Distribution: After intravenous administration in normal subjects, the distribution volume

(Vd) was 8.8 L (113 mL / kg) and the total body clearance (CL) was 47.8 mL / min. Protein
binding is greater than 99.5%.

Metabolism: Glimepiride is completely metabolized by oxidative biotransformation after

intravenous or oral administration. The main metabolites are cyclohexylmethylol
derivatives (M1) and carboxyl derivatives (M2). Cytochrome P450 2C9 has been shown to
be involved in the biotransformation of glimepiride to M1. One or more of the M1 to M2
cytosolic enzymes are further metabolized. In animal models, M1 (but not M2) has about
one-third of the pharmacological activity compared to the mother. However, it is unclear
whether the hypoglycemic effect of M1 has clinical significance in humans.

Genetic polymorphisms may reduce the metabolic capacity of 2C9. Some clinical studies
conducted in a few subjects have shown that genetic polymorphisms of CYP2C9 can affect
the pharmacokinetics of AMARYL, and carriers of CYP2C9 * 3 variants (3-8.5% of whites)
may have lower (18-75%) oral clearance and AMARYL exposure (AUC (0-∞)) were 1.3 to 5.2
times higher. Therefore, individuals expressing this variant genotype may tend to increase
their response to AMARYL. In addition, CYP2C9 * 3 / * 3 and * 2 / * 3 genotypes may
increase the risk of hypoglycemia.

Excretion: When a single oral 14C-glimepiride is taken, the total radioactivity recovered in
the urine within 7 days accounts for about 60%, and the metabolites M1 (main) and M2
account for 80-90% of the urine recovered. The total amount of radioactivity recovered in
the feces is about 40%, while the metabolites M1 and M2 (predominant) account for about
70% of the recovered feces. After intravenous administration to the patient, no significant
bile excretion of glimepiride or its M1 metabolite was observed.

Glimepiride warning

Glimepiride helps control blood sugar but does not cure diabetes. Even if you feel good,
you should continue to take glimepiride. This drug should not be used to treat patients with
type 1 diabetes, a disease in which the body does not produce insulin. If your body
produces insulin naturally, glimepiride will only help lower blood sugar.

In one study, patients taking diabetes-like drugs to treat diabetes were more likely to die of
heart disease than those receiving dietary changes and insulin therapy.

Discuss the risks of this treatment with your doctor.

When taking glimepiride, tell your doctor if:

Pregnancy, planning pregnancy or breastfeeding

Undergoing surgery, including dental surgery

Have had G6PD deficiency (hereditary hematopathy)

Suffer from hormonal diseases involving the adrenal glands, pituitary or thyroid
Suffer from heart, kidney or liver disease

Negative Effects

As with other sulfonylureas, glimepiride is generally well tolerated, and it is uncommon for
adverse reactions to be severe enough to discontinue treatment. The main side effect is
hypoglycemia, which can occur 4 hours after a meal and usually indicates an overdose. Mild
adverse reactions include gastrointestinal reactions (nausea, vomiting, heartburn, upper
abdominal pressure or feeling of fullness, and diarrhea). Very rare severe effects include
anemia, agranulocytosis, pancytopenia, cholestatic jaundice, vasculitis, and transient
changes in liver function, but there is no evidence to link these factors to the drug.

side effect:

As with any type of drug, aryl arenes have some side effects. However, it may affect
different people in different ways. Just because other people have side effects does not
mean you will get these.

If you have problems with these side effects, consult your doctor or pharmacist:

Hair loss

Odour in the mouth

Gain weight

Minor nausea or vomiting

dizziness

Hypoglycemia (hypoglycemia), see above.

This medicine may make your skin sensitive to the sun and may cause a rash or sunburn.
Use sunscreen outdoors. Avoid using fluorescent lamps or sun beds.

Call your doctor immediately if you have any of the following side effects:

Unexplained fever, chills, or sore throat

Abnormal bleeding or bruising

Yellow skin or eyes, dark urine or light bowel movements

Rash or urticaria

Edema, swelling of the legs or unexpected weight gain.

If you have any of the following, stop taking your medication and seek medical help
immediately:

• severe allergic reactions (severe skin reactions, swelling of the throat, lips, tongue,
difficulty breathing or swallowing)

This is not a complete list of side effects. If you have any unexpected effects when taking
Amaryl, contact your doctor or pharmacist.