openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 2 matching rows.
warnings
WARNINGS WARNING: LACTIC ACIDOSIS: Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL (see PRECAUTIONS ). Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g. carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided (see DOSAGE AND ADMINISTRATION , CONTRAINDICATIONS , and PRECAUTIONS ) . If metformin-associated lactic acidosis is suspected, immediately discontinue metformin HCl extended-release tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended (see PRECAUTIONS ).
warnings table
<table border="1" cellpadding="0" cellspacing="0"> <col width="468.3pt"/> <tbody> <tr> <td> <paragraph> <content styleCode="bold">WARNING: LACTIC ACIDOSIS:</content> </paragraph> <paragraph> <content styleCode="bold">Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL (see <linkHtml href="#LINK_e6535e3c-3fe6-4eff-afb5-5f1efadf52a0">PRECAUTIONS</linkHtml>). </content> </paragraph> <paragraph>Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g. carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment. </paragraph> <paragraph>Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided (see <content styleCode="bold"> <content styleCode="bold"> <linkHtml href="#LINK_4750f4cc-a3a5-470c-ad9f-3fa35f6220dc">DOSAGE AND ADMINISTRATION</linkHtml> </content> </content>, <content styleCode="bold"> <content styleCode="bold"> <linkHtml href="#LINK_45c321f6-1e6c-48fb-8a5a-07ce947a65ac">CONTRAINDICATIONS</linkHtml> </content> </content>, and <content styleCode="bold"> <content styleCode="bold"> <linkHtml href="#LINK_e6535e3c-3fe6-4eff-afb5-5f1efadf52a0">PRECAUTIONS</linkHtml> </content>)</content>. </paragraph> <paragraph>If metformin-associated lactic acidosis is suspected, immediately discontinue metformin HCl extended-release tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended (see <content styleCode="bold"> <content styleCode="bold"> <linkHtml href="#LINK_e6535e3c-3fe6-4eff-afb5-5f1efadf52a0">PRECAUTIONS</linkHtml> </content>).</content> </paragraph> </td> </tr> </tbody> </table>
ADVERSE REACTIONS In worldwide clinical trials over 900 patients with type 2 diabetes have been treated with metformin HCl extended-release tablets in placebo- and active-controlled studies. In placebo-controlled trials, 781 patients were administered metformin HCl extended-release tablets and 195 patients received placebo. Adverse reactions reported in greater than 5% of the metformin HCl extended-release tablets patients, and that were more common in metformin HCl extended-release tablets - than placebo-treated patients, are listed in Table 12 . Table 12: Most Common Adverse Reactions (> 5 Percent) in Placebo-Controlled Studies of Metformin HCl Extended-Release Tablets * Metformin HCl Extended-Release Tablets N=781 Placebo N=195 Adverse Reactions % of Patients Diarrhea 9.6 2.6 Nausea / Vomiting 6.5 1.5 * Reactions that were more common in metformin HCl extended-release tablets-than placebo-treated patients. Diarrhea led to discontinuation of study medication in 0.6% of patients treated with metformin HCl extended-release tablets. Additionally, the following adverse reactions were reported in ≥1% to ≤5% of metformin HCl extended-release tablets patients and were more commonly reported with metformin HCl extended-release tablets than placebo: abdominal pain, constipation, distention abdomen, dyspepsia/heartburn, flatulence, dizziness, headache, upper respiratory infection, taste disturbance. Cholestatic, hepatocellular, and mixed hepatocellular liver injury have been reported with postmarketing use of metformin.