In addition to diet and exercise, glimepiride (Amaryl), a long-acting third-generation sulfonylurea, is used to treat people with diabetes mellitus.

Glimepiride (Amaryl) Uses:

• Diabetes mellitus, type 2:

  • Glimepiride is used as an adjunct to diet and exercise to improve diabetic control in adults with type 2 diabetes mellitus

Glimepiride (Amaryl) Dose in Adults

Glimepiride (Amaryl) Dose in the treatment of type 2 Diabetes mellitus: Oral:

• Initially, it can be given as 1 to 2 mg once a day. 
• It can be increased by 1 to 2 mg every 1 to 2 weeks, up to a maximum of 8 mg once per day, depending on how it responds.

Changing from long half-life agent therapy:

• When switching from a long halflife treatment (such chlorpropamide) to glimepiride due to overlapping hypoglycemic effects, monitor the patient  carefully for hypoglycemia for 1 to 2 weeks.

Use in Children:

Not indicated.

Pregnancy Risk Category: C

• Infants born to mothers who took a sulfonylurea during pregnancy can experience severe hypoglycemia that can last up to 10 days. 
• There are not many studies on the effects of glimepiride during pregnancy.
• Avoid exposure to it during pregnancy.
• Congenital malformations and maternal hyperglycemia are associated with adverse pregnancy outcomes.
• By maintaining maternal glucose and HbA1c levels as close to their goal levels as feasible, but without resulting in severe hypoglycemia, it is possible to prevent bad consequences from developing before conception and during pregnancy.
• Pregnant women with diabetes should not be treated with glimepiride alone.

Use of limepiride during lactation

• It is not known whether breast milk secretes it.
• Clinically, hyperglycemia treatment with sulfonylurea must be evaluated.
• The benefits of the therapy should outweigh any risks for breastfeeding mothers. To prevent adverse side effects.
• Hypoglycemia should be monitored in infants.

Glimepiride (Amaryl) Dose in Kidney disease:

It can be taken as little as 1 mg daily at first. To avoid hypoglycemia, the dose titration should be conservative. If eGFR is 15mL/minute/1.73m2, consider alternative treatment.

Glimepiride (Amaryl) Dose in Liver disease:

• It is not known if dose adjustments can be made in liver disease. 
• The studies on dose adjustments are however limited.
• Patients with cirrhosis should be cautiously titrated up to avoid hypoglycemia

Common Side Effects of Glimepiride (Amaryl):

• Endocrine & metabolic:

  • Hypoglycemia

Less Common Side Effects of Glimepiride (Amaryl):

• Central nervous system:

  • Dizziness
  • Headache

• Gastrointestinal:

  • Nausea

• Hepatic:

  • Increased serum ALT

• Respiratory:

  • Flu-like symptoms

• Miscellaneous:

  • Accidental injury

Contraindications to Glimepiride (Amaryl):

• Hypersensitivity to this drug or the sulfonamides is a clear contraindication.
• It is interesting to note that despite the fact that the FDA approved product labelling specifies that this medication  should not be taken with other sulfonamide-containing medications, the scientific validity of this claim has been questioned.
• Due to similar physiochemical properties, cross-sensitities can be allergenic. It is therefore important to exercise caution.

Canadian labeling: Additional contraindications, but not in the US labeling

• Pregnancy.
• Breastfeeding
• Type 1 diabetes.
• Diabetic ketoacidosis, with or without coma
• Grave renal or liver impairment

Warnings and precautions

• Cardiovascular mortality

  • These oral hypoglycemic drugs are associated with higher morbidity and deaths than insulin or insulin plus diet.
  • However, large trials were not conducted to support the above-stated hypothesis.
  • Patients suffering from advanced atherosclerotic diseases should be prescribed additional anti-hyperglycemic agents.

• Hypoglycemia

  • All sulfonylurea medications can cause severe hypoglycemia.
  • Hypoglycemia can be exacerbated by inadequate caloric intake or concomitant use of oral hypoglycemic drugs. It can also be worsened by alcohol ingestion.
  • It is important to exercise caution when prescribing this drug for frail and elderly diabetics.

• Allergy to sulfonamide ("sulfa")

  • Wide ranging contraindications for patients who have previously experienced an adverse reaction to  sulfonamides are listed on FDA-approved product labels for drugs that contain sulfonamide chemical groups.
  • Crossreactivity is possible
  • Crossreactivity concerns have been raised for all compounds with the sulfonamide structural.
  • Recent studies have shown that cross-reactivity between non-antibiotic sulfonamides or antibiotic sulfonamides has been reduced.
  • Recent trials with non-antibiotics sulfonamide have shown that anaphylaxis is not common.
  • Less research has been done on type IV reactions, which are T-cell mediated and include skin rashes including  maculopapular rash. 
  • Based on the most recent results from several investigations, it is impossible to rule out this possibility.
  • Some clinicians will avoid treating patients with severe Stevens-Johnson syndrome (or TEN) if there are any prior cases.

• Deficiency of Glucose-6phosphate dehydrogenase(G6PD) 

  • Patients with G6PD deficits may be more susceptible to hemolytic anaemia brought on by sulfonylureas.
  • Postmarketing surveillance has also shown cases in patients who have not been deficient in G6PD.
  • Patients with G6PD deficiency should exercise caution

• Hepatic impairment

  • Hypoglycemia is more common in patients with hepatic impairment. It is recommended to be cautious.

• Renal impairment

  • In renal diseases, it is a good idea to reduce your dose as it can lead to hypoglycemia.

• Stress-related disorders:

  • When under stress or in a coma, oral hypoglycemic must be switched to insulin.

Glimepiride: Drug Interaction

Monitoring parameters:

• You should be aware of symptoms include extreme appetite, perspiration, and exhaustion.
• Patients who have stable glycemic control and are making progress toward their treatment objectives should have their blood sugar and HbA1c checked at least twice a year.
• Patients who are on therapy change or who are not meeting these targets must test every three months.
• Tests of renal function.

How to administer Glimepiride (Amaryl)?

Oral:

• Take the following instructions orally.
• Patients who are NPOs or have a reduced caloric intake might need to be given lower doses in order to prevent hypoglycemia.

Mechanism of action of Glimepiride (Amaryl):

It raises insulin sensitivity at peripheral target sites, enhances pancreatic beta cell insulin production, and decreases hepatic glucose output.

The onset of action:

• Peak effect: Blood glucose reductions: 2 to 3 hours

Duration:

• 24 hours

Absorption:

• 100%

Protein binding:

• >99.5%

Metabolism:

• Hepatic oxidation via CYP2C9 to M1 metabolite (~33% activity of parent compound); further oxidative metabolism to inactive M2 metabolite

Half-life elimination:

• 5 to 9 hours

Time to peak, plasma:

• 2 to 3 hours

Excretion:

• Urine (60%, 80% to 90% as M1 and M2 metabolites);
• feces (40%, 70% as M1 and M2 metabolites)

International Brand Names of Glimepiride:

• Amaryl
• APO-Glimepiride
• GEN-Glimepiride
• NOVO-Glimepiride
• PMS-Glimepiride
• RATIO-Glimepiride
• SANDOZ Glimepiride
• Acotril
• Aforglim
• Amadiab
• Amagreen
• Amapirid
• Amarax
• Amarel
• Amarine
• Amaryl
• Amarylle
• Amepirise
• Amorin
• Arya
• Aylide
• Azulix
• Azulix-1
• Azulix-2
• Azulix-4
• Betaglid
• Betastimul
• Canzeal
• Daniglim
• Daol
• Diaglime
• Diaglip
• Dialosa
• Diameril
• Diapirid
• Diapride
• Diaryl
• Dimaril
• Dimirel
• Efinex
• Endial
• Euglim
• Fertin
• Getryl
• Getzalim
• Glaryl
• Glazer
• Glemaz
• Glemep
• Glim
• Glimaccord
• Glimaryl
• Glimed 1
• Glimep
• Glimepid
• Glimepigen
• Glimeryl
• Glimide
• Glimirid
• Glimuilin-2
• Glimulin
• Glimvaz
• Glimxl
• Gliparil
• Glipiryl
• Glorion
• Glucozen
• Gludine
• Gluvas
• Glypride
• Hanmaryl
• Hexan
• K-Glim
• Losu-3
• Mapryl
• Melital
• Mepigryl
• Mericle
• Metrix
• Miaryl
• Neoacotril
• Norizec
• Oltar
• Orbide
• Pimaryl
• Sinperan
• Solosa
• Sulfast
• Velacom
• Versibet

Glimepiride Brand Names in Pakistan: