Drug Interactions between Adoxa TT and methotrexate
This report displays the potential drug interactions for the following 2 drugs:
- Adoxa TT (doxycycline)
- methotrexate
Interactions between your drugs
doxycycline methotrexate
Applies to: Adoxa TT (doxycycline) and methotrexate
MONITOR: Concomitant use of tetracyclines may elevate or reduce serum methotrexate concentrations. Tetracyclines are often highly protein-bound and could displace methotrexate, resulting in higher amounts of free methotrexate and possible toxicity. Individual cases of methotrexate toxicity have been reported with doxycycline and tetracycline. In contrast, it has also been reported that oral antibiotics, such as tetracyclines, may reduce the intestinal absorption of methotrexate or interfere with its enterohepatic circulation by inhibiting bowel flora and suppressing the metabolism of methotrexate by bacteria. While the manufacturer labeling suggests this as a possibility for oral antibiotics only, it is possible for intravenous antibiotics to reach the gut and interfere with bowel flora as well. Therefore, this mechanism of interaction is also possible for intravenously administered antibiotics if they penetrate the intestine and are active against the bacteria involved. However, the clinical significance of this effect has not been established.
MANAGEMENT: If these drugs must be used together, close monitoring for evidence of serious methotrexate toxicity or reduced therapeutic efficacy is recommended. If broad-spectrum antibiotic coverage is needed during methotrexate therapy, the use of an alternate anti-infective may need to be considered.
References
- (2002) "Product Information. Methotrexate (methotrexate)." Lederle Laboratories
- Tortajada-Ituren JJ, Ordovas-Baines JP, Llopis-Salvia P, Jimenez-Torres NV (1999) "High-dose methotrexate-doxycycline interaction." Ann Pharmacother, 33, p. 804-8
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Cerner Multum, Inc. "Australian Product Information."
- (2023) "Product Information. Methotrexate (methotrexate)." Hospira Inc
- (2022) "Product Information. Xerava (eravacycline)." PAION Deutschland GmbH
- (2021) "Product Information. Xerava (eravacycline)." Tetraphase Pharmaceuticals, Inc
- (2022) "Product Information. Methotrexate (methotrexate)." Accord Healthcare Inc
- (2023) "Product Information. Jylamvo (methotrexate)." Esteve Pharmaceuticals Ltd
- Arslan A, Zain MA, Mukhtar M, Ullah W, Roomi S (2019) "Methotrexate and doxycycline interaction: a rare cause of pancytopenia." BMJ Case Rep, 12, e229296
Drug and food interactions
methotrexate food
Applies to: methotrexate
MONITOR: Limited data suggest that consumption of greater than 180 mg/day of caffeine may interfere with the efficacy of methotrexate (MTX) in patients with rheumatoid arthritis. The exact mechanism of interaction is unknown but may be related to the antagonistic effect of caffeine on adenosine receptors, as anti-inflammatory properties of MTX is thought to result from the accumulation of adenosine. In a study of 39 patients treated with MTX 7.5 mg/week (without folate supplementation) for 3 months, patients with high caffeine intake (more than 180 mg/day) experienced significantly less improvement in morning stiffness and joint pain from baseline than patients with low caffeine intake (less than 120 mg/day). There were no significant differences between the responses of patients with moderate caffeine intake (120 to 180 mg/day) and those of the other 2 groups. In an interview of 91 patients treated with MTX, 26% of patients who discontinued the drug were regular coffee drinkers compared to only 2% of those still receiving the drug. Because treatment failure was the reason for MTX discontinuation in 80% of patients who discontinued, the investigators suggested that caffeine may have interfered with MTX efficacy.
MANAGEMENT: Until further information is available, the potential for interaction should be considered in patients who consume substantial amounts of caffeine and caffeine-containing foods and are prescribed methotrexate for rheumatoid arthritis. It may be appropriate to limit caffeine intake if an interaction is suspected in cases of treatment failure.
References
- Nesher G, Mates M, Zevin S (2003) "Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis." Arthritis Rheum, 48, p. 571-572
methotrexate food
Applies to: methotrexate
GENERALLY AVOID: Coadministration of methotrexate with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Methotrexate, especially at higher dosages or during prolonged treatment, has been associated with severe hepatotoxicity including acute hepatitis, chronic fibrosis, cirrhosis, and fatal liver failure.
MANAGEMENT: The risk of hepatic injury should be considered when methotrexate is used with other potentially hepatotoxic agents (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Baseline and periodic monitoring of hepatic function is recommended, while liver biopsy may be warranted during long-term use of methotrexate. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, pale stools, and jaundice.
References
- (2002) "Product Information. Methotrexate (methotrexate)." Lederle Laboratories
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2023) "Product Information. Methotrexate (methotrexate)." Hospira Inc
doxycycline food
Applies to: Adoxa TT (doxycycline)
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.
methotrexate food
Applies to: methotrexate
MONITOR: Limited data suggest that consumption of greater than 180 mg/day of caffeine may interfere with the efficacy of methotrexate (MTX) in patients with rheumatoid arthritis. The exact mechanism of interaction is unknown but may be related to the antagonistic effect of caffeine on adenosine receptors, as anti-inflammatory properties of MTX is thought to result from the accumulation of adenosine. In a study of 39 patients treated with MTX 7.5 mg/week (without folate supplementation) for 3 months, patients with high caffeine intake (more than 180 mg/day) experienced significantly less improvement in morning stiffness and joint pain from baseline than patients with low caffeine intake (less than 120 mg/day). There were no significant differences between the responses of patients with moderate caffeine intake (120 to 180 mg/day) and those of the other 2 groups. In an interview of 91 patients treated with MTX, 26% of patients who discontinued the drug were regular coffee drinkers compared to only 2% of those still receiving the drug. Because treatment failure was the reason for MTX discontinuation in 80% of patients who discontinued, the investigators suggested that caffeine may have interfered with MTX efficacy.
MANAGEMENT: Until further information is available, the potential for interaction should be considered in patients who consume substantial amounts of caffeine and caffeine-containing foods and are prescribed methotrexate for rheumatoid arthritis. It may be appropriate to limit caffeine intake if an interaction is suspected in cases of treatment failure.
References
- Nesher G, Mates M, Zevin S (2003) "Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis." Arthritis Rheum, 48, p. 571-572
doxycycline food
Applies to: Adoxa TT (doxycycline)
Chronic alcohol consumption may enhance the elimination of doxycycline. The mechanism is induction of hepatic microsomal enzymes by alcohol. In one study, the half-life of doxycycline in six alcoholics was 10.5 hours, compared with 14.7 hours in six control patients. In addition, half the alcoholic patients had serum concentrations below what is generally considered the minimum therapeutic concentration (0.5 mcg/mL) at 12 to 24 hours after the dose. The investigators suggest that twice-a-day dosing may be indicated in these patients, especially if additional inducing drugs are used. The elimination of other tetracyclines probably is not affected by alcohol consumption.
References
- Neuvonen PJ, Penttila O, Roos M, Tirkkonen J (1976) "Effect of long-term alcohol consumption on the half-life of tetracycline and doxycycline in man." Int J Clin Pharmacol Biopharm, 14, p. 303-7
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.
See also
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
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Check Interactions
To view an interaction report containing 4 (or more) medications, please sign in or create an account.
Save Interactions List
Sign in to your account to save this drug interaction list.