SHARED CARE AGREEMENT for gonadorelin analogues for the treatment of prostate cancer

Shared care agreement (SCA) for gonadorelin analogues time log

Version Date Author Notes Timescale Draft 1 22/12/10 S Murnion For circulation to consultants in Comments to be returned to the acute trusts by the chief [email protected] by pharmacists 23/01/11 SCA to be amended to Completed by S Murnion, 7/2/11 incorporate the consultants feedback Draft 2 S Murnion SCA to be presented at the Document returned by 7/9/2011 for acute trusts D&Ts inclusion in Sept D&T agenda 09/01/13 S Murnion SCA presented at WSH D&T. Document agreed at WSH D&T Committee members made aware that renewed discussions Details of renewed discussions: are taking place with WSH Meeting attended on 8/3/12 at WSH consultant specialists due to the by Dr Jimmy Allen, full urology team, time lag that has occurred since Dr Christopher Browning, Dr Jon the document was previously Ferdinand and Linda Lord. Agreed created and reviewed in that WSH will advise that GPs can 2010/11. prescribe a gonadorelin analogue of their choosing (within licensed indications, so must be Zoladex for neoadjuvant treatment prior to radiotherapy) Draft 3 Dec 2012 L Lord Draft SCA re-sent to WSH Further comments received from Drs urology and oncology teams for Woodward and Rimmer. All comment. Template letters also comments to be returned to included as an appendix. [email protected] .uk by 14/1/13 Draft 4 14/01/13 L Lord All further comments from WSH Document updated and badged specialists incorporated into the WSCCG by L Lord, 14/01/13 draft SCA and now badged for WSCCG L Lord Draft WSCCG SCA to be Document agreed at NHSS D&T presented at the NHS Suffolk 22/1/13 D&T L Lord Draft WSCCG SCA to be Document agreed at WSH D&T presented at WSH D&T 6/2/13 L Lord SCA to be sent to LMC for Document reviewed at LMC meeting consideration on 14/2/13; queries raised by LMC responded to by LL. Document approved by LMC 14/3/13 L Lord Final version of SCA to be Document (version 1) presented and presented at CPG agreed at CPG 8/4/13 Draft 5 12/09/13 L Lord SCA updated to incorporate Document presented at Suffolk CCGs changes to licensed indications D&T 18/09/13 for Decapeptyl SR, further comments from WSH and comments from WSCCG Executive L Lord Updated SCA to be sent to LMC Sent to LMC 19/9/13 L Lord Updated SCA to be presented Presented at WSH D&T 2/10/13 at WSH D&T L Lord Final version of updated SCA to Document (version 2) presented and be presented at CPG agreed at CPG 14/10/13

This shared care agreement should be read in conjunction with the relevant Summary of Product Characteristics

Original template developed by MTRAC in January 2004 for local adaptation and adoption SHARED CARE AGREEMENT for gonadorelin analogues for the treatment of prostate cancer

Shared care agreement for gonadorelin analogues for the treatment of prostate cancer

Gonadorelin analogues: buserelin, goserelin, histrelin, leuprorelin and triptorelin (Note: buserelin is not included in the shared care agreement as continued treatment is administered intranasally)

AREAS OF RESPONSIBILITY FOR THE SHARING OF CARE This shared care agreement outlines suggested ways in which the responsibilities for managing the prescribing of gonadorelin analogues for prostate cancer can be shared between the specialist and general practitioner (GP). GPs are invited to participate. If GPs are not confident to undertake these roles, then they are under no obligation to do so and would have the backing of the Local Medical Committee not to prescribe. In such an event, the total clinical responsibility for the patient for the diagnosed condition remains with the specialist. If a specialist asks the GP to prescribe this drug and the GP does not feel confident to do so they should inform the consultant of this as soon as practicable.

Sharing of care assumes communication between the specialist, GP and patient. The intention to share care should be explained to the patient by the doctor initiating treatment. It is important that patients are consulted about treatment and are in agreement with it. Patients with prostate cancer are under regular specialist follow-up, which provides an opportunity to discuss drug therapy.

The doctor who prescribes the medication legally assumes clinical responsibility for the drug and the consequences of its use.

RESPONSIBILITIES AND ROLES Specialist responsibilities Confirm diagnosis and assess patient’s appropriateness for treatment with gonadorelin analogues Discuss benefits and side effects of treatment with the patient Ask the GP whether he or she is willing to participate in shared care. The request should be sent with the clinic letter, together with an up to date copy of the SCA, while the patient is still under the care of the specialist. If the GP is willing to take over prescribing, the specialist should ensure that the GP is given at least one month’s notice before prescribing is transferred to primary care. The request should be followed up with a phone call if no reply is received Discuss the SCA with the patient, along with an explanation that the GP is not obliged to prescribe and so the patient should not expect that prescribing will transfer to the GP. Similarly, the patient should be given the choice to continue to receive treatment solely from the hospital specialist Initiate treatment for flare-up if required and request GP to prescribe a gonadorelin analogue Regularly review the patient’s condition and communicate promptly with the GP when treatment is changed Monitor response to treatment Advise the GP on the interval of gonadorelin analogue administration (whether it be monthly, three monthly or six monthly), when to stop treatment, and when to consult with the specialist Continue regular review of patient as agreed with GP Ensure clear back-up prescribing support exists for GPs, including direct hospital specialist telephone numbers for advice and support Report adverse events to the MHRA and GP www.mhra.gov.uk/Safetyinformation/Reportingsafetyproblems/index.htm

Primary care prescribers responsibilities Reply to the request for shared care as soon as practicable Take on prescribing if competent to do so and in the best interests of the patient. Prescribing should not be refused on the grounds of cost Prescribe the specified gonadorelin analogue at the recommended dose and duration Report to, and seek advice from, the consultant specialist on any aspect of patient care that is of concern to the GP and may affect treatment Monitor prostate specific antigen (PSA) at regular intervals as advised by the consultant specialist. Refer to the consultant specialist if the patient has symptoms to suggest local, regional or metastatic progression, or if there

This shared care agreement should be read in conjunction with the relevant Summary of Product Characteristics

Original template developed by MTRAC in January 2004 for local adaptation and adoption SHARED CARE AGREEMENT for gonadorelin analogues for the treatment of prostate cancer has been a rise in the PSA. The absolute level and/or rate of rise (doubling time) of PSA as advised by the consultant specialist will indicate when to refer the patient back to secondary care. Prescribe an anti-androgen where requested by the consultant specialist Monitor U&Es and FBC every 6 months. Contact the consultant specialist if potassium or serum creatinine (unless known to have chronic renal failure) are significantly raised and unrelated to diuretic/antihypertensive treatment Refer the patient back to the consultant specialist in the event of deteriorating clinical condition or intolerance occurs Report adverse events to the consultant specialist and MHRA www.mhra.gov.uk/Safetyinformation/Reportingsafetyproblems/index.htm Stop treatment on advice of the consultant specialist

Patient's role Reach a joint, informed decision with the specialist and GP about how on-going prescribing should be managed. This decision should be made at least 1 month before prescribing is transferred to the GP (if GP agrees to the SCA) Report to the consultant specialist or GP: o if he does not have a clear understanding of the treatment plan o any concerns in relation to treatment o any adverse effects

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BACK-UP ADVICE AND SUPPORT FROM WEST SUFFOLK HOSPITAL

Contact details Telephone No. Fax:

Specialist doctor Urology Mr John McLoughlin 01284 712549 01284 712549 Mr James Allan 01284 713160 01284 713160 Miss Georgina Wilson 01284 713520 01284 713732

Oncology Dr Cathryn Woodward 01284 713166 01284 713571 Dr Yvonne Rimmer 01284 712993 01284 713571

Specialist nurse Urology Mrs Jane Thacker 01284 712735 01284 712806

Oncology Mr Fred Tuck 01284 713212 01284 713571

Hospital pharmacy department 01284 713232 01284 713918

Medicines information 01284 713109

SUPPORTING INFORMATION Therapeutic review

Dosage and Administration

Prostate cancer: Patients suitable for hormonal manipulation may receive a depot injection every 28 days, or the longer acting depot every 3 months or 6 months as specified by the consultant specialist. Treatment should always be initiated using a 28-day injection to check for tolerance. For stable patients having long term therapy the 3 monthly or 6 monthly injection is usually recommended. The monthly/28-day gonadorelin analogue preparation is usually recommended for use prior to and with radiotherapy, as the 12-weekly/3-monthly and 6-monthly preparation may result in patients receiving androgen suppression for months beyond the intended period thereby resulting in unnecessary side-effects. Where the agent is to be continued longer-term as adjuvant therapy, it is quite reasonable for the patient to be converted to the longer depot injection, but this should be clearly specified by the consultant specialist. Note that in some cases secondary care will recommend conversion to high dose (150mg) adjuvant oral bicalutamide in view of the superior side-effect profile.

This shared care agreement should be read in conjunction with the relevant Summary of Product Characteristics

Original template developed by MTRAC in January 2004 for local adaptation and adoption SHARED CARE AGREEMENT for gonadorelin analogues for the treatment of prostate cancer

No dosage adjustment is necessary for patients with renal or hepatic impairment, or in the elderly.

Table 1

Table showing summary of recommended treatments

Gonadorelin analogue Bicalutamide Letter from advised if specialist to Cost effective gonadorelin GP and licensed Duration of analogue not (see Indication Treatment details choice* treatment tolerated? appendix 1) Hormone therapy alone. Start with monthly Triptorelin Long term Yes Letter A Locally advanced, non- treatment, then (Decapeptyl® metastatic prostate switch to 3-monthly SR)** cancer, as an alternative treatment if tolerated to surgical castration With radiotherapy (RT): Neoadjuvant and Goserelin Usually 5-6 No Letter B Low/intermediate risk concurrent monthly (Zoladex®) months in total prostate cancer for radical preparation for at RT least 3 injections (low risk at clinician’s before the RT discretion) commences, then during the RT*** With RT: Neoadjuvant, Goserelin At least 3 Before RT - No Letter C High risk prostate cancer concurrent and (Zoladex®) for months before After RT - Yes for RT adjuvant therapy. neoadjuvant RT and during Start with monthly treatment and RT, then treatment, then during RT. continuing for switch to 3-monthly Switch to a total of 3 treatment after RT if triptorelin years unless tolerated (Decapeptyl® not tolerated SR)** after RT Relapsed or metastatic Start with monthly Triptorelin Long term Yes Letter A disease or unfit for radical treatment, then (Decapeptyl® RT switch to 3-monthly SR)** treatment if tolerated

Adjuvant treatment to Rarely used. If PSA Triptorelin Long term Yes Letter A radical prostatectomy in remains elevated (Decapeptyl® patients with locally post surgery, RT SR)** advanced prostate cancer offered. Adjuvant at high risk of disease therapy only progression prescribed if patient fails both surgery and RT or cannot receive RT. If gonadorelin analogue indicated, start with monthly treatment, then switch to 3-monthly treatment if tolerated * Triptorelin (Decapeptyl®SR) is generally the cost effective choice, and is now licensed for all above indications. However, it is not currently the preferred choice of West Suffolk Hospital specialists in the neoadjuvant setting for men who are having potentially curative treatment ** If there is a prostate specific antigen (PSA) rise on Decapeptyl® SR, or after a switch from Zoladex® to Decapeptyl® SR, then the testosterone levels should be measured to ensure adequate suppression is occurring *** The 3-monthly preparations are not recommended because of the time taken for resolution of unwanted side-effects

This shared care agreement should be read in conjunction with the relevant Summary of Product Characteristics

Original template developed by MTRAC in January 2004 for local adaptation and adoption SHARED CARE AGREEMENT for gonadorelin analogues for the treatment of prostate cancer

Intermittent Hormones

Intermittent hormone therapy is increasingly advocated in the management of prostate cancer where long term hormones are indicated, usually only in stable patients. In this situation, patients may be on monthly, 3- monthly or 6-monthly depot injections as it is not possible to determine which patients are suitable for intermittent therapy at the outset. After a minimum of EIGHT months of hormonal treatment, patients are monitored off therapy until such time as the PSA and/or testosterone reaches a predetermined level (as agreed with secondary care) when the depot injection should be re-instituted. It is vital that the potential flare response is averted with anti-androgens at the outset of EACH eight month cycle. The PSA should be monitored at THREE monthly periods whilst the patient is OFF hormonal therapy.

Letter from specialist to GP Letter D applies to intermittent therapy (see appendix 1)

Contraindications

Known hypersensitivity to the active substance, to other gonadorelin analogues, or to any of the excipients of this product. Gonadorelin analogues are not indicated for use in children, as safety and efficacy have not been established in this group of patients.

Cautions

The use of gonadorelin analogues in men at particular risk of developing ureteric obstruction or spinal cord compression should be considered carefully, and the patients monitored closely during the first month of therapy. Consideration should be given to the initial use of an anti-androgen at the start of gonadorelin analogue therapy since this has been reported to prevent the possible sequelae of the initial rise in serum testosterone. Bicalutamide 50mg once daily is the preferred anti-androgen to be utilized for a minimum of THREE days prior to the first depot implant and preferably TWO weeks prior and certainly for TWO weeks after the first depot injection only unless secondary care have advised continuation of the anti-androgen to achieve sustained total androgen blockade. Cyproterone acetate 100mg TDS may also be used but is absolutely contra-indicated in patients with a history of liver disease.

If spinal cord compression or renal impairment due to ureteric obstruction are present or develop, specific standard treatment of these complications should be instituted.

Side Effects

General Rare incidences of hypersensitivity reactions, which may include some manifestations of anaphylaxis, have been reported. If this occurs treatment should be stopped. Arthralgia has been reported. Non-specific paraesthesias have been reported. Skin rashes have been reported which are generally mild, often regressing without discontinuation of therapy. Changes in blood pressure, manifest as hypotension or hypertension, have been occasionally observed in patients administered goserelin. The changes are usually transient, resolving either during continued therapy or after cessation of therapy with goserelin. Rarely, such changes have been sufficient to require medical intervention including withdrawal of treatment from goserelin. As with other agents in this class, very rare cases of pituitary apoplexy have been reported following initial administration. Occasional local reactions include mild bruising at the subcutaneous injection site.

Pharmacological effects in men include hot flushes and sweating and a decrease in libido, seldom requiring withdrawal of therapy. Breast swelling and tenderness have been noted infrequently. Initially, prostate cancer patients may experience a temporary increase in bone pain, which can be managed symptomatically. Isolated cases of ureteric obstruction and spinal cord compression have been recorded. The use of gonadorelin analogues in men may cause a loss of bone mineral density.

This shared care agreement should be read in conjunction with the relevant Summary of Product Characteristics

Original template developed by MTRAC in January 2004 for local adaptation and adoption SHARED CARE AGREEMENT for gonadorelin analogues for the treatment of prostate cancer

All suspected reactions (including those considered not to be serious and even where the causal link is uncertain) should be reported to the MHRA www.mhra.gov.uk/Safetyinformation/Reportingsafetyproblems/index.htm

Monitoring undertaken by the specialist in prostate cancer

Clinical response to therapy, e.g. bone pain and performance status Baseline FBC,U&Es, LFTs, and PSA Radiology and radioisotopes. MRI scans of abdomen and pelvis and bone scans may be performed. These tests will be performed at diagnosis if appropriate and subsequently if indicated by specialists

Drug Interactions None known

Costs

Gonadorelin analogue Strength Cost per Frequency of Cost per vial* administration 4 weeks* Goserelin (Zoladex®) 3.6mg £65 4 weekly £65

Leuprorelin (Prostap® SR DCS) 3.75mg £75.24 monthly £69

Triptorelin (Decapeptyl® SR) 3mg £69 4 weekly £69

Triptorelin (Gonapeptyl Depot®) 3.75mg £81.69 4 weekly £82

Goserelin (Zoladex® LA) 10.8mg £235 12 weekly £78

Leuprorelin (Prostap® 3 DCS) 11.25mg £225.72 3 monthly £69

Triptorelin (Decapeptyl® SR) 11.25mg £207 3 monthly £64

Triptorelin (Decapeptyl® SR) 22.5mg £414 6 monthly £64

Histrelin (Vantas®) 50mg £990 Annually £76

*Prices from BNF 65, March 2013

This shared care agreement should be read in conjunction with the relevant Summary of Product Characteristics

Original template developed by MTRAC in January 2004 for local adaptation and adoption SHARED CARE AGREEMENT for gonadorelin analogues for the treatment of prostate cancer

Appendix 1

Template letters from secondary care specialists to primary care prescribers

Table 1 shows the indications that apply to each of the following letters

Letter A We hope that you will consider prescribing and administering a gonadorelin analogue (lutenising hormone- releasing hormone agonist, LHRHa) on the basis of participation within the shared care agreement. If you have any concerns with this arrangement, then please contact us as soon as possible.

The Clinical Commissioning Group’s (CCG’s) preference for patients on hormonal therapy is triptorelin (Decapeptyl® SR). This is based on cost-effectiveness. We are happy to support this on the basis that there is no evidence of difference in efficacy between the gonadorelin analogues. Patients who are receiving hormonal therapy prior to radiotherapy are not included.

Bicalutamide and 3-monthly gonadorelin analogue therapy (starting with a 4 week trial)

We have dispensed a 28 day course of bicalutamide 150mg daily from clinic today. Please prescribe and administer the following gonadorelin analogue (LHRHa) within the next 7-14 days:

Intramuscular injection triptorelin 3mg (Decapeptyl® SR) This is the CCG’s preferred choice for initiation of treatment.

After 4 weeks, if triptorelin is tolerated, subsequent injections should then be provided every 3 months:

Intramuscular injection triptorelin 11.25mg (Decapeptyl® SR) every 3 months This is the CCG’s preferred choice for on-going treatment.

We have asked the patient to contact your surgery to arrange this with you or the practice nurse. The patient is aware that the full course of bicalutamide must be completed (at least 7 days before the LHRAa and 14 days after the LHRHa is administered to avoid tumour flare).

We will review the patient in clinic in 3-4 months with a repeat PSA. There is an option to offer patients a 6- monthly Decapeptyl® SR injection (22.5mg dose) at the 3-monthly review when PSA is stabilised.

Letter B We hope that you will consider prescribing and administering a gonadorelin analogue (lutenising hormone- releasing hormone agonist, LHRHa) on the basis of participation within the shared care agreement. If you have any concerns with this arrangement, then please contact us as soon as possible.

Bicalutamide and 4-weekly gonadorelin analogue therapy

We have dispensed a 28 day course of bicalutamide 150mg daily from clinic today. Please prescribe and administer the following gonadorelin analogue (LHRHa) within the next 7-14 days:

Subcutaneous injection goserelin 3.6mg implant (Zoladex®)

We have asked the patient to contact your surgery to arrange this with you or the practice nurse. The patient is aware that the full course of bicalutamide must be completed (at least 7 days before the LHRAa and 14 days after the LHRHa is administered to avoid tumour flare).

Subsequent injections of goserelin 3.6mg implant (Zoladex®) will then be due every four weeks. Please prescribe and administer these for approximately five to six months. We will review the patient in clinic in 3-4 months with a repeat PSA and will advise when treatment with a gonadorelin analogue should be stopped.

This shared care agreement should be read in conjunction with the relevant Summary of Product Characteristics

Original template developed by MTRAC in January 2004 for local adaptation and adoption SHARED CARE AGREEMENT for gonadorelin analogues for the treatment of prostate cancer

Letter C We hope that you will consider prescribing and administering a gonadorelin analogue (lutenising hormone- releasing hormone agonist, LHRHa) on the basis of participation within the shared care agreement. If you have any concerns with this arrangement, then please contact us as soon as possible.

Bicalutamide and 4-weekly gonadorelin analogue therapy

We have dispensed a 28 day course of bicalutamide 150mg daily from clinic today. Please prescribe and administer the following gonadorelin analogue (LHRHa) within the next 7-14 days:

Subcutaneous injection goserelin 3.6mg implant (Zoladex®)

We have asked the patient to contact your team to arrange this with you or the practice nurse. The patient is aware that the full course of bicalutamide must be completed (at least 7 days before the LHRAa and 14 days after the LHRHa is administered to avoid tumour flare).

This patient will also be receiving radiotherapy. Please prescribe and administer subsequent subcutaneous injections of goserelin 3.6mg implant (Zoladex®) every four weeks until the patient has completed his radiotherapy treatment, i.e. for six to eight weeks. We will advise when the radiotherapy has been completed. Following radiotherapy, LHRAa treatment should continue, but 3-monthly or 6-monthly LHRHa injections may be more convenient as the treatment is indicated for a total of three years, if tolerated.

The Clinical Commissioning Group’s preference for patients on longer term hormonal therapy is triptorelin (Decapeptyl® SR). This is based on cost-effectiveness. We are happy to support this on the basis that there is no evidence of difference in efficacy between the gonadorelin analogues.

Gonadorelin analogue therapy after radiotherapy

Intramuscular injection triptorelin 3mg (Decapeptyl® SR), commencing 4 weeks after the last dose of goserelin 3.6mg implant (Zoladex®). This is the CCG’s preferred choice for initiation of longer term treatment after radiotherapy.

After 4 weeks, if triptorelin is tolerated, subsequent injections should then be provided every 3 months:

Intramuscular injection triptorelin 11.25mg (Decapeptyl® SR) every 3 months This is the CCG’s preferred choice for on-going treatment.

6-monthly injections of triptorelin 22.5mg (Decapeptyl® SR) are also an option for on-going treatment.

Letter D We hope that you will consider prescribing and administering a gonadorelin analogue (lutenising hormone- releasing hormone agonist, LHRHa) on the basis of participation within the shared care agreement. If you have any concerns with this arrangement, then please contact us as soon as possible.

The Clinical Commissioning Group’s preference for patients on hormonal therapy alone is triptorelin (Decapeptyl® SR). This is based on cost-effectiveness. We are happy to support this on the basis that there is no evidence of difference in efficacy between the gonadorelin analogues. Patients who are receiving hormonal therapy prior to radiotherapy are not included.

Bicalutamide and monthly gonadorelin analogue therapy

We have dispensed a 28 day course of bicalutamide 150mg daily from clinic today. Please prescribe and administer the following gonadorelin analogue (LHRHa) within the next 7-14 days:

Intramuscular injection triptorelin 3mg (Decapeptyl® SR) This is the CCG’s preferred choice.

We have asked the patient to contact your surgery to arrange this with you or the practice nurse. The patient is aware that the full course of bicalutamide must be completed (at least 7 days before the LHRAa and 14 days after the LHRHa is administered to avoid tumour flare).

This shared care agreement should be read in conjunction with the relevant Summary of Product Characteristics

Original template developed by MTRAC in January 2004 for local adaptation and adoption SHARED CARE AGREEMENT for gonadorelin analogues for the treatment of prostate cancer

This patient is receiving intermittent therapy. The likely duration of treatment with monthly depot injections is eight months, then the patient will be monitored off therapy until such time as the PSA and/or testosterone reaches a pre-determined level, when the depot injection should be re-instituted. We will advise when the depot injections should be stopped and when they should be re-started.

References Summaries of Product Characteristics http://www.medicines.org.uk/EMC/searchresults.aspx?term=goserelin&searchtype=QuickSearch http://www.medicines.org.uk/EMC/searchresults.aspx?term=histrelin&searchtype=QuickSearch http://www.medicines.org.uk/EMC/searchresults.aspx?term=leuprorelin&searchtype=QuickSearch http://www.medicines.org.uk/EMC/searchresults.aspx?term=triptorelin&searchtype=QuickSearch

Produced by: Sheila Murnion, Interface Pharmacist, NHS Suffolk 21/12/2010 Updated by: Linda Lord, Head of Medicines Management, WSCCG 14/01/2013 and 12/09/13 Review date: September 2015

This shared care agreement should be read in conjunction with the relevant Summary of Product Characteristics

Original template developed by MTRAC in January 2004 for local adaptation and adoption