Insulins (intermediate-acting) - ATC Code – A10A A

bovine insulin, insulin, beef insulin

Crystalline Insulin Ph Eur (Bovine) 100 IU/ml. Isophane Insulin Injection Ph Eur (Bovine)

Suspension for injection. A white suspension

The treatment of insulin dependent diabetes mellitus. May be used for diabetics requiring a depot insulin of intermediate duration

Usually administered subcutaneously but where necessary it may be given intramuscularly in which case onset is more rapid and overall duration shorter. It should not be given intravenously. Onset of action occurs within 2 hours after subcutaneous injection with an overall duration of 18-24 hours. Maximum effect is exerted between 6-12 hours.

By subcutaneous or intramuscular injection in accordance with individual requirements. Duration approximately 18 - 24 hours.

Hypoglycaemia.

Hypersensitivity to insulin or to any of the excipients

In no circumstances must Hypurin® Bovine Isophane be given intravenously.

Hypoglycaemia: Susceptibility to hypoglycaemia may be increased by an inaccurate or excessive dosage of insulin, the omission of a meal by the patient or increased physical activity. Correct insulin administration and awareness of the symptoms of hypoglycaemia are essential to reduce the risk of hypoglycaemia.

Blood or urinary glucose concentrations should be monitored and the urine tested for ketones by patients on insulin therapy.

Newly diagnosed diabetic patients may experience fluctuating insulin requirements during the first weeks, months or even years of treatment (the so-called 'honeymoon period').

Patients transferred to Hypurin® Bovine insulins from other commercially available preparations may require dosage adjustments.

The warning symptoms of hypoglycaemia may be changed, be less pronounced or absent in certain risk groups who should be advised accordingly. These include patients:

- in whom glycaemic control is greatly improved, e.g. by intensified insulin therapy

- with a long history of diabetes

- who are elderly

- receiving concomitant treatment with certain medicinal products e.g. beta blockers or clonidine.

Elderly diabetic patients are more susceptible to episodes of severe, rapid onset hypoglycaemia.

Combination of Hypurin® insulins with pioglitazone: Cases of cardiac failure have been reported when thiazolidinediones are 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 Hypurin® 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.

Insulin requirements may increase during illness (this includes infection and accidental and surgical trauma), puberty or emotional upset.

Insulin resistance is frequently associated with lipid disorders, hypertension and ischaemic heart disease. Patients with insulin resistance usually require more than 200 units of insulin daily. Insulin resistance of the type manifested by greatly increased insulin requirements may be due to factors including antibody formation although some diseases, such as infections, endocrine hyperfunctional states (e.g. acromegaly, Cushing's syndrome, thyrotoxicosis) or stress can contribute to insulin resistance.

Insulin requirements may decrease with liver disease, disease of the adrenal, pituitary or thyroid glands and coeliac disease. In patients with severe renal impairment, insulin requirements may fall and dosage reduction may be necessary. The compensatory response to hypoglycaemia may also be impaired.

Insulin requirements may be increased in the premenstrual period but may be reduced during or after a menstrual cycle.

Insulin requirements are usually reduced but occasionally increased during periods of increased activity.

Increase in subcutaneous blood flow, brought about by factors such as a hot bath, may increase the rate of absorption of insulin.

Drugs that may increase the requirement for insulin

Antipyschotics: chloropromazine

Corticosteroids

Diazoxide

Diuretics: thiazide diuretics or loop diuretics

Sympathomimetic agents

Thyroid hormone replacement therapy

Smoking may also antagonise the hypoglycaemic effect of insulin

Drugs that may decrease the requirement for insulin

ACE inhibitors

Alcohol: moderate or large amounts of alcohol (more than 2 units per day for women and more than 3 units per day for men) can decrease the requirements for insulin and may lead to hypoglycaemic attacks. Episodic heavy drinking ('binge' drinking) carries a particularly high risk of hypoglycaemic episodes.

Anabolic steroids

Analgesics: NSAIDS, or salicylates, particularly large doses of aspirin

Androgens: testosterone may enhance the hypoglycaemic effect of insulin

Anti-arrhythmics: disopyramide.

Concomitant use of insulin with quinidine may increase the risk of hypoglycaemia occurring.

Anti-depressants: monoamine oxidase inhibitors or fluoxetine.

Concomitant use of amitriptyline with insulin may lead to hypoglycaemia.

Antihypertensives: guanethidine

Antimalarials: concomitant use of insulin with antimalarials such as chloroquine or quinine may increase the risk of hypoglycaemia occurring.

Fenfluramine

Hormone antagonists: octreotide

Lipid-regulating drugs: fibrates

Mebendazole

Pentoxifylline: the hypoglycaemic activity of insulin may be potentiated by concomitant administration of high-dose pentoxifylline injection.

Tetracyclines: tetracyclines such as oxytetracycline

Drugs that may increase or decrease the requirements for insulin

Antihypertensives: clonidine. Signs and symptoms of hypoglycaemia may be masked by clonidine.

Beta blockers: beta blockers. Some of the warning signs of insulin-induced hypoglycaemia may be masked.

Calcium channel blockers: nifedipine may occasionally impair glucose tolerance.

Cyclophosphamide

Isoniazid

Lipid-regulating drugs: gemfibrozil

Oral contraceptives

Metabolic disorders:

• Hypoglycaemia is the most common adverse effect associated with insulin therapy.

• Hypokalaemia may occur with insulin therapy.

• Insulin therapy may lead to weight gain.

General disorders and administration site conditions:

Lipodystrophy (atrophy or hypertrophy of the fat tissue) may occur at the injection site. Stinging or sensations of warmth or burning at the site of injection may also occur.

Immune system disorders:

Insulin hypersensitivity can occur with animal insulins, but appears less likely with purified insulins and there is minimal evidence that such effects occur with Hypurin insulins. Allergic reactions to phenol and m-cresol contained as preservative and to zinc and protamine may occur.

• Local hypersensitivity: Local allergic reactions to insulin such as pruritus, erythema and oedema may occur at the injection site.

• Generalised hypersensitivity: Generalised hypersensitivity may produce urticaria, nausea, dyspnoea or wheezing and, in rare cases, anaphylactic reactions. Severe, angioedema is a rare adverse effect of insulin treatment occurring most often at the initiation of therapy.

Wockhardt UK Ltd

(POM)

10 February 2012