Drug General Information (ID: DDIZWIFKAB)
Drug Name			Metformin		Drug Info		Hydrochlorothiazide		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antidiabetic Agents				Diuretics
Structure

Mechanism of Metformin-Hydrochlorothiazide Interaction (Severity Level: Moderate)
Increased risk of metabolic acidosis Click to Show/Hide Mechanism Graph
Drug Name		Metformin				Hydrochlorothiazide
Mechanism 1		Metabolic acidosis				Metabolic acidosis
Key Mechanism Factor 1
		Factor Name		Metabolic acidosis
		Factor Description		Metabolic acidosis is a clinical disorder defined as a pH below 7.35 and low HCO3 levels. Metabolic acidosis occurs when the body produces too much acid or the kidneys are unable to remove enough acid from the body. Symptoms vary depending on the underlying cause, but some common symptoms are as follows: shortness of breath, confusion, fatigue, shock, fruity taste of the patient's breath (diabetic ketoacidosis), rapid heartbeat, headache, weakness, and nausea.
Mechanism Description		Increased risk of metabolic acidosis by the combination of Metformin and Hydrochlorothiazide
Antagonize the effect of antidiabetic agents Click to Show/Hide Mechanism Graph
Drug Name		Metformin				Hydrochlorothiazide
Mechanism 2		Antidiabetic agent				Hyperglycemia
Key Mechanism Factor 2
		Factor Name		Antidiabetic agents
		Factor Description		The hypoglycemic effect of antidiabetes may be reduced, leading to higher blood glucose, increased blood glucose fluctuations, and the possibility of hyperglycemic complications
Mechanism Description		Antagonize the effect of Metformin when combined with Hydrochlorothiazide
Mechanism 3		Antidiabetic agent				Hyperglycemic effects
Key Mechanism Factor 3
		Factor Name		Antidiabetic agents
		Factor Description		The hypoglycemic effect of antidiabetes may be reduced, leading to higher blood glucose, increased blood glucose fluctuations, and the possibility of hyperglycemic complications
Mechanism Description		Antagonize the effect of Metformin when combined with Hydrochlorothiazide

Recommended Action
Management		Close clinical monitoring is recommended if diuretics are coadministered with antidiabetic agents. Patients should be advised to monitor their blood glucose and to promptly notify their doctor if they experience possible signs of lactic acidosis (such as malaise, myalgia, respiratory distress, hyperventilation, slow or irregular heartbeat, somnolence, abdominal upset) or loss of glycemic control. Dose adjustments of metformin may be required. Likewise, patients should be observed for hypoglycemia if diuretics are withdrawn from their therapeutic regimen.

References
1	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2	Multum Information Services, Inc. Expert Review Panel.
3	Product Information. Glucophage (metformin). Bristol-Myers Squibb, Princeton, NJ.