Nilotinib capsules
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of nilotinib.
Drugs List
Therapeutic Indications
Uses
Philadelphia chromosome positive CML - accelerated phase
Philadelphia chromosome positive CML - chronic phase
For the treatment of adult and paediatric patients with newly diagnosed Philadelphia chromosome positive chronic myelogenous leukaemia (CML) in the chronic phase.
For the treatment of adult patients with chronic phase or accelerated phase Philadelphia chromosome positive CML, with resistance or intolerance to prior therapy including imatinib.
For the treatment of paediatric patients with chronic phase Philadelphia chromosome positive CML with resistance or intolerance to prior therapy including imatinib.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.
Adults
Treatment should be continued as long as clinical benefit is observed or until unacceptable toxicity occurs.
Newly diagnosed chronic phase Ph+ CML
300mg twice daily.
Chronic or accelerated phase Ph+ CML with resistance or intolerance to prior therapy
400mg twice daily.
Children
Newly diagnosed chronic phase Ph+ CML
Children aged 10 up to 18 years
230mg per metre squared twice daily. Maximum single dose 400mg.
Children under 10
Contraindicated.
Chronic phase Ph+ CML with resistance or intolerance to prior therapy
Children aged 6 up to 18 years
230mg per metre squared twice daily. Maximum single dose 400mg.
Children under 6
Contraindicated.
Additional Dosage Information
Missed doses
If a dose is missed, do not take an additional dose, continue with usual prescribed next dose.
Dose modifications for haematological toxicity.
Nilotinib may need to be temporarily withheld and/or dose reduced if haematological toxicities occur that are not related to the underlying leukaemia.
Chronic phase CML
Adult patients
Absolute neutrophil count (ANC) below 1 x 10 to the power of 9 per litre and/or platelet count below 50 x 10 to the power of 9 per litre: Interrupt nilotinib treatment and monitor blood counts. Restart treatment if ANC improves to above 1 x 10 to the power of 9 per litre and/or platelet count improves above 50 x 10 to the power of 9 per litre within 2 weeks. If neutrophils or platelets do not improve, dose reduction to 400mg once daily may be required.
Paediatric patients
First occurrence of absolute neutrophil count (ANC) below 1 x 10 to the power of 9 per litre and/or platelet count below 50 x 10 to the power of 9 per litre: Interrupt nilotinib treatment and monitor blood counts. Restart treatment if ANC improves to above 1.5 x 10 to the power of 9 per litre and/or platelet count improves above 75 x 10 to the power of 9 per litre within 2 weeks. If neutrophils or platelets do not improve, dose reduction to 230mg per metre squared once daily may be required.
Second occurrence of absolute neutrophil count (ANC) below 1 x 10 to the power of 9 per litre and/or platelet count below 50 x 10 to the power of 9 per litre: Consider discontinuation.
Accelerated phase CML
Adult patients
Absolute neutrophil count (ANC) below 0.5 x 10 to the power of 9 per litre and/or platelet count below 10 x 10 to the power of 9 per litre: Interrupt nilotinib treatment and monitor blood counts. Restart treatment if ANC improves to above 1 x 10 to the power of 9 per litre and/or platelet count improves above 20 x 10 to the power of 9 per litre within 2 weeks. If neutrophils or platelets do not improve, dose reduction to 400mg once daily may be required.
Dose modifications for non-haematological toxicity.
Moderate or severe non-haematological toxicity
Adult patients: Interrupt nilotinib treatment until toxicity resolves. If prior dose was 300mg or 400mg twice daily, resume treatment at 400mg once daily. If patient's dose was already reduced discontinue treatment.
Paediatric patients: Interrupt nilotinib treatment until toxicity resolves. If prior dose was 230mg per metre squared twice daily, resume treatment at 230mg per metre squared once daily. If patient's dose was already reduced discontinue treatment.
Serum lipase elevations
Adult patients (Grade 3 or above elevations): Reduce dose to 400mg once daily, or interrupt treatment.
Paediatric patients (Grade 2 or above elevations): Interrupt nilotinib treatment until levels return to grade 1 or lower. If prior dose was 230mg per metre squared twice daily, resume treatment at 230mg per metre squared once daily. If patient's dose was already reduced, discontinue treatment.
Bilirubin or hepatic transaminase elevations
Adult patients (Grade 3 or above elevations): Reduce dose to 400mg once daily, or interrupt treatment.
Paediatric patients (Grade 2 or above elevations): Interrupt nilotinib treatment until levels return to grade 1 or lower. If prior dose was 230mg per metre squared twice daily, resume treatment at 230mg per metre squared once daily. If patient's dose was already reduced and recovery takes longer than 28 days, discontinue treatment.
Modifications for adult patients who have achieved a sustained deep molecular response. Treatment is usually continued for as long as the patient gains benefit.
Discontinuation can be considered in patients that achieve a sustained deep molecular response provided they are confirmed to express typical BCR-ABL transcripts, e13a2/b2a2 or e14a2/b3a2 and meet the following criteria:
Chronic phase CML treated with nilotinib as a first line therapy: Received nilotinib 300mg twice daily for at least 3 years and deep molecular response sustained for at least 1 year. Chronic phase CML treated with nilotinib following prior imatinib therapy: Received nilotinib for at least 3 years and deep molecular response sustained for at least 1 year. Eligible patients who discontinue treatment require monitoring of BCR-ABL transcript levels and complete differential blood counts every month for the first year, every 6 weeks for the second year and every 12 weeks thereafter to ensure remission is maintained. Loss of remission following treatment discontinuation - Patients who had received nilotinib as a first line therapy for chronic CML:
Loss of MR4 but not MMR (major molecular response): Increase monitoring of BCR-ABL transcript levels to every 2 weeks until BCR-ARL levels return to a range between MR4 and MR4.5. Return to original monitoring schedule once levels are maintained between MMR and MR4 for a minimum of 4 consecutive measurements. Loss of MMR: Restart treatment within 4 weeks of when remission was lost. Restart at 300mg twice daily or for patients previously on a dose reduction restart at 400mg once daily. Monitor BCR-ABL transcript levels monthly until MMR is re-established and every 12 weeks thereafter. If MMR is not re-established within 3 months of restarting treatment perform BCR-ABL kinase domain mutation testing. Loss of remission following treatment discontinuation - Patients who had received nilotinib for chronic phase CML following prior imatinib therapy:
Loss of MR4 or loss of MMR: Restart treatment within 4 weeks of when remission was lost. Restart at either 300mg twice daily or 400mg twice daily. Monitor BCR-ABL transcript levels monthly until previous MMR or MR4 level is re-established and every 12 weeks thereafter. If MMR is not re-established within 3 months of restarting treatment perform BCR-ABL kinase domain mutation testing.
Administration
For oral administration.
For patients who are unable to swallow capsules, the contents of each capsule may be dispersed in one teaspoon of apple sauce and should be taken immediately. Not more than one teaspoon may be taken, and no other food other than apple sauce must be used.
Contraindications
Children under 6 years
Breastfeeding
Galactosaemia
Long QT syndrome
Pregnancy
Torsade de pointes
Precautions and Warnings
Children aged 6 to 10 years
Elevated serum transaminases - greater than 2.5 times upper limit of normal
Family history of long QT syndrome
Bradycardia
Cardiac disorder
Congestive cardiac failure
Dehydration
Electrolyte imbalance
Gastrectomy
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of hepatitis B
History of pancreatitis
History of torsade de pointes
Lactose intolerance
Neutrophil count below 0.5 x 10 to the power of 9/L - in accelerated CML
Neutrophil count below 1 x 10 to the power of 9/L - if treating chronic CML
Platelet count below 10 x 10 to the power of 9/L - in accelerated CML
Platelet count below 50 x 10 to the power of 9/L - if treating chronic CML
Recent myocardial infarction
Serum bilirubin above 1.5 times upper limit of normal
Unstable angina
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Before initiating screen all patients for hepatitis B infection
Consider premedication with hypouricaemic agent
Evaluate patients for cardiovascular disease prior to treatment
Hepatitis B: Refer prior to initiation to liver disease specialist
Maintain adequate hydration of patient prior / during treatment
Monitor growth of children during treatment
Not all available strengths are licensed for all indications
Treatment to be initiated and supervised by a specialist
Contains lactose
Advise patient to have no food for 2 hours before and 1 hour after dose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor blood glucose before and during treatment
Monitor serum lipids before treatment, at months 3 and 6, then annually
Monitor blood counts every 2 weeks for 2 months, then monthly
Monitor ECG in patients at risk of QT prolongation
Monitor ECG prior to and during treatment in existing cardiac abnormalities
Monitor for active hepatitis B during therapy and for several months after
Monitor for signs of rapid weight gain may indicate severe fluid retention
Monitor liver function tests monthly during treatment
Monitor patients for signs of tumour lysis syndrome
Monitor serum electrolytes
Serum lipase levels should be tested monthly
Dose reduction may be required in myelosuppression &/or bone marrow aplasia
Reactivation of hepatitis B may occur in chronic carriers
Consider discontinuing after remission in eligible patients
Consider reducing or interrupting treatment if lipase levels are elevated
Suspend treatment and/or reduce dose if grade 3 or higher hepatotoxicity
Suspend treatment and/or reduce dose in grade 3 non-haematological toxicity
Not licensed for all indications in all age groups
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Female: Contraception required during and for 2 weeks after treatment
Breastfeeding: Do not breastfeed during & for 2 weeks after treatment
Advise patients to report any new or worsening cardiovascular symptoms
Pregnancy and Lactation
Pregnancy
Nilotinib is contraindicated during pregnancy.
The manufacturer does not recommend using nilotinib during pregnancy. If used, the patient must be warned of potential risks to the foetus. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.
Lactation
Nilotinib is contraindicated during breastfeeding.
Use of nilotinib when breastfeeding is contraindicated by the manufacturer. Animal data reports significant levels of nilotinib in the breast milk, however presence in human breast milk is unknown. Effects on exposed infants are unknown.
Side Effects
Abnormal liver function
Alopecia
Anaemia
Angina pectoris
Anxiety
Arrhythmias
Arterial stenosis
Asthenia
Blood glucose disturbances
Bradycardia
Cardiac failure
CNS haemorrhage
Conjunctivitis
Coronary artery disorder
Cough
Creatine phosphokinase increased
Cyanosis
Depression
Diabetes mellitus
Disturbances of appetite
Dizziness
Dysaesthesia
Dysphonia
Dyspnoea
Electrolyte disturbances
Elevated amylase levels
Elevated serum lipase
Eosinophilia
Erectile dysfunction
Erythema
Eye disorder
Fatigue
Febrile neutropenia
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal symptoms
Gastroesophageal reflux
Growth retardation (children)
Gynaecomastia
Haematoma
Haemoglobin decrease
Haemorrhage
Headache
Heart murmur
Hepatitis
Hypercalcaemia
Hypercholesterolaemia
Hyperhidrosis
Hyperkalaemia
Hyperlipidaemia
Hypertension
Hypertensive crisis
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Hypophosphataemia
Increase in alkaline phosphatase
Increase in serum ALT/AST
Infections
Insomnia
Intermittent claudication
Interstitial lung disease
Jaundice
Leukocytosis
Lymphopenia
Melaena
Micturition disorders
Mouth ulcers
Musculoskeletal disturbances
Neutropenia
Night sweats
Ocular haemorrhage
Ocular oedema
Oedema
Pain
Palpitations
Pancreatitis
Pancytopenia
Paraesthesia
Pericardial effusion
Peripheral vascular disorders
Pleural effusion
Pleurisy
Prolongation of QT interval
Pruritus
Pyrexia
Rash
Reduced visual acuity
Serum bilirubin increased
Skin disorder
Skin papilloma
Stomatitis
Syncope
Thrombocythaemia
Thrombocytopenia
Thyroid abnormalities
Tremor
Tumour lysis syndrome
Vertigo
Weight changes
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: June 2019
Reference Sources
Summary of Product Characteristics: Tasigna 50mg hard capsules. Novartis. Revised November 2019.
Summary of Product Characteristics: Tasigna 150mg hard capsules. Novartis. Revised November 2019.
Summary of Product Characteristics: Tasigna 200mg hard capsules. Novartis. Revised November 2019.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 10 June 2019
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.