Interactions between Premphase 14/14 and Tipranavir
1 drug interaction and 43 additional warnings found for the following 2 drugs:
- Premphase 14/14 (conjugated estrogens/medroxyprogesterone)
- tipranavir
Drug interactions
Moderate drug interactions
Moderate:
conjugated estrogens tipranavir
Applies to: Premphase 14 / 14 (conjugated estrogens / medroxyprogesterone) and tipranavir
Monitor
Use of tipranavir in combination with estrogens may be associated with an increased risk of skin rash. The mechanism has not been described. Mild to moderate rashes including urticarial rash, maculopapular rash, and possible photosensitivity have been reported in 14% of females and 8% to 10% of males receiving tipranavir in combination with low-dose ritonavir in phase 2 and 3 trials. However, in one drug interaction trial, 33% of healthy female volunteers administered a single dose of ethinyl estradiol followed by tipranavir/ritonavir developed a rash. Rash accompanied by joint pain or stiffness, throat tightness, or generalized pruritus has also been reported in both men and women.
Management
Women who use estrogens should be advised of a potentially increased risk of skin rash during concomitant treatment with tipranavir. If a rash occurs, it is usually mild to moderate. Nevertheless, patients should be instructed to contact their physician promptly, as a temporary discontinuation of tipranavir or the estrogen may be necessary.
References (1)
- (2005) "Product Information. Aptivus (tipranavir)." Boehringer-Ingelheim
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
tipranavir Food/Lifestyle
Applies to: tipranavir
Adjust dosing interval
Food does not appear to substantially alter the pharmacokinetics of tipranavir. When tipranavir capsules or oral solution was coadministered with ritonavir capsules at steady-state, no clinically significant changes in tipranavir peak plasma concentration (Cmax) and systemic exposure (AUC) were observed under fed conditions (500 to 682 kcal, 23% to 25% calories from fat) relative to fasted conditions. The effect of food on tipranavir exposure during coadministration with ritonavir tablets has not been evaluated. High-fat foods may enhance the gastrointestinal absorption of tipranavir. In a multiple-dose study, administration of tipranavir capsules with a high-fat meal (868 kcal, 53% from fat, 31% from carbohydrates) increased the oral bioavailability of tipranavir by 31% compared to administration with toast and skimmed milk, but did not significantly affect tipranavir Cmax. Thus, tipranavir may be safely taken with standard or high-fat meals.
Management
Tipranavir coadministered with low-dose ritonavir should be taken with food to improve the gastrointestinal tolerability of ritonavir. According to the product labeling, tipranavir coadministered with ritonavir capsules or solution can be taken with or without meals, whereas tipranavir coadministered with ritonavir tablets must be taken with meals.
References (4)
- (2005) "Product Information. Aptivus (tipranavir)." Boehringer-Ingelheim
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Cerner Multum, Inc. "Australian Product Information."
Minor food/lifestyle interactions
Minor:
conjugated estrogens Food/Lifestyle
Applies to: Premphase 14 / 14 (conjugated estrogens / medroxyprogesterone)
Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.
References (2)
- Weber A, Jager R, Borner A, et al. (1996) "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception, 53, p. 41-7
- Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T (1995) "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet, 20, p. 219-24
Disease interactions
41 potential interactions Applies to: 28 conditions, including High Blood Pressure, High Cholesterol, Depression, Migraine, and Weight Loss.
Abnormal Glucose Tolerance
Moderate:
tipranavir
Tipranavir has a moderate potential interaction with Abnormal Glucose Tolerance.
New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, hyperglycemia, and some cases of diabetic ketoacidosis have been reported during postmarketing surveillance in HIV-infected patients treated with protease inhibitors. Some patients required either initiation or dosage adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, hyperglycemia persisted despite discontinuation of protease inhibitor therapy. A causal relationship has not been established between protease inhibitor therapy and these events. Monitoring patients for hyperglycemia, new onset diabetes mellitus, or exacerbation of diabetes mellitus should be considered during protease inhibitor therapy.
Abnormal Uterine Bleeding
Major:
Premphase 14/14
The medroxyPROGESTERone in Premphase 14/14 has a major potential interaction with Abnormal Uterine Bleeding.
The use of medroxyprogesterone in women with undiagnosed vaginal bleeding is contraindicated. Most women using medroxyprogesterone experience disruption of menstrual bleeding patterns. Altered menstrual bleeding patterns include amenorrhea, irregular or unpredictable bleeding or spotting, prolonged spotting or bleeding, and heavy bleeding. Rule out the possibility of organic pathology if abnormal bleeding persists or is severe, and institute appropriate treatment.
Major:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
Major:
Premphase 14/14
The medroxyPROGESTERone in Premphase 14/14 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.
Angioedema
Moderate:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
Asthma
Moderate:
Premphase 14/14
The conjugated estrogens and medroxyPROGESTERone in Premphase 14/14 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.
Breast Cancer
Major:
Premphase 14/14
The medroxyPROGESTERone in Premphase 14/14 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.
Major:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
Cerebral Vascular Disorder
Major:
Premphase 14/14
The medroxyPROGESTERone in Premphase 14/14 has a major potential interaction with Cerebral Vascular Disorder.
The use of progestogens, in general, is considered by manufacturers to be contraindicated in patients with active thrombophlebitis, cerebrovascular disease, or a current or past history of thromboembolic disorders. While the role of progestogens in the development of thromboembolic events associated with hormonal therapy is often unclear and thought to be secondary to that of estrogens, it may not be insignificant. Medroxyprogesterone, a common progestational agent, has been shown to produce a hypercoagulable state in high dosages. Whether or not this effect contributes to the development of thrombotic events is unknown. However, thrombophlebitis and pulmonary embolism have been reported with megestrol, an antineoplastic and progestational agent. In addition, an increased risk of nonfatal venous thrombosis has been associated with oral contraceptive combinations containing desogestrel or gestodene relative to those that contain other progestins (e.g., levonorgestrel, norethindrone), suggesting some degree of hemostatic effect by progestogens.
Major:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
Coagulation Defects and Disorders
Moderate:
tipranavir
Tipranavir has a moderate potential interaction with Coagulation Defects and Disorders.
There have been reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis, in patients with hemophilia type A and B treated with protease inhibitors; however, a causal relationship has not been established. In some patients, additional factor VIII was given. In more than half of the reported cases, protease inhibitor therapy was continued or reintroduced. Patients with hemophilia or other coagulation defects should be monitored closely for bleeding during protease inhibitor therapy.
Depression
Moderate:
Premphase 14/14
The medroxyPROGESTERone in Premphase 14/14 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.
Diabetes Mellitus
Moderate:
Premphase 14/14
The conjugated estrogens and medroxyPROGESTERone in Premphase 14/14 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.
Moderate:
tipranavir
Tipranavir has a moderate potential interaction with Diabetes Mellitus.
New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, hyperglycemia, and some cases of diabetic ketoacidosis have been reported during postmarketing surveillance in HIV-infected patients treated with protease inhibitors. Some patients required either initiation or dosage adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, hyperglycemia persisted despite discontinuation of protease inhibitor therapy. A causal relationship has not been established between protease inhibitor therapy and these events. Monitoring patients for hyperglycemia, new onset diabetes mellitus, or exacerbation of diabetes mellitus should be considered during protease inhibitor therapy.
Fluid Retention
Moderate:
Premphase 14/14
The conjugated estrogens and medroxyPROGESTERone in Premphase 14/14 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.
Gallbladder Disease
Moderate:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
Heart Failure
Moderate:
Premphase 14/14
The conjugated estrogens and medroxyPROGESTERone in Premphase 14/14 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.
Hepatic Tumor
Major:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
High Blood Pressure
Major:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
Moderate:
Premphase 14/14
The medroxyPROGESTERone in Premphase 14/14 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.
High Cholesterol
Moderate:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
Moderate:
Premphase 14/14
The medroxyPROGESTERone in Premphase 14/14 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.
Moderate:
tipranavir
Tipranavir has a moderate potential interaction with High Cholesterol.
Treatment with ritonavir alone or in combination with other protease inhibitors (e.g., lopinavir, saquinavir, tipranavir, fosamprenavir) has resulted in substantial increases in the concentration of total cholesterol and triglycerides. These effects have also been reported with other protease inhibitors but may be the most dramatic with ritonavir. The clinical significance of these elevations is unclear. Marked elevation in triglyceride levels is a risk factor for development of pancreatitis. Triglyceride and cholesterol testing is recommended before starting ritonavir (with or without other protease inhibitors) and periodically during therapy. Lipid disorders should be managed as clinically appropriate.
History, Thrombotic/Thromboembolic Disorder
Major:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
Major:
Premphase 14/14
The medroxyPROGESTERone in Premphase 14/14 has a major potential interaction with History, Thrombotic/Thromboembolic Disorder.
The use of progestogens, in general, is considered by manufacturers to be contraindicated in patients with active thrombophlebitis, cerebrovascular disease, or a current or past history of thromboembolic disorders. While the role of progestogens in the development of thromboembolic events associated with hormonal therapy is often unclear and thought to be secondary to that of estrogens, it may not be insignificant. Medroxyprogesterone, a common progestational agent, has been shown to produce a hypercoagulable state in high dosages. Whether or not this effect contributes to the development of thrombotic events is unknown. However, thrombophlebitis and pulmonary embolism have been reported with megestrol, an antineoplastic and progestational agent. In addition, an increased risk of nonfatal venous thrombosis has been associated with oral contraceptive combinations containing desogestrel or gestodene relative to those that contain other progestins (e.g., levonorgestrel, norethindrone), suggesting some degree of hemostatic effect by progestogens.
Hypoparathyroidism
Moderate:
Premphase 14/14
The conjugated estrogens and medroxyPROGESTERone in Premphase 14/14 both have 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.
Ischemic Heart Disease
Major:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
Liver Disease
Major:
Premphase 14/14
The medroxyPROGESTERone in Premphase 14/14 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.
Major:
tipranavir
Tipranavir has a major potential interaction with Liver Disease.
The use of tipranavir is contraindicated in patients with moderate to severe (Child-Pugh Class B and C) hepatic impairment. Tipranavir is primarily metabolized by the liver and may accumulate substantially in such patients. In addition, tipranavir coadministered with ritonavir 200 mg has been associated with reports of clinical hepatitis and hepatic decompensation, including some fatalities. Most cases occurred in patients with advanced HIV disease taking multiple concomitant medications, thus a causal relationship to tipranavir/ritonavir could not be established. Nevertheless, extra caution is recommended if tipranavir and ritonavir are prescribed to patients with chronic hepatitis B or C coinfection or elevations in liver transaminases, as these patients have an approximately 2.5- fold increased risk of developing further transaminase elevations or hepatic decompensation. In clinical studies, Grade 3 and 4 increases in hepatic transaminases were observed in 6% of healthy volunteers and HIV subjects. Liver function tests should be performed prior to initiating therapy and frequently throughout the duration of treatment. Patients should be advised to promptly discontinue tipranavir/ritonavir therapy and seek medical attention if they experience signs or symptoms suggestive of hepatotoxicity such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice.
Moderate:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
Migraine
Major:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
Moderate:
Premphase 14/14
The conjugated estrogens and medroxyPROGESTERone in Premphase 14/14 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.
Neoplasia, Estrogen Dependent
Major:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
Osteoporosis
Major:
Premphase 14/14
The medroxyPROGESTERone in Premphase 14/14 has a major potential interaction with Osteoporosis.
The use of intramuscular medroxyprogesterone for contraception has been shown to induce bone loss, particularly during the early years of therapy. With continued use, the decline in bone density subsequently approaches the normal rate of age-related loss. Therapy with parenteral medroxyprogesterone should be administered cautiously in patients with osteoporosis or chronic use of drugs that can reduce bone mass, such as anticonvulsants or corticosteroids.
Pancreatitis
Moderate:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
Renal Dysfunction
Moderate:
Premphase 14/14
The conjugated estrogens and medroxyPROGESTERone in Premphase 14/14 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.
Seizures
Moderate:
Premphase 14/14
The conjugated estrogens and medroxyPROGESTERone in Premphase 14/14 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.
Thrombotic/Thromboembolic Disorder
Major:
Premphase 14/14
The medroxyPROGESTERone in Premphase 14/14 has a major potential interaction with Thrombotic/Thromboembolic Disorder.
The use of progestogens, in general, is considered by manufacturers to be contraindicated in patients with active thrombophlebitis, cerebrovascular disease, or a current or past history of thromboembolic disorders. While the role of progestogens in the development of thromboembolic events associated with hormonal therapy is often unclear and thought to be secondary to that of estrogens, it may not be insignificant. Medroxyprogesterone, a common progestational agent, has been shown to produce a hypercoagulable state in high dosages. Whether or not this effect contributes to the development of thrombotic events is unknown. However, thrombophlebitis and pulmonary embolism have been reported with megestrol, an antineoplastic and progestational agent. In addition, an increased risk of nonfatal venous thrombosis has been associated with oral contraceptive combinations containing desogestrel or gestodene relative to those that contain other progestins (e.g., levonorgestrel, norethindrone), suggesting some degree of hemostatic effect by progestogens.
Major:
Premphase 14/14
The conjugated estrogens in Premphase 14/14 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.
Thyroid Disease
Moderate:
Premphase 14/14
The conjugated estrogens and medroxyPROGESTERone in Premphase 14/14 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.
Weight Loss
Minor:
Premphase 14/14
The medroxyPROGESTERone in Premphase 14/14 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.
More resources
Premphase 14/14
A total of 449 drugs are known to interact with Premphase 14/14.
- Premphase 14/14 is in the drug class sex hormone combinations.
- Premphase 14/14 is used to treat the following conditions:
tipranavir
A total of 426 drugs are known to interact with tipranavir.
- Tipranavir is in the drug class protease inhibitors.
- Tipranavir is used to treat HIV-1 Infection.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
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