CONTRATO DE SEGURO
10 3 MERCANTILIDAD DEL CONTRATO.
10.8 EL PRINCIPIO DE EXQUISTA BUENA FE.
23. Gefitinib-250 (Iressa) (CTIS 1653)
Gefitinib 250mg Oral once a day Continuous treatment Interval between cycles: Continuous treatment, repeat tests every 30 days initially, once
stabilised repeat tests every 2-3 months
Number of cycles: In line with NICE (TA192) for 1st line treatment of patients with locally advanced or metastatic non small cell lung cancer if the patient tests
positive for the epidermal growth factor receptor tyrosine kinase (EGFR-TK) AND gefitinib is
provided at the fixed price under the patient access scheme (see additional information;
Tests before starting course of chemo FBC, U&Es, LFTs,
Tests to OK/Confirm each cycle of chemo: FBC, U&Es, LFTs initially with each cycle once stabilised tests every 2-3 cycle Supportive drugs with each cycle: No routine medications
Patient information: Chemotherapy treatment booklet (local information/Macmillan) Your chemotherapy record (NWLCN red book)
NWLCN Chemotherapy alert card
Macmillan drug specific information sheets/information prescriptions as appropriate
NWLCN Neutropenia DVD Additional information (SPC):
See SPC for list of drug interactions.
Swallow whole with or without food about the same time every day. See SPC for details of dispersing tablets in water.
If a dose of gefitinib is missed;
If it is more than 12 hours until the next dose, then it should be taken as soon as the patient remembers.
If it is less than 12 hours to the next dose, then the patient should not take the missed dose.
Patients should NOT take double dose (two doses at the same time) to make up for the forgotten dose.
NICE Information on patient access scheme
The manufacturer has agreed with the Dept of Health a patient access scheme in which gefitinib for 1st line treatment of NSCLC will be available at a single fixed cost of £12,200 per patient irrespective of the duration of treatment. The manufacturer will not invoice the NHS until the 3rd monthly pack of gefitinib is supplied. This means that patients who need less than 3 months of treatment will not incur a charge. The Dept of Health considered that this patient access scheme does not constitute an excessive administrative burden on the NHS.
Each NHS patient must have
funding approved by the PCT before starting treatment
been registered and accepted by the manufacturer for the patient access scheme (SPA). This is done using the single payment access scheme patient registration form (Form 1) which is completed and sent to pharmacy.
a SPA order form completed for each cycle (pharmacy to complete)
only one cycle can be ordered at a time. Manufacturers guarantee that orders received by 12pm will be delivered the following day.
Reference: IPASS Study
IPASS data supports 1st line use in chemo naïve, never or light ex smokers, with adenocarcinoma, PS0-2, stage IIIB or IV
Dose modifications: see table below
Side effect: Gefitinib (Iressa) Dose Modification(SPC)
Haematology (SPC) Neutrophils Platelets x109/L x109/L 1.5 100 <1.5 <100 Full dose
Discuss with consultant Renal function (SPC)
Crcl >20mls/min
≤20mls/min Full dose Do not give regimen. Discuss with consultant Hepatic function (SPC)
Side effect: Gefitinib (Iressa) Dose Modification(SPC)
Moderate to severe hepatic impairment (child Pugh B or C) due to cirrhosis have increased plasma concentration of gefitinib
Elevated Aspartate Transaminases (AST), alkaline phosphate or bilirubin due to liver metastases did NOT have increase plasma levels of gefitinib.
Monitor closely for adverse events.
No dose modification necessary.
Diarrhoea (SPC)
Patients with poorly tolerated diarrhoea adverse reactions, 1st occurrence
Repeat recurrence after break in therapy
Patients with poorly tolerated diarrhoea adverse
reactions may be successfully managed by providing a brief (up to 14 days) therapy interruption followed by reinstatement of the 250mg dose
If unable to tolerate treatment after a therapy interruption, gefitinib should be discontinued. Skin Reactions (SPC)
Patients with poorly tolerated skin adverse reactions, 1st occurrence
Repeat recurrence after break in therapy
Patients with poorly tolerated skin adverse reactions may be successfully managed by providing a brief (up to 14 days) therapy interruption followed by
reinstatement of the 250mg dose
If unable to tolerate treatment after a therapy interruption, gefitinib should be discontinued.
Patients possessing EGFR Activating Mutations
Relapse
24. Erlotinib-150 (Tarceva) (CTIS 1174)
For additional ‘Private Care’ unless local NDP approved/PCT agreement to fund
Erlotinib 150mg Oral once a day continuous treatment Take at least 1 hour before or 2 hours after food
Interval between cycles: Continuous treatment, repeat tests every 30 days initially, once stabilised repeat tests every 2-3 months
Number of cycles: For additional ‘Private Care’ unless
local NDP approved/PCT agreement to fund
for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one
prior chemotherapy regimen (SPC) Treat until progression. Tests before starting course of chemo Baseline Chest X-Ray, FBC, U&Es, LFTs, Tests to OK/Confirm each cycle of chemo: Monitor for symptoms and biochemical
signs of dehydration
FBC, U&Es, LFTs initially with each cycle
once stabilised tests every 2-3 cycles Supportive drugs with each cycle: Consider prophylactic use of emollient
Sunscreen SPF15 or higher
Patient information: Chemotherapy treatment booklet (local information/Macmillan) Your chemotherapy record (NWLCN red book)
NWLCN Chemotherapy alert card
Macmillan drug specific information sheets /information prescriptions as appropriate
NWLCN Neutropenia DVD Additional information:
Plasma concentrations of erlotinib are reduced in patients who smoke.
High stomach pH can reduce bioavailability of erlotinib by up to 50%. Do not administer PPI with erlotinib. Roche recommend ranitidine 150mg BD, Erlotinib should be taken 2 hours before or 10 hours after ranitidine. See SPC for information about other drug interactions. See SPC for drug interactions with erlotinib.
NPSA Information on safety concern Summary (issued June 2009)
Patients receiving tarceva/erlotinib are at increased risk of developing gastrointestinal perforations.
Patients receiving concomitant anti-angiogenic agents, corticosteroids, NSAIDs and/or taxane based chemotherapy, or who have a prior history of peptic ulceration or diverticular disease are at increased risk.
Tarceva/erlotinib should be permanently discontinued in patients who develop gastrointestinal perforation.
Dose modifications: See table below
SPC states where dose adjustment is required, the dose should be reduced in 50mg steps.
Reference: Erlotinib SPC
Roche table of UK Expert Consensus for management of erlotinib- associated skin toxicity (TARC00595 July 2010)
Table: Erlotinib
Side effect: Erlotinib Dose Modification(SPC)
Haematology (SPC) Neutrophils Platelets x109/L x109/L 1.5 100 <1.5 <100 Full dose
Do not give, discuss with consultant Renal function (SPC)
Approx 9% renal elimination
Crcl (EDTA) 30mls/min
<30mls/min Full dose Discuss with consultant. No data below 15mls/min Hepatic function (SPC)
90% excreted as by hepatic metabolism and biliary excretion
Mild/moderate hepatic impairment Severe hepatic impairment AST/SGOT and ALT/SGPT ≥ 5 x ULN
Caution; Dose reduction or interruption should be considered if severe adverse reactions occur Do not give, not been studied
Do not give, not been studied Rash
Occurs in approx 75% of patients, (median time to onset 8 days). In general, rash manifests as a mild or moderate erythematous and
papulopustular rash, which may occur or worsen in sun exposed areas.
Patients who are exposed to sun should wear protective clothing, and/or use sun screen
Side effect: Erlotinib Dose Modification(SPC)
Mild skin reaction
Usually localised, minimally symptomatic, no impact on activities of daily life (ADL), no ulceration, weeping or infection
Moderate skin reaction
Localised or generalised, mild symptoms (eg pruritus, tenderness), minimal impact on ADL, no ulceration, weeping or infection
Severe skin reaction
Usually generalised, severe symptoms (eg pruritus, tenderness), significant impact on ADL, ulceration, weeping or infection present
Roche table of UK Expert Consensus for
management of erlotinib-associated skin toxicity
o Continue erlotinib at current dose and monitor for change in severity.
o No treatment or if necessary consider topical hydrocortisone 1% or 2.5% (pulsed treatment) and/or topical clindamycin 1%
o Reassess after 2 weeks (either by healthcare professional or patient self report); if reactions worsen or do not improve proceed to advice for moderate reactions
Continue erlotinib at current dose and monitor for change in severity. Continue treatment of skin reaction with following
Topical clindamycin 1% PLUS hydrocortisone 2.5% cream PLUS oxytetracycline 500mg oral BD
Reassess after 2 weeks (either by healthcare professional or patient self report); if reactions worsen or do not improve proceed to advice for severe reactions
Reduce dose of erlotinib and monitor for change in severity. Continue treatment of skin reaction with following
Topical clindamycin 1% PLUS hydrocortisone 2.5% cream PLUS oxytetracycline 500mg oral BD PLUS prednisolone 25mg oral for 7 days, then reduce by 5mg/day over 5 days
Reassess after 2 weeks; if reactions worsen dose interruption or discontinuation may be necessary
Diarrhoea (SPC)
Occurs in approx 50% of patients, median time to onset 12days
Moderate/severe diarrhoea
Severe or persistent diarrhoea, nausea, anorexia or vomiting associated with dehydration
Treat with loperamide
In some cases dose reduction may be necessary. Clinical studies reduced doses in 50mg steps. Dose reduction in 25mg steps has not been investigated STOP erlotinib and take appropriate measures to treat dehydration. See SPC.
Gastrointestinal perforation Permanently Discontinue erlotinib Interstitial lung disease (ILD)-like events
(SPC)
ILD-like events, including fatalities, have
Side effect: Erlotinib Dose Modification(SPC)
receiving erlotinib. dyspnoea, cough and fever, interrupt erlotinib therapy pending diagnostic evaluation.
If ILD is diagnosed discontinue erlotinib.