weight loss

Presentation

Oral formulations of lenalidomide.

Drugs List

Therapeutic Indications

Uses

Follicular non-Hodgkin's lymphoma
Mantle cell lymphoma (MCL)
Myeloma - multiple
Transfusion-dependent anaemia due to myelodysplastic syndrome

Treatment of adult patients with newly diagnosed multiple myeloma who have undergone autologous stem cell transplantation.

Treatment of previously untreated multiple myeloma in combination with dexamethasone, or bortezomib and dexamethasone, or melphalan and prednisone in patients not eligible for transplant.

Treatment of multiple myeloma in combination with dexamethasone in patients who have received at least one prior therapy.

Treatment of transfusion dependent anaemia due to low or intermediate -1 risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.

Treatment of adult patients with relapsed or refractory mantle cell lymphoma.

Treatment of adult patients with previously treated follicular lymphoma (Grade 1-3a) in combination with rituximab.

Dosage

Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent is not included.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.

Contraindications

Children under 18 years
Patients not compliant with Pregnancy Prevention Programme
Patients not registered with Pregnancy Prevention Programme
ANC below 0.5x10 to power of 9/L at baseline - if treating MDS
ANC below 1x10 to power of 9/L at baseline - if treating multiple myeloma
ANC below 1x10 to power of 9/L at baseline- if treating follicular lymphoma
Breastfeeding
Galactosaemia
Platelet count below 25x10 to power of 9/L at baseline- if treating MDS
Platelet count below 50 x 10 to power of 9/L at baseline - if treating FL
Platelet count below 50x10 to power of 9/L at baseline- if treating myeloma
Pregnancy

Precautions and Warnings

Females of childbearing potential
History of herpes zoster infection
Patients over 75 years
Predisposition to infection
Predisposition to thromboembolic disease
Risk factors for cardiovascular disorder
Dehydration
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of hepatitis B
Lactose intolerance
Renal impairment - creatinine clearance below 50ml/minute
Thrombosis
Thyroid dysfunction

Reduce dose in patients with 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
Do not initiate if history of severe rash associated with thalidomide
Evaluate patient for cardiopulmonary disease before and during treatment
Female: Do not exceed 4 weeks treatment on one prescription
Maintain adequate hydration of patient prior / during treatment
May be increased risk of skin cancer
Premedicate with a hypouricaemic agent
Staff & patients: Must comply with Pregnancy Prevention Programme
Treatment to be initiated and supervised by a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor hepatic function before treatment and regularly during treatment
Monitor renal function before treatment and regularly during treatment
Monitor thyroid function prior to and periodically during treatment
Elderly: Monitor renal function and consider dose modification
Exclude pregnancy before issuing each prescription
Monitor closely patient at risk of cardiovascular disorders
Monitor for signs of tumour flare reaction
Monitor full blood count regularly
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
Monitor patients with high tumour burden closely during therapy
Monitor visual status
Advise patient to report signs of neuropathy
Advise patient to report symptoms of infection immediately
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Advise patients to report any signs of dyspnoea, chest pain or ankle oedema
Consider treatment with blood growth factors if severe cytopenias develop
Discontinue treatment if DRESS is suspected
Discontinue treatment if Stevens-Johnson Syndrome suspected
Discontinue treatment if toxic epidermal necrolysis is suspected
Reactivation of hepatitis B may occur in chronic carriers
Reactivation of herpes zoster may occur
Consider suspending treatment if grade 2 or 3 skin reaction occurs
Discontinue if angioedema occurs
Discontinue if grade 4 skin reaction occurs
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if serious allergic or anaphylactic reaction occurs
Interrupt treatment and/or reduce dose for any grade 3 toxicity
MDS: Discontinue if no minor erythroid response within 4 months
MDS: Suspend therapy if platelet count falls below 25 x 10 to power of 9/L
MM: Suspend therapy if platelet count falls below 25 x 10 to power of 9/L
Suspend therapy if neutrophils fall below 0.5 x 10 to the power of 9 / L
Suspend treatment if thromboembolic events occur
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 advised if partner pregnant or may become pregnant
Male: Use of condoms required during and for 1 week after treatment
Advise patients to report skin rash
Patients must not donate blood during or for 1 week after treatment

Cases of hyperthyroidism and hypothyroidism have been reported, control of co-morbid conditions influencing thyroid function is recommended prior to treatment.

Cases of viral reactivation have been reported following treatment with lenalidomide, particularly in patients previously infected with hepatitis B or herpes zoster. Cases of hepatitis B reactivation have been reported and in some cases progressed to hepatic failure requiring antiviral treatment and discontinuation of lenalidomide. Reactivation of herpes zoster led in some cases to disseminated herpes zoster, meningitis herpes zoster or ophthalmic herpes zoster and patients in these cases needed to discontinue the treatment with lenalidomide.

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 lenalidomide treatment. The use of other erythropoietic agents including hormone replacement therapy should be used with caution. A haemoglobin concentration of 12g/dl should lead to discontinuation of erythropoietic agents.

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 Prevention Programme
Lenalidomide is structurally related to thalidomide. Thalidomide is a powerful human teratogen, inducing a high frequency of severe and life-threatening birth defects. Lenalidomide 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.

Neutropenia and thrombocytopenia
A complete blood count, including white blood cell count with differential count, platelet count, haemoglobin and haematocrit should be performed at baseline and every week for the first 8 weeks of lenalidomide and monthly thereafter.

In mantle cell lymphoma patients, complete blood count should be monitored every 2 weeks in cycles 3 and 4, and then at the start of each subsequent treatment cycle.

In follicular lymphoma patients, complete blood count should be monitored weekly for the first 3 weeks of cycle 1, every 2 weeks during cycles 2 to 4 and then at the start of each subsequent treatment cycle.

Pregnancy and Lactation

Pregnancy

Lenalidomide is contraindicated during pregnancy.

The manufacturer states that lenalidomide is contraindicated during pregnancy. There have been no reports of human pregnancies exposed to lenalidomide but as it is an analogue of thalidomide which is a known human teratogen that causes life-threatening birth defects, the teratogenic effect of lenalidomide can be expected. Animal studies in have shown teratogenicity similar to thalidomide. Refer to the manufacturers documentation for requirements and responsibilities under the Pregnancy Prevention Programme in the event of pregnancy.

Lactation

Lenalidomide is contraindicated during breastfeeding.

The manufacturer states that breastfeeding should be discontinued during therapy with lenalidomide. Animal studies have shown thalidomide, an analogue of lenalidomide, to be excreted into breast milk. It is not known if lenalidomide 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 lenalidomide and its metabolites in breast milk are unknown.

Counselling

Take a missed dose if less than 12 hours has elapsed. If more than 12 hours has elapsed do not take the dose but take the next dose as normal the following day.

Advise patients to report shortness of breath, chest pain, arm or leg swelling.

Advise patients to report unexplained fever, sore throat, bruising or bleeding.

Advise patients to report skin rash.

Advise patients to report symptoms of infection immediately.

Advise patients to report signs of neuropathy.

Advise patients not to donate blood during or within 1 week of stopping treatment.

Advise patients they must comply fully with the Pregnancy Prevention Program (PPP).

Female patients of child bearing potential must use one effective method of contraception for at least 4 weeks before starting, during and for at least a further 4 weeks after stopping treatment with lenalidomide.

Male patients must use condoms during treatment and for 1 week after treatment if their partner is pregnant or is of childbearing potential not using effective contraception.

Advise patients that their ability to drive or operate machinery may be affected by side effects.

Side Effects

Abdominal pain
Abnormal liver function tests
Anaemia
Anaphylactic reaction
Angioedema
Arrhythmias
Asthenia
Ataxia
Blindness
Blood pressure changes
Blurred vision
Bronchitis
Cataracts
Cerebral ischaemia
Cerebrovascular accident
Coagulation disorders
Congestive cardiac failure
Constipation
Deafness
Decreased appetite
Deep vein thrombosis (DVT)
Dehydration
Depression
Diabetes mellitus
Diarrhoea
Dizziness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dysaesthesia
Dysgeusia
Dysphagia
Dyspnoea
Electrolyte disturbances
Erectile dysfunction
Fanconi syndrome
Fatigue
Febrile neutropenia
Gastro-intestinal symptoms
Haematuria
Haemolysis
Haemolytic anaemia
Haemorrhage
Headache
Hepatic failure
Hepatotoxicity
Herpes zoster
Hyperglycaemia
Hyperhidrosis
Hypersensitivity reactions
Increased susceptibility to infection
Influenza
Influenza-like syndrome
Insomnia
Intracranial bleeding
Ischaemia
Joint swelling
Leucopenia
Loss of balance
Loss of libido
Lymphopenia
Micturition disorders
Muscle spasm
Myocardial infarction
Nasopharyngitis
Neuralgia
Neutropenia
Oedema
Pancytopenia
Paraesthesia
Peripheral neuropathy
Pharyngitis
Photosensitivity
Pneumonia
Progressive multifocal leukoencephalopathy (PML)
Pruritus
Pulmonary embolism
Pulmonary hypertension
Pyrexia
Rash
Reduced visual acuity
Renal failure
Renal tubular necrosis
Respiratory distress
Respiratory tract infection
Second primary malignancies
Sepsis
Sinusitis
Skin discolouration
Stevens-Johnson syndrome
Stomatitis
Syncope
Thrombocytopenia
Thyroid abnormalities
Tinnitus
Toxic epidermal necrolysis
Transient ischaemic attack
Tremor
Tumour lysis syndrome
Vasculitis
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 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.

Summary of Product Characteristics: Revlimid 2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg and 25mg Hard Capsules. Celgene Ltd. Revised November 2020.

Pregnancy Prevention Program information for healthcare professionals.
Available at: www.palliativedrugs.com/download/6723%20HCP%20sections%20r12%20email%20version.pdf
Last accessed: 10 July 2019

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

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 1 July 2019