HUMALOG SIDE EFFECTS

SIDE EFFECTS

Observed With HUMALOG U-100

The following adverse reactions are discussed elsewhere:

• Hypoglycemia
• Hypokalemia

Clinical Trial Experience

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 clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below.

Table 1: Treatment-Emergent Adverse Events in Patients with Type 1 Diabetes Mellitus (adverse events with frequency ≥5%)

Table 2: Treatment-Emergent Adverse Events in Patients with Type 2 Diabetes Mellitus (adverse events with frequency ≥5%)

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.

Lipodystrophy

Long-term use of insulin, including HUMALOG, can cause lipodystrophy at the site of repeated insulin injections or infusion. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue), and may affect insulin absorption. Rotate insulin injection or infusion sites within the same region to reduce the risk of lipodystrophy.

Weight Gain

Weight gain can occur with insulin therapy, including HUMALOG, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.

Peripheral Edema

Insulin, including HUMALOG, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

Adverse Reactions With Continuous Subcutaneous Insulin Infusion (CSII) — HUMALOG U-100

In a 12-week, randomized, crossover study in adult patients with type 1 diabetes (n=39), the rates of catheter occlusions and infusion site reactions were similar for HUMALOG U-100 and regular human insulin treated patients (see Table 3).

Table 3: Catheter Occlusions and Infusion Site Reactions

In a randomized, 16-week, open-label, parallel design study of children and adolescents with type 1 diabetes, adverse event reports related to infusion-site reactions were similar for insulin lispro and insulin aspart (21% of 100 patients versus 17% of 198 patients, respectively). In both groups, the most frequently reported infusion site adverse events were infusion site erythema and infusion site reaction.

Allergic Reactions

Local Allergy

As with any insulin therapy, patients taking HUMALOG may experience redness, swelling, or itching at the site of the injection. These minor reactions usually resolve in a few days to a few weeks, but in some occasions, may require discontinuation of HUMALOG. In some instances, these reactions may be related to factors other than insulin, such as irritants in a skin cleansing agent or poor injection technique.

Systemic Allergy

Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with any insulin, including HUMALOG. Generalized allergy to insulin may cause whole body rash (including pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis.

In controlled clinical trials, pruritus (with or without rash) was seen in 17 patients receiving regular human insulin (n=2969) and 30 patients receiving HUMALOG (n=2944).

Localized reactions and generalized myalgias have been reported with injected metacresol, which is an excipient in HUMALOG.

Antibody Production

In large clinical trials with patients with type 1 (n=509) and type 2 (n=262) diabetes mellitus, anti-insulin antibody (insulin lispro-specific antibodies, insulin-specific antibodies, cross-reactive antibodies) formation was evaluated in patients receiving both regular human insulin and HUMALOG (including patients previously treated with human insulin and naive patients). As expected, the largest increase in the antibody levels occurred in patients new to insulin therapy. The antibody levels peaked by 12 months and declined over the remaining years of the study. These antibodies do not appear to cause deterioration in glycemic control or necessitate an increase in insulin dose. There was no statistically significant relationship between the change in the total daily insulin dose and the change in percent antibody binding for any of the antibody types.

Postmarketing Experience

HUMALOG U-100

The following additional adverse reactions have been identified during post-approval use of HUMALOG. 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 have been identified during postapproval use.

SRC: NLM .