metformin/repaglinide (Rx)

Type 2 Diabetes Mellitus

Indicated as adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already treated with a meglitinide and metformin, or who have inadequate glycemic control on a meglitinide alone or metformin alone

Currently using comcomitant repaglinide and metformin

• Start initial PrandiMet dose similar to patient's current repaglinide/metformin dosage, but do not exceed; titrate as necessary to acheive targeted glycemic control

Inadequately controlled with either metformin or a meglitinide monotherapy

• 500 mg/1 mg PO q12hr ac initially
• May gradually increase dose based on glycemic response

Dosage Modifications

Hepatic impairment: Do not administer

Renal impairment

• Obtain eGFR before starting metformin
• eGFR <30 mL/min/1.73 m²: Contraindicated
• eGFR 30-45 mL/min/1.73 m²: Not recommended to initiate treatment
• Monitor eGFR at least annually or more often for those at risk for renal impairment (eg, elderly)
• If eGFR falls below 45mL/min/1.73 m² while taking metformin, risks and benefits of continuing therapy should be evaluated
• If eGFR falls below 30 mL/min/1.73 m²: while taking metformin, discontinue the drug

Safety and efficacy not established; not recommended for use in children

Currently using comcomitant repaglinide and metformin

Start initial PrandiMet dose similar to patient's current repaglinide/metformin dosage, but do not exceed; titrate as necessary to acheive targeted glycemic control

Do not administer to patients >80 years before assessing renal function and determined to be normal

Inadequately controlled with either metformin or meglitinide monotherapy

500 mg/1 mg PO q12hr ac initially

May gradually and conservatively increase dose based on glycemic response

Do not administer to patients >80 years before assessing renal function and determined to be normal

Contraindicated (1)

• gemfibrozil

  gemfibrozil will increase the level or effect of repaglinide by Other (see comment). Contraindicated. Repaglinide is a CYP2C8 substrate. Gemfibrozil inhibits CYP2C8 and substantially increases repaglinide levels.

Serious - Use Alternative (37)

• abametapir

  abametapir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

• apalutamide

  apalutamide will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• carbamazepine

  carbamazepine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cimetidine

  cimetidine will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• clarithromycin

  clarithromycin will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• clopidogrel

  clopidogrel will increase the level or effect of repaglinide by Other (see comment). Avoid or Use Alternate Drug. Clopidogrel inhibits CYP2C8. Coadministration significantly increases repaglinide serum levels. If unable to avoid coadministration, decrease initial repaglinide dose to 0.5 mg/meal and do not exceed 4 mg/day.

• contrast media (iodinated)

  contrast media (iodinated) increases levels of metformin by decreasing renal clearance. Contraindicated. Acute renal failure or lactic acidosis may result. D/c metformin 48 hr before and after imaging study.

• eluxadoline

  repaglinide increases levels of eluxadoline by decreasing metabolism. Avoid or Use Alternate Drug. Decrease eluxadoline dose to 75 mg PO BID if coadministered with OATP1B1 inhibitors. .

• erythromycin base

  erythromycin base will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin stearate

  erythromycin stearate will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ethanol

  ethanol, repaglinide. Other (see comment). Contraindicated. Comment: Excessive EtOH consumption may alter glycemic control. Some sulfonylureas may produce a disulfiram like rxn.
  
  ethanol increases toxicity of metformin by Other (see comment). Contraindicated. Comment: Excessive EtOH consumption may alter glycemic control. Some sulfonylureas may produce a disulfiram like rxn; alcohol may potentiate the risk of lactic acidosis.

• fexinidazole

  fexinidazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• ioversol

  ioversol increases levels of metformin by decreasing renal clearance. Contraindicated. Acute renal failure or lactic acidosis may result. D/c metformin 48 hr before and after imaging study.

• idelalisib

  idelalisib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

• ivosidenib

  ivosidenib will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ketoconazole

  ketoconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• leniolisib

  leniolisib will increase the level or effect of repaglinide by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, an OATP1B1 and OATP1B3 inhibitor, may increase systemic exposure of these substrates

• letermovir

  letermovir, repaglinide. Either increases levels of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations. When letermovir is coadministered with cyclosporine, avoid use with repaglinide.

• levoketoconazole

  levoketoconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lumacaftor/ivacaftor

  lumacaftor/ivacaftor will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repaglinide is metabolized by CYP3A and CYP2C8. Lumacaftor /ivacaftor is a strong CYP3A4 inducer and may also induce CYP2C8.

• methylene blue

  methylene blue will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• nefazodone

  nefazodone will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pacritinib

  pacritinib will increase the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Concomitant administration of pacritinib (OCT1 inhibitor) with OCT1 substrates may increase the plasma concentrations of these substrates.

• ranolazine

  ranolazine will increase the level or effect of metformin by decreasing elimination. Avoid or Use Alternate Drug. Limit metformin dose to 1700 mg/day when used together with ranolazine 1000 mg twice daily; monitor closelly for signs or symptoms of metformin toxicity

• rifabutin

  rifabutin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifampin

  rifampin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• St John's Wort

  St John's Wort will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• risdiplam

  risdiplam will increase the level or effect of metformin by decreasing elimination. Avoid or Use Alternate Drug. Risdiplam inhibits MATE1 and MATE2-K. If unable to avoid coadministration with MATE substrates, consider dosage reduction of MATE substrate.

• selegiline

  selegiline will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• selegiline transdermal

  selegiline transdermal will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• tafenoquine

  tafenoquine will increase the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.

• tedizolid

  tedizolid will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• tranylcypromine

  tranylcypromine will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• trilaciclib

  trilaciclib will decrease the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.

• trofinetide

  trofinetide will increase the level or effect of repaglinide by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.

Monitor Closely (306)

• acetazolamide

  acetazolamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

• albiglutide

  albiglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
  
  albiglutide, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• alogliptin

  alogliptin, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of alogliptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue .

• amiodarone

  amiodarone will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• amlodipine

  amlodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• amobarbital

  amobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• apalutamide

  apalutamide will decrease the level or effect of repaglinide by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces OATP1B1 and may decrease systemic exposure of drugs that are OATP1B1 substrates.

• aprepitant

  aprepitant will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• aripiprazole

  aripiprazole, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  aripiprazole, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• armodafinil

  armodafinil will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• asenapine

  asenapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• artemether/lumefantrine

  artemether/lumefantrine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• asenapine

  asenapine, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• atazanavir

  atazanavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  atazanavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• atorvastatin

  repaglinide increases toxicity of atorvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• benazepril

  benazepril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• benzphetamine

  benzphetamine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• betamethasone

  betamethasone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• bexagliflozin

  bexagliflozin, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin secretagogue to avoid hypoglycemia when coadministered with bexagliflozin.

• bexarotene

  bexarotene increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Based on the mechanism of action, bexarotene capsules may increase the action of insulin enhancing agents, resulting in hypoglycemia. Hypoglycemia has not been associated with bexarotene monotherapy.

• bictegravir

  bictegravir will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely. Bictegravir inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE1) in vitro. Coadministration with OCT2 and MATE1 substrates may increase their plasma concentrations. Metformin dose reduction may be required.

• bitter melon

  bitter melon increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia.
  
  bitter melon increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia.

• bosentan

  bosentan will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• brexpiprazole

  brexpiprazole decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• budesonide

  budesonide will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bumetanide

  bumetanide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• bupropion

  bupropion increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Bupropion may inhibit OCT2 mediated renal excretion of metformin.

• butabarbital

  butabarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• butalbital

  butalbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• canagliflozin

  repaglinide, canagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with canagliflozin.

• cannabidiol

  cannabidiol will increase the level or effect of repaglinide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

• captopril

  captopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• cariprazine

  cariprazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• cenobamate

  cenobamate will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• cephalexin

  cephalexin increases toxicity of metformin by decreasing renal clearance. Use Caution/Monitor. particularly in patients who may have other risk factors for metformin toxicity. .

• ceritinib

  ceritinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ceritinib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• chloramphenicol

  chloramphenicol will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• chlorpromazine

  chlorpromazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• cholic acid

  repaglinide increases toxicity of cholic acid by decreasing elimination. Modify Therapy/Monitor Closely. Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP). May exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is necessary, monitor serum transaminases and bilirubin.

• cimetidine

  cimetidine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• cinnamon

  cinnamon increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.
  
  cinnamon increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.

• ciprofloxacin

  ciprofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Hyper and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Careful monitoring of blood glucose is recommended.
  
  ciprofloxacin increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Hyper and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Careful monitoring of blood glucose is recommended.

• citalopram

  citalopram increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• clozapine

  clozapine, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• clevidipine

  clevidipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• clozapine

  clozapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• cobicistat

  cobicistat will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• colesevelam

  colesevelam increases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• conivaptan

  conivaptan will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conjugated estrogens

  conjugated estrogens decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• corticotropin

  corticotropin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• cortisone

  cortisone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• crizotinib

  crizotinib increases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

• crofelemer

  crofelemer increases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• cyclosporine

  cyclosporine will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cyclosporine increases low dose repaglinide exposures by 2.5 fold. Do not exceed 6 mg/day of repaglinide. Consider increasing frequency of glucose monitoring if coadministered.

• dabrafenib

  dabrafenib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
  
  dabrafenib will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• dalfampridine

  metformin, dalfampridine. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Metformin and dalfampridine are organic cation transporter 2 (OCT2) substrates; both drugs may compete for renal tubular uptake and could potentially increase systemic exposure of either drug when administered concomitantly.

• dapagliflozin

  repaglinide, dapagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with dapagliflozin.

• darifenacin

  darifenacin will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• darunavir

  darunavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  darunavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• dasatinib

  dasatinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• desogestrel

  desogestrel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• deferasirox

  deferasirox will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Consider repaglinide dose reduction and carefully monitor blood glucose levels when repaglinide is used concomitantly with deferasirox.

• dexamethasone

  dexamethasone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• DHEA, herbal

  DHEA, herbal will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diatrizoate

  diatrizoate increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• diatrizoate meglumine/diatrizoate sodium

  diatrizoate meglumine/diatrizoate sodium increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• diazoxide

  diazoxide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• dichlorphenamide

  dichlorphenamide, metformin. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.

• dienogest/estradiol valerate

  dienogest/estradiol valerate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• diethylpropion

  diethylpropion decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• digoxin

  digoxin, metformin. Either increases levels of the other by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor. Measure serum digoxin concentrations before initiating metformin. Monitor patients who take both metformin and digoxin for possible digoxin toxicity and lactic acidosis. Reduce the digoxin and/or metformin dose as necessary.

• diltiazem

  diltiazem decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
  
  diltiazem will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor glucose and hypoglycemic symptoms (eg, headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, palpitations).

• dofetilide

  dofetilide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• dronedarone

  dronedarone will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dolutegravir

  dolutegravir will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely. Dolutegravir inhibits the renal organic cation transporter, OCT2; when used with metformin, limit total daily dose of metformin to 1,000 mg either when starting metformin or dolutegravir; when stopping dolutegravir, adjustment of metformin dose may be necessary; monitor blood glucose when initiating concomitant use and after withdrawal of dolutegravir

• drospirenone

  drospirenone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• dulaglutide

  dulaglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
  
  dulaglutide, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• efavirenz

  efavirenz will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• enalapril

  enalapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• elagolix

  elagolix decreases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

• eltrombopag

  eltrombopag increases levels of repaglinide by decreasing metabolism. Use Caution/Monitor. OATP transporter protein inhibition.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• empagliflozin

  empagliflozin, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with SGLT2 inhibitors.

• encorafenib

  encorafenib, repaglinide. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
  
  encorafenib will increase the level or effect of repaglinide by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 inhibitor) may increase the concentration and toxicities of OATP1B1 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

• entecavir

  entecavir, metformin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration of entecavir with metformin may increase the risk of lactic acidosis.

• enzalutamide

  enzalutamide will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erdafitinib

  metformin increases levels of erdafitinib by decreasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.

• ertugliflozin

  ertugliflozin, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.

• escitalopram

  escitalopram increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• eslicarbazepine acetate

  eslicarbazepine acetate will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estradiol

  estradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• estrogens conjugated synthetic

  estrogens conjugated synthetic decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• estropipate

  estropipate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethacrynic acid

  ethacrynic acid decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethinylestradiol

  ethinylestradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethiodized oil

  ethiodized oil increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• etonogestrel

  etonogestrel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• etravirine

  etravirine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• everolimus

  everolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• exenatide injectable solution

  exenatide injectable solution, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
  
  exenatide injectable solution, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• exenatide injectable suspension

  exenatide injectable suspension, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
  
  exenatide injectable suspension, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• fedratinib

  fedratinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• felodipine

  felodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• fleroxacin

  fleroxacin increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
  
  fleroxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• fluconazole

  fluconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluoxetine

  fluoxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• fludrocortisone

  fludrocortisone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluphenazine

  fluphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• fluvastatin

  repaglinide increases toxicity of fluvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• fluvoxamine

  fluvoxamine will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  fluvoxamine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• fosamprenavir

  fosamprenavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  fosamprenavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• fosaprepitant

  fosaprepitant will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosinopril

  fosinopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• fosphenytoin

  fosphenytoin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  fosphenytoin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• fostemsavir

  fostemsavir will increase the level or effect of repaglinide by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits OATP1B1/3 transporter. If possible, avoid coadministration or modify dose of OATP1B1/3 substrates coadministered with fostemsavir.

• gemifloxacin

  gemifloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• gemifloxacin

  gemifloxacin increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• glecaprevir/pibrentasvir

  repaglinide will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors
  
  glecaprevir/pibrentasvir will increase the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

• glucagon intranasal

  glucagon intranasal decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• glycopyrrolate

  glycopyrrolate increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. May require a dose reduction.

• goserelin

  goserelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• grapefruit

  grapefruit will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• griseofulvin

  griseofulvin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• histrelin

  histrelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• hydrocortisone

  hydrocortisone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hydroxyprogesterone caproate (DSC)

  hydroxyprogesterone caproate (DSC) decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• iloperidone

  iloperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  iloperidone, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  iloperidone increases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

• imidapril

  imidapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• indinavir

  indinavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• indinavir

  indinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• insulin aspart

  metformin, insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin aspart protamine/insulin aspart

  metformin, insulin aspart protamine/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin degludec

  metformin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin degludec/insulin aspart

  metformin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin detemir

  metformin, insulin detemir. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin glargine

  metformin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin glulisine

  metformin, insulin glulisine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin inhaled

  metformin, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin isophane human/insulin regular human

  metformin, insulin isophane human/insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin lispro

  metformin, insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin lispro protamine/insulin lispro

  metformin, insulin lispro protamine/insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin NPH

  metformin, insulin NPH. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin regular human

  metformin, insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• iodixanol

  iodixanol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• ioflupane I 123

  ioflupane I 123 increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• iohexol

  iohexol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• iopamidol

  iopamidol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• iopromide

  iopromide increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• ioversol

  ioversol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• ioxilan

  ioxilan increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• isocarboxazid

  isocarboxazid will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• isoniazid

  isoniazid decreases effects of metformin by unspecified interaction mechanism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
  
  isoniazid will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isradipine

  isradipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• istradefylline

  istradefylline will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• itraconazole

  itraconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ketotifen, ophthalmic

  ketotifen, ophthalmic, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC.
  
  ketotifen, ophthalmic, metformin. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC.

• lanreotide

  lanreotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• lapatinib

  lapatinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lenacapavir

  lenacapavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• leuprolide

  leuprolide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• levofloxacin

  levofloxacin increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
  
  levofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• levonorgestrel intrauterine

  levonorgestrel intrauterine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• liraglutide

  liraglutide, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• levonorgestrel oral

  levonorgestrel oral decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• levothyroxine

  levothyroxine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• linezolid

  linezolid will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• liothyronine

  liothyronine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• liotrix

  liotrix decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• liraglutide

  liraglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• lisinopril

  lisinopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• lithium

  metformin decreases levels of lithium by Other (see comment). Use Caution/Monitor. Comment: SGLT2 inhibitors with lithium may decrease serum lithium concentrations; monitor serum lithium concentration more frequently during therapy initiation and dosage changes.

• lonapegsomatropin

  lonapegsomatropin decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Closely monitor blood glucose when treated with antidiabetic agents. Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.
  
  lonapegsomatropin decreases effects of repaglinide by Other (see comment). Use Caution/Monitor. Comment: Closely monitor blood glucose when treated with antidiabetic agents. Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.

• lopinavir

  lopinavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  lopinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• lorlatinib

  lorlatinib will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lurasidone

  lurasidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• lumefantrine

  lumefantrine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lurasidone

  lurasidone, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• marijuana

  marijuana decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
  
  marijuana will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  marijuana decreases effects of repaglinide by pharmacodynamic antagonism. Use Caution/Monitor.

• mecasermin

  mecasermin increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.
  
  mecasermin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.

• medroxyprogesterone

  medroxyprogesterone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• methylprednisolone

  methylprednisolone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• methamphetamine

  methamphetamine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• methazolamide

  methazolamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

• metreleptin

  repaglinide, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.

• metronidazole

  metronidazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• miconazole vaginal

  miconazole vaginal will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mifepristone

  mifepristone will increase the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Inhibits CYP2C8/2C9; use smallest recommended doses for substrates and monitor
  
  mifepristone will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mitotane

  mitotane decreases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

• moexipril

  moexipril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• moxifloxacin

  moxifloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
  
  moxifloxacin increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• nafcillin

  nafcillin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nelfinavir

  nelfinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• nelfinavir

  nelfinavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nevirapine

  nevirapine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• niacin

  niacin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nicardipine

  nicardipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nifedipine

  nifedipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
  
  nifedipine will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nilotinib

  nilotinib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
  
  nilotinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nimodipine

  nimodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• ofloxacin

  ofloxacin increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• nisoldipine

  nisoldipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nizatidine

  nizatidine will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely.

• norelgestromin

  norelgestromin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• norethindrone

  norethindrone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• norgestimate

  norgestimate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• octreotide

  octreotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ofloxacin

  ofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• olanzapine

  olanzapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  olanzapine, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• omacetaxine

  omacetaxine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• omaveloxolone

  omaveloxolone will decrease the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP2C8 substrates. Check prescribing information of substrate if dosage modification is needed.
  
  omaveloxolone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP3A4 substrates. Check prescribing information of substrate if dosage modification is needed.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Monitor for signs of onset of lactic acidosis such as respiratory distress, somnolence, and non-specific abdominal distress or worsening renal function; concomitant metformin use in patients with renal insufficiency or hepatic impairment not recommended.

• ondansetron

  ondansetron increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Ondansetron inhibition of transporters (MATE or OCTs), which are responsible for active renal secretion of metformin may play a role.

• opuntia ficus indica

  opuntia ficus indica increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.
  
  opuntia ficus indica increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor.

• oxcarbazepine

  oxcarbazepine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• paliperidone

  paliperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• paliperidone

  paliperidone, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• paroxetine

  paroxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• pasireotide

  pasireotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• patiromer

  patiromer will decrease the level or effect of metformin by drug binding in GI tract. Modify Therapy/Monitor Closely. Separate administration by at least 3 hr from patiromer

• pentamidine

  pentamidine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• pentobarbital

  pentobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• perindopril

  perindopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• perphenazine

  perphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• phendimetrazine

  phendimetrazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• phenelzine

  phenelzine will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• phenobarbital

  phenobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• phentermine

  phentermine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• phenytoin

  phenytoin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenytoin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• posaconazole

  posaconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• procainamide

  metformin will increase the level or effect of procainamide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• pravastatin

  repaglinide increases toxicity of pravastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• prednisone

  prednisone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• primidone

  primidone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• procarbazine

  procarbazine will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• prochlorperazine

  prochlorperazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• progesterone intravaginal gel

  progesterone intravaginal gel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• progesterone micronized

  progesterone micronized decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• progesterone, natural

  progesterone, natural decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• promethazine

  promethazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• quetiapine

  quetiapine, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  quetiapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• quinapril

  quinapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• quinupristin/dalfopristin

  quinupristin/dalfopristin will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinidine

  quinidine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• ramipril

  ramipril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• ranolazine

  ranolazine increases toxicity of repaglinide by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• rasagiline

  rasagiline will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• ribociclib

  ribociclib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifapentine

  rifapentine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• risperidone

  risperidone, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  risperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• ritonavir

  ritonavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
  
  ritonavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ropeginterferon alfa 2b

  ropeginterferon alfa 2b will increase the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates. Therefore, monitor patients who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index from toxicities to such drugs.

• saquinavir

  saquinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• rosuvastatin

  repaglinide increases toxicity of rosuvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• rucaparib

  rucaparib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

• rufinamide

  rufinamide will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• sacubitril/valsartan

  repaglinide will increase the level or effect of sacubitril/valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

• saquinavir

  saquinavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• secobarbital

  secobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• semaglutide

  semaglutide, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin secretagogues with GLP-1 agonists may increase hypoglycemia risk. Lowering the insulin secretagogue dose may reduce hypoglycemia risk. .

• sertraline

  sertraline increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• shark cartilage

  shark cartilage increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction.
  
  shark cartilage increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction.

• simvastatin

  repaglinide increases toxicity of simvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• sirolimus

  sirolimus decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• sofosbuvir/velpatasvir

  sofosbuvir/velpatasvir increases levels of repaglinide by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

• somapacitan

  somapacitan decreases effects of metformin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating somapacitan. .

• somatropin

  somatropin decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• spironolactone

  spironolactone will increase the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Spironolactone inhibits CYP2C8; repaglinice dose may need to be adjusted as it is metabolized by CYP2C8

• stiripentol

  stiripentol, repaglinide. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
  
  stiripentol will increase the level or effect of repaglinide by Other (see comment). Modify Therapy/Monitor Closely. Stiripentol is a CYP2C8 inhibitor. Consider dosage reduction for CYP2C8 substrates if adverse effects are experienced when coadministered.

• sulfadiazine

  sulfadiazine increases levels of repaglinide by plasma protein binding competition. Use Caution/Monitor.

• sulfamethoxazole

  sulfamethoxazole increases levels of repaglinide by plasma protein binding competition. Use Caution/Monitor.

• sulfamethoxypyridazine

  sulfamethoxypyridazine increases effects of repaglinide by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.
  
  sulfamethoxypyridazine increases effects of metformin by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• sulfisoxazole

  sulfisoxazole increases levels of repaglinide by plasma protein binding competition. Use Caution/Monitor.

• tacrolimus

  tacrolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• tazemetostat

  tazemetostat will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• teclistamab

  teclistamab will increase the level or effect of repaglinide by altering metabolism. Use Caution/Monitor. Teclistamab causes release of cytokines that may suppress activity of CYP450 enzymes, resulting in increased exposure of CYP substrates. Monitor for increased concentrations or toxicities of sensitive CYP substrates. Adjust dose of CYP substrate drug as needed.

• tecovirimat

  tecovirimat will increase the level or effect of repaglinide by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Monitor for adverse effects if coadministered with substrates of these enzymes. Monitor blood glucose and monitor for hypoglycemic symptoms.
  
  tecovirimat will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• temsirolimus

  temsirolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• tenofovir DF

  tenofovir DF increases levels of metformin by decreasing renal clearance. Use Caution/Monitor. Increased risk of lactic acidosis.

• teriflunomide

  teriflunomide increases levels of repaglinide by Other (see comment). Use Caution/Monitor. Comment: Teriflunomide inhibits CYP2C8; caution when coadministered with CYP2C8 substrates.

• thioridazine

  thioridazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• thyroid desiccated

  thyroid desiccated decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• tibolone

  tibolone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• tipranavir

  tipranavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
  
  tipranavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  tipranavir, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Tipranavir's effect on oral hypoglycemics via hepatic CYP2C9 unknown; carefully monitor blood glucose.

• topiramate

  topiramate will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  topiramate increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

• torsemide

  torsemide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• triamcinolone acetonide injectable suspension

  triamcinolone acetonide injectable suspension decreases effects of repaglinide by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.

• trandolapril

  trandolapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• triamcinolone acetonide injectable suspension

  triamcinolone acetonide injectable suspension decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.

• trifluoperazine

  trifluoperazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• trimethoprim

  trimethoprim increases levels of repaglinide by decreasing metabolism. Use Caution/Monitor. Hepatic cytochrome P450 2C8.
  
  trimethoprim increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Trimethoprim may inhibit active renal tubular secretion of metformin (eg, via OCT2, MATE1); dose adjustments may be necessary.

• triptorelin

  triptorelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• trofinetide

  trofinetide will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).

• trospium chloride

  metformin will decrease the level or effect of trospium chloride by increasing renal clearance. Use Caution/Monitor. Coadministration reduced steady state trospium systemic exposure (decreased AUC and Cmax) by competing for renal tubular secretion

• valsartan

  repaglinide will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

• vandetanib

  vandetanib increases levels of metformin by Other (see comment). Modify Therapy/Monitor Closely. Comment: Vandetanib inhibits the uptake of substrates of organic cation transporter type 2 (OCT2).

• verapamil

  verapamil decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Verapamil may inhibit hepatic uptake of metformin by OCT1 and/or other transporters.
  
  verapamil will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vilazodone

  vilazodone increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• voriconazole

  voriconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vorinostat

  vorinostat decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• vortioxetine

  vortioxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• xipamide

  xipamide decreases levels of repaglinide by increasing renal clearance. Use Caution/Monitor.
  
  xipamide decreases levels of metformin by increasing renal clearance. Use Caution/Monitor.

• zafirlukast

  zafirlukast will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ziprasidone

  ziprasidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• ziprasidone

  ziprasidone, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• zonisamide

  zonisamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

Minor (100)

• acetazolamide

  acetazolamide will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• agrimony

  agrimony increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  agrimony increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• American ginseng

  American ginseng increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  American ginseng increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• amitriptyline

  amitriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  amitriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• amoxapine

  amoxapine increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  amoxapine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• anamu

  anamu increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.
  
  anamu increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.

• anastrozole

  anastrozole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• bendroflumethiazide

  bendroflumethiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• bendroflumethiazide

  bendroflumethiazide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• budesonide

  budesonide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  budesonide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.

• chlorothiazide

  chlorothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  chlorothiazide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• chlorthalidone

  chlorthalidone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  chlorthalidone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• chromium

  chromium increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  chromium increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• clomipramine

  clomipramine increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  clomipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• clonidine

  clonidine decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, repaglinide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  clonidine decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, metformin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• cornsilk

  cornsilk increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
  
  cornsilk increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• cortisone

  cortisone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  cortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• cyanocobalamin

  metformin decreases levels of cyanocobalamin by unspecified interaction mechanism. Minor/Significance Unknown. It may take several years of metformin therapy to develop vitamin B12 deficiency.

• cyclopenthiazide

  cyclopenthiazide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• cyclopenthiazide

  cyclopenthiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• cyclophosphamide

  cyclophosphamide will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• damiana

  damiana decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.
  
  damiana decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.

• danazol

  danazol increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  danazol increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• deflazacort

  deflazacort decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  deflazacort decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• desipramine

  desipramine increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  desipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• devil's claw

  devil's claw increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  devil's claw increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• dexamethasone

  dexamethasone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  dexamethasone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• diltiazem

  diltiazem will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• doxepin

  doxepin increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• doxepin

  doxepin increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• elderberry

  elderberry increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (in vitro research).
  
  elderberry increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (in vitro research).

• eucalyptus

  eucalyptus increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.
  
  eucalyptus increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.

• famotidine

  famotidine increases levels of metformin by decreasing renal clearance. Minor/Significance Unknown.

• fludrocortisone

  fludrocortisone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.

• fludrocortisone

  fludrocortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• fluoxymesterone

  fluoxymesterone increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  fluoxymesterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• fo-ti

  fo-ti increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  fo-ti increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• folic acid

  metformin decreases levels of folic acid by unspecified interaction mechanism. Minor/Significance Unknown.

• forskolin

  forskolin increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Colenol, a compound found in Coleus root, may stimulate insulin release.

• forskolin

  forskolin increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Colenol, a compound found in Coleus root, may stimulate insulin release.

• furosemide

  metformin decreases levels of furosemide by unspecified interaction mechanism. Minor/Significance Unknown.
  
  furosemide increases levels of metformin by unspecified interaction mechanism. Minor/Significance Unknown. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• gotu kola

  gotu kola increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).
  
  gotu kola increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).

• guanfacine

  guanfacine, metformin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  guanfacine decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  guanfacine decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  guanfacine, repaglinide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• gymnema

  gymnema increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  gymnema increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• horse chestnut seed

  horse chestnut seed increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  horse chestnut seed increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• hydrochlorothiazide

  hydrochlorothiazide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  hydrochlorothiazide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  hydrochlorothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• hydrocortisone

  hydrocortisone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  hydrocortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• ibuprofen/famotidine

  ibuprofen/famotidine increases levels of metformin by decreasing renal clearance. Minor/Significance Unknown.

• imipramine

  imipramine increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• imipramine

  imipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• indapamide

  indapamide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  indapamide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• isoniazid

  isoniazid decreases effects of repaglinide by unspecified interaction mechanism. Minor/Significance Unknown.

• L-methylfolate

  metformin decreases levels of L-methylfolate by unspecified interaction mechanism. Minor/Significance Unknown.

• juniper

  juniper increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• juniper

  juniper increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• larotrectinib

  larotrectinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lofepramine

  lofepramine increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  lofepramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• lycopus

  lycopus increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
  
  lycopus increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• maitake

  maitake increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (animal research).
  
  maitake increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (animal research).

• maprotiline

  maprotiline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  maprotiline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• memantine

  memantine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mesterolone

  mesterolone increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• mesterolone

  mesterolone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• methyclothiazide

  methyclothiazide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  methyclothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  methyclothiazide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• methylprednisolone

  methylprednisolone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  methylprednisolone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• methyltestosterone

  methyltestosterone increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  methyltestosterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• metolazone

  metolazone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  metolazone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• midodrine

  metformin will increase the level or effect of midodrine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nettle

  nettle increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).

• nettle

  nettle increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).

• nifedipine

  nifedipine increases levels of metformin by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• nortriptyline

  nortriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  nortriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• ofloxacin

  ofloxacin, repaglinide. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.
  
  metformin will increase the level or effect of ofloxacin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  ofloxacin, metformin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.

• oxandrolone

  oxandrolone increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  oxandrolone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• oxymetholone

  oxymetholone increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  oxymetholone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• pegvisomant

  pegvisomant increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  pegvisomant increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• potassium acid phosphate

  potassium acid phosphate increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
  
  potassium acid phosphate increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

• potassium chloride

  potassium chloride increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
  
  potassium chloride increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

• potassium citrate

  potassium citrate increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
  
  potassium citrate increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

• prednisolone

  prednisolone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  prednisolone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.

• prednisone

  prednisone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  prednisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• protriptyline

  protriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  protriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• quinine

  metformin will increase the level or effect of quinine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sage

  sage increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• sage

  sage increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• stevia

  stevia increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  stevia increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• sulfamethoxazole

  sulfamethoxazole will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• testosterone

  testosterone increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• testosterone

  testosterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• testosterone buccal system

  testosterone buccal system increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  testosterone buccal system increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• testosterone topical

  testosterone topical increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  testosterone topical increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• tongkat ali

  tongkat ali increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia.
  
  tongkat ali increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia.

• trazodone

  trazodone increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  trazodone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• triamterene

  metformin will increase the level or effect of triamterene by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trimipramine

  trimipramine increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• trimethoprim

  metformin will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trimipramine

  trimipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• vanadium

  vanadium increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  vanadium increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• verapamil

  metformin will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• voclosporin

  voclosporin will increase the level or effect of repaglinide by Other (see comment). Minor/Significance Unknown. Information suggests voclosporin (an OATP1B1 inhibitor) may increase in the concentration of OATP1B1 substrates is possible. Monitor for adverse reactions of OATP1B1 substrates when coadministered with voclosporin.

• abametapir

  Serious - Use Alternative (1)abametapir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

• acetazolamide

  Monitor Closely (1)acetazolamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.Minor (1)acetazolamide will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• agrimony

  Minor (2)agrimony increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  agrimony increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• albiglutide

  Monitor Closely (2)albiglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
  
  albiglutide, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• alogliptin

  Monitor Closely (1)alogliptin, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of alogliptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue .

• American ginseng

  Minor (1)American ginseng increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• amiodarone

  Monitor Closely (1)amiodarone will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• amitriptyline

  Minor (2)amitriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  amitriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• amlodipine

  Monitor Closely (1)amlodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• amobarbital

  Monitor Closely (1)amobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amoxapine

  Minor (2)amoxapine increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  amoxapine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• anamu

  Minor (2)anamu increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.
  
  anamu increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.

• anastrozole

  Minor (1)anastrozole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• apalutamide

  Monitor Closely (1)apalutamide will decrease the level or effect of repaglinide by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces OATP1B1 and may decrease systemic exposure of drugs that are OATP1B1 substrates.Serious - Use Alternative (1)apalutamide will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• aprepitant

  Monitor Closely (1)aprepitant will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• aripiprazole

  Monitor Closely (2)aripiprazole, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  aripiprazole, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• armodafinil

  Monitor Closely (1)armodafinil will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• artemether/lumefantrine

  Monitor Closely (1)artemether/lumefantrine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• asenapine

  Monitor Closely (2)asenapine, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  asenapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• atazanavir

  Monitor Closely (2)atazanavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  atazanavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• atorvastatin

  Monitor Closely (1)repaglinide increases toxicity of atorvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• benazepril

  Monitor Closely (1)benazepril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• bendroflumethiazide

  Minor (2)bendroflumethiazide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  bendroflumethiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• benzphetamine

  Monitor Closely (1)benzphetamine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• betamethasone

  Monitor Closely (1)betamethasone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• bexagliflozin

  Monitor Closely (1)bexagliflozin, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin secretagogue to avoid hypoglycemia when coadministered with bexagliflozin.

• bexarotene

  Monitor Closely (1)bexarotene increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Based on the mechanism of action, bexarotene capsules may increase the action of insulin enhancing agents, resulting in hypoglycemia. Hypoglycemia has not been associated with bexarotene monotherapy.

• bictegravir

  Monitor Closely (1)bictegravir will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely. Bictegravir inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE1) in vitro. Coadministration with OCT2 and MATE1 substrates may increase their plasma concentrations. Metformin dose reduction may be required.

• bitter melon

  Monitor Closely (2)bitter melon increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia.
  
  bitter melon increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia.

• bosentan

  Monitor Closely (1)bosentan will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• brexpiprazole

  Monitor Closely (1)brexpiprazole decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• budesonide

  Monitor Closely (1)budesonide will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)budesonide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  budesonide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.

• bumetanide

  Monitor Closely (1)bumetanide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• bupropion

  Monitor Closely (1)bupropion increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Bupropion may inhibit OCT2 mediated renal excretion of metformin.

• butabarbital

  Monitor Closely (1)butabarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• butalbital

  Monitor Closely (1)butalbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• canagliflozin

  Monitor Closely (1)repaglinide, canagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with canagliflozin.

• cannabidiol

  Monitor Closely (1)cannabidiol will increase the level or effect of repaglinide by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

• captopril

  Monitor Closely (1)captopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• carbamazepine

  Serious - Use Alternative (1)carbamazepine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cariprazine

  Monitor Closely (1)cariprazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• cenobamate

  Monitor Closely (1)cenobamate will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• cephalexin

  Monitor Closely (1)cephalexin increases toxicity of metformin by decreasing renal clearance. Use Caution/Monitor. particularly in patients who may have other risk factors for metformin toxicity. .

• ceritinib

  Monitor Closely (2)ceritinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ceritinib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• chloramphenicol

  Monitor Closely (1)chloramphenicol will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• chlorothiazide

  Minor (2)chlorothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  chlorothiazide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• chlorpromazine

  Monitor Closely (1)chlorpromazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• chlorthalidone

  Minor (2)chlorthalidone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  chlorthalidone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• cholic acid

  Monitor Closely (1)repaglinide increases toxicity of cholic acid by decreasing elimination. Modify Therapy/Monitor Closely. Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP). May exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is necessary, monitor serum transaminases and bilirubin.

• chromium

  Minor (2)chromium increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  chromium increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• cimetidine

  Monitor Closely (1)cimetidine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.Serious - Use Alternative (1)cimetidine will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cinnamon

  Monitor Closely (2)cinnamon increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.
  
  cinnamon increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.

• ciprofloxacin

  Monitor Closely (2)ciprofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Hyper and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Careful monitoring of blood glucose is recommended.
  
  ciprofloxacin increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Hyper and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Careful monitoring of blood glucose is recommended.

• citalopram

  Monitor Closely (1)citalopram increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• clarithromycin

  Serious - Use Alternative (1)clarithromycin will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• clevidipine

  Monitor Closely (1)clevidipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• clomipramine

  Minor (2)clomipramine increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  clomipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• clonidine

  Minor (4)clonidine decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, repaglinide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  clonidine decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, metformin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• clopidogrel

  Serious - Use Alternative (1)clopidogrel will increase the level or effect of repaglinide by Other (see comment). Avoid or Use Alternate Drug. Clopidogrel inhibits CYP2C8. Coadministration significantly increases repaglinide serum levels. If unable to avoid coadministration, decrease initial repaglinide dose to 0.5 mg/meal and do not exceed 4 mg/day.

• clozapine

  Monitor Closely (2)clozapine, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  clozapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• cobicistat

  Monitor Closely (1)cobicistat will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• colesevelam

  Monitor Closely (1)colesevelam increases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• conivaptan

  Monitor Closely (1)conivaptan will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conjugated estrogens

  Monitor Closely (1)conjugated estrogens decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• contrast media (iodinated)

  Serious - Use Alternative (1)contrast media (iodinated) increases levels of metformin by decreasing renal clearance. Contraindicated. Acute renal failure or lactic acidosis may result. D/c metformin 48 hr before and after imaging study.

• cornsilk

  Minor (2)cornsilk increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
  
  cornsilk increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• corticotropin

  Monitor Closely (1)corticotropin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• cortisone

  Monitor Closely (1)cortisone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)cortisone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  cortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• crizotinib

  Monitor Closely (1)crizotinib increases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

• crofelemer

  Monitor Closely (1)crofelemer increases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• cyanocobalamin

  Minor (1)metformin decreases levels of cyanocobalamin by unspecified interaction mechanism. Minor/Significance Unknown. It may take several years of metformin therapy to develop vitamin B12 deficiency.

• cyclopenthiazide

  Minor (2)cyclopenthiazide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  cyclopenthiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• cyclophosphamide

  Minor (1)cyclophosphamide will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Monitor Closely (1)cyclosporine will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cyclosporine increases low dose repaglinide exposures by 2.5 fold. Do not exceed 6 mg/day of repaglinide. Consider increasing frequency of glucose monitoring if coadministered.

• dabrafenib

  Monitor Closely (2)dabrafenib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
  
  dabrafenib will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• dalfampridine

  Monitor Closely (1)metformin, dalfampridine. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Metformin and dalfampridine are organic cation transporter 2 (OCT2) substrates; both drugs may compete for renal tubular uptake and could potentially increase systemic exposure of either drug when administered concomitantly.

• damiana

  Minor (2)damiana decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.
  
  damiana decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.

• danazol

  Minor (2)danazol increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  danazol increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• dapagliflozin

  Monitor Closely (1)repaglinide, dapagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with dapagliflozin.

• darifenacin

  Monitor Closely (1)darifenacin will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• darunavir

  Monitor Closely (2)darunavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  darunavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• dasatinib

  Monitor Closely (1)dasatinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• deferasirox

  Monitor Closely (1)deferasirox will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Consider repaglinide dose reduction and carefully monitor blood glucose levels when repaglinide is used concomitantly with deferasirox.

• deflazacort

  Minor (2)deflazacort decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  deflazacort decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• desipramine

  Minor (2)desipramine increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  desipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• desogestrel

  Monitor Closely (1)desogestrel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• devil's claw

  Minor (2)devil's claw increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  devil's claw increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• dexamethasone

  Monitor Closely (1)dexamethasone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)dexamethasone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  dexamethasone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• DHEA, herbal

  Monitor Closely (1)DHEA, herbal will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diatrizoate

  Monitor Closely (1)diatrizoate increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• diatrizoate meglumine/diatrizoate sodium

  Monitor Closely (1)diatrizoate meglumine/diatrizoate sodium increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• diazoxide

  Monitor Closely (1)diazoxide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• dichlorphenamide

  Monitor Closely (1)dichlorphenamide, metformin. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.

• dienogest/estradiol valerate

  Monitor Closely (1)dienogest/estradiol valerate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• diethylpropion

  Monitor Closely (1)diethylpropion decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• digoxin

  Monitor Closely (1)digoxin, metformin. Either increases levels of the other by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor. Measure serum digoxin concentrations before initiating metformin. Monitor patients who take both metformin and digoxin for possible digoxin toxicity and lactic acidosis. Reduce the digoxin and/or metformin dose as necessary.

• diltiazem

  Monitor Closely (2)diltiazem decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
  
  diltiazem will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor glucose and hypoglycemic symptoms (eg, headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, palpitations).Minor (1)diltiazem will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• dofetilide

  Monitor Closely (1)dofetilide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• dolutegravir

  Monitor Closely (1)dolutegravir will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely. Dolutegravir inhibits the renal organic cation transporter, OCT2; when used with metformin, limit total daily dose of metformin to 1,000 mg either when starting metformin or dolutegravir; when stopping dolutegravir, adjustment of metformin dose may be necessary; monitor blood glucose when initiating concomitant use and after withdrawal of dolutegravir

• doxepin

  Minor (2)doxepin increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  doxepin increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• dronedarone

  Monitor Closely (1)dronedarone will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• drospirenone

  Monitor Closely (1)drospirenone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• dulaglutide

  Monitor Closely (2)dulaglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
  
  dulaglutide, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• efavirenz

  Monitor Closely (1)efavirenz will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• elagolix

  Monitor Closely (1)elagolix decreases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

• elderberry

  Minor (2)elderberry increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (in vitro research).
  
  elderberry increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (in vitro research).

• eltrombopag

  Monitor Closely (1)eltrombopag increases levels of repaglinide by decreasing metabolism. Use Caution/Monitor. OATP transporter protein inhibition.

• eluxadoline

  Serious - Use Alternative (1)repaglinide increases levels of eluxadoline by decreasing metabolism. Avoid or Use Alternate Drug. Decrease eluxadoline dose to 75 mg PO BID if coadministered with OATP1B1 inhibitors. .

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• empagliflozin

  Monitor Closely (1)empagliflozin, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with SGLT2 inhibitors.

• enalapril

  Monitor Closely (1)enalapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• encorafenib

  Monitor Closely (2)encorafenib, repaglinide. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
  
  encorafenib will increase the level or effect of repaglinide by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 inhibitor) may increase the concentration and toxicities of OATP1B1 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

• entecavir

  Monitor Closely (1)entecavir, metformin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration of entecavir with metformin may increase the risk of lactic acidosis.

• enzalutamide

  Monitor Closely (1)enzalutamide will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erdafitinib

  Monitor Closely (1)metformin increases levels of erdafitinib by decreasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.

• ertugliflozin

  Monitor Closely (1)ertugliflozin, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.

• erythromycin base

  Serious - Use Alternative (1)erythromycin base will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  Serious - Use Alternative (1)erythromycin ethylsuccinate will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  Serious - Use Alternative (1)erythromycin lactobionate will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin stearate

  Serious - Use Alternative (1)erythromycin stearate will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• escitalopram

  Monitor Closely (1)escitalopram increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• eslicarbazepine acetate

  Monitor Closely (1)eslicarbazepine acetate will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estradiol

  Monitor Closely (1)estradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• estrogens conjugated synthetic

  Monitor Closely (1)estrogens conjugated synthetic decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• estropipate

  Monitor Closely (1)estropipate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethacrynic acid

  Monitor Closely (1)ethacrynic acid decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethanol

  Serious - Use Alternative (2)ethanol, repaglinide. Other (see comment). Contraindicated. Comment: Excessive EtOH consumption may alter glycemic control. Some sulfonylureas may produce a disulfiram like rxn.
  
  ethanol increases toxicity of metformin by Other (see comment). Contraindicated. Comment: Excessive EtOH consumption may alter glycemic control. Some sulfonylureas may produce a disulfiram like rxn; alcohol may potentiate the risk of lactic acidosis.

• ethinylestradiol

  Monitor Closely (1)ethinylestradiol decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ethiodized oil

  Monitor Closely (1)ethiodized oil increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• etonogestrel

  Monitor Closely (1)etonogestrel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• etravirine

  Monitor Closely (1)etravirine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eucalyptus

  Minor (2)eucalyptus increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.
  
  eucalyptus increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.

• everolimus

  Monitor Closely (1)everolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• exenatide injectable solution

  Monitor Closely (2)exenatide injectable solution, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
  
  exenatide injectable solution, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• exenatide injectable suspension

  Monitor Closely (2)exenatide injectable suspension, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
  
  exenatide injectable suspension, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• famotidine

  Minor (1)famotidine increases levels of metformin by decreasing renal clearance. Minor/Significance Unknown.

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• felodipine

  Monitor Closely (1)felodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• fexinidazole

  Serious - Use Alternative (1)fexinidazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fleroxacin

  Monitor Closely (2)fleroxacin increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
  
  fleroxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• fluconazole

  Monitor Closely (1)fluconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fludrocortisone

  Monitor Closely (1)fludrocortisone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)fludrocortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  fludrocortisone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.

• fluoxetine

  Monitor Closely (1)fluoxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• fluoxymesterone

  Minor (2)fluoxymesterone increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  fluoxymesterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• fluphenazine

  Monitor Closely (1)fluphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• fluvastatin

  Monitor Closely (1)repaglinide increases toxicity of fluvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• fluvoxamine

  Monitor Closely (2)fluvoxamine will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  fluvoxamine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• fo-ti

  Minor (2)fo-ti increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  fo-ti increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• folic acid

  Minor (1)metformin decreases levels of folic acid by unspecified interaction mechanism. Minor/Significance Unknown.

• forskolin

  Minor (2)forskolin increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Colenol, a compound found in Coleus root, may stimulate insulin release.
  
  forskolin increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Colenol, a compound found in Coleus root, may stimulate insulin release.

• fosamprenavir

  Monitor Closely (2)fosamprenavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  fosamprenavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• fosaprepitant

  Monitor Closely (1)fosaprepitant will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosinopril

  Monitor Closely (1)fosinopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• fosphenytoin

  Monitor Closely (2)fosphenytoin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  fosphenytoin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• fostemsavir

  Monitor Closely (1)fostemsavir will increase the level or effect of repaglinide by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits OATP1B1/3 transporter. If possible, avoid coadministration or modify dose of OATP1B1/3 substrates coadministered with fostemsavir.

• furosemide

  Minor (2)metformin decreases levels of furosemide by unspecified interaction mechanism. Minor/Significance Unknown.
  
  furosemide increases levels of metformin by unspecified interaction mechanism. Minor/Significance Unknown. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• gemfibrozil

  Contraindicated (1)gemfibrozil will increase the level or effect of repaglinide by Other (see comment). Contraindicated. Repaglinide is a CYP2C8 substrate. Gemfibrozil inhibits CYP2C8 and substantially increases repaglinide levels.

• gemifloxacin

  Monitor Closely (2)gemifloxacin increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
  
  gemifloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• glecaprevir/pibrentasvir

  Monitor Closely (2)repaglinide will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors
  
  glecaprevir/pibrentasvir will increase the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

• glucagon intranasal

  Monitor Closely (1)glucagon intranasal decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• glycopyrrolate

  Monitor Closely (1)glycopyrrolate increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. May require a dose reduction.

• goserelin

  Monitor Closely (1)goserelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• gotu kola

  Minor (2)gotu kola increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).
  
  gotu kola increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).

• grapefruit

  Monitor Closely (1)grapefruit will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• griseofulvin

  Monitor Closely (1)griseofulvin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• guanfacine

  Minor (4)guanfacine, metformin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  guanfacine decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  guanfacine decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  guanfacine, repaglinide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• gymnema

  Minor (2)gymnema increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  gymnema increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• histrelin

  Monitor Closely (1)histrelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• horse chestnut seed

  Minor (2)horse chestnut seed increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  horse chestnut seed increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• hydrochlorothiazide

  Minor (3)hydrochlorothiazide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  hydrochlorothiazide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  hydrochlorothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• hydrocortisone

  Monitor Closely (1)hydrocortisone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)hydrocortisone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  hydrocortisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• hydroxyprogesterone caproate (DSC)

  Monitor Closely (1)hydroxyprogesterone caproate (DSC) decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ibuprofen/famotidine

  Minor (1)ibuprofen/famotidine increases levels of metformin by decreasing renal clearance. Minor/Significance Unknown.

• idelalisib

  Serious - Use Alternative (1)idelalisib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

• iloperidone

  Monitor Closely (3)iloperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  iloperidone, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  iloperidone increases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

• imidapril

  Monitor Closely (1)imidapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• imipramine

  Minor (2)imipramine increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  imipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• indapamide

  Minor (2)indapamide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  indapamide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• indinavir

  Monitor Closely (2)indinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
  
  indinavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• insulin aspart

  Monitor Closely (1)metformin, insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin aspart protamine/insulin aspart

  Monitor Closely (1)metformin, insulin aspart protamine/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin degludec

  Monitor Closely (1)metformin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin degludec/insulin aspart

  Monitor Closely (1)metformin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin detemir

  Monitor Closely (1)metformin, insulin detemir. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin glargine

  Monitor Closely (1)metformin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin glulisine

  Monitor Closely (1)metformin, insulin glulisine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin inhaled

  Monitor Closely (1)metformin, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin isophane human/insulin regular human

  Monitor Closely (1)metformin, insulin isophane human/insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin lispro

  Monitor Closely (1)metformin, insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin lispro protamine/insulin lispro

  Monitor Closely (1)metformin, insulin lispro protamine/insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin NPH

  Monitor Closely (1)metformin, insulin NPH. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• insulin regular human

  Monitor Closely (1)metformin, insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

• iodixanol

  Monitor Closely (1)iodixanol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• ioflupane I 123

  Monitor Closely (1)ioflupane I 123 increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• iohexol

  Monitor Closely (1)iohexol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• iopamidol

  Monitor Closely (1)iopamidol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• iopromide

  Monitor Closely (1)iopromide increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• ioversol

  Monitor Closely (1)ioversol increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .Serious - Use Alternative (1)ioversol increases levels of metformin by decreasing renal clearance. Contraindicated. Acute renal failure or lactic acidosis may result. D/c metformin 48 hr before and after imaging study.

• ioxilan

  Monitor Closely (1)ioxilan increases toxicity of metformin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Administration of intravascular iodinated contrast agents in metformin-treated patients has led to rare cases of acute decrease in renal function and the occurrence of lactic acidosis. The American College of Radiology Guidelines (2018) recommend temporarily stopping metformin in patients with eGFR is <30 mL/min/1.73 m2 or who are undergoing arterial catheter studies that might result in emboli to the renal arteries. Continue to withhold metformin for 48 hr subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal. .

• isocarboxazid

  Monitor Closely (1)isocarboxazid will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• isoniazid

  Monitor Closely (2)isoniazid decreases effects of metformin by unspecified interaction mechanism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
  
  isoniazid will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)isoniazid decreases effects of repaglinide by unspecified interaction mechanism. Minor/Significance Unknown.

• isradipine

  Monitor Closely (1)isradipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• istradefylline

  Monitor Closely (1)istradefylline will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• itraconazole

  Monitor Closely (1)itraconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ivosidenib

  Serious - Use Alternative (1)ivosidenib will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• juniper

  Minor (2)juniper increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
  
  juniper increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• ketoconazole

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ketotifen, ophthalmic

  Monitor Closely (2)ketotifen, ophthalmic, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC.
  
  ketotifen, ophthalmic, metformin. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC.

• L-methylfolate

  Minor (1)metformin decreases levels of L-methylfolate by unspecified interaction mechanism. Minor/Significance Unknown.

• lanreotide

  Monitor Closely (1)lanreotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• lapatinib

  Monitor Closely (1)lapatinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• larotrectinib

  Minor (1)larotrectinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lenacapavir

  Monitor Closely (1)lenacapavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• leniolisib

  Serious - Use Alternative (1)leniolisib will increase the level or effect of repaglinide by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, an OATP1B1 and OATP1B3 inhibitor, may increase systemic exposure of these substrates

• letermovir

  Serious - Use Alternative (1)letermovir, repaglinide. Either increases levels of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations. When letermovir is coadministered with cyclosporine, avoid use with repaglinide.

• leuprolide

  Monitor Closely (1)leuprolide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• levofloxacin

  Monitor Closely (2)levofloxacin increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
  
  levofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• levoketoconazole

  Serious - Use Alternative (1)levoketoconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• levonorgestrel intrauterine

  Monitor Closely (1)levonorgestrel intrauterine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• levonorgestrel oral

  Monitor Closely (1)levonorgestrel oral decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• levothyroxine

  Monitor Closely (1)levothyroxine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• linezolid

  Monitor Closely (1)linezolid will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• liothyronine

  Monitor Closely (1)liothyronine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• liotrix

  Monitor Closely (1)liotrix decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• liraglutide

  Monitor Closely (2)liraglutide, metformin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.
  
  liraglutide, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Concurrent use may increase risk of hypoglycemia; monitor glucose levels.

• lisinopril

  Monitor Closely (1)lisinopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• lithium

  Monitor Closely (1)metformin decreases levels of lithium by Other (see comment). Use Caution/Monitor. Comment: SGLT2 inhibitors with lithium may decrease serum lithium concentrations; monitor serum lithium concentration more frequently during therapy initiation and dosage changes.

• lofepramine

  Minor (2)lofepramine increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  lofepramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• lonapegsomatropin

  Monitor Closely (2)lonapegsomatropin decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Closely monitor blood glucose when treated with antidiabetic agents. Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.
  
  lonapegsomatropin decreases effects of repaglinide by Other (see comment). Use Caution/Monitor. Comment: Closely monitor blood glucose when treated with antidiabetic agents. Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.

• lopinavir

  Monitor Closely (2)lopinavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  lopinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

• lorlatinib

  Monitor Closely (1)lorlatinib will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lumacaftor/ivacaftor

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repaglinide is metabolized by CYP3A and CYP2C8. Lumacaftor /ivacaftor is a strong CYP3A4 inducer and may also induce CYP2C8.

• lumefantrine

  Monitor Closely (1)lumefantrine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lurasidone

  Monitor Closely (2)lurasidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  lurasidone, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• lycopus

  Minor (2)lycopus increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
  
  lycopus increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).

• maitake

  Minor (2)maitake increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (animal research).
  
  maitake increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (animal research).

• maprotiline

  Minor (2)maprotiline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  maprotiline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• marijuana

  Monitor Closely (3)marijuana decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
  
  marijuana will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  marijuana decreases effects of repaglinide by pharmacodynamic antagonism. Use Caution/Monitor.

• mecasermin

  Monitor Closely (2)mecasermin increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.
  
  mecasermin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.

• medroxyprogesterone

  Monitor Closely (1)medroxyprogesterone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• memantine

  Minor (1)memantine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mesterolone

  Minor (2)mesterolone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  mesterolone increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• methamphetamine

  Monitor Closely (1)methamphetamine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• methazolamide

  Monitor Closely (1)methazolamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

• methyclothiazide

  Minor (3)methyclothiazide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  methyclothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  methyclothiazide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• methylene blue

  Serious - Use Alternative (1)methylene blue will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• methylprednisolone

  Monitor Closely (1)methylprednisolone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)methylprednisolone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  methylprednisolone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• methyltestosterone

  Minor (2)methyltestosterone increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  methyltestosterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• metolazone

  Minor (2)metolazone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  metolazone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• metreleptin

  Monitor Closely (1)repaglinide, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.

• metronidazole

  Monitor Closely (1)metronidazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• miconazole vaginal

  Monitor Closely (1)miconazole vaginal will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• midodrine

  Minor (1)metformin will increase the level or effect of midodrine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mifepristone

  Monitor Closely (2)mifepristone will increase the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Inhibits CYP2C8/2C9; use smallest recommended doses for substrates and monitor
  
  mifepristone will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mitotane

  Monitor Closely (1)mitotane decreases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

• moexipril

  Monitor Closely (1)moexipril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• moxifloxacin

  Monitor Closely (2)moxifloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
  
  moxifloxacin increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.

• nafcillin

  Monitor Closely (1)nafcillin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nefazodone

  Serious - Use Alternative (1)nefazodone will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nelfinavir

  Monitor Closely (2)nelfinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
  
  nelfinavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nettle

  Minor (2)nettle increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).
  
  nettle increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).

• nevirapine

  Monitor Closely (1)nevirapine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• niacin

  Monitor Closely (1)niacin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nicardipine

  Monitor Closely (1)nicardipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nifedipine

  Monitor Closely (2)nifedipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
  
  nifedipine will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)nifedipine increases levels of metformin by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• nilotinib

  Monitor Closely (2)nilotinib decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.
  
  nilotinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nimodipine

  Monitor Closely (1)nimodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nisoldipine

  Monitor Closely (1)nisoldipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nizatidine

  Monitor Closely (1)nizatidine will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely.

• norelgestromin

  Monitor Closely (1)norelgestromin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• norethindrone

  Monitor Closely (1)norethindrone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• norgestimate

  Monitor Closely (1)norgestimate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• nortriptyline

  Minor (2)nortriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  nortriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• octreotide

  Monitor Closely (1)octreotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• ofloxacin

  Monitor Closely (2)ofloxacin increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
  
  ofloxacin increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.Minor (3)ofloxacin, repaglinide. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.
  
  metformin will increase the level or effect of ofloxacin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  ofloxacin, metformin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.

• olanzapine

  Monitor Closely (2)olanzapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  olanzapine, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• omacetaxine

  Monitor Closely (1)omacetaxine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• omaveloxolone

  Monitor Closely (2)omaveloxolone will decrease the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP2C8 substrates. Check prescribing information of substrate if dosage modification is needed.
  
  omaveloxolone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP3A4 substrates. Check prescribing information of substrate if dosage modification is needed.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  Monitor Closely (1)ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Monitor for signs of onset of lactic acidosis such as respiratory distress, somnolence, and non-specific abdominal distress or worsening renal function; concomitant metformin use in patients with renal insufficiency or hepatic impairment not recommended.

• ondansetron

  Monitor Closely (1)ondansetron increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Ondansetron inhibition of transporters (MATE or OCTs), which are responsible for active renal secretion of metformin may play a role.

• opuntia ficus indica

  Monitor Closely (2)opuntia ficus indica increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.
  
  opuntia ficus indica increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor.

• oxandrolone

  Minor (2)oxandrolone increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  oxandrolone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• oxcarbazepine

  Monitor Closely (1)oxcarbazepine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• oxymetholone

  Minor (2)oxymetholone increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  oxymetholone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• pacritinib

  Serious - Use Alternative (1)pacritinib will increase the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Concomitant administration of pacritinib (OCT1 inhibitor) with OCT1 substrates may increase the plasma concentrations of these substrates.

• paliperidone

  Monitor Closely (2)paliperidone, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  paliperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• paroxetine

  Monitor Closely (1)paroxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• pasireotide

  Monitor Closely (1)pasireotide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• patiromer

  Monitor Closely (1)patiromer will decrease the level or effect of metformin by drug binding in GI tract. Modify Therapy/Monitor Closely. Separate administration by at least 3 hr from patiromer

• pegvisomant

  Minor (2)pegvisomant increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  pegvisomant increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• pentamidine

  Monitor Closely (1)pentamidine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• pentobarbital

  Monitor Closely (1)pentobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• perindopril

  Monitor Closely (1)perindopril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• perphenazine

  Monitor Closely (1)perphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• phendimetrazine

  Monitor Closely (1)phendimetrazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• phenelzine

  Monitor Closely (1)phenelzine will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• phenobarbital

  Monitor Closely (1)phenobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• phentermine

  Monitor Closely (1)phentermine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• phenytoin

  Monitor Closely (2)phenytoin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenytoin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• posaconazole

  Monitor Closely (1)posaconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• potassium acid phosphate

  Minor (2)potassium acid phosphate increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
  
  potassium acid phosphate increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

• potassium chloride

  Minor (2)potassium chloride increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
  
  potassium chloride increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

• potassium citrate

  Minor (2)potassium citrate increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
  
  potassium citrate increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.

• pravastatin

  Monitor Closely (1)repaglinide increases toxicity of pravastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• prednisolone

  Minor (2)prednisolone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  prednisolone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.

• prednisone

  Monitor Closely (1)prednisone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (2)prednisone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  prednisone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown.

• primidone

  Monitor Closely (1)primidone will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• procainamide

  Monitor Closely (1)metformin will increase the level or effect of procainamide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• procarbazine

  Monitor Closely (1)procarbazine will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• prochlorperazine

  Monitor Closely (1)prochlorperazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• progesterone intravaginal gel

  Monitor Closely (1)progesterone intravaginal gel decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• progesterone micronized

  Monitor Closely (1)progesterone micronized decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• progesterone, natural

  Monitor Closely (1)progesterone, natural decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• promethazine

  Monitor Closely (1)promethazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• protriptyline

  Minor (2)protriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  protriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• quetiapine

  Monitor Closely (2)quetiapine, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  quetiapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• quinapril

  Monitor Closely (1)quinapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• quinidine

  Monitor Closely (1)quinidine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• quinine

  Minor (1)metformin will increase the level or effect of quinine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• quinupristin/dalfopristin

  Monitor Closely (1)quinupristin/dalfopristin will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ramipril

  Monitor Closely (1)ramipril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• ranolazine

  Monitor Closely (1)ranolazine increases toxicity of repaglinide by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.Serious - Use Alternative (1)ranolazine will increase the level or effect of metformin by decreasing elimination. Avoid or Use Alternate Drug. Limit metformin dose to 1700 mg/day when used together with ranolazine 1000 mg twice daily; monitor closelly for signs or symptoms of metformin toxicity

• rasagiline

  Monitor Closely (1)rasagiline will increase the level or effect of metformin by unspecified interaction mechanism. Use Caution/Monitor.

• ribociclib

  Monitor Closely (1)ribociclib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifabutin

  Serious - Use Alternative (1)rifabutin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifampin

  Serious - Use Alternative (1)rifampin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifapentine

  Monitor Closely (1)rifapentine will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• risdiplam

  Serious - Use Alternative (1)risdiplam will increase the level or effect of metformin by decreasing elimination. Avoid or Use Alternate Drug. Risdiplam inhibits MATE1 and MATE2-K. If unable to avoid coadministration with MATE substrates, consider dosage reduction of MATE substrate.

• risperidone

  Monitor Closely (2)risperidone, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  risperidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• ritonavir

  Monitor Closely (2)ritonavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
  
  ritonavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ropeginterferon alfa 2b

  Monitor Closely (1)ropeginterferon alfa 2b will increase the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates. Therefore, monitor patients who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index from toxicities to such drugs.

• rosuvastatin

  Monitor Closely (1)repaglinide increases toxicity of rosuvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• rucaparib

  Monitor Closely (1)rucaparib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

• rufinamide

  Monitor Closely (1)rufinamide will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• sacubitril/valsartan

  Monitor Closely (1)repaglinide will increase the level or effect of sacubitril/valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

• sage

  Minor (2)sage increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  sage increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• saquinavir

  Monitor Closely (2)saquinavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
  
  saquinavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• secobarbital

  Monitor Closely (1)secobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• selegiline

  Serious - Use Alternative (1)selegiline will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• selegiline transdermal

  Serious - Use Alternative (1)selegiline transdermal will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• semaglutide

  Monitor Closely (1)semaglutide, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin secretagogues with GLP-1 agonists may increase hypoglycemia risk. Lowering the insulin secretagogue dose may reduce hypoglycemia risk. .

• sertraline

  Monitor Closely (1)sertraline increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• shark cartilage

  Monitor Closely (2)shark cartilage increases effects of repaglinide by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction.
  
  shark cartilage increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction.

• simvastatin

  Monitor Closely (1)repaglinide increases toxicity of simvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

• sirolimus

  Monitor Closely (1)sirolimus decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• sofosbuvir/velpatasvir

  Monitor Closely (1)sofosbuvir/velpatasvir increases levels of repaglinide by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

• somapacitan

  Monitor Closely (1)somapacitan decreases effects of metformin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating somapacitan. .

• somatropin

  Monitor Closely (1)somatropin decreases levels of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• spironolactone

  Monitor Closely (1)spironolactone will increase the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Spironolactone inhibits CYP2C8; repaglinice dose may need to be adjusted as it is metabolized by CYP2C8

• St John's Wort

  Serious - Use Alternative (1)St John's Wort will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• stevia

  Minor (2)stevia increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  stevia increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• stiripentol

  Monitor Closely (2)stiripentol, repaglinide. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
  
  stiripentol will increase the level or effect of repaglinide by Other (see comment). Modify Therapy/Monitor Closely. Stiripentol is a CYP2C8 inhibitor. Consider dosage reduction for CYP2C8 substrates if adverse effects are experienced when coadministered.

• sulfadiazine

  Monitor Closely (1)sulfadiazine increases levels of repaglinide by plasma protein binding competition. Use Caution/Monitor.

• sulfamethoxazole

  Monitor Closely (1)sulfamethoxazole increases levels of repaglinide by plasma protein binding competition. Use Caution/Monitor.Minor (1)sulfamethoxazole will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulfamethoxypyridazine

  Monitor Closely (2)sulfamethoxypyridazine increases effects of repaglinide by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.
  
  sulfamethoxypyridazine increases effects of metformin by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• sulfisoxazole

  Monitor Closely (1)sulfisoxazole increases levels of repaglinide by plasma protein binding competition. Use Caution/Monitor.

• tacrolimus

  Monitor Closely (1)tacrolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• tafenoquine

  Serious - Use Alternative (1)tafenoquine will increase the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.

• tazemetostat

  Monitor Closely (1)tazemetostat will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• teclistamab

  Monitor Closely (1)teclistamab will increase the level or effect of repaglinide by altering metabolism. Use Caution/Monitor. Teclistamab causes release of cytokines that may suppress activity of CYP450 enzymes, resulting in increased exposure of CYP substrates. Monitor for increased concentrations or toxicities of sensitive CYP substrates. Adjust dose of CYP substrate drug as needed.

• tecovirimat

  Monitor Closely (2)tecovirimat will increase the level or effect of repaglinide by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Monitor for adverse effects if coadministered with substrates of these enzymes. Monitor blood glucose and monitor for hypoglycemic symptoms.
  
  tecovirimat will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• tedizolid

  Serious - Use Alternative (1)tedizolid will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• temsirolimus

  Monitor Closely (1)temsirolimus decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• tenofovir DF

  Monitor Closely (1)tenofovir DF increases levels of metformin by decreasing renal clearance. Use Caution/Monitor. Increased risk of lactic acidosis.

• teriflunomide

  Monitor Closely (1)teriflunomide increases levels of repaglinide by Other (see comment). Use Caution/Monitor. Comment: Teriflunomide inhibits CYP2C8; caution when coadministered with CYP2C8 substrates.

• testosterone

  Minor (2)testosterone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  testosterone increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• testosterone buccal system

  Minor (2)testosterone buccal system increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  testosterone buccal system increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• testosterone topical

  Minor (2)testosterone topical increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  testosterone topical increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• thioridazine

  Monitor Closely (1)thioridazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• thyroid desiccated

  Monitor Closely (1)thyroid desiccated decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• tibolone

  Monitor Closely (1)tibolone decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• tipranavir

  Monitor Closely (3)tipranavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
  
  tipranavir will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  tipranavir, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Tipranavir's effect on oral hypoglycemics via hepatic CYP2C9 unknown; carefully monitor blood glucose.

• tongkat ali

  Minor (2)tongkat ali increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia.
  
  tongkat ali increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia.

• topiramate

  Monitor Closely (2)topiramate will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  topiramate increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

• torsemide

  Monitor Closely (1)torsemide decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• trandolapril

  Monitor Closely (1)trandolapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

• tranylcypromine

  Serious - Use Alternative (1)tranylcypromine will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

• trazodone

  Minor (2)trazodone increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.
  
  trazodone increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• triamcinolone acetonide injectable suspension

  Monitor Closely (2)triamcinolone acetonide injectable suspension decreases effects of repaglinide by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.
  
  triamcinolone acetonide injectable suspension decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.

• triamterene

  Minor (1)metformin will increase the level or effect of triamterene by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trifluoperazine

  Monitor Closely (1)trifluoperazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• trilaciclib

  Serious - Use Alternative (1)trilaciclib will decrease the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.

• trimethoprim

  Monitor Closely (2)trimethoprim increases levels of repaglinide by decreasing metabolism. Use Caution/Monitor. Hepatic cytochrome P450 2C8.
  
  trimethoprim increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Trimethoprim may inhibit active renal tubular secretion of metformin (eg, via OCT2, MATE1); dose adjustments may be necessary.Minor (1)metformin will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trimipramine

  Minor (2)trimipramine increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  trimipramine increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• triptorelin

  Monitor Closely (1)triptorelin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• trofinetide

  Monitor Closely (1)trofinetide will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).Serious - Use Alternative (1)trofinetide will increase the level or effect of repaglinide by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.

• trospium chloride

  Monitor Closely (1)metformin will decrease the level or effect of trospium chloride by increasing renal clearance. Use Caution/Monitor. Coadministration reduced steady state trospium systemic exposure (decreased AUC and Cmax) by competing for renal tubular secretion

• tucatinib

  Serious - Use Alternative (1)tucatinib will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• valsartan

  Monitor Closely (1)repaglinide will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

• vanadium

  Minor (2)vanadium increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.
  
  vanadium increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• vandetanib

  Monitor Closely (1)vandetanib increases levels of metformin by Other (see comment). Modify Therapy/Monitor Closely. Comment: Vandetanib inhibits the uptake of substrates of organic cation transporter type 2 (OCT2).

• verapamil

  Monitor Closely (2)verapamil decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Verapamil may inhibit hepatic uptake of metformin by OCT1 and/or other transporters.
  
  verapamil will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)metformin will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• vilazodone

  Monitor Closely (1)vilazodone increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• voclosporin

  Minor (1)voclosporin will increase the level or effect of repaglinide by Other (see comment). Minor/Significance Unknown. Information suggests voclosporin (an OATP1B1 inhibitor) may increase in the concentration of OATP1B1 substrates is possible. Monitor for adverse reactions of OATP1B1 substrates when coadministered with voclosporin.

• voriconazole

  Monitor Closely (1)voriconazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vorinostat

  Monitor Closely (1)vorinostat decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• vortioxetine

  Monitor Closely (1)vortioxetine increases effects of metformin by pharmacodynamic synergism. Use Caution/Monitor.

• voxelotor

  Serious - Use Alternative (1)voxelotor will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

• xipamide

  Monitor Closely (2)xipamide decreases levels of repaglinide by increasing renal clearance. Use Caution/Monitor.
  
  xipamide decreases levels of metformin by increasing renal clearance. Use Caution/Monitor.

• zafirlukast

  Monitor Closely (1)zafirlukast will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ziprasidone

  Monitor Closely (2)ziprasidone, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
  
  ziprasidone, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• zonisamide

  Monitor Closely (1)zonisamide increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.