Version July 2025
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/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.
Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), ≥65 years, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, 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 in the full prescribing information.
If metformin-associated lactic acidosis is suspected, immediately discontinue metformin and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.
Diabetes mellitus, type 2, treatment: Note: Allow 1 to 2 weeks between dose titrations. Generally, clinically significant responses are not seen at doses less than 1,500 to 2,000 mg/day (Ref); however, a lower recommended starting dose with a gradual increase in dosage is recommended to minimize GI symptoms.
Immediate release: Children ≥10 years and Adolescents: Oral: Initial: 500 to 1,000 mg once daily or 500 mg twice daily; increase by 500 mg every 1 to 2 weeks as tolerated; maximum dose: 1,000 mg twice daily or 850 mg 3 times daily (Ref).
Extended release: Note: Fewer GI effects may be seen with extended-release products; however, no pediatric studies have compared extended-release products to standard metformin (Ref).
Children ≥10 years and Adolescents: Limited data available: Oral: Initial: 500 to 1,000 mg once daily for 7 days; may increase dose by 500 mg increments every 1 to 2 weeks as tolerated; maximum daily dose: 2,000 mg/day (Ref). Note: If glycemic control is not achieved at maximum dose, may divide dose and administer twice daily (Ref).
Surgical patients (Ref):
Minor surgeries (surgery lasting <2 hours, with or without sedation or anesthesia, where rapid recovery is anticipated and patient is expected to be able to eat within 2 to 4 hours): Discontinue metformin the day of surgery; monitor glucose closely; administer rapid- or short-acting insulin if needed; resume metformin after oral intake is tolerated.
Major surgeries (any surgery under anesthesia that is more than minor, typically lasting >2 hours with a high likelihood of postoperative nausea, vomiting, and/or inability to adequately feed after procedure): Discontinue metformin the day of surgery; monitor glucose closely; administer rapid- or short-acting insulin if needed. Withhold metformin for 24 hours following surgery and until normal renal function has been confirmed.
Obesity; severe, adjunct therapy with lifestyle interventions: Limited data available; data have shown modest efficacy; reported mean BMI reduction −0.86 to −1.16 kg/m2, although reported efficacy endpoints/outcomes in trials are variable (Ref). Overall, due to limited efficacy, some experts do not consider metformin a weight loss treatment option for pediatric obesity (Ref). Optimal treatment duration not established; duration in trials varied from 3 to 12 months. Daily multivitamin supplement may be considered with therapy (Ref).
Immediate release: Dosing regimens variable: Children ≥6 years and Adolescents: Oral: Initial: 500 mg once or twice daily, may titrate upward at weekly intervals by 500 mg/day increments; reported final doses: 1,000 to 2,000 mg/day in 2 divided doses; a meta-analysis showed that metformin 2,000 mg/day intervention was most identified as most effective relative to lower doses or lifestyle modifications in adolescents without diabetes (Ref). Age-dependent efficacy findings are conflicting; some data suggest that metformin may have greater efficacy in prepubertal children and others have shown a greater effect in pubertal subjects (11 to 17 years) (Ref). A low dose (850 mg/day) over a prolonged period (24 months) showed positive effects on body composition (weight and BMI standard deviation scores) and other metabolic and inflammatory markers (eg, fat mass, liver fat, leptin, highly sensitive C-reactive protein) in a small, placebo-controlled trial of 22 subjects (metformin=13; age range: 6 to 13 years) (Ref).
Extended release: Adolescents: Oral: Initial: 500 mg once daily with dinner for 2 weeks; increase to 1,000 mg once daily for 2 weeks, and then 2,000 mg once daily; may slow titration if adverse GI effects (Ref).
Weight gain, atypical antipsychotic induced, treatment: Limited data available:
Immediate release: Note: In trials, all patients were diagnosed with autism spectrum disorder; trials used metformin oral solution and slowly titrated the dose to minimize GI effects and maximize tolerability. After 16 weeks of therapy, patients receiving metformin had a statistically significant decrease in BMI z-scores (primary efficacy outcome) as well as other secondary outcomes (eg, raw weight, BMI) compared to placebo. A 16-week, open-label extension study showed results achieved in the treatment group were maintained without further decreases (Ref).
6 to 9 years: Oral: Initial: 250 mg with evening meal for 1 week, then 250 mg twice daily for 1 week, then 500 mg twice daily.
10 to 17 years: Oral: Initial: 250 mg with evening meal for 1 week, then 250 mg twice daily for 1 week, then 500 mg twice daily for 1 week, then 850 mg twice daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥10 years and Adolescents: Oral: Immediate release, extended release:
eGFR >45 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 30 to 45 mL/minute/1.73 m2:
Preexisting impairment: Initiation of therapy is not recommended.
During therapy:
If eGFR falls between 30 and <45 mL/minute/1.73 m2: Consider risk/benefit ratio for continuing therapy.
If eGFR falls to <30 mL/minute/1.73 m2:Discontinue therapy.
eGFR <30 mL/minute/1.73 m2: Use is contraindicated.
Children ≥10 years and Adolescents: Avoid metformin; liver disease is a risk factor for the development of lactic acidosis during metformin therapy.
(For additional information see "Metformin: Drug information")
Antipsychotic-induced weight gain, treatment (off-label use):
Note: When used as an early intervention strategy, the goal is plateau of weight gain; however, reversal of weight gain may also be possible. With weight loss, goals of at least 5% of baseline body weight within 6 months are suggested (Ref).
Immediate release: Oral: Initial: 500 mg once or twice daily; to minimize GI effects gradually increase dose based on response and tolerability in increments of 500 mg every 1 to 2 weeks up to a target dose of 1 g twice daily (Ref).
Extended release: Oral: 500 mg once daily; to minimize GI effects gradually increase dose based on response and tolerability in increments of 500 mg every 1 to 2 weeks up to a target dose of 2 g once daily (Ref).
Diabetes mellitus, type 2, prevention (off-label use):
Note: For select patients with prediabetes, particularly for those with BMI ≥35 kg/m2, age <60 years, and patients with prior gestational diabetes mellitus, in whom lifestyle interventions fail to improve glycemic indices (Ref).
Immediate release: Oral: Initial: 850 mg once daily for 1 month, then increase to 850 mg twice daily; unless GI adverse effects warrant a longer titration period (Ref).
Diabetes mellitus, type 2, treatment:
Note: In patients in whom glycemic targets are not met despite diet, exercise, and metformin, combination therapy is necessary to achieve optimal results (Ref).
Immediate release:
Initial: Oral: 500 mg once or twice daily or 850 mg once daily (Ref).
Dosage adjustments: Oral: The dose should be increased gradually to minimize GI adverse effects. Titration strategies vary widely, but usually done in 500 mg or 850 mg increments every 7 days (range: 5 days to 1 month).
Usual maintenance dosage: Oral: 1 g twice daily or 850 mg twice daily (Ref).
Maximum: Oral: 2.55 g/day. Modest additional benefit has been observed with doses up to ~2.5 g/day; however, GI adverse effects may limit use (Ref). If doses >2 g/day are needed, consider administering in 3 divided doses to minimize GI adverse effects.
Extended release:
Initial: Oral: 500 mg to 1 g once daily
Dosage adjustments: Oral: The dose should be increased gradually to minimize GI adverse effects. Titration strategies vary widely, but usually done in 500 mg increments every 7 days (range: 7 days to 6 weeks).
Maximum: Oral: 2 g/day. If glycemic control is not achieved at maximum dose given once daily, may divide maximum dose and administer twice daily.
Gestational diabetes mellitus, treatment (alternative agent) (off-label use): Immediate release: Oral: Initial: 500 mg once or twice daily; increase dosage to meet glycemic targets, typically over 1 to 2 weeks, up to a maximum of 2 to 2.5 g daily in 2 to 3 divided doses. If targets not achieved with metformin alone, insulin may be added (Ref). Note: Insulin is the preferred medication for gestational diabetes as it does not cross the placenta to a measurable extent; all oral agents lack long-term safety data (Ref).
Ovarian hyperstimulation syndrome prevention in patients with polycystic ovary syndrome undergoing in vitro fertilization/intracytoplasmic sperm injection (alternative agent) (off-label use ):
Note: For use prior to and/or during ovarian stimulation in patients undergoing a gonadotropin-releasing hormone agonist protocol (Ref).
Immediate release: Oral: Initial: 500 mg once daily; increase dose gradually as tolerated up to 2 g/day in divided doses (Ref). Dosage range studied in trials: 1 to 2.55 g/day in 2 or 3 divided doses; use of ER products may reduce GI adverse effects (Ref). Discontinue metformin with a positive pregnancy test (Ref).
Metformin conversion recommendations:
Conversion from IR to ER dosage forms: Patients receiving metformin immediate-release may be switched to metformin extended-release once daily at the same total daily dose, up to 2 g once daily. However, in patients who are doing well with immediate-release metformin, some experts recommend they continue using it, as there is little additional benefit documented with ER tablets (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary. Monitor renal function at least annually.
eGFR >45 to <60 mL/minute/1.73 m2: No dosage adjustment necessary. Metformin plasma concentrations may be higher compared to patients with an eGFR ≥60 mL/minute/1.73 m2; increase monitoring of renal function (eg, every 3 to 6 months) (Ref).
eGFR 30 to 45 mL/minute/1.73 m2:
Initiation of therapy: Use generally not recommended (Ref); however, initial therapy with 500 mg once daily with the evening meal titrated to 500 mg twice daily, if tolerated, with close monitoring of kidney function has been recommended by some experts (Ref).
Continuation of existing therapy: May continue at a reduced dose up to a maximum of 500 mg twice daily with close monitoring of kidney function (Ref).
eGFR <30 mL/minute/1.73 m2: Use is contraindicated.
Acute kidney injury during therapy: If acute kidney injury occurs or if risk factors are present (eg, severe vomiting or diarrhea), instruct patient to temporarily hold metformin (Ref).
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Note: Metformin is not metabolized by the liver and is primarily eliminated unchanged by the kidney; however, the liver is the primary site of lactic acid metabolism. Metformin increases lactic acid production in a dose-dependent manner and may result in overt lactic acidosis when coupled with liver impairment. Lactic acid–producing events, such as active alcohol consumption, dehydration, hypotension, sepsis, reduced cardiac function, or reduced kidney function, may enhance accumulation of lactic acid (Ref).
Liver impairment prior to treatment initiation:
Initial or dose adjustment in patients with preexisting liver cirrhosis:
Note: In patients with concurrent kidney impairment, eGFR ≤45 mL/minute/1.73 m2 and Child-Turcotte-Pugh A or B, defer to dosing in altered kidney function in adults (Ref). Monitor kidney function frequently (eg, every 1 to 3 months) (Ref) during continuation of therapy (Ref).
Child-Turcotte-Pugh class A : No dosage adjustment necessary (Ref).
Child-Turcotte-Pugh class B : 500 mg once daily; may increase by ≤500 mg/day increments every 30 days based on tolerability and response (Ref); consider slower titration (eg, every 60 days) in patients on concurrent agents that cause diarrhea (eg, lactulose) or fluid loss (eg, diuretics) (Ref); maximum dose: 1.5 g/day (Ref). Note: Do not initiate in patients at risk for lactic acid–producing events (eg, active alcohol consumption, dehydration, hypotension, sepsis, reduced cardiac function, reduced kidney function) (Ref).
Child-Turcotte-Pugh class C: Avoid use (Ref).
Liver impairment developing in patient already receiving metformin:
Chronic disease progression (eg, outpatient):
Note: In patients with concurrent kidney impairment, eGFR ≤45 mL/minute/1.73 m2 and Child-Turcotte-Pugh A or B, defer to dosing in altered kidney function in adults (Ref). Monitor kidney function frequently (eg, every 1 to 3 months) (Ref) during continuation of therapy (Ref).
Baseline to Child-Turcotte-Pugh class A: No dosage adjustment necessary (Ref).
Child-Turcotte-Pugh class B: No dosage adjustment necessary; however, a dose reduction may be required in patients at risk for lactic acid–producing events (eg, active alcohol consumption, dehydration, hypotension, sepsis, reduced cardiac function, reduced kidney function) (Ref).
Child-Turcotte-Pugh class C: If tolerating with appropriate clinical endpoints, use with caution; discontinue metformin therapy in patients at risk for or who experienced a lactic acid–producing event (eg, active alcohol consumption, dehydration, hypotension, sepsis, reduced cardiac function, reduced kidney function) (Ref).
Acute worsening of liver function (eg, requiring hospitalization): Discontinue metformin during the acute event (Ref). Once the acute event has resolved, may resume metformin at pre-event doses (Ref). Permanent discontinuation should be considered for patients who recently experienced lactic acidosis, are at high risk of recurrent decompensation, or at risk of lactic acid–producing events (Ref).
Metformin-induced liver injury: Permanently discontinue metformin therapy. Although metformin is not metabolized by the liver, rare cases of metformin-induced hepatotoxicity have been reported within weeks of initiation, but concurrent use of other hepatotoxic medications is common. Most patients present with jaundice, fatigue, and elevated AST/ALT. Upon discontinuation of metformin, LFTs normalize over days to weeks and reoccurs upon rechallenge (Ref).
Transient and/or reversible gastrointestinal (GI) adverse reactions, including diarrhea, nausea, flatulence, dyspepsia, vomiting, and abdominal pain, among others, are the most commonly reported adverse reactions with metformin use; intolerance to these reactions is often a reason for discontinuation of therapy (Ref).
Mechanism: Dose-related; mechanism not fully understood. Multiple mechanisms have been proposed that may contribute, including alterations in transporters (eg, organic cation transporter 1 [OCT1]), direct serotoninergic-like effects, increased gut motility, direct or indirect increases in glucagon-like peptide 1 (GLP-1), and disruptions in bile (Ref).
Onset: Varied; typically occurs at initiation of therapy; however, late onset of diarrhea has been reported (Ref). GI adverse reactions generally subside after several weeks of therapy; however, some patients require discontinuation.
Risk factors:
• Rapid dose escalation
• Use of IR formulations (Ref)
• Chronic asymptomatic gastritis (Ref)
• Helicobacter pylori infection (Ref)
• Concomitant use of OCT1-inhibiting agents (eg, verapamil, proton pump inhibitors) may be a potential risk factor (Ref)
Metformin-associated hepatoxicity is limited to case reports and can present as cholestatic (eg, elevated bilirubin and alkaline phosphatase), hepatocellular (eg, elevated alanine aminotransferase), or mixed and resolve after cessation of therapy (Ref).
Mechanism: Non–dose-related; idiosyncratic (Ref).
Onset: Varied; 4 days to 8 weeks after initiation; however, latency up to 10 years has been noted (Ref).
Risk factors:
• Concurrent use of other hepatotoxic substances (Ref)
• Age >50 years (Ref)
• Male sex (Ref)
Postmarketing cases of metformin-associated lactic acidosis (MALA) have resulted in hypothermia, hypotension, resistant bradyarrhythmias, and death. The onset is often subtle, accompanied by nonspecific symptoms (eg, malaise, myalgia, respiratory distress, somnolence, abdominal pain); elevated blood lactate levels (>5 mmol/L); anion gap acidosis (without evidence of ketonuria or ketonemia); and/or increased lactate:pyruvate ratio. Lactic acidosis should be suspected in any patient with diabetes receiving metformin with evidence of acidosis but without evidence of ketoacidosis. Safety data for use in advanced heart failure (stage D) is lacking (Ref).
Mechanism: Dose-related; inhibition of mitochondrial electron transport, an effect that favors anaerobic metabolism and the accumulation of lactate (Ref), resulting in lactic acidosis without evidence of tissue hypoxia (type B lactic acidosis). In addition, if accumulation occurs (eg, in patients with kidney impairment) or if high doses are administered (eg, in overdose), glucose utilization decreases and hepatic production of lactate increases (Ref).
Onset: Varied; may occur at any time during treatment.
Risk factors: In general, risk is increased with increased metformin concentration, decreased lactate clearance, and/or increased lactate production.
• Kidney impairment; risk increases with the severity of kidney impairment
• Hepatic impairment
• Reduced tissue perfusion such as in unstable heart failure (Ref)
• Concomitant use of certain drugs that impair kidney function, cause significant hemodynamic changes, interfere with acid-base balance, or increase metformin accumulation
• Patients ≥65 years of age
• Radiologic study with contrast
• Surgery and other procedures due to potential for volume depletion, hypotension, and kidney impairment
• Hypoxic states (eg, acute heart failure, acute myocardial infarction, sepsis, shock)
• Excessive alcohol intake
Long-term use of metformin has been associated with reversible vitamin B12 deficiency and subsequent anemia and neuropathy (Ref).
Mechanism: Time-related; long-term use metformin interferes with the absorption of vitamin B12 (Ref); potential mechanism includes interference of vitamin B12-intrinsic factor absorption in the terminal ileum (Ref).
Onset: Delayed; occurs with chronic use of metformin.
Risk factors:
• Duration of therapy (Ref)
• Higher doses (eg, >1,000 mg/day) (Ref)
• Inadequate B12 stores, poor underlying nutrition, and inadequate calcium intake or absorption (Ref)
• Older patients (eg, >65 years of age) (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Gastrointestinal: Diarrhea (IR tablet: 53%; ER tablet: 10%) (table 1), flatulence (12%) (table 2), nausea and vomiting (IR tablet: 26%; ER tablet: 7%) (table 3)
|
Drug (Metformin) |
Placebo |
Dose |
Dosage Form |
Number of Patients (Metformin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
53% |
12% |
Up to 2,550 mg/day |
IR tablet |
141 |
145 |
|
10% |
3% |
N/A |
ER tablet |
781 |
195 |
|
Drug (Metformin) |
Placebo |
Dose |
Dosage Form |
Number of Patients (Metformin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
12% |
6% |
Up to 2,550 mg/day |
IR tablet |
141 |
145 |
|
Drug (Metformin) |
Placebo |
Dose |
Dosage Form |
Number of Patients (Metformin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
26% |
8% |
Up to 2,550 mg/day |
IR tablet |
141 |
145 |
|
7% |
2% |
N/A |
ER tablet |
781 |
195 |
1% to 10%:
Cardiovascular: Chest discomfort, flushing, palpitations
Dermatologic: Diaphoresis, nail disease
Endocrine & metabolic: Hypoglycemia, vitamin B12 deficiency (7%)
Gastrointestinal: Abdominal distention, abdominal distress (6%), abdominal pain, abnormal stools, dyspepsia (7%) (table 4), heartburn
|
Drug (Metformin) |
Placebo |
Dose |
Dosage Form |
Number of Patients (Metformin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
7% |
4% |
Up to 2,550 mg/day |
IR tablet |
141 |
145 |
Nervous system: Asthenia (9%), chills, dizziness, headache (6%)
Neuromuscular & skeletal: Myalgia
Respiratory: Dyspnea, flu-like symptoms, upper respiratory tract infection
Postmarketing:
Dermatologic: Fixed drug eruption (Ref), lichen planus (Ref)
Endocrine & metabolic: Lactic acidosis (Ref)
Gastrointestinal: Pancreatitis (Ref)
Hematologic & oncologic: Hemolytic anemia (Ref)
Hepatic: Hepatotoxicity (cholestatic, hepatocellular, and mixed) (Ref)
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms (Ref), hypersensitivity angiitis (Ref)
Nervous system: Encephalopathy (Ref)
Hypersensitivity to metformin or any component of the formulation; severe renal dysfunction (eGFR <30 mL/minute/1.73 m2); acute or chronic metabolic acidosis with or without coma (including diabetic ketoacidosis).
Canadian labeling: Additional contraindications (not in US labeling): End-stage renal disease, patients on dialysis, or when renal function is unknown; unstable and/or insulin-dependent (type 1) diabetes mellitus; history of ketoacidosis with or without coma; history of lactic acidosis (regardless of precipitating factors); excessive alcohol intake (acute or chronic); severe hepatic dysfunction or clinical or laboratory evidence of hepatic disease; patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials; cardiovascular collapse and disease states associated with hypoxemia, including cardiorespiratory insufficiency, which are often associated with hyperlactacidemia; stress conditions (eg, severe infection, trauma, surgery and postoperative recovery phase); severe dehydration; pregnancy; breastfeeding.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Disease-related concerns:
• Bariatric surgery: Presurgical assessment of the indication for use, symptoms, and goals of therapy should be documented to enable postsurgical assessment. DPP4 inhibitors, GLP1 inhibitors, insulin, and metformin are preferred in the treatment of diabetes after bariatric surgery. Despite a single-dose pharmacokinetic study showing increased metformin bioavailability and a single case report of fatal metformin exposure after bariatric surgery, a study found decreased lactic acid levels at 3 months postsurgery (Blanchot 2024; Deden 2018; Padwal 2011). The risk of metformin-associated lactic acidosis (MALA) following bariatric surgery is minimal unless there are co-existing risk factors (eg, kidney insufficiency) (Deden 2018). Monitor for continued efficacy and tolerability after bariatric surgery and consider switching to an alternate medication if condition worsens.
• Heart failure: Metformin may be used in patients with stable heart failure (ADA 2023). Use cautiously or avoid in hypoperfusion.
• Hepatic impairment: Use cautiously in patients at risk for lactic acidosis (Brackett 2010; Crowley 2017; Zhang 2014). An increased risk of mortality has been observed with higher metformin doses (eg, >1 g) and more severe liver dysfunction (eg, Child-Turcotte-Pugh C>B>>>A) (Yen 2022). Cases of metformin-induced hepatotoxicity have also been reported (LiverTox 2020; Zheng 2016).
• Renal impairment: Metformin is substantially excreted by the kidney; dosing adjustments may be required.
• Stress-related states: It may be necessary to discontinue metformin and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery).
Dosage form specific issues:
• ER tablet: A soft mass resembling the tablet may appear in the stool.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.
Other warnings/precautions:
• Appropriate use: Not indicated for use in patients with type 1 diabetes mellitus or with diabetic ketoacidosis.
• Iodinated contrast: Administration of iodinated contrast agents has been associated with postcontrast acute kidney injury (AKI); acute decreases in renal function have been associated with an increased risk of lactic acidosis due to reduced metformin excretion (ACR 2021; manufacturer’s labeling). Current guidelines recommend temporarily withholding metformin prior to or at the time of iodinated contrast administration in patients with known AKI or severe chronic kidney disease (eGFR <30 mL/minute/1.73 m2), or who are undergoing arterial catheter studies (ACR 2021). Some experts also temporarily withhold metformin in patients with an eGFR <45 mL/minute/1.73 m2 or risk factors for lactic acidosis (eg, hypotension, vascular instability, potential hypoperfusion) (Rudnick 2021; Wexler 2021b). If metformin is withheld, reassess kidney function ≥48 hours after contrast administration and resume therapy if kidney function is acceptable (ACR 2021).
• Surgical procedures: Metformin-containing products should be withheld the day of surgery; restart after renal function is stable (ADA 2023).
Riomet ER suspension has been discontinued in the United States for >1 year.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Oral, as hydrochloride:
Riomet: 500 mg/5 mL (118 mL, 473 mL) [contains propylene glycol; strawberry flavor]
Riomet: 500 mg/5 mL (118 mL, 473 mL) [contains saccharin calcium; cherry flavor]
Generic: 500 mg/5 mL (5 mL, 8.5 mL [DSC], 118 mL, 473 mL)
Tablet, Oral, as hydrochloride:
Generic: 500 mg, 625 mg, 750 mg, 850 mg, 1000 mg
Tablet Extended Release 24 Hour, Oral, as hydrochloride:
Fortamet: 500 mg [DSC], 1000 mg [DSC]
Glumetza: 500 mg [DSC], 1000 mg [DSC]
Generic: 500 mg, 750 mg, 1000 mg
Yes
Solution (metFORMIN HCl Oral)
500 mg/5 mL (per mL): $1.35
Solution (Riomet Oral)
500 mg/5 mL (per mL): $1.69
Tablet, 24-hour (metFORMIN HCl ER (MOD) Oral)
500 mg (per each): $55.59 - $55.99
1000 mg (per each): $120.22 - $120.23
Tablet, 24-hour (metFORMIN HCl ER (OSM) Oral)
500 mg (per each): $4.52 - $17.24
1000 mg (per each): $6.38 - $31.40
Tablet, 24-hour (metFORMIN HCl ER Oral)
500 mg (per each): $0.05 - $1.08
750 mg (per each): $0.09 - $1.61
Tablets (metFORMIN HCl Oral)
500 mg (per each): $0.02 - $1.80
625 mg (per each): $37.06
750 mg (per each): $37.83
850 mg (per each): $0.03 - $1.20
1000 mg (per each): $0.03 - $2.40
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral, as hydrochloride:
Glucophage: 500 mg, 850 mg
Glycon: 500 mg [DSC], 850 mg [DSC]
Generic: 500 mg, 850 mg, 1000 mg
Tablet Extended Release 24 Hour, Oral, as hydrochloride:
Glumetza: 500 mg
Glumetza: 1000 mg [contains fd&c blue #2 (indigotine,indigo carmine), fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow)]
Generic: 500 mg, 1000 mg
Oral: Administer with a meal (to decrease GI upset).
Immediate release: Administer in divided doses with meals. Administer oral solution with supplied dosing cup.
Extended release:
Oral suspension: Administer with evening meal. Shake well at least 10 seconds before use; use supplied dosing cup to measure dose. Rinse dosing cup with water only after each use to clean.
Tablet: Administer once-daily doses with the evening meal; swallow whole; do not cut, crush, or chew.
Oral: Administer with a meal (to decrease GI upset). Administer solution and suspension with supplied dosing cup.
ER tablets: Swallow whole; do not crush, cut, or chew. Administer once-daily doses with the evening meal.
Bariatric surgery: Metformin is available in an ER formulation and the release characteristics may be significantly altered in an unknown manner in patients who have undergone bariatric surgery. Providers should determine if the condition being treated can be safely monitored or if a switch to an alternative formulation is necessary (Ref). Metformin is also available as an IR formulation.
Oral solution (immediate release): Store at 15°C to 30°C (59°F to 86°F).
Oral suspension (extended release): Store at 20°C to 25°C (68°F to 77°F); excursion permitted to 15°C to 30°C (59°F to 86°F). Discard unused portion of reconstituted suspension after 100 days.
Tablets: Store at 20°C to 25°C (68°F to 77°F); excursion permitted to 15°C to 30°C (59°F to 86°F). Protect from light and moisture.
Management of type 2 diabetes mellitus when hyperglycemia cannot be managed with diet and exercise alone (Immediate release [tablets, oral solution]: FDA approved in ages ≥10 years and adults; extended release: Oral suspension [Riomet ER]: FDA approved in ages ≥10 years and adults; Tablets: FDA approved in adults); has also been used for weight loss in pediatric patients with severe obesity and insulin resistance in conjunction with a comprehensive lifestyle weight management program; treatment of weight-gain secondary to antitypical antipsychotic use.
MetFORMIN may be confused with metroNIDAZOLE
Glucophage may be confused with Glucotrol, Glutofac
Dianben [Spain] may be confused with Diovan brand name for valsartan [US, Canada, and multiple international markets].
Glucon brand name for metformin [Malaysia, Singapore] is also the brand name for glucosamine [Singapore]
Substrate of MATE1/2-K, OCT1, OCT2;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Abemaciclib: May increase serum concentration of MetFORMIN. Risk C: Monitor
Alcohol (Ethyl): May increase adverse/toxic effects of MetFORMIN. Specifically, excessive alcohol ingestion (acute or chronic) may potentiate the risk of lactic acidosis. Risk X: Avoid
Alpha-Lipoic Acid: May increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor
Androgens: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Arimoclomol: May increase serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Beta-Blockers (Beta1 Selective): May increase adverse/toxic effects of Antidiabetic Agents. Specifically, beta-blockers may mask the hypoglycemic symptoms of antidiabetic agents. Risk C: Monitor
Beta-Blockers (Nonselective): May increase hypoglycemic effects of Antidiabetic Agents. Beta-Blockers (Nonselective) may increase adverse/toxic effects of Antidiabetic Agents. Specifically, beta-blockers may mask the hypoglycemic symptoms of antidiabetic agents. Risk C: Monitor
Bictegravir: May increase serum concentration of MetFORMIN. Risk C: Monitor
Bortezomib: May increase therapeutic effects of Antidiabetic Agents. Bortezomib may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Carbonic Anhydrase Inhibitors: May increase adverse/toxic effects of MetFORMIN. Specifically, the risk of developing lactic acidosis may be increased. Risk C: Monitor
Cephalexin: May increase serum concentration of MetFORMIN. Risk C: Monitor
Cimetidine: May increase serum concentration of MetFORMIN. Management: Consider alternatives to cimetidine in patients receiving metformin due to a potential for increased metformin concentrations and toxicity (including lactic acidosis). Risk D: Consider Therapy Modification
Copanlisib: May decrease therapeutic effects of MetFORMIN. Copanlisib may increase serum concentration of MetFORMIN. Risk C: Monitor
Direct Acting Antiviral Agents (HCV): May increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor
Dofetilide: MetFORMIN may increase serum concentration of Dofetilide. Risk C: Monitor
Dolutegravir: May increase serum concentration of MetFORMIN. Management: Consider alternatives to this combination or use of lower metformin doses. Carefully weigh the risk of metformin toxicities (including lactic acidosis) against the benefit of combining dolutegravir with metformin. Risk D: Consider Therapy Modification
Etilefrine: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Fedratinib: May increase serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Fedratinib: May increase serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Fexinidazole: May increase serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of fexinidazole with MATE1/2-K substrates when possible. If combined, monitor for increased MATE1/2-K substrate toxicities. Risk D: Consider Therapy Modification
Fexinidazole: May increase serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of fexinidazole with OCT2 substrates when possible. If combined, monitor for increased OCT2 substrate toxicities. Risk D: Consider Therapy Modification
Fludeoxyglucose F 18: Coadministration of MetFORMIN and Fludeoxyglucose F 18 may alter diagnostic results. Management: Consider holding metformin for 48 hours or longer prior to PET scans using fludeoxyglucose F18 (FDG-F18) when imaging of the colon or intestine is required. Consider increased monitoring of blood glucose when metformin is held. Risk D: Consider Therapy Modification
Foslevodopa: May increase serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Gilteritinib: May increase serum concentration of OCT1 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Givinostat: May increase serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Glycopyrrolate (Systemic): May increase serum concentration of MetFORMIN. Risk C: Monitor
Guanethidine: May increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor
Guar Gum (Partially Hydrolyzed): May decrease serum concentration of MetFORMIN. Risk C: Monitor
Hyperglycemia-Associated Agents: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Hypoglycemia-Associated Agents: Antidiabetic Agents may increase hypoglycemic effects of Hypoglycemia-Associated Agents. Risk C: Monitor
Iodinated Contrast Agents: May increase adverse/toxic effects of MetFORMIN. Renal dysfunction that may be caused by iodinated contrast agents may lead to metformin-associated lactic acidosis. Management: Management advice varies. Refer to the full drug interaction monograph content for details. Risk D: Consider Therapy Modification
LamoTRIgine: May increase serum concentration of MetFORMIN. Management: The lamotrigine Canadian product monograph states that coadministration of these drugs is not recommended. Risk C: Monitor
Maitake: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
MATE1/2-K Inhibitors: May increase serum concentration of MetFORMIN. Risk C: Monitor
Mavorixafor: May decrease serum concentration of MetFORMIN. Risk C: Monitor
Methylol Cephalexin: May increase serum concentration of MetFORMIN. Risk C: Monitor
Monoamine Oxidase Inhibitors: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents: May increase adverse/toxic effects of MetFORMIN. Risk C: Monitor
Ombitasvir, Paritaprevir, and Ritonavir: May increase adverse/toxic effects of MetFORMIN. Specifically, the risk for lactic acidosis may be increased. Risk C: Monitor
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase adverse/toxic effects of MetFORMIN. Specifically, the risk for lactic acidosis may be increased. Risk C: Monitor
Ondansetron: May increase serum concentration of MetFORMIN. Risk C: Monitor
Patiromer: May decrease serum concentration of MetFORMIN. Management: Administer metformin at least 3 hours before or 3 hours after patiromer. Risk D: Consider Therapy Modification
Pegvisomant: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Prothionamide: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Quinolones: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Quinolones may decrease therapeutic effects of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor
Ranolazine: May increase serum concentration of MetFORMIN. Management: Limit the metformin dose to a maximum of 1,700 mg per day when used together with ranolazine 1,000 mg twice daily. Monitor patients for metformin toxicities, including lactic acidosis and carefully weigh the risks and benefits of this combination. Risk D: Consider Therapy Modification
Reproterol: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Risdiplam: May increase serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of risdiplam with MATE substrates if possible. If the combination cannot be avoided, monitor closely for adverse effects. Consider a reduced dose of the MATE substrate according to that substrate's labeling if appropriate. Risk D: Consider Therapy Modification
Ritodrine: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Salicylates: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Selective Serotonin Reuptake Inhibitor: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Tafenoquine: May increase serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of MATE substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the MATE substrate and consider a reduced dose of the MATE substrate according to that substrate's labeling. Risk D: Consider Therapy Modification
Tafenoquine: May increase serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of OCT2 substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the OCT2 substrate and consider a reduced dose of the OCT2 substrate according to that substrate's labeling. Risk D: Consider Therapy Modification
Thiazide and Thiazide-Like Diuretics: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Topiramate: May increase adverse/toxic effects of MetFORMIN. Specifically, the risk for lactic acidosis may be increased. MetFORMIN may increase serum concentration of Topiramate. Topiramate may increase serum concentration of MetFORMIN. Risk C: Monitor
Verapamil: May decrease therapeutic effects of MetFORMIN. Risk C: Monitor
Vimseltinib: May increase serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid concomitant use of vimseltinib and OCT2 substrates when possible. If combined, monitor for increased effects and toxicities of the OCT2 substrate and consider dose adjustments. Risk D: Consider Therapy Modification
Vitamin K Antagonists: MetFORMIN may decrease anticoagulant effects of Vitamin K Antagonists. Vitamin K Antagonists may increase hypoglycemic effects of MetFORMIN. Risk C: Monitor
Food decreases the extent and slightly delays the absorption. Management: Administer with a meal.
Drug may cause GI upset; take with food (to decrease GI upset). Take at the same time(s) each day. Dietary modification based on ADA recommendations is a part of therapy.
Metformin is approved for the treatment of type 2 diabetes mellitus; however, it is not preferred for use if pregnancy should occur. Regardless of treatment, patients with diabetes who could become pregnant should use effective contraception and those planning to become pregnant should continue contraception until glycemic control is achieved. When diet and exercise alone are not enough for the treatment of type 2 diabetes mellitus, metformin may be continued in select patients who are well controlled prior to pregnancy, such as those who are unwilling or unable to use insulin (ACOG 2018; ADA 2023).
Adjunctive use of metformin may reduce the risk of ovarian hyperstimulation syndrome and miscarriage in patients with polycystic ovary syndrome (PCOS) who are undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with a gonadotrophin releasing hormone antagonist long protocol. Metformin should be discontinued once there is a positive pregnancy test unless it is needed for another indication (Teede 2023).
Metformin monotherapy may be considered as an alternative agent for ovulation induction in patients with PCOS who have anovulatory infertility and no other infertility factors; however, other treatments (eg, clomiphene, letrozole) are more effective at improving ovulation (Teede 2023). When used in the management of PCOS, metformin may reduce the risk of preterm delivery; however, the incidence of gestational diabetes, miscarriage, or preeclampsia are not affected (Cao 2021). Metformin monotherapy has not been found to improve the live birth rate in patients with PCOS when used for ovulation induction or IVF or ICSI (Magzoub 2022; Tso 2020; Wu 2020).
Metformin crosses the placenta; concentrations may be comparable to or higher than those found in the maternal plasma (ADA 2023; Charles 2006; de Oliveira Baraldi 2011; Eyal 2010; Vanky 2005).
Outcome data following first trimester exposure from paternal (Rotem 2024; Wensink 2022) and maternal (Cao 2021; Cassina 2014; Gilbert 2006; Panchaud 2018; Scherneck 2018; Zeng 2016) use of metformin are available. Maternal and fetal/neonatal outcomes are influenced by underlying maternal disease (eg, gestational diabetes mellitus [GDM] or polycystic ovary syndrome [PCOS]) (Cao 2021; Panchaud 2018; Zeng 2016). An increased risk of birth defects or adverse fetal/neonatal outcomes has not been observed following maternal use of metformin for gestational diabetes mellitus or type 2 diabetes mellitus when glycemic control is maintained (Balani 2009; Coetzee 1984; Ekpebegh 2007; Niromanesh 2012; Rowan 2008; Rowan 2010; Tertti 2008). Studies which evaluated children up to 12 years of age with previous in utero exposure to metformin have shown conflicting outcomes related to BMI and other growth parameters; however, results may be confounded by underlying maternal disease (eg, GDM, PCOS) and concomitant therapy (eg, insulin) (ADA 2023; Brand 2022; Paavilainen 2022; Skibinska 2021). Additional long-term data are needed (Toft 2024).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of metformin may be altered. Maternal plasma concentrations may be decreased during pregnancy due to increased renal clearance and return to prepregnancy values during the first 2 weeks postpartum (de Oliveira Baraldi 2011; Espnes 2022; Eyal 2010; Hughes 2006; Liao 2020).
Poorly controlled diabetes during pregnancy is associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia (ACOG 2018). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2023).
Agents other than metformin are currently recommended to treat diabetes mellitus in during pregnancy (ADA 2023). Metformin may be considered for the treatment of GDM in patients who cannot safely or effectively use insulin (eg, due to cost, language barriers, comprehension, cultural issues). However, metformin monotherapy fails to provide adequate glycemic control in all patients. Metformin should not be used in patients with hypertension, preeclampsia, or those at risk for intrauterine growth restriction due to risk of fetal growth restriction or acidosis in the setting of placental restriction. Metformin is not the preferred treatment of type 2 diabetes mellitus during pregnancy (ADA 2023). Metformin, in addition to insulin, may be considered for some pregnant patients with type 2 diabetes mellitus due to potential maternal and neonatal benefits (eg, reduced insulin requirements, less maternal weight gain, fewer caesarean births, reduced incidence of macrosomia), although additional long-term data are needed (Benham 2021; Feig 2020).
PCOS is also associated with adverse pregnancy outcomes, including an increased risk of GDM, miscarriage, pregnancy-induced hypertension, preeclampsia, and preterm delivery. Discontinue once there is a positive pregnancy test in patients with PCOS using metformin for ovulation induction, in vitro fertilization, or intracytoplasmic sperm injection (ADA 2023; Teede 2023).
Plasma glucose (individualize frequency based on treatment regimen, hypoglycemia risk, and other patient-specific factors; some patients may be candidates for continuous glucose monitoring) (ADA 2023); electrolytes; renal function (at diagnosis and at least annually); hepatic function, hematologic parameters (annually), vitamin B12 serum concentrations (every 2 to 3 years); folate (if megaloblastic anemia is suspected) (manufacturer's labeling). Monitor weight, height (or length if <24 months), and BMI every 3 months in pediatric patients <7 years with type 1 diabetes (ISPAD [Sundberg 2022]).
HbA1c: Monitor every 3 months; some recommendations suggest at least twice yearly may be considered in patients who have stable glycemic control and are meeting treatment goals (ADA 2023; ISPAD [de Bock 2022]; ISPAD [Shah 2022]). Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2023; KDIGO 2020).
Plasma Blood Glucose and HbA1c Goals for Patients with Diabetes: Note: Postprandial blood glucose should be measured when there is a discrepancy between preprandial blood glucose concentrations and HbA1c values and to help assess glycemia for patients who receive basal/bolus or pump regimens. It is usually drawn 1 to 2 hours after starting a meal and is considered to be the "peak."
Children and Adolescents:
Blood glucose:
Type 2 diabetes:
Fasting plasma glucose: 70 to 110 mg/dL (SI: 3.9 to 6.1 mmol/L) (ISPAD [Shah 2022]).
Postprandial glucose: 70 to 140 mg/dL (SI: 3.9 to 7.8 mmol/L) (ISPAD [Shah 2022]).
HbA1c: <7%; target should be individualized; a more stringent goal (<6.5%) may be reasonable if it can be achieved without significant hypoglycemia and is reasonable in many patients with type 2 diabetes; less aggressive goals (<7.5%) may be appropriate in patients who are at increased risk of hypoglycemia (ADA 2023; ISPAD [de Bock 2022]; ISPAD [Shah 2022]).
Surgical patients (ISPAD [Kapellen 2022]):
Intraoperative: 90 to 180 mg/dL.
ICU, postsurgery: 140 to 180 mg/dL.
Decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity (increases peripheral glucose uptake and utilization)
Onset of action: Within days; maximum effects up to 2 weeks.
Distribution: Vd: 654 ± 358 L; partitions into erythrocytes; concentrates in liver, kidney, and GI tract.
Protein binding: Negligible.
Metabolism: Not metabolized by the liver.
Bioavailability: Absolute: Fasting: 50% to 60%.
Half-life elimination: Plasma: 4 to 9 hours; Blood ~17.6 hours.
Time to peak, serum: Immediate release: 2 to 3 hours; ER tablet: 6 to 8 hours; ER suspension: 4.5 hours (range: 3.5 to 6.5 hours).
Excretion: Urine (90% as unchanged drug; active secretion).
Altered kidney function: Peak and systemic exposure is increased, and oral and renal clearance is decreased.
Pediatric: Obesity: In 22 pediatric patients who were obese (mean age: 14.5 ± 1.8 years; range: 11.1 to 17.5 years), pharmacokinetic analysis showed that clearance significantly increases and AUC decreases with increasing total body weight (van Rongen 2018).
Older adult: Total plasma clearance is decreased, half-life is prolonged, and Cmax is increased.
