Interactions between Climodien and Ethambutol
1 drug interaction and 28 additional warnings found for the following 2 drugs:
- Climodien (estradiol)
- ethambutol
Drug interactions
Moderate drug interactions
Moderate:
ethambutol estradiol
Applies to: ethambutol and Climodien (estradiol)
Monitor
The effectiveness of estrogen-containing medications may be impaired by concomitant treatment with antimicrobial agents. During metabolism, the estrogen component is conjugated, resulting in sulfation or glucuronidation of the original estrogenic steroid. The conjugates reach the intestine via the bile duct, where hydrolytic enzymes of intestinal bacteria break them down into free, active estrogenic hormone. The active hormone is then available for enterohepatic cycling, which helps maintain estrogen levels. Notably, the progestin component of a combined hormonal product does not undergo this process. It has been suggested that broad-spectrum antibiotics may reduce the effectiveness of estrogen-containing contraceptives because they may reduce intestinal bacteria and thus interfere with enterohepatic cycling of estrogen. Most research regarding this possible interaction has been conducted with oral contraceptives, but all estrogens appear to undergo enterohepatic recirculation, so theoretically this interaction is a possibility with estrogen-containing medications that are being used for alternative purposes. However, the risk appears to be small, and supportive data are primarily limited to anecdotal evidence from case reports and findings from uncontrolled or poorly controlled studies. Further, the Centers for Disease Control and Prevention do not consider most broad-spectrum antibiotics to significantly interfere with the effectiveness of combined hormonal contraception. Most antimicrobials, with the exception of enzyme-inducing medications such as the rifamycins and possibly griseofulvin, have not been shown to significantly increase the clearance of oral contraceptive estrogens. It is possible that a small number of women may be more sensitive to the effects of antimicrobials on estrogen disposition in vivo, but risk factors or genetic predispositions have yet to be identified.
Management
If concomitant use of an estrogen-containing oral contraceptive with antibiotic therapy is necessary, some manufacturers advise using a back-up method of birth control for varying amounts of time. If estrogen is used for a purpose other than contraception, there is a theoretical possibility of lower systemic estrogen levels during antibiotic treatment. These patients should be counseled to report any changes in the efficacy of the hormonal product to their healthcare provider. Additionally, some illnesses and certain antibiotics may cause nausea, vomiting, and/or diarrhea. If vomiting occurs within a few hours of taking an oral contraceptive pill, the product labeling should be consulted for instructions on what to do in the event of a missed pill. Some authorities recommend a back-up method of birth control if an individual has persistent vomiting or diarrhea. Individual product labeling for the estrogen-containing product, particularly oral contraceptives, and antibiotic being used should be consulted for more specific guidance.
References (45)
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Food/lifestyle interactions
Minor food/lifestyle interactions
Minor:
estradiol Food/Lifestyle
Applies to: Climodien (estradiol)
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
27 potential interactions Applies to: 24 conditions, including High Blood Pressure, High Cholesterol, Migraine, Heart Failure, and Asthma.
Abnormal Uterine Bleeding
Major:
Climodien
The estradiol in Climodien 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.
Angioedema
Moderate:
Climodien
The estradiol in Climodien 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:
Climodien
The estradiol in Climodien has a moderate potential interaction with Asthma.
Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.
Breast Cancer
Major:
Climodien
The estradiol in Climodien 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:
Climodien
The estradiol in Climodien 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.
Diabetes Mellitus
Moderate:
Climodien
The estradiol in Climodien has a moderate potential interaction with Diabetes Mellitus.
Impaired glucose tolerance has been observed in some patients administered oral contraceptives and appears to be related primarily to the estrogen dose. However, progestogens can increase insulin secretion and produce insulin resistance to varying degrees, depending on the agent. Caution and close monitoring are recommended in patients with diabetes mellitus during therapy with estrogens and/or progestogens, and adjustments made accordingly in their antidiabetic regimen.
Fluid Retention
Moderate:
Climodien
The estradiol in Climodien has a moderate potential interaction with Fluid Retention.
Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.
Gallbladder Disease
Moderate:
Climodien
The estradiol in Climodien 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.
Gout
Moderate:
ethambutol
Ethambutol has a moderate potential interaction with Gout.
Ethambutol may commonly cause hyperuricemia, which has been reported in up to two-thirds of treated patients. Occasionally, it has led to joint arthralgias and gouty arthritis after 1 to 2 months of therapy. Serum uric acid levels should be monitored in patients with preexisting hyperuricemia or gout during ethambutol therapy, and appropriate measures (e.g., administration of uricosuric agents) taken to prevent the development or exacerbation of gout.
Heart Failure
Moderate:
Climodien
The estradiol in Climodien has a moderate potential interaction with Heart Failure.
Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.
High Blood Pressure
Major:
Climodien
The estradiol in Climodien 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.
High Cholesterol
Moderate:
Climodien
The estradiol in Climodien 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.
History, Thrombotic/Thromboembolic Disorder
Major:
Climodien
The estradiol in Climodien 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.
Hypoparathyroidism
Moderate:
Climodien
The estradiol in Climodien 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.
Ischemic Heart Disease
Major:
Climodien
The estradiol in Climodien 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
Moderate:
Climodien
The estradiol in Climodien 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.
Moderate:
ethambutol
Ethambutol has a moderate potential interaction with Liver Disease.
Liver toxicities including fatalities have been reported when using ethambutol. Caution is advised, especially if using in patients with hepatic impairment. Baseline and periodic assessment of hepatic function should be performed.
Migraine
Major:
Climodien
The estradiol in Climodien 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:
Climodien
The estradiol in Climodien has a moderate potential interaction with Migraine.
Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.
Neoplasia, Estrogen Dependent
Major:
Climodien
The estradiol in Climodien 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.
Pancreatitis
Moderate:
Climodien
The estradiol in Climodien 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:
Climodien
The estradiol in Climodien has a moderate potential interaction with Renal Dysfunction.
Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.
Moderate:
ethambutol
Ethambutol has a moderate potential interaction with Renal Dysfunction.
Ethambutol is primarily eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from ethambutol, including optic neuritis, due to decreased drug clearance. Therapy with ethambutol should be administered cautiously in patients with renal impairment. Dosage adjustments are recommended in moderate renal impairment but should be based on serum levels of ethambutol.
Seizures
Moderate:
Climodien
The estradiol in Climodien has a moderate potential interaction with Seizures.
Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.
Thrombotic/Thromboembolic Disorder
Major:
Climodien
The estradiol in Climodien 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:
Climodien
The estradiol in Climodien has a moderate potential interaction with Thyroid Disease.
When administering estrogen and/or progestogen therapy in patients with thyroid disorders, clinicians should be aware that these hormones may affect thyroid function tests. Patients on thyroid replacement therapy may require higher doses of thyroid hormone and appropriate monitoring. Changes have mostly been reported with the use of combination oral contraceptives. Specifically, thyroid-binding globulin (TBG) may be increased, resulting in elevated circulating total thyroid hormone, as measured by PBI (protein-bound iodine), T4 by column or radioimmunoassay, or T3 by radioimmunoassay. Free T3 resin uptake may be decreased. On the contrary, a decrease in TBG and, consequently, thyroxine concentration, has been reported by the manufacturers of the progestin-only (norethindrone) oral contraceptives.
Visual Defect/Disturbance
Major:
ethambutol
Ethambutol has a major potential interaction with Visual Defect/Disturbance.
Ethambutol is contraindicated in patients with known optic neuritis unless clinical judgement determines that it may be used. Ethambutol can produce decreases in visual acuity which appear to be due to optic neuritis. This may be related to dose and duration of treatment, and is generally reversible when administration of the drug is discontinued promptly. However, irreversible blindness has been reported. Ethambutol should not be used in patients who are unable to identify and report visual side effects or changes in vision such as young children or unconscious patients. It should be administered cautiously and only after careful consideration of risks and benefits in patients with preexisting visual defects such as cataracts, diabetic retinopathy, or recurrent inflammatory conditions of the eye. Ophthalmologic testing of visual acuity, visual field, and color discrimination is required before and during treatment. However, visual changes may be difficult to evaluate in some cases, since they may be related to the underlying disease rather than the drug.
More resources
Climodien
A total of 446 drugs are known to interact with Climodien.
- Climodien is in the drug class estrogens.
- Climodien is used to treat Postmenopausal Symptoms.
ethambutol
A total of 172 drugs are known to interact with ethambutol.
- Ethambutol is in the drug class miscellaneous antituberculosis agents.
- Ethambutol is used to treat the following conditions:
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
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.