List of Natioanl Advisory Group Recommendations Since April 2002 s2

SMC Advice - Formulary Decisions August-September 2014

Scottish Medicines Consortium Recommendations Date Product/Manufacturer SMC Advice Decision of ADTC Rationale August simeprevir 150mg hard capsules (Olysio ®) simeprevir (Olysio®) is accepted for use within NHS Scotland. Included on the Fife SMC simeprevir (Olysio) 2014 Janssen Formulary. 988/14 Indication under review: in combination with other medicinal products for the Simeprevir is to be used in combination with other treatment of chronic hepatitis C in adult patients. Hospital specialist use only. medicinal products for the treatment of chronic hepatitis C (CHC) in adult patients In four double-blind phase III studies, when given as part of triple regimen in Boceprevir to be removed combination with peginterferon-alfa and ribavirin, simeprevir was superior to from the Fife Formulary. Comparator Medicines: placebo in treatment naive and prior relapsed patients and non-inferior to The standard treatment for genotype 1 HCV is another direct acting antiviral drug in treatment experienced patients with peginterferon and weight-based ribavirin plus a genotype 1 hepatitis C virus. telaprevir, boceprevir or sofosbuvir with RGT determining treatment duration in certain groups (24 to 48 weeks). For patients with genotype 4, standard treatment is with PR ± sofusbuvir. The only peginterferon-free comparator regimen is sofosbuvir plus ribavirin.

August fingolimod, 0.5mg, hard capsules (Gilenya®) fingolimod (Gilenya®) is accepted for restricted use within NHS Scotland. Included on the Fife SMC fingolimod 2014 Novartis Pharmaceuticals UK Formulary for the treatment of (Gilenya) 992/14 Indication under review: as a single disease modifying therapy in highly patients with rapidly evolving Fingolimod is indicated as a single disease active relapsing remitting multiple sclerosis for the following adult patient severe relapsing remitting modifying therapy in highly active relapsing groups: multiple sclerosis. remitting multiple sclerosis for the following adult patient groups: - Patients with high disease activity despite treatment with at least one disease Alternative to natalizumab. modifying therapy. - Patients with high disease activity despite or Hospital use only. treatment with at least one disease modifying - Patients with rapidly evolving severe relapsing remitting multiple sclerosis therapy. defined by two or more disabling relapses in one year, and with one or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 These patients may be defined as those who have lesion load as compared to a previous recent MRI. failed to respond to a full and adequate course (normally at least one year of treatment) of beta- SMC restriction: For use in patients with rapidly evolving severe relapsing interferon. Patients should have had at least one remitting multiple sclerosis. SMC has previously published advice concerning relapse in the previous year while on therapy, and patients with high disease activity despite treatment with beta-interferon but not have at least nine T2-hyperintense lesions in other disease modifying therapies. cranial magnetic resonance imaging (MRI) or at least one Gadolinium-enhancing lesion. A “non- Fingolimod reduced the annualised relapse rate significantly more than a beta- responder” could also be defined as a patient with interferon in patients with clinically active relapsing remitting multiple sclerosis. an unchanged or increased relapse rate or ongoing severe relapses, as compared to the This SMC advice takes account of the benefits of a Patient Access Scheme previous year. (PAS) that improves the cost-effectiveness of fingolimod. This advice is contingent upon the continuing availability of the patient access scheme in or NHS Scotland or a list price that is equivalent or lower. - Patients with rapidly evolving severe relapsing remitting multiple sclerosis defined by two or more disabling relapses in one year, and with one or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI. 1 of 7 SMC Advice - Formulary Decisions August-September 2014

Comparator Medicines: There are a number of medicines licensed for the treatment of RRMS, including interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate and natalizumab. Of these, only natalizumab is specifically licensed for the treatment of RES RRMS, as defined above, and it has been accepted for use within NHS Scotland for this indication. Dimethyl fumarate has only recently been accepted for use within NHS Scotland, so was not considered a comparator in the economic analysis.

August alogliptin, 25mg, 12.5mg, 6.25mg, film-coated alogliptin (Vipidia®) is accepted for restricted use within NHS Scotland. Not included on the Fife Not preferred. 2014 tablets (Vipidia®) Formulary as clinicians do not 937/14 Takeda Pharma A/S Indication under review: For adults aged 18 years and older with type 2 support formulary inclusion. Fife Formulary choice diabetes mellitus to improve glycaemic control in combination with other gliptins are – In adults aged 18 years and older with type 2 glucose lowering medicinal products including insulin, when these, together 1st choice sitagliptin diabetes mellitus to improve glycaemic control in with diet and exercise, do not provide adequate glycaemic control. 2nd choice saxagliptin combination with other glucose lowering medicinal products including insulin, when these, together SMC restriction: dual therapy http://www.fifeadtc.scot. with diet and exercise, do not provide adequate  In combination with metformin, when metformin alone, together with diet nhs.uk/formulary/6- glycaemic control and exercise does not provide adequate glycaemic control in patients for endocrine.aspx whom the addition of a sulfonylurea is inappropriate. Comparator Medicines:  In combination with a sulfonylurea, when sulfonylurea alone, together with SMC alogliptin (Vipidia) The DPP-4 inhibitors (linagliptin, saxagliptin, diet and exercise does not provide adequate glycaemic control in patients sitagliptin, and vildagliptin) have marketing for whom the addition of metformin is inappropriate due to contra- authorisations for the indication under review, with indications or intolerance. the exception of linagliptin which is not licensed for use as dual therapy in combination with a Treatment with alogliptin reduces glycosylated haemoglobin, HbA1c, sulfonylurea. significantly more than placebo when used in combination with metformin or sulfonylurea.

SMC cannot recommend the use of alogliptin as single therapy or triple therapy as the company’s submission related only to its use in dual therapy August golimumab, 50mg and 100mg solution for golimumab (Simponi®) is not recommended for use within NHS Scotland. Not recommended for the Lack of robust economic 2014 injection (Simponi®) treatment of moderately to analysis. 946/13 Merck Sharp & Dohme Ltd Indication under review: treatment of moderately to severely active ulcerative severely active ulcerative colitis in adult patients who have had an inadequate response to conventional colitis. SMC golimumab Treatment of moderately to severely active therapy including corticosteroids and 6-mercaptopurine or azathioprine, or who (Simponi) ulcerative colitis in adult patients who have had an are intolerant to or have medical contraindications for such therapies. Requires submission and inadequate response to conventional therapy approval of an IPTR for this including corticosteroids and 6-mercaptopurine (6- In a study of adults with moderately to severely active ulcerative colitis who indication. MP) or azathioprine (AZA), or who are intolerant had inadequate response or intolerance to conventional therapy, a greater to or have medical contraindications for such proportion of patients given golimumab induction therapy achieved a clinical therapies. response compared with placebo. In patients who had a clinical response to golimumab induction, golimumab maintenance treatment was associated with Comparator Medicines: a greater clinical response rate over 54 weeks, compared with placebo. Other biologic agents with marketing authorisations for the treatment of UC in patients The company did not present a sufficiently robust economic analysis to gain with intolerance or refractory to conventional acceptance by SMC. 2 of 7 SMC Advice - Formulary Decisions August-September 2014

therapy include the TNFα inhibitors infliximab and adalimumab. In NHS Scotland, SMC has not recommended these agents for use in adults.

August tetracaine / lidocaine (Pliaglis 70 mg/g + 70 Not recommended. Non-submission 2014 mg/g cream®) ADVICE: in the absence of a submission from the holder of the marketing 1000/14 Galderma (UK) Ltd authorisation Requires submission and SMC tetracaine lidocaine (No: 956/14) approval of an IPTR. (Pliaglis) tetracaine / lidocaine (Pliaglis®) is not recommended for use within NHS Scotland.

Indication under review: local dermal anaesthesia on intact skin prior to dermatological procedures in adults

The holder of the marketing authorisation has not made a submission to SMC regarding this product in this indication. As a result we cannot recommend its use within NHSScotland.

September capsaicin, 179mg, cutaneous patch (Qutenza®) capsaicin (Qutenza®) is accepted for restricted use within NHS Scotland. Included on the Fife SMC capsaicin (Qutenza) 2014 Astellas Pharma Ltd Formulary for restricted use. 673/11 Indication under review: For the treatment of peripheral neuropathic pain in Resubmission non-diabetic adults either alone or in combination with other medicinal Restricted to the treatment of products for pain. adults with peripheral Capsaicin (Qutenza®) cutaneous patch is neuropathic pain (non- indicated for the treatment of peripheral SMC restriction: to use in patients who have not achieved adequate pain diabetics) or post-herpetic neuropathic pain in non-diabetic adults either relief from, or have not tolerated, conventional first and second line treatments. neuralgia who have not alone or in combination with other medicinal achieved adequate pain relief products for pain. A phase IV, open-label, randomised, controlled study showed that capsaicin from or who have not patch was non-inferior to an oral analgesic in adult patients with peripheral tolerated conventional first Comparator Medicines: neuropathic pain second and third-line oral There are a number of medicines recommended treatments. in treatment guidelines for the treatment of neuropathic pain, including: amitriptyline, Hospital use only by gabapentin, pregabalin, imipramine, nortriptyline, specialists in pain duloxetine*, carbamazepine, lidocaine plaster, management. ketamine∆.

*SMC advice restricts the use of duloxetine to patients with diabetic PNP, so it is not considered a comparator for the indication under review in this submission. ∆Oral ketamine is an unlicensed “special”, September brentuximab vedotin (Adcetris®) 50mg powder for brentuximab vedotin (Adcetris®) is accepted for restricted use within NHS Included on the Fife SMC brentuximab 2014 concentrate for solution for infusion Scotland. Formulary for the treatment of vedotin (Adcetris) 989/14 Takeda UK Ltd adult patients with relapsed or (No: 956/14) Indication under review: treatment of adult patients with relapsed or refractory CD30+ Hodgkin For treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL): lymphoma (HL): refractory CD30+ Hodgkin lymphoma (HL): 1. following autologous stem cell transplant (ASCT) or 1.following autologous stem 1. following autologous stem cell transplant 2. following at least two prior therapies when ASCT or multi-agent cell transplant (ASCT) or (ASCT) or chemotherapy is not a treatment option and 2.following at least two prior 2. following at least two prior therapies when treatment of adult patients with relapsed or refractory systemic anaplastic large therapies when ASCT or multi- ASCT or multi-agent chemotherapy is not a cell lymphoma (sALCL). agent chemotherapy is not a 3 of 7 SMC Advice - Formulary Decisions August-September 2014

treatment option treatment option. and SMC restriction: treatment of adult patients with relapsed or refractory CD30+ treatment of adult patients with relapsed or Hodgkin lymphoma (HL): Hospital use only by refractory systemic anaplastic large cell 1. following autologous stem cell transplant (ASCT) or haematology. lymphoma (sALCL). 2. following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option Comparator Medicines: In an open-label, single-arm study, patients with relapsed or refractory Hodgkin There is no current standard of care for patients lymphoma treated with brentuximab vedotin achieved an objective response with relapsed or refractory disease after ASCT rate of 75%. Controlled data with clinical outcomes are currently lacking. and patients may be treated with a range of salvage options with multi-agent chemotherapy This advice takes account of the views from a Patient and Clinician (including off-label use of gemcitabine, vinblastine Engagement (PACE) meeting. or vinorelbine). For patients who have received at least two prior therapies when ASCT or multi- Brentuximab is also indicated for the treatment of adult patients with relapsed agent chemotherapy is not a treatment option, or refractory systemic anaplastic large cell lymphoma (sALCL). SMC cannot further treatment options are limited. recommend use in sALCL as the company did did not include evidence for use in this indication in its submission.

September posaconazole 100mg gastro-resistant tablets posaconazole tablets (Noxafil®) is accepted for restricted use within NHS Included on the Fife SMC posaconazole 2014 (Noxafil®) Scotland. Formulary as an alternative to (Noxafil) 999/14 MSD Limited posaconazole suspension. Indication under review: in the treatment of the following fungal infections in Posaconazole tablets are adults: cost saving compared to Restricted hospital use only. Product Update - Invasive aspergillosis in patients with disease that is refractory to the suspension when amphotericin B or itraconazole or in patients who are intolerant of used for treatment but these medicinal products; (See restricted antimicrobial are more expensive than - Fusariosis in patients with disease that is refractory to amphotericin list) the suspension when B or in patients who are intolerant of amphotericin B; used for prophylaxis. - Chromoblastomycosis and mycetoma in patients with disease that is refractory to itraconazole or in patients who are intolerant of itraconazole; - Coccidioidomycosis in patients with disease that is refractory to amphotericin B, itraconazole or fluconazole or in patients who are intolerant of these medicinal products. for prophylaxis of invasive fungal infections in the following patients: - Patients receiving remission-induction chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) expected to result in prolonged neutropenia and who are at high risk of developing invasive fungal infections; - Hematopoietic stem cell transplant (HSCT) recipients who are undergoing high-dose immunosuppressive therapy for graft versus host disease and who are at high risk of developing invasive fungal infections.

SMC restriction: to patients in whom there is a specific risk of Aspergillus infection or where fluconazole or itraconazole are not tolerated on the advice of local microbiologists or specialists in infectious diseases.

Posaconazole plasma concentrations are generally higher following administration of posaconazole tablets than posaconazole oral suspension. The tablet and oral suspension are therefore not to be used interchangeably. 4 of 7 SMC Advice - Formulary Decisions August-September 2014

While the tablets are cost saving when administered for treatment they are significantly more expensive than the oral suspension when administered for prophylaxis.

September lurasidone, 18.5mg, 37mg, 74mg film-coated lurasidone (Latuda®) is accepted for restricted use within NHS Scotland. Not included on the Fife Not preferred. 2014 tablets (Latuda®) Formulary because NHS Fife’s Sunovion Indication under review: For the treatment of schizophrenia in adults aged 18 decision is that the medicine Current Fife Formulary 994/14 years and over. does not represent sufficient antipsychotics are – For the treatment of schizophrenia in adults aged added benefit to other 1st Choice 18 years and over SMC Restriction: as an alternative treatment option in patients in whom it is comparator medicines. Chlorpromazine, important to avoid weight gain and metabolic adverse effects. Olanzapine and Comparator Medicines: Risperidone. Experts consulted by SMC indicate that Lurasidone demonstrated benefit over placebo in mean change from baseline 2nd Choice Amisulpride, aripiprazole is the relevant comparator as it would in Positive and Negative Syndrome Scale (PANSS) total score after six weeks Aripiprazole (Abilify®), be used where avoidance of weight of treatment and was non-inferior to another second generation antipsychotic Haloperidol and gain/metabolic adverse events is important. medicine for time to relapse over 12 months. Quetiapine (standard tablets).

http://www.fifeadtc.scot. nhs.uk/formulary/4- central-nervous- system.aspx

SMC lurasidone (Latuda)

September misoprostol, 200 microgram, vaginal delivery misoprostol (Mysodelle®) is accepted for use within NHS Scotland. Not included on the Fife SMC misoprostol 2014 system (Mysodelle®) Formulary pending protocol. (Mysodelle) 996/14 Ferring Pharmaceuticals Ltd Indication under review: Induction of labour in women with an unfavourable cervix, from 36 weeks gestation, in whom induction is clinically indicated. Induction of labour in women with an unfavourable cervix, from 36 weeks gestation, in whom Misoprostol vaginal delivery system significantly reduced the time to vaginal induction is clinically indicated. delivery, with a similar rate of caesarean section, compared with an active comparator Comparator Medicines: Dinoprostone vaginal delivery system, vaginal tablet and vaginal gel.

September alogliptin 12.5mg plus metformin1000mg alogliptin plus metformin combination tablet (Vipdomet®) is accepted for Not included on the Fife Not preferred 2014 combination tablet (Vipdomet®) restricted use within NHS Scotland. Formulary as clinicians do not 998/14 Takeda UK support formulary inclusion. Fife Formulary choice Indication under review: in the treatment of adult patients aged 18 years and gliptins are – Product Update older with type 2 diabetes mellitus: 1st choice sitagliptin nd  as an adjunct to diet and exercise to improve glycaemic control in adult 2 choice saxagliptin patients, inadequately controlled on their maximal tolerated dose of metformin alone, or those already being treated with the combination of http://www.fifeadtc.scot. alogliptin and metformin. nhs.uk/formulary/6- endocrine.aspx  in combination with pioglitazone (i.e. triple combination therapy) as an adjunct to diet and exercise in adult patients inadequately controlled on SMC alogliptin plus their maximal tolerated dose of metformin and pioglitazone. metformin (Vipdomet) 5 of 7 SMC Advice - Formulary Decisions August-September 2014

 in combination with insulin (i.e. triple combination therapy) as an adjunct to diet and exercise to improve glycaemic control in patients when insulin at a stable dose and metformin alone do not provide adequate glycaemic control. SMC restriction: to use in patients for whom this fixed dose combination of alogliptin and metformin is an appropriate choice of therapy and only when the addition of a sulphonylurea to metformin monotherapy is not appropriate.

For patients in whom dual combination therapy with metformin and aloglitpin is appropriate it has the potential to reduce the pill burden at no additional cost.

Alogliptin/metformin is licensed for use in triple combination therapy with pioglitazone or as add-on to insulin. The manufacturer’s submission related only to the use of alogliptin/ metformin in dual therapy, therefore SMC cannot recommend the use of alogliptin/ metformin in triple therapy with either pioglitazone or insulin.

September azelastine hydrochloride 137micrograms plus azelastine hydrochloride plus fluticasone propionate nasal spray Not included on the Fife Not preferred. 2014 fluticasone propionate 50micrograms per (Dymista®) is accepted for use within NHS Scotland. Formulary as clinicians do not 921/13 actuation nasal spray (Dymista® nasal spray) support formulary inclusion. Fife Formulary choice Meda Pharmaceuticals Indication under review: for the relief of symptoms of moderate to severe steroid nasal sprays are seasonal and perennial allergic rhinitis if monotherapy with either intranasal – Beclometasone Product Update antihistamine or glucocorticoid is not considered sufficient. Mometasone Futicasone furoate For patients in whom the combination of azelastine hydrochloride and (Avamys®) fluticasone propionate nasal spray is an appropriate choice of therapy, Dymista® provides the two ingredients in a single nasal spray. http://www.fifeadtc.scot. nhs.uk/formulary/12-ear,- This SMC advice takes account of the benefits of a Patient Access Scheme nose-and-throat.aspx (PAS) that improves the cost-effectiveness of Dymista®. This SMC advice is contingent upon the continuing availability of the Patient Access Scheme in SMC azelastine NHS Scotland or a list price that is equivalent or lower. hydrochloride + fluticasone propionate (Dymista)

September dabigatran etexilate, 110mg, 150mg capsules dabigatran etexilate (Pradaxa®) is accepted for use within NHS Scotland. Not included on the Fife Not preferred. 2014 (Pradaxa®) Formulary as clinicians do not 995/14 Boehringer Ingelheim Ltd Indication under review: treatment of deep vein thrombosis (DVT) and support formulary inclusion. Fife Formulary choice pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults. NOAC for this indication Treatment of deep vein thrombosis (DVT) and is rivaroxaban. pulmonary embolism (PE), and prevention of Dabigatran etexilate was non-inferior to a vitamin K antagonist for recurrent recurrent DVT and PE in adults. symptomatic venous thromboembolism events (VTE) and death related to VTE http://www.fifeadtc.scot. in three phase III studies (two in the treatment of DVT/PE and one in the nhs.uk/formulary/2- Comparator Medicines: prevention of recurrent DVT/PE). cardiovascular.aspx Rivaroxaban, or LMWH plus warfari The economic case was based on evidence relating to a maximum of 18 SMC dabigatran etexilate months treatment so the cost-effectiveness of longer term use is uncertain (Pradaxa)

September empagliflozin 10mg and 25mg tablet (Jardiance®) empagliflozin (Jardiance®) is accepted for restricted use within NHS Not included on the Fife Not preferred. 6 of 7 SMC Advice - Formulary Decisions August-September 2014

2014 Boehringer Ingelheim / Eli Lilly Scotland. Formulary as clinicians do not 993/14 support formulary inclusion. Fife Formulary ‘gliflozin’ Treatment of type 2 diabetes to improve Indication under review: Treatment of type 2 diabetes to improve glycaemic is dapagliflozin. glycaemic control in adults as add-on combination control in adults as add-on combination therapy: in combination with other (Restricted to use with therapy: in combination with other glucose– glucose–lowering medicinal products including insulin, when these, together insulin only). lowering medicinal products including insulin, with diet and exercise, do not provide adequate glycaemic control. when these, together with diet and exercise, do http://www.fifeadtc.scot. not provide adequate glycaemic control. SMC restriction: to use in the following situations: nhs.uk/formulary/6-  dual therapy in combination with metformin, when a sulphonylurea is endocrine.aspx As monotherapy, when diet and exercise alone do inappropriate not provide adequate glycaemic control in patients  triple therapy in combination with metformin plus standard of care SMC empagliflozin for whom use of metformin is considered  add-on to insulin therapy in combination with insulin plus standard of (Jardiance) inappropriate due to intolerance care

Comparator Medicines: Empagliflozin was superior to placebo for glycaemic control in combination A variety of anti-diabetic medicines can be used in with various anti-diabetic medicines (metformin; metformin plus sulphonylurea; combination with metformin as dual- or triple- thiazolidinedione ± metformin; and insulin) and it was non-inferior to a therapy and as add-on to insulin. These include sulphonylurea in combination with metformin. sulphonylureas, dipeptidyl-peptidase-4 (DPP-4) inhibitors, TDZ, SGLT-2 inhibitors and glucagon- Empagliflozin is also indicated as monotherapy in patients who cannot tolerate like peptide-1 (GLP-1) agonists metformin. SMC cannot recommend the use of empagliflozin as monotherapy as the company’s submission did not include evidence of cost-effectiveness in this setting September trastuzumab emtansine, 100mg and 160mg, trastuzumab emtansine (Kadcyla ®) is not recommended for use within NHS Not recommended. Lack of evidence of 2014 powder for concentrate for solution for infusion Scotland. health benefits 990/14 (Kadcyla ®) Indication under review: as a single agent, for the treatment of adult patients compared to the cost of Requires submission and Roche Products Ltd with human epidermal growth factor type 2 (HER2)-positive, unresectable treatment. approval of an IPTR. locally advanced or metastatic breast cancer who previously received As a single agent, is indicated for the treatment of trastuzumab and a taxane, separately or in combination. Patients should have SMC trastuzumab adult patients with HER2-positive, unresectable either: emtansine (Kadcyla) locally advanced or metastatic breast cancer who • Received prior therapy for locally advanced or metastatic disease, or previously received trastuzumab and a taxane, • Developed disease recurrence during or within six months of completing separately or in combination. Patients should adjuvant therapy. have either: • Received prior therapy for locally advanced or In a randomised phase III open-label study, trastuzumab emtansine (Kadcyla®) metastatic disease, or conferred a median six months additional survival benefit compared with an • Developed disease recurrence during or within active comparator. six months of completing adjuvant therapy The submitting company’s justification of the treatment’s cost in relation to its Comparator Medicines: health benefits was not sufficient to gain acceptance by SMC. Oral capecitabine, oral or intravenous vinorelbine. Off-label use of trastuzumab. This advice takes account of the views from a Patient and Clinician Engagement (PACE) meeting

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