Saxagliptin and Metformin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, variable release, oral:

Kombiglyze XR 2.5/1000: Saxagliptin 2.5 mg [immediate release] and metformin hydrochloride 1000 mg [extended release]

Kombiglyze XR 5/500: Saxagliptin 5 mg [immediate release] and metformin hydrochloride 500 mg [extended release]

Kombiglyze XR 5/1000: Saxagliptin 5 mg [immediate release] and metformin hydrochloride 1000 mg [extended release]

Pharmacology

Mechanism of Action

Saxagliptin inhibits dipeptidyl peptidase IV (DPP-IV) enzyme resulting in prolonged active incretin levels. Incretin hormones (eg, glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta cells and decreasing glucagon secretion from pancreatic alpha cells. Decreased glucagon secretion results in decreased hepatic glucose production. Under normal physiologic circumstances, incretin hormones are released by the intestine throughout the day and levels are increased in response to a meal; incretin hormones are rapidly inactivated by the DPP-IV enzyme.

Metformin decreases hepatic glucose production, decreasing intestinal absorption of glucose and improves insulin sensitivity (increases peripheral glucose uptake and utilization).

Use: Labeled Indications

Diabetes mellitus, type 2: Management of adults with type 2 diabetes mellitus as an adjunct to diet and exercise when treatment with both saxagliptin and metformin is appropriate.

Contraindications

US labeling: History of serious hypersensitivity reaction (eg, anaphylaxis, angioedema, exfoliative skin conditions) to saxagliptin, metformin, or any component of the formulation; severe renal impairment (eGFR <30 mL/minute/1.73 m²); acute or chronic metabolic acidosis including diabetic ketoacidosis

Canadian labeling: Hypersensitivity to saxagliptin, another dipeptidyl peptidase-4 inhibitor, metformin, or any component of the formulation; unstable and/or insulin-dependent (Type 1) diabetes mellitus; acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma, history of ketoacidosis with or without coma; history of lactic acidosis (regardless of precipitating factors); presence of renal disease or impairment and patients with serum creatinine levels above the upper limit of normal range or abnormal creatinine clearance (<60 mL/minute), which may also result from conditions such as cardiovascular collapse, acute myocardial infarction, and septicemia or when renal function is unknown; excessive ethanol intake (acute or chronic); moderate and severe hepatic impairment; cases of cardiovascular collapse and disease states associated with hypoxemia such as cardiorespiratory insufficiency which are often associated with hyperlactacidemia; during stress conditions (eg, severe infection, trauma, surgery and postoperative recovery phase); severe dehydration; pregnancy; breast-feeding

Dosage and Administration

Dosing: Adult

Diabetes mellitus, type 2: Oral:

Extended release (ER) formulation: Note: Initial doses should be based on current daily dose of saxagliptin and metformin. Daily dose should generally be administered once daily. Maximum: Saxagliptin 5 mg/metformin 2 g ER per day.

Patients inadequately controlled on metformin alone: Initial: Saxagliptin 2.5 to 5 mg once daily plus current daily dose of metformin. Patients who require saxagliptin 2.5 mg and metformin >1 g/day should not be switched to the combination product.

Patients inadequately controlled on saxagliptin 5 mg alone: Initial dose: Saxagliptin 5 mg/metformin 500 mg ER once daily. Patients who require saxagliptin 2.5 mg and are metformin-naive or require metformin >1 g/day should not be switched to the combination product.

Concomitant use with strong CYP3A4/5 inhibitors: Maximum: Saxagliptin 2.5 mg/metformin 1 g once daily

Concomitant use with insulin or insulin secretagogues: Reduced dose of insulin or insulin secretagogues (eg, sulfonylureas) may be needed.

Immediate release formulation [Canadian product]: Initial doses should be based on current dose of saxagliptin and metformin; daily dose should be divided into 2 equal doses given with meals. Maximum: Saxagliptin 5 mg/metformin 2 g per day

Patients inadequately controlled on metformin alone: Initial dose: Saxagliptin 2.5 mg twice daily plus current dose of metformin.

Concomitant use with insulin: Reduced dose of insulin may be needed.

Dosing: Geriatric

Refer to adult dosing. The initial and maintenance dosing should be conservative, due to the potential for decreased renal function (monitor).

Administration

Oral: Administer extended release (ER) tablets once daily with the evening meal. Swallow whole; do not crush, cut, or chew ER tablets.

Immediate release formulation [Canadian product] should be administered twice daily with meals (eg, breakfast and dinner).

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

Drug Interactions

Abemaciclib: May increase the serum concentration of MetFORMIN. Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of MetFORMIN. Specifically, alcohol may potentiate the risk of lactic acidosis Avoid combination

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Bictegravir: May increase the serum concentration of MetFORMIN. Monitor therapy

Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of MetFORMIN. Specifically, the risk of developing lactic acidosis may be increased. Exceptions: Brinzolamide; Dorzolamide. Monitor therapy

Cephalexin: May increase the serum concentration of MetFORMIN. Monitor therapy

Cimetidine: May increase the 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). Consider therapy modification

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of SAXagliptin. Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of SAXagliptin. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of SAXagliptin. Management: Limit the saxagliptin dose to 2.5 mg daily when combined with strong CYP3A4 inhibitors. When using the saxagliptin combination products saxagliptin/dapagliflozin or saxagliptin/dapagliflozin/metformin, avoid use with strong CYP3A4 inhibitors. Consider therapy modification

Dalfampridine: MetFORMIN may increase the serum concentration of Dalfampridine. Dalfampridine may increase the serum concentration of MetFORMIN. Monitor therapy

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Dofetilide: MetFORMIN may increase the serum concentration of Dofetilide. Monitor therapy

Dolutegravir: May increase the serum concentration of MetFORMIN. Management: Consider the risks and benefits of this combination. If combined, limit the daily metformin dose to 1,000 mg when used with dolutegravir. Monitor for increased metformin effects/toxicities (including lactic acidosis) during concomitant use. Consider therapy modification

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Erdafitinib: May increase the serum concentration of OCT2 Substrates. Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Glycopyrrolate (Systemic): May increase the serum concentration of MetFORMIN. Monitor therapy

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Insulins: Dipeptidyl Peptidase-IV Inhibitors may enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Iodinated Contrast Agents: May enhance the adverse/toxic effect 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. Exceptions: Diatrizoate Meglumine; Diatrizoate Sodium; Ethiodized Oil. Consider therapy modification

Isavuconazonium Sulfate: May increase the serum concentration of MetFORMIN. Monitor therapy

LamoTRIgine: May increase the serum concentration of MetFORMIN. Management: The lamotrigine Canadian product monograph states that coadministration of these drugs is not recommended. Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Avoid combination

Lumacaftor and Ivacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor and Ivacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of MetFORMIN. Monitor therapy

Ondansetron: May increase the serum concentration of MetFORMIN. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Patiromer: May decrease the serum concentration of MetFORMIN. Management: Administer metformin at least 3 hours before or 3 hours after patiromer. Consider therapy modification

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Ranolazine: May increase the 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. Consider therapy modification

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Sulfonylureas: Dipeptidyl Peptidase-IV Inhibitors may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Tafenoquine: May increase the serum concentration of MATE1 Substrates. 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. Consider therapy modification

Tafenoquine: May increase the serum concentration of OCT2 Substrates. 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. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Topiramate: May enhance the adverse/toxic effect of MetFORMIN. Monitor therapy

Trimethoprim: May increase the serum concentration of MetFORMIN. Monitor therapy

Trospium: MetFORMIN may decrease the serum concentration of Trospium. Monitor therapy

Vandetanib: May increase the serum concentration of MetFORMIN. Monitor therapy

Verapamil: May diminish the therapeutic effect of MetFORMIN. Monitor therapy

Adverse Reactions

See individual agents.

Warnings/Precautions

Concerns related to adverse effects:

• Arthralgia: Severe and disabling arthralgia has been reported with DPP-IV inhibitor use; onset may occur within one day to years after treatment initiation and may resolve with discontinuation of therapy. Some patients may experience a recurrence of symptoms if DPP-IV inhibitor therapy resumed.
• Bullous pemphigoid: DPP-4 inhibitor use has been associated with development of bullous pemphigoid; cases have typically resolved with topical or systemic immunosuppressive therapy and discontinuation of DPP-4 inhibitor therapy. Advise patients to report development of blisters or erosions. Discontinue therapy if bullous pemphigoid is suspected and consider referral to a dermatologist.
• Hematologic: Dose-related decrease in lymphocyte count has been observed with saxagliptin; clinical significance is not known. Monitoring of lymphocyte counts may be warranted in patients with unusual or persistent infection.
• Hypersensitivity reactions: Rare hypersensitivity reactions, including anaphylaxis, angioedema, and exfoliative dermatologic reactions have been reported with saxagliptin use; discontinue if signs/symptoms of severe hypersensitivity reaction occur. Events have generally been noted within the first 3 months of therapy, and may occur with the initial dose. Use with caution if patient has experienced angioedema with other DPP-IV inhibitor use.
• Lactic acidosis: [US Boxed Warning]: Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset is often subtle, accompanied by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, somnolence, abdominal pain); elevated blood lactate levels (>5 mmol/L); anion gap acidosis (without evidence of ketonuria or ketonemia); increased lactate:pyruvate ratio; metformin plasma levels generally >5 mcg/mL. Risk factors for lactic acidosis include patients with renal impairment; concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), ≥65 years of age, having a radiologic study with contrast, surgery and other procedures, hypoxic states (eg, acute heart failure), excessive alcohol intake, and hepatic impairment. Discontinue immediately if lactic acidosis is suspected; prompt hemodialysis is recommended. Lactic acidosis should be suspected in any patient with diabetes receiving metformin with evidence of acidosis but without evidence of ketoacidosis. Discontinue use in patients with conditions associated with dehydration, hypoperfusion, sepsis, or hypoxemia. Temporarily discontinue therapy in patients with restricted food and fluid intake. The risk of accumulation and lactic acidosis increases with the degree of impairment of renal function.
• Pancreatitis: Cases of acute pancreatitis have been reported with saxagliptin use. Monitor for signs/symptoms of pancreatitis; discontinue use immediately if pancreatitis is suspected and initiate appropriate management. Use with caution in patients with a history of pancreatitis as it is not known if this population is at greater risk.
• Vitamin B₁₂ concentrations: Long-term metformin use is associated with vitamin B₁₂ deficiency; monitor vitamin B₁₂ serum concentrations periodically with long-term therapy. Monitoring of B₁₂ serum concentrations should be considered in all patients receiving metformin and in particular those with peripheral neuropathy or anemia (ADA 2019).

Disease-related concerns:

• Bariatric surgery:

– Altered absorption: Use alternative agents after surgery. Absorption may be altered given the anatomic and transit changes created by gastric bypass and sleeve gastrectomy surgery. ER tablets may have a reduced effect after gastric bypass or sleeve gastrectomy due to the direct bypass of the stomach and proximal small bowel with gastric bypass or a more rapid gastric emptying and proximal small bowel transit with sleeve gastrectomy (Mechanick 2013; Melissas 2013). After gastric bypass (Roux-en-Y gastric bypass [RYGB]), administration of IR tablets led to increased absorption (AUC_0-∞ increased by 21%) and bioavailability (increased by 50%) (Padwal 2011). Lactate levels decrease after gastric bypass (RYGB)-induced weight loss irrespective of the use of metformin. Routinely lowering metformin dose after gastric bypass is not necessary as long as normal renal function is preserved (Deden 2018).

– Glucagon-like peptide-1 exposure and therapeutic efficacy: Closely monitor for signs and symptoms of pancreatitis; gastric bypass and sleeve gastrectomy may increase endogenous secretion of glucagon-like peptide-1 (Korner 2009; Peterli 2012). A single-dose, placebo-controlled study evaluated short-term therapy (4 weeks) with sitagliptin in gastric bypass patients having persistent or recurrent type 2 diabetes and found it to be well tolerated and provided a small, but significant, reduction in postprandial blood glucose (Shah 2018).

• Heart failure: Metformin may be used in patients with stable heart failure; avoid use in unstable or hospitalized patients with heart failure (ADA 2019). The risk of lactic acidosis may be increased secondary to hypoperfusion. Use of metformin in patients with heart failure may be associated with reduced mortality and reduction in hospital readmission for heart failure (Crowley 2017; Eurich 2013). Heart failure that may require hospitalization has been reported with saxagliptin in a multi-center, randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes with a history of, or at risk for, cardiovascular events; risk was increased in patients with preexisting heart failure or renal impairment and during the first 12 months of therapy (Scirica 2013; Scirica 2014). A population-based retrospective study in an ambulatory setting with relatively lower baseline cardiovascular risk factors failed to demonstrate increased risk in patients on saxagliptin compared to other agents (eg, sitagliptin, pioglitazone, sulfonylureas, insulin) (Toh 2016). Monitor for signs and symptoms of heart failure during therapy and consider discontinuation if condition develops. In a scientific statement from the American Heart Association, saxagliptin and metformin have been determined to be agents that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]). The ADA recommends avoiding use of saxagliptin in patients with heart failure (ADA 2019).
• Hepatic impairment: The manufacturer recommends to generally avoid metformin use in patients with hepatic impairment due to potential for lactic acidosis. However, continued use of metformin in patients with diabetes with liver dysfunction, including cirrhosis, may be associated with a survival benefit in carefully selected patients (Brackett 2010; Crowley 2017; Zhang 2014).
• Renal impairment: Metformin is substantially excreted by the kidney; assess renal function prior to initiation of therapy and periodically thereafter using eGFR. The risk of metformin accumulation and lactic acidosis increases with degree of renal impairment. Use is contraindicated in patients with eGFR <30 mL/minute/1.73 m². Assess benefits/risks of metformin use in patients with eGFR 30 to 45 mL/minute/1.73 m²; if used, dosage reduction is recommended (ADA [Lipska 2011]; Inzucchi 2014; McCulloch 2017). Saxagliptin dosage reduction is also required. Use of concomitant medications that may affect renal function (ie, affect tubular secretion) may also affect metformin disposition. Metformin should be withheld in patients with dehydration and/or prerenal azotemia.
• Stress-related states: It may be necessary to discontinue metformin and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution; the risk of metformin associated lactic acidosis is increased with age.

Other warnings/precautions:

• Appropriate use: Not for use in patients with diabetic ketoacidosis or patients with type 1 diabetes mellitus.
• Ethanol use: Instruct patients to avoid excessive acute or chronic ethanol use; ethanol may potentiate metformin's effect on lactate metabolism.
• Iodinated contrast: According to the manufacturer, it is recommended to temporarily discontinue metformin at the time of or before iodinated contrast imaging procedures in patients with an eGFR 30 to 60 mL/minute/1.73 m²; or with a history of hepatic disease, alcoholism, or heart failure; or in patients who will receive intra-arterial iodinated contrast. Reevaluate eGFR 48 hours after imaging procedure; restart if renal function is stable. Alternatively, the American College of Radiology (ACR) guidelines recommend that metformin may be used prior to or following administration of iodinated contrast media in patients with no evidence of acute kidney injury (AKI) and with an eGFR ≥30 mL/minute/1.73 m²; ACR guidelines recommend temporary discontinuation of metformin in patients with known AKI or severe chronic kidney disease ([stage IV or V [ie, eGFR <30 mL/minute/1.73 m²]) or who are undergoing arterial catheter studies (ACR 2017).
• Patient education: Diabetes self-management education is essential to maximize the effectiveness of therapy.
• Surgical procedures: Metformin should be withheld the day of surgery (all other oral hypoglycemic agents should be withheld the morning of surgery or procedure) (ADA 2019).

Monitoring Parameters

Urine for glucose and ketones; plasma glucose; HbA_1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2019]); initial and periodic monitoring of hematologic parameters (eg, hemoglobin/hematocrit, red blood cell indices, and lymphocyte counts if unusual or persistent infection); hepatic function; renal function (eGFR) should be performed prior to initiation of therapy and at least annually (more often in patients at risk of developing renal impairment; every 3 to 6 months if eGFR 45 to <60 mL/minute/1.73 m²; every 3 months if eGFR 30 to <45 mL/minute/1.73 m² [Lipska 2011]); vitamin B₁₂ serum concentrations every 2 to 3 years; folate (if megaloblastic anemia is suspected); signs/symptoms of pancreatitis and/or heart failure

Pregnancy

Pregnancy Considerations

Metformin crosses the placenta (ADA 2020). Refer to individual monographs.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience nausea, vomiting, diarrhea, passing gas, loss of strength and energy, headache, common cold symptoms, stuffy nose, or runny nose. Have patient report immediately to prescriber signs of lactic acidosis (fast breathing, fast heartbeat, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, severe dizziness, feeling cold, or muscle pain or cramps), signs of a urinary tract infection (blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain), signs of heart problems (cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), chest pain, chills, sore throat, skin blisters, skin breakdown, persistent joint pain, or severe joint pain (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.