Guidelines for the Safe Use of Oral Draft

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Pharmacy Guidelines for the safe use of oral

anti-cancer medicines

Produced on behalf of the Greater Manchester and Cheshire Cancer Network by

the

Network

Oncology

Pharmacy

Group

July

2008

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1. Introduction

2. Individual Monographs

Bexarotene

Busulfan

Capecitabine

Chlorambucil

Cyclophosphamide

Dasatinib

Erlotinib

Etoposide

Fludarabine

Hydroxycarbamide

Idarubicin

Imatinib

Lapatinib

Lenalidomide

Lomustine

Melphalan

Mercaptopurine

Methotrexate

Mitotane

Procarbazine

Sorafenib

Sunitinib

Tegafur/Uracil

Temozolomide

Thalidomide

Tioguanine

Treosulfan

Tretinoin

Vinorelbine

3. Dose Modifications

4. Oral Chemotherapy Regimen Summary

5. Acknowledgements

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Introduction

In January 2008 the National Patient Safety Agency (NPSA) issued a Rapid Response Report entitled ‘Risks of Incorrect Dosing of Oral Anticancer Medicines’. This report highlights the potential for fatal outcomes if incorrect doses of oral anticancer therapy are prescribed, dispensed or administered. The NPSA indicate there were at least three deaths and over four hundred patient safety incidents concerning oral anticancer therapy between November 2003 and July 2007.

The principles of the chemotherapy standards in the Manual of Cancer Standards should always be applied. This covers actions required by the NPSA report and is as follows:- All cancer patients receiving active anti-cancer treatment should have treatment initiated by, and be under the care of, specialist oncology/haematology staff.

Local Trust chemotherapy policies and procedures must explicitly encompass oral as well as parenteral chemotherapy.

All anticancer drugs, whether conventional or non-conventional cytotoxics, should be regarded as potentially hazardous, regardless of the intended route of administration. Formal risk assessment should be applied to determine for each drug the level of risk posed and hence the risk reduction and management strategy needed.

The prescribing and dispensing of oral chemotherapy should be carried out and monitored to the same standards as those for parenteral chemotherapy.

Responsibility for administration of oral drugs ultimately lies with the patient (or a relative or carer) but it is the responsibility of all members of the multidisciplinary

oncology/haematology team to ensure as far as practically possible they are adequately prepared for this.

Effective communication between primary and secondary care and with patients is pivotal to safe and effective treatment.

Other than in exceptional and clearly defined and mutually agreed circumstances, prescribing and dispensing should remain the sole responsibility of the hospital-based oncologist/haematologist and pharmacy respectively.

How to use this guide

This document is primarily intended as a reference source for pharmacy and nursing staff to enable them to support patients receiving oral anticancer medicines.

The guide covers actions required by the NPSA Rapid Response Report for the Risks of Incorrect Dosing of Oral Anticancer Medicines. Some issues are dealt with in detail in this guide, while others are documented as requiring inclusion in individual Trust Policies.

Prescribing, dispensing and labelling, patient education and information, patient access to advice and support when at home, general risk management, and audit are followed by individual monographs for the oral anticancer drugs currently used within the GMCCN.

There is then a section on regimens containing oral anticancer medicines.

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involved in the prescribing, supply or administration of anti-cancer medication should always consult the primary literature and original protocols when providing care for individual patients.

The full protocol must always be consulted for full information on indications, dose, scheduling, dose modifications, drug interactions, side-effects and contra-indications. The regimen summaries do give an indication of when dose reductions may be necessary, but the Summary of Product Characteristics or British Oncology Pharmacy Association (BOPA) guidance must be consulted for specific details and clarified with the prescriber as appropriate.

The document does not contain information on oral anticancer medicines that are not in use in the NHS Greater Manchester and Cheshire Cancer Network (GMCCN), i.e. medicines that do not have GMCCN D&T approval. As new medicines are approved additional drug monographs will be prepared and issued via the Network website(s). Some medicines given in the monographs may be unlicensed or used for unlicensed indications. Inclusion of individual medicines in this handbook does not imply that funding streams exist in all circumstances.

For the purposes of this document the term "Oral Anticancer Medicine’ is used to refer to all drugs with direct anti-tumour activity, orally administered to cancer patients, including traditional cytotoxic chemotherapy such as capecitabine, hydroxycarbamide, chlorambucil and small molecule/ antibody treatments such as imatinib, erlotinib, sunitinib and other agents such as thalidomide or lenalidomide. It does not include hormonal or anti-hormonal agents such as tamoxifen and anastrazole.

The monographs do not cover the use of oral anticancer agents in the context of clinical trials, however the basic principles contained within this document should still be applied.

Guidance in this handbook is intended to promote the safe use of oral medicines used to treat cancer. Where the use of these medicines is for non-cancer treatment, a risk assessment should be undertaken and the guidance applied as appropriate.

Monographs contain patient counselling points for dispensary/clinic staff.

Prescribing

Prescribers should have expert guidance and support at the point of prescribing. All anticancer drugs should be prescribed only in the context of written protocols. Non-specialists who prescribe or administer ongoing oral anticancer medicines should also have ready access to appropriate written protocols and treatment plans including guidance on monitoring and treatment of toxicity.

The treatment plan should be documented in the notes and should include criteria for modifying and stopping treatment.

Electronic systems, or prescription proformas or templates, similar to those for parenteral chemotherapy should be used.

Prescriptions must state clearly for each course of treatment, the dose, frequency of administration, intended start date, duration of treatment and, where relevant, the intended stop date.

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For drugs for which a variety of schedules are in common use it is especially important that the intended schedule is unambiguously specified on every prescription.

(Capecitabine, for example, may be given 2 weeks on treatment & 1 week off, 3 weeks on and 1 week off, 2 weeks on and 2 weeks off or continuously).

All intended deviations from protocol, such as dose modifications, should be clearly identified as such.

Without specialist advice, live vaccines should not be given to individuals with impaired immune response eg. those taking immunosuppressive drugs. Live vaccines should not be given to those being treated for malignant conditions with chemotherapy (the

response to all vaccines may be reduced and there is a risk of generalised infection with live vaccines).

Dispensing & labelling

Prescriptions must be screened by authorised pharmacists before dispensing.

All pharmacy staff who are or could be involved with dispensing oral anticancer drugs must have access to full copies of all the relevant protocols.

The information available to dispensary staff must address the management of toxicity, the criteria for dose adjustments or stopping treatment, and identify circumstances and drugs in which continuous rather than intermittent treatment may be used.

This applies to all treatment, both in and outwith the context of Clinical Trials

Dispensary staff should work to detailed operating procedures analogous to those used for dispensing parenteral chemotherapy. Staff dispensing oral anticancer medicines should be able to confirm that the prescribed dose is appropriate for the patient, and that the patient is aware of the required

monitoring arrangements, by having access to information in the written protocol and treatment plan from the hospital where treatment is initiated and advice from a pharmacist with experience in cancer treatment in that hospital. Local policy must document how specific checks, such as checking a patient’s blood results, are undertaken and recorded according to local systems of practice, as the GMCCN

considers this is not necessarily the responsibility of the individual pharmacist at the time of dispensing.

The format and detail of dosing instruction should be standardised and approved by an appropriate senior pharmacist. Label directions must be clear and unambiguous and include where relevant, the intended period of treatment, start and stop dates (for short term or intermittent treatment) and an appropriate indication of the need for safe handling.

Whilst it is essential that all patents receive a manufacturer's PIL with their oral

chemotherapy drugs the use of unbroken patient packs may also pose risks to patients if they are then given more tablets than are needed for the intended course of treatment. The decision on whether or not to issue whole packs should therefore be based on a documented local risk assessment.

Manufacturers' PILs must be given (further copies can be downloaded as necessary) and may be supplemented with locally developed information and counselling points as in the following monographs.

Consideration must be given to the management of patients with swallowing difficulties. Avoid breaking/crushing tablets or opening capsules whenever possible: Queries should be directed to the local pharmacy medicines information service: the advice of an

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solution is preferred and a suitable preparation should be obtained from an NHS hospital pharmacy or commercial compounding/manufacturing facility with appropriate safe-handling facilities.

Patient Education & Information

Before every treatment cycle, all patients should be seen by a specialist pharmacist or nurse.

The pharmacist/technician handing the drugs to the patient (or relative or carer) must ensure that they fully understand :-

• how and when to take their medicines. Some patients may find it particularly hard to remember the idea of repeated short courses of treatment with 'gaps' between them

• what to do in the event of missing one or more doses • what to do in case of vomiting after taking a dose • likely adverse effects and what to do about them

• the need for and how to obtain further supplies-only from the hospital and not the GP

• the role their GP is expected to play in their treatment • principles of safe handling, storage and disposal

• that if used, medicine spoons or measures should be disposable and used once only.

• arrangements for monitoring • contact details for specialist advice

• do not take other people’s medication and do not give your medication to others • keep the medication in the container in which it was supplied with the dispensing

labels.

It should be ensured that patients are informed they should not receive live vaccines while taking such medication and for a time afterwards. Specialist advice must be sought should any vaccination be required (see section on prescribing).

Patients should receive verbal and written information about their oral anticancer medication from the initiating hospital, including details of the intended regimen and treatment plan, taken from the original protocol. Counselling points for individual drugs

are given in the following monographs. As much of this information as possible should first be given at the pre-treatment visit

and reinforced on subsequent visits.

This responsibility should be confined to staff who have received training specifically for the role. When drugs are handed to the patient by non-pharmacy staff this should be the responsibility of a specialist nurse trained to the same standard.

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Patients' access to advice and support when at home

Patients should be provided with details of appropriate and readily accessible 24-hour points of contact with medical, nursing and pharmacy staff to which they can direct queries. NHS cancer websites should be promoted to provide information for patients and carers at home as well as for healthcare staff.

General risk management

Prescribing and dispensing arrangements and procedures should take into account the Risk of wastage due to the possible need for interruption of treatment, dose

modifications, inappropriate storage, loss of medicines by a patient

Risk to others, especially young children, if the medicine is not safely stored in the home.

Spillage of oral anticancer medicines eg. liquids should be dealt with according to the GMCCN policy for the Safe Handling of Spillages.

Trusts should also consider the implications of the changes in activity type on their contract income. This will further depend on whether treatment consists of single agent oral therapy or an oral & i.v. combination regimen.

Audit

All aspects of practice should be subject to regular audit

Disclaimer

All information given on the use of drugs in this handbook is for reference purposes only. Whilst every care has been taken to ensure accuracy of the information, it is not intended to be a comprehensive guide to using these medicines. For full information on the dosage, administration and possible adverse affects of the drugs and regimens listed we recommend that the manufacturer’s data sheets (SPC) and patient information leaflets (PILS) be consulted. www.medicine.org.uk. All drug doses are given as a guide only, chemotherapy must always be prescribed by an oncology or haematology specialist. Oral chemotherapy for solid tumours should be given in accordance with an approved patient pathway. Full Chemotherapy regimen protocols can be found on the Network websites:

Acknowledgements

This booklet is based on the North East Cancer Network document and thanks go to them for permission to adapt their document.

All comments on contents and accuracy of document should be addressed to: Geoff Saunders, Consultant Pharmacist, Christie Hospital

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BEXAROTENE

Information for Nursing and Pharmacy Staff: Available as: 75mg soft capsules

Used for: Skin manifestations of advanced stage cutaneous T-cell lymphoma (CTCL) in

patients refractory to at least one systemic treatment.

Regimens:

• CTCL: initially 300mg/m2_{/day continuously; can be increased up to}

650mg/m2_{/day in individual patients. Continue treatment for as long as the patient}

derives benefit.

Dose modifications:

Haematological: Delay treatment until counts recovered. Dose reductions for leucopenia

recommended.

Hepatic impairment: Dose reduction recommended in hepatic impairment

(transaminases or bilirubin greater than 3 times the upper limit of normal)

Renal impairment: No dose modifications recommended. Monitor patients with renal

insufficiency

The 300mg/m2_{/day dose may be reduced to 200mg/m}2_{/day then to 100mg/m}2_{/day or}

temporarily suspended if toxicity occurs. When toxicity is controlled, the dose may be carefully increased again.

Emetogenic potential: Low to moderate especially in higher doses over 300mg/m2/day.

Safe handling: No special requirements.

Pharmaceutical Care Issues:

• Measure fasting blood lipid levels at baseline, weekly until the lipid response of treatment is established (usually 2-4 weeks), then monthly. Fasting triglycerides should be normal before starting treatment. Antilipidaemic therapy may be

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• Patients with risk factors for pancreatitis should not be treated with Bexarotene. • LFTs should be measured at baseline, weekly for one month, then monthly.

Consider suspension or discontinuation of treatment if results reach greater than three times the upper limit of normal.

• Baseline thyroid function should be obtained, then monitored at least monthly or if symptoms of hypothyroidism emerge. Symptomatic hypothyroidism may be treated with levothyroxine. Dose modification may also be needed.

• White blood cell counts should be obtained at baseline, weekly for one month, then monthly. If leucopoenia develops reduce the dose or discontinue

Bexarotene (see above).

• The haemoglobin level should also be measured at baseline, weekly for a month then monthly and treatment initiated if anaemia develops. Dose modifications may also need to be considered.

• Bexarotene may enhance the action of insulin and some oral antidiabetic agents including sulphonylureas and thiazolidinediones. Monitor BMs closely and consider reducing the dose of these agents.

• Caution in patients with known hypersensitivity to retinoids • Monitor patients with renal insufficiency

Drug Interactions:

Bexarotene is metabolised by CYP3A4.

Itraconazole, Ketoconazole, Erythromycin, Clarithromycin, Rifampicin, Dexamethasone, Phenytoin, Phenobarbital, Clozapine, Digoxin, Gemfibrozil, Protease inhibitors,

Tamoxifen, Oral contraceptives.

Information for patients (counselling points):

Missed dose: If you forget one dose, take your daily dose with your next meal on the

same day, and then take your usual dose as normal, the following day. Do not take a double dose in one day to make up for a missed dose the previous day.

Post dose vomiting: Do not take an extra capsule without consulting your doctor. Side effects:

• Low white blood cell count, anaemia • Thyroid disorders

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• Hyperlipidaemia

• Headache, fatigue, dizziness, eye disorders • Skin reactions

• Nausea, vomiting, diarrhoea, constipation • Bone pain, muscle and joint aches

Storage: Room temperature. Keep the bottle tightly closed.

Disposal of medication: If your doctor decides to stop the treatment, return any

remaining tablets to the pharmacist to be disposed of in a manner appropriate for disposal of cytotoxic & cytostatic medicines.

Advice for patients:

• Capsules should be swallowed whole, not chewed. • Take as a single daily dose with a meal.

• Avoid grapefruit juice

• If taking vitamin A supplements limit intake to ≤ 15000 IU/day.

• Patients should report all symptoms and signs suggestive of infection, especially sore throat.

• If dizziness or visual disturbance occurs do not drive or operate machinery. Report any visual disturbances as an eye test will be required.

• Minimise exposure to sunlight and avoid sun lamps.

• Following administration to a man or woman conception should be avoided by using an effective contraceptive method for at least 1 month after using bexarotene. Bexarotene may decrease the efficacy of oral contraceptives therefore women should use a non-hormonal form of contraception. • Patients should not breast feed whilst taking Bexarotene.

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BUSULFAN

Information for Nursing and Pharmacy Staff:

Available as: 2mg tablets (25mg capsules are available as a special from Nova

Laboratories)

Used for: CML (chronic myeloid leukaemia) and as conditioning regimen prior to bone

marrow transplant

Common regimens:

• CML Initial induction dose 0.06 mg/kg/day (max PO 4mg once daily) Monitor counts at least weekly and stop once response achieved.

• CML Maintenance dose 0.5-2mg PO once daily, if daily dose less than 2mg intermittent dosing is used e.g. 2 mg twice a week.

• Bone marrow transplant: 0.8-1 mg/kg PO every 6 hours for 4 days for a total of 16 doses; may be used in combination with other drugs

• Myeloproliferative disorders e.g. Primary thrombocythaemia/Essential thrombocythaemia: 2-4mg PO once daily.

Note: Extremely stem cell toxic, can cause irreversible bone marrow damage if

continued too long. Monitor closely for toxicity. Use with extreme caution if not familiar with use.

Dosing based on body surface area or adjusted ideal body weight should be considered in the obese (see SPC).

Haematological: Monitor closely for myelosuppression and reduce dose if occurs. Hepatic impairment: Consider dose reduction.

Renal impairment: No adjustment necessary.

Emetogenic potential: Low/non-emetogenic

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• Discontinue if lung toxicity develops.

• Seizures can occur with conditioning dosages-use prophylactic anticonvulsants (normally phenytoin).

Drug interactions: paracetamol, phenytoin, metronidazole, itraconazole, ketoconazole,

clozapine, cyclophosphamide, tioguanine, grapefruit juice (avoid three days before and one day after busulfan)

Information for patients (counselling points):

Missed dose: Do not double next dose, inform doctor and keep to normal dosing

schedule.

Post dose vomiting advice: Tell doctor as soon as possible; do not take an extra tablet

without consulting doctor.

Side effects:

• Anaemia/tiredness from bone marrow suppression • Hyperpigmentation

• Mucositis • Diarrhoea

• High temperature/unexplained bruising/bleeding, contact doctor

Storage: Not above 25°C.

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CAPECITABINE

Information for Nursing and Pharmacy Staff: Available as: 150mg tablets & 500mg tablets

Used for: Colorectal, Breast and Head and Neck Cancers. Please note that not all the

regimens are approved.

Regimens:

Gastrointestinal Tract:

ECX: Capecitabine 625mg/ m2_{bd on days 1-21 with epirubicin and cisplatin}

Repeat every 21 days.

EOX:Capecitabine 625mg/ m2_{bd on days 1-21 with epirubicin and oxaliplatin}

MCX: Capecitabine 625mg/m2_{bd on days 1-21 with mitomycin and cisplatin}

OX-Cap / XELOX: Capecitabine 800-1000mg/m2 bd on days 1-14 with oxaliplatin Repeat every 21 days

Ir-Cap: Capecitabine 1000mg/m2 bd bd on days 1-14 with irinotecan Repeat every 21 days.

Single agent Capecitabine: Capecitabine 1250 mg/m2_{bd on days 1-14}

Capecitabine with XRT: Capecitabine up to 5 weeks including/excluding weekends: 825mg/m2_{bd 5 weeks. There may be different dosage regimens used by different}

consultants.

MCap: Capecitabine 625 mg/m2_{bd on days 1-21 with mitomycin on alternate cycles.}

Head and Neck:

Capecitabine with XRT: Capecitabine 500mg/m2 bd including weekends start day before XRT and stop on the evening of last fraction of XRT.

Cisplatin/Xeloda (XP):

Capecitabine: 1000mg/ m2_{bd on days 1-14 with cisplatin}

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Breast Cancer:

Single agent Capecitabine: Capecitabine 1250mg/m2 bd on days 1-14 Repeat every 21 days.

Docetaxel/capecitabine: Capecitabine 1000mg/m2 bd on days 1-14 with docetaxel Repeat every 21 days.

Vinorelbine/capecitabine: Capecitabine 1000mg/m2_{bd on days 1-14 with vinorelbine}

Haematological: Delay treatment until counts recovered. Dose reduction recommended. Hepatic impairment: Mild to moderate hepatic impairment thought to be due to liver

metastases does not warrant dose reduction. There is no information on the use of capecitabine in hepatic impairment due to other causes eg: cirrhosis. Treatment with capecitabine is contraindicated in severe hepatic impairment.

Renal impairment: Mild renal impairment (CrCL >51ml/min) no dose reduction

necessary. Moderate renal impairment (CrCL 30-50 ml/min) dose reduction may be necessary. Contraindicated in patients with severe renal impairment (CrCL <30ml/min).

Emetogenic potential: Low/moderate. Safe handling: No special requirements.

• No liquid form available therefore unsuitable for those who can’t swallow. Can recommend dissolving tablets in lukewarm water, stir for 15 minutes to dissolve then swallow with orange juice or other flavouring to mask the bitter taste.

• Pyridoxine 50mg three times daily has been traditionally prescribed for hand and foot syndrome, however there is no evidence of the effectiveness of this treatment so should not be routinely used.

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Missed dose: Do not double-up doses or take extra doses at the end of the treatment

cycle to make up for the missed doses. If remember 30 to 90 minutes after they should have taken their tablets, then take the missed dose; if it is near to the time when their next dose is due, do not take missed dose. Inform doctor/ chemotherapy unit and keep to normal dosing schedule.

Post dose vomiting advice: Tell doctor as soon as possible. Side effects:

• Altered taste

• Gastrointestinal disturbances (diarrhoea, constipation, abdominal pain, nausea) • Stomatitis (mouth ulcers)

• Hand-foot syndrome (pain, swelling or redness in hands and/ or feet) • Fatigue

Storage: Do not store above 30°C

• Take tablets 12 hours apart within 30 minutes after a meal/with food.

• Swallow whole with a full glass of water. Tablets may be dispersed if patients are unable to swallow.

• Caution with driving/operating machinery – can cause dizziness, fatigue and nausea.

• Advise patients about the strong possibility of developing hand-foot syndrome and discuss options for managing this eg: emollients, pyridoxine.

• Contact chemotherapy hotline or day unit day unit if: Diarrhoea: >4 bowel movements/day or diarrhoea at night Vomiting: >once in 24 hours

Nausea: loss of appetite/eating less food than normal Stomatitis: pain/redness/swelling/sores in mouth

Hand-and-foot skin-reaction: pain/swelling/redness on hands and feet Fever or infection: temp >38°C or other signs

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CHLORAMBUCIL

Information for Nursing and Pharmacy Staff: Available as: 2mg tablets

Used for: chronic leukaemias, lymphomas

Regimens:

• NHL: 20mg/m2_{once daily for 3 days (with dexamethasone 4mg twice daily for 5}

days)

• CLL/NHL: 30mg once daily for 4 days weeks 1-4, 6, 8, 10 and 12 (prophylactic phenytoin 300mg nocte for 5 days with each cycle in patients > 60 years old starting night before first chlorambucil dose). This is a high dose regimen –

always double check.

• CLL: CLL4 trial: 10mg/m2_{for 7 days every 28 days (can divide dose into 3 to}

reduce sickness)

• Lymphoma: PECC: 20mg/m2 _{days 1-4 (with etoposide, lomustine and}

prednisolone) • Hodgkins Disease:

- LOPP: 10mg daily for 1-10 days (with procarbazine and prednisolone) - ChlVPP - EVA: chlorambucil 6mg/m2_{od for 7 days with procarbazine,}

prednisolone and etoposide repeated every 28 days for 6 cycles

- CLVPP & PVACE-BOP: 6mg/m2_{once daily (max 10mg) for 14 days with oral}

procarbazine, prednisolone (oral etoposide in PVACE-BOP) • Low grade Non Hodgkins Lymphoma

- Patients < 70 years of age: Chlorambucil 6mg/m2_{od (usually 10mg)}

continuously for 6 weeks initially then pulsed therapy on days 1-14 of a 28 day cycle for a further 3 months.

- Patients > 70 years of age or poor performance status: Chlorambucil 6mg/m2

od (usually 10mg) on days 1-14 of a 28 day cycle for 6 cycles. (NB for patients over 80 years of age the dose may be further reduced to 6 or 8mg od)

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Haematological: Because chlorambucil is capable of producing irreversible bone marrow

suppression, close monitoring of full blood counts should take place for patients on this treatment

Therapeutic doses of chlorambucil may reduce levels of lymphocytes, however its effects on neutrophils, platelets and haemoglobin may be less profound. It may not be necessary to discontinue treatment with chlorambucil at the first sign of a fall in

neutrophils, however this fall may continue for 10 or more days after the last dose.

Hepatic Impairment: Doses should be reduced if patients have gross hepatic

dysfunction. The dose should be modified according to the response.

Renal Impairment: No dose reduction is required, however patients should be monitored

carefully as they may be more prone to myelosuppression.

Emetogenic potential: Low

Safe handling: Provided the outer coating of chlorambucil is intact, there is no risk in

handling. Urine produced for up to 48 hours after a dose should be handled wearing protective clothing.

• Only available in tablet form therefore unsuitable for patients who cannot swallow • Cross sensitivity with melphalan can manifest as a rash.

Drug interactions: None significant

Missed dose: Do not take double next dose, inform doctor and keep to normal dosing

schedule.

Post dose vomiting: Tell doctor as soon as possible; do not take another tablet without

consulting doctor.

Side effects:

• Bone marrow suppression • Mouth ulcers/loss of appetite

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• Rash – treatment should be discontinued if develops.

Storage: Refrigerate (between 2-8°C)

• Not to be broken/crushed/chewed. • Swallow with water.

• Tell doctor if more tired than usual, unexplained bruising/bleeding, persistent cough, weakness in muscles.

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CYCLOPHOSPHAMIDE

Used for: Myeloma, chronic leukaemias, lymphoma, breast, ovarian cancer

Regimens:

• Myeloma:

- 500mg weekly (with dexamethasone 40mg/day on days 1-4)

- 400mg/m2_{weekly (with prednisolone 40mg/m}2_{alternate days for 6 weeks with}

tail off weeks 7-8). Dose reduce in renal impairment to 200mg/m2_weekly.

- CTD: 500mg weekly (days 1,8,15 of 3 weekly CTD) - CTDa: 500mg weekly (days 1,8,15, 22 of 4 weekly CTD)

- CVAD: 500mg days 1,8 and 15 with Dexamethasone days 1-4 and 12-15, with IV Doxorubicin 36mg/m2_{days 1-4 and IV Vincristine 1.6mg days 1-4}

- Weekly cyclo: 250-500mg weekly

- Velcade Cyclo dex: 50mg days 1-21, with bortezomib IV 1.3mg/m2_{days 1,4,8}

and 11 and dexamethasone 20mg days 1, 2, 4, 5, 8, 9, 11 & 12 • CLL:

- LYOS trial (with fludarabine): 250mg/m2_{from days 1-3}

- CLL4 trial (with fludarabine): 150mg/m2_{daily for 5 days}

- FC: 150mg/m2/day for 5 days (days 1-5 of 4 weekly FC)

• Breast: CMF 100 mg/m2_{/day for 14 days (days 1-14 of 3 weekly CMF)}

• Ovarian: 50mg od continuously with mesna 400mg od

Note also used for non- cancer indications, e.g. vasculitis, rheumatology

Haematological: Delay treatment until counts recovered. Dose reduction recommended. Hepatic impairment: Cyclophosphamide is a pro-drug that is converted by hepatic

microsomal enzymes to alkylating metabolites. Manufacturer recommends dosage reduction. However, exposure to active metabolites may not be increased, suggesting that dose reduction may not be necessary. Clinical decision.

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Emetogenic potential: Moderate to high dependent on dose (onset 4-12 hours,

duration 4-10+ hrs)

Safe handling: Pregnant or breast-feeding women should not handle tablets. Urine and

faeces produced for up to 72 hours and 5 days respectively after a dose should be handled wearing protective clothing. Also present in sweat and saliva; advise caution for 72 hours after a dose when bathing the patient or carrying out oral procedures.

• Report any signs of cystitis; cyclophosphamide should be avoided until treated. • Tablets are coated and should not be divided.

• Antiemetics should be given before and during therapy to reduce nausea and vomiting.

Drug interactions: clozapine, warfarin, phenytoin, digoxin, chloramphenicol, pentostatin

Missed dose: Take as soon as remember if it is the same day. If a days worth of

tablets is missed, contact the doctor. Never take more tablets in one day than you were meant to. Do not take double next dose, inform doctor and keep to normal dosing schedule.

consulting doctor. Anti-emetics should be given before and during therapy to reduce nausea and vomiting.

Side effects:

• Nausea, vomiting

• Hair loss/thinning (20%) within 3 weeks re-growth after 3 months of treatment • Headaches

• Nail/skin colour changes

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• Pregnant or breast-feeding women should not handle tablets.

• Swallow whole preferably on an empty stomach but if gastrointestinal irritation is severe, can be taken with food.

• Taken early in the day and plenty water through day to avoid cystitis. • Any sign of cystitis should be reported to doctor.

• When in combination with fludarabine – take cyclophosphamide at breakfast and fludarabine at lunchtime.

• All courses of cyclophosphamide will be prescribed and dispensed from the hospital. Your own GP will be informed of your treatment but should not prescribe it.

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DASATINIB

Information for Nursing and Pharmacy Staff: Available as: 20mg, 50mg and 70mg tablets

Used for: Leukaemias with resistance or intolerance to prior therapy

• Leukaemias: 100mg od – 100mg bd continuously (dependant on diagnosis)

Haematological: Dose reduction or treatment interruption for severe neutropenia and

thrombocytopenia are recommended.

Hepatic Impairment: No data available; hepatically metabolised therefore advise caution

in moderate to severe hepatic impairment.

Renal Impairment: No data available; <4% renally cleared therefore not thought to be a

problem.

Non-haematological adverse reaction: Treatment may be withheld until the event

improves or resolves. Thereafter, treatment can be resumed at a reduced dose as appropriate depending on the severity of the initial event.

Emetogenic potential: Low/moderate Safe handling: No special precautions.

Drug interactions: Dasatinib is metabolised by CYP3A4 therefore potential drug

interactions are numerous.

• Concomitant use of dasatinib and medicinal products that induce CYP3A4 (e.g. dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital and St. John's Wort) may significantly reduce exposure to dasatinib.

• Concomitant use of dasatinib and medicinal products that inhibit CYP3A4 (eg: ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, telithromycin) may significantly increase exposure to dasatinib.

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cisapride, pimozide, quinidine or ergot alkaliods). Dasatinib may increase the plasma concentration of other CYP3A4 metabolised drugs (e.g.simvastatin). • Antacids, H2Antagonists and proton pump inhibitors reduce dasatinib exposure.

Antacids should not be within taken 2 hours before or 2 hours after dasatinib dose. H2Antagonists and proton pump inhibitors should be avoided.

schedule.

Post dose vomiting advice: Do not take an extra tablet without consulting doctor. Side effects:

• Oedema

• Gastrointestinal disturbances (nausea, vomiting, diarrhoea, dyspnoea) • Pyrexia

• Haemorrhage • Headache • Rash

Storage: Original packaging, below 30°C.

• Swallow whole (do not crush).

• Caution with driving/operating machinery (possibility of blurred vision/dizziness). • This medication interacts with many other medicines including paracetamol.

Therefore, if you are commencing any new medicines, either prescribed or purchased over the counter please check with the pharmacist.

• Antacids should not be taken within 2 hours before or 2 hours after dasatinib dose (avoid using H2Antagonists and proton pump inhibitors).

(24)

ERLOTINIB

Information for Nursing and Pharmacy Staff:

Available as: Presented as 25mg, 100mg and 150mg tablets Used for: Non-small cell lung cancer, pancreatic cancer

Regimens:

• NSCLC - 150mg od continuously, until disease progression.

• Pancreatic cancer – 100mg od continuously in combination with gemcitabine.

Dose Modifications:

Haematological: Not applicable

Hepatic Impairment: Eliminated by hepatic metabolism and biliary excretion so dose

reduction or interruption should be considered if severe adverse reactions occur. Not recommended in severe hepatic impairment.

Renal Impairment: No dose adjustments appear necessary with mild or moderate renal

impairment. Not recommended in severe renal impairment.

Emetogenic potential: Low/Moderate. Antiemetic not usually required but can be

controlled with metoclopramide if needed.

Safe handling: No special precautions. Pharmaceutical Care Issues:

• Erlotinib must be taken at least one hour before or two hours after the ingestion of food.

• Standard dose is 150mg daily; patients may be dose reduced to either 100mg or 50mg daily depending on severity of side effects.

• Patients taking erlotinib must be supplied with loperamide 2mg prn (max 16mg in 24 hours) and advised to take for diarrhoea as required.

• Provide emollients e.g. Diprobase, Epaderm, E45 or Neutrogena and encourage patients to use regularly to prevent skin dryness.

(25)

• Smoking – Patients should be advised to stop smoking as the plasma

concentrations of erlotinib in smokers compared to non-smokers are significantly reduced.

Drug interactions

Systemic anti-fungals e.g. ketoconazole, itraconazole, voriconazole; ciprofloxacin, protease inhibitors, erythromycin and SSRI’s e.g. fluoxetine, fluvoxamine, rifampicin, phenytoin, carbamazepine, phenobarbital or St John’s Wort.

Proton Pump Inhibitors such as omeprazole (and probably other drugs affecting Gastric pH) will reduce absorption by around 50%. Dose escalation does not compensate.

Missed dose If the scheduled days dosing is missed, advise patient to not to take dose

and contact their named chemotherapy contact.

Post dose vomiting: if the patient vomits after taking an erlotinib tablet, the patient

should NOT take another tablet, until the next dose is due.

Side effects:

• Skin rash (may be severe and warrant treatment delay or dose reduction) • Nausea and vomiting

• Diarrhoea • Fatigue

Storage: Between 10-25°C.

remaining tablets to the pharmacist to be disposed of in a manner appropriate for disposal of cytotoxic & cytostatic medicines.

• Erlotinib should be taken with water 1 hour prior to or 2 hours after food • Avoid strong sunlight or use a good sunscreen SPF 15 or higher

• Patients should be counselled on how to manage most common side effects of skin rash and diarrhoea.

(26)

ETOPOSIDE

Information for Nursing and Pharmacy Staff: Available as: 50mg, 100mg caps

Used for: Ovarian cancer, Lung cancer, Lymphomas, NSGCT/Teratomas, Sarcomas,

Refractory leukaemias

Regimens:

• Ovarian cancer: Rotterdam; Etoposide 50mg od on days 1-15 and days 29-43 of a single 8 week cycle followed by a maintenance dose of 50mg/m2 _{od on days}

1-21 of a 28 day cycle until disease progression.

• Lymphoma: VAPEC B etoposide 100mg/m2_{od on days 1-5 on weeks 3 and 7 of}

a 7 week cycle. • Hodgkins Disease:

- ChlVPP/EVA: etoposide 75mg/m2_{od on days 1-5 of the first cycle (28 days)}

and increased to 100mg/m2_{od on days 1-5 with subsequent cycles if grade 1 or}

less mucositis (with chlorambucil, vincristine, procarbazine, prednisolone, vinblastine and doxorubicin)

- VEPEMB etoposide 60mg/m2_{on days 15 to 19 of 28 day cycle.}

- Recurrent Hodgkins Lymphoma after high dose chemotherapy: Etoposide 100mg daily for 7 to 14 days every 28 days according to degree of

myelosuppression.

• Sarcoma: Etoposide 50mg once daily days 1 to 14 of 21 day cycle. Dose and schedule may vary dependent on tolerance.

• Lung: Carbo/Etop or Cis/Etop consider oral etoposide in place of IV at 240mg/m2

od on days 2 and 3 of a 21 day cycle.

• Teratoma: Palliative treatment – 50-100mg od for 7-21 days with a 7-21 day break between treatment. Dose and schedule dependent on tolerance.

• Refractory leukaemia: 50-100mg od continuous dosing depending on response and toxicity.

(27)

Haematological: Delay treatment until counts recovered. Dose modification necessary. Hepatic impairment: Etoposide is hepatically metabolised, therefore consider dose

reduction. The manufacturer states that etoposide is contraindicated in patients with severe hepatic dysfunction.

Renal impairment: 45% of dose is excreted in the urine. Therefore consider dose

reduction.

Emetogenic potential: Low. Onset 3-8hrs, duration 12hrs

Safe handling: Do not open blister if there is evidence of capsule leakage. Urine and

faeces produced for up to 4 and 7 days, respectively after a dose should be handled wearing protective clothing.

• If patient is unable to swallow capsules, the injection, can be given orally as an alternative. If the injection is to be used as an oral liquid the equivalent dose is 70% of the oral capsule dose. This should be packed into oral syringes in pharmacy. The injection is unpleasant to take, the taste can be masked by advising patient to swallow with orange juice. (NB: this is an unlicensed use of a licensed product.)

• There is an interaction with grapefruit juice which should be avoided 48 hours before and on the day of dose.

Drug interactions

Care needs to be taken when giving etoposide with high doses of ciclosporin as this can lead to a decrease in etoposide clearance.

St John’s Wort – may increase the metabolism of etoposide. Warfarin – monitor INR.

Glucosamine – decreases effect of etoposide. Atovoquone – increases etoposide levels.

(28)

schedule.

consulting doctor.

Side effects:

• Nausea and vomiting • Alopecia (reversible)

• Altered taste / loss of appetite • Hand and food syndrome

Storage: Between 10-25°C.

• To be taken on an empty stomach. • Grapefruit juice should be avoided.

(29)

FLUDARABINE PHOSPHATE

Information for Nursing and Pharmacy Staff: Available as: 10mg film coated tablets

Used for: B-cell Chronic Lymphocytic Leukaemia (CLL), lymphomas

Regimens:

• CLL

- Single agent: 40mg/m2_{od for 5 days every 28 days}

- FC (± R) 24mg/m² once daily on days 1 to 5 (with cyclophosphamide 150mg/m² +/- rituximab)

- LYOS trial (with cyclophosphamide): 40mg/m2_{from days 1-3}

• CLL/lymphoma: FMD (oral) 40mg/m2_{od on days 2 and 3 (with IV Fludarabine}

and Mitoxantrone day 1) every 28 days

Note: Trial regimens may use differing dosing schedules of fludarabine. Round doses to the nearest 10mg (whole tablet).

The oral dose corresponds to 1.6 times the recommended intravenous dose of fludarabine phosphate.

Dose modifications

Haematological: Dose delays or dose reductions may be required following

myelosuppression according to local policy/regimen guidelines. Treatment may be initiated provided granulocytes above 1.0x109_{and platelets above 100x10}9_{, otherwise}

treatment should be postponed for a maximum of 2 weeks, in which case the dose should be reduced.

Hepatic impairment: No data concerning use in patients with hepatic impairment. In this

group of patients use in caution and administer only if the perceived benefits outweigh potential risk.

Renal impairment: Monitor renal function, dose reduction needed with mild renal failure

(CrCl <70 ml/min); contraindicated if CrCl<30ml/min. Between 30-70 ml/min the dose should be reduced by up to 50% and close haematological monitoring should be used to assess for toxicity.

(30)

Emetogenic potential: Low/ transient (30% patients). The reported incidences of

nausea/vomiting are higher with the oral than with the IV formulation.

Safe handling: Should not be handled by pregnant women. Pharmaceutical Care Issues:

• Unless contra-indicated, co-trimoxazole (960mg once or twice a day on Monday, Wednesday and Friday of each week) may be required for PCP prophylaxis, prescribed during treatment and continuing for 1 month after final dose. • Antifungal prophylaxis, oral Fluconazole 50mg od prescribed during treatment

and continuing for 1 month after final dose.

• Allopurinol may be required for tumour lysis in patients with a large tumour burden, for 1-2 cycles only.

• Aciclovir may be considered as prophylaxis or in those patients with a previous history of VZV or HSV reactivation.

• Potentially life-threatening transfusion-related graft-versus-host-disease can occur in patients with severe lymphopenia; patients receiving fludarabine should receive irradiated blood products, effectively eliminating this risk (see guidelines for the use of fludarabine and purine analogues).

Drug interactions: pentostatin, dipyridamole

Missed dose: Should be taken at the same time every treatment day. Missed tablets

should be taken at the earliest opportunity and a compromise reached for subsequent doses. No other dose should be taken within 12 hours of taking the drug. A gap of 18-24 hours should ideally be left between doses.

Post dose vomiting: Do not repeat the dose for that day. Continue with the next dose

on the next day. If vomiting is proving an issue for patients, it is advised they speak to their doctor or nurse regarding use of anti-emetics.

Side effects:

• Myelosupression • Infection

(31)

• Fatigue

• Peripheral neuropathy • Visual disturbances

• Gastrointestinal disturbances (nausea, vomiting, diarrhoea, anorexia) • Stomatitis

• Skin rashes

Storage: No special storage precautions.

• Take on empty stomach or together with food, swallowed whole with water. • Do not chew or break tablets.

• Tablets should not be handled by pregnant women.

• Females of child bearing age must take contraceptive measures during and for at least 6 months after cessation of therapy.

• During and after treatment with fludarabine, vaccination with live vaccines should be avoided.

(32)

HYDROXYCARBAMIDE (formerly known as Hydroxyurea) Information for Nursing and Pharmacy Staff:

Available as: 500mg capsules Used for: CML, AML

Regimens:

• CML: Usual initial dose 1000-2000mg/m2_{continuous until remission then;}

Maintenance 500-1000mg/m2_{continuous (dose is titrated to response)}

• AML: Initial WBC reduction prior to IV chemotherapy up to 6000mg a day. • Also used for Primary thrombocythaemia (PT)/ Essential thrombocythaemia,

sickle cell disease, dose titrated according to response.

Note: capsules only available as 500mg therefore the total weekly dose should be calculated and divided into manageable daily doses i.e. if dose works out 800mg/day (5600mg/week) a dosing regimen may be 500mg on Monday, Wednesday and Friday and 1000mg on other days.

Haematological: Dose delays or dose reductions may be required following

myelosuppression according to local policy/regimen guidelines. If WBC falls below 2.5x109_{or platelet count to <100x10}9_{, therapy should be interrupted.}

Hepatic impairment: No data concerning use in patients with hepatic impairment. In this

group of patients use in caution and administer only if the perceived benefits outweigh potential risk.

Renal impairment: Caution if CrCl<50ml/min. Initial dose reduction may be required and

close haematological monitoring should be used to assess for toxicity.

Emetogenic potential: Low (drug rapidly absorbed)

Safe handling: The contents of capsules should not be inhaled or allowed to come into

contact with the skin or mucous membranes. Urine produced for up to 48 hours after a dose should be handled wearing protective clothing.

(33)

• Not to be used in combination with antiretroviral treatments for HIV. May cause treatment failure and toxicities in HIV patients.

Drug interactions: Didanosine and Stavudine - hepatotoxicity

schedule.

Post dose vomiting: Tell doctor as soon as possible; do not take another capsule

without consulting doctor. Due to low emetogenic potential it is unlikely to be a problem.

Side effects:

• Anaemia

• Bone marrow suppression • Diarrhoea or constipation • Malaise

• Loss of appetite • Mucositis

Storage: Not greater than 25°C

• Take on empty stomach or with food

• The contents of the capsules may be emptied into a glass of water, stirred and taken immediately. Particles floating on the top of water are the inactive bulking agent.

(34)

IDARUBICIN

Information for Nursing and Pharmacy Staff:

Available as: 5mg, 10mg and 25mg capsules Used for: Myeloma, refractory AML.

• Refractory AML: Up to 20mg/m2_{daily for 3 days every 21 days}

• Myeloma: Z-Dex : Idarubicin 10mg/m2_{/day on days 1-4 (with dexamethasone}

40mg/day)

Haematological: Neutrophils should be > 1 x 109/L and platelets > 50 x 109/L prior to

treatment unless low due to bone marrow infiltration. Subsequent courses should be dose reduced depending on the neutrophil nadir (approx day 14).

o ANC < 0.2 x 109_{/l 75 % dose reduction}

o ANC < 0.5 x 109_{/l 55 % dose reduction}

Hepatic Impairment: Reduce dose by 50% if bilirubin 20-50 micromol/L. If bilirubin > 50

micromol/L idarubicin should be avoided.

Renal Impairment: No data available. Dose reduction may be considered in renal

impairment as partially eliminated by this route.

Non-haematological adverse reaction: Treatment may be withheld until the event

improves or resolves. Thereafter, treatment can be resumed at a reduced dose as appropriate depending on the severity of the initial event.

Emetogenic potential: High (80%)

Safe handling: If accidental contact with powder from capsule into the eye, skin or

mucosa, immediately rise with water and seek medical attention.

• Cardiac toxicity is cumulative across members of the anthracycline (doxorubicin, epirubicin, daunorubicin, idarubicin) class of drugs. Patients who have received these agents are at increased risk of toxicity, and should be carefully monitored.

(35)

• Drug Interactions: None significant

Information for patients (counselling points):

schedule.

consulting doctor.

Side effects:

• Alopecia (reversible)

• Gastrointestinal disturbances (nausea, vomiting, diarrhoea) • Cardiac toxicity

• Rash • Fever/chills

• Sore mouth (can appear 3-10 days post treatment)

Storage: In a dry place

Advice for patient:

• Intact capsules should be swallowed whole with water, not sucked, bitten or chewed.

• Take with a light meal.

(36)

IMATINIB

Information for Nursing and Pharmacy Staff: Available as: 100mg & 400mg tablets

Used for: Leukaemias, Gastro Intestinal Stromal Tumour (GIST)

• Leukaemias: 400-800mg od continuously (depending on diagnosis) NB: Doses of 800mg should be given as 400mg bd

• GIST: 400mg od

Haematological: Dose reduction or treatment interruption for severe neutropenia and

thrombocytopenia are recommended.

Hepatic impairment: Imatinib is mainly metabolised through the liver. Patients with mild,

moderate or severe liver dysfunction should be given the minimum recommended dose of 400 mg daily. The dose can be reduced if not tolerated.

Renal impairment: Renal clearance of imatinib is negligible. Manufacturer recommends

that patients with a creatinine clearance of <60ml/min be commenced on a dose of 400mg od. The dose can be reduced if not tolerated, or increased for lack of efficacy.

Non-haematological adverse reaction: Treatment may be withheld until the event has

resolved. Thereafter, treatment can be resumed as appropriate depending on the initial severity of the event.

Emetogenic potential: Low/moderate (10%) Safe handling: No special precautions.

Drug interactions: Imatinib is metabolised by CYP3A4 therefore potential drug

interactions are numerous.

• Concomitant use of imatinib and medicinal products that induce CYP3A4 (e.g. dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital and St. John's Wort) may significantly reduce exposure to imatinib.

(37)

• Concomitant use of imatinib and medicinal products that inhibit CYP3A4 (eg: ketoconazole, itraconazole, erythromycin, clarithromycin) may significantly

increase exposure to imatinib.

• Caution is recommended when administering imatinib with CYP3A4 substrates with a narrow therapeutic window (e.g. ciclosporin or pimozide). Imatinib may increase plasma concentration of other CYP3A4 metabolised drugs (e.g. some benzodiazepines, dihydropyridine calcium channel blockers, certain HMG-CoA reductase inhibitors, i.e. statins, etc.)

• Because warfarin is metabolised by CYP2C9, patients who require anticoagulation should receive low-molecular-weight or standard heparin. • Imatinib has been shown to inhibit paracetamol O-glucuronidation in vitro.

Therefore, caution should be exercised when using imatinib and paracetamol concomitantly, especially with high doses of paracetamol.

• In thyroidectomy patients receiving levothyroxine, the plasma exposure to levothyroxine may be decreased when imatinib is co-administered. The mechanism of the observed interaction is presently unknown.

schedule.

Post dose vomiting advice: Do not take an extra tablet without consulting doctor. Side effects:

• Headache

• Gastrointestinal disturbances (nausea, vomiting, diarrhoea, dyspepsia, abdominal pain)

• Muscle cramps

• Oedema (if water retention severe, tell doctor immediately) • Rash

• Blurred vision

Storage: Original packaging, below 30°C.

(38)

• Take with food and large glass of water to minimise the risk of gastrointestinal irritations.

• Caution with driving/operating machinery (possibility of blurred vision/dizziness). • This medication interacts with many other medicines including paracetamol.

Therefore, if you are commencing any new medicines, either prescribed or purchased over the counter, please check with the pharmacist.

• For patients unable to swallow, the film-coated tablets may be dispersed in a glass of mineral water or apple juice. The required number of tablets should be placed in the appropriate volume of beverage (approximately 50 ml for a 100 mg tablet, and 200 ml for a 400 mg tablet) and stirred with a spoon. The suspension should be administered immediately after complete disintegration of the tablet(s). • Doses of 400 mg or 600 mg should be administered once daily, whereas a daily

dose of 800 mg should be administered as 400 mg twice a day, in the morning and in the evening.

(39)

LAPATINIB

Used for: Advanced or metastatic breast cancer with HER2 over expression, in

combination with capecitabine after prior therapies.

Regimens:

• Breast cancer: 1250mg od continuously (days 1 through 21) in combination with capecitabine 1000mg/m2_{/day bd on days 1 to 14 of a 21 day cycle until treatment}

progression or unacceptable toxicity

Haematological: Low risk. Some reports of thrombocytopenia in patients concurrently

receiving capecitabine. Dose reduction for myleosupression not likely to be necessary.

Hepatic impairment: The manufacturer states that lapatinib should be discontinued in

severe hepatic impairment and patients should not be retreated. They advise caution in mild to moderate hepatic impairment but make no dosage recommendations. However, dose reduction to 750mg of lapatinib daily could be considered in patients with severe hepatic impairment1.

Renal impairment: Renal excretion of lapatinib accounts for < 2%. No dose reduction

necessary.

Cardiac toxicity: Lapatinib should be discontinued in patients with symptoms associated

with decreased LVEf grade 3 or greater or if their LVEF drops below the instituiona lower limit of normal. Lapatinib may be recommenced at a reduced dose of 1000mg od after a minimum of 2 weeks provided that the LVEF has recovered to within normal limits and the patient is asymptomatic.

Emetogenic potential: Low

(40)

• Evaluate left ventricular ejection fraction (LVEF) prior to the initiation of treatment with lapatinib and periodically during therapy.

• Monitor for pulmonary symptoms, as interstitial lung disease and pneumonitis have occurred in patients receiving lapatinib as monotherapy or in combination with chemotherapy. Discontinue lapatinib in patients who develop grade 3 or higher pulmonary symptoms that are indicative of interstitial lung disease/pneumonitis

• No liquid form available therefore unsuitable for those who can’t swallow.

Drug Interactions

If possible, concomitant use of strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) and grapefruit juice should be avoided. If the co-administration of a strong CYP3A4 inhibitor is necessary, the dose of lapatinib should be reduced to 500mg orally once daily. After discontinuation of a strong CYP3A4 inhibitor, a 1-week washout period should be allowed before the dose of lapatinib is increased to the normal dose. If possible, concomitant use of strong CYP3A4 inducers (e.g. dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital, St John's Wort) should be avoided. If the co-administration of a strong CYP3A4 inducer is necessary, the dose of lapatinib should be gradually titrated from 1250mg daily up to 4500 mg/day, as tolerated. After discontinuation of a strong CYP3A4 inducer, the dose of lapatinib should be reduced to the normal dose. Drugs that prolong the QT interval (eg: nilotinib) should be avoided if possible.

Information for patients (counselling points): Missed dose:

Missed doses should not be replace and the dosing should resume with the next scheduled dose.

Post dose vomiting advice:

Tell doctor as soon as possible.

Side effects:

(41)

• Prolonged QT interval

• Interstitial lung disease, dyspnoea, pneumonitis • Anaemia, thrombocytopenia

• Deranged liver function tests

• Diarrhoea, nausea, vomiting, stomatitis • Pain in the back, arms, or legs.

• Palmar plantar erythrodysaethesia • Insomnia

Storage: Do not store above 30°C

• Lapatinib tablets should be taken at least 1 hour before or 1 hour after meals and should not be divided into multiple doses (doses should be taken as one daily dose).

• All courses of lapatinib will be prescribed and dispensed from the hospital. Your own GP will be informed of your treatment but should not prescribe it.

• Avoid grapefruit juice during treatment with lapatinib.

(42)

LENALIDOMIDE

Information for Nursing and Pharmacy Staff:

Available as: 5mg, 10mg, 15mg and 25 mg capsule Used for: Myeloma

• Myeloma: with Dexamethasone; Lenalidomide 25mg daily for 3 weeks (but can be reduced see below). Dexamethasone 40mg od days 1-4, 9-12 and 17-20 for first 4 cycles then days 1-4. Repeated every 4 weeks.

• CLL: 10mg od for 28 days, increase dose by 5mg every 28 days to a maximum of 25mg dependant on tolerability and response.

Haematological: Dose reductions for Neutropenia and Thrombocytopenia - see

Healthcare Professional Information Pack.

Hepatic impairment: Not been studied but mainly renally eliminated unchanged Renal impairment: Dose reduction - see Healthcare Professional Information Pack.

Emetogenic potential: Low to moderate

Safe handling: Do not break or chew the capsules.

• Patients must get a patient info brochure and sign the consent form for the Pregnancy Prevention Programme (PPP)

• Advice to patient and PPP precautions depend on whether the patient is a: 1) Woman of non-childbearing potential

2) Woman of childbearing potential 3) Man

• If woman of childbearing potential must be established on contraception for at least 4 weeks

(43)

• If women of childbearing potential using oral contraceptives check no other medication prescribed that reduces their effectiveness (see BNF).

o If these drugs must be used concurrently, contact prescriber as other reliable methods of contraception are needed.

• Pharmacies must register with Celgene (Pharmacy registration requires that pharmacies perform an annual internal audit of the process)

• A Prescription Authorisation form must be completed and accompany each prescription unless content of the form is incorporated into trust prescription • All healthcare professionals involved in the prescribing or dispensing of

Lenalidomide must confirm that they have read the prescription authorisation form (or prescription)

• Dispensing must take place within 7 days of the prescribing date • Redispensing cannot occur within 13 days of a previous supply

• Dose adjustments for Thrombocytopenia, Neutropenia and Renal impairment (see Healthcare Professional Information Pack)

Drug interactions: Digoxin, Warfarin, Clozapine, Drugs that increase VTE risk

Information for patients (counselling points):

Missed dose:

• Less than 12 hours have passed: take their capsule immediately.

• More than 12 hours have passed: do not take. Take next capsule at the usual time the next day. Inform doctor of any missed doses at next clinic visit.

Post dose vomiting: Contact prescriber as soon as possible who will advise on next

step to take.

Side effects:

• Neutropenia • Thrombocytopenia • DVT/PE

• Patients must contact hospital team urgently if they feel unwell or develop:

(44)

o Gum/nose bleeds or unusual bruising o Chest pain or difficulty breathing o Pain or swelling in their arms or legs o Any other symptom that causes concern

• Patients must contact hospital team urgently if they suspect that they or their

female partner is pregnant • Other common side-effects are:

o muscle cramps or weakness o diarrhoea

o constipation

o nausea (feeling sick) o tiredness

o difficulty sleeping o changes in body weight

Storage: Store at room temperature

• Swallow capsules whole, preferably with water, once a day. Capsules can be taken either with or without food.

• Should be taken at about the same time each day. • Taken for 21 days followed by a 7 day rest

• Do not break or chew the capsules.

Information regarding pregnancy/sexual intercourse: Information for men

• Lenalidomide may be harmful to an unborn baby

• It is not known whether Lenalidomide passes into human semen

• A condom must be used every time they have sexual contact with a woman who is able to become pregnant and who does not use effective contraception

• Even if they have had a vasectomy they must use a condom throughout their Lenalidomide treatment, during any breaks in treatment and for 1 week after stopping treatment

Guidelines for the Safe Use of Oral Draft

Pharmacy Guidelines for the safe use of oral

anti-cancer medicines

Produced on behalf of the Greater Manchester and Cheshire Cancer Network by

the

Network

Oncology

Pharmacy

Group

July

2008

Contents

1. Introduction

2.

Individual Monographs

Bexarotene

Busulfan

Capecitabine

Chlorambucil

Cyclophosphamide

Dasatinib

Erlotinib

Etoposide

Fludarabine

Hydroxycarbamide

Idarubicin

Imatinib

Lapatinib

Lenalidomide

Lomustine

Melphalan

Mercaptopurine

Methotrexate

Mitotane

Procarbazine

Sorafenib

Sunitinib

Tegafur/Uracil

Temozolomide

Thalidomide

Tioguanine

Treosulfan

Tretinoin

Vinorelbine

3.

Dose Modifications

4.

Oral Chemotherapy Regimen Summary

5. Acknowledgements

Introduction

All aspects of practice should be subject to regular audit

BUSULFAN

Information for Nursing and Pharmacy Staff:

Information for patients (counselling points):

IDARUBICIN

Information for Nursing and Pharmacy Staff:

Information for patients (counselling points):

LENALIDOMIDE

Information for Nursing and Pharmacy Staff:

Information for patients (counselling points):