2014 Physicians' Desk Reference - (Page 2138)
NOVOLOG MIX 70/30
* Do not use during episodes of hypoglycemia (4).
* Do not use in patients with hypersensitivity to NovoLog
Mix 70/30 or one of its excipients (4).
-----------WARNINGS AND PRECAUTIONS-----------
* NovoLog Mix 70/30 should not be mixed with any other
insulin product (5.1).
* Hypoglycemia is the most common adverse effect of
insulin therapy. Glucose monitoring is recommended for
all patients with diabetes. Any change of insulin dose
should be made cautiously and only under medical supervision (5.1, 5.2).
* Insulin, particularly when given in settings of poor glycemic control, can cause hypokalemia. Use caution in patients predisposed to hypokalemia (5.3).
* Like all insulins, NovoLog Mix 70/30 requirements may be
reduced in patients with renal impairment or hepatic impairment (5.4, 5.5).
* Severe, life-threatening, generalized allergy, including
anaphylaxis, may occur with insulin products, including
NovoLog Mix 70/30 (5.6).
* Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPARgamma agonists, and insulin, including NovoLog Mix
Adverse reactions observed with insulin therapy include hypoglycemia, allergic reactions, local injection site reactions,
lipodystrophy, rash and pruritus (6).
To report SUSPECTED ADVERSE REACTIONS, contact
Novo Nordisk Inc. at 1-800-727-6500 or FDA at 1-800-FDA1088 or www.fda.gov/medwatch.
* The following may increase the blood-glucose-lowering effect and susceptibility to hypoglycemia: oral antidiabetic
products, pramlintide, ACE inhibitors, disopyramide, ﬁbrates, ﬂuoxetine, monoamine oxidase (MAO) inhibitors,
propoxyphene, salicylates, somatostatin analog (e.g. octreotide), sulfonamide antibiotics (7).
* The following may reduce the blood-glucose-lowering effect: corticosteroids, niacin, danazol, diuretics, sympathomimetic agents (e.g., epinephrine, salbutamol, terbutaline), isoniazid, phenothiazine derivatives, somatropin,
thyroid hormones, estrogens, progestogens (e.g., in oral
contraceptives), atypical antipsychotics (7).
* Beta-blockers, clonidine, lithium salts, and alcohol may either potentiate or weaken the blood-glucose-lowering effect of insulin (7).
* Pentamidine may cause hypoglycemia, which may be followed by hyperglycemia (7).
* The signs of hypoglycemia may be reduced or absent in
patients taking sympatholytic products such as betablockers, clonidine, guanethidine, and reserpine (7).
See 17 for PATIENT COUNSELING INFORMATION
and FDA-approved patient labeling
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
3 DOSAGE FORMS AND STRENGTHS
5 WARNINGS AND PRECAUTIONS
5.4 Renal Impairment
5.5 Hepatic Impairment
5.6 Hypersensitivity and Allergic Reactions
5.7 Antibody Production
5.8 Fluid retention and heart failure can occur with
concomitant use of PPAR-gamma agonists
6 ADVERSE REACTIONS
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
14.1 NovoLog Mix 70/30 versus Novolin 70/30
HELP PATIENTS SAVE on RX DRUGS: PDR.net/PHARMACYDISCOUNTCARD
14.2 Combination Therapy: Insulin and Oral Agents in
Patients with Type 2 Diabetes
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Recommended Storage
17 PATIENT COUNSELING INFORMATION
17.1 Physician Instructions
* Sections or subsections omitted from the full prescribing
information are not listed
FULL PRESCRIBING INFORMATION
INDICATIONS AND USAGE
NovoLog Mix 70/30 is an insulin analog indicated to improve glycemic control in patients with diabetes mellitus.
Important Limitations of Use:
In premix insulins, such as NovoLog Mix 70/30, the proportions of rapid acting and long acting insulins are ﬁxed and
do not allow for basal versus prandial dose adjustments.
DOSAGE AND ADMINISTRATION
NovoLog Mix 70/30 is an insulin analog with an earlier onset and intermediate duration of action in comparison to the
basal human insulin premix. The addition of protamine to
the rapid-acting aspart insulin analog (NovoLog) results in
insulin activity that is 30% short-acting and 70% longacting. NovoLog Mix 70/30 is typically dosed on a twicedaily basis (with each dose intended to cover 2 meals or a
meal and a snack). The dosage of NovoLog Mix 70/30 must
be individualized. The written prescription for NovoLog Mix
70/30 should include the full name, to avoid confusion with
NovoLog (insulin aspart) and Novolin 70/30 (human premix).
NovoLog Mix 70/30 should appear uniformly white and
cloudy. Do not use it if it looks clear or if it contains solid
particles. NovoLog Mix 70/30 should not be used after the
printed expiration date.
NovoLog Mix 70/30 should be administered by subcutaneous injection in the abdominal region, buttocks, thigh, or
upper arm. NovoLog Mix 70/30 has a faster onset of action
than human insulin premix 70/30 and should be dosed
within 15 minutes before meal initiation for patients with
type 1 diabetes. For patients with type 2 diabetes, dosing
should occur within 15 minutes before or after meal initiation. Injection sites should be rotated within the same region to reduce the risk of lipodystrophy. As with all insulins,
the duration of action may vary according to the dose,
injection site, blood ﬂow, temperature, and level of physical
NovoLog Mix 70/30 should not be administered intravenously or used in insulin infusion pumps. Dose regimens of
NovoLog Mix 70/30 will vary among patients and should be
determined by the health care professional familiar with
the patient's recommended glucose treatment goals, metabolic needs, eating habits, and other lifestyle variables.
NovoLog Mix 70/30 is a suspension that must be visually
inspected and resuspended immediately before use.
The NovoLog Mix 70/30 vial should be rolled gently in your
hands in a horizontal position 10 times to mix it. The rolling
procedure must be repeated until the suspension appears
uniformly white and cloudy. Inject immediately. Resuspension is easier when the insulin has reached room temperature.
The NovoLog Mix 70/30 FlexPen should be rolled 10 times
gently between your hands in a horizontal position. Thereafter, turn the NovoLog Mix 70/30 FlexPen upside down so
that the glass ball moves from one end of the reservoir to
the other. Do this at least 10 times. The rolling and turning
procedure must be repeated until the suspension appears
uniformly white and cloudy. Inject immediately. Before each
subsequent injection, turn the disposable NovoLog Mix
70/30 FlexPen upside down so that the glass ball moves
from one end of the reservoir to the other at least 10 times
and until the suspension appears uniformly white and
cloudy. Inject immediately.
DOSAGE FORMS AND STRENGTHS
NovoLog Mix 70/30 is available in the following package
sizes: each presentation contains 100 units of insulin
aspart per mL (U-100).
* 10 mL vials
* 3 mL NovoLog Mix 70/30 FlexPen
NovoLog Mix 70/30 is contraindicated
* during episodes of hypoglycemia
* in patients with hypersensitivity to NovoLog Mix 70/30
or one of its excipients.
WARNINGS AND PRECAUTIONS
The short and long-acting components of insulin mixes, including NovoLog Mix 70/30, cannot be titrated indepen-
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dently. Because NovoLog Mix 70/30 has peak pharmacodynamic activity between 1-4 hours after injection, it should
be administered within 15 minutes of meal initiation [see
Clinical Pharmacology (12)]. The dose of insulin required to
provide adequate glycemic control for one of the meals may
result in hyper- or hypoglycemia for the other meal. The
pharmacodynamic proﬁle may also be inadequate for patients who require more frequent meals.
NovoLog Mix 70/30 should not be mixed with any other
NovoLog Mix 70/30 should not be used intravenously.
NovoLog Mix 70/30 should not be used in insulin infusion
Glucose monitoring is recommended for all patients with diabetes. Any change of insulin dose should be made cautiously and only under medical supervision. Changing from
one insulin product to another or changing the insulin
strength may result in the need for a change in dosage.
Changes may also be necessary during illness, emotional
stress, and other physiologic stress in addition to changes in
meals and exercise.
The pharmacokinetic and pharmacodynamic proﬁles of all
insulins may be altered by the site used for injection and the
degree of vascularization of the site. Smoking, temperature,
and exercise contribute to variations in blood ﬂow and
insulin absorption. These and other factors contribute to
inter- and intra-patient variability.
Needles and NovoLog Mix 70/30 FlexPen must not be
Hypoglycemia is the most common adverse effect of insulin
therapy, including NovoLog Mix 70/30. Severe hypoglycemia may lead to unconsciousness and/or convulsions and
may result in temporary or permanent impairment of brain
function or even death. Severe hypoglycemia requiring the
assistance of another person and/or parenteral glucose infusion or glucagon administration has been observed in clinical trials with insulin, including trials with NovoLog Mix
The timing of hypoglycemia may reﬂect the time-action proﬁle of the insulin formulation [see Clinical Pharmacology
(12)]. Other factors, such as changes in dietary intake (e.g.,
amount of food or timing of meals), injection site, exercise,
and concomitant medications may also alter the risk of hypoglycemia [see Drug Interactions (7)]. As with all insulins,
use caution in patients with hypoglycemia unawareness
and in patients who may be predisposed to hypoglycemia
(e.g. patients who are fasting or have erratic food intake).
The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk
in situations where these abilities are especially important,
such as driving or operating machinery.
Rapid changes in serum glucose levels 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 [see Drug Interactions (7)].
All insulin products, including NovoLog Mix 70/30, cause a
shift in potassium from the extracellular to intracellular
space, possibly leading to hypokalemia that, if left untreated, may cause respiratory paralysis, ventricular arrhythmia, and death. Use caution in patients who may be at
risk for hypokalemia (e.g. patients using potassiumlowering medications or patients taking medications sensitive to potassium concentrations).
Clinical or pharmacology studies with NovoLog Mix 70/30
in diabetic patients with various degrees of renal impairment have not been conducted. As with other insulins, the
requirements for NovoLog Mix 70/30 may be reduced in patients with renal impairment [see Clinical Pharmacology
Clinical or pharmacology studies with NovoLog Mix 70/30
in diabetic patients with various degrees of hepatic impairment have not been conducted. As with other insulins, the
requirements for NovoLog Mix 70/30 may be reduced in patients with hepatic impairment [see Clinical Pharmacology
Hypersensitivity and Allergic Reactions
Local Reactions- As with other insulin therapy, patients
may experience reactions such as erythema, edema or pruritus at the site of NovoLog Mix 70/30 injection. These reactions usually resolve in a few days to a few weeks, but in
some occasions, may require discontinuation of NovoLog
Mix 70/30. In some instances, these reactions may be related to the insulin molecule, other components in the
insulin preparation including protamine and cresol, components in skin cleansing agents, or injection techniques. Localized reactions and generalized myalgias have been reported with the use of cresol as an injectable excipient.
Table of Contents for the Digital Edition of 2014 Physicians' Desk Reference
Manufacturers’ Index (White Pages)
Brand and Generic Name Index (Pink Pages)
Generic/Brand Cross-Reference Table
Product Category Index (Blue Pages)
Key to Controlled Substances Schedule
Key to FDA Use-in-Pregnancy Ratings
U.S. Food and Drug Administration Telephone Directory
Drugs Excreted in Breast Milk
Product Identification Guide
Healthcare Provider Resource Center
2014 Physicians' Desk Reference