Interactions between Cephradine and Xelria Fe
1 drug interaction and 44 additional warnings found for the following 2 drugs:
- cephradine
- Xelria Fe (ethinyl estradiol/norethindrone)
Drug interactions
Moderate drug interactions
Moderate:
cephradine ethinyl estradiol
Applies to: cephradine and Xelria Fe (ethinyl estradiol / norethindrone)
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)
- Friedman CI, Huneke AL, Kim MH, Powell J (1980) "The effect of ampicillin on oral contraceptive effectiveness." Obstet Gynecol, 55, p. 33-7
- 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
- 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
- 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
- Baciewicz AM (1985) "Oral contraceptive drug interactions." Ther Drug Monit, 7, p. 26-35
- Bint AJ, Burtt I (1980) "Adverse antibiotic drug interactions." Drugs, 20, p. 57-68
- Dossetor J (1975) "Drug interactions with oral contraceptives." Br Med J, 4, p. 467-8
- DeSano EA, Hurley SC (1982) "Possible interactions of antihistamines and antibiotics with oral contraceptive effectiveness." Fertil Steril, 37, p. 853-4
- 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
- Barnett ML (1985) "Inhibition of oral contraceptive effectiveness by concurrent antibiotic administration." J Periodontol, 56, p. 18-20
- (2001) "Product Information. Declomycin (demeclocycline)." Lederle Laboratories
- London BM, Lookingbill DP (1994) "Frequency of pregnancy in acne patients taking oral antibiotics and oral contraceptives." Arch Dermatol, 130, p. 392-3
- Bacon JF, Shenfield GM (1980) "Pregnancy attributable to interaction between tetracycline and oral contraceptives." Br Med J, 280, p. 293
- Fazio A (1991) "Oral contraceptive drug interactions: important considerations." South Med J, 84, p. 997-1002
- Back DJ, Orme ML (1990) "Pharmacokinetic drug interactions with oral contraceptives." Clin Pharmacokinet, 18, p. 472-84
- 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
- Orme ML, Back DJ (1986) "Interactions between oral contraceptive steroids and broad-spectrum antibiotics." Clin Exp Dermatol, 11, p. 327-31
- 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
- Silber TJ (1983) "Apparent oral contraceptive failure associated with antibiotic administration." J Adolesc Health Care, 4, p. 287-9
- Bollen M (1995) "Use of antibiotics when taking the oral contraceptive pill." Aust Fam Physician, 24, p. 928-9
- Kleier DJ, Tucker JE (1987) "Oral contraceptive failure secondary to dentally prescribed drugs: fact or fiction?" J Colo Dent Assoc, 66, p. 5-6
- 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
- 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
- Weisberg E (1999) "Interactions between oral contraceptives and antifungals antibacterials - Is contraceptive failure the result?." Clin Pharmacokinet, 36, p. 309-13
- Burroughs KE, Chambliss ML (2000) "Antibiotics and oral contraceptive failure." Arch Fam, 9, p. 81-2
- Weaver K, Glasier A (1999) "Interaction between broad-spectrum antibiotics and the combined oral contraceptive pill: a literature review." Contraception, 59, p. 71-8
- King VJ (1997) "OC failure rates and oral antibiotics." J Fam Pract, 45, p. 104-5
- Zachariassen RD (1994) "Loss of oral contraceptive efficacy by concurrent antibiotic administration." Women Health, 22, p. 17-26
- 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
- Archer JS, Archer DF (2002) "Oral contraceptive efficacy and antibiotic interaction: A myth debunked." J Am Acad Dermatol, 46, p. 917-23
- Orme M, Back DJ (1991) "Oral contraceptive steroids--pharmacological issues of interest to the prescribing physician." Adv Contracept, 7, p. 325-31
- DeRossi SS, Hersh EV (2002) "Antibiotics and oral contraceptives." Dent Clin North Am, 46, p. 653-64
- (2005) "FFPRHC Guidance (April 2005). Drug interactions with hormonal contraception." J Fam Plann Reprod Health Care, 31, p. 139-51
- 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
- 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
- (2018) "Product Information. Arikayce (amikacin liposome)." Insmed Incorporated
- (2021) "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma
- (2022) "Product Information. Nextstellis (drospirenone-estetrol)." Mayne Pharma International Pty Ltd, v 2.0
- 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
- 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
- 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/
- 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
- 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
- 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
- Allen K (2012) "Contraception - common issues and practical suggestions." Aust Fam Physician, 41, p. 770-2
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
norethindrone Food/Lifestyle
Applies to: Xelria Fe (ethinyl estradiol / norethindrone)
Monitor
Grapefruit or grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
Management
Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.
References (32)
- Edgar B, Bailey D, Bergstrand R, et al. (1992) "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance." Eur J Clin Pharmacol, 42, p. 313-7
- Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
- Bailey DG, Arnold JM, Munoz C, Spence JD (1993) "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther, 53, p. 637-42
- Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
- Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
- Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
- Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
- (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
- Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
- Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
- Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
- Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
- Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
- Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
- Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A (1998) "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet, 23, p. 55-9
- Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
- Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
- Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
- Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
- Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
- Lilja JJ, Kivisto KT, Neuvonen PJ (1999) "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther, 66, p. 118-27
- Eagling VA, Profit L, Back DJ (1999) "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol, 48, p. 543-52
- Damkier P, Hansen LL, Brosen K (1999) "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol, 48, p. 829-38
- Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
- Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
- Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
- Takanaga H, Ohnishi A, Maatsuo H, et al. (2000) "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol, 49, p. 49-58
- Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
- Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
- Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
- Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
- Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286
Moderate:
cephradine multivitamins with minerals
Applies to: cephradine
Adjust dosing interval
Oral products containing zinc such as mineral supplements and multivitamins may interfere with the gastrointestinal absorption of cephalexin, ceftibuten or cephradine. In one pharmacokinetic study (n=12), concurrent administration of zinc sulfate (250 mg, single oral dose) and cephalexin (500 mg, single oral dose) decreased cephalexin maximum concentration (Cmax) and systemic exposure (AUC; 0-inf) by 31.05% and 27.4%, respectively. However, in the same study, when zinc sulfate was administered 3 hours after the cephalexin dose, no significant alteration in cephalexin pharmacokinetics were observed.
Management
Oral medications or mineral supplements that contain zinc are recommended to be administered at least 3 hours after the cephalexin, ceftibuten or cephradine dose.
References (3)
- Ding Y, Jia Y, Li F, et al. (2011) "The Effect of Staggered Administration of Zinc Sulfate on the Pharmacokinetics of Oral Cephalexin*" Br J Clin Pharmacol, 73, p. 422-7
- World Health Organization (2020) WHO Public Assessment Reports (WHOPARs) https://extranet.who.int/pqweb/medicines/prequalification-reports/whopars
- Okamura M, Terada t, KatsuraT, Saito H, Inui K (2003) "Inhibitory effect of zinc on PEPT1-mediated transport of glycylsarcosine and beta-lactam antibiotics in human intestinal cell line Caco-2" Pharm Res, 20, p. 1389-93
Moderate:
ethinyl estradiol Caffeine
Applies to: Xelria Fe (ethinyl estradiol / norethindrone)
Monitor
Coadministration of ethinyl estradiol may increase the plasma concentrations of drugs that are primarily metabolized by CYP450 1A2. In a study of 30 healthy volunteers administered the CYP450 1A2 substrate tizanidine, the systemic exposure (AUC) of tizanidine was 3.9 times greater in women using an oral contraceptive containing ethinyl estradiol.
Management
Patients should be monitored for increased adverse effects of the CYP450 1A2 substrate during concomitant use with ethinyl estradiol. Product labeling for the specific CYP450 1A2 substrate should be consulted for additional recommendations.
References (1)
- Granfors MT, Backman JT, Laitila J, Neuvonen PJ (2005) "Oral contraceptives containing ethinyl estradiol and gestodene markedly increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P450 1A2." Clin Pharmacol Ther, 78, p. 400-11
Minor food/lifestyle interactions
Minor:
ethinyl estradiol Food/Lifestyle
Applies to: Xelria Fe (ethinyl estradiol / norethindrone)
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
Minor:
ethinyl estradiol Alcohol (Ethanol)
Applies to: Xelria Fe (ethinyl estradiol / norethindrone)
The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.
References (1)
- Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80
Minor:
norethindrone Alcohol (Ethanol)
Applies to: Xelria Fe (ethinyl estradiol / norethindrone)
The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.
References (1)
- Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80
Disease interactions
38 potential interactions Applies to: 28 conditions, including High Blood Pressure, High Cholesterol, Depression, Migraine, and Weight Loss.
Abnormal Uterine Bleeding
Major:
Xelria Fe
The norethindrone in Xelria Fe has a major potential interaction with Abnormal Uterine Bleeding.
The use of contraceptives is contraindicated when there is an undiagnosed abnormal genital bleeding. Adequate diagnostic measures should be undertaken to rule out the presence of any malignancy.
Major:
Xelria Fe
The ethinyl estradiol in Xelria Fe 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:
Xelria Fe
The ethinyl estradiol in Xelria Fe 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:
Xelria Fe
The ethinyl estradiol and norethindrone in Xelria Fe both have a moderate potential interaction with Asthma.
Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.
Breast Cancer
Major:
Xelria Fe
The norethindrone in Xelria Fe has a major potential interaction with Breast Cancer.
The use of progestogens is considered by manufacturers to be contraindicated in patients with existing or suspected malignancy of the breast. Some supportive data are available for medroxyprogesterone. Specifically, medroxyprogesterone treatment may be associated with breast cancer, primarily when the drug is administered intramuscularly. A pooled analysis of two case-control studies, one from the World Health Organization and the other from New Zealand, revealed a small overall relative risk of breast cancer in women who have ever used intramuscular medroxyprogesterone acetate. The relative risk was higher in the subgroup of women who had initiated therapy within the previous 5 years. Thus, an increased risk (approximately 2-fold) is associated with intramuscular medroxyprogesterone use in the first 5 years. A more recent U.S. study also found a statistically significant increase in breast cancer risk among recent users (defined as last use within the past five years) who used depo-medroxyprogesterone acetate for 12 months or longer.
Major:
Xelria Fe
The ethinyl estradiol in Xelria Fe 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:
Xelria Fe
The norethindrone in Xelria Fe has a major potential interaction with Cerebral Vascular Disorder.
The use of progestogens, in general, is considered by manufacturers to be contraindicated in patients with active thrombophlebitis, cerebrovascular disease, or a current or past history of thromboembolic disorders. While the role of progestogens in the development of thromboembolic events associated with hormonal therapy is often unclear and thought to be secondary to that of estrogens, it may not be insignificant. Medroxyprogesterone, a common progestational agent, has been shown to produce a hypercoagulable state in high dosages. Whether or not this effect contributes to the development of thrombotic events is unknown. However, thrombophlebitis and pulmonary embolism have been reported with megestrol, an antineoplastic and progestational agent. In addition, an increased risk of nonfatal venous thrombosis has been associated with oral contraceptive combinations containing desogestrel or gestodene relative to those that contain other progestins (e.g., levonorgestrel, norethindrone), suggesting some degree of hemostatic effect by progestogens.
Major:
Xelria Fe
The ethinyl estradiol in Xelria Fe 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.
Depression
Moderate:
Xelria Fe
The ethinyl estradiol and norethindrone in Xelria Fe both have a moderate potential interaction with Depression.
The use of oral contraceptives has been associated with an increased incidence of depression. It is uncertain whether this effect is related to the estrogenic or the progestogenic component of the contraceptive, although excess progesterone activity is associated with depression. Patients with a history of depression receiving estrogen and/or progestogen therapy should be followed closely. The manufacturer of medroxyprogesterone recommends monitoring patients who have a history of depression and to not re- administer medroxyprogesterone if depression recurs.
Diabetes Mellitus
Moderate:
Xelria Fe
The ethinyl estradiol and norethindrone in Xelria Fe both have a moderate potential interaction with Diabetes Mellitus.
Impaired glucose tolerance has been observed in some patients administered oral contraceptives and appears to be related primarily to the estrogen dose. However, progestogens can increase insulin secretion and produce insulin resistance to varying degrees, depending on the agent. Caution and close monitoring are recommended in patients with diabetes mellitus during therapy with estrogens and/or progestogens, and adjustments made accordingly in their antidiabetic regimen.
Fluid Retention
Moderate:
Xelria Fe
The ethinyl estradiol and norethindrone in Xelria Fe both have a moderate potential interaction with Fluid Retention.
Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.
Gallbladder Disease
Moderate:
Xelria Fe
The ethinyl estradiol in Xelria Fe 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:
Xelria Fe
The ethinyl estradiol and norethindrone in Xelria Fe both have a moderate potential interaction with Heart Failure.
Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.
Hemodialysis
Moderate:
cephradine
Cephradine has a moderate potential interaction with Hemodialysis.
Most cephalosporin antibiotics are removed by hemodialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis. Cefonicid, cefixime, and ceftriaxone are not significantly removed by hemodialysis.
Hepatic Tumor
Major:
Xelria Fe
The ethinyl estradiol and norethindrone in Xelria Fe both have a major potential interaction with Hepatic Tumor.
The use of oral contraceptives is contraindicated in patients with liver tumors. An increased risk of benign hepatic adenomas and hepatocellular carcinomas has been associated with long-term, oral estrogen- progestin contraceptive use of at least 4 years and 8 years, respectively. Although these tumors are rare and have not been reported with other types of estrogen or progestogen therapies, any preparation containing estrogens and/or progestogens should probably be avoided in patients with existing tumors of the liver. Hepatic hemangiomas and nodular hyperplasia of the liver have been reported with isolated estrogen therapy.
High Blood Pressure
Major:
Xelria Fe
The ethinyl estradiol in Xelria Fe has a major potential interaction with High Blood Pressure.
The risk of myocardial infarction and strokes, including those associated with oral contraceptive use and some estrogen use, is increased in patients with hypertension. Moreover, estrogens (and progestogens) may elevate blood pressure and worsen the hypertension, thus compounding the risk. Clinically significant blood pressure increases have been reported during estrogen therapy, particularly in patients receiving high dosages or treated with oral contraceptive combinations having high progestational activity. These effects also increase with duration of therapy and patient age. Therapy with estrogens should be administered cautiously in patients with preexisting hypertension. Some estrogen-based therapies, such as combined hormonal contraceptives, may be contraindicated in patients with uncontrolled hypertension or hypertension with vascular disease. Patients should be monitored for changes in cardiovascular status, and their antihypertensive regimen adjusted or estrogen therapy withdrawn as necessary. In patients requiring contraception, alternative methods should be considered for those who are hypertensive, over age 35, and smoke.
Moderate:
Xelria Fe
The norethindrone in Xelria Fe has a moderate potential interaction with High Blood Pressure.
Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.
High Cholesterol
Moderate:
Xelria Fe
The ethinyl estradiol in Xelria Fe has a moderate potential interaction with High Cholesterol.
Estrogens may cause adverse lipid changes. Use of estrogens has been associated with elevations in triglyceride levels, particularly in women with pre-existing hypertriglyceridemia. Discontinue therapy if elevated triglycerides lead to pancreatitis. Manage hypercholesterolemia appropriately as indicated.
Moderate:
Xelria Fe
The norethindrone in Xelria Fe has a moderate potential interaction with High Cholesterol.
Some progestogenic agents may elevate plasma LDL levels and/or lower HDL levels, although data have been inconsistent. Patients with preexisting hyperlipidemia may require closer monitoring during progestogen therapy, and adjustments made accordingly in their lipid-lowering regimen.
History, Thrombotic/Thromboembolic Disorder
Major:
Xelria Fe
The ethinyl estradiol in Xelria Fe has a major potential interaction with History, Thrombotic/Thromboembolic Disorder.
The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.
Major:
Xelria Fe
The norethindrone in Xelria Fe has a major potential interaction with History, Thrombotic/Thromboembolic Disorder.
The use of progestogens, in general, is considered by manufacturers to be contraindicated in patients with active thrombophlebitis, cerebrovascular disease, or a current or past history of thromboembolic disorders. While the role of progestogens in the development of thromboembolic events associated with hormonal therapy is often unclear and thought to be secondary to that of estrogens, it may not be insignificant. Medroxyprogesterone, a common progestational agent, has been shown to produce a hypercoagulable state in high dosages. Whether or not this effect contributes to the development of thrombotic events is unknown. However, thrombophlebitis and pulmonary embolism have been reported with megestrol, an antineoplastic and progestational agent. In addition, an increased risk of nonfatal venous thrombosis has been associated with oral contraceptive combinations containing desogestrel or gestodene relative to those that contain other progestins (e.g., levonorgestrel, norethindrone), suggesting some degree of hemostatic effect by progestogens.
Ischemic Heart Disease
Major:
Xelria Fe
The ethinyl estradiol in Xelria Fe 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:
Xelria Fe
The norethindrone in Xelria Fe has a major potential interaction with Liver Disease.
The use of progestogens, in general, is contraindicated in patients with impaired hepatic function or liver disease. There are little or no data concerning the pharmacokinetic disposition of the different progestogens in patients with hepatic disease. However, most hormones, including progestational hormones, are known to be extensively metabolized by the liver. Medroxyprogesterone should not be used by women with significant liver disease and should be discontinued if jaundice or disturbances of liver function occur.
Moderate:
Xelria Fe
The ethinyl estradiol in Xelria Fe 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.
Melasma
Moderate:
Xelria Fe
The ethinyl estradiol in Xelria Fe has a moderate potential interaction with Melasma.
The use of exogenous estrogens may occasionally cause chloasma, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking combination oral contraceptives.
Migraine
Major:
Xelria Fe
The ethinyl estradiol in Xelria Fe 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:
Xelria Fe
The ethinyl estradiol and norethindrone in Xelria Fe both have a moderate potential interaction with Migraine.
Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.
Neoplasia, Estrogen Dependent
Major:
Xelria Fe
The ethinyl estradiol in Xelria Fe 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.
Noninfectious Colitis
Major:
cephradine
Cephradine has a major potential interaction with Noninfectious Colitis.
Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.
Pancreatitis
Moderate:
Xelria Fe
The ethinyl estradiol in Xelria Fe 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:
cephradine
Cephradine has a moderate potential interaction with Renal Dysfunction.
Most beta-lactam antibiotics are eliminated by the kidney as unchanged drug and, in some cases, also as metabolites. The serum concentrations of beta-lactam antibiotics and their metabolites may be increased and the half-lives prolonged in patients with impaired renal function. Dosage adjustments may be necessary and modifications should be based on the degree of renal impairment as well as severity of infection in accordance with the individual product package labeling. Renal function tests should be performed periodically during prolonged and/or high-dose therapy, since nephrotoxicity and alterations in renal function have occasionally been associated with the use of these drugs.
Moderate:
Xelria Fe
The ethinyl estradiol and norethindrone in Xelria Fe both have a moderate potential interaction with Renal Dysfunction.
Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.
Seizures
Moderate:
Xelria Fe
The ethinyl estradiol and norethindrone in Xelria Fe both have a moderate potential interaction with Seizures.
Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.
Smoking
Major:
Xelria Fe
The ethinyl estradiol in Xelria Fe has a major potential interaction with Smoking.
Cigarette smoking increases the risk of serious cardiovascular events from estrogen-containing combination oral contraceptives (COC). This risk increases with age, particularly in females over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs are contraindicated in females who are over 35 years of age and smoke.
Thrombotic/Thromboembolic Disorder
Major:
Xelria Fe
The ethinyl estradiol in Xelria Fe 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.
Major:
Xelria Fe
The norethindrone in Xelria Fe has a major potential interaction with Thrombotic/Thromboembolic Disorder.
The use of progestogens, in general, is considered by manufacturers to be contraindicated in patients with active thrombophlebitis, cerebrovascular disease, or a current or past history of thromboembolic disorders. While the role of progestogens in the development of thromboembolic events associated with hormonal therapy is often unclear and thought to be secondary to that of estrogens, it may not be insignificant. Medroxyprogesterone, a common progestational agent, has been shown to produce a hypercoagulable state in high dosages. Whether or not this effect contributes to the development of thrombotic events is unknown. However, thrombophlebitis and pulmonary embolism have been reported with megestrol, an antineoplastic and progestational agent. In addition, an increased risk of nonfatal venous thrombosis has been associated with oral contraceptive combinations containing desogestrel or gestodene relative to those that contain other progestins (e.g., levonorgestrel, norethindrone), suggesting some degree of hemostatic effect by progestogens.
Thyroid Disease
Moderate:
Xelria Fe
The ethinyl estradiol and norethindrone in Xelria Fe both have a moderate potential interaction with Thyroid Disease.
When administering estrogen and/or progestogen therapy in patients with thyroid disorders, clinicians should be aware that these hormones may affect thyroid function tests. Patients on thyroid replacement therapy may require higher doses of thyroid hormone and appropriate monitoring. Changes have mostly been reported with the use of combination oral contraceptives. Specifically, thyroid-binding globulin (TBG) may be increased, resulting in elevated circulating total thyroid hormone, as measured by PBI (protein-bound iodine), T4 by column or radioimmunoassay, or T3 by radioimmunoassay. Free T3 resin uptake may be decreased. On the contrary, a decrease in TBG and, consequently, thyroxine concentration, has been reported by the manufacturers of the progestin-only (norethindrone) oral contraceptives.
Weight Loss
Minor:
Xelria Fe
The norethindrone in Xelria Fe has a minor potential interaction with Weight Loss.
Progestogens can cause weight gain, which may be significant (as is the case with parenteral medroxyprogesterone) and undesirable in obese patients attempting to lose weight.
More resources
cephradine
A total of 68 drugs are known to interact with cephradine.
- Cephradine is in the drug class first generation cephalosporins.
- Cephradine is used to treat the following conditions:
Xelria Fe
A total of 534 drugs are known to interact with Xelria Fe.
- Xelria fe is in the drug class contraceptives.
- Xelria fe is used to treat Birth Control.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
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