Drug Interactions between lapatinib and Progynova

Take lapatinib on an empty stomach 1 hour before or 1 hour after a meal unless otherwise directed by your doctor. This will make it easier for your body to absorb the medication. The lapatinib dose is administered once daily and should not be divided. The usual dose of lapatinib is equal to 5 tablets. You may swallow each tablet one at a time, but take the entire lapatinib dose at the same time each day. If you are receiving therapy with lapatinib you should be advised to avoid grapefruits and grapefruit juice. Grapefruit can raise the levels of lapatinib in your body and lead to dangerous side effects.

Information for this minor interaction is available on the professional version.

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.

QT prolongation was observed in patients treated with certain EGFR inhibitors. These agents should be administered with caution in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Serum electrolytes should be corrected prior to initiating therapy with these agents. Periodic monitoring of ECGs and electrolytes is recommended in these patients. Permanently discontinue the use of these agents in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia.

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.

QT prolongation was observed in patients treated with certain EGFR inhibitors. These agents should be administered with caution in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Serum electrolytes should be corrected prior to initiating therapy with these agents. Periodic monitoring of ECGs and electrolytes is recommended in these patients. Permanently discontinue the use of these agents in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia.

Cutaneous reactions, in some cases severe, have been reported with the use of EGFR inhibitors. Monitor patients who develop dermatologic or soft tissue toxicities while receiving these agents for the development of inflammatory or infectious sequelae. It is recommended to withhold treatment, and appropriate measures should be instituted as appropriate or discontinue the use of these agents for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Advise patients to wear sunscreen and hats and limit sun exposure while receiving therapy with these agents as exposure to sunlight can exacerbate dermatologic toxicities.

The use of certain EGFR inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, permanently discontinue these agents and institute appropriate measures.

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.

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.

Lapatinib undergoes extensive metabolism in the liver. Hepatotoxicity has been associated with the use of lapatinib and it may be severe and fatal. The hepatotoxicity may occur days to several months after initiation of treatment. Therapy with lapatinib should be administered cautiously in patients with severe hepatic impairment and a dose reduction should be considered for patients with severe pre-existing hepatic impairment. Clinical monitoring of hepatic function (transaminases, bilirubin, and alkaline phosphatase) is recommended before initiation of treatment, every 4 to 6 weeks during treatment, and as clinically indicated. In patients who develop severe hepatotoxicity while on therapy, lapatinib should be discontinued and patients should not be retreated.

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.

Pulmonary toxicity, sometimes fatal has been reported with agents that block HER2 activity. Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest may be at increased risk of pulmonary toxicity and appear to have more severe toxicity. Patients should be monitored for pulmonary symptoms. Permanently discontinue treatment with these agents in patients diagnosed with interstitial lung disease or pneumonitis and institute appropriate care.

The use of certain EGFR inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, permanently discontinue these agents and institute appropriate measures.

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.

Cardiomyopathy was observed in clinical trials of certain EGFR inhibitors. Assess Left Ventricular Ejection Fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan before initiation of these agents and then at 3 month intervals while on treatment. Caution is recommended when prescribing these agents to patients with conditions that could impair left ventricular function and it is recommended to withhold treatment with these agents if ejection fraction drops below the established lower limit of normal. For symptomatic congestive heart failure or persistent, asymptomatic LV dysfunction that does not resolve within 4 weeks, permanently discontinue these agents.

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.

Decreases in left ventricular ejection fraction (LVEF) have been reported with agents that block HER2 activity. Patients who have received prior anthracyclines, those who received anthracycline after stopping therapy with agents that block HER2 activity, or patients who received prior radiotherapy to the chest area may be at higher risk of decreased LVEF. Therapy with these agents should be administered cautiously in patients with a previous history of heart conditions. Evaluate cardiac function before, during, and upon completion of treatment. Withhold or discontinue therapy with agents that block HER2 activity as appropriate, and for a confirmed clinically significant decrease in left ventricular function, or if the LVEF has not improved or has declined further. It is recommended to monitor overall cardiac function and LVEF by echocardiogram or MUGA scan as appropriate.

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.

Decreases in left ventricular ejection fraction (LVEF) have been reported with agents that block HER2 activity. Patients who have received prior anthracyclines, those who received anthracycline after stopping therapy with agents that block HER2 activity, or patients who received prior radiotherapy to the chest area may be at higher risk of decreased LVEF. Therapy with these agents should be administered cautiously in patients with a previous history of heart conditions. Evaluate cardiac function before, during, and upon completion of treatment. Withhold or discontinue therapy with agents that block HER2 activity as appropriate, and for a confirmed clinically significant decrease in left ventricular function, or if the LVEF has not improved or has declined further. It is recommended to monitor overall cardiac function and LVEF by echocardiogram or MUGA scan as appropriate.

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.

Decreases in left ventricular ejection fraction (LVEF) have been reported with agents that block HER2 activity. Patients who have received prior anthracyclines, those who received anthracycline after stopping therapy with agents that block HER2 activity, or patients who received prior radiotherapy to the chest area may be at higher risk of decreased LVEF. Therapy with these agents should be administered cautiously in patients with a previous history of heart conditions. Evaluate cardiac function before, during, and upon completion of treatment. Withhold or discontinue therapy with agents that block HER2 activity as appropriate, and for a confirmed clinically significant decrease in left ventricular function, or if the LVEF has not improved or has declined further. It is recommended to monitor overall cardiac function and LVEF by echocardiogram or MUGA scan as appropriate.

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.

Decreases in left ventricular ejection fraction (LVEF) have been reported with agents that block HER2 activity. Patients who have received prior anthracyclines, those who received anthracycline after stopping therapy with agents that block HER2 activity, or patients who received prior radiotherapy to the chest area may be at higher risk of decreased LVEF. Therapy with these agents should be administered cautiously in patients with a previous history of heart conditions. Evaluate cardiac function before, during, and upon completion of treatment. Withhold or discontinue therapy with agents that block HER2 activity as appropriate, and for a confirmed clinically significant decrease in left ventricular function, or if the LVEF has not improved or has declined further. It is recommended to monitor overall cardiac function and LVEF by echocardiogram or MUGA scan as appropriate.

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.

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.

Decreases in left ventricular ejection fraction (LVEF) have been reported with agents that block HER2 activity. Patients who have received prior anthracyclines, those who received anthracycline after stopping therapy with agents that block HER2 activity, or patients who received prior radiotherapy to the chest area may be at higher risk of decreased LVEF. Therapy with these agents should be administered cautiously in patients with a previous history of heart conditions. Evaluate cardiac function before, during, and upon completion of treatment. Withhold or discontinue therapy with agents that block HER2 activity as appropriate, and for a confirmed clinically significant decrease in left ventricular function, or if the LVEF has not improved or has declined further. It is recommended to monitor overall cardiac function and LVEF by echocardiogram or MUGA scan as appropriate.

Decreases in left ventricular ejection fraction (LVEF) have been reported with agents that block HER2 activity. Patients who have received prior anthracyclines, those who received anthracycline after stopping therapy with agents that block HER2 activity, or patients who received prior radiotherapy to the chest area may be at higher risk of decreased LVEF. Therapy with these agents should be administered cautiously in patients with a previous history of heart conditions. Evaluate cardiac function before, during, and upon completion of treatment. Withhold or discontinue therapy with agents that block HER2 activity as appropriate, and for a confirmed clinically significant decrease in left ventricular function, or if the LVEF has not improved or has declined further. It is recommended to monitor overall cardiac function and LVEF by echocardiogram or MUGA scan as appropriate.

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.

Lapatinib pharmacokinetics have not been specifically studied in patients with renal impairment or in patients undergoing hemodialysis. Close monitoring is recommended.

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.

Thrombocytopenia has been reported with the use of agents that block HER2 activity. Monitor platelet counts prior to initiation of therapy and prior to each dose. If appropriate modify the dose according to clinical guidelines. Patients with decreased platelet count and patients on anti-coagulant treatment should be closely monitored during treatment with these agents.

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.