Lantus 100 UNT/ML Injectable Solution
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 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: 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.
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.
DESCRIPTION
LANTUS (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 [ See Clinical Pharmacology (12) ].
LANTUS is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (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 A-Gly-30 Ba-L-Arg-30 Bb-L-Arg-human insulin and has the empirical formula C 267H 404N 72O 78S 6 and a molecular weight of 6063.
Insulin glargine has the following structural formula: LANTUS consists of insulin glargine dissolved in a clear aqueous fluid.
Each milliliter of LANTUS (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 has a pH of approximately 4.
MM1
CLINICAL STUDIES
The safety and effectiveness of LANTUS 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), whose primary efficacy aim was the assessment of effects on blood glucose, as measured by HbA1c.
In general, the reduction in glycated hemoglobin (HbA1c) with LANTUS was similar to that with NPH insulin.
The overall rates of hypoglycemia did not differ between patients with diabetes treated with LANTUS compared to NPH insulin [See Adverse Reactions (6.1)] .
In the 12,537-participants, 6 to 7 year ORIGIN trial LANTUS was compared to standard glycemic management (largely non-insulin) in reducing cardiovascular (CV) risk as measured by CV outcome events.
Type 1 Diabetes–Adult (see Table 9).
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 or NPH insulin.
Regular human insulin was administered before each meal.
LANTUS 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 or NPH insulin.
Insulin lispro was used before each meal.
LANTUS was administered once daily at bedtime and NPH insulin was administered once or twice daily.
In these 3 studies, LANTUS and NPH insulin had similar effects on HbA1c (Table 9) with a similar overall rate of hypoglycemia [See Adverse Reactions (6.1)] .
Table 9: Type 1 Diabetes Mellitus–Adult Study A Study B Study C Treatment duration Treatment in combination with 28 weeks Regular insulin 28 weeks Regular insulin 16 weeks Insulin lispro LANTUS NPH LANTUS NPH LANTUS NPH Number of subjects treated 292 293 264 270 310 309 HbA1c Baseline HbA1c 8.0 8.0 7.7 7.7 7.6 7.7 Adj.
mean change from baseline +0.2 +0.1 -0.2 -0.2 -0.1 -0.1 LANTUS – NPH +0.1 +0.1 0.0 95% CI for Treatment difference (0.0; +0.2) (-0.1; +0.2) (-0.1; +0.1) Basal insulin dose Baseline mean 21 23 29 29 28 28 Mean change from baseline -2 0 -4 +2 -5 +1 Total insulin dose Baseline mean 48 52 50 51 50 50 Mean change from baseline -1 0 0 +4 -3 0 Fasting blood glucose (mg/dL) Baseline mean 167 166 166 175 175 173 Adj.
mean change from baseline -21 -16 -20 -17 -29 -12 Body weight (kg) Baseline mean 73.2 74.8 75.5 75.0 74.8 75.6 Mean change from baseline 0.1 -0.0 0.7 1.0 0.1 0.5 Type 1 Diabetes–Pediatric (see Table 10).
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 was administered once daily at bedtime and NPH insulin was administered once or twice daily.
Similar effects on HbA1c (Table 10) and the incidence of hypoglycemia were observed in both treatment groups [See Adverse Reactions (6.1)] .
Table 10: Type 1 Diabetes Mellitus–Pediatric Study D Treatment duration 28 weeks Treatment in combination with Regular insulin LANTUS NPH Number of subjects treated 174 175 HbA1c Baseline mean 8.5 8.8 Adj.
mean change from baseline +0.3 +0.3 LANTUS – NPH 0.0 95% CI for Treatment difference (-0.2; +0.3) Basal insulin dose Baseline mean 19 19 Mean change from baseline -1 +2 Total insulin dose Baseline mean 43 43 Mean change from baseline +2 +3 Fasting blood glucose (mg/dL) Baseline mean 194 191 Adj.
mean change from baseline -23 -12 Body weight (kg) Baseline mean 45.5 44.6 Mean change from baseline 2.2 2.5 Type 2 Diabetes–Adult (see Table 11).
In a randomized, controlled clinical study (Study E) (n=570), LANTUS was evaluated for 52 weeks in combination with oral anti-diabetic medications (a sulfonylurea, metformin, acarbose, or combinations of these drugs).
LANTUS administered once daily at bedtime was as effective as NPH insulin administered once daily at bedtime in reducing HbA1c and fasting glucose (Table 11).
The rate of hypoglycemia was similar in LANTUS and NPH insulin treated patients [See Adverse Reactions (6.1)] .
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 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 had similar effectiveness as either once- or twice-daily NPH insulin in reducing HbA1c and fasting glucose (Table 11) with a similar incidence of hypoglycemia [See Adverse Reactions (6.1)] .
In a randomized, controlled clinical study (Study G), patients with type 2 diabetes were randomized to 5 years of treatment with once-daily LANTUS or twice-daily NPH insulin.
For patients not previously treated with insulin, the starting dose of LANTUS 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 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 and NPH insulin doses to a target fasting plasma glucose ≤100 mg/dL.
After the LANTUS or NPH insulin dose was adjusted, other anti-diabetic agents, including pre-meal insulin were to be adjusted or added.
The LANTUS 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 group (Table 11).
Both treatment groups had a similar incidence of reported symptomatic hypoglycemia.
The incidences of severe symptomatic hypoglycemia are given in Table 6 [See Adverse Reactions (6.1)] .
Table 11: Type 2 Diabetes Mellitus–Adult Study E Study F Study G Treatment duration 52 weeks 28 weeks 5 years Treatment in combination with Oral agents Regular insulin Regular insulin LANTUS NPH LANTUS NPH LANTUS NPH Number of subjects treated 289 281 259 259 513 504 HbA1c Baseline mean 9.0 8.9 8.6 8.5 8.4 8.3 Adj.
mean change from baseline -0.5 -0.4 -0.4 -0.6 -0.6 -0.8 LANTUS – NPH -0.1 +0.2 +0.2 95% CI for Treatment difference (-0.3; +0.1) (0.0; +0.4) (+0.1, +0.4) Basal insulin dose * Baseline mean 14 15 44.1 45.5 39 44 Mean change from baseline +12 +9 -1 +7 +23 +30 Total insulin dose Baseline mean 14 15 64 67 48 53 Mean change from baseline +12 +9 +10 +13 +41 +40 Fasting blood glucose (mg/dL) Baseline mean 179 180 164 166 190 180 Adj.
mean change from baseline -49 -46 -24 -22 -45 -44 Body weight (kg) Baseline mean 83.5 82.1 89.6 90.7 100 99 Adj.
mean change from baseline 2.0 1.9 0.4 1.4 3.7 4.8 In Study G, the baseline dose of basal or total insulin was the first available on-treatment dose prescribed during the study (on visit month 1.5).
The ORIGIN (Outcome Reduction with Initial Glargine INtervention) trial was a, international, multicenter, randomized, 2×2 factorial design study conducted in 12,537 participants with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or early type 2 diabetes mellitus and evidence of CV disease.
Participants were randomized to receive LANTUS (n=6264), titrated to a FPG of 95 mg/dL (5.3mM) or less, or Standard Care (n=6273).
At baseline participants had a mean age of 63.5 years, mean duration of diabetes of 5.8 years in those with pre-existing diabetes, and median HbA1c of 6.4%.
Median duration of follow-up was approximately 6.2 years.
At the end of the trial 81% of participants randomized to take LANTUS were still on treatment.
Median on-treatment HbA1c values ranged from 5.9 to 6.4 % in the LANTUS group, and 6.2% to 6.6% in the Standard Care group throughout the duration of follow-up.
Median FPG in the LANTUS group was at target (≤95mg/dL) following dose titration for the duration of the study.
The incidences of severe symptomatic hypoglycemia are given in Table 7 [See Adverse Reactions (6.1)] .
The median of the change in body weight from baseline to the last on-treatment visit was 2.2 kg greater in the Lantus group than in the Standard Care group.
The primary objective of this trial was to examine the effect of LANTUS on two co-primary composite efficacy outcomes.
The first one was the time to the first occurrence of CV death, nonfatal myocardial infarction (MI), or nonfatal stroke, and the second one was the time to the first occurrence of any of the first co-primary events, or revascularization procedure (cardiac, carotid, or peripheral), or hospitalization for heart failure.
Secondary endpoints were: all-cause mortality a composite microvascular outcome development of type 2 diabetes, in participants with IGT and/or IFG at baseline The primary and secondary outcome results, as well as the results for each component of the coprimary outcomes, are displayed in the two tables (table 12 for the time-to-event analyses, and, for the non-time-to-event analysis of development of diabetes, table 13) below.
Table 12: ORIGIN: Time to Onset of each Primary and Secondary Endpoint LANTUS N=6264 Standard care N=6273 Lantus vs Standard care Participants with Events N (%) Participants with Events N (%) Hazard Ratio (95% CI) Primary endpoints CV death, nonfatal myocardial infarction (MI), or nonfatal stroke 1041 (16.6) 1013 (16.1) 1.02 (0.94, 1.11) CV death, nonfatal myocardial infarction (MI), or nonfatal stroke, or hospitalization for heart failure or revascularization procedure 1792 (28.6) 1727 (27.5) 1.04 (0.97, 1.11) Secondary endpoints All-cause mortality 951 (15.2) 965 (15.4) 0.98 (0.90, 1.08) Composite microvascular outcome * 1323 (21.1) 1363 (21.7) 0.97 (0.90, 1.05) Components of coprimary endpoint CV death 580 (9.3) 576 (9.2) 1.00 (0.89, 1.13) MI (fatal or non-fatal) 336 (5.4) 326 (5.2) 1.03 (0.88, 1.19) stroke(fatal or non-fatal) 331 (5.3) 319 (5.1) 1.03 (0.89, 1.21) Revascularizations 908 (14.5) 860 (13.7) 1.06 (0.96, 1.16) Hospitalization for heart failure 310 (4.9) 343 (5.5) 0.90 (0.77, 1.05) with components of: laser photocoagulation or vitrectomy or blindness for diabetic retinopathy; progression in albuminuria; or doubling of serum creatinine or development of the need for renal replacement therapy Table 13: Incidence Rate of Diabetes by end of study OGTT * Treatment (N) LANTUS (6264) Standard Care (6273) Number of Participants † 737 719 # participants who developed diabetes (%) 182 (24.7) 224 (31.2) Odds Ratio (95% CI) 0.72 (0.58 to 0.91) End of study OGTT was performed 3–4 weeks after discontinuing LANTUS Participants with prediabetes (IFG or IGT) at baseline, based on an OGTT performed then; There were no statistical significant differences between treatment groups in the overall incidence of cancer (all types combined) or death from cancer.
The time to first event of any cancer or new cancer during the study was similar between the two treatment groups with respective hazard ratios of 0.99 (0.88, 1.11) and 0.96 (0.85, 1.09).
Participation in ORIGIN for a median of approximately 6.2 years showed that treatment with Lantus did not alter the risk for cardiovascular outcomes, all-cause mortality or cancer, when compared to standard glucose lowering therapy.
In addition, metabolic control was maintained at a lower level of glycemia, with a decrease in the percentage of participants developing diabetes, at a cost of a modest increase in hypoglycemia and weight gain.
LANTUS Timing of Daily Dosing (see Table 14).
The safety and efficacy of LANTUS 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 administered at different times of the day resulted in similar reductions in HbA1c compared to that with bedtime administration (see Table 11).
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 regardless of time of administration.
In this study, 5% of patients in the LANTUS-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 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 given before breakfast was at least as effective in lowering HbA1c as LANTUS given at bedtime or NPH insulin given at bedtime (see Table 12).
Table 14: LANTUS Timing of Daily Dosing in Type 1 (Study H) and Type 2 (Study I) Diabetes Mellitus Study H Study I Treatment duration 24 weeks 24 weeks Treatment in combination with: Insulin lispro Glimepiride LANTUS Breakfast LANTUS Dinner LANTUS Bedtime LANTUS Breakfast LANTUS Bedtime NPH Bedtime Number of subjects treated * 112 124 128 234 226 227 HbA1c Baseline mean 7.6 7.5 7.6 9.1 9.1 9.1 Mean change from baseline -0.2 -0.1 0.0 -1.3 -1.0 -0.8 Basal insulin dose (U) Baseline mean 22 23 21 19 20 19 Mean change from baseline 5 2 2 11 18 18 Total insulin dose (U) NA † NA NA Baseline mean 52 52 49 Mean change from baseline 2 3 2 Body weight (kg) Baseline mean 77.1 77.8 74.5 80.7 82 81 Mean change from baseline 0.7 0.1 0.4 3.9 3.7 2.9
HOW SUPPLIED
LANTUS solution for injection 100 units per mL (U-100) is available as: Dosage Unit/Strength Package size NDC # 0088 10 mL vials 100 Units/mL Pack of 1 2220-33 3 mL cartridge system * 100 Units/mL package of 5 2220-52 3 mL SoloStar ® disposable insulin device 100 Units/mL package of 5 2219-05 Cartridge systems are for use only in OptiClik Needles are not included in the packs.
BD Ultra-Fine™ needles 1 to be used in conjunction with SoloStar and OptiClik are sold separately and are manufactured by BD.
The brands listed are the registered trademarks of their respective owners and are not trademarks of sanofi-aventis U.S.
LLC LANTUS should not be stored in the freezer and should not be allowed to freeze.
Discard LANTUS if it has been frozen.
Unopened Vial/Cartridge system/SoloStar disposable insulin device: Unopened LANTUS vials, cartridge systems and SoloStar device should be stored in a refrigerator, 36°F – 46°F (2°C – 8°C).
Discard after the expiration date.
Open (In-Use) Vial: Vials must be discarded 28 days after being opened.
If refrigeration is not possible, the open vial can be kept unrefrigerated for up to 28 days away from direct heat and light, as long as the temperature is not greater than 86°F (30°C).
Open (In-Use) Cartridge system: The opened (in-use) cartridge system in OptiClik should NOT be refrigerated but should be kept at room temperature (below 86°F [30°C]) away from direct heat and light.
The opened (in-use) cartridge system in OptiClik must be discarded 28 days after being opened.
Do not store OptiClik , with or without cartridge system, in a refrigerator at any time.
Open (In-Use) SoloStar disposable insulin device: The opened (in-use) SoloStar should NOT be refrigerated but should be kept at room temperature (below 86°F [30°C]) away from direct heat and light.
The opened (in-use) SoloStar device must be discarded 28 days after being opened.
These storage conditions are summarized in the following table: Not in-use (unopened) Refrigerated Not in-use (unopened) Room Temperature In-use (opened) (See Temperature Below) 10 mL Vial Until expiration date 28 days 28 days Refrigerated or room temperature 3 mL Cartridge system Until expiration date 28 days 28 days Refrigerated or room temperature 3 mL Cartridge system inserted into OptiClik ® 28 days Room temperature only (Do not refrigerate) 3 mL SoloStar ® disposable insulin device Until expiration date 28 days 28 days Room temperature only (Do not refrigerate) Parenteral drug products should be inspected visually prior to administration whenever the solution and the container permit.
LANTUS must only be used if the solution is clear and colorless with no particles visible.
Mixing and diluting: LANTUS must NOT be diluted or mixed with any other insulin or solution [S ee Warnings and Precautions (5.2)] .
Vial: The syringes must not contain any other medicinal product or residue.
Cartridge system/SoloStar: If OptiClik, the Insulin Delivery Device used with the LANTUS cartridge system, or SoloStar disposable insulin device, malfunctions, LANTUS may be drawn from the cartridge system or from SoloStar into a U-100 syringe and injected.
DOSAGE FORMS AND STRENGTHS
DOSAGE FORMS & STRENGTHS LANTUS solution for injection 100 Units per mL is available as: -10 mL Vial (1000 Units/10 mL)-3 mL Cartridge systems for use only in OptiClik ® (300 Units/3 mL)-3 mL SoloStar ® disposable insulin device (300 Units/3 mL)
INDICATIONS AND USAGE
INDICATIONS & USAGE LANTUS 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 is not recommended for the treatment of diabetic ketoacidosis.
Intravenous short-acting insulin is the preferred treatment for this condition.
WARNING AND CAUTIONS
WARNINGS AND PRECAUTIONS Dose adjustment and monitoring: Monitor blood glucose in all patients treated with insulin.
Insulin regimens should be modified cautiously and only under medical supervision ( 5.1) Administration: Do not dilute or mix with any other insulin or solution.
Do not administer subcutaneously via an insulin pump or intravenously because severe hypoglycemia can occur ( 5.2) Do not share reusable or disposable insulin devices or needles between patients ( 5.2) Hypoglycemia: Most common adverse reaction of insulin therapy and may be life-threatening ( 5.3, 6.1) Allergic reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur ( 5.4, 6.1) Renal or hepatic impairment: May require a reduction in the LANTUS dose ( 5.5, 5.6) 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 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 intravenously or via an insulin pump.
The intended duration of activity of LANTUS is dependent on injection into subcutaneous tissue Intravenous administration of the usual subcutaneous dose could result in severe hypoglycemia [see Warnings and Precautions (5.3)] .
Do not dilute or mix LANTUS with any other insulin or solution.
If LANTUS 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 and the mixed insulin may be altered in an unpredictable manner.
When LANTUS 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 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.
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.
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 [ See Drug Interactions (7) ].
The prolonged effect of subcutaneous LANTUS may delay recovery from hypoglycemia.
Patients being switched from twice daily NPH insulin to once-daily LANTUS should have their initial LANTUS dose reduced by 20% from the previous total daily NPH dose to reduce the risk of hypoglycemia [see Dosage and Administration (2.3)].
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.
Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including LANTUS.
Due to its long duration of action, Lantus 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 dose may be required in patients with renal impairment because of reduced insulin metabolism, similar to observations found with other insulins.
[See Clinical Pharmacology (12.3)].
Due to its long duration of action, Lantus 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 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.
[See Clinical Pharmacology (12.3)].
Some medications may alter insulin requirements and subsequently increase the risk for hypoglycemia or hyperglycemia [See Drug Interactions (7)].
INFORMATION FOR PATIENTS
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 and other insulins, particularly short-acting insulins, have been reported.
To avoid medication errors between LANTUS and other insulins, patients should be instructed to always check the insulin label before each injection.
LANTUS must only be used if the solution is clear and colorless with no particles visible .
Patients must be advised that LANTUS 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 “Patient Information” for additional information.
See attached document at end of Full Prescribing Information.
DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION The starting dose should be individualized based on the type of diabetes and whether the patient is insulin-naïve ( 2.1, 2.2, 2.3) Administer subcutaneously once daily at any time of day, but at the same time every day.
( 2.1) Rotate injection sites within an injection area (abdomen, thigh, or deltoid) to reduce the risk of lipodystrophy.
( 2.1) Converting from other insulin therapies may require adjustment of timing and dose of LANTUS.
Closely monitor glucoses especially upon converting to LANTUS and during the initial weeks thereafter.
( 2.3) LANTUS 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 exhibits a relatively constant glucose-lowering profile over 24 hours that permits once-daily dosing.
LANTUS may be administered at any time during the day.
LANTUS should be administered subcutaneously once a day at the same time every day.
The dose of LANTUS 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, should only do so under medical supervision with appropriate glucose monitoring [see Warnings and Precautions (5.1) .] In patients with type 1 diabetes, LANTUS must be used in regimens with short-acting insulin.
The intended duration of activity of LANTUS is dependent on injection into subcutaneous tissue [see Clinical pharmacology (12.2)] .
LANTUS should not be administered intravenously or via an insulin pump.
Intravenous administration of the usual subcutaneous dose could result in severe hypoglycemia [see Warnings and Precautions (5.3)] .
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 [See Adverse Reactions (6.1)].
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 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 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 should be adjusted according to blood glucose measurements.
The dosage of LANTUS should be individualized under the supervision of a healthcare provider in accordance with the needs of the patient.
If changing from a treatment regimen with an intermediate- or long-acting insulin to a regimen with LANTUS, the amount and timing of shorter-acting insulins and doses of any oral anti-diabetic drugs may need to be adjusted.
If transferring patients from once-daily NPH insulin to once-daily LANTUS, the recommended initial LANTUS dose is the same as the dose of NPH that is being discontinued.
If transferring patients from twice-daily NPH insulin to once-daily LANTUS, the recommended initial LANTUS dose is 80% of the total NPH dose that is being discontinued.
This dose reduction will lower the likelihood of hypoglycemia [ see Warnings and Precautions (5.3)].