Interactions between Metformin / repaglinide and Momelotinib

The metFORMIN and repaglinide in metformin / repaglinide both have a moderate potential interaction with Adrenal Insufficiency.

Hypoglycemia may commonly occur during treatment with insulin and/or oral hypoglycemic agents. Care should be taken in patients who may be particularly susceptible to the development of hypoglycemic episodes during the use of these drugs, including those who are debilitated or malnourished, those with defective counterregulatory mechanisms (e.g., autonomic neuropathy and adrenal or pituitary insufficiency), and those receiving beta-adrenergic blocking agents.

The metFORMIN in metformin / repaglinide has a major potential interaction with Alcoholism.

Metformin is contraindicated in patients with acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Risk factors include renal dysfunction, age 65 years and older, hypoxic states, excessive alcohol intake, and liver dysfunction. Lactic acidosis has been associated with metformin accumulation in plasma at levels generally exceeding 5 mcg/mL. The risk of metformin-associated lactic acidosis increases with the patient's age because patients 65 years and older have a greater likelihood of having hepatic, renal, or cardiac impairment. Renal function should be assessed more frequently in older adult patients. Several postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure, especially when accompanied by hypoperfusion and hypoxemia; cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia (e.g., severe anemia, asphyxia) have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, metformin should be discontinued. Dehydration (e.g., severe diarrhea or vomiting) may increase the risk for volume depletion, hypotension, and renal impairment; such patients may be at increased risk for lactic acidosis. Alcohol potentiates the effect of metformin on lactate metabolism; patients should be advised against excessive alcohol intake while receiving metformin. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary). If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, as well as immediate discontinuation of metformin. If lactic acidosis is diagnosed or strongly suspected, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin. Patients and their families should be educated about the symptoms of lactic acidosis and, if these symptoms occur, they should be instructed to discontinue metformin and contact their health care provider.

The metFORMIN in metformin / repaglinide has a major potential interaction with Anemia.

Metformin is contraindicated in patients with acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Risk factors include renal dysfunction, age 65 years and older, hypoxic states, excessive alcohol intake, and liver dysfunction. Lactic acidosis has been associated with metformin accumulation in plasma at levels generally exceeding 5 mcg/mL. The risk of metformin-associated lactic acidosis increases with the patient's age because patients 65 years and older have a greater likelihood of having hepatic, renal, or cardiac impairment. Renal function should be assessed more frequently in older adult patients. Several postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure, especially when accompanied by hypoperfusion and hypoxemia; cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia (e.g., severe anemia, asphyxia) have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, metformin should be discontinued. Dehydration (e.g., severe diarrhea or vomiting) may increase the risk for volume depletion, hypotension, and renal impairment; such patients may be at increased risk for lactic acidosis. Alcohol potentiates the effect of metformin on lactate metabolism; patients should be advised against excessive alcohol intake while receiving metformin. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary). If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, as well as immediate discontinuation of metformin. If lactic acidosis is diagnosed or strongly suspected, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin. Patients and their families should be educated about the symptoms of lactic acidosis and, if these symptoms occur, they should be instructed to discontinue metformin and contact their health care provider.

The metFORMIN in metformin / repaglinide has a moderate potential interaction with Anemia Associated with Vitamin B12 Deficiency.

Metformin may interfere with vitamin B12 absorption from the B12-intrinsic factor complex. A decrease to subnormal levels of previously normal serum vitamin B12 levels was reported in about 7% of patients treated with metformin during clinical trials. Such decrease may be associated with anemia but appears to be rapidly reversible with metformin discontinuation or vitamin B12 supplementation. Certain patients (those with inadequate vitamin B12 or calcium intake or absorption) appear to be predisposed to developing subnormal levels of vitamin B12; caution may be warranted when metformin is administered to these patients. It is recommended to measure vitamin B12 every 2 to 3 years and hematologic parameters annually in patients on metformin. Any abnormalities should be managed.

The metFORMIN and repaglinide in metformin / repaglinide both have a moderate potential interaction with Anorexia/Feeding Problems.

Hypoglycemia may commonly occur during treatment with insulin and/or oral hypoglycemic agents. Care should be taken in patients who may be particularly susceptible to the development of hypoglycemic episodes during the use of these drugs, including those who are debilitated or malnourished, those with defective counterregulatory mechanisms (e.g., autonomic neuropathy and adrenal or pituitary insufficiency), and those receiving beta-adrenergic blocking agents.

The metFORMIN in metformin / repaglinide has a major potential interaction with Asphyxia.

Metformin is contraindicated in patients with acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Risk factors include renal dysfunction, age 65 years and older, hypoxic states, excessive alcohol intake, and liver dysfunction. Lactic acidosis has been associated with metformin accumulation in plasma at levels generally exceeding 5 mcg/mL. The risk of metformin-associated lactic acidosis increases with the patient's age because patients 65 years and older have a greater likelihood of having hepatic, renal, or cardiac impairment. Renal function should be assessed more frequently in older adult patients. Several postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure, especially when accompanied by hypoperfusion and hypoxemia; cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia (e.g., severe anemia, asphyxia) have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, metformin should be discontinued. Dehydration (e.g., severe diarrhea or vomiting) may increase the risk for volume depletion, hypotension, and renal impairment; such patients may be at increased risk for lactic acidosis. Alcohol potentiates the effect of metformin on lactate metabolism; patients should be advised against excessive alcohol intake while receiving metformin. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary). If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, as well as immediate discontinuation of metformin. If lactic acidosis is diagnosed or strongly suspected, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin. Patients and their families should be educated about the symptoms of lactic acidosis and, if these symptoms occur, they should be instructed to discontinue metformin and contact their health care provider.

The metFORMIN and repaglinide in metformin / repaglinide both have a moderate potential interaction with Autonomic Neuropathy.

Hypoglycemia may commonly occur during treatment with insulin and/or oral hypoglycemic agents. Care should be taken in patients who may be particularly susceptible to the development of hypoglycemic episodes during the use of these drugs, including those who are debilitated or malnourished, those with defective counterregulatory mechanisms (e.g., autonomic neuropathy and adrenal or pituitary insufficiency), and those receiving beta-adrenergic blocking agents.

The repaglinide in metformin / repaglinide has a major potential interaction with Cardiovascular Conditions and Disorders.

The use of oral hypoglycemic agents may be associated with an increased risk of cardiovascular mortality compared to treatment with diet alone or diet with insulin. This warning is based on the University Group Diabetes Program (UGDP) study, a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. Patients treated with diet plus a fixed dosage of either tolbutamide (a sulfonylurea) or phenformin (a biguanide) for 5 to 8 years had a cardiovascular mortality rate approximately 2.5 times that of patients treated with diet alone, resulting in discontinuation of both these treatments in the study. Despite controversy regarding interpretation of these results, clinicians and patients should be aware of the potential risk when making treatment decisions for diabetes, particularly in the presence of underlying cardiovascular disease. Data are not available for other sulfonylureas or biguanides, nor for hypoglycemic agents belonging to other classes. However, given the similarities in chemical structure and/or mode of action, the same caution should be applied.

Momelotinib has a major potential interaction with Cardiovascular Conditions and Disorders.

In a major safety study of a Janus kinase (JAK) inhibitor, tofacitinib, in rheumatoid arthritis patients 50 years and older with at least 1 cardiovascular risk factor, higher rates of all-cause mortality (including sudden cardiovascular death) and major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) were observed with the JAK inhibitor when compared with tumor necrosis factor (TNF) blockers. Patients who were current or past smokers had an additional increased risk. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including baricitinib, upadacitinib, ruxolitinib, fedratinib, ritlecitinib, deuruxolitinib, and pacritinib. Consider the benefits and risks for each individual patient prior and during treatment with JAK inhibitors, especially in patients with other cardiovascular risk factors, history of cardiovascular events, and patients who are current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and what to do if they occur.

The metFORMIN in metformin / repaglinide has a major potential interaction with Dehydration.

Metformin is contraindicated in patients with acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Risk factors include renal dysfunction, age 65 years and older, hypoxic states, excessive alcohol intake, and liver dysfunction. Lactic acidosis has been associated with metformin accumulation in plasma at levels generally exceeding 5 mcg/mL. The risk of metformin-associated lactic acidosis increases with the patient's age because patients 65 years and older have a greater likelihood of having hepatic, renal, or cardiac impairment. Renal function should be assessed more frequently in older adult patients. Several postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure, especially when accompanied by hypoperfusion and hypoxemia; cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia (e.g., severe anemia, asphyxia) have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, metformin should be discontinued. Dehydration (e.g., severe diarrhea or vomiting) may increase the risk for volume depletion, hypotension, and renal impairment; such patients may be at increased risk for lactic acidosis. Alcohol potentiates the effect of metformin on lactate metabolism; patients should be advised against excessive alcohol intake while receiving metformin. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary). If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, as well as immediate discontinuation of metformin. If lactic acidosis is diagnosed or strongly suspected, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin. Patients and their families should be educated about the symptoms of lactic acidosis and, if these symptoms occur, they should be instructed to discontinue metformin and contact their health care provider.

The repaglinide in metformin / repaglinide has a major potential interaction with Diabetes, Type 1.

The use of meglitinides is contraindicated in patients with type I diabetes or for the treatment of diabetic ketoacidosis, with or without coma.

The repaglinide in metformin / repaglinide has a moderate potential interaction with Diabetes Mellitus.

Patients with severely reduced renal function treated with repaglinide had elevated plasma drug concentrations. Patients with type 2 diabetes who have severe renal function impairment should initiate repaglinide therapy with the 0.5 mg dose and subsequently, patients should be carefully titrated.

The repaglinide in metformin / repaglinide has a major potential interaction with Diabetic Ketoacidosis.

The use of meglitinides is contraindicated in patients with type I diabetes or for the treatment of diabetic ketoacidosis, with or without coma.

The metFORMIN in metformin / repaglinide has a major potential interaction with Diabetic Ketoacidosis.

Metformin is contraindicated in patients with acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Risk factors include renal dysfunction, age 65 years and older, hypoxic states, excessive alcohol intake, and liver dysfunction. Lactic acidosis has been associated with metformin accumulation in plasma at levels generally exceeding 5 mcg/mL. The risk of metformin-associated lactic acidosis increases with the patient's age because patients 65 years and older have a greater likelihood of having hepatic, renal, or cardiac impairment. Renal function should be assessed more frequently in older adult patients. Several postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure, especially when accompanied by hypoperfusion and hypoxemia; cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia (e.g., severe anemia, asphyxia) have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, metformin should be discontinued. Dehydration (e.g., severe diarrhea or vomiting) may increase the risk for volume depletion, hypotension, and renal impairment; such patients may be at increased risk for lactic acidosis. Alcohol potentiates the effect of metformin on lactate metabolism; patients should be advised against excessive alcohol intake while receiving metformin. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary). If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, as well as immediate discontinuation of metformin. If lactic acidosis is diagnosed or strongly suspected, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin. Patients and their families should be educated about the symptoms of lactic acidosis and, if these symptoms occur, they should be instructed to discontinue metformin and contact their health care provider.

The metFORMIN in metformin / repaglinide has a major potential interaction with Diarrhea.

Metformin is contraindicated in patients with acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Risk factors include renal dysfunction, age 65 years and older, hypoxic states, excessive alcohol intake, and liver dysfunction. Lactic acidosis has been associated with metformin accumulation in plasma at levels generally exceeding 5 mcg/mL. The risk of metformin-associated lactic acidosis increases with the patient's age because patients 65 years and older have a greater likelihood of having hepatic, renal, or cardiac impairment. Renal function should be assessed more frequently in older adult patients. Several postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure, especially when accompanied by hypoperfusion and hypoxemia; cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia (e.g., severe anemia, asphyxia) have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, metformin should be discontinued. Dehydration (e.g., severe diarrhea or vomiting) may increase the risk for volume depletion, hypotension, and renal impairment; such patients may be at increased risk for lactic acidosis. Alcohol potentiates the effect of metformin on lactate metabolism; patients should be advised against excessive alcohol intake while receiving metformin. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary). If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, as well as immediate discontinuation of metformin. If lactic acidosis is diagnosed or strongly suspected, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin. Patients and their families should be educated about the symptoms of lactic acidosis and, if these symptoms occur, they should be instructed to discontinue metformin and contact their health care provider.

The metFORMIN in metformin / repaglinide has a moderate potential interaction with Folic Acid/Cyanocobalamin Deficiency.

Metformin may interfere with vitamin B12 absorption from the B12-intrinsic factor complex. A decrease to subnormal levels of previously normal serum vitamin B12 levels was reported in about 7% of patients treated with metformin during clinical trials. Such decrease may be associated with anemia but appears to be rapidly reversible with metformin discontinuation or vitamin B12 supplementation. Certain patients (those with inadequate vitamin B12 or calcium intake or absorption) appear to be predisposed to developing subnormal levels of vitamin B12; caution may be warranted when metformin is administered to these patients. It is recommended to measure vitamin B12 every 2 to 3 years and hematologic parameters annually in patients on metformin. Any abnormalities should be managed.

The metFORMIN in metformin / repaglinide has a major potential interaction with Heart Attack.

Metformin is contraindicated in patients with acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Risk factors include renal dysfunction, age 65 years and older, hypoxic states, excessive alcohol intake, and liver dysfunction. Lactic acidosis has been associated with metformin accumulation in plasma at levels generally exceeding 5 mcg/mL. The risk of metformin-associated lactic acidosis increases with the patient's age because patients 65 years and older have a greater likelihood of having hepatic, renal, or cardiac impairment. Renal function should be assessed more frequently in older adult patients. Several postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure, especially when accompanied by hypoperfusion and hypoxemia; cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia (e.g., severe anemia, asphyxia) have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, metformin should be discontinued. Dehydration (e.g., severe diarrhea or vomiting) may increase the risk for volume depletion, hypotension, and renal impairment; such patients may be at increased risk for lactic acidosis. Alcohol potentiates the effect of metformin on lactate metabolism; patients should be advised against excessive alcohol intake while receiving metformin. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary). If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, as well as immediate discontinuation of metformin. If lactic acidosis is diagnosed or strongly suspected, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin. Patients and their families should be educated about the symptoms of lactic acidosis and, if these symptoms occur, they should be instructed to discontinue metformin and contact their health care provider.

The metFORMIN in metformin / repaglinide has a major potential interaction with Heart Failure.

Metformin is contraindicated in patients with acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Risk factors include renal dysfunction, age 65 years and older, hypoxic states, excessive alcohol intake, and liver dysfunction. Lactic acidosis has been associated with metformin accumulation in plasma at levels generally exceeding 5 mcg/mL. The risk of metformin-associated lactic acidosis increases with the patient's age because patients 65 years and older have a greater likelihood of having hepatic, renal, or cardiac impairment. Renal function should be assessed more frequently in older adult patients. Several postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure, especially when accompanied by hypoperfusion and hypoxemia; cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia (e.g., severe anemia, asphyxia) have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, metformin should be discontinued. Dehydration (e.g., severe diarrhea or vomiting) may increase the risk for volume depletion, hypotension, and renal impairment; such patients may be at increased risk for lactic acidosis. Alcohol potentiates the effect of metformin on lactate metabolism; patients should be advised against excessive alcohol intake while receiving metformin. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary). If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, as well as immediate discontinuation of metformin. If lactic acidosis is diagnosed or strongly suspected, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin. Patients and their families should be educated about the symptoms of lactic acidosis and, if these symptoms occur, they should be instructed to discontinue metformin and contact their health care provider.

Momelotinib has a moderate potential interaction with Infection.

Momelotinib increases the risk of serious and fatal infections. Patients should be evaluated for active infection before and during treatment with momelotinib, and administration should be avoided if infection is detected.

Momelotinib has a moderate potential interaction with Infectious Hepatitis.

Janus kinase (JAK) inhibitors, including momelotinib, have been shown to increase hepatitis B viral load with or without elevations in ALT and AST levels in chronic hepatitis B virus (HBV) infections. Obtain hepatitis B serologies in patients with HBV infections prior to initiating therapy. Consider consulting a hepatologist regarding monitoring or prophylactic hepatitis B therapy if a positive HBsAg and/or total anti-HBc is positive. Patients with chronic HBV infection taking momelotinib should be treated and monitored according to guidelines.

The metFORMIN in metformin / repaglinide has a major potential interaction with Lactic Acidosis.

Metformin is contraindicated in patients with acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Risk factors include renal dysfunction, age 65 years and older, hypoxic states, excessive alcohol intake, and liver dysfunction. Lactic acidosis has been associated with metformin accumulation in plasma at levels generally exceeding 5 mcg/mL. The risk of metformin-associated lactic acidosis increases with the patient's age because patients 65 years and older have a greater likelihood of having hepatic, renal, or cardiac impairment. Renal function should be assessed more frequently in older adult patients. Several postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure, especially when accompanied by hypoperfusion and hypoxemia; cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia (e.g., severe anemia, asphyxia) have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, metformin should be discontinued. Dehydration (e.g., severe diarrhea or vomiting) may increase the risk for volume depletion, hypotension, and renal impairment; such patients may be at increased risk for lactic acidosis. Alcohol potentiates the effect of metformin on lactate metabolism; patients should be advised against excessive alcohol intake while receiving metformin. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary). If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, as well as immediate discontinuation of metformin. If lactic acidosis is diagnosed or strongly suspected, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin. Patients and their families should be educated about the symptoms of lactic acidosis and, if these symptoms occur, they should be instructed to discontinue metformin and contact their health care provider.

The metFORMIN in metformin / repaglinide has a major potential interaction with Liver Disease.

Metformin decreases the liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in at-risk patients. There have been reports of cases of metformin-associated lactic acidosis in patients with liver dysfunction. Metformin should generally be avoided in patients with evidence of hepatic disease.

The repaglinide in metformin / repaglinide has a moderate potential interaction with Liver Disease.

Repaglinide is almost completely metabolized in the liver to pharmacologically inactive substances. Patients with impaired liver function may be exposed to higher concentrations of repaglinide and its associated metabolites. Higher serum drug levels, in addition to diminished gluconeogenic capacity secondary to hepatic insufficiency, may increase the potential for severe hypoglycemic episodes. Therapy with repaglinide should be administered cautiously in patients with liver disease. Longer intervals between dosage adjustments may be required.

Momelotinib has a moderate potential interaction with Liver Disease.

Momelotinib has been reported to cause worsening elevations of ALT, AST, and bilirubin in patients. The AUC and Cmax of momelotinib are increased in patients with severe hepatic impairment (Child-Pugh C). The patient's liver enzyme levels should be monitored prior to initiation and during treatment with momelotinib. Patients with acute and chronic liver disease should be treated before initiating treatment and the hepatic impairment dosing regimen should be followed during treatment.

The metFORMIN and repaglinide in metformin / repaglinide both have a moderate potential interaction with Malnourishment.

Hypoglycemia may commonly occur during treatment with insulin and/or oral hypoglycemic agents. Care should be taken in patients who may be particularly susceptible to the development of hypoglycemic episodes during the use of these drugs, including those who are debilitated or malnourished, those with defective counterregulatory mechanisms (e.g., autonomic neuropathy and adrenal or pituitary insufficiency), and those receiving beta-adrenergic blocking agents.

The metFORMIN and repaglinide in metformin / repaglinide both have a moderate potential interaction with Panhypopituitarism.

Hypoglycemia may commonly occur during treatment with insulin and/or oral hypoglycemic agents. Care should be taken in patients who may be particularly susceptible to the development of hypoglycemic episodes during the use of these drugs, including those who are debilitated or malnourished, those with defective counterregulatory mechanisms (e.g., autonomic neuropathy and adrenal or pituitary insufficiency), and those receiving beta-adrenergic blocking agents.

The metFORMIN in metformin / repaglinide has a major potential interaction with Renal Dysfunction.

Metformin is contraindicated in patients with acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Risk factors include renal dysfunction, age 65 years and older, hypoxic states, excessive alcohol intake, and liver dysfunction. Lactic acidosis has been associated with metformin accumulation in plasma at levels generally exceeding 5 mcg/mL. The risk of metformin-associated lactic acidosis increases with the patient's age because patients 65 years and older have a greater likelihood of having hepatic, renal, or cardiac impairment. Renal function should be assessed more frequently in older adult patients. Several postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure, especially when accompanied by hypoperfusion and hypoxemia; cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia (e.g., severe anemia, asphyxia) have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, metformin should be discontinued. Dehydration (e.g., severe diarrhea or vomiting) may increase the risk for volume depletion, hypotension, and renal impairment; such patients may be at increased risk for lactic acidosis. Alcohol potentiates the effect of metformin on lactate metabolism; patients should be advised against excessive alcohol intake while receiving metformin. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary). If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, as well as immediate discontinuation of metformin. If lactic acidosis is diagnosed or strongly suspected, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin. Patients and their families should be educated about the symptoms of lactic acidosis and, if these symptoms occur, they should be instructed to discontinue metformin and contact their health care provider.

The metFORMIN in metformin / repaglinide has a major potential interaction with Renal Dysfunction.

The use of metformin is contraindicated in patients with severe renal dysfunction (estimated GFR [eGFR] less than 30 mL/min/1.73 m2). Metformin is substantially excreted by the kidney; the risk of metformin accumulation and lactic acidosis increases with the degree of renal dysfunction. Before starting metformin, an eGFR should be obtained. Initiation of metformin is not recommended in patients with eGFR between 30 and 45 mL/min/1.73 m2. An eGFR should be obtained at least annually in all patients; in those at risk of developing renal dysfunction (e.g., older adult patients), renal function should be assessed more frequently. In patients whose eGFR falls below 45 mL/min/1.73 m2, the benefit/risk of continuing therapy should be assessed. Postmarketing cases of metformin-associated lactic acidosis primarily occurred with significant renal dysfunction; metformin plasma levels generally exceeded 5 mcg/mL.

The repaglinide in metformin / repaglinide has a moderate potential interaction with Renal Dysfunction.

Patients with severely reduced renal function treated with repaglinide had elevated plasma drug concentrations. Patients with type 2 diabetes who have severe renal function impairment should initiate repaglinide therapy with the 0.5 mg dose and subsequently, patients should be carefully titrated.

The metFORMIN in metformin / repaglinide has a major potential interaction with Shock.

Metformin is contraindicated in patients with acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Risk factors include renal dysfunction, age 65 years and older, hypoxic states, excessive alcohol intake, and liver dysfunction. Lactic acidosis has been associated with metformin accumulation in plasma at levels generally exceeding 5 mcg/mL. The risk of metformin-associated lactic acidosis increases with the patient's age because patients 65 years and older have a greater likelihood of having hepatic, renal, or cardiac impairment. Renal function should be assessed more frequently in older adult patients. Several postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure, especially when accompanied by hypoperfusion and hypoxemia; cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia (e.g., severe anemia, asphyxia) have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, metformin should be discontinued. Dehydration (e.g., severe diarrhea or vomiting) may increase the risk for volume depletion, hypotension, and renal impairment; such patients may be at increased risk for lactic acidosis. Alcohol potentiates the effect of metformin on lactate metabolism; patients should be advised against excessive alcohol intake while receiving metformin. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary). If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, as well as immediate discontinuation of metformin. If lactic acidosis is diagnosed or strongly suspected, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin. Patients and their families should be educated about the symptoms of lactic acidosis and, if these symptoms occur, they should be instructed to discontinue metformin and contact their health care provider.

Momelotinib has a major potential interaction with Smoking.

Malignancies (including lymphomas and solid tumors) have been reported in patients treated with tofacitinib, baricitinib, upadacitinib, deuruxolitinib and other Janus kinase (JAK) inhibitors used to treat inflammatory conditions. Patients who are current or past smokers are at additional increased risk of malignancies. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including ruxolitinib, pacritinib, and fedratinib. Before starting or continuing therapy, the benefits and risks for the individual patient should be considered, especially in patients with a known malignancy (other than successfully treated nonmelanoma skin cancer), patients who develop a malignancy during therapy, and patients who are current or past smokers. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

Momelotinib has a major potential interaction with Smoking.

In a major safety study of a Janus kinase (JAK) inhibitor, tofacitinib, in rheumatoid arthritis patients 50 years and older with at least 1 cardiovascular risk factor, higher rates of all-cause mortality (including sudden cardiovascular death) and major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) were observed with the JAK inhibitor when compared with tumor necrosis factor (TNF) blockers. Patients who were current or past smokers had an additional increased risk. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including baricitinib, upadacitinib, ruxolitinib, fedratinib, ritlecitinib, deuruxolitinib, and pacritinib. Consider the benefits and risks for each individual patient prior and during treatment with JAK inhibitors, especially in patients with other cardiovascular risk factors, history of cardiovascular events, and patients who are current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and what to do if they occur.

The metFORMIN in metformin / repaglinide has a major potential interaction with Vomiting.

Metformin is contraindicated in patients with acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Risk factors include renal dysfunction, age 65 years and older, hypoxic states, excessive alcohol intake, and liver dysfunction. Lactic acidosis has been associated with metformin accumulation in plasma at levels generally exceeding 5 mcg/mL. The risk of metformin-associated lactic acidosis increases with the patient's age because patients 65 years and older have a greater likelihood of having hepatic, renal, or cardiac impairment. Renal function should be assessed more frequently in older adult patients. Several postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure, especially when accompanied by hypoperfusion and hypoxemia; cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia (e.g., severe anemia, asphyxia) have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, metformin should be discontinued. Dehydration (e.g., severe diarrhea or vomiting) may increase the risk for volume depletion, hypotension, and renal impairment; such patients may be at increased risk for lactic acidosis. Alcohol potentiates the effect of metformin on lactate metabolism; patients should be advised against excessive alcohol intake while receiving metformin. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary). If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, as well as immediate discontinuation of metformin. If lactic acidosis is diagnosed or strongly suspected, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin. Patients and their families should be educated about the symptoms of lactic acidosis and, if these symptoms occur, they should be instructed to discontinue metformin and contact their health care provider.