Apidra Information
Apidra () Indications And Usage
Apidra () is indicated to improve glycemic control in adults and children with diabetes mellitus.
Apidra () Dosage And Administration
Apidra () is a recombinant insulin analog that is equipotent to human insulin (i.e. one unit of Apidra () has the same glucose-lowering effect as one unit of regular human insulin) when given intravenously. When given subcutaneously, Apidra () has a more rapid onset of action and a shorter duration of action than regular human insulin.
The dosage of Apidra () must be individualized. Blood glucose monitoring is essential in all patients receiving insulin therapy.
The total daily insulin requirement may vary and is usually between 0.5 to 1 Unit/kg/day. Insulin requirements may be altered during stress, major illness, or with changes in exercise, meal patterns, or coadministered drugs.
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 reduce the risk of lipodystrophy .
Apidra () may be administered by continuous subcutaneous infusion in the abdominal wall. Do not use diluted or mixed insulins in external insulin pumps. Infusion sites should be rotated within the same region to reduce the risk of lipodystrophy . 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 () :
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 carefully evaluate information on pump use in the Apidra () prescribing information, Patient Information Leaflet, and the pump manufacturer's manual. 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.
Based on studies which have shown loss of the preservative, metacresol and insulin degradation, Apidra () in the reservoir should be changed at least every 48 hours. Apidra () in clinical use should not be exposed to temperatures greater than 98.6°F (37°C). .
Apidra () Dosage Forms And Strengths
Apidra () 100 units per mL (U-100) is available as:
Apidra () Contraindications
Apidra () is contraindicated:
Apidra () Warnings And Precautions
Glucose monitoring is essential for patients receiving insulin therapy. Changes to an insulin regimen should be made cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type, or method of administration may result in the need for a change in insulin dose. Concomitant oral antidiabetic treatment may need to be adjusted.
As with all insulin preparations, the time course of action for Apidra () may vary in different individuals or at different times in the same individual and is dependent on many conditions, including the site of injection, local blood supply, or local temperature. Patients who change their level of physical activity or meal plan may require adjustment of insulin dosages.
Hypoglycemia is the most common adverse reaction of insulin therapy, including Apidra () . The risk of hypoglycemia increases with tighter glycemic control. Patients must be educated to recognize and manage hypoglycemia. Severe hypoglycemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or death. Severe hypoglycemia requiring the assistance of another person and/or parenteral glucose infusion or glucagon administration has been observed in clinical trials with insulin, including trials with Apidra () .
The timing of hypoglycemia usually reflects the time-action profile of the administered insulin formulations. Other factors such as changes in food intake (e.g., amount of food or timing of meals), injection site, exercise, and concomitant medications may also alter the risk of hypoglycemia .
As with all insulins, use caution in patients with hypoglycemia unawareness and in patients who may be predisposed to hypoglycemia (e.g., the pediatric population and patients who fast or have erratic food intake). The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery.
Rapid changes in serum glucose levels may induce symptoms similar to hypoglycemia in persons with diabetes, regardless of the glucose value. Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as longstanding diabetes, diabetic nerve disease, use of medications such as beta-blockers , or intensified diabetes control. These situations may result in severe hypoglycemia (and, possibly, loss of consciousness) prior to the patient's awareness of hypoglycemia.
Intravenously administered insulin has a more rapid onset of action than subcutaneously administered insulin, requiring closer monitoring for hypoglycemia.
Apidra () for subcutaneous injection should not be mixed with insulin preparations other than NPH insulin. If Apidra () is mixed with NPH insulin, Apidra () should be drawn into the syringe first. Injection should occur immediately after mixing.
Do not mix Apidra () with other insulins for intravenous administration or for use in a continuous subcutaneous infusion pump.
Apidra () for intravenous administration should not be diluted with solutions other than 0.9% sodium chloride (normal saline). The efficacy and safety of mixing Apidra () with diluents or other insulins for use in external subcutaneous infusion pumps have not been established.
When used in an external insulin pump for subcutaneous infusion, Apidra () should not be diluted or mixed with any other insulin. Apidra () in the reservoir should be changed at least every 48 hours. Apidra () should not be exposed to temperatures greater than 98.6°F (37°C).
Malfunction of the insulin pump or infusion set or insulin degradation can rapidly lead to hyperglycemia and ketosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Interim subcutaneous injections with Apidra () may be required. Patients using continuous subcutaneous insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure..
When Apidra () is administered intravenously, glucose and potassium levels must be closely monitored to avoid potentially fatal hypoglycemia and hypokalemia.
Do not mix Apidra () with other insulins for intravenous administration. Apidra () may be diluted only in normal saline solution.
Apidra () Adverse Reactions
The following adverse reactions are discussed elsewhere:
Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.
The frequencies of adverse drug reactions during Apidra () clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below.
The following adverse reactions have been identified during post-approval use of Apidra () .
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure.
Medication errors have been reported in which other insulins, particularly long-acting insulins, have been accidentally administered instead of Apidra () .
Apidra () Drug Interactions
A number of drugs affect glucose metabolism and may necessitate insulin dose adjustment and particularly close monitoring.
Drugs that may increase the blood glucose-lowering effect of insulins including Apidra () , and therefore increase the risk of hypoglycemia, include oral antidiabetic products, pramlintide, ACE inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, propoxyphene, pentoxifylline, salicylates, somatostatin analogs, and sulfonamide antibiotics.
Drugs that may reduce the blood-glucose-lowering effect of Apidra () include corticosteroids, niacin, danazol, diuretics, sympathomimetic agents (e.g., epinephrine, albuterol, terbutaline), glucagon, isoniazid, phenothiazine derivatives, somatropin, thyroid hormones, estrogens, progestogens (e.g., in oral contraceptives), protease inhibitors, and atypical antipsychotics.
Beta-blockers, clonidine, lithium salts, and alcohol may either increase or decrease the blood-glucose-lowering effect of insulin.
Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.
The signs of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs such as beta-blockers, clonidine, guanethidine, and reserpine.
Apidra () Use In Specific Populations
The safety and effectiveness of subcutaneous injections of Apidra () have been established in pediatric patients (age 4 to 17 years) with type 1 diabetes . 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 blood glucose.
Apidra () Overdosage
Excess insulin may cause hypoglycemia and, particularly when given intravenously, hypokalemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes of hypoglycemia with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately.
Apidra () Description
Apidra () (insulin glulisine [rDNA origin] injection) is a rapid-acting human insulin analog used to lower blood glucose. Insulin glulisine is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of (K12). Insulin glulisine differs from human insulin in that the amino acid asparagine at position B3 is replaced by lysine and the lysine in position B29 is replaced by glutamic acid. Chemically, insulin glulisine is 3-lysine-29-glutamic acid-human insulin, has the empirical formula CHNOSand a molecular weight of 5823 and has the following structural formula:
Apidra () is a sterile, aqueous, clear, and colorless solution. Each milliliter of Apidra () contains 100 units (3.49 mg) insulin glulisine, 3.15 mg metacresol, 6 mg tromethamine, 5 mg sodium chloride, 0.01 mg polysorbate 20, and water for injection. Apidra () has a pH of approximately 7.3. The pH is adjusted by addition of aqueous solutions of hydrochloric acid and/or sodium hydroxide.
Apidra () Clinical Pharmacology
Regulation of glucose metabolism is the primary activity of insulins and insulin analogs, including insulin glulisine. Insulins lower blood glucose by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulins inhibit lipolysis and proteolysis, and enhance protein synthesis.
The glucose lowering activities of Apidra () and of regular human insulin are equipotent when administered by the intravenous route. After subcutaneous administration, the effect of Apidra () is more rapid in onset and of shorter duration compared to regular human insulin.
Studies in healthy volunteers and patients with diabetes demonstrated that Apidra () has a more rapid onset of action and a shorter duration of activity than regular human insulin when given subcutaneously.
In a study in patients with type 1 diabetes (n= 20), the glucose-lowering profiles of Apidra () and regular human insulin were assessed at various times in relation to a standard meal at a dose of 0.15 Units/kg. (Figure 1.)
The maximum blood glucose excursion (ΔGLU; baseline subtracted glucose concentration) for Apidra () injected 2 minutes before a meal was 65 mg/dL compared to 64 mg/dL for regular human insulin injected 30 minutes before a meal (see ), and 84 mg/dL for regular human insulin injected 2 minutes before a meal (see ). The maximum blood glucose excursion for Apidra () injected 15 minutes after the start of a meal was 85 mg/dL compared to 84 mg/dL for regular human insulin injected 2 minutes before a meal (see ).
Figure 1.
In a randomized, open-label, two-way crossover study, 16 healthy male subjects received an intravenous infusion of Apidra () or regular human insulin with saline diluent at a rate of 0.8 milliUnits/kg/min for two hours. Infusion of the same dose of Apidra () or regular human insulin produced equivalent glucose disposal at steady state.
Apidra () Clinical Studies
The safety and efficacy of Apidra () was studied in adult patients with type 1 and type 2 diabetes (n =1833) and in children and adolescent patients (4 to 17 years) with type 1 diabetes (n=572). The primary efficacy parameter in these trials was glycemic control, assessed using glycated hemoglobin (GHb reported as HbA equivalent).
Apidra () How Supplied/storage And Handling
Pen needles are not included in the packs.
BD Ultra-Fine™ pen needles to be used in conjunction with OptiClik are sold separately and are manufactured by Becton Dickinson and Company.
Solostar is compatible with all pen needles from Becton Dickinson and Company, Ypsomed and Owen Mumford.
Apidra () Patient Counseling Information
See FDA-approved patient labeling.
Patients should be instructed on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia.
Patients must be instructed on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, and skipped meals.
Refer patients to the Apidra () Patient Information Leaflet for additional information.
Women with diabetes should be advised to inform their doctor if they are pregnant or are contemplating pregnancy.
Accidental mix-ups between Apidra () and other insulins, particularly long-acting insulins, have been reported. To avoid medication errors between Apidra () and other insulins, patients should be instructed to always check the insulin label before each injection.
Patients using external pump infusion therapy should be trained appropriately.
The following insulin pumps have been used in Apidra () clinical trials conducted by sanofi-aventis, the manufacturer of Apidra () :
Before using a different insulin pump with Apidra () , read the pump label to make sure the pump has been evaluated with Apidra () .
To minimize insulin degradation, infusion set occlusion, and loss of the preservative (metacresol), the infusion sets (reservoir, tubing, and catheter) and the Apidra () in the reservoir should be replaced every 48 hours and a new infusion site should be selected. The temperature of the insulin may exceed ambient temperature when the pump housing, cover, tubing or sport case is exposed to sunlight or radiant heat. Insulin exposed to temperatures higher than 98.6°F (37°C) should be discarded. Infusion sites that are erythematous, pruritic, or thickened should be reported to the healthcare professional, and a new site selected because continued infusion may increase the skin reaction or alter the absorption of Apidra () .
Pump or infusion set malfunctions or insulin degradation can lead to rapid hyperglycemia and ketosis. This is especially pertinent for rapid-acting insulin analogs that are more rapidly absorbed through skin and have a shorter duration of action. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Problems include pump malfunction, infusion set occlusion, leakage, disconnection or kinking, and degraded insulin. Less commonly, hypoglycemia from pump malfunction may occur. If these problems cannot be promptly corrected, patients should resume therapy with subcutaneous insulin injection and contact their healthcare professional. .
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