Drug Interaction Report
6 potential interactions and/or warnings found for the following 2 drugs:
- LevomefolatePNV (multivitamin, prenatal)
- Pylera (bismuth subcitrate potassium / metronidazole / tetracycline)
Interactions between your drugs
tetracycline multivitamin, prenatal
Applies to: Pylera (bismuth subcitrate potassium / metronidazole / tetracycline), LevomefolatePNV (multivitamin, prenatal)
GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration. Therapeutic failure may result. The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%. In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%. Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg. Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline. Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally. It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.
MANAGEMENT: Coadministration of a tetracycline with any iron-containing product should be avoided if possible. Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.
References
- Neuvonen PJ (1976) "Interactions with the absorption of tetracyclines." Drugs, 11, p. 45-54
- Gothoni G, Neuvonen PJ, Mattila M, Hackman R (1972) "Iron-tetracycline interaction: effect of time interval between the drugs." Acta Med Scand, 191, p. 409-11
- Venho VM, Salonen RO, Mattila MJ (1978) "Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal." Eur J Clin Pharmacol, 14, p. 277-80
- (2002) "Product Information. Minocin (minocycline)." Lederle Laboratories
- Campbell NR, Hasinoff BB (1991) "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol, 31, p. 251-5
- Bateman FJ (1970) "Effects of tetracyclines." Br Med J, 4, p. 802
- Neuvonen PJ, Gothoni G, Hackman R, Bjorksten K (1970) "Interference of iron with the absorption of tetracyclines in man." Br Med J, 4, p. 532-4
- Greenberger NJ (1971) "Absorption of tetracyclines: interference by iron." Ann Intern Med, 74, p. 792-3
- Neuvonen PJ, Penttila O (1974) "Effect of oral ferrous sulphate on the half-life of doxycycline in man." Eur J Clin Pharmacol, 7, p. 361-3
- (2018) "Product Information. Seysara (sarecycline)." Allergan Inc
- (2018) "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc.
tetracycline bismuth subcitrate potassium
Applies to: Pylera (bismuth subcitrate potassium / metronidazole / tetracycline), Pylera (bismuth subcitrate potassium / metronidazole / tetracycline)
ADJUST DOSING INTERVAL: Administration of a bismuth-containing preparation within two to three hours of a tetracycline may significantly decrease serum tetracycline concentrations. Data are available for tetracycline and doxycycline. The proposed mechanism is chelation of tetracycline by bismuth.
MANAGEMENT: Administration of a tetracycline and bismuth-containing preparation should be separated by two to three hours. Patients should be monitored for diminished tetracycline efficacy.
References
- Ericsson CD, Feldman S, Pickering LK, Cleary TG (1982) "Influence of subsalicylate bismuth on absorption of doxycycline." JAMA, 247, p. 2266-7
- Albert KS, Welch RD, DeSante KA, DiSanto AR (1979) "Decreased tetracycline bioavailability caused by a bismuth subsalicylate antidiarrheal mixture." J Pharm Sci, 68, p. 586-8
- (2018) "Product Information. Seysara (sarecycline)." Allergan Inc
- (2018) "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc.
Drug and food interactions
metroNIDAZOLE food
Applies to: Pylera (bismuth subcitrate potassium / metronidazole / tetracycline)
CONTRAINDICATED: Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients. There have been a few case reports involving metronidazole, although data overall are not convincing. The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by metronidazole in a manner similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. However, some investigators have questioned the disulfiram-like properties of metronidazole. One study found neither elevations in blood acetaldehyde nor objective or subjective signs of a disulfiram-like reaction to ethanol in six subjects treated with metronidazole (200 mg three times a day for 5 days) compared to six subjects who received placebo.
MANAGEMENT: Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction. Consumption of alcoholic beverages and products containing propylene glycol is specifically contraindicated during and for at least 3 days after completion of metronidazole and benznidazole therapy according to their product labeling.
References
- Giannini AJ, DeFrance DT (1983) "Metronidazole and alcohol: potential for combinative abuse." J Toxicol Clin Toxicol, 20, p. 509-15
- Alexander I (1985) "Alcohol-antabuse syndrome in patients receiving metronidazole during gynaecological treatment." Br J Clin Pract, 39, p. 292-3
- Harries DP, Teale KF, Sunderland G (1990) "Metronidazole and alcohol: potential problems." Scott Med J, 35, p. 179-80
- (2001) "Product Information. Flagyl (metronidazole)." Searle
- Edwards DL, Fink PC, Van Dyke PO (1986) "Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole." Clin Pharm, 5, p. 999-1000
- Williams CS, Woodcock KR (2000) "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother, 34, p. 255-7
- Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP (2002) "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother, 36, p. 971-4
- Krulewitch CJ (2003) "An unexpected adverse drug effect." J Midwifery Womens Health, 48, p. 67-8
- (2017) "Product Information. Benznidazole (benznidazole)." Everett Laboratories Inc
tetracycline food
Applies to: Pylera (bismuth subcitrate potassium / metronidazole / tetracycline)
ADJUST DOSING INTERVAL: Administration with food, particularly dairy products, significantly reduces tetracycline absorption. The calcium content of these foods forms nonabsorbable chelates with tetracycline.
MANAGEMENT: Tetracycline should be administered one hour before or two hours after meals.
References
- (2001) "Product Information. Achromycin (tetracycline)." Lederle Laboratories
- (2001) "Product Information. Declomycin (demeclocycline)." Lederle Laboratories
multivitamin, prenatal food
Applies to: LevomefolatePNV (multivitamin, prenatal)
ADJUST DOSING INTERVAL: Concomitant use of some oral medications may reduce the bioavailability of orally administered iron, and vice versa.
Food taken in conjunction with oral iron supplements may reduce the bioavailability of the iron. However, in many patients intolerable gastrointestinal side effects occur necessitating administration with food.
MANAGEMENT: Ideally, iron products should be taken on an empty stomach (i.e., at least 1 hour before or 2 hours after meals), but if this is not possible, administer with meals and monitor the patient more closely for a subtherapeutic effect. Some studies suggest administration of iron with ascorbic acid may enhance bioavailability. In addition, administration of oral iron products and some oral medications should be separated whenever the bioavailability of either agent may be decreased. Consult the product labeling for specific separation times and monitor clinical responses as appropriate.
References
- "Product Information. Feosol (ferrous sulfate)." SmithKline Beecham
- (2021) "Product Information. Accrufer (ferric maltol)." Shield Therapeutics
tetracycline food
Applies to: Pylera (bismuth subcitrate potassium / metronidazole / tetracycline)
GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration. Therapeutic failure may result. The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%. In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%. Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg. Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline. Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally. It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.
MANAGEMENT: Coadministration of a tetracycline with any iron-containing product should be avoided if possible. Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.
References
- Neuvonen PJ (1976) "Interactions with the absorption of tetracyclines." Drugs, 11, p. 45-54
- Gothoni G, Neuvonen PJ, Mattila M, Hackman R (1972) "Iron-tetracycline interaction: effect of time interval between the drugs." Acta Med Scand, 191, p. 409-11
- Venho VM, Salonen RO, Mattila MJ (1978) "Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal." Eur J Clin Pharmacol, 14, p. 277-80
- (2002) "Product Information. Minocin (minocycline)." Lederle Laboratories
- Campbell NR, Hasinoff BB (1991) "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol, 31, p. 251-5
- Bateman FJ (1970) "Effects of tetracyclines." Br Med J, 4, p. 802
- Neuvonen PJ, Gothoni G, Hackman R, Bjorksten K (1970) "Interference of iron with the absorption of tetracyclines in man." Br Med J, 4, p. 532-4
- Greenberger NJ (1971) "Absorption of tetracyclines: interference by iron." Ann Intern Med, 74, p. 792-3
- Neuvonen PJ, Penttila O (1974) "Effect of oral ferrous sulphate on the half-life of doxycycline in man." Eur J Clin Pharmacol, 7, p. 361-3
- (2018) "Product Information. Seysara (sarecycline)." Allergan Inc
- (2018) "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc.
Therapeutic duplication warnings
No duplication 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.
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. |
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