Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 15 May 2018
4 CONTRAINDICATIONS APIDRA is contraindicated: during episodes of hypoglycemia in patients who are hypersensitive to APIDRA or to any of its excipients When used in patients with known hypersensitivity to APIDRA or its excipients,
(6.1) To report SUSPECTED
The frequencies of
Table 1: Treatment -emergent
5 %) APIDRA, % (n=950) All comparatorsInsulin lispro, regular human insulin, insulin aspart, % (n=641) Nasopharyngitis 10.6 12.9 HypoglycemiaOnly
5 %) APIDRA, % (n=883) Regular human insulin, % (n=883) Upper respiratory tract
Table 3: Treatment -emergent
5 %) APIDRA, % (n=277) Lispro, % (n=295) Nasopharyngitis 9.0 9.5 Upper respiratory tract
The rates and incidence of
In the phase 3 clinical trial, children and adolescents with type 1 diabetes had a higher incidence of
(see Table 4) [See Clinical Studies (14)].
Type 1 Diabetes Adults 12 weeks with insulin glargine Type 1 Diabetes Adults 26 weeks with insulin glargine Type 2 Diabetes Adults 26 weeks with NPH human insulin Type 1 Diabetes Pediatrics 26 weeks APIDRA Pre-meal APIDRA Post-meal Regular Human Insulin APIDRA Insulin Lispro APIDRA Regular Human Insulin APIDRA Insulin Lispro Events per month per patient 0.05 0.05 0.13 0.02 0.02 0.00 0.00 0.09 0.08 Percent of patients (n/total N) 8.4 % (24/286) 8.4 % (25/296) 10.1 % (28/278) 4.8 % (16/339) 4.0 % (13/333) 1.4 % (6/416) 1.2 % (5/420) 16.2 % (45/277) 19.3 % (57/295) Insulin initiation and intensification of glucose control Intensification or
Lipodystrophy Long-term use of insulin, including APIDRA, can cause lipodystrophy at the site of repeated insulin injections or infusion.
Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue), and may affect insulin absorption.
Rotate insulin injection or infusion sites within the same region to
[See Dosage and Administration (2.2, 2.3)].
Peripheral Edema Insulin, including APIDRA, may cause sodium retention and edema, particularly if previously
Table 5: Catheter Occlusions and Infusion Site Reactions.
APIDRA (n=29) insulin aspart (n=30) Catheter occlusions/month 0.08 0.15 Infusion site reactions 10.3 % (3/29) 13.3 % (4/30)
In some instances, these reactions may be related to factors other than insulin, such as
Localized reactions and generalized myalgias have been reported with the use of metacresol, which is an excipient of APIDRA. Antibody
In a study in patients with type 2 diabetes (n=411), a similar
The clinical significance of these antibodies is not known.
APIDRA did not elicit a
6.2 Postmarketing experience The following
Because these reactions are reported voluntarily from
2 DOSAGE AND ADMINISTRATION The dosage of APIDRA must be individualized (2.1) Subcutaneous Injection Administer within 15 minutes before a meal or within 20 minutes after starting a meal.
Use in a regimen with an intermediate or long-acting insulin.
(2.1, 2.2) Continuous Subcutaneous Infusion Pump APIDRA must not be mixed or diluted when used in an external insulin infusion pump.
(2.3) Intravenous Infusion Infuse intravenously (0.05 Units/mL to 1 Units/mL APIDRA in 0.9 % sodium chloride using polyvinyl chloride infusion bags) only under
When given subcutaneously,
The dosage of
APIDRA must be individualized.
Blood glucose monitoring is essential in all patients receiving insulin therapy.
Insulin requirements may be altered during
2.2 Subcutaneous administration APIDRA should be given within 15 minutes before a meal or within 20 minutes after starting a meal.
APIDRA given by subcutaneous injection should generally be used in regimens with an intermediate or long-acting insulin.
APIDRA should be administered by subcutaneous injection in the abdominal wall, thigh, or upper arm.
Injection sites should be rotated within the same region (abdomen, thigh or upper arm) from one injection to the next to
2.3 Continuous subcutaneous infusion (insulin pump) APIDRA may be administered by continuous subcutaneous infusion in the abdominal wall.
Infusion sites should be rotated within the same region to
The initial programming of the external insulin infusion pump should be based on the total daily insulin dose of the previous regimen.
The following insulin pumps have been used in APIDRA clinical trials conducted by sanofi-aventis, the manufacturer of APIDRA: Disetronic® H-Tron® plus V100 and D-Tron® with Disetronic catheters (Rapid™,
Before using a different insulin pump with APIDRA, read the pump label to make sure the pump has been evaluated with APIDRA. Physicians and patients should
APIDRA-specific information should be followed for in-use time, frequency of changing infusion sets, or other details specific to APIDRA usage, because APIDRA-specific information may differ from general pump manual instructions.
Patients administering APIDRA by continuous subcutaneous infusion must have an alternative insulin delivery system in case of
Based on in_vitro studies which have shown
In clinical use, the infusion sets and the APIDRA in the reservoir must be changed at least every 48 hours [See Warnings and Precautions (5.8) and How Supplied/Storage and Handling (16.2)].
2.4 Intravenous administration APIDRA can be administered intravenously under
For intravenous use, APIDRA should be used at concentrations of 0.05 Units/mL to 1 Unit/mL insulin glulisine in infusion systems using polyvinyl chloride (PVC) bags.
APIDRA has been shown to be stable only in normal saline solution (0.9 % sodium chloride).
Parenteral drug products should be inspected visually for particulate matter and
Do not administer insulin mixtures intravenously.
8 USE IN SPECIFIC POPULATIONS APIDRA has not been studied in children under 4 years of age (8.4) 8.1 Pregnancy Pregnancy Category C: Reproduction and teratology studies have been performed with insulin glulisine in
Insulin glulisine was given to female
Insulin glulisine was given to female rabbits throughout pregnancy at subcutaneous doses up to 1.5 Units/ kg/day (dose resulting in an exposure 0.5 times the
The effects of insulin glulisine did not differ from those observed with subcutaneous regular human insulin at the same doses and were attributed to secondary effects of maternal hypoglycemia.
Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential
It is essential for patients with diabetes or a history of gestational diabetes to maintain
8.3 Nursing mothers It is unknown whether insulin glulisine is excreted in human milk.
Because many drugs are excreted in human milk,
8.4 Pediatric use
APIDRA has not been studied in pediatric patients with type 1 diabetes younger than 4 years of age and in pediatric patients with type 2 diabetes.
As in adults, the dosage of APIDRA must be individualized in pediatric patients based on metabolic needs and frequent monitoring of
8.5 Geriatric use In clinical trials (n=2408), APIDRA was administered to 147 patients?65 years of age and 27 patients?75 years of age.
The majority of this
The change in HbA1c values and hypoglycemia frequencies did not differ by age.
|Agency product number||7XIY785AZD|
|Date Last Revised||19-03-2015|
|Type||HUMAN PRESCRIPTION DRUG|
|Storage and handling||
Unopened Vial/SoloStar Unopened APIDRA vials and SoloStar should be stored in a refrigerator, 36°F-46°F (2°C-8°C).
APIDRA should not be stored in the freezer and it should not be allowed to freeze.
Unopened vials/SoloStar not stored in a refrigerator must be used within 28 days.
If refrigeration is not possible, the open vial in use can be kept unrefrigerated for up to 28 days away from direct heat and light, as long as
The opened (in-use)
Infusion sets (reservoirs, tubing, and catheters) and
Intravenous use: Infusion bags prepared as indicated under DOSAGE AND ADMINISTRATION (2.4) are stable at room temperature for 48 hours.
|Marketing authorisation holder||Sanofi-Aventis U.S. LLC|