Apidra (insulin glulisine) - Sanofi Canada

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Table 11: Type 1 Diabetes Mellitus–Adult Treatment duration Treatment in combination with following basal insulin: 12 weeks LANTUS 12 weeks 12 weeks ® LANTUS (insulin glargine) ® LANTUS (insulin glargine) ® (insulin glargine) APIDRA APIDRA Regular Human Insulin Pre-meal Post-meal Pre-meal Number of subjects treated 286 296 278 A1c (%) Endstudy mean 7.46 7.58 7.52 Adjusted mean change from baseline* -0.26 -0.11 -0.13 Basal insulin dose (U/day) Endstudy mean 29.49 28.77 28.46 Adjusted mean change from baseline 0.99 0.24 0.65 Short-acting insulin dose Endstudy mean (U/day) 28.44 28.06 29.23 Adjusted mean change from baseline -0.88 -0.47 1.75 Severe hypoglycemia** Number of subjects (%) 24/286 (8.4) 25/296 (8.4) 28/278 (10.1) Rate (events/month/patient) 0.05 0.05 0.13 Mean number of short-acting insulin injections per day 3.15 3.13 3.03 * Adjusted mean change from baseline treatment difference (98.33% Confidence Interval for treatment difference): APIDRA premeal vs. Regular Human Insulin - 0.13 (-0.26; 0.01); APIDRA post meal vs. Regular Human Insulin 0.02 (-0.11; 0.16); APIDRA post meal vs. pre meal 0.15 (0.02; 0.29). ** Events requiring assistance from third party for the entire treatment phase. Continuous Subcutaneous Insulin Infusion (CSII) (Type 1 Diabetes): To evaluate the use of APIDRA for administration using an external pump, a 12-week randomized, open-label, active-control study (APIDRA versus insulin aspart) was conducted in Type 1 diabetes patients (n = 59). A low monthly rate of catheter occlusion in both treatment groups was observed (APIDRA: 0.08 occlusions/month; insulin aspart: 0.15 occlusions/ month). A similar incidence of infusion site reactions was seen with APIDRA (n = 3/29; 10.3%) and insulin aspart (n = 4/30; 13.3%). APIDRA has been studied in the following pumps and infusion sets: Disetronic ® H-Tron ® plus V100 and D-Tron TM , with Disetronic catheters (Rapid TM , Rapid C TM and D TM , and Tender TM ); and with MiniMed ® Models 506, 507, 507c and 508 with MiniMed catheters (Sof-set Ultimate QR TM , and Quick-set TM ). Page 32 of 61
TOXICOLOGY Single and Repeated Dose Toxicity Single- and repeated-dose toxicity studies were conducted in mice, rats and dogs in order to predict the safety profile for the therapeutic use of insulin glulisine in humans; all studies used normoglycemic animals. After a single injection of insulin glulisine, the approximate LD50 was >1000 U/kg in rats and mice and 40 U/kg in dogs. After repeated once daily subcutaneous injection of insulin glulisine, the No Observable Adverse Effect Level (NOAEL) in rats were 50 U/kg after 1 month and 5 U/kg after 6 months. The NOAEL in dogs were 1 U/kg in both the 1month and 6-month studies. The toxicological profile of insulin glulisine was limited to the effects resulting from excessive hypoglycemia attributed to the exaggerated pharmacodynamic action of the compound after high doses in normoglycemic animals. Repeated-dose toxicity studies in rats and dogs did not reveal any unexpected findings different from human regular insulin. Insulin glulisine-related effects in toxicity studies were dose-dependent, reversible and restricted to toxic dose levels. Clinical observations and pathological findings obtained in these studies were similar or comparable to those in human beings observed after hyperinsulinemia/ hypoglycemia. In some cases, excessive hypoglycemia caused the deaths of animals. These findings in healthy, non-diabetic animals are not indicative of any specific toxicity on insulin glulisine in patients, where it is used for controlled glucose-lowering effects at therapeutic doses. Carcinogenesis In Sprague Dawley rats, a 12-month repeat dose toxicity study was conducted with insulin glulisine at doses of 2.5, 5, 20 or 50 U/kg twice daily (dose resulting in an exposure equivalent to approximately 26, 54, 258, 662 times the human Cmax at the average human dose, respectively). The incidence of mortality increased dose dependently in 2x20 and 2x50 U/kg insulin glulisine or IU/kg human insulin treated groups respectively. Generally, males were more severely affected than females and mortality at the comparable dose levels was always higher in the human insulin treated groups. In this study, the effects of insulin glulisine on cellular proliferation in mammary glands were evaluated using Ki-67 immunohistochemistry. There were no significant differences in mammary cell proliferation between insulin glulisine, regular human insulin and control groups. Page 33 of 61
Page 1 and 2: PRODUCT MONOGRAPH APIDRA ® insulin
Page 3 and 4: PRODUCT MONOGRAPH APIDRA ® insulin
Page 5 and 6: PHARMACOLOGY). APIDRA given by subc
Page 7 and 8: Hyperglycemia: The use of too low i
Page 9 and 10: and reduced insulin metabolism, sim
Page 11 and 12: Occupational Hazards The patient’
Page 13 and 14: Table 2 - Number (percentage) of pe
Page 15 and 16: Table 4 - Common (≥1%) Adverse Dr
Page 17 and 18: Table 5- Established or Potential D
Page 19 and 20: APIDRA should be administered by su
Page 21 and 22: ACTION AND CLINICAL PHARMACOLOGY Ph
Page 23 and 24: Table 7. Pharmacokinetic and Pharma
Page 25 and 26: gender did not show differences in
Page 27 and 28: Opened APIDRA SoloSTAR should not b
Page 29 and 30: glargine followed by randomization.
Page 31: treatment regimens. No differences
Page 35 and 36: Table 14: Reproductive & Developmen
Page 37 and 38: Table 15: Reproductive & Developmen
Page 39 and 40: PART III: CONSUMER INFORMATION APID
Page 41 and 42: INTERACTIONS WITH THIS MEDICATION O
Page 43 and 44: 12. Make sure the tip of the needle
Page 45 and 46: Hyperglycemia Hyperglycemia (too mu
Page 47 and 48: MORE INFORMATION Your physician, ph
Page 49 and 50: APIDRA should be given within 15 mi
Page 51 and 52: Do not take a double dose to make u
Page 53 and 54: history of diabetes, or in patients
Page 55 and 56: MORE INFORMATION Your physician, ph
Page 57 and 58: efore or within 20 minutes after st
Page 59 and 60: Preparing the Dose 1. To avoid medi
Page 61: • redness, itching, swelling, or

Apidra (insulin glulisine) - Sanofi Canada

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