Glimepiride

Chemical formula: C₂₄H₃₄N₄O₅S  Molecular mass: 490.62 g/mol  PubChem compound: 3476

Interactions

Glimepiride interacts in the following cases:

Alcohol

Alcohol intake may potentiate or weaken the hypoglycaemic action of glimepiride in an unpredictable fashion.

H₂ antagonists, beta-blockers, clonidine, reserpine

H2 antagonists, beta-blockers, clonidine and reserpine may lead to either potentiation or weakening of the blood-glucose-lowering effect.

Under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation to hypoglycaemia may be reduced or absent.

Coumarin derivatives

Glimepiride may either potentiate or weaken the effects of coumarin derivatives.

Drugs that enhance weakening of the blood-glucose-lowering effect

Weakening of the blood-glucose-lowering effect and, thus raised blood glucose levels may occur when one of the following medicinal products is taken for example:

  • Oestrogens and progestogens.
  • Saluretics, thiazide diuretics.
  • Thyroid stimulating agents, glucocorticoids.
  • Phenothiazine derivatives, chlorpromazine.
  • Adrenaline and sympathicomimetics.
  • Nicotinic acid (high dosages) and nicotinic acid derivatives.
  • Laxatives (long term use).
  • Phenytoin, diazoxide.
  • Glucagon, barbiturates and rifampicin.
  • Acetazolamide.

CYP2C9 inducers, CYP2C9 inhibitors

Glimepiride is metabolized by cytochrome P450 2C9 (CYP2C9). Its metabolism is known to be influenced by concomitant administration of CYP2C9 inducers (e.g. rifampicin) or inhibitors (e.g. fluconazole).

Results from an in-vivo interaction study reported in literature show that glimepiride AUC is increased approximately 2-fold by fluconazole, one of the most potent CYP2C9 inhibitors.

Ciclosporin

Glimepiride increases the activity of cyclosporin.

Colesevelam

Colesevelam binds to glimepiride and reduces glimepiride absorption from the gastro-intestinal tract. No interaction was observed when glimepiride was taken at least 4 hours before colesevelam. Therefore, glimepiride should be administered at least 4 hours prior to colesevelam.

Drugs that enhance blood-glucose-lowering effect

Potentiation of the blood-glucose-lowering effect and, thus in some instances hypoglycaemia may occur when one of the following medicinal products is taken, for example:

  • Phenylbutazone, azapropazone and oxyfenbutazone.
  • Insulin and oral antidiabetic products, such as metformin.
  • Salicylates and p-amino-salicylic acid.
  • Anabolic steroids and male sex hormones.
  • Chloramphenicol, certain long acting sulfonamides, tetracyclines, quinolone antibiotics and clarithromycin.
  • Coumarin anticoagulants.
  • Fenfluramine.
  • Disopyramide.
  • Fibrates.
  • ACE inhibitors.
  • Fluoxetine, MAO-inhibitors.
  • Allopurinol, probenecid sulfinpyrazone.
  • Sympatholytics.
  • Cyclophosphamide, trophosphamide and iphosphamides.
  • Miconazole, fluconazole.
  • Pentoxifylline (high dose parenteral).
  • Tritoqualine

Pregabalin

Concomitant administration of glimepiride with prigabaline increases the risk of edema.

G6PD-deficiency

Treatment of patients with G6PD-deficiency with sulfonylurea agents can lead to hemolytic anaemia.

Since glimepiride belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD-deficiency and a non-sulfonylurea alternative should be considered.

Pregnancy

Risk related to the diabetes

Abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities and perinatal mortality. So the blood glucose level must be closely monitored during pregnancy in order to avoid the teratogenic risk. The use of insulin is required under such circumstances. Patients who consider pregnancy should inform their physician.

Risk related to glimepiride

There are no adequate data from the use of glimepiride in pregnant women. Animal studies have shown reproductive toxicity which likely was related to the pharmacologic action (hypoglycaemia) of glimepiride.

Consequently, glimepiride should not be used during the whole pregnancy. In case of treatment by glimepiride, if the patient plans to become pregnant or if a pregnancy is discovered, the treatment should be switched as soon as possible to insulin therapy.

Nursing mothers

The excretion in human milk is unknown. Glimepiride is excreted in rat milk. As other sulfonylureas are excreted in human milk and because there is a risk of hypoglycaemia in nursing infants, breast-feeding is advised against during treatment with glimepiride.

Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

The patient’s 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. It should be considered whether it is advisable to drive or operate machinery in these circumstances.

Adverse reactions


The following adverse reactions from clinical investigations were based on experience with glimepiride and other sulfonylureas, were listed below by system organ class and in order of decreasing incidence (very common: ≥1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1,000 to <1/100; rare: ≥1/10,000 to <1/1,000; very rare: <1/10,000), not known (cannot be estimated from the available data).

Blood and lymphatic system disorders

Rare: thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, erythropenia, haemolytic anaemia and pancytopenia, which are in general reversible upon discontinuation of medication.

Not known: severe thrombocytopenia with platelet count less than 10,000/µl and thrombocytopenic purpura.

Immune system disorders

Very rare: leukocytoclastic vasculitis, mild hypersensitivity reactions that may develop into serious reactions with dyspnoea, fall in blood pressure and sometimes shock.

Not known: cross-allergenicity with sulfonylureas, sulfonamides or related substances is possible.

Metabolism and nutrition disorders

Rare: hypoglycaemia.

These hypoglycaemic reactions mostly occur immediately, may be severe and are not always easy to correct. The occurrence of such reactions depends, as with other hypoglycaemic therapies, on individual factors such as dietary habits and dosage.

Eye disorders

Not known: visual disturbances, transient, may occur especially on initiation of treatment, due to changes in blood glucose levels.

Gastrointestinal disorders

Very rare: nausea, vomiting, diarrhoea, abdominal distension, abdominal discomfort and abdominal pain, which seldom lead to discontinuation of therapy.

Hepato-biliary disorders

Very rare: hepatic function abnormal (e.g. with cholestasis and jaundice), hepatitis and hepatic failure.

Not known: hepatic enzymes increased.

Skin and subcutaneous tissue disorders

Not known: hypersensitivity reactions of the skin may occur as pruritus, rash, urticaria and photosensitivity.

Investigations

Very rare: blood sodium decrease.

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