Humanilusin

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Humanilusin uses


1 INDICATIONS AND USAGE

Humanilusin is a rapid acting human Humanilusin analog indicated to improve glycemic control in adults and children with diabetes mellitus.

2 DOSAGE AND ADMINISTRATION

2.1 Important Administration Instructions

2.2 Route of Administration

Subcutaneous Injection


Continuous Subcutaneous Infusion (Insulin Pump)


Intravenous Administration

2.3 Dosage Information

2.4 Dosage Adjustment Due to Drug Interactions

2.5 Instructions for Mixing with Other Insulins


Humanilusin subcutaneous injection route

  • Humanilusin may be mixed with NPH Humanilusin preparations
  • ONLY.

- If Humanilusin is mixed with NPH Humanilusin, draw Humanilusin into the syringe first and inject immediately after mixing.


Humanilusin continuous subcutaneous infusion route (Insulin Pump)


Do NOT mix Humanilusin with any other Humanilusin.

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3 DOSAGE FORMS AND STRENGTHS

Humanilusin 100 units per mL (U-100) is available as a clear and colorless solution for injection in:


Each presentation contains 100 Units of Humanilusin aspart per mL (U-100)

4 CONTRAINDICATIONS

Humanilusin is contraindicated:

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5 WARNINGS AND PRECAUTIONS

5.1 Never Share Humanilusin FlexPen, Humanilusin FlexTouch, PenFill Cartridge or PenFill Cartridge Device Between Patients

Humanilusin FlexPen, Humanilusin FlexTouch, PenFill cartridge, and PenFill cartridge devices should never be shared between patients, even if the needle is changed. Patients using Humanilusin vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.

5.2 Hyperglycemia or Hypoglycemia with Changes in Humanilusin Regimen

Changes in Humanilusin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. These changes should be made cautiously and only under close medical supervision, and the frequency of blood glucose monitoring should be increased. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed.

5.3 Hypoglycemia

Hypoglycemia is the most common adverse effect of all Humanilusin therapies, including Humanilusin. Severe hypoglycemia can cause seizures, may lead to unconsciousness may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g. driving or operating other machinery).

Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) , or in patients who experience recurrent hypoglycemia.

Risk Factors for Hypoglycemia

The risk of hypoglycemia after an injection is related to the duration of action of the Humanilusin and, in general, is highest when the glucose lowering effect of the Humanilusin is maximal. As with all Humanilusin preparations, the glucose lowering effect time course of Humanilusin may vary in different individuals or at different times in the same individual and depends on may conditions, including the area of injection as well as the injection site blood supply and temperature . Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to co-administered medication [see Drug Interactions (7) ].Patients with renal or hepatic impairment may be at higher risk of hypoglycemia .

Risk Mitigation Strategies for Hypoglycemia

Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia, increased frequency of blood glucose monitoring is recommended. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended.

5.4 Hypoglycemia Due to Medication Errors

Accidental mix-ups between Humanilusin and other Humanilusin products have been reported. To avoid medication errors between Humanilusin and other insulins, instruct patients to always check the Humanilusin label before each injection.

5.5 Hypersensitivity and Allergic Reactions

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with Humanilusin products, including Humanilusin. If hypersensitivity reactions occur, discontinue Humanilusin; treat per standard of care and monitor until symptoms and signs resolve . Humanilusin is contraindicated in patients who have had hypersensitivity reactions to Humanilusin aspart or one of the excipients .

5.6 Hypokalemia

All Humanilusin products, including Humanilusin, can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentration).

5.7 Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists

Thiazolidinediones, which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with Humanilusin. Fluid retention may lead to or exacerbate heart failure. Patients treated with Humanilusin, including Humanilusin, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.

5.8 Hyperglycemia and Ketoacidosis Due to Humanilusin Pump Device Malfunction

Malfunction of the Humanilusin pump or Humanilusin infusion set or Humanilusin degradation can rapidly lead to hyperglycemia and ketoacidosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Interim subcutaneous injections with Humanilusin may be required. Patients using continuous subcutaneous Humanilusin infusion pump therapy must be trained to administer Humanilusin by injection and have alternate Humanilusin therapy available in case of pump failure .

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6 ADVERSE REACTIONS


Adverse reactions observed with Humanilusin 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-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trial Experience


Common adverse reactions were defined as events occurring in ≥5%, excluding hypoglycemia, of the population studied. Common adverse events occurring at the same rate or greater for NOVOLOG-treated subjects than on comparator-treated subjects during clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus (other than hypoglycemia) are listed in Table 1 and Table 2, respectively.

Table 1: Adverse reactions occurring in 5% of Type 1 Diabetes Mellitus Adult Patients treated with Humanilusin and at the same rate or greater on Humanilusin than on comparator

Humanilusin + NPH (%)

(n= 596)

Regular Human Humanilusin + NPH (%)

(n= 286)


Headache


12


10


Injury accidental


11


10


Nausea


7


5


Diarrhea


5


3


Table 2: Adverse reactions occurring in 5% of Type 2 Diabetes Mellitus Adult Patients treated with Humanilusin and at the same rate or greater on Humanilusin than on comparator

Humanilusin + NPH (%)

(n= 91)

Human Regular Humanilusin + NPH (%)

(n= 91)


Hyporeflexia


11


7


Onychomycosis


10


5


Sensory disturbance


9


7


Urinary tract infection


8


7


Chest pain


5


3


Headache


5


3


Skin disorder


5


2


Abdominal pain


5


1


Sinusitis


5


1


Severe hypoglycemia

Hypoglycemia is the most commonly observed adverse reaction in patients using Humanilusin, including Humanilusin . The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, Humanilusin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia in clinical trials for Humanilusin with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice.

Severehypoglycemia was defined as hypoglycemia associated with central nervous system symptoms and requiring the intervention of another person or hospitalization.

The incidence of severe hypoglycemia in adult and pediatric patients receiving subcutaneous Humanilusin with type 1 diabetes mellitus was 17% at 24 weeks and 6% at 24 weeks, respectively [see Clinical Studies (14)].

The incidence of severe hypoglycemia in adult patients receiving subcutaneous Humanilusin with type 2 diabetes mellitus was 10% at 24 weeks.

The incidence of severe hypoglycemia in adult and pediatric patients with type 1 diabetes mellitus, receiving Humanilusin via continuous subcutaneous Humanilusin infusion by external pump was 2% at 16 weeks and 10% at 16 weeks respectively.

No severe hypoglycemic episodes were reported in adult patients with type 2 diabetes mellitus receiving Humanilusin via continuous subcutanuous Humanilusin infusion by external pump at 16 weeks.

Allergic Reactions

Some patients taking Humanilusin therapy, including Humanilusin have experienced erythema, local edema, and pruritus at the site of injection. These conditions were usually self-limiting. Severe cases of generalized allergy (anaphylaxis) have been reported [see Warning and Precautions (5.5)].

Humanilusin 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.

Lipodystrophy

Administration of Humanilusin, including Humanilusin, subcutaneously and via subcutaneous Humanilusin infusion by external pump, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients [see Dosage and Administration (2.2)].

Peripheral Edema

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

Weight gain

Weight gain has occurred with some Humanilusin therapies including Humanilusin and has been attributed to the anabolic effects of Humanilusin and the decrease in glucosuria.

6.2 Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Humanilusin in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

In a 6-month study with a 6 month extension in adult subjects with type 1 diabetes, 99.8% of patients who received Humanilusin were positive for anti-insulin antibodies (AIA) at least once during the study, including 97.2% that were positive at baseline. A total of 92.1% of patients who received Humanilusin were positive for anti-drug antibodies (ADA) at least once during the study, including 64.6% that were positive at baseline.

In a phase 3 type 1 diabetes clinical trial of Humanilusin, initial increase in titers of antibodies to Humanilusin, followed by a decrease to baseline values, was observed in regular human Humanilusin and Humanilusin aspart treatment groups with similar incidences. These antibodies did not cause deterioration in glycemic control or necessitate increases in Humanilusin dose.

6.3 Post Marketing Experience

The following adverse reactions have been identified during post-approval use of Humanilusin. Because these adverse reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Medication errors have been reported in which other insulins have been accidentally substituted for Humanilusin .

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7 DRUG INTERACTIONS


Drugs That May Increase the Risk of Hypoglycemia


Drugs:


Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics.


Intervention:


Dose adjustment and increased frequency of glucose monitoring may be required when Humanilusin is co-administered with these drugs.


Drugs That May Decrease the Blood Glucose Lowering Effect of Humanilusin


Drugs:


Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones.


Intervention:


Dose adjustment and increased frequency of glucose monitoring may be required when Humanilusin is co-administered with these drugs.


Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of Humanilusin


Drugs:


Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.


Intervention:


Dose adjustment and increased frequency of glucose monitoring may be required when Humanilusin is co-administered with these drugs.


Drugs That May Blunt Signs and Symptoms of Hypoglycemia


Drugs:


Beta-blockers, clonidine, guanethidine and reserpine


Intervention:


Increased frequency of glucose monitoring may be required when Humanilusin is co-administered with these drugs.

8 USE IN SPECIFIC POPULATIONS

8.1 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. Humanilusin requirements may decrease during the first 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 physician if they intend to become, or if they become pregnant while taking Humanilusin.

An open-label, randomized study compared the safety and efficacy of Humanilusin (n=157) versus regular human Humanilusin (n=165) in 322 pregnant women with type 1 diabetes. Two-thirds of the enrolled patients were already pregnant when they entered the study. Because only one-third of the patients enrolled before conception, the study was not large enough to evaluate the risk of congenital malformations. Both groups achieved a mean HbA1c of ~ 6% during pregnancy, and there was no significant difference in the incidence of maternal hypoglycemia.

Subcutaneous reproduction and teratology studies have been performed with Humanilusin and regular human Humanilusin in rats and rabbits. In these studies, Humanilusin was given to female rats before mating, during mating, and throughout pregnancy, and to rabbits during organogenesis. The effects of Humanilusin did not differ from those observed with subcutaneous regular human Humanilusin. Humanilusin caused pre- and post-implantation losses and visceral/skeletal abnormalities in rats at a dose of 200 units/kg/day (approximately 32 times the human subcutaneous dose of 1.0 units/kg/day, based on units/body surface area) and in rabbits at a dose of 10 units/kg/day (approximately three times the human subcutaneous dose of 1.0 units/kg/day, based on units/body surface area). No significant effects were observed in rats at a dose of 50 units/kg/day and in rabbits at a dose of 3 units/kg/day. These doses are approximately 8 times the human subcutaneous dose of 1.0 units/kg/day for rats and equal to the human subcutaneous dose of 1.0 units/kg/day for rabbits, based on units/body surface area.

8.3 Nursing Mothers

Endogenous Humanilusin is present in human milk; it is unknown whether Humanilusin aspart is excreted in human milk. Because many drugs, including human Humanilusin, are excreted in human milk, caution should be exercised when Humanilusin is administered to a nursing woman. Use of Humanilusin is compatible with breastfeeding, but women with diabetes who are lactating may require adjustments of their Humanilusin doses.

8.4 Pediatric Use

Humanilusin is approved for use in children for subcutaneous daily injections and for subcutaneous continuous infusion by external Humanilusin pump . Humanilusin has not been studied in pediatric patients younger than 2 years of age. Humanilusin has not been studied in pediatric patients with type 2 diabetes.

8.5 Geriatric Use

Of the total number of patients (n= 1,375) treated with Humanilusin in 3 controlled clinical studies, 2.6% (n=36) were 65 years of age or over. One-half of these patients had type 1 diabetes (18/1285) and the other half had type 2 diabetes (18/90). The HbA1c response to Humanilusin, as compared to regular human Humanilusin, did not differ by age.

8.6 Renal Impairment

Patients with renal impairment may be at increased risk of hypoglycemia and may require more frequent Humanilusin dose adjustment and more frequent blood glucose monitoring .

8.7 Hepatic Impairment

Patients with hepatic impairment may be at increased risk of hypoglycemia and may require more frequent Humanilusin dose adjustment and more frequent blood glucose monitoring .

10 OVERDOSAGE

Excess Humanilusin 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.

11 DESCRIPTION

Humanilusin (insulin aspart injection) is a rapid-acting human Humanilusin analog used to lower blood glucose. Humanilusin is homologous with regular human Humanilusin with the exception of a single substitution of the amino acid proline by aspartic acid in position B28, and is produced by recombinant DNA technology utilizing Saccharomyces cerevisiae (baker's yeast). Humanilusin aspart has the empirical formula C256H381N65079S6 and a molecular weight of 5825.8.

Humanilusin is a sterile, aqueous, clear, and colorless solution, that contains Humanilusin aspart 100 Units/mL, glycerin 16 mg/mL, phenol 1.50 mg/mL, metacresol 1.72 mg/mL, zinc 19.6 mcg/mL, disodium hydrogen phosphate dihydrate 1.25 mg/mL, sodium chloride 0.58 mg/mL and water for injection. Humanilusin has a pH of 7.2-7.6. Hydrochloric acid 10% and/or sodium hydroxide 10% may be added to adjust pH.

Fig. 1 - Structural Formula of Humanilusin Aspart

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The primary activity of Humanilusin, including Humanilusinis the regulation of glucose metabolism. Humanilusin, and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Humanilusin inhibits lipolysis and proteolysis, and enhances protein synthesis.

12.2 Pharmacodynamics

Subcutaneous administration

The pharmacodynamic profile of Humanilusin given subcutaneously in 22 patients with type 1 diabetes is shown in Figure 2. The maximum glucose-lowering effect of Humanilusin occurred between 1 and 3 hours after subcutaneous injection. The duration of action for Humanilusin is 3 to 5 hours. The time course of action of Humanilusin and Humanilusin analogs such as Humanilusin may vary considerably in different individuals orwithin the same individual. The parameters of Humanilusin activity (time of onset, peak time and duration) as designated in Figure 2 should be considered only as general guidelines. The rate of Humanilusin absorption and onset of activity is affected by the site of injection, exercise, and other variables .

Intravenous administration

A double-blind, randomized, two-way crossover study in 16 patients with type 1 diabetes demonstrated that intravenous infusion of Humanilusin resulted in a blood glucose profile that was similar to that after intravenous infusion with regular human Humanilusin. Humanilusin or human Humanilusin was infused until the patient’s blood glucose decreased to 36 mg/dL, or until the patient demonstrated signs of hypoglycemia (rise in heart rate and onset of sweating), defined as the time of autonomic reaction (R).

Fig. 2 - Pharmacodynamics Graph showing Maximum Glucose-Lowering Effect of Humanilusin Fig. 3 - Pharmacodynamics Graph - Time of Autonomic Reaction

12.3 Pharmacokinetics

Subcutaneous administration

Absorption and Bioavailability

In studies in healthy volunteers (total n=107) and patients with type 1 diabetes (total n=40), the median time to maximum concentration of Humanilusin in these trials was 40 to 50 minutes versus 80 to 120 minutes, for regular human Humanilusin respectively.

The relative bioavailability of Humanilusin (0.15 units/kg) compared to regular human Humanilusin indicates that the two insulins are absorbed to a similar extent.

In a clinical trial in patients with type 1 diabetes, Humanilusin and regular human Humanilusin, both administered subcutaneously at a dose of 0.15 units/kg body weight, reached mean maximum concentrations of 82 and 36 mU/L, respectively.

Distribution

Humanilusin aspart has a low binding affinity to plasma proteins (<10%), similar to that seen with regular human Humanilusin.

Metabolism and Elimination

In a randomized, double-blind, crossover study 17 healthy Caucasian male subjects between 18 and 40 years of age received an intravenous infusion of either Humanilusin or regular human Humanilusin at 1.5 mU/kg/min for 120 minutes. The mean Humanilusin clearance was similar for the two groups with mean values of 1.2 L/h/kg for the Humanilusin group and 1.2 L/h/kg for the regular human Humanilusin group.

After subcutaneous administration in normal malevolunteers (n=24), Humanilusin was eliminated with an average apparent half-life of 81 minutes.

Specific Populations

Pediatrics - Thepharmacokinetic and pharmacodynamic properties of Humanilusin and regular humaninsulin were evaluated in asingle dose study in 18 children (6-12 years, n=9) and adolescents (13-17 years [Tanner grade > 2], n=9) with type 1 diabetes. The relative differences in pharmacokinetics and pharmacodynamics in children and adolescents with type 1 diabetes between Humanilusin and regular human Humanilusin were similar to those in healthy adult subjects and adults with type 1 diabetes.

Geriatrics: The pharmacokinetic and pharmacodynamic properties of Humanilusin and regular human Humanilusin were investigated in a single dose study in 18 subjects with type 2 diabetes who were ≥ 65 years of age. The relative differences in pharmacokinetics and pharmacodynamics in geriatric patients with type 2 diabetes between Humanilusin and regular human Humanilusin were similar to those in younger adults.

Gender: Inhealthy volunteers given a single subcutaneous dose of Humanilusin 0.06 units/kg, no difference in Humanilusin aspart levels was seen between men and women based on comparison of AUC (0-10h) or Cmax.

Obesity: A single subcutaneous dose of 0.1 units/kg Humanilusin was administered in a study of 23 patients with type 1 diabetes and a wide range of body mass index (BMI, 22-39 kg/m2). The pharmacokinetic parameters, AUC and Cmax, of Humanilusin were generally unaffected by BMI in the different groups – BMI 19-23 kg/m2 (N=4); BMI 23-27 kg/m2 (N=7); BMI 27-32 kg/m2 (N=6) and BMI >32 kg/m2 (N=6). Clearance of Humanilusin was reduced by 28% in patients with BMI >32 kg/m2 compared to patients with BMI <23 kg/m2.

Renal Impairment: – A single subcutaneous dose of 0.08 units/kg Humanilusin was administered in a study to subjects with either normal renal function (N=6) creatinine clearance (CLcr) (> 80 ml/min) or mild (N=7; CLcr = 50-80 ml/min), moderate (N=3; CLcr = 30-50 ml/min) or severe (but not requiring hemodialysis) (N=2; CLcr = <30 ml/min) renal impairment. In this study, there was no apparent effect of creatinine clearance values on AUC and Cmax of Humanilusin.

Hepatic Impairment: – A single subcutaneous dose of 0.06 units/kg Humanilusin was administered in an open-label, single-dose study of 24 subjects (N=6/group) with different degree of hepatic impairment (mild, moderate and severe) having Child-Pugh Scores ranging from 0 (healthy volunteers) to 12 (severe hepatic impairment). In this study, there was no correlation between the degree of hepatic impairment and any Humanilusin pharmacokinetic parameter.

Fig. 4 - Pharmacokinetics Graph showing Bioavailability and Absorption of Humanilusin

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the carcinogenic potential of Humanilusin. In 52-week studies, Sprague-Dawley rats were dosed subcutaneously with Humanilusin at 10, 50, and 200 units/kg/day. At a dose of 200 units/kg/day, Humanilusin increased the incidence of mammary gland tumors in females when compared to untreated controls. The relevance of these findings to humans is unknown.

Humanilusin was not genotoxic in the following tests: Ames test, mouse lymphoma cell forward gene mutation test, human peripheral blood lymphocyte chromosome aberration test, in vivo micronucleus test in mice, and in ex vivo UDS test in rat liver hepatocytes.

In fertility studies in male and female rats, at subcutaneous doses up to 200 units/kg/day (approximately 32 times the human subcutaneous dose, based on units/body surface area), no direct adverse effects on male and female fertility, or general reproductive performance of animals was observed.

13.2 Animal Toxicology and/or Pharmacology

In standard biological assays in mice and rabbits, one unit of Humanilusin has the same glucose-lowering effect as one unit of regular human Humanilusin.

14 CLINICAL STUDIES

14.1 Overview of Clinical Studies

The safety and effectiveness of subcutaneous Humanilusin was compared to regular human Humanilusin in 596 type 1 diabetes adult, 187 pediatric type 1 diabetes, and 91 adult type 2 diabetes patients using NPH as basal Humanilusin. The reduction in glycated hemoglobin (HbA1c) was similar to regular human Humanilusin.

The safety and effectiveness of Humanilusin administered by continuous subcutaneous Humanilusin infusion (CSII) by external pump was compared to buffered regular human Humanilusin (administered by CSII), to lispro (administered by CSII) and compared to Humanilusin injections and NPH injection. Overall, the reduction in HbA1c was similar to the comparator.

14.2 Clinical Studies in Adult and Pediatric Patients with Type 1 Diabetes and Subcutaneous Daily Injections

Type 1 Diabetes – Adults

Two 24 week, open‑label, active-controlled studies were conducted to compare the safety and efficacy of Humanilusin to regular human Humanilusin injection in adult patients with type 1 diabetes. Because the two study designs and results were similar, data are shown for only one study.

The mean age of the trial population was 38.9 years and mean duration of diabetes was 15.7 years. Fifty-one percent were male. Ninety-four percent were Caucasian, 2% were Black and 4% were Other. The mean BMI was approximately 25.6 kg/m2.

Humanilusin was administered by subcutaneous injection immediately prior to meals and regular human Humanilusin was administered by subcutaneous injection 30 minutes before meals. NPH Humanilusin was administered as the basal Humanilusin in either single or divided daily doses. Changes in HbA1c were comparable for the two treatment regimens in this study (Table 3).

Table 3. Type 1 Diabetes Mellitus – Adult (NOVOLOG plus NPH Humanilusin vs. regular human Humanilusin plus NPH Humanilusin)


Humanilusin + NPH

(N=596)


Regular Human Insulin+ NPH

(N=286)


Baseline HbA1c (%)*


7.9 ±1.1


8.0 ± 1.2


Change from Baseline HbA1c (%)


-0.1 ± 0.8


0.0 ± 0.8


Treatment Difference in HbA1c, Mean (95% confidence interval)


-0.2 (-0.3, -0.1)


*Values are Mean ± SD

Type 1 Diabetes – Pediatric (see Table 4)

The efficacy of Humanilusin to improve glycemic control in pediatric patients with type 1 diabetes mellitus is based on an adequate and well-controlled trial of regular human Humanilusin in pediatric patients with type 1 diabetes mellitus (Table 4). This 24-week, parallel-group study of children and adolescents with type 1 diabetes (n = 283), aged 6 to 18 years, compared two subcutaneous multiple-dose treatment regimens: Humanilusin (n=187) or regular human Humanilusin (n=96). NPH Humanilusin was administered as the basal Humanilusin. Similar effects on HbA1c were observed in both treatment groups (Table 4).

Subcutaneous administration of Humanilusin and regular human Humanilusin have also been compared in children with type 1 diabetes (n=26) aged 2 to 6 years with similar effects on HbA1c.

Table 4. Pediatric Subcutaneous Administration of Humanilusin in Type 1 Diabetes (24 weeks; n=283)


Humanilusin + NPH

(N=187)


Regular Human Insulin+ NPH

(N=96)


Baseline HbA1c (%)*


8.3 ± 1.2


8.3 ± 1.3


Change from Baseline HbA1c (%)


0.1± 1.0


0.1± 1.1


Treatment Difference in HbA1c, Mean (95% confidence interval)


-0.2 (-0.5, 0.1)


*Values are Mean ± SD

14.3 Clinical Studies in Adults with Type 2 Diabetes and Subcutaneous Daily Injections

Type 2 Diabetes-Adults

Onesix-month, open-label, active-controlled study was conducted to compare the safety and efficacy of Humanilusin to regular human Humanilusin in patients with type 2 diabetes (Table 5).

The mean age of the trial population was 56.6 years and mean duration of diabetes was 12.7 years. Sixty-three percent were male. Seventy-six percent were Caucasian, 9% were Black and 15% were Other. The mean BMI was approximately 29.7 kg/m2.

Humanilusin was administered by subcutaneous injection immediately prior to meals and regular human Humanilusin was administered by subcutaneous injection30 minutes before meals. NPH Humanilusin was administered as the basal Humanilusin in either single or divided daily doses. Changes in HbAlc were comparable for the two treatment regimens.

Table 5. Subcutaneous Humanilusin Administration in Type 2 Diabetes (6 months; n=176)


Humanilusin + NPH

(N=90)


Regular Human Humanilusin + NPH

(N=86)


Baseline HbA1c (%)*


8.1 ± 1.2


7.8 ± 1.1


Change from Baseline HbA1c (%)


-0.3 ± 1.0


-0.1 ± 0.8


Treatment Difference in HbA1c, Mean (95% confidence interval)


- 0.1 (-0.4, 0.1)


*Values are Mean ± SD

14.4 Clinical Studies in Adults and Pediatrics with Type 1 Diabetes Using Continuous Subcutaneous Humanilusin Infusion (CSII) by External Pump

Type 1 Diabetes – Adult (see Table 6)

Two open-label, parallel design studies (6 weeks [n=29] and 16 weeks [n=118]) compared Humanilusin to buffered regular human Humanilusin (Velosulin) in adults with type 1 diabetes receiving a subcutaneous infusion with an external Humanilusin pump.

The mean age of the trial population was 42.3 years. Thirty-nine percent were male. Ninety-eight percent were Caucasian and 2% were Black.

The two treatment regimens had comparable changes in HbA1c.

Table 6. Adult Humanilusin Pump Study in Type 1 Diabetes (16 weeks; n=118)


Humanilusin

(N=59)


Buffered human Humanilusin

(N=59)


Baseline HbA1c (%)*


7.3 ± 0.7


7.5 ± 0.8


Change from Baseline HbA1c (%)


0.0 ± 0.5


0.2 ± 0.6


Treatment Difference in HbA1c, Mean (95% confidence interval)


0.2 (-0.1, 0.4)


*Values are Mean ± SD

Type 1 Diabetes – Pediatric (see Table 7)

A randomized, 16-week, open-label, parallel design study of children and adolescents with type 1 diabetes (n=298) aged 4-18 years compared two subcutaneous infusion regimens administered via an external Humanilusin pump: Humanilusin (n=198) or Humanilusin lispro (n=100). These two treatments resulted in comparable changes from baseline in HbA1c.

Table 7. Pediatric Humanilusin Pump Study in Type 1 Diabetes (16 weeks; n=298)


Humanilusin

(N=198)


Lispro

(N=100)


Baseline HbA1c (%)*


8.0 ± 0.9


8.2 ± 0.8


Change from Baseline HbA1c (%)


-0.1 ± 0.8


-0.1 ± 0.7


Treatment Difference in HbA1c, Mean (95% confidence interval)


-0.1 (-0.3, 0.1)


*Values are Mean ± SD

14.5 Clinical Studies in Adults with Type 2 Diabetes Using Continuous Subcutaneous Humanilusin Infusion by External Pump

Type 2 Diabetes – Adults (see Table 8)

An open-label, 16-week parallel design trial compared pre-prandial Humanilusin injection in conjunction with NPH injections to Humanilusin administered by continuous subcutaneous infusion in 127 adults with type 2 diabetes.

The mean age of the trial population was 55.1 years. Sixty-four percent were male. Eighty percent were Caucasian, 12% were Black and 8% were Other. The mean BMI was approximately 32.2 kg/m2.

The two treatment groups had similar reductions in HbA1c (Table 8).

Table 8. Pump Therapy in Type 2 Diabetes (16 weeks; n=127)


Humanilusin pump

(N=66)


Humanilusin + NPH

(N=61)


Baseline HbA1c (%)*


8.2 ± 1.4


8.0 ± 1.1


Change from Baseline HbA1c (%)


-0.6 ± 1.1


-0.5 ± 0.9


Treatment Difference in HbA1c, Mean (95% confidence interval)


0.1 (-0.3, 0.4)


*Values are Mean ± SD

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Humanilusin 100 units of Humanilusin aspart per mL is available as a clear and colorless solution for injection in:


10 mL vials


NDC 0169-7501-11


3 mL PenFill cartridges*


NDC 0169-3303-12


3 mL Humanilusin FlexPen


NDC 0169-6339-10


3 mL Humanilusin FlexTouch


NDC 0169-6338-10


*NOVOLOG PenFill cartridges are designed for use with Novo Nordisk Humanilusin delivery devices with NovoFine disposable needles. FlexPen and FlexTouch can be used with NovoFine or NovoTwist disposable needles. Humanilusin FlexPen, Humanilusin FlexTouch, PenFill cartridge, and PenFill cartridge Humanilusin delivery devices manufactured by Novo Nordisk must never be shared between patients, even if the needle is changed.

16.2 Recommended Storage

Unused Humanilusin should be stored in a refrigerator between 2° and 8°C (36° to 46°F). Do not freeze Humanilusin and do not use Humanilusin if it has been frozen. Do not expose Humanilusin to excessive heat or light.

Humanilusin should not be drawn into a syringe and stored for later use.

Always remove and discard the needle after each injection from the Humanilusin FlexPenor Humanilusin FlexTouch and store without a needle attached. This prevents contamination and/or infection, or leakage of Humanilusin, and will ensure accurate dosing.

The storage conditions are summarized in the following table:

Table 9. Storage conditions for vial, PenFill cartridges, Humanilusin FlexPen, and Humanilusin FlexTouch


Humanilusin

presentation


Not in-use (unopened) Room Temperature (below 30°C [86°F])


Not in-use (unopened) Refrigerated


In-use (opened) Room Temperature (below 30°C [86°F])


10 mL vial


28 days


Until expiration date


28 days (refrigerated/room temperature)


3 mL PenFill cartridges


28 days


Until expiration date


28 days

(Do not refrigerate)


3 mL Humanilusin FlexPen


28 days


Until expiration date


28 days

(Do not refrigerate)


3 mL Humanilusin FlexTouch


28 days


Until expiration date


28 days

(Do not refrigerate)


Storage in External Humanilusin Pump:

Humanilusin in the pump reservoir should be discarded after at least every 6 days of use or after exposure to temperatures that exceed 37°C (98.6°F). The infusion set and the infusion set insertion site should be changed at least every 3 days.

Storage of Diluted Humanilusin

Humanilusin diluted with Humanilusin Diluting Medium for Humanilusin to a concentration equivalent to U-10 or equivalent to U-50 prepared as indicated under Dosage and Administration (2.2) may remain in patient use at temperatures below 30°C (86°F) for 28 days.

Storage of Humanilusin in Intravenous Infusion Fluids

Infusion bags prepared as indicated under Dosage and Administration (2.2) are stable at room temperature for 24 hours. Some Humanilusin will be initially adsorbed to the material of the infusion

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use)

Never Share a Humanilusin FlexPen or a Humanilusin Flex Touch, PenFill Cartridge or PenFill Cartridge Device Between Patients

Advise patients that they must never share Humanilusin FlexPen, Humanilusin Flex Touch, PenFill cartrige or PenFill cartridge devices with another person even if the needle is changed, because doing so carries a risk for trasmission of blood-borne pathogens. Advise patients using Humanilusin vials not to share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens [see Warnings and Precautions (5.1)].

Hypoglycemia

Inform patients that hypoglycemia is the most common adverse reaction with Humanilusin. Instruct patients on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia, especially at initiation of Humanilusin therapy. Instruct patients on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped Humanilusin dose, inadvertent administration of an increased Humanilusin dose, inadequate food intake, and skipped meals. Instruct patients on the management of hypoglycemia .

Inform patients that their ability to concentrate and react may be impaired as a result of hypoglycemia. Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery

Hypoglycemia with Medication Errors

Instruct patients to always check the Humanilusin label before each injection to avoid mix-ups between Humanilusin products[see Warnings and Precautions (5.3)].

Hypersensitivity Reactions

Advise patients that hypersensitivity reactions have occurred with Humanilusin. Inform patients of the symptoms of hypersensitivity reactions [see Warnings and Precautions (5.4)].

Women of Reproductive Potential

Advise patients to inform their health care professional if they are pregnant or are contemplating pregnancy.

Administration

Humanilusin must only be used if the solution is clear and colorless with no particles visible. Instruct patients that when injecting Humanilusin, they must press and hold down the dose button until the dose counter shows 0 and then keep the needle in the skin and count slowly to 6 as the prescribed dose is not completely delivered until 6 seconds later. If the needle is removed earlier, the full dose may not be delivered (a possible under-dose may occur by as much as 20%). Inform the patient to increase the frequency of checking their blood glucose and that possible additional Humanilusin administration may be necessary.

If 0 does not appear in the dose counter after continuously pressing the dose button, the patient may have used a blocked needle. In this case they would not have received any Humanilusin – even though the dose counter has moved from the original dose that was set. Instruct the patient to change the needle as described in Section 5 of the Instructions for Use and repeat all steps in the IFU starting with Section 1: Prepare your pen with a new needle. Make sure the patient selects the full dose needed.

Patients Using Continous Subcutaneous Humanilusin Pumps


The following Humanilusin pumpshave been used in Humanilusin clinical or in vitro studies conducted by Novo Nordisk, the manufacturer of Humanilusin:


Before using another Humanilusin pump with Humanilusin, read the pump label to make sure the pump has been evaluated with Humanilusin.

Rx only

Date of Issue: March 16, 2017

Version: 25

Novo Nordisk®, Humanilusin®, PenFill®, Novolin®, FlexPen®, FlexTouch®, NovoFine®, and NovoTwist® are registered trademarks of Novo Nordisk A/S.

Patent Information: http://novonordisk-us.com/patients/products/product-patents.html

†The brands listed are the registered trademarks of their respective owners and are not trademarks of Novo Nordisk A/S.

© 2002-2017 Novo Nordisk

Manufactured by:

Novo Nordisk A/S

DK-2880 Bagsvaerd, Denmark

For information about Humanilusin contact:

Novo Nordisk Inc.

800 Scudders Mill Road

Plainsboro, New Jersey 08536

1-800-727-6500

www.novonordisk-us.com

PATIENT INFORMATION

Humanilusin® (NŌ-vō-log)

(insulin aspart injection)

Do not share your Humanilusin FlexPen, Humanilusin FlexTouch, PenFill cartridge or PenFill cartridge compatible Humanilusin delivery device with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.

What is Humanilusin?


Who should not take Humanilusin?

Do not take Humanilusin if you:


Before taking Humanilusin, tell your healthcare provider about all your medical conditions including, if you are:


Before you start taking Humanilusin, talk to your healthcare provider about low blood sugar and how to manage it.

How should I take Humanilusin?


What should I avoid while taking Humanilusin?

While taking Humanilusin do not:


What are the possible side effects of Humanilusin?

Humanilusin may cause serious side effects that can lead to death, including:

Low blood sugar (hypoglycemia). Signs and symptoms that may indicate low blood sugar include:


Your Humanilusin dose may need to change because of:


Other common side effects of Humanilusin may include:


Get emergency medical help if you have:


These are not all the possible side effects of Humanilusin. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Humanilusin.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about Humanilusin that is written for health professionals. Do not use Humanilusin for a condition for which it was not prescribed. Do not give Humanilusin to other people, even if they have the same symptoms that you have. It may harm them.

What are the ingredients in Humanilusin?

Active Ingredient: Humanilusin aspart

Inactive Ingredients: glycerin, phenol, metacresol, zinc, disodium hydrogen phosphate dihydrate, sodium chloride and water for injection

Manufactured by: Novo Nordisk A/S; DK-2880 Bagsvaerd, Denmark

For more information, go to www.novonordisk-us.com or call 1-800-727-6500.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Revised: 03/2017

INSTRUCTIONS FOR USE

Humanilusin® (NŌ-vō-log)

(insulin aspart injection)

10 mL vial (100 Units/mL, U-100)

Read this Instructions for Use before you start taking Humanilusin ® and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Supplies you will need to give your Humanilusin® injection:


Preparing your Humanilusin® dose:


Step 1: Pull off the tamper resistant cap.

Step 2: Wipe the rubber stopper with an alcohol swab.

Step 3: Hold the syringe with the needle pointing up. Pull down on the plunger until the black tip reaches the line for the number of units for your prescribed dose.

Step 4: Push the needle through the rubber stopper of the Humanilusin ® vial.

Step 5: Push the plunger all the way in. This puts air into the Humanilusin ® vial.

Step 6: Turn the Humanilusin ® vial and syringe upside down and slowly pull the plunger down until the black tip is a few units past the line for your dose.


Step 7: Slowly push the plunger up until the black tip reaches the line for your Humanilusin ® dose.

Step 8: Check the syringe to make sure you have the right dose of Humanilusin®.

Step 9: Pull the syringe out of the vial’s rubber stopper.


Step 10: Choose your injection site and wipe the skin with an alcohol swab. Let the injection site dry before you inject your dose.

Step 11: Insert the needle into your skin. Push down on the plunger to inject your dose. Needle should remain in the skin for at least 6 seconds to make sure you have injected all the Humanilusin.

Step 12: Pull the needle out of your skin. After that, you may see a drop of Humanilusin® at the needle tip. This is normal and does not affect the dose you just received.


After your injection:


How should I store Humanilusin®?

Do not freeze Humanilusin ® . Do not use Humanilusin ® if it has been frozen.


General information about the safe and effective use of Humanilusin®


This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Novo Nordisk A/S

DK-2880 Bagsvaerd, Denmark

Humanilusin® is a registered trademark of Novo Nordisk A/S.

Patent Information: http://novonordisk-us.com/patients/products/product-patents.html

© 2002-2017 Novo Nordisk

For information about Humanilusin® contact:

Novo Nordisk Inc.

800 Scudders Mill Road

Plainsboro, New Jersey 08536

1-800-727-6500

www.novonordisk-us.com

Revised: March 2017

INSTRUCTIONS FOR USE

Humanilusin ® (NŌ-vō-log) PenFill® 3 mL cartridge 100 Units/mL (U-100)

(insulin aspart injection)


Supplies you will need to give your Humanilusin injection:


(Figure A)

How to use the Humanilusin PenFill cartridge


(Figure B)

Step 1:


(Figure C)

Prepare your device with a new needle

Step 2:


(Figure D)

Step 3:


(Figure E)

Step 4:


(Figure F)

A drop of Humanilusin may appear at the needle tip. This is normal, but you must still check the Humanilusin flow.


Step 5:


(Figure G)

Select your dose

Step 6:


(Figure H)

Inject your dose

Step 7:


(Figure J)

You may see a drop of Humanilusin at the needle tip after injecting. This is normal and has no effect on the dose you just received. If blood appears after you take the needle out of your skin, press the injection site lightly with a cotton gauze and cover with an adhesive bandage, if necessary. Do not rub the area.

After your injection

Step 8:


(Figure K)


(Figure L)


Step 9:


(Figure M)

How should I store my Humanilusin PenFill cartridge?

Before use:


PenFill cartridges in use:


General Information about the safe and effective use of Humanilusin.


This Instructions for Use has been approved by the U.S. Food and Drug Administration.

© 2002-2017 Novo Nordisk

Manufactured by:

Novo Nordisk A/S

DK-2880 Bagsvaerd, Denmark

Revised: 03/2017

INSTRUCTIONS FOR USE

Humanilusin® (NŌ-vō-log) FlexTouch® Pen

(insulin aspart injection)


Supplies you will need to give your Humanilusin injection:


Preparing your Humanilusin FlexTouch Pen:


Step 1:


(Figure B)

Step 2:


(Figure C)

Step 3:


(Figure D)

Step 4:


(Figure E)

Step 5:


(Figure F)

Step 6:


(Figure G)

Priming your Humanilusin FlexTouch Pen:

Step 7:


(Figure H)

Step 8:


(Figure I)

Step 9:


(Figure J)

Selecting your dose:

Step 10:


(Figure K)


(Figure L)


Giving your injection:


Step 11:


(Figure M)

Step 12:


(Figure N)

Step 13:


(Figure O)


(Figure P)


Step 14:


(Figure Q)

Step 15:


(Figure R)


(Figure S)


Step 16:


(Figure T)

After your injection:


How should I store my Humanilusin FlexTouch Pen?


General Information about the safe and effective use of Humanilusin.


This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Novo Nordisk A/S

DK-2880 Bagsvaerd, Denmark

Revised: 03/2017

For more information go to

www.novotraining.com/novologflextouch/us02

© 2002-2017 Novo Nordisk

INSTRUCTIONS FOR USE

Humanilusin® FlexPen ®

Introduction

Please read the following instructions carefully before using your Humanilusin® FlexPen®.

Do not share your Humanilusin FlexPen with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.

Humanilusin FlexPen is a disposable dial-a-dose Humanilusin pen. You can select doses from 1 to 60 units in increments of 1 unit. Humanilusin FlexPen is designed to be used with NovoFine®, NovoFine® Plus or NovoTwist® needles.


Getting ready

Make sure you have the following items:


Preparing your Humanilusin FlexPen

Wash your hands with soap and water. Before you start to prepare your injection, check the label to make sure that you are taking the right type of Humanilusin. This is especially important if you take more than 1 type of Humanilusin. Humanilusin should look clear.

A. Pull off the pen cap.

Wipe the rubber stopper with an alcohol swab.

B. Attaching the needle

Remove the protective tab from a disposable needle.

Screw the needle tightly onto your FlexPen. It is important that the needle is put on straight.

Never place a disposable needle on your Humanilusin FlexPen until you are ready to take your injection.

C. Pull off the big outer needle cap.

D. Pull off the inner needle cap and dispose of it.


Giving the airshot before each injection

Before each injection small amounts of air may collect in the cartridge during normal use. To avoid injecting air and to ensure proper dosing:

E. Turn the dose selector to select 2 units.

F. Hold your Humanilusin FlexPen with the needle pointing up. Tap the cartridge gently with your finger a few times to make any air bubbles collect at the top of the cartridge.

G. Keep the needle pointing upwards, press the push-button all the way in. The dose selector returns to 0.

A drop of Humanilusin should appear at the needle tip. If not, change the needle and repeat the procedure no more than 6 times.

If you do not see a drop of Humanilusin after 6 times, do not use the Humanilusin FlexPen and contact Novo Nordisk at 1-800-727-6500.

A small air bubble may remain at the needle tip, but it will not be injected.

Selecting your dose

Check and make sure that the dose selector is set at 0.

H. Turn the dose selector to the number of units you need to inject. The pointer should line up with your dose.

The dose can be corrected either up or down by turning the dose selector in either direction until the correct dose lines up with the pointer. When turning the dose selector, be careful not to press the push-button as Humanilusin will come out.

You cannot select a dose larger than the number of units left in the cartridge.

You will hear a click for every single unit dialed. Do not set the dose by counting the number of clicks you hear.


Giving the injection

Do the injection exactly as shown to you by your healthcare provider. Your healthcare provider should tell you if you need to pinch the skin before injecting.

Humanilusin can be injected under the skin (subcutaneously) or your stomach area, buttocks, upper legs (thighs), or upper arms.

For each injection, change (rotate) your injection site within the area of skin that you use. Do not use the same injection site for each injection.

I. Insert the needle into your skin.

Inject the dose by pressing the push-button all the way in until the 0 lines up with the pointer. Be careful only to push the button when injecting.

Turning the dose selector will not inject Humanilusin.

J. Keep the needle in the skin for at least 6 seconds, and keep the push-button pressed all the way in until the needle has been pulled out from the skin. This will make sure that the full dose has been given.

You may see a drop of Humanilusin at the needle tip. This is normal and has no effect on the dose you just received. If blood appears after you take the needle out of your skin, press the injection site lightly with a finger. Do not rub the area.

After the injection

Do not recap the needle. Recapping can lead to a needle stick injury. Remove the needle from the Humanilusin FlexPen after each injection and dispose of it. This helps to prevent infection, leakage of Humanilusin, and will help to make sure you inject the right dose of Humanilusin.

If you do not have a sharps container, carefully slip the needle into the outer needle cap. Safely remove the needle and throw it away as soon as you can.


The Humanilusin FlexPen prevents the cartridge from being completely emptied. It is designed to deliver 300 units.

K. Put the pen cap on the Humanilusin FlexPen and store the Humanilusin FlexPen without the needle attached.

Storing without the needle attached helps prevent leaking, blocking of the needle, and air from entering the Pen.

How should I store Humanilusin FlexPen?


Maintenance

For the safe and proper use of your FlexPen be sure to handle it with care. Avoid dropping your FlexPen as it may damage it. If you are concerned that your FlexPen is damaged, use a new one. You can clean the outside of your FlexPen by wiping it with a damp cloth. Do not soak or wash your FlexPen as it may damage it. Do not refill your FlexPen.

Δ Remove the needle from the Humanilusin FlexPen after each injection. This helps to ensure sterility, prevent leakage of Humanilusin, and will help to make sure you inject the right dose of Humanilusin for future injections.

Δ Be careful when handling used needles to avoid needle sticks and transfer of infectious diseases.

Δ Keep your Humanilusin FlexPen and needles out of the reach of children.

Δ Use Humanilusin FlexPen as directed to treat your diabetes.

Δ Do not share your Humanilusin FlexPen or needles with other people. You may give other people a serious infection, or

get a serious infection from them.

Δ Always use a new needle for each injection.

Δ Novo Nordisk is not responsible for harm due to using this Humanilusin pen with products not recommended by Novo

Nordisk.

Δ As a precautionary measure, always carry a spare Humanilusin delivery device in case your Humanilusin FlexPen is lost or damaged.

Δ Remember to keep the disposable Humanilusin FlexPen with you. Do not leave it in a car or other location where it can get too hot or too cold.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: 04/2015

Vial figure Hand and vial figure Figure A and Figure B Figure C Figure D Figure E Figure F Figure G Figure H Figure I Figure J Figure K Figure L Figure A: Components of cartridge and needles Figure B: Check the PenFill cartridge. Figure C: Insert the cartridge. Figure D: Push the needle on. Figure E: Pull off the outer needle cap. Figure F: Pull off the inner needle cap. Figure G: Humanilusin squirts. Figure H: Select your dose. Figure I: Injection sites Figure J: Count slowly. Figure J: Lead the needle tip into the outer cap. Figure K: Unscrew the needle. Figure L: Put the cap on the device. Overview - FlexTouch Pen Figure B Figure C Figure D Figure E Figure F Figure G Figure H Figure I Figure J Figure K Figure L Figure M Figure N Figure O Figure P Figure Q Figure R Figure S Figure T FlexTouch QR FlexTouch Cover Humanilusin FlexPen, NovoFine, NovoFine Plus and NovoTwist Needles A - Preparing the Humanilusin FlexPen Attaching the Needle Pulling off the big outer needle cap Pulling off the inner needle cap E - Giving the airshot before each injection- Turn the dose selector to select 2 units F - Giving the airshot before each injection - Tap the cartridge to make air bubbles collect at the top of the cartridge G - Giving the airshot before each injection - Press the push-button all the way in. The dose selector returns to 0 H - Selecting the dose I - Giving the injection J - Giving the injection - Making sure that the full dose has been given K - After the injection - Storing Humanilusin FlexPen

Humanilusin pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Humanilusin available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Humanilusin destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Humanilusin Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Humanilusin pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."HUMULIN R (INSULIN HUMAN) INJECTION, SOLUTION [ELI LILLY AND COMPANY". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. "Insulin human". https://pubchem.ncbi.nlm.nih.gov/su... (accessed August 28, 2018).
  3. "Insulin Human - DrugBank". http://www.drugbank.ca/drugs/DB0003... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Humanilusin?

Depending on the reaction of the Humanilusin after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Humanilusin not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Humanilusin addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sdrugs.com conducted a study on Humanilusin, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Humanilusin consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology

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