INFO - Medscape: interaction between MTX and penicillins

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Severe Interaction: Methotrexate/Penicillins

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discontinuing any drug or commencing any course of treatment.

MONOGRAPH TITLE: Methotrexate/Penicillins

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the

risk of severe adverse interaction.

MECHANISM OF ACTION: Penicillins may compete with the renal tubular

secretion of methotrexate.

CLINICAL EFFECTS: The concurrent use of methotrexate and penicillins

may result in elevated levels of methotrexate and methotrexate

toxicity.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving concurrent therapy with

methotrexate and penicillins should be monitored closely for elevated

methotrexate levels and methotrexate toxicity. The dose and duration

of leucovorin rescue therapy may need to be increased.

DISCUSSION: Elevated methotrexate levels, signs of methotrexate

toxicity, and death have been reported following the concurrent use of

methotrexate (both low dose and high dose) and penicillin derivatives.

In a patient being treated with high-dose methotrexate (8 G/m2), the

concurrent use of amoxicillin resulted in a 56% decrease in the

clearance of methotrexate and signs of methotrexate toxicity.(1) There

are two cases of methotrexate toxicity following the addition of

amoxicillin to low-dose methotrexate therapy (7.5 mg-10 mg weekly) for

psoriasis. In another case, a patient was found to have a toxic

methotrexate level 12 days after her last dose of weekly methotrexate

(7.5 mg). The patient had been treated with amoxicillin followed by

flucloxacillin.(2)

In a case report, dicloxacillin decreased methotrexate clearance 93%.(4)

Flucloxacillin was shown to increase the area-under-curve (AUC) of

methotrexate by 7.3% in a study in 10 subjects.(5) In a case report, a

patient on low-dose methotrexate (5 mg) developed methotrexate

pneumonia following the addition of flucloxacillin to his regimen.(5)

In a patient being treated with high-dose methotrexate (12 G/m2), the

concurrent use of mezlocillin increased the half-life of methotrexate

from 10.1 to 27.2 hours.(6)

In a case report, a patient developed methotrexate toxicity following

the addition of penicillin V potassium to his methotrexate (50 mg

weekly).(7)

In a case report, penicillin decreased methotrexate clearance 36%.(4)

In one report, leucovorin rescue therapy had to be continued for 192

hours following the concurrent use of methotrexate (3 G/m2) and

piperacillin. During cycles without concurrent piperacillin,

leucovorin rescue therapy was only required for 72 hours.(8) There are

two reports of neutropenia and death following the concurrent use of

piperacillin and low-dose methotrexate (2.5 mg three times weekly in

one patient, 5 mg weekly in another) for psoriasis. One of these

patients also received flucloxacillin. (3) In another case report, the

concurrent use of piperacillin decreased methotrexate clearance by

67%.(4)

In a case report, ticarcillin decreased methotrexate clearance by 60%.(4)

REFERENCES:

1.Ronchera CL, T, Peris JE, F, Granero L, Jimenez NV,

Pla JM. Pharmacokinetic interaction between high-dose methotrexate and

amoxycillin. Ther Drug Monit 1993 Oct;15(5):375-9.

2.Engelbrecht JA, Calhoon SL, Scherrer JJ. Methotrexate pneumonitis

after low-dose therapy for rheumatoid arthritis. Arthritis Rheum 1983

Oct; 26(10):1275-8.

3.Mayall B, Poggi G, Parkin JD. Neutropenia due to low-dose

methotrexate therapy for psoriasis and rheumatoid arthritis may be

fatal. Med J Aust 1991 Oct 7;155(7):480-4.

4.Bloom EJ, Ignoffo RJ, Reis CA, Cadman E. Delayed clearance (CL) of

methotrexate (MTX) associated with antibiotics and antiinflammatory

agents. Clin Res 1986;34(2):560A.

5.Herrick AL, Grennan DM, Griffen K, s L, Gifford LA. Lack of

interaction between flucloxacillin and methotrexate in patients with

rheumatoid arthritis. Br J Clin Pharmacol 1996 Mar;41(3):223-7.

6.Dean R, Nachman J, Lorenzana AN. Possible methotrexate-mezlocillin

interaction. Am J Pediatr Hematol Oncol 1992 Spring;14(1):88-9.

7.Nierenberg DW, Mamelok RD. Toxic reaction to methotrexate in a

patient receiving penicillin and furosemide: a possible interaction.

Arch Dermatol 1983 Jun;119(6):449-50.

8.Yamamoto K, Sawada Y, Matsushita Y, Moriwaki K, Bessho F, Iga T.

Delayed elimination of methotrexate associated with piperacillin

administration. Ann Pharmacother 1997 Oct;31(10):1261-2.

http://www.medscape.com/druginfo/monoinfobyid?cid=med & monotype=druginter & monoid=\

1112 & mononame=PENICILLINS%2FMETHOTREXATE & drugid=1531 & drugname=Amoxicillin+Oral & i\

ntertype=server

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