Drug General Information (ID: DDI1ZXFDNV)
Drug Name			Chlorthalidone		Drug Info		Metformin		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antihypertensive Agents				Antidiabetic Agents
Structure

Mechanism of Chlorthalidone-Metformin Interaction (Severity Level: Moderate)
Increased risk of metabolic acidosis Click to Show/Hide Mechanism Graph
Drug Name		Chlorthalidone				Metformin
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 Chlorthalidone and Metformin
Antagonize the effect of antidiabetic agents Click to Show/Hide Mechanism Graph
Drug Name		Chlorthalidone				Metformin
Mechanism 2		Hyperglycemia				Antidiabetic agent
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 Chlorthalidone
Mechanism 3		Hyperglycemic effects				Antidiabetic agent
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 Chlorthalidone

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.