Humalog Information
Humalog (Insulin) Indications And Usage
Humalog (Insulin) is an insulin analog indicated to improve glycemic control in adults and children with diabetes mellitus.
Humalog (Insulin) Dosage And Administration
When given subcutaneously, Humalog (Insulin) has a more rapid onset of action and a shorter duration of action than regular human insulin.
The dosage of Humalog (Insulin) 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.
Humalog (Insulin) should be given within 15 minutes before a meal or immediately after a meal.
Humalog (Insulin) given by subcutaneous injection should generally be used in regimens with an intermediate- or long-acting insulin.
Humalog (Insulin) administered by subcutaneous injection should be given in the abdominal wall, thigh, upper arm, or buttocks. Injection sites should be rotated within the same region (abdomen, thigh, upper arm, or buttocks) from one injection to the next 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 variability among patients, approximately 50% of the total dose is usually given as meal-related boluses of Humalog (Insulin) and the remainder is given as a basal infusion. Humalog (Insulin) is recommended for use in pump systems suitable for insulin infusion such as MiniMed, Disetronic, and other equivalent pumps .
Humalog (Insulin) Dosage Forms And Strengths
Humalog (Insulin) 100 units per mL (U-100) is available as:
Humalog (Insulin) Contraindications
Humalog (Insulin) is contraindicated:
Humalog (Insulin) 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 Humalog (Insulin) 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 effect associated with insulins, including Humalog (Insulin) . The risk of hypoglycemia increases with tighter glycemic control. Patients must be educated to recognize and manage hypoglycemia. Hypoglycemia can happen suddenly and symptoms may be different for each person and may change from time to time. Severe hypoglycemia can cause seizures and may be life-threatening or cause death.
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.
Humalog (Insulin) for subcutaneous injection should not be mixed with insulin preparations other than NPH insulin. If Humalog (Insulin) is mixed with NPH insulin, Humalog (Insulin) should be drawn into the syringe first. Injection should occur immediately after mixing.
Do not mix Humalog (Insulin) with other insulins for use in an external subcutaneous infusion pump.
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 Humalog (Insulin) 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 .
Humalog (Insulin) 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 with those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.
The frequencies of Treatment-Emergent Adverse Events during Humalog (Insulin) clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below.
The following additional adverse reactions have been identified during post-approval use of Humalog (Insulin) . Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Medication errors in which other insulins have been accidentally substituted for Humalog (Insulin) have been identified during postapproval use .
Humalog (Insulin) Drug Interactions
A number of drugs affect glucose metabolism and may require insulin dose adjustment and particularly close monitoring.
Following are some of the examples:
Humalog (Insulin) Use In Specific Populations
Pregnancy Category B. All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and may be decreased with good metabolic control. It is essential for patients with diabetes or history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. In patients with diabetes or gestational diabetes 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. Therefore, female patients should be advised to tell their physicians if they intend to become, or if they become pregnant while taking Humalog (Insulin) .
Although there are limited clinical studies of the use of Humalog (Insulin) in pregnancy, published studies with human insulins suggest that optimizing overall glycemic control, including postprandial control, before conception and during pregnancy improves fetal outcome.
In a combined fertility and embryo-fetal development study, female rats were given subcutaneous insulin lispro injections of 5 and 20 units/kg/day (0.8 and 3 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area, respectively) from 2 weeks prior to cohabitation through Gestation Day 19. There were no adverse effects on female fertility, implantation, or fetal viability and morphology. However, fetal growth retardation was produced at the 20 units/kg/day-dose as indicated by decreased fetal weight and an increased incidence of fetal runts/litter.
In an embryo-fetal development study in pregnant rabbits, insulin lispro doses of 0.1, 0.25, and 0.75 unit/kg/day (0.03, 0.08, and 0.24 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area, respectively) were injected subcutaneously on Gestation days 7 through 19. There were no adverse effects on fetal viability, weight, and morphology at any dose.
Humalog (Insulin) is approved for use in children for subcutaneous daily injections and for subcutaneous continuous infusion by external insulin pump. Humalog (Insulin) has not been studied in pediatric patients younger than 3 years of age. Humalog (Insulin) has not been studied in pediatric patients with type 2 diabetes .
As in adults, the dosage of Humalog (Insulin) must be individualized in pediatric patients based on metabolic needs and results of frequent monitoring of blood glucose.
Humalog (Insulin) Overdosage
Excess insulin administration may cause hypoglycemia and 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 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.
Humalog (Insulin) Description
Humalog (Insulin) (insulin lispro injection, USP [rDNA origin]) is a rapid-acting human insulin analog used to lower blood glucose. Insulin lispro is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of . Insulin lispro differs from human insulin in that the amino acid proline at position B28 is replaced by lysine and the lysine in position B29 is replaced by proline. Chemically, it is Lys(B28), Pro(B29) human insulin analog and has the empirical formula CHNOS and a molecular weight of 5808, both identical to that of human insulin.
Humalog (Insulin) has the following primary structure:
Humalog (Insulin) is a sterile, aqueous, clear, and colorless solution. Each milliliter of Humalog (Insulin) contains insulin lispro 100 units, 16 mg glycerin, 1.88 mg dibasic sodium phosphate, 3.15 mg Metacresol, zinc oxide content adjusted to provide 0.0197 mg zinc ion, trace amounts of phenol, and Water for Injection. Insulin lispro has a pH of 7.0 to 7.8. The pH is adjusted by addition of aqueous solutions of hydrochloric acid 10% and/or sodium hydroxide 10%.
Humalog (Insulin) Clinical Pharmacology
Humalog (Insulin) has been shown to be equipotent to human insulin on a molar basis. One unit of Humalog (Insulin) has the same glucose-lowering effect as one unit of regular human insulin. Studies in normal volunteers and patients with diabetes demonstrated that Humalog (Insulin) has a more rapid onset of action and a shorter duration of activity than regular human insulin when given subcutaneously.
The time course of action of insulin and insulin analogs, such as Humalog (Insulin) , may vary considerably in different individuals or within the same individual. The parameters of Humalog (Insulin) activity (time of onset, peak time, and duration) as designated in should be considered only as general guidelines. 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 .
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Humalog (Insulin) Nonclinical Toxicology
Standard 2-year carcinogenicity studies in animals have not been performed. In Fischer 344 rats, a 12-month repeat-dose toxicity study was conducted with insulin lispro at subcutaneous doses of 20 and 200 units/kg/day (approximately 3 and 32 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area). Insulin lispro did not produce important target organ toxicity including mammary tumors at any dose.
Insulin lispro was not mutagenic in the following genetic toxicity assays: bacterial mutation, unscheduled DNA synthesis, mouse lymphoma, chromosomal aberration and micronucleus assays.
Male fertility was not compromised when male rats given subcutaneous insulin lispro injections of 5 and 20 units/kg/day (0.8 and 3 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area) for 6 months were mated with untreated female rats. In a combined fertility, perinatal, and postnatal study in male and female rats given 1, 5, and 20 units/kg/day subcutaneously (0.16, 0.8, and 3 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area), mating and fertility were not adversely affected in either gender at any dose.
Humalog (Insulin) Clinical Studies
The safety and efficacy of Humalog (Insulin) were studied in children, adolescent, and adult patients with type 1 diabetes (n=789) and adult patients with type 2 diabetes (n=722).
Humalog (Insulin) How Supplied/storage And Handling
Do not use after the expiration date.
Unopened Humalog (Insulin) should be stored in a refrigerator (36° to 46°F [2° to 8°C]), but not in the freezer. Do not use Humalog (Insulin) if it has been frozen. In-use Humalog (Insulin) vials, cartridges, pens, and Humalog (Insulin) KwikPen should be stored at room temperature, below 86°F (30°C) and must be used within 28 days or be discarded, even if they still contain Humalog (Insulin) . Protect from direct heat and light. See table below:
Humalog (Insulin) 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 Humalog (Insulin) 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 Humalog (Insulin) and other insulins have been reported. To avoid medication errors between Humalog (Insulin) 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 tested in Humalog (Insulin) clinical trials conducted by Eli Lilly and Company.
Humalog (Insulin) is recommended for use in pump systems suitable for insulin infusion such as MiniMed, Disetronic, and other equivalent pumps. Before using Humalog (Insulin) in a pump system, read the pump label to make sure the pump is indicated for continuous delivery of fast-acting insulin. Humalog (Insulin) is recommended for use in any reservoir and infusion sets that are compatible with insulin and the specific pump. Please see recommended reservoir and infusion sets in the pump manual.
To avoid insulin degradation, infusion set occlusion, and loss of the preservative (metacresol), insulin in the reservoir should be replaced at least every 7 days; infusion sets and infusion set insertion sites should be changed at least every 3 days.
Insulin exposed to temperatures higher than 98.6°F (37°C) should be discarded.
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 professionals. .
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Humalog (Insulin) , Humalog (Insulin) KwikPen™, HumaPen, HumaPen Memoir™, HumaPen Luxura™ and HumaPen Luxura™ HD are trademarks of Eli Lilly and Company.
Other product and company names may be the trademarks of their respective owners.
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