NOVOMIX 30 PENFILL 100U / ml injection suspension in cartridge medication leaflet

NovoMix 30 Penfill 100 units/ml suspension for injection in cartridge

NovoMix 30 FlexPen 100 units/ml suspension for injection in pre-filled pen

NovoMix 30 Penfill1 ml of the suspension contains 100 units soluble insulin aspart*/protamine-crystallised insulin aspart*in the ratio 30/70 (equivalent to 3.5 mg). 1 cartridge contains 3 ml equivalent to 300 units.

NovoMix 30 FlexPen1 ml of the suspension contains 100 units soluble insulin aspart*/protamine-crystallised insulin aspart*in the ratio 30/70 (equivalent to 3.5 mg). 1 pre-filled pen contains 3 ml equivalent to 300 units.

*Insulin aspart is produced in Saccharomyces cerevisiae by recombinant DNA technology.

For the full list of excipients, see section 6.1.

Suspension for injection.

The suspension is cloudy, white and aqueous.

NovoMix 30 is indicated for treatment of diabetes mellitus in adults, adolescents and children aged10 years and above.

The potency of insulin analogues, including insulin aspart, is expressed in units, whereas the potencyof human insulin is expressed in international units.

NovoMix 30 dosing is individual and determined in accordance with the needs of the patient. Bloodglucose monitoring and insulin dose adjustments are recommended to achieve optimal glycaemiccontrol.

In patients with type 2 diabetes, NovoMix 30 can be given as monotherapy. NovoMix 30 can also begiven in combination with oral antidiabetic medicinal products and/or GLP-1 receptor agonists. Forpatients with type 2 diabetes, the recommended starting dose of NovoMix 30 is 6 units at breakfast and6 units at dinner (evening meal). NovoMix 30 can also be initiated once daily with 12 units at dinner(evening meal). When using NovoMix 30 once daily, it is generally recommended to move to twicedaily when reaching 30 units by splitting the dose into equal breakfast and dinner doses. If twice dailydosing with NovoMix 30 results in recurrent daytime hypoglycaemic episodes, the morning dose canbe split into morning and lunchtime doses (thrice daily dosing).

VV-LAB-103275 1.0 .

The following titration guideline is recommended for dose adjustments:

Pre-meal blood glucose level NovoMix 30 doseadjustment<4.4 mmol/l <80 mg/dl -2 units4.4-6.1 mmol/l 80-110 mg/dl 06.2-7.8 mmol/l 111-140 mg/dl +2 units7.9-10 mmol/l 141-180 mg/dl +4 units>10 mmol/l >180 mg/dl +6 units

The lowest of the three previous days’ pre-meal blood glucose levels should be used. The dose shouldnot be increased if hypoglycaemia occurred within these days. Dose adjustments can be made once aweek until target HbA1c is reached. Pre-meal blood glucose levels should be used to evaluate theadequacy of the preceding dose.

In patients with type 2 diabetes, a dose reduction of 20% is recommended for patients with an HbA1cless than 8% when a GLP-1 receptor agonist is added to NovoMix 30, to minimise the risk ofhypoglycaemia. For patients with an HbA1c higher than 8% a dose reduction should be considered.

Subsequently, dosage should be adjusted individually.

In patients with type 1 diabetes, the individual insulin requirement is usually between 0.5 and1.0 unit/kg/day. NovoMix 30 may fully or partially meet this requirement.

Adjustment of dose may be necessary if patients undertake increased physical activity, change theirusual diet or during concomitant illness.

NovoMix 30 can be used in elderly patients; however there is limited experience with the use of

NovoMix 30 in combination with oral antidiabetic medicinal products in patients older than 75 years.

In elderly patients, glucose monitoring should be intensified and the insulin aspart dose adjusted on anindividual basis.

Renal or hepatic impairment may reduce the patient’s insulin requirements.

In patients with renal or hepatic impairment, glucose monitoring should be intensified and the insulinaspart dose adjusted on an individual basis.

NovoMix 30 can be used in adolescents and children aged 10 years and above when premixed insulinis preferred. There is limited clinical experience with NovoMix 30 in children aged 6-9 years (seesection 5.1).

No data are available for NovoMix 30 in children below 6 years of age.

Transfer from other insulin medicinal products

When transferring a patient from biphasic human insulin to NovoMix 30, start with the same dose andregimen. Then titrate according to individual needs (see the titration guideline in the table above).

Close glucose monitoring is recommended during the transfer and in the initial weeks thereafter (seesection 4.4).

NovoMix 30 is a biphasic suspension of the insulin analogue, insulin aspart. The suspension containsrapid-acting and intermediate-acting insulin aspart in the ratio 30/70.

VV-LAB-103275 1.0 .

NovoMix 30 is for subcutaneous administration only.

NovoMix 30 is administered subcutaneously by injection in the thigh or in the abdominal wall. Ifconvenient, the gluteal or deltoid region may be used. Injection sites should always be rotated withinthe same region in order to reduce the risk of lipodystrophy and cutaneous amyloidosis (see sections4.4 and 4.8). The influence of different injection sites on the absorption of NovoMix 30 has not beeninvestigated. The duration of action will vary according to the dose, injection site, blood flow,temperature and level of physical activity.

NovoMix 30 has a faster onset of action than biphasic human insulin and should generally be givenimmediately before a meal. When necessary, NovoMix 30 can be given soon after a meal.

For detailed user instructions, please refer to the package leaflet.

NovoMix 30 Penfill

Administration with an insulin delivery system

NovoMix 30 Penfill is designed to be used with Novo Nordisk insulin delivery systems and NovoFineor NovoTwist needles. NovoMix 30 Penfill is only suitable for subcutaneous injections from areusable pen. If administration by syringe is necessary, a vial should be used.

NovoMix 30 FlexPen

Administration with FlexPen

NovoMix 30 FlexPen is a pre-filled pen (colour-coded) designed to be used with NovoFine or

NovoTwist needles. FlexPen delivers 1-60 units in increments of 1 unit. NovoMix 30 FlexPen is onlysuitable for subcutaneous injections. If administration by syringe is necessary, a vial should be used.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

NovoMix 30 must not be administered intravenously, as it may result in severe hypoglycaemia.

Intramuscular administration should be avoided. NovoMix 30 is not to be used in insulin infusionpumps.

Before travelling between different time zones, the patient should seek the doctor’s advice since thismay mean that the patient has to take the insulin and meals at different times.

Inadequate dosing or discontinuation of treatment, especially in type 1 diabetes, may lead tohyperglycaemia and diabetic ketoacidosis. Usually, the first symptoms of hyperglycaemia developgradually over a period of hours or days. They include thirst, increased frequency of urination, nausea,vomiting, drowsiness, flushed dry skin, dry mouth, loss of appetite as well as acetone odour of breath.

In type 1 diabetes, untreated hyperglycaemic events eventually lead to diabetic ketoacidosis, which ispotentially lethal.

Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia.

Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. In caseof hypoglycaemia or if hypoglycaemia is suspected, NovoMix must not be injected. After stabilisationof the patient’s blood glucose, adjustment of the dose should be considered (see sections 4.2, pct. 4.8 and4.9).

VV-LAB-103275 1.0 .

Compared with biphasic human insulin, NovoMix 30 may have a more pronounced glucose loweringeffect up to 6 hours after injection. This may have to be compensated for in the individual patientthrough adjustment of insulin dose and/or food intake.

Patients whose blood glucose control is greatly improved, e.g. by intensified insulin therapy, mayexperience a change in their usual warning symptoms of hypoglycaemia and should be advisedaccordingly. Usual warning symptoms may disappear in patients with longstanding diabetes.

Tighter control of glucose levels can increase the potential for hypoglycaemic episodes and thereforerequire special attention during dose intensification as outlined in section 4.2.

Since NovoMix 30 should be administered in immediate relation to a meal, the rapid onset of actionshould be considered in patients with concomitant diseases or treatment where a delayed absorption offood might be expected.

Concomitant illness, especially infections and feverish conditions, usually increases the patient’sinsulin requirements. Concomitant diseases in the kidney, liver or affecting the adrenal, pituitary orthyroid gland can require changes in the insulin dose.

When patients are transferred between different types of insulin medicinal products, the early warningsymptoms of hypoglycaemia may change or become less pronounced than those experienced with theirprevious insulin.

Transfer from other insulin medicinal products

Transferring a patient to another type or brand of insulin should be done under strict medicalsupervision. Changes in strength, brand (manufacturer), type, origin (animal insulin, human insulin orinsulin analogue) and/or method of manufacture (recombinant DNA versus animal source insulin) mayresult in the need for a change in dose. Patients transferred to NovoMix 30 from another type of insulinmay require an increased number of daily injections or a change in dose from that used with their usualinsulin medicinal products. If an adjustment is needed, it may occur with the first dose or during thefirst few weeks or months.

As with any insulin therapy, injection site reactions may occur and include pain, redness, hives,inflammation, bruising, swelling and itching. Continuous rotation of the injection site within a givenarea reduces the risk of developing these reactions. Reactions usually resolve in a few days to a fewweeks. On rare occasions, injection site reactions may require discontinuation of NovoMix 30.

Patients must be instructed to perform continuous rotation of the injection site to reduce the risk ofdeveloping lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulinabsorption and worsened glycaemic control following insulin injections at sites with these reactions. Asudden change in the injection site to an unaffected area has been reported to result in hypoglycaemia.

Blood glucose monitoring is recommended after the change in the injection site from an affected to anunaffected area, and dose adjustment of antidiabetic medications may be considered.

Combination of NovoMix with pioglitazone

Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin,especially in patients with risk factors for development of cardiac heart failure. This should be kept inmind if treatment with the combination of pioglitazone and NovoMix is considered. If the combinationis used, patients should be observed for signs and symptoms of heart failure, weight gain and oedema.

Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs.

VV-LAB-103275 1.0 .

Avoidance of accidental mix-ups/medication errors

Patients must be instructed to always check the insulin label before each injection to avoid accidentalmix-ups between NovoMix and other insulin products.

Insulin administration may cause insulin antibodies to form. In rare cases, the presence of such insulinantibodies may necessitate adjustment of the insulin dose in order to correct a tendency to hyper- orhypoglycaemia.

In order to improve the traceability of biological medicinal products, the name and the batch numberof the administered product should be clearly recorded.

A number of medicinal products are known to interact with the glucose metabolism.

The following substances may reduce the patient’s insulin requirements:

Oral antidiabetic medicinal products, GLP-1 receptor agonists, monoamine oxidase inhibitors (MAOI),beta-blockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids andsulfonamides.

The following substances may increase the patient’s insulin requirements:

Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics, growthhormone and danazol.

Beta-blockers may mask the symptoms of hypoglycaemia.

Octreotide/lanreotide may either increase or decrease the insulin requirement.

Alcohol may intensify or reduce the hypoglycaemic effect of insulin.

There is limited clinical experience with NovoMix 30 in pregnancy.

Animal reproduction studies have not revealed any differences between insulin aspart and humaninsulin regarding embryotoxicity or teratogenicity.

In general, intensified blood glucose control and monitoring of pregnant women with diabetes arerecommended throughout pregnancy and when contemplating pregnancy. Insulin requirements usuallyfall in the first trimester and increase subsequently during the second and third trimesters. Afterdelivery, insulin requirements return rapidly to pre-pregnancy levels.

There are no restrictions on treatment with NovoMix 30 during breast-feeding. Insulin treatment of thenursing mother presents no risk to the baby. However, the NovoMix 30 dose may need to be adjusted.

VV-LAB-103275 1.0 .

Animal reproduction studies have not revealed any differences between insulin aspart and humaninsulin regarding fertility.

The patient’s ability to concentrate and react may be impaired as a result of hypoglycaemia. This mayconstitute a risk in situations where these abilities are of special importance (e.g. driving a car oroperating machinery).

Patients should be advised to take precautions to avoid hypoglycaemia while driving or operating amachine. This is particularly important in those who have reduced or absent awareness of the warningsigns of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving oroperating a machine should be considered in these circumstances.

Adverse reactions observed in patients using NovoMix are mainly due to the pharmacological effect ofinsulin aspart.

The most frequently reported adverse reaction during treatment is hypoglycaemia. The frequencies ofhypoglycaemia vary with patient population, dose regimens and level of glycaemic control, please see

Description of selected adverse reactions below.

At the beginning of the insulin treatment, refraction anomalies, oedema and injection site reactions(pain, redness, hives, inflammation, bruising, swelling and itching at the injection site) may occur.

These reactions are usually of a transitory nature. Fast improvement in blood glucose control may beassociated with acute painful neuropathy, which is usually reversible. Intensification of insulin therapywith abrupt improvement in glycaemic control may be associated with temporary worsening ofdiabetic retinopathy, while long-term improved glycaemic control decreases the risk of progression ofdiabetic retinopathy.

The adverse reactions listed below are based on clinical trial data and classified according to MedDRAfrequency and System Organ Class. Frequency categories are defined according to the followingconvention: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare(≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the availabledata).

Immune system disorders Uncommon - Urticaria, rash, eruptions

Very rare - Anaphylactic reactions*

Metabolism and nutrition Very common - Hypoglycaemia*disorders

Nervous system disorders Rare - Peripheral neuropathy (painful neuropathy)

Eye disorders Uncommon - Refraction disorders

Uncommon - Diabetic retinopathy

VV-LAB-103275 1.0 .

Skin and subcutaneous tissue Uncommon - Lipodystrophy*disorders

Not known - Cutaneous amyloidosis*†

General disorders and Uncommon - Oedemaadministration site conditions

Uncommon - Injection site reactions

* see Description of selected adverse reactions† ADR from postmarketing sources.

Anaphylactic reactions:

The occurrence of generalised hypersensitivity reactions (including generalised skin rash, itching,sweating, gastrointestinal upset, angioneurotic oedema, difficulties in breathing, palpitation andreduction in blood pressure) is very rare but can potentially be life-threatening.

The most frequently reported adverse reaction is hypoglycaemia. It may occur if the insulin dose is toohigh in relation to the insulin requirement. Severe hypoglycaemia may lead to unconsciousness and/orconvulsions and may result in temporary or permanent impairment of brain function or even death.

The symptoms of hypoglycaemia usually occur suddenly. They may include cold sweats, cool paleskin, fatigue, nervousness or tremor, anxiousness, unusual tiredness or weakness, confusion, difficultyin concentrating, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation.

In clinical trials, the frequency of hypoglycaemia varied with patient population, dose regimens andlevel of glycaemic control. During clinical trials, the overall rates of hypoglycaemia did not differbetween patients treated with insulin aspart compared to human insulin.

Lipodystrophy (including lipohypertrophy, lipoatrophy) and cutaneous amyloidosis may occur at theinjection site and delay local insulin absorption. Continuous rotation of the injection site within thegiven injection area may help to reduce or prevent these reactions (see section 4.4).

Based on post-marketing sources and clinical trials, the frequency, type and severity of adversereactions observed in the paediatric population do not indicate any differences to the broaderexperience in the general population.

Based on post-marketing sources and clinical trials, the frequency, type and severity of adversereactions observed in elderly patients and in patients with renal or hepatic impairment do not indicateany differences to the broader experience in the general population.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

VV-LAB-103275 1.0 .

A specific overdose for insulin cannot be defined, however, hypoglycaemia may develop oversequential stages if too high doses relative to the patient’s requirement are administered:

* Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugaryproducts. It is therefore recommended that the diabetic patient always carries sugar-containingproducts.

* Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated withglucagon (0.5 to 1 mg) given intramuscularly or subcutaneously by a trained person, or withglucose given intravenously by a healthcare professional. Glucose must be given intravenously,if the patient does not respond to glucagon within 10 to 15 minutes. Upon regainingconsciousness, administration of oral carbohydrates is recommended for the patient in order toprevent a relapse.

Pharmacotherapeutic group: Drugs used in diabetes. Insulins and analogues for injection, intermediate-or long-acting combined with fast-acting. ATC code: A10AD05.

NovoMix 30 is a biphasic suspension of 30% soluble insulin aspart (rapid-acting human insulinanalogue) and 70% protamine-crystallised insulin aspart (intermediate-acting human insulin analogue).

Mechanism of action and pharmacodynamic effects

The blood glucose lowering effect of insulin aspart is due to the facilitated uptake of glucose followingbinding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucoseoutput from the liver.

NovoMix 30 is a biphasic insulin, which contains 30% soluble insulin aspart. This has a rapid onset ofaction, thus allowing it to be given closer to a meal (within zero to 10 minutes of the meal) whencompared to soluble human insulin. The crystalline phase (70%) consists of protamine-crystallisedinsulin aspart, which has an activity profile similar to that of human NPH insulin.

When NovoMix 30 is injected subcutaneously, the onset of action will occur within 10 to 20 minutesof injection. The maximum effect is exerted between 1 and 4 hours after injection. The duration ofaction is up to 24 hours (Figure 1).

VV-LAB-103275 1.0 .

Glucoseinfusion rate

Hours

Figure 1: Activity profile of NovoMix 30 (___) and biphasic human insulin 30 (---) in healthy subjects.

In a 3 month trial in patients with type 1 and type 2 diabetes, NovoMix 30 showed equal control ofglycosylated haemoglobin compared to treatment with biphasic human insulin 30. Insulin aspart isequipotent to human insulin on a molar basis. Compared to biphasic human insulin 30, administrationof NovoMix 30 before breakfast and dinner resulted in lower postprandial blood glucose after bothmeals (breakfast and dinner).

A meta-analysis including nine trials in patients with type 1 and type 2 diabetes showed that fastingblood glucose was higher in patients treated with NovoMix 30, than in patients treated with biphasichuman insulin 30.

In one study, 341 patients with type 2 diabetes were randomised to treatment with NovoMix 30 eitheralone or in combination with metformin, or to metformin together with sulfonylurea. The primaryefficacy variable - HbA1c after 16 weeks of treatment - did not differ between patients with NovoMix30 combined with metformin and patients with metformin plus sulfonylurea. In this trial, 57% of thepatients had baseline HbA1c above 9%; in these patients, treatment with NovoMix 30 in combinationwith metformin resulted in significantly lower HbA1c than metformin in combination withsulfonylurea.

In one study, patients with type 2 diabetes, insufficiently controlled on oral hypoglycaemic agentsalone, were randomised to treatment with twice daily NovoMix 30 (117 patients) or once daily insulinglargine (116 patients). After 28 weeks of treatment following the dosing guideline outlined in section4.2, the mean reduction in HbA1c was 2.8% with NovoMix 30 (mean at baseline = 9.7%). With

NovoMix 30, 66% and 42% of the patients reached HbA1c levels below 7% and 6.5%, respectively,and mean FPG was reduced by about 7 mmol/l (from 14.0 mmol/l at baseline to 7.1 mmol/l).

In patients with type 2 diabetes, a meta-analysis showed a reduced risk of overall nocturnalhypoglycaemic episodes and major hypoglycaemia with NovoMix 30 compared to biphasic humaninsulin 30. The risk of overall daytime hypoglycaemic episodes was increased in patients treated with

NovoMix 30.

A 16-week clinical trial comparing postprandial glycaemic control of meal-related NovoMix 30 withmeal-related human insulin/biphasic human insulin 30 and bedtime NPH insulin was performed in167 patients aged 10 to 18 years. Mean HbA1c remained similar to baseline throughout the trial in bothtreatment groups, and there was no difference in hypoglycaemia rate with NovoMix 30 or biphasic

VV-LAB-103275 1.0 .

human insulin 30.

In a smaller (54 patients) and younger (age range 6 to 12 years) population, treated in a double-blind,cross-over trial (12 weeks on each treatment), the rate of hypoglycaemic episodes and the postprandialglucose increase were significantly lower with NovoMix 30 compared to biphasic human insulin 30.

Final HbA1c was significantly lower in the biphasic human insulin 30 treated group compared with

NovoMix 30.

Absorption, distribution and elimination

In insulin aspart, substitution of amino acid proline with aspartic acid at position B28 reduces thetendency to form hexamers as observed with soluble human insulin. The insulin aspart in the solublephase of NovoMix 30 comprises 30% of the total insulin; this is absorbed more rapidly from thesubcutaneous layer than the soluble insulin component of biphasic human insulin. The remaining 70%is in crystalline form as protamine-crystallised insulin aspart; this has a prolonged absorption profilesimilar to human NPH insulin.

The maximum serum insulin concentration is, on average, 50% higher with NovoMix 30 than withbiphasic human insulin 30. The time to maximum concentration is, on average, half of that for biphasichuman insulin 30. In healthy volunteers, a mean maximum serum concentration of 140 ± 32 pmol/lwas reached about 60 minutes after a subcutaneous dose of 0.20 unit/kg body weight. The mean halflife (t½) of NovoMix 30, reflecting the absorption rate of the protamine bound fraction, was about 8-9 hours. Serum insulin levels returned to baseline 15-18 hours after a subcutaneous dose. In type 2diabetic patients, the maximum concentration was reached about 95 minutes after dosing, andconcentrations well above zero for not less than 14 hours post-dosing were measured.

The pharmacokinetics of NovoMix 30 have not been investigated in elderly patients or in patients withrenal or hepatic impairment.

The pharmacokinetics of NovoMix 30 have not been investigated in children or adolescents. However,the pharmacokinetic and pharmacodynamic properties of soluble insulin aspart have been investigatedin children (6-12 years) and adolescents (13-17 years) with type 1 diabetes. Insulin aspart was rapidlyabsorbed in both age groups, with similar tmax as in adults. However, Cmax differed between the agegroups, stressing the importance of the individual titration of insulin aspart.

Non-clinical data reveal no special hazard for humans based on conventional studies of safetypharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development.

In in vitro tests, including binding to insulin and IGF-1 receptor sites and effects on cell growth,insulin aspart behaved in a manner that closely resembled human insulin. Studies also demonstrate thatthe dissociation of binding to the insulin receptor of insulin aspart is equivalent to human insulin.

VV-LAB-103275 1.0 .

Glycerol

Phenol

Metacresol

Zinc chloride

Disodium phosphate dihydrate

Sodium chloride

Protamine sulfate

Hydrochloric acid (for pH adjustment)

Sodium hydroxide (for pH adjustment)

Water for injections

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinalproducts.

Before opening: 2 years.

During use or when carried as a spare: The product can be stored for a maximum of 4 weeks.

Before opening: Store in a refrigerator (2°C-8°C). Keep away from the cooling element. Do notfreeze.

NovoMix 30 Penfill

During use or when carried as a spare: Store below 30°C. Do not refrigerate. Do not freeze.

Keep the cartridge in the outer carton in order to protect it from light.

NovoMix 30 FlexPen

During use or when carried as a spare: Store below 30°C. Do not refrigerate. Do not freeze.

Keep the cap on FlexPen in order to protect it from light.

NovoMix 30 Penfill3 ml suspension in cartridge (type 1 glass) with a plunger (bromobutyl) and a rubber closure(bromobutyl/polyisoprene). The cartridge contains a glass ball to facilitate resuspension.

Pack sizes of 5 and 10 cartridges. Not all pack sizes may be marketed.

NovoMix 30 FlexPen3 ml suspension in cartridge (type 1 glass) with a plunger (bromobutyl) and a rubber closure(bromobutyl/polyisoprene) contained in a pre-filled multidose disposable pen made of polypropylene.

The cartridge contains a glass ball to facilitate resuspension.

Pack sizes of 1 (with or without needles), 5 (without needles) and 10 (without needles) pre-filled pens.

Not all pack sizes may be marketed.

VV-LAB-103275 1.0 .

After removing NovoMix 30 Penfill or NovoMix 30 FlexPen from the refrigerator, it is recommendedto allow NovoMix 30 Penfill or NovoMix 30 FlexPen to reach room temperature before resuspendingthe insulin as instructed for first time use.

Do not use this medicinal product if you notice that the resuspended liquid is not uniformly white,cloudy and aqueous.

The necessity of resuspending the NovoMix 30 suspension immediately before use is to be stressed tothe patient.

NovoMix 30 which has been frozen must not be used.

The patient should be advised to discard the needle after each injection.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

Needles, cartridges and pre-filled pens must not be shared.

The cartridge must not be refilled.

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd

Denmark

NovoMix 30 Penfill

EU/1/00/142/004

EU/1/00/142/005

NovoMix 30 FlexPen

EU/1/00/142/009

EU/1/00/142/010

EU/1/00/142/023

EU/1/00/142/024

EU/1/00/142/025

Date of first authorisation: 1 August 2000

Date of last renewal: 2 July 2010

Detailed information on this medicinal product is available on the website of the European Medicines

Agency http://www.ema.europa.eu.

VV-LAB-103275 1.0 .