Malix Tablets 5.0mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Malix* (Glibenclamide) Tablets 5.0mg.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains glibenclamide BP 5mg.
3 PHARMACEUTICAL FORM
Tablet.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Glibenclamide is a hypoglycaemic agent, indicated for the oral treatment of patients with non-insulin dependent diabetes who respond inadequately to dietary measures alone.
4.2 Posology and method of administration
Glibenclamide should be taken with or immediately after food. There were no changes to the reference product information in the report period. The total daily dosage is preferably given as a single dose at breakfast or with the first main meal, but due consideration should be given to the patients meal habits and daily activity when apportioning dosage.
Adults:
New Diabetics:
In maturity-onset diabetes of mild to moderate severity, treatment should be started at 5mg daily, or 2.5mg in debilitated or elderly patients. If this dosage is not sufficient for proper control it should be increased by 2.5mg at intervals of one week, or as directed by the clinician. The total daily dosage rarely exceeds 15mg and increasing the daily dosage above this does not generally produce any additional effect.
Transfer from other oral sulphonylureas:
Transfer to Glibenclamide can usually be carried out with any break in therapy.
Treatment is commenced with the equivalent dose of glibenclamide without exceeding an initial dose of 10mg. If response is inadequate, the dose can be raised in a stepwise fashion to 15mg daily. One 5mg tablet of glibenclamide is approximately equivalent to 1g tolbutamine or glymidine, 250mg chlorpropamide or tolazamide, 500mg acetohexamide, 25mg glibornuride or 5mg glipizide.
Changeover from Biguanides:
The biguanide should be withdrawn and glibenclamide treatment started with one 2.5mg tablet. The dosage should then be adjusted by increments of 2.5mg to achieve control.
Combination with biguanides: If adequate control is not possible with diet and 15mg of glibenclamide, control may be established by combined administration of glibenclamide and a biguanide derivative.
Changeover from insulin:
While it is appreciated that most patients who are on insulin therapy will continue to need it, there may be few patients, particularly those on low dosage, who will remain stabilised if transferred to Glibenclamide.
Children:
No dosage recommendations can be made for the administration of Glibenclamide to children.
Method of administration: Oral
4.3 Contraindications
Glibenclamide is contra-indicated in:
1. The treatment of juvenile or unstable diabetes.
2. Patients who have had serious metabolic decompensation with ketosis and, in particular, diabetic pre-coma and coma.
3. Serious impairment of renal, hepatic, thyroid or adrenocortical function.
4. Pregnancy. After delivery, glibenclamide therapy can be started or resumed.
5. Patients with porphyria.
6. Insulin dependant diabetes mellitus
7. Circumstances of unusual stress such as surgery, severe infection and trauma
8. Hypersensitivity to glibenclamide or any of the other excipients in the product
9. Breastfeeding
10. Patients currently being treated with bosentan
4.4 Special warnings and precautions for use
Treatment with sulphonylureas has been associated with occasional disturbances of liver function and cholestatic jaundice. If clinical jaundice occurs, glibenclamide should be discontinued.
Care is necessary in elderly, debilitated or malnourished patients who are particularly susceptible to the hypoglycaemic effects of sulphonylureas, and during excessive exercise as hypoglycaemia may be provoked.
Patients with mild to moderate renal impairement. In long-term clinical trials with renal insufficiency have been treated satisfactorily using glibenclamide at reduced doses with careful patient monitoring.
Patients with adrenal or pituitary insufficiency.
4.5 Interaction with other medicinal products and other forms of interaction
Bosentan: An increased incidence of elevated liver enzymes was observed in patients receiving glibenclamide concomitantly with bosentan.
Both glibenclamide and bosentan inhibit the bile salt export pump, leading to intracellular accumulation of cytotoxic bile salts. Therefore this combination should not be used.
The hypoglycaemic action of oral anti-diabetic agents including Glibenclamide may be enhanced by anabolic steroids, alcohol, ACE inhibitors, captopril, enalapril, anti-inflammatory/analgesics (e.g. phenylbutazone, salicylates) ciprofloxacin, dicoumarin anticoagulants and heparin, anti-infectives (chloramphenicol, fluconazole miconazole, sulphonomides including co-trimoxazole), lipid regulating agents (e.g. clofibrate), H2-blockers, cimetidine, ranitidine, fenfluramine, methyldopa sulphinpyrazone, some antidepressants (monoamine-oxidase inhibitors, Doxepin, nortriptyline) chloramphenicol and tuberculostatics, necessitating dosage reduction. Conversely, thiazide diuretics and beta-blockers, furosemide, ethacrynic acid, phenothiazines, oral contraceptives containing oestrogens, corticosteroids and rifampicin, may diminish hypoglycaemic activity necessitating dosage increase. Beta-blockers may mask some of the symptoms of hypoglycaemia. Alcohol may interact with the sulphonylureas, provoking facial flushing, and has a variable effect on blood sugar levels.
Calcium channel blockers and lithium may occasionally impair glucose tolerance.
Glibenclamide may either potentiate or weaken the effect of coumarin derivatives.
Immunosuppressants: there is the potential for glibenclamide to raise plasma levels of ciclosporin, which would necessitate a dose reduction of ciclosporin.
4.6 Fertility, Pregnancy and lactation
There is no information on the use of glibenclamide in human pregnancy, but it has been in wide, general use for many years without apparent ill consequence. Animal studies have shown no hazard. It has not yet been established whether glibenclamide is transferred to human milk. However, other sulphonylureas have been found in milk and there is no evidence to suggest that glibenclamide differs from the group in this respect.
4.7 Effects on ability to drive and use machines
Alertness and reactions may be impaired by hypo-or hyperglycaemic episodes, especially when beginning or after altering treatment, or when Glibenclamide is not taken regularly. This may affect the ability to drive or operate machinery.
4.8 Undesirable effects
Blood disorders
Potentially life-threatening changes in the blood picture may occur. They may include - rarely - mild to severe, thrombocytopenia (e.g. presenting as purpura), - isolated cases - leucopenia, agranulocytosis and (e.g. due to myelosupression) pancytopenia, haemolytic anaemia, erythrocytopenia, granulocytopenia.
Immune system disorders
Hypersensitivity including dyspnoea and swelling of the lips, face, throat or tongue. Endocrine disorders
Infrequently a syndrome of inappropriate secretion of antidiuretic hormone may be induced which may give rise to reduced serum sodium levels.
Metabolism and nutritional disorders:
Hypoglycaemia
Hypoglycaemia, sometimes prolonged and even life-threatening, may occur as a result of the blood glucose lowering action of Glibenclamide. Possible symptoms of hypoglycaemia include headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness, disordered sleep, restlessness, aggressiveness, impaired concentration, alertness, and reactions, depression, confusion, speech disorders, aphasia, visual disorders, tremor, pareses, sensory disturbances, dizziness, helplessness, loss of self control, delirium, cerebral convulsions, somnolence and loss of consciousness up to and including coma, shallow respiration and bradycardia.
Increased appetite and weight gain may occur.
Signs of adrenergic counter-regulation may be present such as sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmias.
The clinical picture of a severe hypoglycaemic attack may resemble that of a stroke. The symptoms of hypoglycaemia nearly always subside when hypoglycaemia is corrected.
Eye disorders
Temporary visual impairment. Gastrointestinal disorders
Gastrointestinal symptoms such as nausea, vomiting, heartburn, anorexia, metallic taste, sensations of pressure or fullness in the epigastrium, abdominal pain, diarrhoea may occur.
Hepatobiliary disorders
In isolated cases, there may be elevation of liver enzyme levels and even impairment of liver function (e.g. with cholestatic jaundice and hepatitis which can regress after withdrawal of Glibenclamide, although they may lead to life-threatening liver failure).
Skin and subcutaneous tissue disorders
Occasionally, allergic or pseudoallergic reactions may occur, e.g. in the form of itching or rashes.
In isolated cases, photosensitivity may occur, and mild reactions in the form of urticaria may develop into serious and even life-threatening reactions.
Severe manifestations of hypersensitivity include fever, cholestatic jaundice, aplastic anaemia, and other changes in the blood (see blood disorders above), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis and erythema nodosum.
See also sub-section 4.4 Special warnings and precautions for use.
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
4.9 Overdose
In acute poisoning the stomach should be emptied by emesis or lavage. Hypoglycaemia should be treated urgently in the conscious patient with oral glucose.
If patient is comatose, glucose should be administered as an intravenous infusion. Bolus glucose injections are not recommended because of the possibility of rebound hypoglycaemia. Alternatively, glucagon may be administered in a dose of 1mg subcutaneously or intramuscularly to restore consciousness. The patient should be observed over several days in case hypoglycaemia recurs.
5.1 Pharmacodynamic properties
Glibenclamide in an oral hypoglycaemic agent of the sulphonylurea type.
ATC Code: A10BB01
5.2 Pharmacokinetic properties
Glibenclamide is rapidly absorbed and is extensively bound to plasma proteins, but is not readily displaced by acidic drugs. It is extensively metabolised by the liver and excreted as metabolites in the urine and bile. The following pharmacokinetic particulars were obtained with Malix* Tablets
|
5mg: | |
|
T/a |
=2.85 hours. |
|
T/p |
=2.49 hours. |
|
Tmax |
=3.843 hours. |
|
Cmax |
=35.278ng/ml. |
|
AUC |
=369.3 6ng/ml/hour s |
5.3 Preclinical safety data
There are no preclinical safety data of relevance to the prescriber.
6.1 List of excipients
Lactose, maize starch, gelatin, sodium carboxymethylcellulose, talc and magnesium stearate.
6.2 Incompatibilities
Not known.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Store below 25°C. Protect from light.
6.5 Nature and contents of container
|
(i) |
Polypropylene securitainers with polyethylene closures. |
|
(ii) |
Amber glass bottles with aluminium rolls on pilfer-proof closures. |
Pack sizes: 28, 30, 56, 60, 84, 90, 100, 112, 120, 250, 500 and 1,000.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Ennogen Pharma Limited Unit G4,
Riverside Industrial Estate,
Riverside Way,
Dartford DA1 5BS UK
MARKETING AUTHORISATION NUMBER(S)
PL 40147/0044
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10
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
27/06/1983 / 26/07/2005
DATE OF REVISION OF THE TEXT
16/04/2014