ADVERSE REACTIONS
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 to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.
Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including NovoLog [see Warnings and Precautions (5)
].
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Insulin initiation and glucose control intensification
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.
Long-term use of insulin, including NovoLog, 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 can occur with some insulin therapies, including NovoLog, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.
Insulin may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.
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Frequencies of adverse drug reactions
The frequencies of adverse drug reactions during NovoLog 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% and occurring more frequently with NovoLog compared to human regular insulin are listed)
|
NovoLog + NPH
N= 596
|
Human Regular Insulin + NPH
N= 286
|
Preferred Term
|
N
|
(%)
|
N
|
(%)
|
Hypoglycemia
|
448
|
75%
|
205
|
72%
|
Headache
|
70
|
12%
|
28
|
10%
|
Injury accidental
|
65
|
11%
|
29
|
10%
|
Nausea
|
43
|
7%
|
13
|
5%
|
Diarrhea
|
28
|
5%
|
9
|
3%
|
Table 2: Treatment-Emergent Adverse Events in Patients with Type 2 Diabetes Mellitus (except for hypoglycemia, adverse events with frequency ≥ 5% and occurring more frequently with NovoLog compared to human regular insulin are listed)
|
NovoLog + NPH
N= 91
|
Human Regular Insulin + NPH
N= 91
|
|
N
|
(%)
|
N
|
(%)
|
Hypoglycemia
|
25
|
27%
|
33
|
36%
|
Hyporeflexia
|
10
|
11%
|
6
|
7%
|
Onychomycosis
|
9
|
10%
|
5
|
5%
|
Sensory disturbance
|
8
|
9%
|
6
|
7%
|
Urinary tract infection
|
7
|
8%
|
6
|
7%
|
Chest pain
|
5
|
5%
|
3
|
3%
|
Headache
|
5
|
5%
|
3
|
3%
|
Skin disorder
|
5
|
5%
|
2
|
2%
|
Abdominal pain
|
5
|
5%
|
1
|
1%
|
Sinusitis
|
5
|
5%
|
1
|
1%
|
Postmarketing Data
The following additional adverse reactions have been identified during postapproval use of NovoLog. Because these adverse reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency. Medication errors in which other insulins have been accidentally substituted for NovoLog have been identified during postapproval use [see Patient Counseling Information
].
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