LANTUS SIDE EFFECTS

SIDE EFFECTS

The following adverse reactions are discussed elsewhere:

• Hypoglycemia
• Hypoglycemia Due to Medication Errors
• Hypersensitivity Reactions
• Hypokalemia

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice.

The data in Table 1 reflect the exposure of 2,327 patients with type 1 diabetes to LANTUS or NPH in Studies A, B, C, and D. The type 1 diabetes population had the following characteristics: Mean age was 39 years. Fifty-four percent were male, 97% were Caucasian, 22% were Black or African American and 33% were Hispanic. The mean BMI was 25.1 kg/m².

The data in Table 2 reflect the exposure of 1,563 patients with type 2 diabetes to LANTUS or NPH in Studies E, F, and G. The type 2 diabetes population had the following characteristics: Mean age was 59 years. Fifty-eight percent were male, 87% were Caucasian, 8% were Black or African American and 9% were Hispanic. The mean BMI was 29.2 kg/m².

The frequencies of adverse reactions during LANTUS clinical studies in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below (Tables 1, 2, 3, and 4).

Table 1: Adverse Reactions Occurring ≥5% in Pooled Clinical Studies up to 28 Weeks Duration in Adults with Type 1 Diabetes

Table 2: Adverse Reactions Occurring ≥5% in Pooled Clinical Studies up to 1 Year Duration in Adults with Type 2 Diabetes

Table 3: Adverse Reactions Occurring ≥10% in a 5-Year Study of Adults with Type 2 Diabetes

Table 4: Adverse Reactions Occurring ≥5% in a 28-Week Clinical Study in Pediatric Patients with Type 1 Diabetes

Severe Hypoglycemia

Hypoglycemia was the most commonly observed adverse reaction in patients treated with LANTUS. Tables 5, 6, and 7 summarize the incidence of severe hypoglycemia in the LANTUS clinical studies. Severe symptomatic hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring the assistance of another person and associated with either a blood glucose below 50 mg/dL (≤56 mg/dL in the 5-year study and ≤36 mg/dL in the ORIGIN study) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration.

Percentages of LANTUS-treated adult patients who experienced severe symptomatic hypoglycemia in the LANTUS clinical studie were comparable to percentages of NPH-treated patients for all treatment regimens (see Tables 5 and 6). In the pediatric clinical study, pediatric patients with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia in the two treatment groups compared to the adult studies with type 1 diabetes.

Table 5: Severe Symptomatic Hypoglycemia in Patients with Type 1 Diabetes

Table 6: Severe Symptomatic Hypoglycemia in Patients with Type 2 Diabetes

Table 7 displays the proportion of patients who experienced severe symptomatic hypoglycemia in the LANTUS and Standard Care groups in the ORIGIN study [see Clinical Studies].

Table 7: Severe Symptomatic Hypoglycemia in the ORIGIN Study

Peripheral Edema

Some patients taking LANTUS have experienced sodium retention and edema, particularly if previously poor metabolic control was improved by intensified insulin therapy.

Lipodystrophy

Administration of insulin subcutaneously, including LANTUS, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients.

Insulin Initiation And Intensification Of Glucose Control

Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy.

Weight Gain

Weight gain has occurred with insulin including LANTUS and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.

Hypersensitivity Reactions

Local Reactions

Patients taking LANTUS experienced injection site reactions, including redness, pain, itching, urticaria, edema, and inflammation. In clinical studies in adult patients, there was a higher incidence of injection site pain in LANTUS-treated patients (2.7%) compared to NPH insulintreated patients (0.7%). The reports of pain at the injection site did not result in discontinuation of therapy.

Systemic Reactions

Severe, life-threatening, generalized allergy, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock have occurred with insulin, including LANTUS and may be life threatening.

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. All insulin products can elicit the formation of insulin antibodies. The presence of such insulin antibodies may increase or decrease the efficacy of insulin and may require adjustment of the insulin dose. In clinical studies of LANTUS, increases in titers of antibodies to insulin were observed in NPH insulin and LANTUS treatment groups with similar incidences.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of LANTUS. 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 have been reported in which rapid-acting insulins and other insulins, have been accidentally administered instead of LANTUS

Localized cutaneous amyloidosis at the injection site has occurred. Hyperglycemia has been reported with repeated insulin injections into areas of localized cutaneous amyloidosis; hypoglycemia has been reported with a sudden change to an unaffected injection site.

SRC: NLM .