Lantus Information
Lantus (Insulin) . Indications And Usage
Lantus (Insulin) is indicated to improve glycemic control in adults and children with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus.
Important Limitations of Use:
Lantus (Insulin) . Dosage And Administration
Lantus (Insulin) is a recombinant human insulin analog for once daily subcutaneous administration with potency that is approximately the same as the potency of human insulin. Lantus (Insulin) exhibits a relatively constant glucose-lowering profile over 24 hours that permits once-daily dosing.
Lantus (Insulin) may be administered at any time during the day. Lantus (Insulin) should be administered subcutaneously once a day at the same time every day. The dose of Lantus (Insulin) must be individualized based on clinical response. Blood glucose monitoring is essential in all patients receiving insulin therapy.
Patients adjusting the amount or timing of dosing with Lantus (Insulin) , should only do so under medical supervision with appropriate glucose monitoring .]
In patients with type 1 diabetes, Lantus (Insulin) must be used in regimens with short-acting insulin.
The intended duration of activity of Lantus (Insulin) is dependent on injection into subcutaneous tissue . Lantus (Insulin) should not be administered intravenously or via an insulin pump. Intravenous administration of the usual subcutaneous dose could result in severe hypoglycemia .
As with all insulins, injection sites should be rotated within the same region (abdomen, thigh, or deltoid) from one injection to the next to reduce the risk of lipodystrophy
In clinical studies, there was no clinically relevant difference in insulin glargine absorption after abdominal, deltoid, or thigh subcutaneous administration. As for all insulins, the rate of absorption, and consequently the onset and duration of action, may be affected by exercise and other variables, such as stress, intercurrent illness, or changes in co-administered drugs or meal patterns
The recommended starting dose of Lantus (Insulin) in patients with type 1 diabetes should be approximately one-third of the total daily insulin requirements. Short-acting, premeal insulin should be used to satisfy the remainder of the daily insulin requirements.
The recommended starting dose of Lantus (Insulin) in patients with type 2 diabetes who are not currently treated with insulin is 10 units (or 0.2 Units/kg) once daily, which should subsequently be adjusted to the patient's needs.
The dose of Lantus (Insulin) should be adjusted according to blood glucose measurements. The dosage of Lantus (Insulin) should be individualized under the supervision of a healthcare provider in accordance with the needs of the patient.
Lantus (Insulin) . Dosage Forms And Strengths
Lantus (Insulin) solution for injection 100 Units per mL is available as:
Lantus (Insulin) . Contraindications
Lantus (Insulin) is contraindicated in patients with hypersensitivity to Lantus (Insulin) or one of its excipients.
Lantus (Insulin) . Warnings And Precautions
Glucose monitoring is essential for all 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 or an adjustment in concomitant oral anti-diabetic treatment.
As with all insulin preparations, the time course of action for Lantus (Insulin) may vary in different individuals or at different times in the same individual and is dependent on many conditions, including the local blood supply, local temperature, and physical activity.
Do not administer Lantus (Insulin) intravenously or via an insulin pump. The intended duration of activity of Lantus (Insulin) is dependent on injection into subcutaneous tissue
Intravenous administration of the usual subcutaneous dose could result in severe hypoglycemia .
Do not dilute or mix Lantus (Insulin) with any other insulin or solution. If Lantus (Insulin) is diluted or mixed, the solution may become cloudy, and the pharmacokinetic or pharmacodynamic profile (e.g., onset of action, time to peak effect) of Lantus (Insulin) and the mixed insulin may be altered in an unpredictable manner. When Lantus (Insulin) and regular human insulin were mixed immediately before injection in dogs, a delayed onset of action and a delayed time to maximum effect for regular human insulin was observed. The total bioavailability of the mixture was also slightly decreased compared to separate injections of Lantus (Insulin) and regular human insulin. The relevance of these observations in dogs to humans is unknown.
Do not share disposable or reusable insulin devices or needles between patients, because doing so carries a risk for transmission of blood-borne pathogens.
Hypoglycemia is the most common adverse reaction of insulin, including Lantus (Insulin) . The risk of hypoglycemia increases with intensive glycemic control. Patients must be educated to recognize and manage hypoglycemia. Severe hypoglycemia can lead to unconsciousness or convulsions and may result in temporary or permanent impairment of brain function or death. Severe hypoglycemia requiring the assistance of another person or parenteral glucose infusion or glucagon administration has been observed in clinical trials with insulin, including trials with Lantus (Insulin) .
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), exercise, and concomitant medications may also alter the risk of hypoglycemia [].
The prolonged effect of subcutaneous Lantus (Insulin) may delay recovery from hypoglycemia. Patients being switched from twice daily NPH insulin to once-daily Lantus (Insulin) should have their initial Lantus (Insulin) dose reduced by 20% from the previous total daily NPH dose to reduce 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.
Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as longstanding diabetes, diabetic neuropathy, use of medications such as beta-blockers, or intensified glycemic control. These situations may result in severe hypoglycemia (and, possibly, loss of consciousness) prior to the patient's awareness of hypoglycemia.
Due to its long duration of action, Lantus (Insulin) is not recommended during periods of rapidly declining renal function because of the risk for prolonged hypoglycemia.
Although studies have not been performed in patients with diabetes and renal impairment, a reduction in the Lantus (Insulin) dose may be required in patients with renal impairment because of reduced insulin metabolism, similar to observations found with other insulins.
Due to its long duration of action, Lantus (Insulin) is not recommended during periods of rapidly declining hepatic function because of the risk for prolonged hypoglycemia.
Although studies have not been performed in patients with diabetes and hepatic impairment, a reduction in the Lantus (Insulin) dose may be required in patients with hepatic impairment because of reduced capacity for gluconeogenesis and reduced insulin metabolism, similar to observations found with other insulins.
Lantus (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 to 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 Lantus (Insulin) 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 Lantus (Insulin) .
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 short-acting insulins, have been accidentally administered instead of Lantus (Insulin) ]. To avoid medication errors between Lantus (Insulin) and other insulins, patients should be instructed to always verify the insulin label before each injection.
Lantus (Insulin) . Drug Interactions
A number of drugs affect glucose metabolism and may require insulin dose adjustment and particularly close monitoring.
The following are examples of drugs that may increase the blood-glucose-lowering effect of insulins including Lantus (Insulin) and, therefore, increase the susceptibility to hypoglycemia: oral anti-diabetic products, pramlintide, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, propoxyphene, pentoxifylline, salicylates, somatostatin analogs, and sulfonamide antibiotics.
The following are examples of drugs that may reduce the blood-glucose-lowering effect of insulins including Lantus (Insulin) : 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 antipsychotic medications (e.g. olanzapine and clozapine).
Beta-blockers, clonidine, lithium salts, and alcohol may either potentiate or weaken 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 sympatholytic drugs such as beta-blockers, clonidine, guanethidine, and reserpine.
Lantus (Insulin) . Use In Specific Populations
The safety and effectiveness of subcutaneous injections of Lantus (Insulin) have been established in pediatric patients (age 6 to 15 years) with type 1 diabetes. Lantus (Insulin) has not been studied in pediatric patients younger than 6 years of age with type 1 diabetes. Lantus (Insulin) has not been studied in pediatric patients with type 2 diabetes.
Based on the results of a study in pediatric patients, the dose recommendation when switching to Lantus (Insulin) is the same as that described for adults andAs in adults, the dosage of Lantus (Insulin) must be individualized in pediatric patients based on metabolic needs and frequent monitoring of blood glucose.
In controlled clinical studies comparing Lantus (Insulin) to NPH insulin, 593 of 3890 patients (15%) with type 1 and type 2 diabetes were ≥65 years of age and 80 (2%) patients were ≥75 years of age. The only difference in safety or effectiveness in the subpopulation of patients ≥65 years of age compared to the entire study population was a higher incidence of cardiovascular events typically seen in an older population in both Lantus (Insulin) and NPH insulin-treated patients.
Nevertheless, caution should be exercised when Lantus (Insulin) is administered to geriatric patients. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in the elderly
Lantus (Insulin) . Overdosage
An excess of insulin relative to food intake, energy expenditure, or both may lead to severe and sometimes prolonged and life-threatening hypoglycemia. Mild episodes of hypoglycemia can usually be treated with oral carbohydrates. 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. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid recurrence of hypoglycemia.
Lantus (Insulin) . Description
Lantus (Insulin) (insulin glargine [rDNA origin] injection) is a sterile solution of insulin glargine for use as a subcutaneous injection. Insulin glargine is a recombinant human insulin analog that is a long-acting (up to 24-hour duration of action), parenteral blood-glucose-lowering agent []. Lantus (Insulin) is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of (K12) as the production organism. Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain. Chemically, insulin glargine is 21-Gly-30a-L-Arg-30b-L-Arg-human insulin and has the empirical formula CHNOSand a molecular weight of 6063. Insulin glargine has the following structural formula:
Lantus (Insulin) consists of insulin glargine dissolved in a clear aqueous fluid. Each milliliter of Lantus (Insulin) (insulin glargine injection) contains 100 Units (3.6378 mg) insulin glargine.
The 10 mL vial presentation contains the following inactive ingredients per mL: 30 mcg zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, 20 mcg polysorbate 20, and water for injection.
The 3 mL cartridge presentation contains the following inactive ingredients per mL: 30 mcg zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, and water for injection.
The pH is adjusted by addition of aqueous solutions of hydrochloric acid and sodium hydroxide. Lantus (Insulin) has a pH of approximately 4.
Lantus (Insulin) . Clinical Pharmacology
Insulin glargine is a human insulin analog that has been designed to have low aqueous solubility at neutral pH. At pH 4, as in the Lantus (Insulin) injection solution, insulin glargine is completely soluble. After injection into the subcutaneous tissue, the acidic solution is neutralized, leading to formation of microprecipitates from which small amounts of insulin glargine are slowly released, resulting in a relatively constant concentration/time profile over 24 hours with no pronounced peak. This profile allows once-daily dosing as a basal insulin.
In clinical studies, the glucose-lowering effect on a molar basis (i.e., when given at the same doses) of intravenous insulin glargine is approximately the same as that for human insulin. In euglycemic clamp studies in healthy subjects or in patients with type 1 diabetes, the onset of action of subcutaneous insulin glargine was slower than NPH insulin. The effect profile of insulin glargine was relatively constant with no pronounced peak and the duration of its effect was prolonged compared to NPH insulin. shows results from a study in patients with type 1 diabetes conducted for a maximum of 24 hours after the injection. The median time between injection and the end of pharmacological effect was 14.5 hours (range: 9.5 to 19.3 hours) for NPH insulin, and 24 hours (range: 10.8 to >24.0 hours) (24 hours was the end of the observation period) for insulin glargine.
Figure 1. Activity Profile in Patients with Type 1 Diabetes
* Determined as amount of glucose infused to maintain constant plasma glucose levels (hourly mean values); indicative of insulin activity.
The longer duration of action (up to 24 hours) of Lantus (Insulin) is directly related to its slower rate of absorption and supports once-daily subcutaneous administration. The time course of action of insulins, including Lantus (Insulin) , may vary between individuals and within the same individual.
Lantus (Insulin) . Clinical Studies
The safety and effectiveness of Lantus (Insulin) given once-daily at bedtime was compared to that of once-daily and twice-daily NPH insulin in open-label, randomized, active-controlled, parallel studies of 2,327 adult patients and 349 pediatric patients with type 1 diabetes mellitus and 1,563 adult patients with type 2 diabetes mellitus (see Tables 8–11). In general, the reduction in glycated hemoglobin (HbA1c) with Lantus (Insulin) was similar to that with NPH insulin. The overall rates of hypoglycemia did not differ between patients with diabetes treated with Lantus (Insulin) compared to NPH insulin .
Type 1 Diabetes–Adult (see ).
In two clinical studies (Studies A and B), patients with type 1 diabetes (Study A; n=585, Study B; n=534) were randomized to 28 weeks of basal-bolus treatment with Lantus (Insulin) or NPH insulin. Regular human insulin was administered before each meal. Lantus (Insulin) was administered at bedtime. NPH insulin was administered once daily at bedtime or in the morning and at bedtime when used twice daily.
In another clinical study (Study C), patients with type 1 diabetes (n=619) were randomized to 16 weeks of basal-bolus treatment with Lantus (Insulin) or NPH insulin. Insulin lispro was used before each meal. Lantus (Insulin) was administered once daily at bedtime and NPH insulin was administered once or twice daily.
In these 3 studies, Lantus (Insulin) and NPH insulin had similar effects on HbA1c (Table 8) with a similar overall rate of hypoglycemia .
Type 1 Diabetes–Pediatric (see ).
In a randomized, controlled clinical study (Study D), pediatric patients (age range 6 to 15 years) with type 1 diabetes (n=349) were treated for 28 weeks with a basal-bolus insulin regimen where regular human insulin was used before each meal. Lantus (Insulin) was administered once daily at bedtime and NPH insulin was administered once or twice daily. Similar effects on HbA1c (Table 9) and the incidence of hypoglycemia were observed in both treatment groups .
Type 2 Diabetes–Adult (see ).
In a randomized, controlled clinical study (Study E) (n=570), Lantus (Insulin) was evaluated for 52 weeks in combination with oral anti-diabetic medications (a sulfonylurea, metformin, acarbose, or combinations of these drugs). Lantus (Insulin) administered once daily at bedtime was as effective as NPH insulin administered once daily at bedtime in reducing HbA1c and fasting glucose (Table 10). The rate of hypoglycemia was similar in Lantus (Insulin) and NPH insulin treated patients .
In a randomized, controlled clinical study (Study F), in patients with type 2 diabetes not using oral anti-diabetic medications (n=518), a basal-bolus regimen of Lantus (Insulin) once daily at bedtime or NPH insulin administered once or twice daily was evaluated for 28 weeks. Regular human insulin was used before meals, as needed. Lantus (Insulin) had similar effectiveness as either once- or twice-daily NPH insulin in reducing HbA1c and fasting glucose (Table 10) with a similar incidence of hypoglycemia .
In a randomized, controlled clinical study (Study G), patients with type 2 diabetes were randomized to 5 years of treatment with once-daily Lantus (Insulin) or twice-daily NPH insulin. For patients not previously treated with insulin, the starting dose of Lantus (Insulin) or NPH insulin was 10 units daily. Patients who were already treated with NPH insulin either continued on the same total daily NPH insulin dose or started Lantus (Insulin) at a dose that was 80% of the total previous NPH insulin dose. The primary endpoint for this study was a comparison of the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. HbA1c change from baseline was a secondary endpoint. Similar glycemic control in the 2 treatment groups was desired in order to not confound the interpretation of the retinal data. Patients or study personnel used an algorithm to adjust the Lantus (Insulin) and NPH insulin doses to a target fasting plasma glucose ≤100 mg/dL. After the Lantus (Insulin) or NPH insulin dose was adjusted, other anti-diabetic agents, including pre-meal insulin were to be adjusted or added. The Lantus (Insulin) group had a smaller mean reduction from baseline in HbA1c compared to the NPH insulin group, which may be explained by the lower daily basal insulin doses in the Lantus (Insulin) group (Table 10). Both treatment groups had a similar incidence of reported symptomatic hypoglycemia. The incidences of severe symptomatic hypoglycemia are given in Table 6 .
Lantus (Insulin) Timing of Daily Dosing (see ).
The safety and efficacy of Lantus (Insulin) administered pre-breakfast, pre-dinner, or at bedtime were evaluated in a randomized, controlled clinical study in patients with type 1 diabetes (study H, n=378). Patients were also treated with insulin lispro at mealtime. Lantus (Insulin) administered at different times of the day resulted in similar reductions in HbA1c compared to that with bedtime administration (see ). In these patients, data are available from 8-point home glucose monitoring. The maximum mean blood glucose was observed just prior to injection of Lantus (Insulin) regardless of time of administration.
In this study, 5% of patients in the Lantus (Insulin) -breakfast arm discontinued treatment because of lack of efficacy. No patients in the other two arms discontinued for this reason. The safety and efficacy of Lantus (Insulin) administered pre-breakfast or at bedtime were also evaluated in a randomized, active-controlled clinical study (Study I, n=697) in patients with type 2 diabetes not adequately controlled on oral anti-diabetic therapy. All patients in this study also received glimepiride 3 mg daily. Lantus (Insulin) given before breakfast was at least as effective in lowering HbA1c as Lantus (Insulin) given at bedtime or NPH insulin given at bedtime (see ).
Lantus (Insulin) . How Supplied/storage And Handling
Lantus (Insulin) solution for injection 100 units per mL (U-100) is available as:
Needles are not included in the packs.
BD Ultra-Fine™ needles to be used in conjunction with SoloStar and OptiClik are sold separately and are manufactured by BD.
Parenteral drug products should be inspected visually prior to administration whenever the solution and the container permit. Lantus (Insulin) must only be used if the solution is clear and colorless with no particles visible.
Mixing and diluting: Lantus (Insulin) must NOT be diluted or mixed with any other insulin or solution [S.
Vial:
Cartridge system/SoloStar
Lantus (Insulin) . Patient Counseling Information
Patients should be informed that changes to insulin regimens must be made cautiously and only under medical supervision.
Patients should be informed about the potential side effects of insulin therapy, including lipodystrophy (and the need to rotate injection sites within the same body region), weight gain, allergic reactions, and hypoglycemia. Patients should be informed that the 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. Patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia should be advised to use caution when driving or operating machinery.
Accidental mix-ups between Lantus (Insulin) and other insulins, particularly short-acting insulins, have been reported. To avoid medication errors between Lantus (Insulin) and other insulins, patients should be instructed to always check the insulin label before each injection.
Lantus (Insulin) must only be used if the solution is clear and colorless with no particles visible Patients must be advised that Lantus (Insulin) must NOT be diluted or mixed with any other insulin or solution
Patients should be advised not to share disposable or reusable insulin devices or needles with other patients, because doing so carries a risk for transmission of blood-borne pathogens.
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.
Patients with diabetes should be advised to inform their health care professional if they are pregnant or are contemplating pregnancy.
Refer patients to the Lantus (Insulin) "Patient Information" for additional information.
Lantus (Insulin)
Lantus (Insulin)
Lantus (Insulin)
Lantus (Insulin)
Lantus (Insulin)
Lantus (Insulin)
Lantus (Insulin)
Lantus (Insulin)
Lantus (Insulin)
Lantus (Insulin)
Lantus (Insulin)
