Can you take Dienogest / estradiol with Metformin?

The estradiol in dienogest / estradiol has a major potential interaction with Abnormal Uterine Bleeding.

The use of estrogens is contraindicated in patients with undiagnosed, abnormal vaginal bleeding. Prolonged (greater than 1 year), unopposed estrogen use (i.e. estrogen without concomitant progestin therapy) has been associated with a significant, dose-related risk of endometrial carcinoma. The risk may be offset substantially by the addition of a progestin but may not be completely abolished. Prior to initiating estrogen therapy, appropriate diagnostic tests should be performed in patients with abnormal vaginal bleeding to rule out endometrial malignancy. The same applies if recurrent or persistent bleeding develops during estrogen therapy.

metFORMIN has 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.

metFORMIN 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.

metFORMIN 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.

metFORMIN 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 estradiol in dienogest / estradiol has a moderate potential interaction with Angioedema.

The use of exogenous estrogens may induce or exacerbate symptoms of angioedema, particularly in women with hereditary angioedema. Consider the risk versus benefits of estrogen therapy. Close monitoring is recommended when prescribing these agents to patients predisposed to angioedema.

metFORMIN has 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.

metFORMIN 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 estradiol in dienogest / estradiol has a moderate potential interaction with Asthma.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

metFORMIN has 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 estradiol in dienogest / estradiol has a major potential interaction with Breast Cancer.

When treated with an estrogen, patients with breast cancer and bone metastases may develop severe hypercalcemia, in which case the drug should be stopped and measures be taken to reduce serum calcium levels.

The estradiol in dienogest / estradiol has a major potential interaction with Cerebral Vascular Disorder.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

metFORMIN 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 estradiol in dienogest / estradiol has a moderate potential interaction with Diabetes Mellitus.

Impaired glucose tolerance has been observed in some patients administered oral contraceptives and appears to be related primarily to the estrogen dose. However, progestogens can increase insulin secretion and produce insulin resistance to varying degrees, depending on the agent. Caution and close monitoring are recommended in patients with diabetes mellitus during therapy with estrogens and/or progestogens, and adjustments made accordingly in their antidiabetic regimen.

metFORMIN 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.

metFORMIN 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 estradiol in dienogest / estradiol has a moderate potential interaction with Fluid Retention.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

metFORMIN 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 estradiol in dienogest / estradiol has a moderate potential interaction with Gallbladder Disease.

A two- to four-fold increase in risk of gallbladder disease has been noted in women receiving postmenopausal estrogen therapy. The risk for gallbladder disease may be less for premenopausal women using oral contraceptives containing low-dose estrogens and/or progestins. Therapy with estrogens should be administered cautiously in patients with preexisting gallbladder disease or a history of pregnancy-related cholestasis.

metFORMIN 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.

metFORMIN 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.

The estradiol in dienogest / estradiol has a moderate potential interaction with Heart Failure.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

The estradiol in dienogest / estradiol has a major potential interaction with High Blood Pressure.

The risk of myocardial infarction and strokes, including those associated with oral contraceptive use and some estrogen use, is increased in patients with hypertension. Moreover, estrogens (and progestogens) may elevate blood pressure and worsen the hypertension, thus compounding the risk. Clinically significant blood pressure increases have been reported during estrogen therapy, particularly in patients receiving high dosages or treated with oral contraceptive combinations having high progestational activity. These effects also increase with duration of therapy and patient age. Therapy with estrogens should be administered cautiously in patients with preexisting hypertension. Some estrogen-based therapies, such as combined hormonal contraceptives, may be contraindicated in patients with uncontrolled hypertension or hypertension with vascular disease. Patients should be monitored for changes in cardiovascular status, and their antihypertensive regimen adjusted or estrogen therapy withdrawn as necessary. In patients requiring contraception, alternative methods should be considered for those who are hypertensive, over age 35, and smoke.

The estradiol in dienogest / estradiol has a moderate potential interaction with High Cholesterol.

Estrogens may cause adverse lipid changes. Use of estrogens has been associated with elevations in triglyceride levels, particularly in women with pre-existing hypertriglyceridemia. Discontinue therapy if elevated triglycerides lead to pancreatitis. Manage hypercholesterolemia appropriately as indicated.

The estradiol in dienogest / estradiol has a major potential interaction with History, Thrombotic/Thromboembolic Disorder.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

The estradiol in dienogest / estradiol has a moderate potential interaction with Hypoparathyroidism.

Estrogens should be used with caution in individuals with severe hypocalcemia or hypoparathyroidism. Estrogen-induced hypocalcemia may occur in patients with hypoparathyroidism; consider whether the benefits of estrogen therapy outweigh the risks.

The estradiol in dienogest / estradiol has a major potential interaction with Ischemic Heart Disease.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

metFORMIN 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.

metFORMIN 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 estradiol in dienogest / estradiol has a moderate potential interaction with Liver Disease.

Estrogens are primarily metabolized by the liver. Use of estrogen therapy is contraindicated in patients with liver dysfunction or disease. Patients with impaired hepatic function may be at increased risk for adverse effects associated with estrogen administration due to decreased drug clearance. Patients with hepatic hemangiomas are at increased risk of exacerbation with use of estrogens. Therapy with estrogens should be administered cautiously in patients with cholestatic jaundice associated with past estrogen use or with pregnancy. In addition, clinicians should be aware that estrogen therapy may affect liver function tests.

metFORMIN has 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 estradiol in dienogest / estradiol has a major potential interaction with Migraine.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

The estradiol in dienogest / estradiol has a moderate potential interaction with Migraine.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

The estradiol in dienogest / estradiol has a major potential interaction with Neoplasia, Estrogen Dependent.

The use of estrogens is generally contraindicated in patients with known or suspected estrogen-dependent neoplasia such as breast and endometrial cancer, since it may stimulate tumor proliferation. High dosages of estrogens may be used for the palliative treatment of inoperable, metastatic breast cancer, but only in appropriately selected men and postmenopausal women.

The estradiol in dienogest / estradiol has a moderate potential interaction with Pancreatitis.

Estrogens may cause adverse lipid changes. Use of estrogens has been associated with elevations in triglyceride levels, particularly in women with pre-existing hypertriglyceridemia. Discontinue therapy if elevated triglycerides lead to pancreatitis. Manage hypercholesterolemia appropriately as indicated.

metFORMIN has 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.

metFORMIN 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.

metFORMIN 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 estradiol in dienogest / estradiol has a moderate potential interaction with Renal Dysfunction.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

The estradiol in dienogest / estradiol has a moderate potential interaction with Seizures.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

metFORMIN 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.

The estradiol in dienogest / estradiol has a major potential interaction with Thrombotic/Thromboembolic Disorder.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

The estradiol in dienogest / estradiol has a moderate potential interaction with Thyroid Disease.

When administering estrogen and/or progestogen therapy in patients with thyroid disorders, clinicians should be aware that these hormones may affect thyroid function tests. Patients on thyroid replacement therapy may require higher doses of thyroid hormone and appropriate monitoring. Changes have mostly been reported with the use of combination oral contraceptives. Specifically, thyroid-binding globulin (TBG) may be increased, resulting in elevated circulating total thyroid hormone, as measured by PBI (protein-bound iodine), T4 by column or radioimmunoassay, or T3 by radioimmunoassay. Free T3 resin uptake may be decreased. On the contrary, a decrease in TBG and, consequently, thyroxine concentration, has been reported by the manufacturers of the progestin-only (norethindrone) oral contraceptives.

metFORMIN 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.