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BROWSE topics
Rapid-Acting Analogues
Navigation (Insulin Classes) |
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Rapid-Acting Analogues
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Insulin Aspart - Novolog ®
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INDICATIONS AND USAGE Treatment of Diabetes Mellitus NovoLog is an insulin analog indicated to improve glycemic control in adults and children with diabetes mellitus. DOSAGE AND ADMINISTRATION Dosing NovoLog is an insulin analog with an earlier onset of action than regular human insulin. The dosage of NovoLog must be individualized. NovoLog given by subcutaneous injection should generally be used in regimens with an intermediate or long-acting insulin [see package insert for Warnings and Precautions (5), How Supplied/Storage and Handling (16.2)]. The total daily insulin requirement may vary and is usually between 0.5 to 1.0 units/kg/day. When used in a meal-related subcutaneous injection treatment regimen, 50 to 70% of total insulin requirements may be provided by NovoLog and the remainder provided by an intermediate-acting or long-acting insulin. Because of NovoLog’s comparatively rapid onset and short duration of glucose lowering activity, some patients may require more basal insulin and more total insulin to prevent pre-meal hyperglycemia when using NovoLog than when using human regular insulin. Do not use NovoLog that is viscous (thickened) or cloudy; use only if it is clear and colorless. NovoLog should not be used after the printed expiration date. Subcutaneous Injection NovoLog should be administered by subcutaneous injection in the abdominal region, buttocks, thigh, or upper arm. Because NovoLog has a more rapid onset and a shorter duration of activity than human regular insulin, it should be injected immediately (within 5-10 minutes) before a meal. Injection sites should be rotated within the same region to reduce the risk of lipodystrophy. As with all insulins, the duration of action of NovoLog will vary according to the dose, injection site, blood flow, temperature, and level of physical activity. NovoLog may be diluted with Insulin Diluting Medium for NovoLog for subcutaneous injection. Diluting one part NovoLog to nine parts diluent will yield a concentration one-tenth that of NovoLog (equivalent to U-10). Diluting one part NovoLog to one part diluent will yield a concentration one-half that of NovoLog (equivalent to U-50). Continuous Subcutaneous Insulin Infusion (CSII) by External Pump NovoLog can also be infused subcutaneously by an external insulin pump [see Warnings and Precautions (5.8, 5.9), How Supplied/Storage and Handling (16.2)]. Diluted insulin should not be used in external insulin pumps. Because NovoLog has a more rapid onset and a shorter duration of activity than human regular insulin, pre-meal boluses of NovoLog should be infused immediately (within 5-10 minutes) before a meal. 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. Although there is significant interpatient variability, approximately 50% of the total dose is usually given as meal-related boluses of NovoLog and the remainder is given as a basal infusion. Change the NovoLog in the reservoir at least every 6 days, change the infusion sets and the infusion set insertion site at least every 3 days. The following insulin pumps† have been used in NovoLog clinical or in vitro studies conducted by Novo Nordisk, the manufacturer of NovoLog: Medtronic Paradigm® 512 and 712 MiniMed 508 Disetronic® D-TRON® and H-TRON® Before using a different insulin pump with NovoLog, read the pump label to make sure the pump has been evaluated with NovoLog. Intravenous Use NovoLog can be administered intravenously under medical supervision for glycemic control with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia [see package insert for Warnings and Precautions (5), How Supplied/Storage and Handling (16.2)]. For intravenous use, NovoLog should be used at concentrations from 0.05 U/mL to 1.0 U/mL insulin aspart in infusion systems using polypropylene infusion bags. NovoLog has been shown to be stable in infusion fluids such as 0.9% sodium chloride. Inspect NovoLog for particulate matter and discoloration prior to parenteral administration. DOSAGE FORMS AND STRENGTHS NovoLog is available in the following package sizes: each presentation contains 100 units of insulin aspart per mL (U-100). 10 mL vials 3 mL PenFill cartridges for the 3 mL PenFill cartridge delivery device (with or without the addition of a NovoPen® 3 PenMate®) with NovoTwist® or NovoFine® disposable needles 3 mL NovoLog FlexPen CONTRAINDICATIONS NovoLog is contraindicated: -during episodes of hypoglycemia -in patients with hypersensitivity to NovoLog or one of its excipients. CLINICAL PHARMACOLOGY Mechanism of Action The primary activity of NovoLog is the regulation of glucose metabolism. Insulins, including NovoLog, bind to the insulin receptors on muscle and fat cells and lower blood glucose by facilitating the cellular uptake of glucose and simultaneously inhibiting the output of glucose from the liver. Pharmacodynamics Studies in normal volunteers and patients with diabetes demonstrated that subcutaneous administration of NovoLog has a more rapid onset of action than regular human insulin. In a study in patients with type 1 diabetes (n=22), the maximum glucose-lowering effect of NovoLog occurred between 1 and 3 hours after subcutaneous injection. The duration of action for NovoLog is 3 to 5 hours. The time course of action of insulin and insulin analogs such as NovoLog may vary considerably in different individuals or within the same individual. The parameters of NovoLog activity (time of onset, peak time and duration) as designated in Figure 2 should be considered only as general guidelines. The rate of insulin absorption and onset of activity is affected by the site of injection, exercise, and other variables Pharmacokinetics The single substitution of the amino acid proline with aspartic acid at position B28 in NovoLog reduces the molecule's tendency to form hexamers as observed with regular human insulin. NovoLog is, therefore, more rapidly absorbed after subcutaneous injection compared to regular human insulin. In a randomized, double-blind, crossover study 17 healthy Caucasian male subjects between 18 and 40 years of age received an intravenous infusion of either NovoLog or regular human insulin at 1.5 mU/kg/min for 120 minutes. The mean insulin clearance was similar for the two groups with mean values of 1.2 l/h/kg for the NovoLog group and 1.2 l/h/kg for the regular human insulin group. Bioavailability and Absorption - NovoLog has a faster absorption, a faster onset of action, and a shorter duration of action than regular human insulin after subcutaneous injection. The relative bioavailability of NovoLog compared to regular human insulin indicates that the two insulins are absorbed to a similar extent. In studies in healthy volunteers (total n=107) and patients with type 1 diabetes (total n=40), NovoLog consistently reached peak serum concentrations approximately twice as fast as regular human insulin. The median time to maximum concentration in these trials was 40 to 50 minutes for NovoLog versus 80 to 120 minutes for regular human insulin. In a clinical trial in patients with type 1 diabetes, NovoLog and regular human insulin, both administered subcutaneously at a dose of 0.15 U/kg body weight, reached mean maximum concentrations of 82 and 36 mU/L, respectively. Pharmacokinetic/pharmacodynamic characteristics of insulin aspart have not been established in patients with type 2 diabetes. The intra-individual variability in time to maximum serum insulin concentration for healthy male volunteers was significantly less for NovoLog than for regular human insulin. The clinical significance of this observation has not been established. In a clinical study in healthy non-obese subjects, the pharmacokinetic differences between NovoLog and regular human insulin described above, were observed independent of the site of injection (abdomen, thigh, or upper arm). Distribution and Elimination - NovoLog has low binding to plasma proteins (<10%), similar to that seen with regular human insulin. After subcutaneous administration in normal male volunteers (n=24), NovoLog was more rapidly eliminated than regular human insulin with an average apparent half-life of 81 minutes compared to 141 minutes for regular human insulin. Recommended Storage Unused NovoLog should be stored in a refrigerator between 2° and 8°C (36° to 46°F). Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze NovoLog and do not use NovoLog if it has been frozen. NovoLog should not be drawn into a syringe and stored for later use. Vials: After initial use a vial may be kept at temperatures below 30°C (86°F) for up to 28 days, but should not be exposed to excessive heat or sunlight. Opened vials may be refrigerated. Unpunctured vials can be used until the expiration date printed on the label if they are stored in a refrigerator. Keep unused vials in the carton so they will stay clean and protected from light. PenFill cartridges or NovoLog FlexPen: Once a cartridge or a NovoLog FlexPen is punctured, it should be kept at temperatures below 30°C (86°F) for up to 28 days, but should not be exposed to excessive heat or sunlight. A NovoLog FlexPen or cartridge in use must NOT be stored in the refrigerator. Keep the NovoLog FlexPen and all PenFill cartridges away from direct heat and sunlight. Unpunctured NovoLog FlexPen and PenFill cartridges can be used until the expiration date printed on the label if they are stored in a refrigerator. Keep unused NovoLog FlexPen and PenFill cartridges in the carton so they will stay clean and protected from light. Always remove the needle after each injection and store the 3 mL PenFill cartridge delivery device or NovoLog FlexPen without a needle attached. This prevents contamination and/or infection, or leakage of insulin, and will ensure accurate dosing. Always use a new needle for each injection to prevent contamination. Pump: NovoLog in the pump reservoir should be discarded after at least every 6 days of use or after exposure to temperatures that exceed 37°C (98.6°F). The infusion set and the infusion set insertion site should be changed at least every 3 days. Summary of Storage Conditions: The storage conditions are summarized in the following table:
NovoLog diluted with Insulin Diluting Medium for NovoLog to a concentration equivalent to U-10 or equivalent to U-50 may remain in patient use at temperatures below 30°C (86°F) for 28 days. Storage of NovoLog in Infusion Fluids Infusion bags prepared as indicated under Dosage and Administration (2) are stable at room temperature for 24 hours. Some insulin will be initially adsorbed to the material of the infusion bag. |
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Insulin Lispro - Humalog®
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INDICATIONS AND USAGE Humalog is an insulin analog that is indicated in the treatment of patients with diabetes mellitus for the control of hyperglycemia. Humalog has a more rapid onset and a shorter duration of action than Regular human insulin. Therefore, in patients with type 1 diabetes, Humalog should be used in regimens that include a longer–acting insulin. However, in patients with type 2 diabetes, Humalog may be used without a longer–acting insulin when used in combination therapy with sulfonylurea agents. Humalog may be used in an external insulin pump, but should not be diluted or mixed with any other insulin when used in the pump. CLINICAL PHARMACOLOGY Antidiabetic Activity The primary activity of insulin, including Humalog, is the regulation of glucose metabolism. In addition, all insulins have several anabolic and anti–catabolic actions on many tissues in the body. In muscle and other tissues (except the brain), insulin causes rapid transport of glucose and amino acids intracellularly, promotes anabolism, and inhibits protein catabolism. In the liver, insulin promotes the uptake and storage of glucose in the form of glycogen, inhibits gluconeogenesis, and promotes the conversion of excess glucose into fat. Humalog has been shown to be equipotent to human insulin on a molar basis. One unit of Humalog has the same glucose–lowering effect as one unit of Regular human insulin, but its effect is more rapid and of shorter duration. The glucose–lowering activity of Humalog and Regular human insulin is comparable when administered to nondiabetic subjects by the intravenous route. Pharmacokinetics --------------------------------------------------------------- Absorption and Bioavailability Humalog is as bioavailable as Regular human insulin, with absolute bioavailability ranging between 55% to 77% with doses between 0.1 to 0.2 U/kg, inclusive. Studies in nondiabetic subjects and patients with type 1 (insulin–dependent) diabetes demonstrated that Humalog is absorbed faster than Regular human insulin (U–100) (see Figure 1). In nondiabetic subjects given subcutaneous doses of Humalog ranging from 0.1 to 0.4 U/kg, peak serum concentrations were observed 30 to 90 minutes after dosing. When nondiabetic subjects received equivalent doses of Regular human insulin, peak insulin concentrations occurred between 50 to 120 minutes after dosing. Similar results were seen in patients with type 1 diabetes. The pharmacokinetic profiles of Humalog and Regular human insulin are comparable to one another when administered to nondiabetic subjects by the intravenous route. Humalog was absorbed at a consistently faster rate than Regular human insulin in healthy male volunteers given 0.2 U/kg Regular human insulin or Humalog at abdominal, deltoid, or femoral subcutaneous sites, the three sites often used by patients with diabetes. After abdominal administration of Humalog, serum drug levels are higher and the duration of action is slightly shorter than after deltoid or thigh administration (see DOSAGE AND ADMINISTRATION). Humalog has less intra– and inter–patient variability compared with Regular human insulin. Distribution The volume of distribution following injection of Humalog is identical to that of Regular human insulin, with a range of 0.26 to 0.36 L/kg. Metabolism Human metabolism studies have not been conducted. However, animal studies indicate that the metabolism of Humalog is identical to that of Regular human insulin. Elimination When Humalog is given subcutaneously, its t1/2 is shorter than that of Regular human insulin (1 versus 1.5 hours, respectively). When given intravenously, Humalog and Regular human insulin show identical dose–dependent elimination, with a t1/2 of 26 and 52 minutes at 0.1 U/kg and 0.2 U/kg, respectively. Pharmacodynamics Studies in nondiabetic subjects and patients with diabetes demonstrated that Humalog has a more rapid onset of glucose–lowering activity, an earlier peak for glucose–lowering, and a shorter duration of glucose–lowering activity than Regular human insulin. The earlier onset of activity of Humalog is directly related to its more rapid rate of absorption. The time course of action of insulin and insulin analogs, such as Humalog, may vary considerably in different individuals or within the same individual. The rate of insulin absorption and consequently the onset of activity is known to be affected by the site of injection, exercise, and other variables Special Populations------------------------- Age and Gender Information on the effect of age and gender on the pharmacokinetics of Humalog is unavailable. However, in large clinical trials, sub-group analysis based on age and gender did not indicate any difference in postprandial glucose parameters between Humalog and Regular human insulin. Smoking The effect of smoking on the pharmacokinetics and pharmacodynamics of Humalog has not been studied. Pregnancy The effect of pregnancy on the pharmacokinetics and pharmacodynamics of Humalog has not been studied. Obesity The effect of obesity and/or subcutaneous fat thickness on the pharmacokinetics and pharmacodynamics of Humalog has not been studied. In large clinical trials, which included patients with Body Mass Index up to and including 35 kg/m2, no consistent differences were observed between Humalog and Humulin® R with respect to postprandial glucose parameters. Renal Impairment Some studies with human insulin have shown increased circulating levels of insulin in patients with renal failure. In a study of 25 patients with type 2 diabetes and a wide range of renal function, the pharmacokinetic differences between Humalog and Regular human insulin were generally maintained. However, the sensitivity of the patients to insulin did change, with an increased response to insulin as the renal function declined. Careful glucose monitoring and dose reductions of insulin, including Humalog, may be necessary in patients with renal dysfunction. Hepatic Impairment Some studies with human insulin have shown increased circulating levels of insulin in patients with hepatic failure. In a study of 22 patients with type 2 diabetes, impaired hepatic function did not affect the subcutaneous absorption or general disposition of Humalog when compared with patients with no history of hepatic dysfunction. In that study, Humalog maintained its more rapid absorption and elimination when compared with Regular human insulin. Careful glucose monitoring and dose adjustments of insulin, including Humalog, may be necessary in patients with hepatic dysfunction. CONTRAINDICATIONS Humalog is contraindicated during episodes of hypoglycemia and in patients sensitive to Humalog or any of its excipients. WARNINGS This human insulin analog differs from Regular human insulin by its rapid onset of action as well as a shorter duration of activity. When used as a meal-time insulin, the dose of Humalog should be given within 15 minutes before or immediately after the meal. Because of the short duration of action of Humalog, patients with type 1 diabetes also require a longer–acting insulin to maintain glucose control (except when using an external insulin pump). Glucose monitoring is recommended for all patients with diabetes and is particularly important for patients using an external insulin pump. Hypoglycemia is the most common adverse effect associated with insulins, including Humalog. As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. Glucose monitoring is recommended for all patients with diabetes. Any change of insulin should be made cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type (e.g., Regular, NPH, analog), species, or method of manufacture may result in the need for a change in dosage. External Insulin Pumps: When used in an external insulin pump, Humalog should not be diluted or mixed with any other insulin. Patients should carefully read and follow the external insulin pump manufacturer’s instructions and the Patient Information leaflet before using Humalog. Physicians should carefully evaluate information on external insulin pump use in this Humalog physician package insert and in the external insulin pump manufacturer’s instructions. If unexplained hyperglycemia or ketosis occurs during external insulin pump use, prompt identification and correction of the cause is necessary. The patient may require interim therapy with subcutaneous insulin injection PRECAUTIONS General Hypoglycemia and hypokalemia are among the potential clinical adverse effects associated with the use of all insulins. Because of differences in the action of Humalog and other insulins, care should be taken in patients in whom such potential side effects might be clinically relevant (e.g., patients who are fasting, have autonomic neuropathy, or are using potassium–lowering drugs or patients taking drugs sensitive to serum potassium level). Lipodystrophy and hypersensitivity are among other potential clinical adverse effects associated with the use of all insulins. As with all insulin preparations, the time course of Humalog action may vary in different individuals or at different times in the same individual and is dependent on site of injection, blood supply, temperature, and physical activity. Adjustment of dosage of any insulin may be necessary if patients change their physical activity or their usual meal plan. Insulin requirements may be altered during illness, emotional disturbances, or other stress. Hypoglycemia — As with all insulin preparations, hypoglycemic reactions may be associated with the administration of Humalog. Rapid changes in serum glucose concentrations may induce symptoms of 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 long duration of diabetes, diabetic nerve disease, use of medications such as beta–blockers, or intensified diabetes control. Renal Impairment — The requirements for insulin may be reduced in patients with renal impairment. Hepatic Impairment — Although impaired hepatic function does not affect the absorption or disposition of Humalog, careful glucose monitoring and dose adjustments of insulin, including Humalog, may be necessary. Allergy — Local Allergy — As with any insulin therapy, patients may experience redness, swelling, or itching at the site of injection. These minor reactions usually resolve in a few days to a few weeks. In some instances, these reactions may be related to factors other than insulin, such as irritants in the skin cleansing agent or poor injection technique. Systemic Allergy — Less common, but potentially more serious, is generalized allergy to insulin, which may cause rash (including pruritus) over the whole body, shortness of breath, wheezing, reduction in blood pressure, rapid pulse, or sweating. Severe cases of generalized allergy, including anaphylactic reaction, may be life threatening. In controlled clinical trials, pruritus (with or without rash) was seen in 17 patients receiving Humulin R (N=2969) and 30 patients receiving Humalog (N=2944) (p=0.053). Localized reactions and generalized myalgias have been reported with the use of cresol as an injectable excipient. Antibody Production — In large clinical trials, antibodies that cross–react with human insulin and insulin lispro were observed in both Humulin R– and Humalog–treatment groups. As expected, the largest increase in the antibody levels during the 12–month clinical trials was observed with patients new to insulin therapy. Usage in External Insulin Pumps — The infusion set (reservoir syringe, tubing, and catheter), Disetronic® D–TRON®2,3 or D–TRON®2,3plus cartridge adapter, and Humalog in the external insulin pump reservoir should be replaced and a new infusion site selected every 48 hours or less. Humalog in the external insulin pump should not be exposed to temperatures above 37°C (98.6°F). In the D–TRON®2,3 or D–TRON®2,3plus pump, Humalog 3 mL cartridges may be used for up to 7 days. However, as with other external insulin pumps, the infusion set should be replaced and a new infusion site should be selected every 48 hours or less. When used in an external insulin pump, Humalog should not be diluted or mixed with any other insulin DOSAGE AND ADMINISTRATION Humalog is intended for subcutaneous administration, including use in select external insulin pumps (see DOSAGE AND ADMINISTRATION, External Insulin Pumps). Dosage regimens of Humalog will vary among patients and should be determined by the healthcare provider familiar with the patient’s metabolic needs, eating habits, and other lifestyle variables. Pharmacokinetic and pharmacodynamic studies showed Humalog to be equipotent to Regular human insulin (i.e., one unit of Humalog has the same glucose–lowering effect as one unit of Regular human insulin), but with more rapid activity. The quicker glucose–lowering effect of Humalog is related to the more rapid absorption rate from subcutaneous tissue. An adjustment of dose or schedule of basal insulin may be needed when a patient changes from other insulins to Humalog, particularly to prevent pre–meal hyperglycemia. When used as a meal–time insulin, Humalog should be given within 15 minutes before or immediately after a meal. Regular human insulin is best given 30 to 60 minutes before a meal. To achieve optimal glucose control, the amount of longer–acting insulin being given may need to be adjusted when using Humalog. The rate of insulin absorption and consequently the onset of activity are known to be affected by the site of injection, exercise, and other variables. Humalog was absorbed at a consistently faster rate than Regular human insulin in healthy male volunteers given 0.2 U/kg Regular human insulin or Humalog at abdominal, deltoid, or femoral sites, the three sites often used by patients with diabetes. When not mixed in the same syringe with other insulins, Humalog maintains its rapid onset of action and has less variability in its onset of action among injection sites compared with Regular human insulin (see PRECAUTIONS). After abdominal administration, Humalog concentrations are higher than those following deltoid or thigh injections. Also, the duration of action of Humalog is slightly shorter following abdominal injection, compared with deltoid and femoral injections. As with all insulin preparations, the time course of action of Humalog may vary considerably in different individuals or within the same individual. Patients must be educated to use proper injection techniques. Humalog in a vial may be diluted with STERILE DILUENT for Humalog®, Humulin® N, Humulin® R, Humulin® 70/30, and Humulin® R U-500 to a concentration of 1:10 (equivalent to U–10) or 1:2 (equivalent to U–50). Diluted Humalog may remain in patient use for 28 days when stored at 5°C (41°F) and for 14 days when stored at 30°C (86°F). Do not dilute Humalog contained in a cartridge or Humalog used in an external insulin pump. Parenteral drug products should be inspected visually before use whenever the solution and the container permit. If the solution is cloudy, contains particulate matter, is thickened, or is discolored, the contents must not be injected. Humalog should not be used after its expiration date. The cartridge containing Humalog is not designed to allow any other insulin to be mixed in the cartridge or for the cartridge to be refilled with insulin. External Insulin Pumps — Humalog was tested in MiniMed®1 Models 506, 507, and 508 insulin pumps using MiniMed®1 Polyfin®1 infusion sets. Humalog was also tested in the Disetronic®2 H–TRONplus® V100 insulin pump (with plastic 3.15 mL insulin reservoir) and the Disetronic D–TRON®2,3 and D–TRON®2,3plus pumps (with Humalog 3 mL cartridges) using Disetronic Rapid®2 infusion sets. Humalog should not be diluted or mixed with any other insulin when used in an external insulin pump. Storage — Unopened Humalog should be stored in a refrigerator [2° to 8°C (36° to 46°F)], but not in the freezer. Do not use Humalog if it has been frozen. Unrefrigerated [below 30°C (86°F)] vials, cartridges, Pens, and Humalog KwikPen must be used within 28 days or be discarded, even if they still contain Humalog. Protect from direct heat and light. See table below:
Use in an External Insulin Pump — A Humalog 3 mL cartridge used in the D–TRON®2,3 or D–TRON®2,3plus should be discarded after 7 days, even if it still contains Humalog. Infusion sets, D–TRON®2,3 and D–TRON®2,3plus cartridge adapters, and Humalog in the external insulin pump reservoir should be discarded every 48 hours or less. |
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Insulin Glulisine- Apidra®
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INDICATIONS AND USAGE APIDRA is a rapid acting human insulin analog indicated to improve glycemic control in adults and children with diabetes mellitus. DOSAGE AND ADMINISTRATION The dosage of APIDRA must be individualized:
Dosage considerations 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. 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 reduce the risk of lipodystrophy Continuous subcutaneous infusion (insulin pump) 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 [See Adverse Reactions (6.1)]. 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 pumps1 have been used in APIDRA clinical trials conducted by sanofi-aventis, the manufacturer of 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 in vitro 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). Intravenous administration APIDRA can be administered intravenously under medical supervision for glycemic control with close monitoring of blood glucose and serum potassium to avoid hypoglycemia and hypokalemia. 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 discoloration prior to administration, whenever solution and container permit. Do not administer insulin mixtures intravenously. DOSAGE FORMS AND STRENGTHS APIDRA 100 units/mL (U-100) is available as:
CONTRAINDICATIONS
Adverse reactions commonly associated with APIDRA include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, and rash. To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch DRUG INTERACTIONS
APIDRA has not been studied in children under 4 years of age Pregnancy Pregnancy Category C: Reproduction and teratology studies have been performed with insulin glulisine in rats and rabbits using regular human insulin as a comparator. Insulin glulisine was given to female rats throughout pregnancy at subcutaneous doses up to 10 Units/kg once daily (dose resulting in an exposure 2 times the average human dose, based on body surface area comparison) and did not have any remarkable toxic effects on embryo-fetal development. 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 average human dose, based on body surface area comparison). Adverse effects on embryo-fetal development were only seen at maternal toxic dose levels inducing hypoglycemia. Increased incidence of post-implantation losses and skeletal defects were observed at a dose level of 1.5 Units/kg once daily (dose resulting in an exposure 0.5 times the average human dose, based on body surface area comparison) that also caused mortality in dams. A slight increased incidence of post-implantation losses was seen at the next lower dose level of 0.5 Units/kg once daily (dose resulting in an exposure 0.2 times the average human dose, based on body surface area comparison) which was also associated with severe hypoglycemia but there were no defects at that dose. No effects were observed in rabbits at a dose of 0.25 Units/kg once daily (dose resulting in an exposure 0.1 times the average human dose, based on body surface area comparison). 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. There are no well-controlled clinical studies of the use of APIDRA in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is essential for patients with diabetes or a history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. Insulin requirements may decrease during the first trimester, generally increase during the second and third trimesters, and rapidly decline after delivery. Careful monitoring of glucose control is essential in these patients. Nursing mothers It is unknown whether insulin glulisine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when APIDRA is administered to a nursing woman. Use of APIDRA is compatible with breastfeeding, but women with diabetes who are lactating may require adjustments of their insulin doses. Pediatric use 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. 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 small subset of elderly patients had type 2 diabetes. The
change in HbA1c values and hypoglycemia frequencies did not differ by age.
Nevertheless, caution should be exercised when APIDRA is administered to
geriatric patients.CLINICAL PHARMACOLOGY Mechanism of action 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. Pharmacodynamics 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. The maximum blood glucose excursion (  GLUmax; 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, and 84
mg/dL for regular human insulin injected 2 minutes before a meal. 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.Storage Do not use after the expiration date (see carton and container). Unopened Vial/Cartridge System/SoloStar Unopened APIDRA vials, cartridge systems and SoloStar should be stored in a refrigerator, 36°F–46°F (2°C–8°C). Protect from light. APIDRA should not be stored in the freezer and it should not be allowed to freeze. Discard if it has been frozen. Unopened vials/cartridge systems/SoloStar not stored in a refrigerator must be used within 28 days. Open (In-Use) Vial: Opened vials, whether or not refrigerated, 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 temperature is not greater than 77°F (25°C). Open (In-Use) Cartridge System: The opened (in-use) cartridge system inserted in OptiClik® should NOT be refrigerated but should be kept below 77°F (25°C) away from direct heat and light. The opened (in-use) cartridge system must be discarded after 28 days. Do not store OptiClik®, with or without cartridge system, in a refrigerator at any time. Open (In-Use) SoloStar prefilled pen: The opened (in-use) SoloStar should NOT be refrigerated but should be kept below 77°F (25°C) away from direct heat and light. The opened (in-use) SoloStar kept at room temperature must be discarded after 28 days. Infusion sets: Infusion sets (reservoirs, tubing, and catheters) and the APIDRA in the reservoir should be discarded after 48 hours of use or after exposure to temperatures that exceed 98.6°F (37°C). Intravenous use: Infusion bags prepared as indicated under DOSAGE AND ADMINISTRATION (2.4) are stable at room temperature for 48 hours. Preparation and handling After dilution for intravenous use, the solution should be inspected visually for particulate matter and discoloration prior to administration. Do not use the solution if it has become cloudy or contains particles; use only if it is clear and colorless. APIDRA is not compatible with Dextrose solution and Ringers solution and, therefore, cannot be used with these solution fluids. The use of APIDRA with other solutions has not been studied and is, therefore, not recommended. Cartridge system: If OptiClik® (the Insulin Delivery Device for APIDRA) malfunctions, APIDRA may be drawn from the cartridge system into a U-100 syringe and injected. |
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Disclaimer |
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| The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. Read the disclaimer | ||||||||||||||||||||||||||||||||
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