Drug Interactions between estradiol topical and mobocertinib

You should avoid consumption of grapefruit and grapefruit juice during treatment with mobocertinib. Grapefruit juice can increase the blood levels of mobocertinib. This may increase the risk of side effects such as diarrhea, nausea, vomiting, rash, fatigue, musculoskeletal pain, mouth sores and inflammation, heart failure, and rare but potentially serious and life-threatening irregular heart rhythm disorders. Talk to your doctor if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

The use of estrogens is contraindicated in patients with undiagnosed, abnormal vaginal bleeding. Prolonged (> 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.

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 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.

Mobocertinib can cause life-threatening QTc prolongation, including torsades de pointes, which can be fatal, and requires monitoring of QTc and electrolytes. QTc and electrolytes should be assessed at baseline and abnormalities in sodium, potassium, calcium, and magnesium should be corrected before starting mobocertinib. QTc and electrolytes should be monitored periodically during therapy. Monitoring frequency should be increased in patients with risk factors for QTc prolongation (such as patients with congenital long QT syndrome, heart disease, or electrolyte abnormalities); caution is recommended in these patients. Therapy should be withheld, the dose should be reduced, or mobocertinib should be discontinued based on the severity of QTc prolongation.

Mobocertinib can cause life-threatening QTc prolongation, including torsades de pointes, which can be fatal, and requires monitoring of QTc and electrolytes. QTc and electrolytes should be assessed at baseline and abnormalities in sodium, potassium, calcium, and magnesium should be corrected before starting mobocertinib. QTc and electrolytes should be monitored periodically during therapy. Monitoring frequency should be increased in patients with risk factors for QTc prolongation (such as patients with congenital long QT syndrome, heart disease, or electrolyte abnormalities); caution is recommended in these patients. Therapy should be withheld, the dose should be reduced, or mobocertinib should be discontinued based on the severity of QTc prolongation.

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.

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 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.

Mobocertinib can cause life-threatening QTc prolongation, including torsades de pointes, which can be fatal, and requires monitoring of QTc and electrolytes. QTc and electrolytes should be assessed at baseline and abnormalities in sodium, potassium, calcium, and magnesium should be corrected before starting mobocertinib. QTc and electrolytes should be monitored periodically during therapy. Monitoring frequency should be increased in patients with risk factors for QTc prolongation (such as patients with congenital long QT syndrome, heart disease, or electrolyte abnormalities); caution is recommended in these patients. Therapy should be withheld, the dose should be reduced, or mobocertinib should be discontinued based on the severity of QTc prolongation.

Mobocertinib can cause life-threatening QTc prolongation, including torsades de pointes, which can be fatal, and requires monitoring of QTc and electrolytes. QTc and electrolytes should be assessed at baseline and abnormalities in sodium, potassium, calcium, and magnesium should be corrected before starting mobocertinib. QTc and electrolytes should be monitored periodically during therapy. Monitoring frequency should be increased in patients with risk factors for QTc prolongation (such as patients with congenital long QT syndrome, heart disease, or electrolyte abnormalities); caution is recommended in these patients. Therapy should be withheld, the dose should be reduced, or mobocertinib should be discontinued based on the severity of QTc prolongation.

Mobocertinib can cause life-threatening QTc prolongation, including torsades de pointes, which can be fatal, and requires monitoring of QTc and electrolytes. QTc and electrolytes should be assessed at baseline and abnormalities in sodium, potassium, calcium, and magnesium should be corrected before starting mobocertinib. QTc and electrolytes should be monitored periodically during therapy. Monitoring frequency should be increased in patients with risk factors for QTc prolongation (such as patients with congenital long QT syndrome, heart disease, or electrolyte abnormalities); caution is recommended in these patients. Therapy should be withheld, the dose should be reduced, or mobocertinib should be discontinued based on the severity of QTc prolongation.

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.

Mobocertinib can cause life-threatening QTc prolongation, including torsades de pointes, which can be fatal, and requires monitoring of QTc and electrolytes. QTc and electrolytes should be assessed at baseline and abnormalities in sodium, potassium, calcium, and magnesium should be corrected before starting mobocertinib. QTc and electrolytes should be monitored periodically during therapy. Monitoring frequency should be increased in patients with risk factors for QTc prolongation (such as patients with congenital long QT syndrome, heart disease, or electrolyte abnormalities); caution is recommended in these patients. Therapy should be withheld, the dose should be reduced, or mobocertinib should be discontinued based on the severity of QTc prolongation.

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 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 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 use of exogenous estrogens may induce or exacerbate symptoms of angioedema, particularly in women with hereditary angioedema. Close monitoring is recommended when prescribing these agents to patients predisposed to angioedema.

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.

Mobocertinib can cause cardiac toxicity (including decreased ejection fraction, cardiomyopathy, and congestive heart failure) resulting in heart failure which can be fatal. Cardiac function (including assessment of left ventricular ejection fraction) should be monitored at baseline and during therapy. Therapy should be withheld, the dose should be reduced, or mobocertinib should be discontinued based on the severity of decreased ejection fraction or heart failure.

Mobocertinib can cause cardiac toxicity (including decreased ejection fraction, cardiomyopathy, and congestive heart failure) resulting in heart failure which can be fatal. Cardiac function (including assessment of left ventricular ejection fraction) should be monitored at baseline and during therapy. Therapy should be withheld, the dose should be reduced, or mobocertinib should be discontinued based on the severity of decreased ejection fraction or 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.

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.

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.

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.

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.

No dosage adjustment of mobocertinib is recommended for patients with mild (total bilirubin up to the upper limit of normal [ULN] and AST greater than ULN or total bilirubin greater than 1 to 1.5 times ULN [1 to 1.5 x ULN] and any AST) or moderate (total bilirubin 1.5 to 3 x ULN and any AST) liver dysfunction. The recommended dosage of mobocertinib has not been established for patients with severe liver dysfunction (total bilirubin greater than 3 times ULN and any AST); caution is recommended in these patients.

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.

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.

Mobocertinib can cause interstitial lung disease (ILD)/pneumonitis, which can be fatal. Care should be exercised when using this drug in patients with preexisting pulmonary impairment. Mobocertinib should be immediately withheld in patients with suspected ILD/pneumonitis and permanently discontinued if ILD/pneumonitis is confirmed. Patients should be monitored for new/worsening pulmonary symptoms indicative of ILD/pneumonitis.

No dosage adjustment of mobocertinib is recommended for patients with mild to moderate renal dysfunction (estimated glomerular filtration rate [eGFR] 30 to 89 mL/min/1.73 m2 by Modification of Diet in Renal Disease equation). The recommended dosage of mobocertinib has not been established for patients with severe renal dysfunction (eGFR less than 30 mL/min/1.73 m2); caution is recommended in these patients.

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.

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.

When administering estrogen and/or progestogen therapy in patients with thyroid disorders, clinicians should be aware that these hormones may affect thyroid function tests. 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. Patients on thyroid replacement therapy may require higher doses of thyroid hormone and appropriate monitoring.