sanofi-aventis

Section 4.4 – Added the following:

Medication errors

Medication errors have been reported in which other insulins, particularly short-acting insulins, have been accidentally administered instead of insulin glargine. Insulin label must always be checked before each injection to avoid medication errors between insulin glargine and other insulins.

Combination of Lantus 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 Lantus 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.

Section 6.6 – Added the following:

Insulin label must always be checked before each injection to avoid medication errors between insulin glargine and other insulins. (see section 4.4)

1, 2, 3, 4.5, 6.1, 6.3, : Minor changes to wording & punctuation

4.2: Changes to the order of the paragraphs, minor changes to wording and punctuation.

Information on use in special populations (elderly, paediatric, renal/hepatic insufficiency) has been revised and moved from 4.4 to 4.2.

4.4 The following text has been added:

Pens to be used with Lantus cartridges

The Lantus cartridges should only be used with the following pens: OptiPen, ClikSTAR and Autopen 24 and should not be used with any other reusable pen as the dosing accuracy has only been established with the listed pens.

4.6: Additional information on use in pregnancy and lactation has been added, including postmarketing evidence of safety in pregnancy, and a section on fertility has been added

4.8: Adverse effects have been tabulated; consequent minor changes to wording and formatting. Information on adverse effects in paediatric population has been revised.

5.1: Minor changes to wording. In addition the following text has been added:

Paediatric population

In a randomised, controlled clinical study, paediatric patients (age range 6 to 15 years) with type 1 diabetes (n = 349) were treated for 28 weeks with a basal-bolus insulin regimen where regular human insulin was used before each meal. Insulin glargine was administered once daily at bedtime and NPH human insulin was administered once or twice daily. Similar effects on glycohemoglobin and the incidence of symptomatic hypoglycemia were observed in both treatment groups, however fasting plasma glucose decreased more from baseline in the insulin glargine group than in the NPH group. There was less severe hypoglycaemia in the insulin glargine group as well. One hundred forty three of the patients treated with insulin glargine in this study continued treatment with insulin glargine in an uncontrolled extension study with mean duration of follow-up of 2 years. No new safety signals were seen during this extended treatment with insulin glargine.

A crossover study comparing insulin glargine plus lispro insulin to NPH plus regular human insulin (each treatment administered for 16 weeks in random order) in 26 adolescent type 1 diabetic patients aged 12 to 18 years was also performed. As in the paediatric study described above, fasting plasma glucose reduction from baseline was greater in the insulin glargine group than in the NPH group. HbA1c changes from baseline were similar between treatment groups; however blood glucose values recorded overnight were significantly higher in the insulin glargine/ lispro group than the NPH/regular group, with a mean nadir of 5.4 mM vs 4.1 mM. Correspondingly, the incidences of nocturnal hypoglycaemia were 32 % in the insulin glargine / lispro group vs 52 % in the NPH / regular group.

5.2: The following has been added:

Paediatric population

No specific pharmacokinetics study in children or adolescents was conducted.

6.6: Minor changes to punctuation. The following has been added:

Lantus must not be mixed with any other insulin or diluted. Mixing or diluting can change its time/action profile and mixing can cause precipitation.

Clarification has been provided on compatible insulin pens:

Insulin pen

The Lantus cartridges are to be used only in conjunction with OptiPen, ClikSTAR or Autopen 24 (see section 4.4). Not all of these pens may be marketed in your country.

The pen should be used as recommended in the information provided by the device manufacturer.

Section 4.4: Harmonisation of the information between all sanofi-aventis insulins regarding the transfer of patient from one insulin to another

'Switching a patient to another type or brand of insulin should be done under strict medical supervision and may require change in dose.' has been replaced with 'Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need for a change in dosage.'

- Section 5.1: Pharmacotherapeutic group - the term 'antidabetic agent' has been removed

- Section 6.6 - update to the instructions for use for the OptiSet prefilled pen - minor changes to the language rather than addition of new information.

e.g. 'Always attach a new needle before each use. Only use needles that are compatible for use with OptiSet.' replaced with 'A new needle must always be attached before each use. Only needles that are compatible for use with OptiSet must be used.'

'Always perform the safety test before each injection' replaced with 'A safety test must always be performed before each injection.'

etc.