Medicines Optimisation Team Standard Operating procedure for Alogliptin Audit:

Transcription

1 Medicines Optimisation Team Standard Operating procedure for Alogliptin Audit: To review type 2 diabetic patients prescribed dipedtidylpeptidase-4 (DPP-4) inhibitors (linagliptin (Trajenta, saxagliptin (Onglyza ), sitagliptin (Januvia ), vildagliptin (Galvus, to determine continued need for prescribing or if appropriate, change therapy to the most cost-effective option, alogliptin. Aim Whilst combination products are not on the formulary, some patients for clinical reason are prescribed these products. This audit will also review patients prescribed DPP-4 inhibitors and metformin combination products to change to a more cost-effective alogliptin and metformin combination. Rationale 1. Alogliptin (Vipidia ) is available as 6.25mg, 12.5mg and, 25mg tablets and is the first line option for DPP-4 inhibitor on the formulary. It is licensed for: o Dual therapy in combination with metformin, a thiazolidinedione, a or o Triple therapy in combination with metformin and sulfonylurea, or o Triple therapy with metformin and a thiazolidinedione or insulin. sulfonylurea or insulin 2. Alogliptin when prescribed on FP10 prescription is 20% lower than other DPP-4- inhibitors. It is worth noting that all DPP-4 inhibitors have a flat pricing structure across strengths and therefore doses should be optimised to the fewest number of tablets taken. See Table Whilst there is no head to head trials comparing DPP-4 inhibitors, NICE, MTRAC and PrescQIPP recommend that (1): o The gliptin with the lowest acquisition cost should be used. o Within licence, gliptins should only be continued if there has been a beneficial metabolic response i.e a reduction by at least 5.5mmol/mol or (0.5%) points in HbA1c in 6 months after initiation. 4. Safety o Alogliptin appeared well tolerated in the two RCTs reviewed within the NICE evidence summary, with most adverse events reported to be of mild or moderate intensity (1). o Due to the increased risk of hypoglycaemia in combination with a sulfonylurea (SU), insulin or combination therapy with thiazolidinedione plus metformin, a lower dose of these medications should be considered to reduce the risk of hypoglycaemia when these medicinal products are used in combination with alogliptin as indicated in the product license.(3) o Dose reductions are needed in patients with renal (3)- refer to Table 1 for 1 P a g e

2 specific doses. o Alogliptin is not recommended for use in patients with severe hepatic (3). o There is limited experience of alogliptin use in clinical trials in patients with congestive heart failure of New York Heart Association (NYHA) functional class III IV. Use is not recommended in these patients(3). o Like the other DPP-4 inhibitors no dosage adjustment is required for elderly ( 65 years) based solely on age. Also like the other DPP-4 inhibitors, experience in patients aged 75 years and older is very limited and caution should be exercised when treating this population. 3 o Acute pancreatitis Like other DPP-4 inhibitors, alogliptin also has a potential risk of developing acute pancreatitis. In most cases, pancreatitis resolved after discontinuation of treatment. The MHRA advises that patients should be informed of the characteristic symptom of acute pancreatitis. If pancreatitis is suspected, alogliptin should be discontinued; if acute pancreatitis is confirmed, alogliptin should not be restarted(4). o Cardiovascular safety Although newer glucose-lowering drugs are effective at reducinghba1c levels, they all lack robust clinical outcome data, particularly around their cardiovascular effects and long-term safety in people with Type-2 diabetes. Improvements in surrogate markers (including HbA1c levels) do not automatically confer benefits on mortality or morbidity, and risks may become apparent only over time when these agents have more widespread use in a diverse population. In 2016 FDA, issued updated warnings on the use of saxagliptan and alogliptin potentially causing heart failure. These have been recently reviewed by UKMI and have concluded that heart failure was not the primary outcome being measured and the numbers were small and the data unreliable to be conclusive from the reporting trials. Also, there is no indication to date 01/10/16 that MHRA or EMA consider that any additional warning is necessary for DPP-4 inhibitors as a group or saxagliptin or alogliptin individually. For present it would be sensible to use the DDP-4 inhibitors of choice and observe the warnings and cautions of the respective SPC and prescribe within the licensed indications. Audit criteria Inclusion criteria All patients on the following list of drugs for the management of type 2 diabetes: o Linagliptin (Trajenta ) o Linagliptin & metformin hydrochloride (Jentadueto ) o Saxagliptin (Onglyza ) o Saxagliptin & metformin hydrochloride (Komboglyze ) o Sitagliptin (Januvia ) o Sitagliptin & metformin hydrochloride (Janumet ) o Vildagliptin (Galvus ) 2 P a g e

3 Exclusion criteria o Vildagliptin & metformin hydrochloride (Eucreas ) o Patients prescribed a gliptin as monotherapy, as alogliptin is unlicensed for monotherapy o Patients prescribed a gliptin for type 1 diabetes as this is unlicensed use of the drug. o Patients with previous intolerance to alogliptin o Previous treatment failure with alogliptin o Patients who have been taking a gliptin for more than 6 months but have not achieved the required reduction of more than 5-6 mmols in HbA1c or achieved their individualised target these patients should be flagged to the GP for review. Please note that the new NICE guidelines discusses individualised care and targets are based on case by case, so review should be based on what has been set for patients. o Patients with heart failure of NYHA class III-IV o Patients who do not have a recent assessment of their renal function in the last 12 months these patients should be identified for the practice to call in for new urea, electrolytes, creatinine and EGFR prior to commencing the switch. o Patients who have rapidly declining renal function or an EGFR less than 30ml/min would be more preferable to be on linaglitpin as this requires no dosage adjustment for renal failure. o Patients who are having renal dialysis or peritoneal dialysis would be preferable to be on linagliptin as it is not expected to be eliminated to a therapeutically significant degree by dialysis. o Patients with severe hepatic (Child-Pugh score >9) o Patients under the age of 18 years o Patients who are pregnant o Patients who are currently breast feeding o Documented intolerance to any of the excipients listed in the SPC o Patients with a history of pancreatitis o Caution for patients >75yrs, no data on adjustment of dose on this population 3 P a g e

4 Method 1. A local agreement should be made at the practice with practice pharmacist to define the process for the dosage switch. 2. A practice based search should be made to determine the eligible patients for the switch based on the inclusion and exclusion criteria above 3. Undertake clinical audit taking into consideration, renal, hepatic and dose equivalence- refer to Table 1 and 2 4. Consent should be obtained from the prescriber of audit results and recommendations before any changes are made to the patient s medication records and prescribed medicines. 5. Ensure that the DPP-4 inhibitor has reduced HbA1c by 5.5mmol/l (0.5%) over 6 months. If criteria has been met consider a switch as below. If criteria has not been met, this needs to be highlighted to practices to review therapy. 6. Reduce dosage in renal as per table 1 and 2. o Reduce dose to 12.5mg daily if creatinine clearance 30 to 50 ml/min. o Reduce dose to 6.25mg daily if creatinine clearance < 30 ml/min. 7. For Patients on Dual Therapy ( Look at Table 1 to consider dosing equivalence ) o In combination with metformin: Consider alogliptin an alternative to sitagliptin or vildagliptin or linagliptin or saxagliptin. o In combination with sulphonylurea : Consider alogliptin an alternative to sitagliptin or vildagliptin or saxagliptin. o In combination with pioglitazone: Consider alogliptin an alternative to sitagliptin or vildagliptin or saxagliptin. o In combination with insulin :Consider alogliptin as an alternative to sitagliptin or vildagliptin or linagliptin or saxagliptin. 5. For Patient on Triple Therapy o In combination with metformin and pioglitazone: Consider alogliptin as an alternative to sitagliptin in combination with metformin and pioglitazone. o In combination with metformin and SU: Consider alogliptin as an alternative to sitagliptin in combination with metformin and SU o In combination with metformin and insulin : Consider alogliptin as an alternative to sitagliptin or vildagliptin or linagliptin or saxagliptin. 6. For patients on DPP-4 inhibitors/metformin combination products 4 P a g e

5 o Combination products are not on the formulary, but if patients are on a gliptin and metformin combination for a specific therapeutic reason and are stable, there is potential for optimisation to review to the most cost effective alogliptin/metformin combination. See Table 2 below for cost comparison. It is left to the clinical discretion of the pharmacist to implement this change. Please see Table 3 for cost comparison of combination products Notes for Practice Pharmacist/ nurse/gp: Ensure that patients who are switched are followed up to review diabetic control and side effects, with recheck of HbA1c in 8-12 weeks. Advise patients who are on insulin to monitor their blood glucose levels and to be vigilant for any changes in levels, particularly hypoglycaemia. Before implementation, liaise with local community pharmacies t to inform in advance of change and also to maximise their opportunity to counsel and offer patients the New Medicines Review (NMS) service. References: 1. PresQiPP Bulletin 78,Alogliptin Nov 2014 Version FDA Drug Safety Communication: FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin 3. Summary of Product Characteristics. Vipidia 6.25mg, 12.5mg, 25mg tablets (alogliptin). Takeda UK Ltd. Last updated 13/1/14. Available from 4. MHRA Drug safety update. Dipeptidylpeptidase-4 inhibitors ( gliptins ): risk of acute pancreatitis.september2012.available via 5 P a g e

6 Appendix 1 data collection form See attached data collection sheet. Date completed: <insert date> 6 P a g e

7 +metformin + sulfonylurea + pioglitazone + metformin + sulfonylurea + metformin + pioglitazone Table 1: DPP-4 licence comparisons and costs (1) Dual therapy Triple therapy Renal (egfr Drug Strengths Doses (maximal or usual) 28 day cost Monotherapy Addition to insulin ml/min/1.73m 2 ) Mild Moderate Severe Hepatic ESRD Sitagliptin 25mg 50mg 100mg 100mg daily Yes Yes Yes Yes Yes Yes Yes +/- only metformin Moderate -50mg daily Severe to ESRD -25mg daily Use cautiously in severe hepatic Vildagliptin 50mg 50mg twice daily Yes Yes Yes Yes Yes No Yes +/- only metformin Moderate to severe -50mg daily ESRD not recommended Not recommended Linagliptin 5mg 5mg daily Yes Yes No No Yes No Yes +/- only metformin No dosage adjustment No reduction but limited experience Saxagliptin 2.5mg 5mg 5mg daily Yes Yes Yes Yes Yes No Yes +/- only metformin Moderate to severe - 2.5mg daily ESRD not recommended Not recommended in severe hepatic 7 P a g e

8 Alogliptin 6.25mg 12.5mg 25mg 25mg daily No Yes Yes Yes Limited data Yes Yes +/- only metformin Moderate 12.5mg daily Severe to ESRD mg daily Not recommended in severe hepatic No dosage adjustment is recommended in elderly patients solely based on age; however caution needed in this population. Refer to the SPCs for complete information. Table 2 : Dose Equivalence Summary Table of DPP-4 inhibitors /renal Renal Function Alogliptin Linagliptin Saxgliptin Sitagliptin Vildagliptin Normal 25mg OD 5mg OD 5mg OD 100mg OD 50mg BD (or 50mg OD with an SU) Mild renal 25mg OD 5mg OD 5mg OD 100mg OD 50mg BD (or 50mg OD with an SU) Moderate renal 12.5mg OD 5mg OD 2.5mg OD 50mg OD 50mg OD Severe renal 6.25mg OD 5mg OD 2.5mg OD 25mg OD 50mg OD End stage renal disease 6.25mg OD 5mg OD Not recommended 25mg OD Not recommended requiring dialysis Hepatic Not recommended in severe hepatic No dose adjustment required for mild to moderate hepatic No reduction but limited experience Use with caution in patients with moderate hepatic but no dose No dose adjustment required for mild to moderate hepatic Chronic kidney disease in adults: UK guidelines for identification, management and referral (March 2006) define renal function as follows: Not recommended 8 P a g e

9 Degree of egfr ml/minute/1.73 m 2 Normal - Stage 1 Mild - Stage 2 More than 90 (with other evidence of kidney damage) (with other evidence of kidney damage) Moderate 1 - Stage Severe - Stage Established renal failure - Stage 5 Less than 15 NICE clinical guideline 73 (September 2008) Chronic kidney disease: Stage 3A egfr 45-59, Stage 3B egfr Table 3 Cost comparison of Combination DPP-4 inhibitor/metformin DPP-4 combination Dose Cost for 56 tablets ( ) Alogliptin 12.5mg plus metformin 1000mg (Vipdomet ) 1 twice daily Sitagliptin 50mg plus metformin 1000mg (Janumet ) 1 twice daily Vildagliptin 50mg plus metformin 850mg (Eucreas ) Vildagliptin 50mg plus metformin 1000mg (Eucreas ) Saxagliptin 2.5mg plus metformin 850mg (Komboglyze ) Saxagliptin 2.5mg plus metformin 1000mg (Komboglyze ) Linagliptin 2.5mg plus metformin 850mg (Jentadueto ) Linagliptin 2.5mg plus metformin 1000mg (Jentadueto ) 1 twice daily twice daily twice daily P a g e

10 Appendix 1 Patient letter Date as Postmark Title Initial Last Name Home Full Address (stacked) Dear Calling Name IMPORTANT INFORMATION As a practice we regularly review prescribing to ensure patients are on appropriate treatments in line with national guidance. We are currently reviewing patients prescribed a group of drugs called gliptins. Gliptins are a recent addition to the types of drugs used to lower blood glucose in type 2 diabetes and are usually added to existing treatments if these are not effective enough on their own. There are a number of different gliptins available. They all work in a similar way and have similar side- effects. According to currently available evidence, no single gliptin has been shown to be more effective than the others. We are therefore changing your current gliptin to an equivalent strength of a gliptpin called alogliptin. Alogliptin represents the best value for money for the NHS compared to the other gliptins. The money saved by prescribing alogliptin can then be used to contribute toward other NHS services. When you next request your medication, you will notice the following change. Old Prescription Drug: Strength: New Prescription Drug: Strength: Dose: Dose: Frequency: Frequency: We have arranged an appointment for you to have a blood test to check your HB1ac in 12 weeks time which will allow us to assess your diabetic control. The appointment will be on : at: If you can t make this appointment please call the practice to rearrange. Yours sincerely, On behalf of <Insert details 10 P a g e

11 Appendix 2 Patient letter alogliptin/metformin combination Date as Postmark Title Initial Last Name Home Full Address (stacked) Dear Calling Name IMPORTANT INFORMATION As a practice we regularly review prescribing to ensure patients are on appropriate treatments in line with national guidance. We are currently reviewing patients prescribed a group of drugs called gliptins. Gliptins are a recent addition to the types of drugs used to lower blood glucose in type 2 diabetes and are usually added to existing treatments if these are not effective enough on their own. Gliptins can be prescribed alone or in combination with another drug called metformin. There are a number of different gliptins/metformin combinations available, the preferred one based on quality and cost is alogliptin/metformin combination. They all work in a similar way and have similar side- effects. According to currently available evidence, no single gliptin/metformin has been shown to be more effective than the others. We are therefore changing your current gliptin/ metformin combination to an equivalent strength of alogliptin/metformin. Alogliptin represents the best value for money for the NHS compared to the other gliptins. The money saved by prescribing alogliptin/metformin can then be used to contribute toward other NHS services. When you next request your medication, you will notice the following change. Old Prescription Drug: Strength: New Prescription Drug: Strength: Dose: Dose: Frequency: Frequency: We have arranged an appointment for you to have a blood test to check your HB1ac in 12 weeks time which will allow us to assess your diabetic control. The appointment will be on : at: If you can t make this appointment please call the practice to rearrange. Yours sincerely, On behalf of <Insert details 11 P a g e

12 Document Change History Version Date Editor Details of significant changes 1.0 April 2017 Shaurna Reddy New Standard Template 2.0 January 2018 Thao Lam Addition of new licensing for triple therapy combinations for alogliptin Hb1ac follow up changed from 8 weeks to 12 weeks Head of Medicines Optimisation GP Prescribing Lead [Stafford and Surrounds CCG] Samantha Buckingham Dr Paddy Hanighan Date January 2018 Date January P a g e