Home' The Source : Third Quarter 2012 Contents Table 3: Catheter Occlusions and Infusion Site Reactions
Regular human insulin
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 ( 1% 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.
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= 969) and 30 patients receiving HUMALOG (n= 944).
Localized reactions and generalized myalgias have been reported with injected
metacresol, which is an excipient in HUMALOG [see Contraindications].
In large clinical trials with patients with type 1 (n=509) and type (n= 6 ) diabetes
mellitus, anti-insulin antibody (insulin lispro-speci c antibodies, insulin-speci c
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 1 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 signi cant 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---The following additional adverse reactions have been
identi ed 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 identi ed during postapproval use.
A number of drugs affect glucose metabolism and may require insulin dose adjustment
and particularly close monitoring.
Following are some of the examples:
t Drugs That May Increase the Blood Glucose Lowering Effect of HUMALOG and
Susceptibility to Hypoglycemia: Oral antidiabetic agents, salicylates, sulfonamide
antibiotics, monoamine oxidase inhibitors, uoxetine, pramlintide, disopyramide,
brates, propoxyphene, pentoxifylline, ACE inhibitors, angiotensin II receptor
blocking agents, and somatostatin analogs (e.g., octreotide).
t Drugs That May Reduce the Blood Glucose Lowering Effect of HUMALOG:
corticosteroids, isoniazid, niacin, estrogens, oral contraceptives, phenothiazines,
danazol, diuretics, sympathomimetic agents (e.g., epinephrine, albuterol,
terbutaline), somatropin, atypical antipsychotics, glucagon, protease inhibitors, and
t Drugs That May Increase or Reduce the Blood Glucose Lowering Effect of
HUMALOG: beta-blockers, clonidine, lithium salts, and alcohol. Pentamidine may
cause hypoglycemia, which may sometimes be followed by hyperglycemia.
t Drugs That May Reduce the Signs of Hypoglycemia: beta-blockers, clonidine,
guanethidine, and reserpine.
USE IN SPECIFIC POPULATIONS
Pregnancy---Pregnancy Category B. All pregnancies have a background risk of birth
defects, loss, or other adverse outcome regardless of drug exposure. This background risk
is increased in pregnancies complicated by hyperglycemia and may be decreased with
good metabolic control. It is essential for patients with diabetes or history of gestational
diabetes to maintain good metabolic control before conception and throughout pregnancy.
In patients with diabetes or gestational diabetes insulin requirements may decrease
during the rst trimester, generally increase during the second and third trimesters, and
rapidly decline after delivery. Careful monitoring of glucose control is essential in these
patients. Therefore, female patients should be advised to tell their physicians if they intend
to become, or if they become pregnant while taking HUMALOG.
Although there are limited clinical studies of the use of HUMALOG in pregnancy,
published studies with human insulins suggest that optimizing overall glycemic control,
including postprandial control, before conception and during pregnancy improves fetal
In a combined fertility and embryo-fetal development study, female rats were given
subcutaneous insulin lispro injections of 5 and 0 units/kg/day (0.8 and 3 times the human
subcutaneous dose of 1 unit/kg/day, based on units/body surface area, respectively) from
weeks prior to cohabitation through Gestation Day 19. There were no adverse effects
on female fertility, implantation, or fetal viability and morphology. However, fetal growth
retardation was produced at the 0 units/kg/day-dose as indicated by decreased fetal
weight and an increased incidence of fetal runts/litter.
In an embryo-fetal development study in pregnant rabbits, insulin lispro doses of 0.1,
0. 5, and 0.75 unit/kg/day (0.03, 0.08, and 0. 4 times the human subcutaneous dose of 1
unit/kg/day, based on units/body surface area, respectively) were injected subcutaneously
on Gestation days 7 through 19. There were no adverse effects on fetal viability, weight,
and morphology at any dose.
Nursing Mothers---It is unknown whether insulin lispro is excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercised when
HUMALOG is administered to a nursing woman. Use of HUMALOG is compatible with
breastfeeding, but women with diabetes who are lactating may require adjustments of
their insulin doses.
Pediatric Use---HUMALOG is approved for use in children for subcutaneous daily
injections and for subcutaneous continuous infusion by external insulin pump. HUMALOG
has not been studied in pediatric patients younger than 3 years of age. HUMALOG has not
been studied in pediatric patients with type diabetes.
As in adults, the dosage of HUMALOG must be individualized in pediatric patients
based on metabolic needs and results of frequent monitoring of blood glucose.
Geriatric Use---Of the total number of subjects (n= 834) in eight clinical studies
of HUMALOG, twelve percent (n=338) were 65 years of age or over. The majority of
these had type diabetes. HbA1c values and hypoglycemia rates did not differ by age.
Pharmacokinetic/pharmacodynamic studies to assess the effect of age on the onset of
HUMALOG action have not been performed.
Excess insulin administration may cause hypoglycemia and hypokalemia. Mild episodes
of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage,
meal patterns, or exercise may be needed. More severe episodes with coma, seizure,
or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or
concentrated intravenous glucose. Sustained carbohydrate intake and observation may be
necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia
must be corrected appropriately.
DOSAGE AND ADMINISTRATION
Dosage Considerations---When given subcutaneously, HUMALOG has a more rapid
onset of action and a shorter duration of action than regular human insulin.
The dosage of HUMALOG must be individualized. Blood glucose monitoring is essential
in all patients receiving insulin therapy.
The total daily insulin requirement may vary and is usually between 0.5 to 1 unit/kg/day.
Insulin requirements may be altered during stress, major illness, or with changes in exercise,
meal patterns, or coadministered drugs.
Subcutaneous Administration---HUMALOG should be given within 15 minutes before a
meal or immediately after a meal.
HUMALOG given by subcutaneous injection should generally be used in regimens with
an intermediate- or long-acting insulin.
HUMALOG administered by subcutaneous injection should be given in the abdominal
wall, thigh, upper arm, or buttocks. Injection sites should be rotated within the same region
(abdomen, thigh, upper arm, or buttocks) from one injection to the next to reduce the risk
of lipodystrophy [see Adverse Reactions].
Continuous Subcutaneous Infusion (Insulin Pump)---HUMALOG may be administered
by continuous subcutaneous infusion by an external insulin pump. Do not use diluted
or mixed insulins in external insulin pumps. Infusion sites should be rotated within the
same region to reduce the risk of lipodystrophy [see Adverse Reactions]. Change the
HUMALOG in the reservoir at least every 7 days, change the infusion sets and the infusion
set insertion site at least every 3 days.
The initial programming of the external insulin infusion pump should be based on the
total daily insulin dose of the previous regimen. Although there is signi cant variability
among patients, approximately 50% of the total dose is usually given as meal-related
boluses of HUMALOG and the remainder is given as a basal infusion. HUMALOG is
recommended for use in pump systems suitable for insulin infusion such as MiniMed,
Disetronic, and other equivalent pumps.
HOW SUPPLIED/STORAGE AND HANDLING
HUMALOG 100 units per mL (U-100) is available as:
10 mL vials
NDC 000 -7510-01 (VL-7510)
3 mL vials
NDC 000 -7510-17 (VL-7533)
5 x 3 mL cartridges1
NDC 000 -7516-59 (VL-7516)
5 x 3 mL pre lled pen
NDC 000 -87 5-59 (HP-87 5)
5 x 3 mL Humalog KwikPen (pre lled)
NDC 000 -8799-59 (HP-8799)
Do not use after the expiration date.
Unopened HUMALOG should be stored in a refrigerator (36 to 46 F [ to 8 C]), but
not in the freezer. Do not use HUMALOG if it has been frozen. In-use HUMALOG vials,
cartridges, pens, and HUMALOG KwikPen® should be stored at room temperature,
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