Interactions between Corticorelin and Estradiol / levonorgestrel

Corticorelin has a moderate potential interaction with Abnormal Glucose Tolerance.

Adrenocorticotropic agents may impair glucose tolerance and cause hyperglycemia. Therapy with these agents should be administered cautiously in patients with diabetes mellitus, glucose intolerance, or a predisposition to hyperglycemia. Patients with diabetes mellitus should be monitored more closely during adrenocorticotropic therapy, and their antidiabetic regimen adjusted accordingly.

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

The use of contraceptives is contraindicated when there is an undiagnosed abnormal genital bleeding. Adequate diagnostic measures should be undertaken to rule out the presence of any malignancy.

The estradiol in estradiol / levonorgestrel 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.

Corticorelin has a major potential interaction with Adrenal Insufficiency.

The use of adrenocorticotropic agents is contraindicated in patients with primary adrenocortical insufficiency because of the lack of adrenal responsiveness.

The estradiol in estradiol / levonorgestrel 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 and levonorgestrel in estradiol / levonorgestrel both have 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.

The levonorgestrel in estradiol / levonorgestrel has a major potential interaction with Breast Cancer.

The use of progestogens is considered by manufacturers to be contraindicated in patients with existing or suspected malignancy of the breast. Some supportive data are available for medroxyprogesterone. Specifically, medroxyprogesterone treatment may be associated with breast cancer, primarily when the drug is administered intramuscularly. A pooled analysis of two case-control studies, one from the World Health Organization and the other from New Zealand, revealed a small overall relative risk of breast cancer in women who have ever used intramuscular medroxyprogesterone acetate. The relative risk was higher in the subgroup of women who had initiated therapy within the previous 5 years. Thus, an increased risk (approximately 2-fold) is associated with intramuscular medroxyprogesterone use in the first 5 years. A more recent U.S. study also found a statistically significant increase in breast cancer risk among recent users (defined as last use within the past five years) who used depo-medroxyprogesterone acetate for 12 months or longer.

The estradiol in estradiol / levonorgestrel 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 estradiol / levonorgestrel 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.

The levonorgestrel in estradiol / levonorgestrel has a moderate potential interaction with Cerebral Vascular Disorder.

The use of levonorgestrel requires careful assessment and caution in conditions of arterial disease, including stroke and myocardial infarction, and also, in patients with increased blood pressure and coagulopathies.

Corticorelin has a moderate potential interaction with Cirrhosis.

Adrenocorticotropic agents may have enhanced effects in patients with cirrhosis. Dosage adjustments may be necessary in these patients.

Corticorelin has a moderate potential interaction with Depression.

Adrenocorticotropic agents may aggravate the symptoms of psychosis and emotional instability. Patients with these conditions should be monitored for increased or worsened symptoms during adrenocorticotropic therapy.

The levonorgestrel in estradiol / levonorgestrel has a moderate potential interaction with Depression.

The use of oral contraceptives has been associated with an increased incidence of depression. It is uncertain whether this effect is related to the estrogenic or the progestogenic component of the contraceptive, although excess progesterone activity is associated with depression. Patients with a history of depression receiving estrogen and/or progestogen therapy should be followed closely. The manufacturer of medroxyprogesterone recommends monitoring patients who have a history of depression and to not re- administer medroxyprogesterone if depression recurs.

Corticorelin has a moderate potential interaction with Diabetes Mellitus.

Adrenocorticotropic agents may impair glucose tolerance and cause hyperglycemia. Therapy with these agents should be administered cautiously in patients with diabetes mellitus, glucose intolerance, or a predisposition to hyperglycemia. Patients with diabetes mellitus should be monitored more closely during adrenocorticotropic therapy, and their antidiabetic regimen adjusted accordingly.

The estradiol and levonorgestrel in estradiol / levonorgestrel both have 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.

Corticorelin has a major potential interaction with Diverticulitis.

Adrenocorticotropic agents may cause gastrointestinal perforation and hemorrhage, usually when given in high dosages or for prolonged periods. They may also mask symptoms of complications such as peritonitis or intraabdominal sepsis. Therapy with adrenocorticotropic agents should be administered cautiously in patients with diverticulitis, nonspecific ulcerative colitis (if there is a probability of impending perforation, abscess, or other pyogenic infection), or recent intestinal anastomoses.

Corticorelin has a major potential interaction with Fluid Retention.

Adrenocorticotropic agents may cause hypernatremia, hypokalemia, fluid retention, and elevation in blood pressure. Therapy with these agents, particularly if intended for longer than brief periods, should be administered cautiously in patients with preexisting fluid retention or conditions that may be aggravated by these effects. Dietary sodium restriction and potassium supplementation may be advisable. The manufacturers consider the use of adrenocorticotropic agents to be contraindicated in patients with congestive heart failure or uncontrolled hypertension.

The estradiol and levonorgestrel in estradiol / levonorgestrel both have 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 estradiol / levonorgestrel 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.

Corticorelin has a moderate potential interaction with Glaucoma/Intraocular Hypertension.

Prolonged use of adrenocorticotropic agents may cause elevated intraocular pressure and glaucoma with possible damage to the optic nerves. Long-term therapy with these agents should be administered cautiously in patients with preexisting glaucoma (particularly open-angle glaucoma) or increased intraocular pressure.

Corticorelin has a major potential interaction with Heart Failure.

Adrenocorticotropic agents may cause hypernatremia, hypokalemia, fluid retention, and elevation in blood pressure. Therapy with these agents, particularly if intended for longer than brief periods, should be administered cautiously in patients with preexisting fluid retention or conditions that may be aggravated by these effects. Dietary sodium restriction and potassium supplementation may be advisable. The manufacturers consider the use of adrenocorticotropic agents to be contraindicated in patients with congestive heart failure or uncontrolled hypertension.

The estradiol and levonorgestrel in estradiol / levonorgestrel both have 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 levonorgestrel in estradiol / levonorgestrel has a major potential interaction with Hepatic Tumor.

The use of oral contraceptives is contraindicated in patients with liver tumors. An increased risk of benign hepatic adenomas and hepatocellular carcinomas has been associated with long-term, oral estrogen- progestin contraceptive use of at least 4 years and 8 years, respectively. Although these tumors are rare and have not been reported with other types of estrogen or progestogen therapies, any preparation containing estrogens and/or progestogens should probably be avoided in patients with existing tumors of the liver. Hepatic hemangiomas and nodular hyperplasia of the liver have been reported with isolated estrogen therapy.

Corticorelin has a major potential interaction with Herpetic Keratitis.

Adrenocorticotropic agents should be used cautiously, if at all, in patients with ocular herpes simplex because of the risk of corneal perforation. The manufacturers consider their use to be contraindicated in such setting.

Corticorelin has a major potential interaction with High Blood Pressure.

Adrenocorticotropic agents may cause hypernatremia, hypokalemia, fluid retention, and elevation in blood pressure. Therapy with these agents, particularly if intended for longer than brief periods, should be administered cautiously in patients with preexisting fluid retention or conditions that may be aggravated by these effects. Dietary sodium restriction and potassium supplementation may be advisable. The manufacturers consider the use of adrenocorticotropic agents to be contraindicated in patients with congestive heart failure or uncontrolled hypertension.

The estradiol in estradiol / levonorgestrel 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 levonorgestrel in estradiol / levonorgestrel has a moderate potential interaction with High Blood Pressure.

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

Some progestogenic agents may elevate plasma LDL levels and/or lower HDL levels, although data have been inconsistent. Patients with preexisting hyperlipidemia may require closer monitoring during progestogen therapy, and adjustments made accordingly in their lipid-lowering regimen.

Corticorelin has a major potential interaction with History, Peptic Ulcer.

Adrenocorticotropic agents may cause peptic ulcer disease and gastrointestinal (GI) hemorrhage, usually when given in high dosages or for prolonged periods. Delayed healing of peptic ulcers has also been reported. Therapy with adrenocorticotropic agents, if necessary, should be administered cautiously in patients with active or latent peptic ulcers or other risk factors for GI bleeding. The manufacturers consider their use to be contraindicated in such setting.

The estradiol in estradiol / levonorgestrel 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.

Corticorelin has a moderate potential interaction with History, Thrombotic/Thromboembolic Disorder.

Adrenocorticotropic agents may increase blood coagulability and have rarely been associated with the development of intravascular thrombosis, thromboembolism, and thrombophlebitis. These agents should be used cautiously in patients with thrombotic or thromboembolic disorders.

The levonorgestrel in estradiol / levonorgestrel has a moderate potential interaction with History, Thrombotic/Thromboembolic Disorder.

The use of levonorgestrel requires careful assessment and caution in conditions of arterial disease, including stroke and myocardial infarction, and also, in patients with increased blood pressure and coagulopathies.

Corticorelin has a major potential interaction with History, Tuberculosis.

In patients with latent tuberculosis or tuberculin reactivity, the use of pharmacologic dosages of adrenocorticotropic agents may cause a reactivation of the disease. Close monitoring for signs and symptoms of tuberculosis is recommended if adrenocorticotropic therapy is administered to these patients. During prolonged use, tuberculosis chemoprophylaxis may be considered.

Corticorelin has a major potential interaction with Hyperadrenocorticism.

The use of adrenocorticotropic agents is contraindicated in patients with adrenocortical hyperfunction. These agents stimulate the release of cortisol and aldosterone and may aggravate symptoms of hyperadrenocorticism.

Corticorelin has a major potential interaction with Hypernatremia.

Adrenocorticotropic agents may cause hypernatremia, hypokalemia, hypocalcemia, and fluid retention. Therapy with these agents, particularly if intended for longer than brief periods, should be administered cautiously in patients with preexisting electrolyte disturbances. Caution is also advised when treating patients with seizure disorders, since electrolyte disturbances may trigger seizure activity.

Corticorelin has a major potential interaction with Hypocalcemia.

Adrenocorticotropic agents may cause hypernatremia, hypokalemia, hypocalcemia, and fluid retention. Therapy with these agents, particularly if intended for longer than brief periods, should be administered cautiously in patients with preexisting electrolyte disturbances. Caution is also advised when treating patients with seizure disorders, since electrolyte disturbances may trigger seizure activity.

Corticorelin has a major potential interaction with Hypokalemia.

Adrenocorticotropic agents may cause hypernatremia, hypokalemia, hypocalcemia, and fluid retention. Therapy with these agents, particularly if intended for longer than brief periods, should be administered cautiously in patients with preexisting electrolyte disturbances. Caution is also advised when treating patients with seizure disorders, since electrolyte disturbances may trigger seizure activity.

The estradiol in estradiol / levonorgestrel 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.

Corticorelin has a major potential interaction with Infection.

The immunosuppressant and anti-inflammatory effects of adrenocorticotropic agents, particularly in higher dosages, may decrease host resistance to infectious agents, decrease the ability to localize infections, and mask the symptoms of infection. Secondary infections may be more likely to develop. In general, adrenocorticotropic agents should not be used in patients with active infections, especially systemic fungal infections, unless they are medically necessary and effective antimicrobial therapy or other appropriate treatment has been instituted. For patients who have received prolonged adrenocorticotropic therapy who develop a severe or life-threatening infection, supplemental doses of rapid-acting corticosteroids may be required, since these patients may have hypothalamic-pituitary insufficiency.

Corticorelin has a major potential interaction with Intestinal Anastomoses.

Adrenocorticotropic agents may cause gastrointestinal perforation and hemorrhage, usually when given in high dosages or for prolonged periods. They may also mask symptoms of complications such as peritonitis or intraabdominal sepsis. Therapy with adrenocorticotropic agents should be administered cautiously in patients with diverticulitis, nonspecific ulcerative colitis (if there is a probability of impending perforation, abscess, or other pyogenic infection), or recent intestinal anastomoses.

The estradiol in estradiol / levonorgestrel 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.

The levonorgestrel in estradiol / levonorgestrel has a major potential interaction with Liver Disease.

The use of progestogens, in general, is contraindicated in patients with impaired hepatic function or liver disease. There are little or no data concerning the pharmacokinetic disposition of the different progestogens in patients with hepatic disease. However, most hormones, including progestational hormones, are known to be extensively metabolized by the liver. Medroxyprogesterone should not be used by women with significant liver disease and should be discontinued if jaundice or disturbances of liver function occur.

The estradiol in estradiol / levonorgestrel 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.

The estradiol in estradiol / levonorgestrel 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 and levonorgestrel in estradiol / levonorgestrel both have 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.

Corticorelin has a moderate potential interaction with Myasthenia Gravis.

While corticotropin has been used effectively in severe, refractory myasthenia gravis to increase muscle strength, it should nevertheless be administered with extreme caution in such setting. Patients must be treated in an intensive care unit and receive respiratory support, since muscle strength will markedly decrease initially. Improvement usually occurs several days after the first or second course of treatment. Similar responses might be expected of other adrenocorticotropic agents, although their use in myasthenia gravis has not been studied extensively.

Corticorelin has a moderate potential interaction with Myoneural Disorder.

Toxic myopathy may occur with the prolonged use of adrenocorticotropic agents, often in patients with disorders of neuromuscular transmission such as myasthenia gravis or in patients receiving neuromuscular blocking agents. Steroid myopathy is generalized and sometimes accompanied by respiratory weakness and dyspnea. In some cases, it has resulted in quadraparesis. Elevations of creatine kinase may also occur, albeit infrequently. After withdrawal of ACTH therapy, recovery may be slow and incomplete. Therapy with adrenocorticotropic agents should be administered cautiously in patients with preexisting myopathy or myoneural disorders, since these conditions may confound the diagnosis of steroid-induced myopathy. The presence of a normal serum CK level, minimal or no changes of myopathy on EMG, and type 2 muscle fiber atrophy on biopsy are helpful in suggesting steroid-induced weakness. If steroid myopathy is suspected, a dosage reduction or discontinuation of adrenocorticotropic therapy should be considered.

Corticorelin has a moderate potential interaction with Myopathy.

Toxic myopathy may occur with the prolonged use of adrenocorticotropic agents, often in patients with disorders of neuromuscular transmission such as myasthenia gravis or in patients receiving neuromuscular blocking agents. Steroid myopathy is generalized and sometimes accompanied by respiratory weakness and dyspnea. In some cases, it has resulted in quadraparesis. Elevations of creatine kinase may also occur, albeit infrequently. After withdrawal of ACTH therapy, recovery may be slow and incomplete. Therapy with adrenocorticotropic agents should be administered cautiously in patients with preexisting myopathy or myoneural disorders, since these conditions may confound the diagnosis of steroid-induced myopathy. The presence of a normal serum CK level, minimal or no changes of myopathy on EMG, and type 2 muscle fiber atrophy on biopsy are helpful in suggesting steroid-induced weakness. If steroid myopathy is suspected, a dosage reduction or discontinuation of adrenocorticotropic therapy should be considered.

The estradiol in estradiol / levonorgestrel 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.

Corticorelin has a major potential interaction with Osteoporosis.

Adrenocorticotropic agents inhibit the absorption of intestinal calcium and increase urinary excretion of calcium, which can result in bone resorption and bone loss during prolonged therapy. In addition, bone matrix may be affected by the protein-catabolic effects of these agents, especially when given in high dosages or for prolonged periods, leading to aseptic necrosis and fractures. Long-term or high-dose adrenocorticotropic therapy should be administered cautiously and only if necessary in patients with or at risk for osteoporosis. The manufacturers consider the use of adrenocorticotropic agents to be contraindicated in such setting.

The estradiol in estradiol / levonorgestrel 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.

Corticorelin has a major potential interaction with Peptic Ulcer.

Adrenocorticotropic agents may cause peptic ulcer disease and gastrointestinal (GI) hemorrhage, usually when given in high dosages or for prolonged periods. Delayed healing of peptic ulcers has also been reported. Therapy with adrenocorticotropic agents, if necessary, should be administered cautiously in patients with active or latent peptic ulcers or other risk factors for GI bleeding. The manufacturers consider their use to be contraindicated in such setting.

Corticorelin has a moderate potential interaction with Psychosis.

Adrenocorticotropic agents may aggravate the symptoms of psychosis and emotional instability. Patients with these conditions should be monitored for increased or worsened symptoms during adrenocorticotropic therapy.

Corticorelin has a major potential interaction with Renal Dysfunction.

Adrenocorticotropic agents may cause hypernatremia, hypokalemia, fluid retention, and elevation in blood pressure. Therapy with these agents, particularly if intended for longer than brief periods, should be administered cautiously in patients with preexisting fluid retention or conditions that may be aggravated by these effects. Dietary sodium restriction and potassium supplementation may be advisable. The manufacturers consider the use of adrenocorticotropic agents to be contraindicated in patients with congestive heart failure or uncontrolled hypertension.

The estradiol and levonorgestrel in estradiol / levonorgestrel both have 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.

Corticorelin has a major potential interaction with Seizures.

Adrenocorticotropic agents may cause hypernatremia, hypokalemia, hypocalcemia, and fluid retention. Therapy with these agents, particularly if intended for longer than brief periods, should be administered cautiously in patients with preexisting electrolyte disturbances. Caution is also advised when treating patients with seizure disorders, since electrolyte disturbances may trigger seizure activity.

The estradiol and levonorgestrel in estradiol / levonorgestrel both have 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.

Corticorelin has a major potential interaction with Systemic Sclerosis.

The use of adrenocorticotropic agents is contraindicated in patients with scleroderma. Adrenocorticotropic agents may precipitate renal crisis with malignant hypertension in these patients, possibly via steroid-induced increases in renin substrate and angiotensin II levels and decreases in vasodilator prostaglandin production. Renal failure may ensue. If treatment is required for inflammatory myositis or pericarditis, glucocorticoids are preferable because of their more predictable pharmacologic effect. However, glucocorticoids should also be avoided in the long-term treatment of patients with scleroderma for similar reasons.

The estradiol in estradiol / levonorgestrel 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.

Corticorelin has a moderate potential interaction with Thrombotic/Thromboembolic Disorder.

Adrenocorticotropic agents may increase blood coagulability and have rarely been associated with the development of intravascular thrombosis, thromboembolism, and thrombophlebitis. These agents should be used cautiously in patients with thrombotic or thromboembolic disorders.

The levonorgestrel in estradiol / levonorgestrel has a moderate potential interaction with Thrombotic/Thromboembolic Disorder.

The use of levonorgestrel requires careful assessment and caution in conditions of arterial disease, including stroke and myocardial infarction, and also, in patients with increased blood pressure and coagulopathies.

The estradiol and levonorgestrel in estradiol / levonorgestrel both have 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.

Corticorelin has a major potential interaction with Tuberculosis, Latent.

In patients with latent tuberculosis or tuberculin reactivity, the use of pharmacologic dosages of adrenocorticotropic agents may cause a reactivation of the disease. Close monitoring for signs and symptoms of tuberculosis is recommended if adrenocorticotropic therapy is administered to these patients. During prolonged use, tuberculosis chemoprophylaxis may be considered.

Corticorelin has a major potential interaction with Ulcerative Colitis.

Adrenocorticotropic agents may cause gastrointestinal perforation and hemorrhage, usually when given in high dosages or for prolonged periods. They may also mask symptoms of complications such as peritonitis or intraabdominal sepsis. Therapy with adrenocorticotropic agents should be administered cautiously in patients with diverticulitis, nonspecific ulcerative colitis (if there is a probability of impending perforation, abscess, or other pyogenic infection), or recent intestinal anastomoses.

Corticorelin has a moderate potential interaction with Underactive Thyroid.

Adrenocorticotropic agents may have enhanced effects in patients with hypothyroidism. Dosage adjustments may be necessary in these patients.

Corticorelin has a major potential interaction with Vaccination.

The administration of live or live, attenuated vaccines is contraindicated in patients receiving large or immunosuppressive doses of adrenocorticotropic agents. Inactivated viral or bacterial vaccines should be used with caution, since their administration may pose a risk of neurological complications in these patients. Additionally, a diminished or inadequate serum antibody response may be anticipated.

The levonorgestrel in estradiol / levonorgestrel has a minor potential interaction with Weight Loss.

Progestogens can cause weight gain, which may be significant (as is the case with parenteral medroxyprogesterone) and undesirable in obese patients attempting to lose weight.