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Drug Interactions between Estro-LA and isoniazid / rifampin

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

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Interactions between your drugs

Major

rifAMPin isoniazid

Applies to: isoniazid / rifampin and isoniazid / rifampin

Using isoniazid together with rifAMPin can cause serious side effects that may affect your liver. Call your doctor immediately if you experience a fever, chills, joint pain or swelling, excessive tiredness or weakness, unusual bleeding or bruising, skin rash or itching, loss of appetite, nausea, vomiting, or yellowing of the skin or the whites of your eyes. If your doctor does prescribe these medications together, you may need a dose adjustment or special tests to safely take both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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Major

rifAMPin estradiol

Applies to: isoniazid / rifampin and Estro-LA (estradiol)

Consumer information for this interaction is not currently available.

MONITOR CLOSELY: Coadministration with rifampin or other rifamycins may reduce the efficacy of estrogen and progestin hormones that are CYP450 3A4 substrates. The interaction stems from accelerated clearance of the hormone(s) as well as decreased plasma concentrations of unbound (active) hormone(s) due to induction of CYP450 enzymatic activity and hormone-binding globulin capacity by rifampin and to a lesser extent with other rifamycins. In a study of 28 healthy premenopausal women on a combination oral contraceptive pill, coadministration with rifampin (300 mg/day for 10 days) reduced ethinyl estradiol peak plasma concentration (Cmax) and systemic exposure (AUC) by 42% and 64%, respectively, while the same dosage of rifabutin reduced ethinyl estradiol Cmax and AUC by 20% and 35%, respectively. Norethindrone AUC was reduced by 60% with rifampin and 20% with rifabutin. In addition, FSH and LH levels increased following rifamycin therapy, and the incidence of spotting was significantly higher after coadministration with rifampin (36.4%) and rifabutin (21.7%) than during the control cycle (3.7%). This interaction is not thought to be clinically relevant for persons using the progestin-only (DMPA) injection (as serum progestin levels are expected to remain adequate), locally acting levonorgestrel-releasing intrauterine systems (as the local effect on the endometrium is unaffected by enzyme induction), and the non-hormonal copper intrauterine device for contraception. Similarly, this interaction may not be as significant for each hormone. A pharmacokinetic study (n=65) in postmenopausal women examined the effects of rifampin (600 mg/day) on the exposure of levonorgestrel (0.03 mg, n=13), norethindrone (0.35 mg, n=14), desogestrel (0.075 mg, n=12), dienogest (2 mg, n=12), and a combination of drospirenone and ethinyl estradiol (3 mg/0.03 mg, n=14). Bound and unbound hormone levels were reviewed. The largest decreases in AUC were observed for etonogestrel (desogestrel's active metabolite), dienogest, and drospirenone at >80%. Levonorgestrel, norethindrone, and ethinyl estradiol had reductions in AUC between 50% and less than 80%.

MANAGEMENT: Caution and close clinical monitoring for reduced efficacy are advised for people using an estrogen and/or progestin-containing product for purposes other than contraception. These patients should be counseled to report any changes in efficacy of the hormonal product to their healthcare provider. Women using estrogens and/or progestins for contraception should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant rifamycin therapy, even when given in short doses. Long-acting progestin-only injections and levonorgestrel-releasing intrauterine systems may be considered as alternative contraceptive agents. For the most current guidance, local relevant guidelines should be consulted. In general, alternative or additional methods of non-hormonal birth control should be used during and for at least 28 days after rifamycin therapy.

The following apply only to the specific medications (combined oral contraception) or situations (emergency contraception) specified:

-If a combination oral contraceptive pill is chosen despite the risks, a regimen containing at least 30 mcg of ethinyl estradiol per day or equivalent should be selected. Some authorities have suggested increasing to 50 mcg of ethinyl estradiol or equivalent; however, they recommend advising the patient that contraceptive effectiveness, even at this dose, may be reduced and that there could be an increased risk of thrombosis if exposure to ethinyl estradiol is increased.

-For emergency contraception in patients who have used a hepatic enzyme inducer in the past 4 weeks, a non-hormonal emergency contraceptive (e.g., copper intrauterine device) is considered preferable. If this is not possible, some authorities recommend that the usual dose of levonorgestrel (1.5 mg) be doubled to 3 mg and taken as a single dose as soon as possible (typically within 72 hours, though some guidelines suggest up to 96 hours, of unprotected sexual intercourse). However, the efficacy of this regimen is unknown.

References

  1. Venkatesan K "Pharmacokinetic drug interactions with rifampicin." Clin Pharmacokinet 22 (1992): 47-65
  2. Borcherding SM, Baciewicz AM, Self TH "Update on rifampin drug interactions." Arch Intern Med 152 (1992): 711-6
  3. Baciewicz AM "Oral contraceptive drug interactions." Ther Drug Monit 7 (1985): 26-35
  4. Joshi JV, Joshi UM, Sankolli GM, et al. "A study of interaction of a low-dose combination oral contraceptive with anti-tubercular drugs." Contraception 21 (1980): 617-29
  5. Bint AJ, Burtt I "Adverse antibiotic drug interactions." Drugs 20 (1980): 57-68
  6. Skolnick JL, Stoler BS, Katz DB, Anderson WH "Rifampin, oral contraceptives, and pregnancy." JAMA 236 (1976): 1382
  7. Dossetor J "Drug interactions with oral contraceptives." Br Med J 4 (1975): 467-8
  8. "Product Information. Mycobutin (rifabutin)." Pharmacia and Upjohn PROD (2001):
  9. "Product Information. Rifadin (rifampin)." Hoechst Marion Roussel PROD (2001):
  10. Baciewicz AM, Self TH "Rifampin drug interactions." Arch Intern Med 144 (1984): 1667-71
  11. Nocke-finck L "Effects of rifampicin on menstral cycle and on estrogen excretion in patients taking oral contraceptives." JAMA 226 (1973): 378
  12. Bolt HM, Bolt M, Kappus H "Interaction of rifampicin treatment with pharmacokinetics and metabolism of ethinyloestradiol in man." Acta Endocrinol (Copenh) 85 (1977): 189-97
  13. Back DJ, Breckenridge AM, Crawford FE, et al. "The effect of rifampicin on the pharmacokinetics of ethynylestradiol in women." Contraception 21 (1980): 135-43
  14. Back DJ, Breckenridge AM, Crawford F, et al. "The effect of rifampicin on norethisterone pharmacokinetics." Eur J Clin Pharmacol 15 (1979): 193-7
  15. Szoka PR, Edgren RA "Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database." Fertil Steril 49 (1988): s31-8
  16. Back DJ, Orme ML "Pharmacokinetic drug interactions with oral contraceptives." Clin Pharmacokinet 18 (1990): 472-84
  17. D'Arcy PF "Drug interactions with oral contraceptives." Drug Intell Clin Pharm 20 (1986): 353-62
  18. Strayhorn VA, Baciewicz AM, Self TH "Update on rifampin drug interactions, III." Arch Intern Med 157 (1997): 2453-8
  19. Michalets EL "Update: clinically significant cytochrome P-450 drug interactions." Pharmacotherapy 18 (1998): 84-112
  20. "Product Information. Priftin (rifapentine)." Hoechst Marion Roussel PROD (2001):
  21. Back DJ, Breckenridge AM, Crawford FE, MacIver M, Orne ML, Rowe PH "Interindividual variation and drug interactions with hormonal steroid contraceptives." Drugs 21 (1981): 46-61
  22. LeBel M, Masson E, Guilbert E, Colborn D, Paquet F, Allard S, Vallee F, Narang PK "Effects of rifabutin and rifampicin on the pharmacokinetics of ethinylestradiol and norethindrone." J Clin Pharmacol 38 (1998): 1042-50
  23. Barditch-Crovo P, Trapnell CB, Ette E, et al. "The effects of rifampin and rifabutin on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive." Clin Pharmacol Ther 65 (1999): 428-38
  24. Weisberg E "Interactions between oral contraceptives and antifungals antibacterials - Is contraceptive failure the result?." Clin Pharmacokinet 36 (1999): 309-13
  25. Weaver K, Glasier A "Interaction between broad-spectrum antibiotics and the combined oral contraceptive pill: a literature review." Contraception 59 (1999): 71-8
  26. Zachariassen RD "Loss of oral contraceptive efficacy by concurrent antibiotic administration." Women Health 22 (1994): 17-26
  27. Dickinson BD, Altman RD, Nielsen NH, Sterling ML "Drug interactions between oral contraceptives and antibiotics." Obstet Gynecol 98(5 Pt 1) (2001): 853-60
  28. Archer JS, Archer DF "Oral contraceptive efficacy and antibiotic interaction: A myth debunked." J Am Acad Dermatol 46 (2002): 917-23
  29. DeRossi SS, Hersh EV "Antibiotics and oral contraceptives." Dent Clin North Am 46 (2002): 653-64
  30. "FFPRHC Guidance (April 2005). Drug interactions with hormonal contraception." J Fam Plann Reprod Health Care 31 (2005): 139-51
  31. Bounds W, Guillebaud J "Observational series on women using the contraceptive Mirena concurrently with anti-epileptic and other enzyme-inducing drugs." J Fam Plann Reprod Health Care 28 (2002): 78-80
  32. Faculty of Sexual & Reproductive Healthcare "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf" (2016):
  33. Curtis KM, Tepper NK, Jatlaoui TC, et al. "U.S. medical eligibility criteria (US MEC) for contraceptive use. https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/index.html" (2023):
  34. Faculty of Sexual & Reproductive Healthcare "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/" (2023):
  35. Allen K "Contraception - common issues and practical suggestions." Aust Fam Physician 41 (2012): 770-2
  36. "Product Information. Isoniazid/Rifapentine 300 mg/300 mg (Macleods) (isoniazid-rifapentine)." Imported (India) 2 (2021):
  37. "Product Information. Priftin (rifapentine)." sanofi-aventis (2021):
  38. Macleods Pharmaceuticals Limited "Rifapentine 300 mg tablets (Macleods Pharmaceuticals Ltd), TB398. WHO-PQ recommended summary of product characteristics. https://extranet.who.int/prequal/sites/default/files/whopar_files/TB398part4v1.pdf" (2024):
  39. Wiesinger H, Klein S, Rottmann A, et al. "The effects of weak and strong CYP3A induction by rifampicin on the pharmacokinetics of five progestins and ethinylestradiol compared to midazolam." Clin Pharmacol Ther 108 (2020): 798-807
View all 39 references
Moderate

isoniazid estradiol

Applies to: isoniazid / rifampin and Estro-LA (estradiol)

Consumer information for this interaction is not currently available.

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 "The effect of ampicillin on oral contraceptive effectiveness." Obstet Gynecol 55 (1980): 33-7
  2. Back DJ, Breckenridge AM, MacIver M, et al. "The effects of ampicillin on oral contraceptive steroids in women." Br J Clin Pharmacol 14 (1982): 43-8
  3. Neely JL, Abate M, Swinker M, D'Angio R "The effect of doxycycline on serum levels of ethinyl estradiol, norethindrone, and endogenous progesterone." Obstet Gynecol 77 (1991): 416-20
  4. Joshi JV, Joshi UM, Sankholi GM, et al. "A study of interaction of low-dose combination oral contraceptive with ampicillin and metronidazole." Contraception 22 (1980): 643-52
  5. Baciewicz AM "Oral contraceptive drug interactions." Ther Drug Monit 7 (1985): 26-35
  6. Bint AJ, Burtt I "Adverse antibiotic drug interactions." Drugs 20 (1980): 57-68
  7. Dossetor J "Drug interactions with oral contraceptives." Br Med J 4 (1975): 467-8
  8. DeSano EA, Hurley SC "Possible interactions of antihistamines and antibiotics with oral contraceptive effectiveness." Fertil Steril 37 (1982): 853-4
  9. Szoka PR, Edgren RA "Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database." Fertil Steril 49(5 Suppl) (1988): s31-8
  10. Barnett ML "Inhibition of oral contraceptive effectiveness by concurrent antibiotic administration." J Periodontol 56 (1985): 18-20
  11. "Product Information. Declomycin (demeclocycline)." Lederle Laboratories PROD (2001):
  12. London BM, Lookingbill DP "Frequency of pregnancy in acne patients taking oral antibiotics and oral contraceptives." Arch Dermatol 130 (1994): 392-3
  13. Bacon JF, Shenfield GM "Pregnancy attributable to interaction between tetracycline and oral contraceptives." Br Med J 280 (1980): 293
  14. Fazio A "Oral contraceptive drug interactions: important considerations." South Med J 84 (1991): 997-1002
  15. Back DJ, Orme ML "Pharmacokinetic drug interactions with oral contraceptives." Clin Pharmacokinet 18 (1990): 472-84
  16. Back DJ, Tjia J, Martin C, Millar E, Mant T, Morrison P, Orme M "The lack of interaction between temafloxacin and combined oral contraceptive steroids." Contraception 43 (1991): 317-23
  17. Orme ML, Back DJ "Interactions between oral contraceptive steroids and broad-spectrum antibiotics." Clin Exp Dermatol 11 (1986): 327-31
  18. Wermeling DP, Chandler MH, Sides GD, Collins D, Muse KN "Dirithromycin increases ethinyl estradiol clearance without allowing ovulation." Obstet Gynecol 86 (1995): 78-84
  19. Silber TJ "Apparent oral contraceptive failure associated with antibiotic administration." J Adolesc Health Care 4 (1983): 287-9
  20. Bollen M "Use of antibiotics when taking the oral contraceptive pill." Aust Fam Physician 24 (1995): 928-9
  21. Kleier DJ, Tucker JE "Oral contraceptive failure secondary to dentally prescribed drugs: fact or fiction?" J Colo Dent Assoc 66 (1987): 5-6
  22. Back DJ, Breckenridge AM, Crawford FE, MacIver M, Orne ML, Rowe PH "Interindividual variation and drug interactions with hormonal steroid contraceptives." Drugs 21 (1981): 46-61
  23. Helms SE, Bredle DL, Zajic J, Jarjoura D, Brodell RT, Krishnarao I "Oral contraceptive failure rates and oral antibiotics." J Am Acad Dermatol 36 (1997): 705-10
  24. Weisberg E "Interactions between oral contraceptives and antifungals antibacterials - Is contraceptive failure the result?." Clin Pharmacokinet 36 (1999): 309-13
  25. Burroughs KE, Chambliss ML "Antibiotics and oral contraceptive failure." Arch Fam 9 (2000): 81-2
  26. Weaver K, Glasier A "Interaction between broad-spectrum antibiotics and the combined oral contraceptive pill: a literature review." Contraception 59 (1999): 71-8
  27. King VJ "OC failure rates and oral antibiotics." J Fam Pract 45 (1997): 104-5
  28. Zachariassen RD "Loss of oral contraceptive efficacy by concurrent antibiotic administration." Women Health 22 (1994): 17-26
  29. Dickinson BD, Altman RD, Nielsen NH, Sterling ML "Drug interactions between oral contraceptives and antibiotics." Obstet Gynecol 98(5 Pt 1) (2001): 853-60
  30. Archer JS, Archer DF "Oral contraceptive efficacy and antibiotic interaction: A myth debunked." J Am Acad Dermatol 46 (2002): 917-23
  31. Orme M, Back DJ "Oral contraceptive steroids--pharmacological issues of interest to the prescribing physician." Adv Contracept 7 (1991): 325-31
  32. DeRossi SS, Hersh EV "Antibiotics and oral contraceptives." Dent Clin North Am 46 (2002): 653-64
  33. "FFPRHC Guidance (April 2005). Drug interactions with hormonal contraception." J Fam Plann Reprod Health Care 31 (2005): 139-51
  34. Bauer KL, Wolf D, Patel M, Vinson DC "Clinical inquiries. Do antibiotics interfere with the efficacy of oral contraceptives?" J Fam Pract 54 (2005): 1079-80
  35. Back DJ, Grimmer SF, Orme ML, Proudlove D, Mann RD, Breckenridge AM "Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics." Br J Clin Pharmacol 25 (1988): 527-32
  36. "Product Information. Arikayce (amikacin liposome)." Insmed Incorporated (2018):
  37. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma (2021):
  38. "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma International Pty Ltd v 2.0 (2022):
  39. Curtis KM, Tepper NK, Jatlaoui TC, et al. "U.S. medical eligibility criteria (US MEC) for contraceptive use. https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/index.html" (2023):
  40. Faculty of Sexual & Reproductive Healthcare "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" (2023):
  41. Faculty of Sexual & Reproductive Healthcare "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/" (2023):
  42. Simmons KB, Haddad LB, Nanda K, Curtis KM "Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systemic review." Am J Obstet Gynecol 218 (2018): 88-97.e14
  43. Zhanel GG, Siemens S, Slayter K, Mandell L "Antibiotic and oral contraceptive drug interactions: is there a need for concern?" Can J Infect Dis 10 (1999): 429-33
  44. Black A, Francoeur D, Rowe T, et al. "SOGC clinical practice guidelines canadian contraception consensus https://www.jogc.com/article/S1701-2163(16)30260-2/pdf" (2023):
  45. Allen K "Contraception - common issues and practical suggestions." Aust Fam Physician 41 (2012): 770-2
View all 45 references

Drug and food interactions

Moderate

rifAMPin food

Applies to: isoniazid / rifampin

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 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 rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.

References

  1. "Product Information. Rifampin (rifAMPin)." Akorn Inc (2022):
  2. "Product Information. Rifampicin (rifampicin)." Mylan Pharmaceuticals Inc (2022):
  3. "Product Information. Rifadin (rifampicin)." Sanofi (2023):
  4. "Product Information. Rifadin (rifaMPICin)." Sanofi-Aventis Australia Pty Ltd (2024):
  5. Peloquin CA, Namdar R, Singleton MD, Nix DE "Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids https://pubmed.ncbi.nlm.nih.gov/9925057/" (2024):
  6. "Product Information. Rofact (rifampin)." Bausch Health, Canada Inc. (2019):
View all 6 references
Moderate

isoniazid food

Applies to: isoniazid / rifampin

Food decreases the levels of isoniazid in your body. Take isoniazid on an empty stomach at least 1 hour before or 2 hours after a meal. This will make it easier for your body to absorb the medication. If nausea occurs, ask your doctor if you can take isoniazid with food. Avoid alcohol while taking isoniazid. Alcohol may increase the risk of damage to the liver during isoniazid treatment. Alcohol can also cause isoniazid side effects to get worse. Contact your doctor if you experience flushing, chills, headache, nausea, vomiting, and diarrhea.

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Minor

estradiol food

Applies to: Estro-LA (estradiol)

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

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.

Further information

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