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Drug Interactions between Estradot 37.5 and isoniazid

This report displays the potential drug interactions for the following 2 drugs:

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Moderate

isoniazid estradiol

Applies to: isoniazid and Estradot 37.5 (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 by way of the bile duct where hydrolytic enzymes of intestinal bacteria break down the conjugates into free, active estrogenic hormone. The active hormone is then available for enterohepatic cycling, which helps to maintain estrogen levels. It is important to note that 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 of their potential to reduce the number of intestinal bacteria and thus interfere with enterohepatic cycling of estrogen. Most of the research regarding this possible interaction has been done 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. Most antimicrobials, with the exception of enzyme inducing medications like 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 a person is using estrogen for a purpose other than contraception, it is important to note that there is a theoretical possibility of lower levels of systemic estrogen available during treatment with an antibiotic due to interference with enterohepatic cycling. These patients should be counseled to report any changes in efficacy of the hormonal product to their healthcare provider. In the case of contraception specifically, the Centers for Disease Control and Prevention do not consider most broad-spectrum antibiotics to significantly interfere with the effectiveness of combined hormonal contraception. However, the manufacturers of certain combined hormonal contraceptives and/or certain antibiotics do recommend using a back-up method of birth control for varying amounts of time; therefore, consulting the product labeling of each medication involved is advised. Some illnesses, as well as some antibiotics, may cause nausea, vomiting, and/or diarrhea. If the patient vomits within a few hours of taking an oral contraceptive pill, consult the product labeling 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.

References

  1. Friedman CI, Huneke AL, Kim MH, Powell J (1980) "The effect of ampicillin on oral contraceptive effectiveness." Obstet Gynecol, 55, p. 33-7
  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
  11. (2001) "Product Information. Declomycin (demeclocycline)." Lederle Laboratories
  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
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  45. Allen K (2012) "Contraception - common issues and practical suggestions." Aust Fam Physician, 41, p. 770-2
View all 45 references

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Drug and food interactions

Moderate

isoniazid food

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

  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.
View all 17 references

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Minor

estradiol food

Applies to: Estradot 37.5 (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

  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

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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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.

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