Safe use of insulin regular concentrated (500 units/ml) in severe insulin resistance

Transcription

1 Safe use of insulin regular concentrated (500 units/ml) in severe insulin resistance Jodie S. Gee, Pharm.D., BCACP, CDE Clinical Pharmacy Specialist-Ambulatory Care Harris Health System

2 Objectives To be able to identify appropriate patients for U-500 insulin therapy Distinguish place in therapy for U-500 insulin Discuss safety recommendations for U-500 insulin Counsel patients on safe use of U-500 Formulate a therapeutic care plan for a patient using U-500

3 Patient Case Chief compliant: My sugars are so high and I m on so much insulin! TH is a 47 y/o Caucasian female who presents to the clinic for evaluation of blood sugars. She reports compliance with her medication regimen Past medical history: Type 2 diabetes (diagnosed in 2000) Hypertension Insomnia Depression Social history: Denies smoking and alcohol

4 Patient case Allergies: NKDA Medications Insulin detemir (Levemir flextouch ) 120 units SC q 12 hours Insulin aspart (Novolog flexpen ) 80 units SC TID AC Metformin 1000 mg BID Atorvastatin 40 mg daily Lisinopril 10 mg daily Sertraline 25 mg daily

5 Patient case Vitals Blood pressure Pulse Height Weight BMI 119/ lbs (124 kg) 47 kg/m 2 Labs (9/15/17) Hemoglobin A1c (%) (H)

6 Patient case Date Fasting Before lunch Before dinner Bedtime 9/ / / / / / / / / / / /16 271

7 Clinical Question What would you do with this patient?

8 Background- Severe insulin resistance Severe insulin resistance Total daily insulin requirement > 200 units/day > 2 units/kg/day Note: typical human pancreas secretes ~ units/day Metabolic disorders Obesity Hypertension Hyperlipidemia Cardiovascular disease Non-alcoholic fatty liver disease (NAFLD) Barnosky AB et al. Postgraduate medicine. 2016; 128 (4):

9 Background- Severe insulin resistance Etiology Type 2 diabetes mellitus with obesity Protease inhibitor use (lipodystrophy) Insulin receptor defects (Type A insulin resistance syndrome) Insulin receptor auto-antibodies (Type B insulin resistance syndrome) High dose glucocorticoids Barnosky AB et al. Postgraduate medicine. 2016; 128 (4):

10 Treatment- Severe insulin resistance Conventional insulin U-100 (100 units/ml) Insulin syringes max 100 units/injection Insulin pen devices max units/injection Increased number of injections Several injections per dose Large volumes injected Poor absorption Suboptimal glycemic control Poor compliance Injection discomfort Leakage Barnosky AB et al. Postgraduate medicine. 2016; 128(4): Lane WS et al. Endocr Pract. 2009; 15(1): 71-79

11 Treatment- Severe insulin resistance Concentrated insulin regular U-500 (500 units/ml) 5 times more concentrated than conventional U-100 insulin 1 ml of U-100 = 100 units 1 ml of U-500 = 500 units Decreased volume with each injection 1/5 volume with U-500 than U-100 Decreased number of injections Improved injection comfort Not necessarily a more powerful or stronger insulin Liquid is reduced with U-500 insulin compared to U-100 Barnosky AB et al. Postgraduate medicine. 2016; 128(4): Lane WS et al. Endocr Pract. 2009; 15(1): 71-79

12 Treatment- Severe insulin resistance U-100 insulin (100 units/ml) vs Concentrated insulin regular U-500 (500 units/ml) Same # of insulin particles/units, less liquid U-100 insulin U-500 insulin

13 Overview of insulin regular concentrated (U-500)

14 Pharmacokinetics- U-500 Insulin Concentrating the insulin alters pharmacodynamics and pharmacokinetics Works as both basal and bolus insulin Action profile similar to NPH insulin Onset: minutes Peak: 4 hours Duration: hours (8 hours in some patients) Typically used as monotherapy Limited data on combining U-500 with other insulins Higher risk of hypoglycemia Barnosky AB et al. Postgraduate medicine. 2016; 128(4): Humulin R U-500 (package insert). Indianapolis, IN: Eli Lilly and Co.; 2016 Garg R et al. Diabetes Metab Res Rev. 2007; 23:

15 Safety concerns with U-500 insulin- Institute for Safe Medication Practices (ISMP) Dose errors (overdose) Utilizing incorrect syringes (U-100 syringes vs tuberculin or U-500 syringes) Accidentally giving 5 times the intended dose Dose conversion/calculation errors (providers and dispensing pharmacists) Dispensing errors Confusing Regular insulin U-100 with Regular insulin U-500 Severe hypoglycemia

16 Selecting patients for U-500 insulin therapy Total daily dose of insulin > 200 units/day or > 2 units/kg/day Type 2 diabetes mellitus with obesity Protease inhibitor use (lipodystrophy) Insulin receptor defects (Type A insulin resistance syndrome) Insulin receptor auto-antibodies (Type B insulin resistance syndrome) High dose glucocorticoids Gestational diabetes with severe insulin resistance Adequate health literacy Compliance with clinic follow-up appointments Lane WS et al. Endocr Pract. 2009; 15(1): 71-79

17 Ziesmer et al. Objective: Evaluate use of U-500 in insulin resistant patients (Type 2 diabetes) previously on U-100 insulin Methods Retrospective chart review (N=66) Follow up > 6 months Data collected: total daily insulin dose, HbA1c, body weight, lipids, episodes of severe hypoglycemia VA North Texas Health Care System Dallas Primary outcome: Change in HbA1c Secondary outcome: Changes in insulin dose, body weight, lipids, frequency of severe hypoglycemia Ziesmer AE et al. Endocr Pract. 2012; 18:34-38

18 Ziesmer et al. Safety- Hospital U-500 Policy Ziesmer AE et al. Endocr Pract. 2012; 18:34-38

19 Ziesmer et al. Safety- U-500 insulin patient contract Ziesmer AE et al. Endocr Pract. 2012; 18:34-38

20 Ziesmer AE et al. Endocr Pract. 2012; 18:34-38 Ziesmer et al. Results Baseline (U-100) End of study (U-500) P value HbA1c (%) <0.001 Insulin (units/day) Weight (kg) BMI (kg/m 2 ) Conclusions U-500 can be safely and effectively used when a strict protocol and close patient monitoring is utilized

21 Initiating U-500 insulin Calculate total daily dose (TDD) of insulin (Basal + bolus) HbA1c >10% ->Increase TDD by 10% HbA1c 8-10% -> Same TDD HbA1c <8% -> Decrease TDD by 10% TDD = units TDD = units TDD > 600 units Two daily injections (60/40) OR Three daily injections (40/30/30, 45/35/20, 40/40/20, 33/33/33)** Three daily injections** OR Four daily injections (30/30/30/10) OR Insulin pump Four daily injections (30/30/30/10- preferred, 25/25/25/25) OR Insulin pump Lane WS et al. Endocr Pract. 2009; 15(1): Reutrakal et al. J Diabetes Sci Technol. 2012; 6(2):

22 Initiating U-500 insulin Injections always given pre-meal Example of dose timings: Two daily injections: 8 am and 6 pm Three daily injections: 8 am, 12 pm, 6 pm Four daily injections: 8 am, 12 pm, 5 pm, 10 pm Discontinue prior insulin therapy (ie. Basal and bolus insulins) Ensure that patient and family members are properly educated Lane WS et al. Endocr Pract. 2009; 15(1): Reutrakal et al. J Diabetes Sci Technol. 2012; 6(2):

23 Safety Safest use of U-500 U-500 syringes Each line is 5 units No conversion necessary U-500 pen No conversion necessary Tuberculin syringes Dosed in ml instead of units Use of U-100 syringes with U-500 (DANGER! CAUTION!) Conversion is needed Potential for errors by providers and pharmacy (miscalculation) Potential for overdose by patients Not the safest option Must divide original dose by 5 to get the volume patient is to draw up May confuse the patients Recommend using terminology on Rx s and instructions Draw up X units volume in a U-100 syringe three times daily before meals

24 Syringes - Dose Conversion Actual dose of U-500 (Dose calculated based on patient s total daily dose) Volume in ml (ie. Tuberculin syringe) (Actual dose 500) Volume marking on U- 100 syringe (patient will draw this up in U-100 syringe) (Actual dose 5) 50 units 0.1 ml 10 units 75 units 0.15 ml 15 units 100 units 0.2 ml 20 units 125 units 0.25 ml 25 units 150 units 0.3 ml 30 units 175 units 0.35 ml 35 units 200 units 0.4 ml 40 units 225 units 0.45 ml 45 units 250 units 0.5 ml 50 units 275 units 0.55 ml 55 units

25 Syringes U-500 syringe - Green Tuberculin syringe

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27 Titration Self monitored glucose reading target Insulin dose to adjust Self monitored glucose value Dose titration Fasting/Prebreakfast Pre-lunch Pre-dinner Pre-dinner Pre-breakfast Pre-lunch <70-10% No change % % > % Obtain at least 3 days worth of glucose readings Titrate to the nearest 5-unit increment Hood et al. Endocr Pract. 2015; 21:

28 Safety- Implementation at Harris Health System Team approach Pharmacy (Clinical pharmacy specialists, dispensing pharmacists, pharmacy supervisors) Clinical pharmacy specialists Inservice pharmacy personnel and physicians/mid-level providers Perform U-500 education on all patients initiated Physicians/mid-level providers Diabetic educators Harris Health Protocol Clinical pharmacy must be consulted by physicians/mid-level providers upon initiating U-500 All dose calculations double checked by a second provider All education on U-500 completed at clinical pharmacist visit Patient not to start taking U-500 until clinical pharmacist visit Dispensing pharmacy (Harris Health pharmacies) pages MD/clinical pharmacist to verify doses on all new U-500 Rx s Use U-500 syringe for Rx s filled at Harris Health pharmacies Use U-500 pen for Rx s filled at outside retail pharmacies

29 Safety- Considerations for Implementation Team approach Education! Education! Education! Strict protocol/process implementation Provider education and reinforcement Patient not to start until after education visit Patient to demonstrate proficiency at education visit with teach back method Consider a patient contract Safety! All dose calculations double checked by 2 providers Try to use U-500 or tuberculin syringes or U-500 pen

30 Patient Counseling Patient education is VERY IMPORTANT! Dosing and use of proper syringes Overdoses with improper use of U-100 syringes!!!!!! Administration 30 minutes before meals Hold dose if skipping meals! Patients should check their blood sugars before every meal and at bedtime Hypoglycemia signs, symptoms, treatment Rule of 15 No self-titration!!!!! Must bring meter and log to every clinic appointment

31 Patient case - Revisited

32 Patient Case- Revisited Chief compliant: My sugars are so high and I m on so much insulin! TH is a 47 y/o Caucasian female who presents to the clinic for evaluation of blood sugars. Past medical history: Type 2 diabetes (diagnosed in 2000) Hypertension Insomnia Depression Social history: Denies smoking and alcohol

33 Patient case Date Fasting Before lunch Before dinner Bedtime 9/ / / / / / / / / / / /16 271

34 Patient case Allergies: NKDA Medications Insulin detemir (Levemir flextouch ) 120 units SC q 12 hours Insulin aspart (Novolog flexpen ) 80 units SC TID AC Metformin 1000 mg BID Atorvastatin 40 mg daily Lisinopril 10 mg daily Sertraline 25 mg daily Patient reports eating 3 meals per day

35 Initiating U-500 insulin Calculate total daily dose (TDD) of insulin (Basal + bolus) HbA1c >10% ->Increase TDD by 10% HbA1c 8-10% -> Same TDD HbA1c <8% -> Decrease TDD by 10% TDD = units TDD = units TDD > 600 units Two daily injections (60/40) OR Three daily injections (40/30/30, 45/35/20, 40/40/20, 33/33/33)** Three daily injections** OR Four daily injections (30/30/30/10) OR Insulin pump Four daily injections (30/30/30/10- preferred, 25/25/25/25) OR Insulin pump Lane WS et al. Endocr Pract. 2009; 15(1): Reutrakal et al. J Diabetes Sci Technol. 2012; 6(2):

36 Syringes - Dose Conversion Actual dose of U-500 (Dose calculated based on patient s total daily dose) Volume in ml (ie. Tuberculin syringe) (Actual dose 500) Volume marking on U- 100 syringe (patient will draw this up in U-100 syringe) (Actual dose 5) 50 units 0.1 ml 10 units 75 units 0.15 ml 15 units 100 units 0.2 ml 20 units 125 units 0.25 ml 25 units 150 units 0.3 ml 30 units 175 units 0.35 ml 35 units 200 units 0.4 ml 40 units 225 units 0.45 ml 45 units 250 units 0.5 ml 50 units 275 units 0.55 ml 55 units

37 Case Step 1: Calculate total daily dose of insulin Insulin detemir (Levemir flextouch ) 120 units SC q 12 hours Insulin aspart (Novolog flexpen ) 80 units SC TID AC Total daily dose = 480 units Step 2: Determine dose frequency Total daily dose = units TID dosing (33/33/33) depending on patient s meal pattern Total daily dose = 480 units 3 = 160 units three times daily before meals Step 3: Choose syringe and convert dosing U-500 syringe/pen - No conversion necessary 160 units three times daily before meals Tuberculin syringe Calculated dose units 500 = 0.32 ml ~ 0.3 ml three times daily before meals U-100 syringe (CAUTION) Calculated dose units 5 = 32 units volume in a U-100 syringe

38 Patient case Follow-up 3 weeks later Date Fasting Before lunch Before dinner Bedtime 10/ / / / / / / HbA1c 3 months later = 7.6

39 Future implications Other concentrated insulins (glargine U-300, degludec U-200, lispro U-200) Better absorption Less variability Safer: Only available in insulin pens More expensive U-400 (BIOD-531) Phase 3 clinical trials Faster onset Shorter duration Ovalle F et al. Curr Med Res Opin. 2018; DOI: /

40 Cost U-500 vial - $0.14/unit Ovalle F et al. Curr Med Res Opin. 2018; DOI: /

41 References Barnosky A, Shah L, Meah F, et al. Postgraduate medicine. 2016; 128(4): Lane WS, Cochran EK, Jackson JA, et al. Endocr Pract. 2009; 15(1): Garg R, Johnston V, McNally PG, et al. Diabetes Metab Res Rev. 2007; 23: Humulin R U-500 (package insert). Indianapolis, IN: Eli Lilly and Co.; 2016 Ziesmer AE, Kelly KC, Guerra PA, et al. Endocr Pract. 2012; 18: Reutrakul S, Wroblewski K, Brown RL. J Diabetes Sci Technol. 2012; 6(2): Hood RC, Arakaki RF, Wysham C, et al. Endocr Pract. 2015; 21: Ovalle F, Segal AR, Anderson JE, et al. Curr Med Res Opin. 2018; DOI: /

42 Safe use of insulin regular concentrated (500 units/ml) in severe insulin resistance Jodie S. Gee, Pharm.D., BCACP, CDE Clinical Pharmacy Specialist-Ambulatory Care Harris Health System