Can you take Dienogest / estradiol with Divalproex sodium?

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.

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.

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.

Divalproex sodium has a moderate potential interaction with Bleeding Disorder.

The use of valproate derivatives may be associated with dose-related thrombocytopenia, the incidence of which is generally low but has been reported at up to 27% in one study using high dosages (approximately 50 mg/kg/day of valproic acid). In that study, platelet counts returned to normal in all patients, some despite continued treatment. Valproate may also inhibit the secondary phase of platelet aggregation, although this effect is unlikely to be of clinical significance except during the concomitant use of other drugs that affect coagulation. However, altered bleeding time, ecchymosis, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage have been reported rarely. Hypofibrinogenemia has also been observed. Therapy with valproate products, particularly at high dosages, should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including hemostatic and/or coagulation defects associated with hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, or severe hepatic impairment. The manufacturers recommend platelet counts and coagulation tests prior to initiating therapy and at periodic intervals thereafter, as well as before planned surgery. The dosage should be reduced or the drug withdrawn if clinical evidence of hemorrhage, bruising, or a disorder of hemostasis or coagulation occurs.

Divalproex sodium has a major potential interaction with Brain Anomalies incl Congenital.

The use of valproate derivatives is contraindicated in patients with hepatic disease or significant hepatic dysfunction. Serious and potentially fatal hepatotoxicity has been reported in patients treated with these agents. The risk appears to be greatest in children less than 2 years of age--particularly those on multiple anticonvulsants and those with congenital metabolic disorders, severe seizure disorders accompanied by intellectual disability, or organic brain disease--and decreases considerably in progressively older patient groups. Therapy with valproate products should be administered with extreme caution and as a sole agent in patients with risk factors for valproate-related hepatotoxicity. In reported cases, the onset has generally been within the first 6 months of treatment and may be preceded by nonspecific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, nausea, vomiting, and a loss of seizure control. Patients should be monitored closely for appearance of these symptoms, and therapy withdrawn immediately if significant hepatic dysfunction occurs. Liver function tests should be performed prior to initiating therapy and at frequent intervals thereafter, especially during the first 6 months. However, clinicians should bear in mind that transient, dose-related, asymptomatic elevations in serum transaminase, amylase and ammonia levels may commonly occur and often return to normal with or without dosage adjustment.

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.

Divalproex sodium has a moderate potential interaction with Coagulation Defects and Disorders.

The use of valproate derivatives may be associated with dose-related thrombocytopenia, the incidence of which is generally low but has been reported at up to 27% in one study using high dosages (approximately 50 mg/kg/day of valproic acid). In that study, platelet counts returned to normal in all patients, some despite continued treatment. Valproate may also inhibit the secondary phase of platelet aggregation, although this effect is unlikely to be of clinical significance except during the concomitant use of other drugs that affect coagulation. However, altered bleeding time, ecchymosis, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage have been reported rarely. Hypofibrinogenemia has also been observed. Therapy with valproate products, particularly at high dosages, should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including hemostatic and/or coagulation defects associated with hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, or severe hepatic impairment. The manufacturers recommend platelet counts and coagulation tests prior to initiating therapy and at periodic intervals thereafter, as well as before planned surgery. The dosage should be reduced or the drug withdrawn if clinical evidence of hemorrhage, bruising, or a disorder of hemostasis or coagulation occurs.

Divalproex sodium has a major potential interaction with Depression.

Antiepileptic drugs can increase depression and suicidal thoughts or behaviors in patients receiving these drugs for any indication. Patients should be monitored for the emergence or worsening of depression, suicidal thoughts and unusual changes in mood or behavior. Caregivers and family should be alert for the emergence or worsening of symptoms. Behaviors of concern should be reported immediately to the healthcare providers.

Divalproex sodium has a moderate potential interaction with Depression.

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.

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.

Divalproex sodium has a moderate potential interaction with Diabetes Mellitus.

Valproate is partially eliminated in the urine as a ketone-containing metabolite, which may lead to a false interpretation of the urine ketone test. Clinicians should be cognizant of this interaction when prescribing or administering valproate products to patients with diabetes.

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.

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.

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.

Divalproex sodium has a moderate potential interaction with HIV-1 Infection.

Some in vitro studies suggest that valproate stimulates the replication of the HIV and CMV viruses under certain experimental conditions. The clinical consequences are unknown, and the relevance of these findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. However, this should be borne in mind when interpreting the results from regular monitoring of the viral load in HIV infected patients receiving valproate or when following CMV infected patients clinically.

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.

Divalproex sodium has a major potential interaction with Intellectual Disability.

The use of valproate derivatives is contraindicated in patients with hepatic disease or significant hepatic dysfunction. Serious and potentially fatal hepatotoxicity has been reported in patients treated with these agents. The risk appears to be greatest in children less than 2 years of age--particularly those on multiple anticonvulsants and those with congenital metabolic disorders, severe seizure disorders accompanied by intellectual disability, or organic brain disease--and decreases considerably in progressively older patient groups. Therapy with valproate products should be administered with extreme caution and as a sole agent in patients with risk factors for valproate-related hepatotoxicity. In reported cases, the onset has generally been within the first 6 months of treatment and may be preceded by nonspecific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, nausea, vomiting, and a loss of seizure control. Patients should be monitored closely for appearance of these symptoms, and therapy withdrawn immediately if significant hepatic dysfunction occurs. Liver function tests should be performed prior to initiating therapy and at frequent intervals thereafter, especially during the first 6 months. However, clinicians should bear in mind that transient, dose-related, asymptomatic elevations in serum transaminase, amylase and ammonia levels may commonly occur and often return to normal with or without dosage adjustment.

Divalproex sodium has a major potential interaction with Intellectual Disability.

Valproic acid and derivative products are contraindicated in patients with known urea cycle disorders (UCD), as hyperammonemic encephalopathy, sometimes fatal, has been reported on these patients following the initiation of treatment. Prior to the initiation of therapy, the evaluation for UCD should be considered in patients with history of unexplained encephalopathy or comma, encephalopathy associated with a protein load, pregnancy- related or postpartum encephalopathy, unexplained intellectual disability, or history of elevated plasma ammonia or glutamine. Also, those with family history of UCD or family history of unexplained infant deaths. Patients who develop symptoms of hyperammonemic encephalopathy while receiving valproate therapy should receive prompt treatment including treatment discontinuation and be evaluated for underlying urea cycle disorders.

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.

Divalproex sodium has a major potential interaction with Liver Disease.

The use of valproate derivatives is contraindicated in patients with hepatic disease or significant hepatic dysfunction. Serious and potentially fatal hepatotoxicity has been reported in patients treated with these agents. The risk appears to be greatest in children less than 2 years of age--particularly those on multiple anticonvulsants and those with congenital metabolic disorders, severe seizure disorders accompanied by intellectual disability, or organic brain disease--and decreases considerably in progressively older patient groups. Therapy with valproate products should be administered with extreme caution and as a sole agent in patients with risk factors for valproate-related hepatotoxicity. In reported cases, the onset has generally been within the first 6 months of treatment and may be preceded by nonspecific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, nausea, vomiting, and a loss of seizure control. Patients should be monitored closely for appearance of these symptoms, and therapy withdrawn immediately if significant hepatic dysfunction occurs. Liver function tests should be performed prior to initiating therapy and at frequent intervals thereafter, especially during the first 6 months. However, clinicians should bear in mind that transient, dose-related, asymptomatic elevations in serum transaminase, amylase and ammonia levels may commonly occur and often return to normal with or without dosage adjustment.

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.

Divalproex sodium has a major potential interaction with Metabolic Disorders.

Valproic acid and derivative products are contraindicated in patients with known urea cycle disorders (UCD), as hyperammonemic encephalopathy, sometimes fatal, has been reported on these patients following the initiation of treatment. Prior to the initiation of therapy, the evaluation for UCD should be considered in patients with history of unexplained encephalopathy or comma, encephalopathy associated with a protein load, pregnancy- related or postpartum encephalopathy, unexplained intellectual disability, or history of elevated plasma ammonia or glutamine. Also, those with family history of UCD or family history of unexplained infant deaths. Patients who develop symptoms of hyperammonemic encephalopathy while receiving valproate therapy should receive prompt treatment including treatment discontinuation and be evaluated for underlying urea cycle disorders.

Divalproex sodium has a major potential interaction with Metabolic Disorders.

The use of valproate derivatives is contraindicated in patients with hepatic disease or significant hepatic dysfunction. Serious and potentially fatal hepatotoxicity has been reported in patients treated with these agents. The risk appears to be greatest in children less than 2 years of age--particularly those on multiple anticonvulsants and those with congenital metabolic disorders, severe seizure disorders accompanied by intellectual disability, or organic brain disease--and decreases considerably in progressively older patient groups. Therapy with valproate products should be administered with extreme caution and as a sole agent in patients with risk factors for valproate-related hepatotoxicity. In reported cases, the onset has generally been within the first 6 months of treatment and may be preceded by nonspecific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, nausea, vomiting, and a loss of seizure control. Patients should be monitored closely for appearance of these symptoms, and therapy withdrawn immediately if significant hepatic dysfunction occurs. Liver function tests should be performed prior to initiating therapy and at frequent intervals thereafter, especially during the first 6 months. However, clinicians should bear in mind that transient, dose-related, asymptomatic elevations in serum transaminase, amylase and ammonia levels may commonly occur and often return to normal with or without dosage adjustment.

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.

Divalproex sodium has a moderate potential interaction with Psychosis.

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.

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.

Divalproex sodium has a moderate potential interaction with Thrombocytopathy.

The use of valproate derivatives may be associated with dose-related thrombocytopenia, the incidence of which is generally low but has been reported at up to 27% in one study using high dosages (approximately 50 mg/kg/day of valproic acid). In that study, platelet counts returned to normal in all patients, some despite continued treatment. Valproate may also inhibit the secondary phase of platelet aggregation, although this effect is unlikely to be of clinical significance except during the concomitant use of other drugs that affect coagulation. However, altered bleeding time, ecchymosis, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage have been reported rarely. Hypofibrinogenemia has also been observed. Therapy with valproate products, particularly at high dosages, should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including hemostatic and/or coagulation defects associated with hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, or severe hepatic impairment. The manufacturers recommend platelet counts and coagulation tests prior to initiating therapy and at periodic intervals thereafter, as well as before planned surgery. The dosage should be reduced or the drug withdrawn if clinical evidence of hemorrhage, bruising, or a disorder of hemostasis or coagulation occurs.

Divalproex sodium has a moderate potential interaction with Thrombocytopenia.

The use of valproate derivatives may be associated with dose-related thrombocytopenia, the incidence of which is generally low but has been reported at up to 27% in one study using high dosages (approximately 50 mg/kg/day of valproic acid). In that study, platelet counts returned to normal in all patients, some despite continued treatment. Valproate may also inhibit the secondary phase of platelet aggregation, although this effect is unlikely to be of clinical significance except during the concomitant use of other drugs that affect coagulation. However, altered bleeding time, ecchymosis, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage have been reported rarely. Hypofibrinogenemia has also been observed. Therapy with valproate products, particularly at high dosages, should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including hemostatic and/or coagulation defects associated with hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, or severe hepatic impairment. The manufacturers recommend platelet counts and coagulation tests prior to initiating therapy and at periodic intervals thereafter, as well as before planned surgery. The dosage should be reduced or the drug withdrawn if clinical evidence of hemorrhage, bruising, or a disorder of hemostasis or coagulation occurs.

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.

Divalproex sodium has a moderate potential interaction with Thyroid Disease.

The manufacturers state that there have been reports of altered thyroid function tests associated with the use of valproate. However, no specific information is given. Clinicians should be cognizant of this potential effect when prescribing or administering valproate products to patients with thyroid disease.

Divalproex sodium has a moderate potential interaction with Vitamin K Deficiency.

The use of valproate derivatives may be associated with dose-related thrombocytopenia, the incidence of which is generally low but has been reported at up to 27% in one study using high dosages (approximately 50 mg/kg/day of valproic acid). In that study, platelet counts returned to normal in all patients, some despite continued treatment. Valproate may also inhibit the secondary phase of platelet aggregation, although this effect is unlikely to be of clinical significance except during the concomitant use of other drugs that affect coagulation. However, altered bleeding time, ecchymosis, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage have been reported rarely. Hypofibrinogenemia has also been observed. Therapy with valproate products, particularly at high dosages, should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including hemostatic and/or coagulation defects associated with hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, or severe hepatic impairment. The manufacturers recommend platelet counts and coagulation tests prior to initiating therapy and at periodic intervals thereafter, as well as before planned surgery. The dosage should be reduced or the drug withdrawn if clinical evidence of hemorrhage, bruising, or a disorder of hemostasis or coagulation occurs.