Dosage Recommendations:
Selecting the starting dose of Pioglitazone Hydrochloride and glimepiride should be based on the patient's current regimen of Pioglitazone Hydrochloride and/or sulfonylurea.
It is recommended that a single dose of the drug be administered once daily with the first main meal.

• Starting dose for patients currently on glimepiride monotherapy:
  Based on the usual starting dose of Pioglitazone Hydrochloride (15 mg or 30 mg daily), therapy may be initiated at 2 mg/30 mg or 4 mg/30 mg tablet once daily, and adjusted after assessing adequacy of therapeutic response.
  
• Starting dose for patients currently on Pioglitazone Hydrochloride monotherapy:
  Based on the usual starting doses of glimepiride (1 mg or 2 mg once daily), and Pioglitazone Hydrochloride 15 mg or 30 mg,therapy may be initiated at 2 mg/ 30 mg tablet once daily, and adjusted after assessing adequacy of therapeutic response.
  
• Starting dose for patients switching from combination therapy of Glimepiride plus Pioglitazone Hydrochloride as separate tablets:
  Therapy may be initiated with 2 mg/30 mg or 4 mg/30 mg tablet based on the dose of Glimepiride and Pioglitazone Hydrochloride already being taken. Patients who are not controlled with 15 mg of Pioglitazone Hydrochloride in combination with Glimepiride should be carefully monitored when switched to combination therapy.
• Starting dose for patients currently on a different sulfonylurea monotherapy or switching from combination therapy of Pioglitazone Hydrochloride plus a different sulfonylurea (e.g. glyburide, glipizide, chlorpropamide, tolbutamide, acetohexamide):
  Based on the maximum starting dose of 2 mg Glimepiride, the dosage should be limited initially to a starting dose of 2 mg/ 30 mg once daily, and adjusted after assessing adequacy of therapeutic response.

Maximum Recommended Dose: The maximum recommended daily dose for Pioglitazone Hydrochloride is 45 mg and the maximum recommended daily dose for glimepiride is 8 mg. The drug should therefore not be given more than once daily at any of the strengths.

CONTRAINDICATIONS
Glimepiride and Pioglitazone Hydrochloride combination is contraindicated in patients with known hypersensitivity to Glimepiride and Pioglitazone Hydrochloride, diabetic ketoacidosis with or without coma, in patients with symptomatic heart failure.

ADVERSE EFFECTS
Headache, vomiting, diarrhea, nausea, limb pain, edema, weight gain, stomach pain, unusual or unexplained tiredness and loss of appetite.

WARNINGS AND SPECIAL PRECAUTIONS
Pregnancy
Pregnancy category C
The drug should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus.
Nursing mothers
It is not known whether Glimepiride or Pioglitazone Hydrochloride are secreted in human milk. Because the potential for hypoglycemia in nursing infants may exist, the drug should not be administered to a lactating mother.
Renal impairment
Glimepiride: A starting dose of 1 mg glimepiride may be given to patients with kidney disease, and the dose may be titrated based on fasting blood glucose levels.
Pioglitazone Hydrochloride: No dose adjustment in patients with renal dysfunction is recommended.
Hepatic impairment
Therapy with Glimepiride and Pioglitazone Hydrochloride combination should not be initiated if the patient exhibits clinical evidence of active liver disease or serum transaminase levels (ALT) exceeds 2.5 times the upper limit of normal.

DRUG INTERACTIONS
Glimepiride
The hypoglycemic action of sulfonylureas may be potentiated by certain drugs, including NSAIDs, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid, monoamineoxidase inhibitors and beta adrenergic blocking agents. Due to the potential drug interaction between these drugs and glimepiride, the patient should be observed closely for hypoglycemia when these drugs are co-administered.
Certain drugs including diuretics, corticosteroids, phenothiazines, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics and isoniazid tend to produce hyperglycemia when co- administered with glimepiride, the patient should be observed for loss of glycemic control.
Pioglitazone Hydrochloride
Gemfibrozil: Concomitant administration of gemfibrozil, an inhibitor of cytochrome P450 with Pioglitazone Hydrochloride resulted in an increase in the plasma concentration of Pioglitazone Hydrochloride.
Rifampin: Concomitant administration of rifampin an inducer of cytochrome P450 with Pioglitazone Hydrochloride resulted in a decrease in the plasma concentration of Pioglitazone Hydrochloride.

OVERDOSAGE
Glimepiride: Over dosage of sulfonylureas, including glimepiride, can produce hypoglycemia. Mild hypoglycemic symptoms should be treated aggressively with oral glucose and adjustments in drug dosage and/or meal patterns. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization.
Pioglitazone Hydrochloride: In case of overdosage, appropriate supportive treatment should be initiated according to patient’s clinical signs and symptoms.

STORAGE
Store at room temperature. Protect from light, heat and moisture. Keep all medicines out of the reach of children.

PRESENTATION
GLIO-P 2 mg/ 30 mg tablets, Pack of 2 x 7’s
GLIO-P 4 mg/ 30 mg tablets, Pack of 2 x 7’