1008 Brief communications
`
`Journal of the
`American Academy of
`Dermatology
`
`Subcutaneous administration of methotrexate
`
`Herschel S. Zackheim, MD San Francisco, California
`
`Two recent reports indicate that subcutaneous
`administration of methotrexate (MTX) has certain
`advantages over the oral and intramuscular routes.
`Balis et al. 1 evaluated subcutaneous versus oral
`MTX in 12 children with leukemia. At a dosage of
`7.5 mg/m 2 peak plasma concentrations for subcu(cid:173)
`taneous and oral administration were approximately
`equal However, at a dosage of 40 mg/m 2, subcuta(cid:173)
`neous injections yielded a considerably higher peak
`plasma concentration . Peak MTX concentration
`and area under the time versus concentration curve
`(AUC) were four and three times higher, respec(cid:173)
`tively, with the subcutaneous as compared with the
`oral route . The injections were well tolerated and
`there was no local toxicity.
`Brooks et al.2 compared the pharmacokinetics of
`MTX in doses up to 25 mg given by the intramus(cid:173)
`cular and subcutaneous routes in five patients with
`rheumatoid arthritis. Serum peak concentration
`values, time to peak concentration, and the AUC
`were not significantly different. The intramuscular
`and subcutaneous routes appeared to be inter(cid:173)
`changeable. Subcutaneous injections were well tol(cid:173)
`erated and less painful than intramuscular ones.
`We have treated 10 patients (seven with psoriasis
`and three with cutaneous T-cell lymphoma [ CTCL])
`with subcutaneous MTX . The injections were given
`in the outer arm with a 25-gauge, % inch needle.
`Nine patients received once-weekly injections and
`one received them on alternate weeks. Doses of 5 mg
`to 87.5 mg were given for periods of 3 to 17 weeks
`(median 13 weeks). Six patients had previously re(cid:173)
`ceived MTX by intramuscular administration.
`All patients had a favorable clinical response to
`the subcutaneous injections and these appeared to be
`similar to those after intramuscular administration.
`Two patients with psoriasis experienced an increase
`
`From the Department of DC1TJJatology1 University of California, San
`Francisco.
`No reprint~ available.
`16/54/35198
`
`in the serum AST level and one had a mild leuko(cid:173)
`penia. One patient with CTCL had oral mucositis.
`However, one patient with psoriasis stated that, al(cid:173)
`though she invariably had nausea after intramuscu(cid:173)
`lar MTX, she had none after subcutaneous admin(cid:173)
`istration. The injections were well tolerated, less
`painful, and easier to administer than when given
`intramuscularly. There was no local reaction. When
`doses more than 50 mg were required, two injection
`sites were used with no greater than 50 mg (2 ml)
`at each site.
`Subcutaneous injections can be self-administered.
`This can be of considerable value for patients who
`require parenteral administration and have diffi(cid:173)
`culty in making weekly office visits. Patients should
`be instructed to use only 1 ml syringes so that gross
`errors in dosage are less likely to occur. Thus doses
`greater than 25 mg require the use of at least two
`syringes.
`The cost of injectable MTX is considerably less
`than the tablets. In a survey of pharmacies in the San
`Francisco-Bay area the average cost of a 2.5 mg
`tablet (Lederle) was $2.87 (range $2.32 to $3.42).
`On the basis of the Lederle 2 ml 50 mg vial (liquid
`preservative protected), the average equivalent cost
`of 2.5 mg ( 0.1 ml) was $0.89 (range $0.65 to $1.24 ).
`Thus the cost of the liquid was approximately 50%
`to 20% that of the tablet. The injectable form is also
`available as a 10 ml (250 mg) vial (Lederle), which
`is about half as expensive per milligram as the 2 ml
`vial. However, this usually needs to be obtained
`through a hospital or clinic~based pharmacy. In ad(cid:173)
`dition, there are competing brands of injectable
`MTX. The need for syringes and needles adds to the
`cost of injectable MTX.
`
`REFERENCES
`I. Balis FM, MirroJ Jr, Reaman GH, et al. Pharmacokinctics
`of subcutaneous methotrexate. J Clin Oncol 1988;6: 1882-6.
`2. Brooks PJ, Spruill WJ, Parish RC, et al. Phamiacokinetics
`of methotrcx.atc administered by intramuscular and subcu(cid:173)
`tanoous injections in patients with rheumatoid arthritis. AI (cid:173)
`lhritis Rheum 1990;33:9 l-4.
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