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Interactions between Isoniazid and Thais

1 drug interaction and 34 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

isoniazid estradiol

Applies to: isoniazid and Thais (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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  2. Back DJ, Breckenridge AM, MacIver M, et al. (1982) "The effects of ampicillin on oral contraceptive steroids in women." Br J Clin Pharmacol, 14, p. 43-8
  3. Neely JL, Abate M, Swinker M, D'Angio R (1991) "The effect of doxycycline on serum levels of ethinyl estradiol, norethindrone, and endogenous progesterone." Obstet Gynecol, 77, p. 416-20
  4. Joshi JV, Joshi UM, Sankholi GM, et al. (1980) "A study of interaction of low-dose combination oral contraceptive with ampicillin and metronidazole." Contraception, 22, p. 643-52
  5. Baciewicz AM (1985) "Oral contraceptive drug interactions." Ther Drug Monit, 7, p. 26-35
  6. Bint AJ, Burtt I (1980) "Adverse antibiotic drug interactions." Drugs, 20, p. 57-68
  7. Dossetor J (1975) "Drug interactions with oral contraceptives." Br Med J, 4, p. 467-8
  8. DeSano EA, Hurley SC (1982) "Possible interactions of antihistamines and antibiotics with oral contraceptive effectiveness." Fertil Steril, 37, p. 853-4
  9. Szoka PR, Edgren RA (1988) "Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database." Fertil Steril, 49(5 Suppl), s31-8
  10. Barnett ML (1985) "Inhibition of oral contraceptive effectiveness by concurrent antibiotic administration." J Periodontol, 56, p. 18-20
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  12. London BM, Lookingbill DP (1994) "Frequency of pregnancy in acne patients taking oral antibiotics and oral contraceptives." Arch Dermatol, 130, p. 392-3
  13. Bacon JF, Shenfield GM (1980) "Pregnancy attributable to interaction between tetracycline and oral contraceptives." Br Med J, 280, p. 293
  14. Fazio A (1991) "Oral contraceptive drug interactions: important considerations." South Med J, 84, p. 997-1002
  15. Back DJ, Orme ML (1990) "Pharmacokinetic drug interactions with oral contraceptives." Clin Pharmacokinet, 18, p. 472-84
  16. Back DJ, Tjia J, Martin C, Millar E, Mant T, Morrison P, Orme M (1991) "The lack of interaction between temafloxacin and combined oral contraceptive steroids." Contraception, 43, p. 317-23
  17. Orme ML, Back DJ (1986) "Interactions between oral contraceptive steroids and broad-spectrum antibiotics." Clin Exp Dermatol, 11, p. 327-31
  18. Wermeling DP, Chandler MH, Sides GD, Collins D, Muse KN (1995) "Dirithromycin increases ethinyl estradiol clearance without allowing ovulation." Obstet Gynecol, 86, p. 78-84
  19. Silber TJ (1983) "Apparent oral contraceptive failure associated with antibiotic administration." J Adolesc Health Care, 4, p. 287-9
  20. Bollen M (1995) "Use of antibiotics when taking the oral contraceptive pill." Aust Fam Physician, 24, p. 928-9
  21. Kleier DJ, Tucker JE (1987) "Oral contraceptive failure secondary to dentally prescribed drugs: fact or fiction?" J Colo Dent Assoc, 66, p. 5-6
  22. Back DJ, Breckenridge AM, Crawford FE, MacIver M, Orne ML, Rowe PH (1981) "Interindividual variation and drug interactions with hormonal steroid contraceptives." Drugs, 21, p. 46-61
  23. Helms SE, Bredle DL, Zajic J, Jarjoura D, Brodell RT, Krishnarao I (1997) "Oral contraceptive failure rates and oral antibiotics." J Am Acad Dermatol, 36, p. 705-10
  24. Weisberg E (1999) "Interactions between oral contraceptives and antifungals antibacterials - Is contraceptive failure the result?." Clin Pharmacokinet, 36, p. 309-13
  25. Burroughs KE, Chambliss ML (2000) "Antibiotics and oral contraceptive failure." Arch Fam, 9, p. 81-2
  26. Weaver K, Glasier A (1999) "Interaction between broad-spectrum antibiotics and the combined oral contraceptive pill: a literature review." Contraception, 59, p. 71-8
  27. King VJ (1997) "OC failure rates and oral antibiotics." J Fam Pract, 45, p. 104-5
  28. Zachariassen RD (1994) "Loss of oral contraceptive efficacy by concurrent antibiotic administration." Women Health, 22, p. 17-26
  29. Dickinson BD, Altman RD, Nielsen NH, Sterling ML (2001) "Drug interactions between oral contraceptives and antibiotics." Obstet Gynecol, 98(5 Pt 1), p. 853-60
  30. Archer JS, Archer DF (2002) "Oral contraceptive efficacy and antibiotic interaction: A myth debunked." J Am Acad Dermatol, 46, p. 917-23
  31. Orme M, Back DJ (1991) "Oral contraceptive steroids--pharmacological issues of interest to the prescribing physician." Adv Contracept, 7, p. 325-31
  32. DeRossi SS, Hersh EV (2002) "Antibiotics and oral contraceptives." Dent Clin North Am, 46, p. 653-64
  33. (2005) "FFPRHC Guidance (April 2005). Drug interactions with hormonal contraception." J Fam Plann Reprod Health Care, 31, p. 139-51
  34. Bauer KL, Wolf D, Patel M, Vinson DC (2005) "Clinical inquiries. Do antibiotics interfere with the efficacy of oral contraceptives?" J Fam Pract, 54, p. 1079-80
  35. Back DJ, Grimmer SF, Orme ML, Proudlove D, Mann RD, Breckenridge AM (1988) "Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics." Br J Clin Pharmacol, 25, p. 527-32
  36. (2018) "Product Information. Arikayce (amikacin liposome)." Insmed Incorporated
  37. (2021) "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma
  38. (2022) "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma International Pty Ltd, v 2.0
  39. Curtis KM, Tepper NK, Jatlaoui TC, et al. (2023) U.S. medical eligibility criteria (US MEC) for contraceptive use. https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/index.html
  40. Faculty of Sexual & Reproductive Healthcare (2023) FSRH CEU response to study: analysis of reports of unintended pregnancies associated with the combined use of non-enzyme inducing antibiotics and hormonal contraceptives - february 2021 https://www.fsrh.org/standards-and-guidance/documents/fsrh-ceu-respo
  41. Faculty of Sexual & Reproductive Healthcare (2023) FSRH CEU guidance: drug interactions with hormonal contraception (may 2022) https://www.fsrh.org/standards-and-guidance/documents/ceu-clinical-guidance-drug-interactions-with-hormonal/
  42. Simmons KB, Haddad LB, Nanda K, Curtis KM (2018) "Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systemic review." Am J Obstet Gynecol, 218, 88-97.e14
  43. Zhanel GG, Siemens S, Slayter K, Mandell L (1999) "Antibiotic and oral contraceptive drug interactions: is there a need for concern?" Can J Infect Dis, 10, p. 429-33
  44. Black A, Francoeur D, Rowe T, et al. (2023) SOGC clinical practice guidelines canadian contraception consensus https://www.jogc.com/article/S1701-2163(16)30260-2/pdf
  45. Allen K (2012) "Contraception - common issues and practical suggestions." Aust Fam Physician, 41, p. 770-2

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

isoniazid Food/Lifestyle

Applies to: isoniazid
Generally avoid

Concurrent use of isoniazid (INH) in patients who ingest alcohol daily may result in an increased incidence of both hepatotoxicity and peripheral neuropathy. The increase in hepatotoxicity may be due to an additive risk as both alcohol and INH are individually associated with this adverse reaction. INH-associated hepatotoxicity is believed to be due to an accumulation of toxic metabolites and may also be partly immune mediated, though the exact mechanisms are not universally agreed upon. INH is metabolized by N-acetyltransferase and CYP450 2E1. The rate of acetylation is genetically determined and generally classified as slow or rapid. Slow acetylators have been identified by some studies as having a higher risk of hepatotoxicity; therefore, this interaction may be more significant for patients who fall into this category. Other studies have postulated that alcohol-mediated CYP450 2E1 induction may play a role, as this isoenzyme is involved in INH metabolism and may be responsible for producing hepatotoxic metabolites. However, available literature is conflicting. The labeling for some INH products lists daily alcohol use or chronic alcoholism as a risk factor for hepatitis, but not all studies have found a significant association between alcohol use and INH-induced hepatotoxicity. Additionally, INH and alcohol are both associated with pyridoxine (B6) deficiency, which may increase the risk of peripheral neuropathy.

Generally avoid

Concomitant administration of isoniazid (INH) with foods containing tyramine and/or histamine may increase the risk of symptoms relating to tyramine- and/or histamine toxicity (e.g., headache, diaphoresis, flushing, palpitations, and hypotension). The proposed mechanism is INH-mediated inhibition of monoamine oxidase (MAO) and diamine oxidase (DAO), enzymes responsible for the metabolism of tyramine and histamine, respectively. Some authors have suggested that the reactions observed are mainly due to INH's effects on DAO instead of MAO or the amounts of histamine instead of tyramine present in the food. A Japanese case report recorded an example in 8 out of 25 patients on the tuberculosis ward who developed an accidental histamine poisoning after ingesting a fish paste (saury). Patients developed allergy-like symptoms, which started between 20 minutes and 2 hours after ingesting the food. A high-level of histamine (32 mg/100 g of fish) was confirmed in the saury paste and all 8 patients were both on INH and had reduced MAO concentrations. The 17 remaining patients were not on INH (n=5) or reported not eating the saury paste (n=12).

Adjust dosing interval

Administration with food significantly reduces oral isoniazid (INH) absorption, increasing the risk of therapeutic failure or resistance. The mechanism is unknown. Pharmacokinetic studies completed in both healthy volunteers (n=14) and tuberculosis patients (n=20 treatment-naive patients during days 1 to 3 of treatment) have resulted in almost doubling the time to reach INH's maximum concentration (tmax) and a reduction in isoniazid's maximum concentration (Cmax) of 42%-51% in patients who consumed high-fat or high-carbohydrate meals prior to INH treatment.

Management

The manufacturer of oral forms of isoniazid (INH) recommends administration on an empty stomach (i.e., 30 minutes before or 2 hours after meals). Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and INH concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with INH. Concomitant pyridoxine (B6) administration is also recommended to reduce the risk of peripheral neuropathy, with some authorities suggesting a dose of at least 10 mg/day. Patients should be advised to avoid foods containing tyramine (e.g., aged cheese, cured meats such as sausages and salami, fava beans, sauerkraut, soy sauce, beer, or red wine) or histamine (e.g., skipjack, tuna, mackerel, salmon) during treatment with isoniazid. Consultation of product labeling for combination products containing isoniazid and/or relevant guidelines may be helpful for more specific recommendations.

References (17)
  1. Smith CK, Durack DT (1978) "Isoniazid and reaction to cheese." Ann Intern Med, 88, p. 520-1
  2. Dimartini A (1995) "Isoniazid, tricyclics and the ''cheese reaction''." Int Clin Psychopharmacol, 10, p. 197-8
  3. Uragoda CG, Kottegoda SR (1977) "Adverse reactions to isoniazid on ingestion of fish with a high histamine content." Tubercle, 58, p. 83-9
  4. Self TH, Chrisman CR, Baciewicz AM, Bronze MS (1999) "Isoniazid drug and food interactions." Am J Med Sci, 317, p. 304-11
  5. (2021) "Product Information. Isoniazid/Rifapentine 300 mg/300 mg (Macleods) (isoniazid-rifapentine)." Imported (India), 2
  6. (2023) "Product Information. Isoniazid (isoniazid)." Chartwell RX, LLC.
  7. (2023) "Product Information. Isoniazid (Arrotex) (isoniazid)." Arrotex Pharmaceuticals Pty Ltd
  8. (2023) "Product Information. Isoniazid (isoniazid)." RPH Pharmaceuticals AB
  9. Saukkonen JJ, Cohn DL, Jasmer RM, et al. (2006) "An official ATS statement: hepatotoxicity of antituberculosis therapy." Am J Respir Crit Care Med, 174, p. 935-52
  10. Bouazzi OE, Hammi S, Bourkadi JE, et al. (2024) First line anti-tuberculosis induced hepatotoxicity: incidence and risk factors. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5326068/
  11. Wang P, Pradhan K, Zhong XB, Ma X (2016) "Isoniazid metabolism and hepatoxicity." Acta Pharm Sin B, 6, p. 384-92
  12. Saktiawati AM, Sturkenboom MG, Stienstra Y, et al. (2016) "Impact of food on the pharmacokinetics of first-line anti-TB drugs in treatment naive TB patients: a randomized cross-over trial." J Antimicrob Chemother, 71, p. 703-10
  13. Hahn JA, Ngabirano C, Fatch R, et al. (2023) "Safety and tolerability of isoniazid preventive therapy for tuberculosis for persons with HIV with and without alcohol use." AIDS, 37, p. 1535-43
  14. Huang YS, Chern HD, Su WJ, et al. (2003) "Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis." Hepatology, 37, p. 924-30
  15. Sousou JM, Griffith EM, Marsalisi C, Reddy P (2024) Pyridoxine deficiency and neurologic dysfunction: an unlikely association. https://www.cureus.com/articles/188310-pyridoxine-deficiency-and-neurologic-dysfunction-an-unlikely-association?score_article=true#!/
  16. Miki M, Ishikawa T, Okayama H (2005) "An outbreak of histamine poisoning after ingestion of the ground saury paste in eight patients taking isoniazid in tuberculous ward." Intern Med, 44, p. 1133-6
  17. (2021) "Product Information. Isotamine (isoniazid)." Bausch Health, Canada Inc.

Minor food/lifestyle interactions

Minor:

estradiol Food/Lifestyle

Applies to: Thais (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)
  1. Weber A, Jager R, Borner A, et al. (1996) "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception, 53, p. 41-7
  2. 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

32 potential interactions Applies to: 27 conditions, including High Blood Pressure, High Cholesterol, Migraine, Heart Failure, and Asthma.

Abnormal Uterine Bleeding

Major:

Thais

The estradiol in Thais 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.

Alcoholism

Major:

isoniazid

Isoniazid has a major potential interaction with Alcoholism.

The use of isoniazid is contraindicated in patients with a history of hepatic injury due to this drug and acute liver disease of any etiology. Caution is advised when using the drug in patients with chronic liver disease or a history of alcoholism. This drug has been associated with severe and sometimes fatal hepatitis, which may occur even after many months of therapy. In a US Public Health Service Surveillance Study of 13,838 persons taking isoniazid, there were 8 deaths among 174 cases of hepatitis. Epidemiologic studies indicate an increased incidence with increasing age, alcohol use, and female gender. As a precautionary measure, routine monitoring of serum transaminases (SGOT, SGPT) and bilirubin may be considered, although a transient and harmless increase in serum transaminase reportedly occurs in 10% to 20% of patients, usually in the first 3 months of therapy. Patients should be advised to promptly discontinue isoniazid therapy and seek medical attention if they experience signs or symptoms suggestive of liver damage such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. Reinstitution of the drug should occur only after symptoms and laboratory abnormalities resolve, with low and gradually increasing dosages.

Major:

isoniazid

Isoniazid has a major potential interaction with Alcoholism.

Isoniazid commonly causes dose-related peripheral neuropathy, which results from the depletion of pyridoxine in the presence of the drug. The neuropathy is usually preceded by paraesthesia's of the feet and hands. Therapy with isoniazid should be administered cautiously in patients with pre-existing peripheral neuropathy or risk factors for developing the condition, such as malnutrition, diabetes and alcoholism. Careful monitoring is recommended on these patients. Pyridoxine (vitamin B6) at a dosage of 10 to 50 mg/day may prevent or attenuate isoniazid-related peripheral neuropathy and is recommended for these patients.

Angioedema

Moderate:

Thais

The estradiol in Thais 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:

Thais

The estradiol in Thais 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:

Thais

The estradiol in Thais 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:

Thais

The estradiol in Thais 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

Major:

isoniazid

Isoniazid has a major potential interaction with Diabetes Mellitus.

Isoniazid commonly causes dose-related peripheral neuropathy, which results from the depletion of pyridoxine in the presence of the drug. The neuropathy is usually preceded by paraesthesia's of the feet and hands. Therapy with isoniazid should be administered cautiously in patients with pre-existing peripheral neuropathy or risk factors for developing the condition, such as malnutrition, diabetes and alcoholism. Careful monitoring is recommended on these patients. Pyridoxine (vitamin B6) at a dosage of 10 to 50 mg/day may prevent or attenuate isoniazid-related peripheral neuropathy and is recommended for these patients.

Moderate:

Thais

The estradiol in Thais 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:

Thais

The estradiol in Thais 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:

Thais

The estradiol in Thais 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:

Thais

The estradiol in Thais 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.

Hemodialysis

Moderate:

isoniazid

Isoniazid has a moderate potential interaction with Hemodialysis.

Isoniazid is substantially removed by hemodialysis and should be administered after dialysis.

High Blood Pressure

Major:

Thais

The estradiol in Thais 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:

Thais

The estradiol in Thais 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:

Thais

The estradiol in Thais 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.

HIV-1 Infection

Moderate:

isoniazid

Isoniazid has a moderate potential interaction with HIV-1 Infection.

Caution and close monitoring is advised when using isoniazid in patients with HIV seropositive patients. Patients with pulmonary tuberculosis and HIV infection may have problems with malabsorption. Screening of antimycobacterial drug levels, especially in patients with advanced HIV disease, may be necessary to prevent the emergence of multi-drug resistant tuberculosis.

Hypoparathyroidism

Moderate:

Thais

The estradiol in Thais 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:

Thais

The estradiol in Thais 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:

isoniazid

Isoniazid has a major potential interaction with Liver Disease.

The use of isoniazid is contraindicated in patients with a history of hepatic injury due to this drug and acute liver disease of any etiology. Caution is advised when using the drug in patients with chronic liver disease or a history of alcoholism. This drug has been associated with severe and sometimes fatal hepatitis, which may occur even after many months of therapy. In a US Public Health Service Surveillance Study of 13,838 persons taking isoniazid, there were 8 deaths among 174 cases of hepatitis. Epidemiologic studies indicate an increased incidence with increasing age, alcohol use, and female gender. As a precautionary measure, routine monitoring of serum transaminases (SGOT, SGPT) and bilirubin may be considered, although a transient and harmless increase in serum transaminase reportedly occurs in 10% to 20% of patients, usually in the first 3 months of therapy. Patients should be advised to promptly discontinue isoniazid therapy and seek medical attention if they experience signs or symptoms suggestive of liver damage such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. Reinstitution of the drug should occur only after symptoms and laboratory abnormalities resolve, with low and gradually increasing dosages.

Moderate:

Thais

The estradiol in Thais 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.

Malnourishment

Major:

isoniazid

Isoniazid has a major potential interaction with Malnourishment.

Isoniazid commonly causes dose-related peripheral neuropathy, which results from the depletion of pyridoxine in the presence of the drug. The neuropathy is usually preceded by paraesthesia's of the feet and hands. Therapy with isoniazid should be administered cautiously in patients with pre-existing peripheral neuropathy or risk factors for developing the condition, such as malnutrition, diabetes and alcoholism. Careful monitoring is recommended on these patients. Pyridoxine (vitamin B6) at a dosage of 10 to 50 mg/day may prevent or attenuate isoniazid-related peripheral neuropathy and is recommended for these patients.

Migraine

Major:

Thais

The estradiol in Thais 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:

Thais

The estradiol in Thais 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:

Thais

The estradiol in Thais 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:

Thais

The estradiol in Thais 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.

Peripheral Neuropathy

Major:

isoniazid

Isoniazid has a major potential interaction with Peripheral Neuropathy.

Isoniazid commonly causes dose-related peripheral neuropathy, which results from the depletion of pyridoxine in the presence of the drug. The neuropathy is usually preceded by paraesthesia's of the feet and hands. Therapy with isoniazid should be administered cautiously in patients with pre-existing peripheral neuropathy or risk factors for developing the condition, such as malnutrition, diabetes and alcoholism. Careful monitoring is recommended on these patients. Pyridoxine (vitamin B6) at a dosage of 10 to 50 mg/day may prevent or attenuate isoniazid-related peripheral neuropathy and is recommended for these patients.

Renal Dysfunction

Moderate:

isoniazid

Isoniazid has a moderate potential interaction with Renal Dysfunction.

Isoniazid may cause cerebellar syndrome in patients with chronic kidney disease. Patients with end-stage renal disease have been reported to have an increased risk of developing tuberculosis. Careful monitoring is recommended if this drug is used in patients with severe renal dysfunction. Dosage adjustments in renal impairment are generally not necessary except in slow acetylators with a creatinine clearance below 10 mL/min. Approximately 50% of Blacks and Caucasians are slow acetylators, and most Eskimos and Asians are rapid acetylators.

Moderate:

Thais

The estradiol in Thais 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.

Seizures

Moderate:

Thais

The estradiol in Thais 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:

Thais

The estradiol in Thais 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:

Thais

The estradiol in Thais 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.

More resources

isoniazid

A total of 742 drugs are known to interact with isoniazid.

Thais

A total of 446 drugs are known to interact with Thais.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.