Actraphane Hm injection

Diabetes Mellitus

Posology
The dosage for each patient is individualised. The individual insulin requirement is usually between 0,3 and 1,0 IU/kg/day. The daily insulin requirement may be higher in patients with insulin resistance (e.g. during puberty or due to obesity) and lower in patients with residual, endogenous insulin production. In patients with diabetes mellitus, optimized metabolic control delays the onset of late diabetic complications. Close blood glucose monitoring, is therefore recommended.
Special populations
Renal and hepatic impairment may reduce insulin requirement.
Method of administration
Avoidance of accidental mix-ups/medication errors
Patients must be instructed to always check the insulin label before each injection to avoid accidental mix-ups between Actraphane u00ae HM (ge) and other insulin products. Actraphane u00ae HM (ge) is administered subcutaneously in the thigh or abdominal wall. If convenient the gluteal or deltoid region may also be used. Subcutaneous injection into the abdominal wall result in a faster absorption than from other injection sites. Injection sites should be rotated within an anatomical region in order to avoid lipodystrophy and cutaneous amyloidosis. Injection into a lifted skin fold minimizes the risk of intramuscular injection. Keep the needle under the skin for at least 6 seconds to make sure the entire dose is injected. Injections using 10 ml vials and conventional syringes. Instructions for use are reflected in the Patient Information Leaflet. Actraphane HM (ge) vials are for use with insulin syringes with a corresponding unit scale.

• Hypoglycaemia
• Hypersensitivity to human insulin or any of the excipients

Actraphane u00ae HM (ge) is not to be administered intravenously. Before travelling between time zones, the patient should seek the doctoru2019s advice, since this may mean that the patient has to take insulin and meals at different times.
Transfer from other insulin products
Transferring a patient to a new type or brand of insulin should be done under strict medical supervision. Changes in strength, brand, type, species (animal, human, human insulin analogue) and/or method of manufacture may result in a change in dosage from that used with their previous insulin. If an adjustment is needed, it may be done with the first dose or during the first few weeks or months. A few patients who have experienced hypoglycaemic reactions after transfer from animal source insulin have reported that the early warning symptoms of hypoglycaemia were less pronounced or different from those experienced with their previous insulin.
Hyperglycaemia
Inadequate dosing or discontinuation of treatment, especially in Type 1 diabetes (insulin dependent diabetes mellitus), may lead to hyperglycaemia. The first symptoms of hyperglycaemia usually come on 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 usually lead to diabetic ketoacidosis which is potentially lethal.
Hypoglycaemia
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia. Severe hypoglycaemia may lead to unconsciousness and /or convulsion 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, anxiety, unusual tiredness or weakness, confusion, difficulty in concentration, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation. Severe hypoglycaemia may lead to unconsciousness and /or convulsion and may result in temporary or permanent impairment of brain function or even death.
Injection site reactions
Injection site reactions (redness, swelling, itching, pain and haematoma at the injection site) may occur during treatment with insulin. Most reactions are transitory and disappear during continued treatment. Skin and subcutaneous tissue disorder Patients must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and cutaneous amyloidosis. 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.
Combination of pioglitazone with Actraphane u00ae HM (ge)
Cases of congestive heart failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for development of congestive heart failure. This should be kept in mind if treatment with the combination of pioglitazone and insulin medicinal products is considered. If the combination is used, patients should be observed for signs and symptoms of congestive heart failure, weight gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs.

A number of medicines are known to interact with glucose metabolism. The following medicines may reduce the patientu2019s insulin requirements: Oral hypoglycaemic medicines (OHAs), monoamine oxidase inhibitors (MAOI), non-selective beta-blocking medicines, angiotensin converting enzyme (ACE) inhibitors, salicylates and alcohol. The following medicines may increase the patientu2019s insulin requirements: Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics, growth hormone and danazol. Beta-blocking medicines may mask the symptoms of hypoglycaemia and delay recovery from hypoglycaemia. Octreotide may both decrease and increase insulin requirements. Alcohol may intensify and prolong the hypoglycaemic effect of insulin.

Pregnancy
There are no restrictions on treatment of diabetes with insulin during pregnancy, as insulin does not pass the placental barrier. Intensified blood glucose control and monitoring of pregnant women with diabetes is recommended throughout pregnancy and when contemplating a pregnancy. Both hypoglycaemia and hyperglycaemia, which can occur in inadequately controlled diabetes therapy, increase the risk of malformations and deaths in utero. Insulin requirements usually fall in the first trimester and increase subsequently during the second and third trimesters. After delivery, insulin requirements return rapidly to pre-pregnancy values.
Breast-feeding
There are no restrictions on treatment of diabetes with insulin during breastfeeding, as insulin does not pass into breast milk.

The patientu2019s 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, whose blood glucose control is greatly improved by e.g. intensified insulin therapy, may experience a change in their usual warning symptoms of hypoglycaemia and should be advised accordingly.

(a) Summary of the safety profile
Side effects observed in patients using Actraphane u00ae HM (ge) are mainly dose-dependent and due to the pharmacological effect of insulin. Hypoglycaemia is the most frequent side effect. It may occur if the insulin dose is too high in relation to the insulin requirement. In clinical trials and during marketed use, the frequency varied with the patient population and dose regimens therefore no specific frequency can be presented.
(b) Tabulated list of adverse reactions
Frequencies of other side effects from clinical trials, which by an overall judgement are considered related to Actraphane u00ae HM (ge) are listed below. The frequencies are defined as:
Very common (u2265 1/10), common (u22651/100, <1/10), uncommon (u22651/1 000, <1/100), rare (u2265 1/0 000, <1/1000). Isolated spontaneous cases are presented as very rare, defined as: u02c21/10 000.
System organ class
Side effect and frequency
Metabolism and nutrition disorders
Very common: Hypoglycaemia
Immune system disorders
Uncommon: Urticaria, rash
Very rare: Anaphylactic reactions
Nervous system disorders
Uncommon: Peripheral neuropathy (painful neuropathy)
Eye disorders
Uncommon: Diabetic retinopathy
Very rare: Refraction disorders
Skin and subcutaneous tissue disorders
Uncommon: Lipodystrophy (including lipohyperthrophy, lipotrophy)
Not known: Cutaneous amyloidosis u03ee
General disorders and administration site conditions
Uncommon: Injection site reactions
Uncommon: Oedema u03ee
ADR from postmarketing sources
(c) Description of selected adverse reactions
Anaphylactic reactions
Symptoms of generalised hypersensitivity may include generalised skin rash, itching, sweating, gastrointestinal upset, angioneurotic oedema, difficulties in breathing, palpitation, reduction in blood pressure and fainting /loss of consciousness. Generalised hypersensitivity reactions are potentially life threatening.
Peripheral neuropathy (painful neuropathy)
Fast improvement in blood glucose control may be associated with a condition termed u201cacute painful neuropathyu201d which is usually reversible. This reaction is usually of transitory nature.
Eye disorders
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 temporary worsening of diabetic retinopathy.
Refraction disorders
Refraction anomalies may occur upon initiation of Actraphane. These symptoms are usually of transitory nature.
Skin and subcutaneous tissue disorders
Lipodystrophy (including lipohyperthrophy, lipoatrophy) and cutaneous amyloidosis may occur at the injection site as a consequence of failure to rotate injection sites within the same area. Continuous rotation of the injection site within the particular injection area may help to reduce the risk of developing these reactions.
Oedema
Oedema may occur upon initiation of insulin treatment. These symptoms are usually of transitory nature.
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 the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications https://www.sahpra.org.za/Publications/Index/8

A specific overdose of insulin cannot be defined; however hypoglycaemia may develop over sequential stages if too high doses relative to the patientu2019s requirements are administered:
u2022 Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary products. It is therefore recommended that the diabetic patient constantly carries some sugar-containing products.
u2022 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 person who has received appropriate instruction, or glucose given intravenously by a medical 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 carbohydrate is recommended for the patient in order to prevent relapse.