NovoMix 30 Penfill

  • Name:

    NovoMix 30 Penfill

  • Company:
    info
  • Active Ingredients:

    Insulin aspart

  • Legal Category:

    Product subject to medical prescription which may be renewed (B)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 27/03/19

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Summary of Product Characteristics last updated on medicines.ie: 17/5/2019

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Novo Nordisk Limited

Novo Nordisk Limited

Company Products

Medicine NameActive Ingredients
Medicine Name Activelle Active Ingredients Estradiol Hemihydrate, Norethisterone acetate
Medicine Name Actrapid 100 international units/ml, Solution for injection in a vial Active Ingredients Human Insulin
Medicine Name Estrofem 2mg Active Ingredients Estradiol Hemihydrate
Medicine Name Fiasp 100 units-mL solution for injection in Cartridge Penfill Active Ingredients Insulin aspart
Medicine Name Fiasp 100 units-mL solution for injection in pre-filled FlexTouch pen Active Ingredients Insulin aspart
Medicine Name Fiasp 100 units-mL solution for injection in vial Active Ingredients Insulin aspart
Medicine Name GlucaGen HypoKit 1 mg powder and solvent for solution for injection Active Ingredients Glucagon hydrochloride
Medicine Name Insulatard 10 ml Vial Active Ingredients Human Insulin
Medicine Name Insulatard InnoLet Active Ingredients Human Insulin
Medicine Name Insulatard Penfill Active Ingredients Human Insulin
Medicine Name Insulatard, Insulatard Penfill, Insulatard InnoLet Active Ingredients Human Insulin
Medicine Name Kliogest 2 mg/1 mg film-coated tablets Active Ingredients Estradiol Hemihydrate, Norethisterone acetate
Medicine Name Levemir FlexPen (Insulin detemir) 100 units/ml solution for injection in pre-filled pen Active Ingredients insulin detemir
Medicine Name Levemir InnoLet (Insulin detemir) 100 units/ml solution for injection in pre-filled pen Active Ingredients insulin detemir
Medicine Name Levemir Penfill (Insulin detemir) 100 units/ml solution for injection in cartridge Active Ingredients insulin detemir
Medicine Name Norditropin FlexPro 10 mg/1.5 ml solution for injection in pre-filled pen Active Ingredients Somatropin
Medicine Name Norditropin FlexPro 15 mg/1.5 ml solution for injection in pre-filled pen Active Ingredients Somatropin
Medicine Name Norditropin FlexPro 5 mg/1.5 ml solution for injection in pre-filled pen Active Ingredients Somatropin
Medicine Name Norditropin SimpleXx 10 mg/1.5 ml, solution for injection Active Ingredients Somatropin
Medicine Name Norditropin SimpleXx 15 mg/1.5 ml, solution for injection Active Ingredients Somatropin
Medicine Name Norditropin SimpleXx 5 mg/1.5 ml, solution for injection in cartridge Active Ingredients Somatropin
Medicine Name Novofem film-coated tablets Active Ingredients Estradiol Hemihydrate, Norethisterone acetate
Medicine Name NovoMix 30 FlexPen Active Ingredients Insulin aspart
Medicine Name NovoMix 30 Penfill Active Ingredients Insulin aspart
Medicine Name NovoNorm 0.5 mg, 1 mg and 2 mg tablets Active Ingredients Repaglinide
1 - 0 of 40 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 17 May 2019 SmPC

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Correction to version number in document footer

Updated on 27 March 2019 PIL

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  • Change to section 1 - what the product is used for
  • Change to section 3 - how to take/use

Updated on 27 March 2019 SmPC

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  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

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Sectoin 4.2: addition of thefollowing:

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

Section 4.5: addition of the following:

GLP-1 receptor agonists

Updated on 22 August 2018 SmPC

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  • File format updated to PDF

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 20 May 2018

Updated on 18 May 2018

Updated on 12 May 2018 SmPC

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  • New SmPC for new product

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Updated on 10 May 2018 SmPC

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Updated on 2 May 2018 SmPC

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  • Change to section 4.2 - Posology and method of administration

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Updated on 27 April 2018 SmPC

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NovoMix 30 Penfill

Administration with an insulin delivery system

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

Updated on 26 April 2018 PIL

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 3 - how to take/use

Updated on 26 January 2017 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

$0$0$0$0$0Section 4.2: "Older people" changed to "elderly" throughout.$0$0$0$0$0Section 4.4: Addition of information, as below- $0$0$0Avoidance of accidental mix-ups/medication errors$0$0Patients must be instructed to always check the insulin label before each injection to avoid accidental mix-ups between NovoMix and other insulin products.$0$0$0

Updated on 26 January 2017 SmPC

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  • New SmPC for new product

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 2 September 2014 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

... Indicates unchanged omitted text



4.4          Special warnings and precautions for use

 ...

Injection site reactions

 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 given area may help to reduces or prevent the risk of developing these reactions. Reactions usually resolve in a few days to a few weeks. On rare occasions, injection site reactions may require discontinuation of NovoMix 30.

 ...

 Insulin antibodies

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

 

4.5          Interaction with other medicinal products and other forms of interaction

 

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, monoamine oxidase inhibitors (MAOI), beta-blockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids and sulfphonamides.

 

...

4.7          Effects on ability to drive and use machines

 

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

 

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

 

4.8          Undesirable effects

 f. Reporting of suspected adverse reactions

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

 

Ireland

HPRA Pharmacovigilance Section

Irish Medicines Board

Kevin O’Malley House

Earlsfort Centre

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 67625177836

Website: www.hpraimb.ie

e-mail: imbpharmacovigilance@imb.iemedsafety@hpra.ie

 

Malta

ADR Reporting

The Medicines Authority

Post-Licensing Directorate

203 Level 3, Rue D'Argens

GŻR-1368 Gżira

Website: www.medicinesauthority.gov.mt

e-mail: postlicensing.medicinesauthority@gov.mt

 

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

 

...

5.            PHARMACOLOGICAL PROPERTIES

 

5.1          Pharmacodynamic properties

 

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 insulin analogue) and 70% protamine-crystallised insulin aspart (intermediate-acting human insulin analogue).

 

... 

 

10.          DATE OF REVISION OF THE TEXT

 

11/201307/2014

 

 

Updated on 2 September 2014 PIL

Reasons for updating

  • New PIL for new product

Updated on 2 September 2014 PIL

Reasons for updating

  • Change to date of revision
  • Addition of information on reporting a side effect.
  • Correction of spelling/typing errors

Updated on 6 March 2014 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to storage instructions
  • Change to side-effects
  • Change to drug interactions
  • Change to information about pregnancy or lactation
  • Change to date of revision
  • Addition of information on reporting a side effect.

Updated on 28 December 2013 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4 - Clinical particulars
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.1 - List of excipients
  • Change to section 6.3 - Shelf life
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 8 - MA number
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Changes are highlighted below.
"..." indicates unchanged text which has been ommited.

1.         NAME OF THE MEDICINAL PRODUCT

 

... unitsU/ml

 

2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

 

... unitsU 

 

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

 

For thea full list of excipients, see section 6.1.

 

 

3.         PHARMACEUTICAL FORM

 

Suspension for injection in cartridge. Penfill.

 

The suspension is cloudy, Wwhite and aqueoussuspension.

 

 

4.         CLINICAL PARTICULARS

 

4.1      Therapeutic indications

 

NovoMix 30 is indicated for Ttreatment of diabetes mellitus in adults, adolescents and children aged 10 to 17 years and above.

 

4.2      Posology and method of administration

 

Posology

 

The potency of insulin analogues, including insulin aspart, is expressed in units (U), whereas the potency of human insulin is expressed in international units (IU).

 

...

In patients with type 2 diabetes, NovoMix 30 can be given as monotherapy. NovoMix 30 can also be given in combination with oral antidiabetic medicinal products if the patient's blood glucose is inadequately controlled with oral antidiabetic medicinal products alone. For patients with type 2 diabetes, the recommended starting dose of NovoMix 30 is 6 unitsU at breakfast and 6 unitsU at dinner (evening meal). NovoMix 30 can also be initiated once daily with 12 unitsU at dinner (evening meal). When using NovoMix 30 once daily, it is generally recommended to move to twice -daily when reaching 30 units by splitting the dose into equal breakfast and dinner doses. If twice daily dosing with NovoMix 30 results in recurrent daytime hypoglycaemic episodes, the morning dose can be split into morning and lunchtime doses (thrice daily dosingdose).

 

The following titration guideline is recommended for dose adjustments:

 

Pre-meal blood glucose level

1.            NovoMix 30 dose adjustment

2.            < 4.4 mmol/l

3.            < 80 mg/dl

4.            - 2 unitsU

5.            4.4 – 6.1 mmol/l

6.            80 – 110 mg/dl

7.            0

8.            6.2 – 7.8 mmol/l

9.            111 – 140 mg/dl

10.         + 2 unitsU

11.         7.9 – 10 mmol/l

12.         141 – 180 mg/dl

13.         + 4 unitsU

> 10 mmol/l

14.         > 180 mg/dl

15.         + 6 unitsU

 

The lowest of the three previous days’ pre-meal blood glucose levels should be used. The dose should not be increased if hypoglycaemia occurred within these days. Dose adjustments can be made once a week until target HbA1c is reached. Pre-meal blood glucose levels should be used to evaluate the adequacy of the preceding dose.

 

The combination of NovoMix 30 with pioglitazone should only be considered following clinical evaluation of the patient’s risk of developing signs or symptoms of fluid-related adverse reactions. The initiation of NovoMix 30 should be undertaken cautiously titrating to the lowest dose required to achieve glycaemic control (see section 4.4).

 

In patients with type 1 diabetes, the individual insulin requirement is usually between 0.5 and 1.0 unitU/kg/day. NovoMix 30 may fully or partially meet this requirement. The daily insulin requirement may be higher in patients with insulin resistance (e.g. due to obesity), and lower in patients with residual endogenous insulin production.

 

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

 

In patients with diabetes mellitus optimised metabolic control effectively delays the onset and slows the progression of diabetic late complications. Optimised metabolic control, including glucose monitoring, is therefore recommended.

 

Special populations

 

ElderlyOlder peopleatients (≥ 65 years old)

NovoMix 30 can be used in older patientselderly 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.

As with all insulin medicinal products, iIn older patientselderly patients, glucose monitoring should be intensified and the insulin aspart dose adjusted on an individual basis.

 

Renal and hepatic impairment

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

As with all insulin medicinal products, iIn patients with renal or hepatic impairment, glucose monitoring should be intensified and the insulin aspart dose adjusted on an individual basis.

 

Paediatric population

 

NovoMix 30 can be used in children and adolescents and children aged 10 years and above when premixed insulin is preferred. For children from 6 to 9 years old limited clinical data exists There is limited clinical experience with NovoMix 30 in children aged 6–9 years (see section 5.1).

No data are available forof NovoMix 30 in children below 6 years of age.No clinical studies with NovoMix 30 have been carried out in children under the age of 6 years.

 

NovoMix 30 should only be used in this age group under careful medical supervision.

 

Transfer from other insulin medicinal products

 

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

As with all insulin medicinal products, cClose glucose monitoring is recommended during the transfer and in the initial weeks thereafter (see section 4.4).

 

Method of administration

 

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

 

NovoMix 30 is for subcutaneous administration only. NovoMix 30 must not be administrated intravenously, as it may result in severe hypoglycaemia. Intramuscular administration should be avoided. NovoMix 30 is not to be used in insulin infusion pumps.

 

NovoMix 30 is administered subcutaneously by injection in the thigh or in the abdominal wall. If convenient, the gluteal or deltoid region may be used. Injection sites should always be rotated within the same region in order to reduce the risk of lipodystrophy. The influence of different injection sites on the absorption of NovoMix 30 has not been investigated. The duration of action will vary according to the dose, injection site, blood flow, temperature and level of physical activity.

 

...

NovoMix 30 Penfill is designed to be used with Novo Nordisk insulin delivery systems and NovoFine or NovoTwist needles. The patient should be advised not to use any counterfeit needles.

 

...

 

NovoMix 30 is administered subcutaneously by injection in the thigh or in the abdominal wall. If convenient, the gluteal or deltoid region may be used. Injection sites should always be rotated within the same region. The influence of different injection sites on the absorption of NovoMix 30 has not been investigated. As with all insulin medicinal products, the duration of action will vary according to the dose, injection site, blood flow, temperature and level of physical activity.

 

4.3      Contraindications

 

Hypersensitivity to the active substance or to any of the excipients (see section 6.1).

 

4.4      Special warnings and precautions for use

 

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 infusion pumps.

 

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

 

Hyperglycaemia

 

Inadequate dosing or discontinuation of treatment, especially in type 1 diabetes, may lead to hyperglycaemia and diabetic ketoacidosis. Usually, the first symptoms of hyperglycaemia develop gradually 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 is potentially lethal.

 

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

 

Hypoglycaemia

 

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 case of hypoglycaemia or if hypoglycaemia is suspected, NovoMix must not be injected. After stabilisation of the patient’s blood glucose, adjustment of the dose should be considered (see sections 4.2, 4.8 and 4.9).

 

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

 

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

 

...


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

 

...

 

Transfer from other insulin medicinal products

 

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

 

Injection site reactions

 

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 given area may help to reduce or prevent these reactions. Reactions usually resolve in a few days to a few weeks. On rare occasions, injection site reactions may require discontinuation of NovoMix 30.

 

...

4.5      Interaction with other medicinal products and other forms of interaction

 

...

 

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

 

...

 

4.7      Effects on ability to drive and use machines

 

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

 

...

 

4.8      Undesirable effects

 

a. Summary of the safety profile

 

Adverse reactions observed in patients using NovoMix are mainly dose-dependent and due to the pharmacological effect of insulin aspart.

 

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

 

At the beginning of the insulin treatment, refraction anomalies, oedema and local injection sitehypersensitivity reactions (pain, redness, hives, inflammation, bruising, swelling and itching at the injection site) may occur.; tThese reactions are usually of transitory nature. Fast improvement in blood glucose control may be associated with acute painful neuropathy, which is usually reversible. Intensification of insulin therapy with abrupt improvement in glycaemic control may be associated with temporary worsening of diabetic retinopathy, while long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy.

 

b. Tabulated list of adverse reactions

 

The aAdverse reactions listed below are based on clinical trial data and classified according to MedDRA frequency and System Organ Class. Frequency categories are defined according to the following convention: 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 available data).

 

Immune system disorders

Uncommon – Urticaria, rash, eruptions

 

Very rare – Anaphylactic reactions*

 

Metabolism and nutrition disorders

 

Very common – Hypoglycaemia*

 

Nervous system disorders

Rare – Peripheral neuropathy (painful neuropathy)

 

Eye disorders

 

 

Uncommon – Refraction disorders

 

Uncommon – Diabetic retinopathy

 

Skin and subcutaneous tissue disorders

Uncommon – Lipodystrophy*

Uncommon - Local hypersensitivity

General disorders and administration site conditions

Uncommon – Oedema

 

Uncommon Injection site reactions

 

* see section c.

 

c. Description of selected adverse reactions

 

Anaphylactic reactions:

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

 

Hypoglycaemia:

The most frequently reported adverse reaction is hypoglycaemia. It may occur if the insulin dose is too high in relation to the insulin requirement. Severe hypoglycaemia may lead to unconsciousness and/or convulsions 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 pale skin, fatigue, nervousness or tremor, anxiousness, unusual tiredness or weakness, confusion, difficulty in concentratingon, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation.

 

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

 

Anaphylactic reactions:

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

 

Lipodystrophy:

Lipodystrophy (including lipohypertrophy, lipoatrophy)is reported as uncommon. It may occur at the injection site. Continuous rotation of the injection site within the particular area reduces the risk of developing these reactions; therefore it is recommended to rotate injection sites within an area.

 

d. Paediatric population

 

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

 

e. Other special populations

 

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

 

f. Reporting of suspected adverse reactions

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

Ireland

Pharmacovigilance Section

Irish Medicines Board

Kevin O’Malley House

Earlsfort Centre

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 67625177836

Website: www.imb.ie

e-mail: imbpharmacovigilance@imb.ie

 

Malta

ADR Reporting

The Medicines Authority

Post-Licensing Directorate

203 Level 3, Rue D'Argens

GŻR-1368 Gżira

Website: www.medicinesauthority.gov.mt

e-mail: postlicensing.medicinesauthority@gov.mt

 

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

 

 

...

 

5.         PHARMACOLOGICAL PROPERTIES

 

5.1      Pharmacodynamic properties

 

...

 

Mechanism of action and pharmacodynamic effects

 

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

 

NovoMix 30 is a biphasic insulin, which contains 30% soluble insulin aspart. This has a rapid onset of action, thus allowing it to be given closer to a meal (within zero to 10 minutes of the meal) when compared to soluble human insulin. The crystalline phase (70%) consists of protamine-crystallised insulin aspart, which has an activity profile that is similar to that of human NPH insulin (Figure 1).

 

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

 

...

 

Clinical efficacy and safety

 

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


...


In one study, patients with type 2 diabetes, insufficiently controlled on oral hypoglycaemic agents alone, were randomised to treatment with twice daily NovoMix 30 (117 patients) or once daily insulin glargine (116 patients). After 28 weeks of treatment following the dosing guideline outlined in section 4.2, 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/lL (from 14.0 mmol/lL at baseline to 7.1 mmol/lL).

 

...

 

Paediatric population

 

A 16-week clinical trial comparing postprandial glycaemic control of meal-related NovoMix 30 with meal-related human insulin/biphasic human insulin 30 and bedtime NPH insulin was performed in 167 patientssubjects aged 10 to 18 years. Mean HbA1c remained similar to baseline throughout the trial in both treatment groups, and there was no difference in hypoglycaemia rate with NovoMix 30 or biphasic human insulin 30.

In a smaller (54 patientssubjects) 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 postprandial glucose increase werewas 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.

 

5.2      Pharmacokinetic properties

 

Absorption, distribution and elimination

 

...

 

The maximum serum insulin concentration is, on average, 50% higher with NovoMix 30 than with biphasic human insulin 30. The time to maximum concentration is, on average, half of that for biphasic human insulin 30. In healthy volunteers, a mean maximum serum concentration of 140 32 pmol/l was reached about 60 minutes after a subcutaneous dose of 0.20 unitU/kg body weight. The mean half life (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 2 diabetic patients, the maximum concentration was reached about 95 minutes after dosing, and concentrations well above zero for not less than 14 hours post-dosing were measured.

 

Special populations

 

The pharmacokinetics of NovoMix 30 has have not been investigated in older patientselderly patients, or in patients with renal or hepatic impairment.

 

Paediatric population

 

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

 

...

 

6.         PHARMACEUTICAL PARTICULARS

 

6.1      List of excipients

 

Glycerol

Phenol

Metacresol

Zinc chloride

Disodium phosphate dihydrate

Sodium chloride

Protamine sulphfate

Hydrochloric acid (for pH adjustment)

Sodium hydroxide (for pH adjustment)

Water for injections

 

...

 

6.3      Shelf life

 

Before opening: 2 years.

 

During use or when carried as a spareAfter first opening: The product can be stored for Aa maximum of 4 weeks. when sStored below 30°C.

 

6.4      Special precautions for storage

 

Before opening: Store in a refrigerator (2°C – 8°C). Keep away from the cooling element. Do not freeze.

 

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

 

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

 

NovoMix 30 Penfill: Keep the cartridge in the outer carton in order to protect it from light.

 

NovoMix 30 FlexPen: Keep the cap on FlexPen in order to protect it from light.

 

For storage conditions of the medicinal product, see section 6.3.NovoMix 30 must be protected from excessive heat and light.

 

6.5      Nature and contents of container

 

NovoMix 30 Penfill:

3 ml suspension in cartridge (type 1 glass) with a plunger (bromobutyl) and a rubber closurestopper (bromobutyl/polyisoprene) in a carton. 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 FlexPen:

3 ml suspension in cartridge (type 1 glass) with a plunger (bromobutyl) and a rubber closurestopper (bromobutyl/polyisoprene) contained in a pre-filled multidose disposable pen made of polypropylene. The cartridge contains a glass ball to facilitate resuspension.

 

...

6.6      Special precautions for disposal and other handling

 

...

 

Do not use this medicinal product if you notice thatNovoMix 30 must not be used if the resuspended liquid isdoes not appear uniformly white, and cloudy and aqueous.

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

 

...

 

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

 

 

...

 

8.         MARKETING AUTHORISATION NUMBER(S)

 

EU/1/00/142/004

EU/1/00/142/005

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

 

...

 

 

10.      DATE OF REVISION OF THE TEXT

 

11/2013

 

Updated on 14 September 2012 PIL

Reasons for updating

  • Addition of information on alternative format leaflets

Updated on 10 May 2012 PIL

Reasons for updating

  • Change due to user-testing of patient information

Updated on 14 September 2011 PIL

Reasons for updating

  • Change to warnings or special precautions for use

Updated on 2 March 2011 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

In section 4.4 Special warnings and precautions for use, the addtion of the follwoing paragraph:-

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 in mind if treatment with the combination of pioglitazone and NovoMix is considered. If the combination is 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.

 


Date of revision

02/2011

Updated on 28 February 2011 SmPC

Reasons for updating

  • Change to section 6.5 - Nature and contents of container
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 6.5 Nature and contents of container

Previous wording:

Pack sizes of 5 and 10 pre-filled pens. Not all pack sizes may be marketed.

Current wording:

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.

Section 10. Date of Revision of the Text

Previous wording: 08/2010

08/2010

Current wording: 10/2010

10/2010

Updated on 24 September 2010 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to storage instructions
  • Change to side-effects
  • Change to information about drinking alcohol
  • Change to information about pregnancy or lactation
  • Change to information about driving or using machinery
  • Change to further information section
  • Change to date of revision
  • Change to dosage and administration

Updated on 24 September 2010 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

In section 4.2, the sentence relating to the types of Novo Nordisk needles which can be used with the Penfill has been updated to include NovoTwist needles, as well as NovoFine needles.

Updated on 15 July 2010 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.3 - Shelf life
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

SmPC changes for NovoMix 30 Penfill and NovoMix 30 FlexPen

 

Renewal – EMEA/H/C/308/R/60

 

 

PREVIOUS WORDING

NEW WORDING

1.    NAME OF THE MEDICINAL PRODUCT

 

NovoMix 30 Penfill 100 U/ml, suspension for injection in a cartridge.

NovoMix 30 FlexPen 100 U/ml, suspension for injection in a pre-filled pen.

 

1.    NAME OF THE MEDICINAL PRODUCT

 

NovoMix 30 Penfill 100 U/ml suspension for injection in cartridge.

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

 

“,” and “a” removed.

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Soluble insulin aspart*/protamine-crystallised insulin aspart*……… 100 U/ml in the ratio of 30/70

 

* produced by recombinant DNA technology in Saccharomyces cerevisiae.

 

One unit of insulin aspart corresponds to 6 nmol, 0.035 mg salt-free anhydrous insulin aspart.

 

2.      QUALITATIVE AND QUANTITATIVE COMPOSITION

 

1 ml of the suspension contains 100 U soluble insulin aspart*/protamine-crystallised insulin aspart* in the ratio 30/70 (equivalent to 3.5 mg).

 

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

 

3.    PHARMACEUTICAL FORM

 

Suspension for injection in a cartridge.

Suspension for injection in a pre-filled pen.

 

NovoMix 30 is a white suspension.

 

3.    PHARMACEUTICAL FORM

 

Suspension for injection in cartridge. Penfill.

Suspension for injection in cartridge. FlexPen.

 

White suspension.

4.1  Therapeutic indications

Treatment of diabetes mellitus.

4.1  Therapeutic indications

Treatment of diabetes mellitus in adults, adolescents and children aged 10 to 17 years.

 

4.2  Posology and method of administration

 

 

 

 

 

 

Dose recommendation

Dosage of NovoMix 30 is individual and determined in accordance with the needs of the patient.

 

 

 

In patients with type 2 diabetes, NovoMix 30 can be given in monotherapy or in combination with oral antidiabetic drugs for which the combination with insulin is approved, when the blood glucose is inadequately controlled with those oral antidiabetic drugs alone.

 

4.2  Posology and method of administration

 

Posology

 

The potency of insulin analogues, including insulin aspart, is expressed in units (U), whereas the potency of human insulin is expressed in international units (IU).

 

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

 

In patients with type 2 diabetes NovoMix 30 can be given as monotherapy. NovoMix 30 can also be given in combination with oral antidiabetic medicinal products if the patient's blood glucose is inadequately controlled with oral antidiabetic medicinal products alone.

 

If twice daily dosing with NovoMix 30 results in recurrent daytime hypoglycaemic episodes, the morning dose can be split into morning and lunchtime doses (thrice daily dosing).

 

If twice daily dosing with NovoMix 30 results in recurrent daytime hypoglycaemic episodes, the morning dose can be split into morning and lunchtime doses (thrice daily dose).

 

The combination of NovoMix 30 with pioglitazone should only be considered following clinical evaluation of the patient’s risk of developing signs or symptoms of fluid-related adverse events.

 

The combination of NovoMix 30 with pioglitazone should only be considered following clinical evaluation of the patient’s risk of developing signs or symptoms of fluid-related adverse reactions.

 

In patients with type 1 diabetes the individual insulin requirement is usually between 0.5 and 1.0 Units/kg/day.

 

In patients with type 1 diabetes the individual insulin requirement is usually between 0.5 and 1.0 U/kg/day.

 

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

 

 

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

 

In patients with diabetes mellitus optimised metabolic control effectively delays the onset and slows the progression of diabetic late complications. Optimised metabolic control, including glucose monitoring, is therefore recommended.

 

 

 

NovoMix 30 can be used in elderly patients; however there is limited experience with the use of NovoMix 30 in combination with OADs in patients older than 75 years.

 

 

 

 

 

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

 

 

 

 

 

 

NovoMix 30 can be used in children and adolescents aged 10 years and above when premixed insulin is preferred. For children from 6 to 9 years old limited clinical data exists (see section 5.1).

No studies have been performed in children under the age of 6 years.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

NovoMix 30 should never be administered intravenously.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

NovoMix 30 is administered subcutaneously in the thigh or in the abdominal wall. If convenient, the gluteal or deltoid region may be used. Injection sites should be rotated within the same region. As with all insulins the duration of action will vary according to the dose, injection site, blood flow, temperature and level of physical activity. The influence of different injection sites on the absorption of NovoMix 30 has not been investigated.

 

Special populations

Elderly (≥ 65 years old)

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.

As with all insulin medicinal products, in elderly patients, glucose monitoring should be intensified and insulin aspart dose adjusted on an individual basis.

 

Renal and hepatic impairment

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

As with all insulin medicinal products, in patients with renal or hepatic impairment, glucose monitoring should be intensified and insulin aspart dose adjusted on an individual basis.

 

Paediatric population

 

NovoMix 30 can be used in children and adolescents aged 10 years and above when premixed insulin is preferred. For children from 6 to 9 years old limited clinical data exists (see section 5.1).

No clinical studies with NovoMix 30 have been carried out in children under the age of 6 years.

NovoMix 30 should only be used in this age group under careful medical supervision.

 

Transfer from other insulin medicinal products

 

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

As with all insulin medicinal products, close glucose monitoring is recommended during the transfer and in the initial weeks thereafter (see section 4.4).

 

Method of administration

 

NovoMix 30 is for subcutaneous administration only. NovoMix 30 must not be administrated intravenously, as it may result in severe hypoglycaemia. Intramuscular administration should be avoided. NovoMix 30 is not to be used in insulin infusion pumps.

 

NovoMix 30 Penfill is designed to be used with Novo Nordisk insulin delivery systems and NovoFine needles. The patient should be advised not to use any counterfeit needles.

 

NovoMix 30 FlexPen are pre-filled pens designed to be used with NovoFine or NovoTwist needles.  FlexPen delivers 1-60 units in increments of 1 unit.  The patient should be advised not to use any counterfeit needles.

 

NovoMix 30 Penfill is accompanied by a package leaflet with detailed instructions for use to be followed.

 

NovoMix 30 FlexPen is colour-coded and accompanied by a package leaflet with detailed instructions for use to be followed.

 

NovoMix 30 is administered subcutaneously by injection in the thigh or in the abdominal wall. If convenient, the gluteal or deltoid region may be used. Injection sites should always be rotated within the same region. The influence of different injection sites on the absorption of NovoMix 30 has not been investigated. As with all insulin medicinal products, the duration of action will vary according to the dose, injection site, blood flow, temperature and level of physical activity.

 

4.3  Contraindications

o      Hypoglycaemia.

 

 

4.4  Special warnings and precautions for use

The use of dosages which are inadequate or discontinuation of treatment, especially in insulin-dependent diabetics, may lead to hyperglycaemia and diabetic ketoacidosis; conditions which are potentially lethal.

 

4.4  Special warnings and precautions for use

Inadequate dosing or discontinuation of treatment, especially in type 1 diabetes, may lead to hyperglycaemia and diabetic ketoacidosis. Usually the first symptoms of hyperglycaemia develop gradually 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 is potentially lethal.

 

 

Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia (see section 4.8 and section 4.9).  Compared with biphasic human insulin, NovoMix 30 may have a more pronounced glucose lowering effect up to 6 hours after injection.

 

Hypoglycaemia

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 (see section 4.8 and 4.9).

 

Compared with biphasic human insulin, NovoMix 30 may have a more pronounced glucose lowering effect up to 6 hours after injection.

 

 

Usual warning symptoms may disappear in patients with longstanding diabetes.

 

NovoMix 30 should be administered in immediate relation to a meal. The rapid onset of action should therefore be considered in patients with concomitant diseases or treatment with other medicinal products where a delayed absorption of food might be expected.

 

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

 

Concomitant illness, especially infections, usually increases the patient’s insulin requirements.

 

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

 

When patients are transferred between different types of insulin products, the early warning symptoms of hypoglycaemia may change or become less pronounced than those experienced with their previous insulin.

 

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

 

 

 

 

Transferring a patient to a new type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type, origin (animal, human, human insulin analogue), and/or method of manufacture (recombinant DNA versus animal source insulin) may result in the need for a change in dosage. Patients taking NovoMix 30 may need a change in dosage from that used with their usual insulin. If a dosage adjustment is needed, it may be done with the first dose or during the first few weeks or months.

 

Transfer from other insulin medicinal products

 

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

 

Adjustment of dosage may also be necessary if patients undertake increased physical activity or change their usual diet. Exercise taken immediately after a meal may increase the risk of hypoglycaemia.

 

Insulin suspensions are not to be used in insulin infusion pumps.

 

 

 

 

As with any insulin therapy, injection site reactions may occur and include pain, itching, hives, swelling and inflammation. Continuous rotation of the injection site within a given area may help to reduce or prevent these reactions. Reactions usually resolve in a few days to a few weeks. On rare occasions, injection site reactions may require discontinuation of NovoMix 30.

 

 

Injection site reactions

 

As with any insulin therapy, injection site reactions may occur and include pain, redness, hives, inflammation, swelling and itching. Continuous rotation of the injection site within a given area may help to reduce or prevent these reactions. Reactions usually resolve in a few days to a few weeks. On rare occasions, injection site reactions may require discontinuation of NovoMix 30.

 

4.5    Interaction with other medicinal products and other forms of interaction

Beta-blocking agents may mask the symptoms of hypoglycaemia.

 

4.5    Interaction with other medicinal products and other forms of interaction

Beta-blockers may mask the symptoms of hypoglycaemia.

 

4.6  Pregnancy and lactation

 

 

 

 

4.6    Fertility, pregnancy and lactation

 

Pregnancy

 

 

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

 

Breast-feeding

 

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

 

 

Fertility

 

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

 

4.7  Effects on ability to drive and use machines

 

No studies on the effects on the ability to drive and use machines have been performed.

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

 

Patients should be advised to take precautions in order to avoid hypoglycaemia whilst driving. This is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving should be considered in these circumstances.

 

4.7    Effects on ability to drive and use machines

 

 

 

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

 

 

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

 

4.8  Undesirable effects

 

 

 

Adverse drug reactions observed in patients using NovoMix products are mainly dose-dependent and due to the pharmacologic effect of insulin. As for other insulin products, hypoglycaemia, in general is the most frequently occurring undesirable effect. It may occur if the insulin dose is too high in relation to the insulin requirement and therefore require special attention during dose intensification as outlined in section 4.2. Severe hypoglycaemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or even death.

 

In clinical trials and during marketed use the frequency varies with patient population and dose regimens therefore no specific frequency can be presented. During clinical trials the overall rates of hypoglycaemia did not differ between patients treated with insulin aspart compared to human insulin.

 

Frequencies of adverse drug reactions from clinical trials, which by an overall judgement are considered related to insulin aspart are listed below. The frequencies are defined as: Uncommon (>1/1,000, <1/100) and rare (>1/10,000, <1/1,000). Isolated spontaneous cases are presented as very rare defined as (<1/10,000), including isolated reports.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

 

 

Immune system disorders

Uncommon – Urticaria, rash, eruptions

 

Very rare – Anaphylactic reactions

Symptoms of generalised hypersensitivity may include generalised skin rash, itching, sweating, gastrointestinal upset, angioneurotic oedema, difficulties in breathing, palpitation and reduction in blood pressure. Generalised hypersensitivity reactions are potentially life threatening.

 

 

Nervous system disorders

Rare – Peripheral neuropathy

Fast improvement in blood glucose control may be associated with a condition termed acute painful neuropathy, which is usually reversible.

 

Eye disorders

Uncommon – Refraction disorder

Refraction anomalies may occur upon initiation of insulin therapy. These symptoms are usually of transitory nature.

 

Uncommon – Diabetic retinopathy

Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. However, intensification of insulin therapy with abrupt improvement in glycaemic control may be associated with worsening of diabetic retinopathy.

 

Skin and subcutaneous tissue disorders

Uncommon – Lipodystrophy

Lipodystrophy may occur at the injection site as a consequence of failure to rotate injection sites within an area.

 

Uncommon – Local hypersensitivity

Local hypersensitivity reactions (redness, swelling and itching at the injection site) may occur during treatment with insulin. These reactions are usually transitory and normally they disappear during continued treatment.

 

General disorders and administration site conditions

Uncommon – Oedema

Oedema may occur upon initiation of insulin therapy. These symptoms are usually of transitory nature. Oedema and weight increase may occur when NovoMix 30 is used in combination with OADs.

 

4.8    Undesirable effects

 

a. Summary of the safety profile

 

Adverse reactions observed in patients using NovoMix are mainly dose-dependent and due to the pharmacologic effect of insulin.

 

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

At the beginning of the insulin treatment, refraction anomalies, oedema and local hypersensitivity reactions (pain, redness, hives, inflammation, swelling and itching at the injection site) may occur; these reactions are usually of transitory nature. Fast improvement in blood glucose control may be associated with acute painful neuropathy, which is usually reversible. Intensification of insulin therapy with abrupt improvement in glycaemic control may be associated with temporary worsening of diabetic retinopathy, while long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy.

 

b. Tabulated list of adverse reactions

 

Adverse reactions listed below are based on clinical trial data and classified according to MedDRA frequency and System Organ Class. Frequency categories are defined according to the following convention: 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 available data).

 

Immune system disorders

Uncommon - Urticaria, rash, eruptions

 

Very rare - Anaphylactic reactions*

 

Metabolism and nutrition disorders

 

Very common – Hypoglycaemia*

 

Nervous system disorders

Rare - Peripheral neuropathy

 

Eye disorders

 

 

Uncommon - Refraction disorders

 

Uncommon - Diabetic retinopathy

 

Skin and subcutaneous tissue disorders

 

 

 

Uncommon – Lipodystrophy*

 

Uncommon - Local hypersensitivity

 

General disorders and administration site conditions

 

 

 

Uncommon – Oedema

 

 

 

 

* see section c.

 

c. Description of selected adverse reactions

 

Hypoglycaemia:

The most frequently reported adverse reaction is hypoglycaemia. It may occur if the insulin dose is too high in relation to the insulin requirement. Severe hypoglycaemia may lead to unconsciousness and/or convulsions 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 pale skin, fatigue, nervousness or tremor, anxiousness, unusual tiredness or weakness, confusion, difficulty in concentration, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation.

 

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

 

Anaphylactic reactions:

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

 

Lipodystrophy:

Lipodystrophy is reported as uncommon. It may occur at the injection site; therefore it is recommended to rotate injection sites within an area.

 

d. Paediatric population

 

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

 

e. Other special populations

 

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

 

4.9  Overdose

 

·                Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary products. It is therefore recommended that the diabetic patient always carry sugar-containing products

·                Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated by glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously by a trained person or glucose given intravenously by a medical professional. Glucose must also be given intravenously if the patient does not respond to glucagon within 10 to 15 minutes. Upon regaining consciousness administration of oral carbohydrate is recommended for the patient in order to prevent relapse.

 

4.9    Overdose

 

•      Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary products. It is therefore recommended that the diabetic patient always carries sugar-containing products

•      Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated with glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously, by a trained person, or with glucose 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 regaining consciousness, administration of oral carbohydrates is recommended for the patient in order to prevent a relapse.

 

5.1  Pharmacodynamic properties

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

5.1  Pharmacodynamic properties

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

 

 

 

The blood glucose lowering effect of insulin occurs when the molecules facilitate the uptake of glucose by binding to insulin receptors on muscle and fat cells - and simultaneously inhibit the output of glucose from the liver.

 

Mechanism of action

 

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

Children and adolescents:

Paediatric population

 

5.2  Pharmacokinetic properties

 

 

 

In insulin aspart substitution of amino acid proline with aspartic acid at position B28 reduces the tendency to form hexamers in the soluble fraction of NovoMix 30, as compared with soluble human insulin.

5.2    Pharmacokinetic properties

 

Absorption, distribution and elimination

 

In insulin aspart substitution of amino acid proline with aspartic acid at position B28 reduces the tendency to form hexamers as observed with soluble human insulin.

 

Children and adolescents:

 

The pharmacokinetics of NovoMix 30 has not been investigated in elderly, or patients with impaired renal or liver function.

 

Special populations

 

The pharmacokinetics of NovoMix 30 has not been investigated in elderly patients, or patients with renal or hepatic impairment.

 

Paediatric population

 

 

5.3  Preclinical safety data

 

Non-clinical data with insulin aspart reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction.

 

5.3    Preclinical safety data

 

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

6.3  Shelf life

 

The in-use shelf life is 4 weeks (not above 30°C).

6.3    Shelf life

 

After first opening: A maximum of 4 weeks when stored below 30°C.

6.4  Special precautions for storage

 

Store in a refrigerator (2°C – 8°C) away from the freezing compartment. Do not freeze.

 

NovoMix 30 Penfill cartridges and NovoMix 30 FlexPen in use or carried as a spare: can be kept at ambient temperature (below 30°C) for up to 4 weeks, but any remainder must then be discarded. Do not refrigerate. Do not store above 30ºC. Keep the cartridges in the outer carton or keep the cap on the pen when NovoMix 30 FlexPen is not in use in order to protect from light.

 

After removing NovoMix 30 Penfill and NovoMix 30 FlexPen from the refrigerator it is recommended to allow them to reach room temperature before resuspending the insulin as instructed for the first time use.

 

6.4    Special precautions for storage

 

Store in a refrigerator (2°C – 8°C). Keep away from the cooling element. Do not freeze.

 

NovoMix 30 Penfill:

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

 

NovoMix 30 FlexPen:

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

 

After first opening or carried as a spare: Do not refrigerate. Store below 30°C.

 

NovoMix 30 must be protected from excessive heat and light.

 

6.5  Nature and contents of container

 

NovoMix 30 Penfill:

A glass (Type 1) cartridge which is closed with a latex-free (bromobutyl) rubber piston at one end and a latex-free (bromobutyl/polyisoprene) rubber closure at the other. The cartridge contains a glass ball to facilitate resuspension. Each cartridge contains 3 ml suspension.

Cartons of 5 or 10 cartridges.

 

 

NovoMix 30 FlexPen:

A glass (Type 1) cartridge which is closed with a latex-free (bromobutyl) rubber piston at one end and a latex-free (bromobutyl/polyisoprene) rubber closure at the other in a multidose disposable pre-filled pen with a pen injector (plastic). The cartridge contains a glass ball to facilitate resuspension. Each pre-filled pen contains 3 ml suspension.

 

Cartons of 5 or 10 pre-filled pens.

6.5    Nature and contents of container

 

NovoMix 30 Penfill:

3 ml suspension in cartridge (type 1 glass) with a plunger (bromobutyl) and a stopper (bromobutyl/polyisoprene) in a carton. 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 FlexPen:

3 ml suspension in cartridge (type 1 glass) with a plunger (bromobutyl) and a stopper (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 5 and 10 pre-filled pens.

 

6.6  Special precautions for disposal and other handling

 

The cartridges are designed to be used with Novo Nordisk delivery systems (durable devices for repeated use) and NovoFine needles. Detailed instruction accompanying the cartridge and delivery system must be followed.

 

NovoFine S needles are designed to be used with the pre-filled pen. Detailed instruction accompanying NovoMix 30 FlexPen must be followed.

 

NovoMix 30 Penfill and NovoMix 30 FlexPen are for use by one person only. The cartridge and NovoMix 30 FlexPen must not be refilled.

 

The resuspended liquid must appear uniformly white and cloudy.

 

Any unused product or waste material should be disposed of in accordance with local requirements.

 

6.6    Special precautions for disposal and other handling

 

 

Needles, NovoMix 30 Penfill and NovoMix 30 FlexPen must not be shared. The cartridge must not be refilled.

 

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

 

NovoMix 30 must not be used if the resuspended liquid does not appear uniformly white and cloudy.

 

 

 

 

9.    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

Date of last renewal: 1 August 2005

 

9.      DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

Date of last renewal: 2 July 2010

 

10.  DATE OF REVISION OF THE TEXT

 

10/2009

 

10.    DATE OF REVISION OF THE TEXT

 

07/2010

 

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.

LEGAL CATEGORY

 

POM (Prescription Only Medicine)

 

 

Updated on 7 April 2010 PIL

Reasons for updating

  • Change of manufacturer
  • Change of contraindications
  • Change to date of revision

Updated on 10 February 2010 PIL

Reasons for updating

  • Improved electronic presentation

Updated on 26 January 2010 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to warnings or special precautions for use
  • Change to storage instructions
  • Change to side-effects
  • Change to further information section
  • Change to date of revision
  • Addition of manufacturer
  • Change to improve clarity and readability

Updated on 3 December 2009 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company



Additonal text is stated in

blue and deleted text is striked through  :

 

4.4 Special warnings and precautions for use

Addition of sentence:

 

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

 

 

4.5 Interaction with other medicinal products and other forms of interaction

Section 4.5 updated:

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

Oral antidiabetic

medicinal products drugs (OAD), octreotide, monoamine oxidase inhibitors (MAOIs), non-selective beta-adrenergic blocking agents, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, alcohol, anabolic steroids and sulphonamides.

 

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

Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics,

 

growth hormone and danazol.

 

 

Octreotide/lanreotide may both increase or decrease insulin requirement.

Alcohol may intensify and prolong the glucose-lowering

or reduce the hypoglycaemic effect of insulin.

 

10. DATE OF REVISION OF THE TEXT

 

10/2009

 

 

Updated on 12 August 2008 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

 4.2    Posology and method of administration

 Inclusion of text concerning transferring patients from biphasic human insulin to NovoMix 30 has been added under the dose recommendation:

 Dose recommendation

“When transferring a patient from biphasic human insulin to NovoMix 30, start with the same dose and regimen. Then titrate according to individual needs (See titration guidelines in table above)”.

 5.1    Pharmacodynamic properties

 The following three paragraphs have been added.
 
  “Compared to biphasic human insulin 30, administration of NovoMix 30 before breakfast and dinner resulted in lower postprandial blood glucose after both meals (breakfast and dinner).

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

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

 10. DATE OF REVISION OF THE TEXT

 Date amended from 06/2008 to: 07/2008

Updated on 10 July 2008 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.6 - Pregnancy and lactation

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

 Section 4.2 Posology and method of administration

 Dose recommendation

 In the second paragraph the statement:

‘When using NovoMix 30 once daily, it is generally recommended to split the dose into two when reaching 30 units and continue titrating the dose.’

has been changed to:

‘When using NovoMix 30 once daily, it is generally recommended to move to twice daily when reaching 30 units by splitting the dose into equal breakfast and dinner doses. If twice daily dosing with NovoMix 30 results in recurrent daytime hypoglycaemic episodes, the morning dose can be split into morning and lunchtime doses (thrice daily dosing).’

 The paragraphs concerning combination of NovoMix 30 with pioglitazone, and insulin requirements in patients with insulin resistance or residual endogenous insulin production are unchanged, but have been moved to follow the titration guideline table. The statements concerning use of pre-breakfast and pre-dinner blood glucose to evaluate adequacy of dosing has also been moved to follow the titration guideline table and has been amended to a more general statement describing use of pre-meal blood glucose levels.

 Section 4.6 Pregnancy and lactation

 The first sentence:

‘There is limited clinical experience with insulin aspart in pregnancy.’

has been changed to:

‘There is limited clinical experience with NovoMix 30 in pregnancy.’

This change is not connected with the three times daily changes, but rather reflects recent changes in the SPC for NovoRapid (insulin aspart) allowing it to be use for the treatment of diabetes during pregnancy.
 

Updated on 8 February 2008 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.1 - List of excipients
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

 

4.2     Posology and method of administration

 The following information has been inserted

 “NovoMix 30 can be used in children and adolescents aged 10 years and above when premixed insulin is preferred. For children 6-9 years limited clinical data exists (see section 5.1)”

 In the last paragraph, the words “with NovoMix 30” has been deleted  in front of the words “in children” and the words “and adolescents” have been deleted. In front of the words” under the age of  the number “18” has been deleted and the number “6” has been inserted in front of “years”.

 4.4     Special warnings and precautions for use

 In the sentence starting with “Compared with biphasic human insulin, NovoMix 30 may have a” the words “more pronounced glucose lowering” have been inserted and the words “stronger hypoglycaemic” have been deleted.

 In the sentence starting with “As with any” the word “insulin” has been inserted.

In the last line of the sentence starting with “Combination of NovoMix 30 with pioglitazone:” the words “in the dose” have been inserted in front of “reduction”

 4.5     Interaction with other medicinal products and other forms of interaction

 The words “antidiabetic drugs (OAD)” have been inserted in front of Oral. The words “hypoglycaemic agents (OHAs”) have been deleted.

 4.8     Undesirable effects

 After the word “NovoMix” the number “30” had been deleted and the word “products” has been inserted.

 5.1     Pharmacodynamic properties

In the first paragraph, the words “for injection” have been inserted in front of the word “analogues”.

The following sentences has been inserted:

“Children and adolescents: A 16 week clinical trial comparing postprandial glycaemic control of meal-related NovoMix 30 with meal-related human insulin/biphasic human insulin 30 and bedtime NPH insulin was performed in 167 subjects aged 10 to 18 years. Mean HbA1c remained similar to baseline throughout the trial in both treatment groups, and there was no difference in hypoglycaemia rate with NovoMix 30 or biphasic human insulin 30.

In a smaller (54 subjects) 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 postprandial glucose increase was 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.”

5.2     Pharmacokinetic properties

The following sentence has been inserted:

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

In the last sentence, the word “children” has been deleted.

6.1     List of excipients

 “(for pH adjustment)” has been added for “Sodium hydroxide”

 “(for pH adjustment)” has been added for “Hydrochloric acid”

6.6     In the heading “Special precautions for disposal and other handling” has been inserted and the words “Instructions for use and handling” have been deleted.

In the second paragraph, the words “NovoMix 30 FlexPen” has been inserted and the words “the delivery system” have been deleted.

In the third paragraph the words “and NovoMix 30 FlexPen” have been inserted.

9.       DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of last renewal: 1 August 2005

10.     DATE OF REVISION OF THE TEXT

12-2007

Updated on 27 November 2007 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 6.4 - Special precautions for storage
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

4.2 Posology and method of administration

In the section dealing with dose recommendations the current text concerning combination of NovoMix 30 with metformin has been broadened to 'oral antidiabetic drugs for which the combination with insulin is approved'. However an additional pragraph has also been included concerning the combination of NovoMix 30 with pioglitazone. This warns of the risk of fluid-related adverse events and advises caution on initiation and titration of NovoMix 30.

A statement has also been included concerning the use of NovoMix 30 in the elderly: 'NovoMix 30 can be used in elderly patients; however there is limited experience with the use of NovoMix 30 in combination with OADs in patients older than 75 years'.

4.4 Special warnings and precautions for use

Two additional statements:

A statement concerning injection site reactions has been included. This is a standard statement; the same statement has recently been included in updates of the NovoRapid and Levemir SPCs.

A statement concerning the combination of NovoMix 30 with pioglitazone has been included. This notes that there have been reports of cardiac failure with pioglitazone in combination with insulin, especially in patients with risk factors for development of cardiac failure. Patients receiving combination NovoMix 30 and pioglitazone shoul be observed for signs and symptoms of heart failure, weight gain and oedema. There is also a warning that because insulin sensitivity is increased, patients may be at risk of dose-related hypoglycaemia and a reduction in dose of the insulin may be required.

4.8 Undesirable effects

Again in relation to combination OAD and NovoMix 30 therapy, an additional adverse event is included under 'General disorders and administration site conditions': 'Oedema and weight increase may occur when NovoMix 30 is used in combination with OADs'.

6.4 Special precautions for storage

it has been found that on first use of NovoMix 30 it is easier to resuspend if first allowed to warm to room temperature. A statement recommending this procedure has been included.

 

Updated on 24 August 2007 PIL

Reasons for updating

  • Change of inactive ingredient
  • Change to date of revision

Updated on 17 August 2007 SmPC

Reasons for updating

  • Change to section 6.1 - List of excipients
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 6.1. List of excipients
Mannitol has been replaced with glycerol.

Updated on 20 February 2007 PIL

Reasons for updating

  • Change of manufacturer

Updated on 11 October 2006 PIL

Reasons for updating

  • New PIL for medicines.ie

Updated on 8 May 2006 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.2 - Incompatibilities
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 20 October 2005 SmPC

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 28 July 2004 SmPC

Reasons for updating

  • Improved electronic presentation

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 10 December 2003 SmPC

Reasons for updating

  • Change to section 6.3 - Shelf life
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 18 August 2003 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 30 June 2003 SmPC

Reasons for updating

  • New SPC for medicines.ie

Legal category: Product subject to medical prescription which may be renewed (B)