Optisulin 100 IU/mL Solution for injection.

For the treatment of adults, adolescents and children aged 2 years and older with diabetes mellitus, where treatment with insulin is required.

Posology:

OPTISULIN is given subcutaneously once daily. It may be administered at any time during the day, however, at the same time every day. The desired blood glucose levels as well as the doses and the timing of any antidiabetic medicine, including OPTISULIN, must be determined and adjusted individually. Dose adjustment may also be required, for example, if the patient's weight or lifestyle changes, or change in timing of the OPTISULIN dose or other circumstances arise that increase susceptibility to hypo- or hyperglycaemia (see section 4.4). Any change to the OPTISULIN dose should be made cautiously and only under medical supervision.

Special populations:

Geriatric use: In elderly patients with diabetes, it is recommended that the initial dosing, dose increments, and maintenance dosage be conservative to avoid hypoglycaemic reactions. Hypoglycaemia may be difficult to recognise in the elderly (see section 4.4 and 4.8).

Paediatric population: The safety and efficacy of OPTISULIN in children under the age of 2 years have not been established. OPTISULIN should not be used in children under 2 years.

Changeover to OPTISULIN: The initial dose of OPTISULIN should be determined individually, depending on the desired blood glucose levels. When changing from a treatment regimen with an intermediate or long-acting insulin to a regimen with OPTISULIN, a change of the dose of the basal insulin is often required and the concomitant antidiabetic treatment may need to be adjusted (dose and timing of additional regular insulins or fast-acting insulin analogues or the dose of oral antidiabetic agents). To reduce the risk of hypoglycaemia, when patients are transferred from once daily insulin glargine 300 units/mL to once daily OPTISULIN, the recommended initial OPTISULIN dose is 80 % of insulin glargine 300 units/mL dose that is being discontinued. When patients are transferred from twice-daily neutral protamine hagedorn (NPH) insulin to OPTISULIN administered once daily, to reduce the risk of nocturnal and early morning hypoglycaemia, the initial dose should usually be reduced by approximately 20 % (daily units of OPTISULIN compared to total daily units of NPH insulin) and then the regimen should be adjusted individually. A programme of close metabolic monitoring is recommended during changeover and in the initial weeks thereafter. This is particularly true for patients on human insulin receiving high doses due to the production of human insulin antibodies. With improved metabolic control and resulting increase in insulin sensitivity, a further adjustment in dosage regimen may become necessary. Dose adjustment may also be required, for example, if the patientu2019s weight or life-style changes or other circumstances arise that increase susceptibility to hypo- or hyperglycaemia (see section 4.4).

Method of administration:

OPTISULIN is administered by subcutaneous injection. OPTISULIN is not intended for intravenous administration. The prolonged duration of action of OPTISULIN is dependent on its injection into subcutaneous tissue. Intravenous administration of the usual subcutaneous dose could result in severe hypoglycaemia. Injection sites must be rotated within a given injection area from one injection to the next to reduce the risk of lipodystrophy and localised cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localised cutaneous amyloidosis. OPTISULIN must not be mixed with any other insulin or diluted. Mixing or diluting can change its time/action profile and mixing can cause precipitation.

OPTISULIN must not be used in:

• Patients hypersensitive to insulin glargine or any of the excipients listed in section 6.1.
• Children < 2 years of age, as in this group efficacy and safety have not been demonstrated.

OPTISULIN should not be used for the treatment of diabetic ketoacidosis. Instead, intravenous regular insulin is recommended in such cases. Patients must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and localised cutaneous amyloidosis (see section 4.8). There is a potential risk of delayed insulin absorption and worsened glycaemic control following insulin injections at sites with these reactions. A sudden change in the injection site to an unaffected area has been reported to result in hypoglycaemia. Blood glucose monitoring is recommended after the change in the injection site, and dose adjustment of antidiabetic medicines may be considered.

Hypoglycaemia: The time of occurrence of hypoglycaemia depends on the action profile of the insulins used and may, therefore, change when the treatment regimen is changed. Particular caution should be exercised, and intensified blood glucose monitoring is advisable in patients in whom sequelae of hypoglycaemic episodes might be of particular clinical relevance, such as in patients with significant stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following hypoglycaemia). Patients should be made aware of circumstances where warning symptoms of hypoglycaemia are diminished. Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the patientu2019s awareness of hypoglycaemia. The prolonged effect of subcutaneous OPTISULIN may delay recovery from hypoglycaemia.

The warning symptoms of hypoglycaemia may be changed, be less pronounced or be absent in certain conditions. These include patients:

• in whom glycaemic control is markedly improved
• in whom hypoglycaemia develops gradually
• who are elderly
• in whom an autonomic neuropathy is present
• with a long history of diabetes
• suffering from a psychiatric illness
• receiving concurrent treatment with certain other medicines (see section 4.5).

In patients with renal impairment, insulin requirements may be diminished due to reduced insulin metabolism. In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin requirements. In patients with severe hepatic impairment, insulin requirements may be diminished due to reduced capacity for gluconeogenesis and reduced insulin metabolism.

Pens to be used with OPTISULIN cartridges: The OPTISULIN cartridges should only be used with the following pen: AllStar. They should not be used with any other reusable pen as the dosing accuracy has only been established with the listed pen.

Medicine errors: Medicine errors have been reported in which other insulins, particularly short-acting insulins, have been accidentally administered instead of OPTISULIN. Insulin label must always be checked before each injection to avoid medicine errors between OPTISULIN and other insulins.

A number of substances affect glucose metabolism and may require dose adjustment of OPTISULIN. Substances that may increase the blood glucose-lowering effect and increase susceptibility to hypoglycaemia include: oral antidiabetic agents; ACE inhibitors; disopyramide; fibrates; fluoxetine; MAO inhibitors; pentoxifylline; propoxyphene; salicylates and sulfonamide antibiotics. Substances that may reduce the blood glucose-lowering effect include: corticosteroids; danazol; diazoxide; diuretics; glucagon; isoniazid; oestrogens and progestogens (e.g. in oral contraceptives); protease inhibitors and atypical antipsychotic medicines (e.g. olanzapine and clozapine); phenothiazine derivatives; somatropin; sympathomimetic agents (e.g. epinephrine (adrenaline), salbutamol, terbutaline) and thyroid hormones. Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the blood glucose-lowering effect of OPTISULIN. Pentamidine may cause hypoglycaemia, which may sometimes be followed by hyperglycaemia. In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent.

Pregnancy: For insulin glargine, as in OPTISULIN, no clinical data on exposed pregnancies from controlled clinical studies are available. A large amount of data on pregnant women (more than 1 000 pregnancy outcomes) indicates no specific adverse effects of insulin glargine on pregnancy and no specific malformities nor feto/neonatal toxicity of insulin glargine, as in OPTISULIN. Animal data do not indicate reproductive toxicity. OPTISULIN can be used during pregnancy, if clinically needed. It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control throughout pregnancy to prevent adverse outcomes associated with hyperglycaemia. Insulin requirements may decrease during the first trimester and generally increase during the second and third trimesters. Immediately after delivery, insulin requirements decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential.

Breastfeeding: Breastfeeding women may require adjustments in insulin dose and diet.

The patientu2019s ability to concentrate and react may be impaired as a result of hypoglycaemia or hyperglycaemia or, for example, as a result of visual impairment. 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 whilst driving. This is particularly important in those who have reduced or absent awareness of the warning symptoms of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving should be considered in these circumstances.

The following frequency rating has been used: Very common: u2265 1/10); Common: u2265 1/100, < 1/10); Uncommon: u2265 1/1000, < 1/100); Rare: u2265 1/10 000, < 1/1000); Very rare: (< 1/10 000), including rare, isolated cases.

Immune system disorders: Rare: Systemic allergic reactions. Immediate-type allergic reactions to OPTISULIN are rare. Such reactions to OPTISULIN or the excipients may, for example, be associated with generalised skin reactions, angioedema, bronchospasm, hypotension and shock, and may be life-threatening.

Endocrine disorders: Very common: Hypoglycaemia. Hypoglycaemia, in general, is the most frequent adverse reaction of OPTISULIN therapy and may occur if the OPTISULIN dose is too high in relation to the insulin requirement. Frequency unknown: OPTISULIN administration may cause neutralising insulin antibodies to form. The presence of such insulin antibodies may necessitate adjustment of the OPTISULIN dose in order to correct a tendency to hyper- or hypoglycaemia.

Metabolism and nutrition disorders: Rare: OPTISULIN may cause sodium retention and oedema, particularly if previously poor metabolic control is improved by intensified OPTISULIN therapy.

Eye disorders: Frequency unknown: A marked change in glycaemic control may cause temporary visual impairment, due to temporary alteration in the turgidity and refractive index of the lens. Intensification of OPTISULIN therapy with abrupt improvement in glycaemic control may be associated with temporary worsening of diabetic retinopathy.

Skin and subcutaneous tissue disorders: Common: Lipohypertrophy. Lipohypertrophy was observed in 1 to 2 % of patients. Uncommon: Lipoatrophy. Continuous rotation of the injection site within the given injection area may help to reduce or prevent these reactions (lipodystrophy). Frequency unknown: Localised cutaneous amyloidosis at the injection site has occurred. Hyperglycaemia has been reported with repeated insulin injections into areas of cutaneous amyloidosis; hypoglycaemia has been reported with a sudden change to an unaffected injection site.

General disorders and administration site conditions: Common: Injection site reactions and local hypersensitivity reactions. In clinical studies, reactions at the injection site were observed in 3 to 4 % of patients. Such reactions include redness, pain, itching, hives, swelling or inflammation. Most minor reactions to insulin usually resolve in a few days to a few weeks.

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of OPTISULIN is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to the South African Health Products Regulatory Authority (SAHPRA) via the u201cAdverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8 Side effects can be reported directly to Sanofiu2019s Pharmacovigilance Unit at [email protected] (email) or 011 256 3700 (tel).

Symptoms: OPTISULIN overdose may lead to severe and sometimes prolonged and life-threatening hypoglycaemia.

Management: Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in drug dosage, meal patterns, or physical activity may be needed. More severe episodes with coma, seizure, or neurological impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycaemia may recur after apparent clinical recovery.