Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3103
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Humalog Mix50/50 (Injection, Suspension)
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dailymed-instance:dosage |
Humalog Mix50/50 is
intended only for subcutaneous administration. Humalog Mix50/50 should
not be administered intravenously. Dosage regimens of Humalog Mix50/50 will
vary among patients and should be determined by the healthcare provider familiar with the patient's metabolic
needs, eating habits, and other lifestyle variables. Humalog has
been shown to be equipotent to Regular human insulin
on a molar basis. One unit of Humalog has
the same glucose���lowering effect as one unit of Regular
human insulin, but its effect is more rapid and of shorter duration. The quicker
glucose���lowering effect of Humalog is
related to the more rapid absorption rate of insulin lispro from
subcutaneous tissue. Direct comparison between Humalog Mix50/50 and
Humulin 50/50 was not performed. However, a cross���study comparison shown
in Figure 3 suggests that Humalog Mix50/50 has
a duration of activity that is similar to Humulin 50/50. The rate of insulin absorption and consequently the onset of
activity are known to be affected by the site of injection, exercise, and
other variables. As with all insulin preparations, the time course of action
of Humalog Mix50/50 may
vary considerably in different individuals or within the same individual.
Patients must be educated to use proper injection techniques. Humalog Mix50/50 should
be inspected visually before use. Humalog Mix50/50 should
be used only if it appears uniformly cloudy after mixing. Humalog Mix50/50 should
not be used after its expiration date.
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dailymed-instance:descripti... |
Humalog Mix50/50���[50% insulin lispro protamine
suspension and 50% insulin lispro injection,
(rDNA origin)] is a mixture of insulin lispro solution, a rapid���acting blood glucose���lowering agent and insulin lispro protamine
suspension, an intermediate���acting blood glucose���lowering agent.
Chemically, insulin lispro is
Lys(B28), Pro(B29) human insulin analog, created when the amino acids at positions
28 and 29 on the insulin B���chain are reversed. Insulin lispro is
synthesized in a special non���pathogenic laboratory strain of Escherichia coli bacteria
that has been genetically altered to produce insulin lispro. Insulin lispro protamine
suspension (NPL component) is a suspension of crystals produced from combining insulin lispro and
protamine sulfate under appropriate conditions for crystal formation. Insulin lispro has the following primary structure: Insulin lispro has the empirical formula CHNOSand a molecular weight of 5808, both identical to that of human
insulin. Humalog Mix50/50 vials
and Pens contain
a sterile suspension of insulin lispro protamine suspension mixed with soluble insulin lispro for
use as an injection. Each milliliter of Humalog Mix50/50 injection
contains insulin lispro 100 units, 0.19 mg protamine sulfate,
16 mg glycerin, 3.78 mg dibasic sodium phosphate,
2.20 mg Metacresol, zinc oxide content adjusted to provide
0.0305 mg zinc ion, 0.89 mg phenol, and Water for Injection. Humalog Mix50/50 has
a pH of 7.0 to 7.8. Hydrochloric acid 10% and/or sodium hydroxide 10% may
have been added to adjust pH.
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dailymed-instance:clinicalP... |
Antidiabetic
Activity: The primary activity of insulin, including Humalog Mix50/50, is
the regulation of glucose metabolism. In addition, all insulins have several
anabolic and anti���catabolic actions on many tissues in the body. In
muscle and other tissues (except the brain), insulin causes rapid transport
of glucose and amino acids intracellularly, promotes anabolism, and inhibits
protein catabolism. In the liver, insulin promotes the uptake and storage
of glucose in the form of glycogen, inhibits gluconeogenesis, and promotes
the conversion of excess glucose into fat. Insulin lispro, the rapid���acting component of Humalog Mix50/50,
has been shown to be equipotent to Regular human insulin
on a molar basis. One unit of Humalog has the same glucose���lowering effect as one unit
of Regular human insulin,
but its effect is more rapid and of shorter duration.<br/>Pharmacokinetics:<br/>Absorption: Studies in nondiabetic
subjects and patients with type 1 (insulin���dependent) diabetes demonstrated
that Humalog,
the rapid���acting component of Humalog Mix50/50, is
absorbed faster than Regular human insulin
(U���100). In nondiabetic subjects given subcutaneous doses of Humalog ranging
from 0.1 to 0.4 U/kg, peak serum concentrations were observed
30 to 90 minutes after dosing. When nondiabetic subjects received equivalent
doses of Regular human insulin,
peak insulin concentrations occurred between 50 to 120 minutes after dosing. Similar
results were seen in patients
with type 1 diabetes. Humalog Mix50/50 has
two phases of absorption. The early phase represents insulin lispro and
its distinct characteristics of rapid onset. The late phase represents the
prolonged action of insulin lispro protamine
suspension. In 30 healthy nondiabetic
subjects given subcutaneous doses (0.3 U/kg) of Humalog Mix50/50, peak
serum concentrations were observed 45 minutes to 13.5 hours (median, 60 minutes)
after dosing (see Figure 1).
In patients with type 1 diabetes, peak serum concentrations were observed
45 minutes to 120 minutes (median, 60 minutes) after dosing. The rapid absorption
characteristics of Humalog are
maintained with Humalog Mix50/50 (see Figure 1). Direct comparison
of Humalog Mix50/50 and
Humulin 50/50 was not performed. However, a cross���study comparison shown
in Figure 1 suggests that Humalog Mix50/50 has
a more rapid absorption than Humulin 50/50.<br/>Distribution: Radiolabeled
distribution studies of Humalog Mix50/50 have
not been conducted. However, the volume of distribution following injection
of Humalog is
identical to that of Regular human insulin,
with a range of 0.26 to 0.36 L/kg.<br/>Metabolism: Human metabolism
studies of Humalog Mix50/50 have
not been conducted. Studies in animals indicate that the metabolism of Humalog,
the rapid���acting component of Humalog Mix50/50, is
identical to that of Regular human insulin.<br/>Elimination: Humalog Mix50/50 has
two absorption phases, a rapid and a prolonged phase, representative of the insulin lispro and insulin lispro protamine
suspension components of the mixture. As with other intermediate���acting
insulins, a meaningful terminal phase half���life cannot be calculated
after administration of Humalog Mix50/50 because
of the prolonged insulin lispro protamine
suspension absorption.<br/>Pharmacodynamics: Studies in nondiabetic subjects and patients
with diabetes demonstrated that Humalog has
a more rapid onset of glucose���lowering activity, an earlier peak for
glucose���lowering, and a shorter duration of glucose���lowering activity
than Regular human insulin.
The early onset of activity of Humalog Mix50/50 is
directly related to the rapid absorption of Humalog.
The time course of action of insulin and insulin analogs, such as Humalog (and hence Humalog Mix50/50), may vary considerably
in different individuals or within the same individual. The parameters of Humalog Mix50/50 activity
(time of onset, peak time, and duration) as presented in Figures 2 and 3 should be considered only as general guidelines.
The rate of insulin absorption and consequently the onset of activity is known
to be affected by the site of injection, exercise, and other variables . In a glucose clamp study performed in 30 nondiabetic
subjects, the onset of action and glucose���lowering activity of Humalog, Humalog Mix50/50, Humalog Mix75/25���,
and insulin lispro protamine
suspension (NPL component) were
compared (see Figure 2).
Graphs of mean glucose infusion rate versus time showed a distinct insulin
activity profile for each formulation. The rapid onset of glucose���lowering
activity characteristic of Humalog was
maintained in Humalog Mix50/50. Direct comparison between Humalog Mix50/50 and
Humulin 50/50 was not performed. However, a cross���study comparison shown
on Figure 3 suggests that Humalog Mix50/50 has
a duration of activity that is similar to Humulin 50/50. Figures 2 and 3 represent insulin activity profiles as measured
by glucose clamp studies in healthy nondiabetic subjects. Figure 2 shows
the time activity profiles of Humalog, Humalog Mix75/25, Humalog Mix50/50, and insulin lispro protamine
suspension (NPL component). Figure 3 is
a comparison of the time activity profiles of Humalog Mix50/50 (see Figure 3a)
and of Humulin 50/50 (see Figure 3b) from two different studies.<br/>Special
Populations:<br/>Age and Gender: Information on
the effect of age on the pharmacokinetics of Humalog Mix50/50 is
unavailable. Pharmacokinetic and pharmacodynamic comparisons between men and
women administered Humalog Mix50/50 showed
no gender differences. In large Humalog clinical
trials, sub���group
analysis based on age and gender
demonstrated that differences between Humalog and Regular human insulin
in postprandial glucose parameters are maintained across sub���groups.<br/>Smoking: The effect of
smoking on the pharmacokinetics and pharmacodynamics
of Humalog Mix50/50 has
not been studied.<br/>Pregnancy: The effect of
pregnancy on the pharmacokinetics and pharmacodynamics
of Humalog Mix50/50 has
not been studied.<br/>Obesity: The effect of
obesity and/or subcutaneous fat thickness on the pharmacokinetics and pharmacodynamics of Humalog Mix50/50 has
not been studied. In large clinical trials, which included patients with Body Mass Index up to and including 35 kg/m,
no consistent differences were observed between Humalog and
Humulin R
with respect to postprandial glucose parameters.<br/>Renal Impairment: The effect of
renal impairment on the pharmacokinetics and pharmacodynamics
of Humalog Mix50/50 has
not been studied. In a study of 25 patients with type 2 diabetes and a wide
range of renal function, the pharmacokinetic differences between Humalog and Regular human insulin were
generally maintained. However, the sensitivity of the patients to insulin
did change, with an increased response to insulin as the renal function declined.
Careful glucose monitoring and dose reductions of insulin, including Humalog Mix50/50, may
be necessary in patients with renal dysfunction.<br/>Hepatic Impairment: Some studies
with human insulin have shown increased circulating levels of insulin in patients
with hepatic failure. The effect of hepatic impairment on the pharmacokinetics
and pharmacodynamics
of Humalog Mix50/50 has
not been studied. However, in a study of 22 patients with type 2 diabetes,
impaired hepatic function did not affect the subcutaneous absorption or general
disposition of Humalog when
compared with patients with no history of hepatic dysfunction. In that study, Humalog maintained
its more rapid absorption and elimination when compared with Regular
human insulin. Careful glucose monitoring and dose adjustments of insulin,
including Humalog Mix50/50, may
be necessary in patients with hepatic dysfunction.
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Humalog Mix50/50 is
contraindicated during episodes of hypoglycemia and in patients sensitive
to insulin lispro or
any of the excipients contained in the formulation.
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dailymed-instance:supply |
Humalog Mix50/50 [50% insulin lispro protamine
suspension and 50% insulin lispro injection,
(rDNA origin)] is available in the following package sizes: each
presentation containing 100 units insulin lispro per mL (U-100). Storage���Humalog Mix50/50 should
be stored in a refrigerator [2��to 8��C (36��to 46��F)],
but not in the freezer. Do not use Humalog Mix50/50 if
it has been frozen. Unrefrigerated [below 30��C (86��F)] vials must be used
within 28 days or be discarded, even if they still contain Humalog Mix50/50. Unrefrigerated [below 30��C (86��F)] Pens, and KwikPens must be used
within 10 days or be discarded, even if they still contain Humalog Mix50/50. Protect from
direct heat and light. See table below:
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dailymed-ingredient:Dibasic_sodium_phosphate,
dailymed-ingredient:Glycerin,
dailymed-ingredient:Hydrochloric_acid,
dailymed-ingredient:Metacresol,
dailymed-ingredient:Phenol,
dailymed-ingredient:Protamine_sulfate,
dailymed-ingredient:Sodium_hydroxide,
dailymed-ingredient:Water,
dailymed-ingredient:Zinc
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dailymed-instance:precautio... |
General: Hypoglycemia and hypokalemia are among the potential clinical adverse
effects associated with the use of all insulins. Because of differences in
the action of Humalog Mix50/50 and
other insulins, care should be taken in patients in whom such potential side
effects might be clinically relevant (e.g., patients who are fasting, have
autonomic neuropathy, or are using potassium���lowering drugs or patients
taking drugs sensitive to serum potassium level). Lipodystrophy and hypersensitivity
are among other potential clinical adverse effects associated with the use
of all insulins. As with all insulin preparations, the time course of Humalog Mix50/50 action may vary in
different individuals or at different times in the same individual and is
dependent on site of injection, blood supply, temperature, and physical activity. Adjustment of dosage of any insulin may be necessary if patients change
their physical activity or their usual meal plan. Insulin requirements may
be altered during illness, emotional disturbances, or other stress. Hypoglycemia���As with all insulin preparations, hypoglycemic reactions may be associated
with the administration of Humalog Mix50/50. Rapid
changes in serum glucose concentrations may induce symptoms of hypoglycemia
in persons with diabetes, regardless of the glucose value. Early warning symptoms
of hypoglycemia may be different or less pronounced under certain conditions,
such as long duration of diabetes, diabetic nerve disease, use of medications
such as beta-blockers, or intensified diabetes control. Renal Impairment���As with other insulins, the requirements for Humalog Mix50/50 may
be reduced in patients with renal impairment. Hepatic Impairment���Although impaired hepatic function does not affect the absorption or disposition
of Humalog,
careful glucose monitoring and dose adjustments of insulin, including Humalog Mix50/50, may
be necessary. Allergy���Local Allergy���As with any insulin therapy, patients may experience redness, swelling, or
itching at the site of injection. These minor reactions usually resolve in
a few days to a few weeks. In some instances, these reactions may be related
to factors other than insulin, such as irritants in the skin cleansing agent
or poor injection technique. Systemic
Allergy���Less common, but potentially more serious, is generalized
allergy to insulin, which may cause rash (including pruritus) over the whole
body, shortness of breath, wheezing, reduction in blood pressure, rapid pulse,
or sweating. Severe cases of generalized allergy, including anaphylactic reaction,
may be life threatening. Localized reactions and generalized myalgias have
been reported with the use of cresol as an injectable excipient. Antibody
Production���In clinical trials, antibodies that cross-react with human insulin and insulin lispro were
observed in both human insulin mixtures and insulin lispro mixtures
treatment groups.<br/>Information
for Patients: Patients should be informed of the potential risks and advantages of Humalog Mix50/50 and
alternative therapies. Patients should not mix Humalog Mix50/50 with
any other insulin. They should also be informed about the importance of proper
insulin storage, injection technique, timing of dosage, adherence to meal
planning, regular physical activity, regular blood glucose monitoring, periodic hemoglobin Atesting,
recognition and management of hypo- and hyperglycemia, and periodic assessment
for diabetes complications. Patients should be advised to inform their physician if they are pregnant
or intend to become pregnant. Refer patients to the Patient Information leaflet for information
on normal appearance, timing of dosing (within 15 minutes before a meal),
storing, and common adverse effects. For
Patients Using Insulin Pen Delivery Devices: Before starting therapy,
patients should read the Patient Information leaflet that accompanies
the drug product and the User Manual that accompanies the delivery device
and re-read them each time the prescription is renewed. Patients should be
instructed on how to properly use the delivery device, prime the Pen, and
properly dispose of needles. Patients should be advised not to share their
Pens with others.<br/>Laboratory
Tests: As with all insulins, the therapeutic response to Humalog Mix50/50 should
be monitored by periodic blood glucose tests. Periodic measurement of hemoglobin Aisrecommended for the monitoring of long���term glycemic control.<br/>Drug
Interactions: Insulin requirements may be increased by medications with hyperglycemic
activity such as corticosteroids, isoniazid, certain lipid���lowering
drugs (e.g., niacin), estrogens, oral contraceptives, phenothiazines, and
thyroid replacement therapy. Insulin requirements may be decreased in the presence of drugs that increase insulin sensitivity
or have hypoglycemic activity, such as oral antidiabetic agents,
salicylates, sulfa antibiotics, certain antidepressants (monoamine oxidase
inhibitors), angiotensin���converting���enzyme inhibitors, angiotensin
II receptor blocking agents, beta���adrenergic blockers, inhibitors of
pancreatic function (e.g., octreotide), and alcohol. Beta���adrenergic
blockers may mask the symptoms of hypoglycemia in some patients.<br/>Carcinogenesis,
Mutagenesis, Impairment of Fertility: Long���term studies in animals have not been performed to evaluate
the carcinogenic potential of Humalog, Humalog Mix75/25, or Humalog Mix50/50. Insulin lispro was
not mutagenic in a battery of in
vitro and in
vivo genetic toxicity assays (bacterial mutation tests, unscheduled
DNA synthesis, mouse lymphoma assay, chromosomal aberration tests, and a micronucleus
test). There is no evidence from animal studies of impairment of fertility
induced by insulin lispro.<br/>Pregnancy:<br/>Teratogenic Effects���Pregnancy Category
B: Reproduction studies with insulin lispro have been performed in pregnant rats and rabbits at parenteral doses up
to 4 and 0.3 times, respectively, the average human dose (40 units/day) based
on body surface area. The results have revealed no evidence of impaired fertility
or harm to the fetus due to insulin lispro. There are, however, no adequate and well���controlled studies with Humalog, Humalog Mix75/25, or Humalog Mix50/50 in
pregnant women. Because animal reproduction studies are not always predictive
of human response, this drug should be used during pregnancy only if clearly
needed.<br/>Nursing
Mothers: It is unknown whether insulin lispro is excreted in significant amounts in human milk. Many drugs, including
human insulin, are excreted in human milk. For this reason, caution should
be exercised when Humalog Mix50/50 is
administered to a nursing woman. Patients with diabetes who are lactating
may require adjustments in Humalog Mix50/50 dose,
meal plan, or both.<br/>Pediatric
Use: Safety and effectiveness of Humalog Mix50/50 in
patients less than 18 years of age have not been established.<br/>Geriatric
Use: Clinical studies of Humalog Mix50/50 did
not include sufficient numbers of patients aged 65 and over to determine whether
they respond differently than younger patients. In general, dose selection
for an elderly patient should take into consideration the greater frequency
of decreased hepatic, renal, or cardiac function,and of concomitant disease
or other drug therapy in this population.
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Hypoglycemia
may occur as a result of an excess of insulin relative to food intake, energy
expenditure, or both. 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.
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dailymed-instance:genericMe... |
Insulin lispro
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dailymed-instance:fullName |
Humalog Mix50/50 (Injection, Suspension)
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dailymed-instance:adverseRe... |
Clinical studies comparing Humalog Mix50/50 with
human insulin mixtures did not demonstrate a difference in frequency of adverse
events between the two treatments. Adverse events commonly associated with human
insulin therapy include the following: Body
as a Whole���allergic reactions . Skin
and Appendages���injection site reaction, lipodystrophy,
pruritus, rash. Other���hypoglycemia .
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dailymed-instance:warning |
Humalog differs
from Regular human insulin
by its rapid onset of action as well as a shorter duration of activity. Therefore,
the dose of Humalog Mix50/50 should
be given within 15 minutes before a meal. Hypoglycemia
is the most common adverse effect associated with the use of insulins, including Humalog Mix50/50. As
with all insulins, the timing of hypoglycemia may differ among various insulin
formulations. Glucose monitoring is recommended for all patients with diabetes. Any change of
insulin should be made cautiously and only under medical supervision. Changes
in insulin strength, manufacturer, type (e.g., Regular,
NPH, analog), species,
or method of manufacture may
result in the need for a change in dosage.
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dailymed-instance:indicatio... |
Humalog Mix50/50, a
mixture of 50% insulin lispro protamine
suspension and 50% insulin lispro injection, (rDNA
origin), is indicated in the treatment of patients with diabetes
mellitus for the control of hyperglycemia. Based on cross���study comparisons
of the pharmacodynamics of Humalog Mix50/50 and
Humulin 50/50, it is likely that Humalog Mix50/50 has
a more rapid onset of glucose���lowering activity compared with Humulin
50/50 while having a similar duration of action. This profile is achieved
by combining the rapid onset of Humalog with
the intermediate action of insulin lispro protamine suspension.
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dailymed-instance:name |
Humalog Mix50/50
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