Abstract
The objective of this study was to investigate risk factors for cytopenia when a prophylactic dose of trimethoprim-sulfamethoxazole (TMP-SMX) was co-administered with methotrexate (MTX). Patients who received MTX with or without a prophylactic dose of TMP-SMX were included. Patients who received a therapeutic dose of TMP-SMX were excluded. The MTX-alone and MTX with TMP-SMX groups (MTX group and MTX + TMP-SMX group, respectively) were matched in a 4:1 ratio according to age, creatinine level, mean corpuscular volume and MTX dose. Cytopenia was defined as a haemoglobin level decrease by > 2 g/dl, platelet count of < 150,000/mm3 or white blood cell count of < 3500/mm3. The Cox proportional hazards model was used to evaluate risk factors for cytopenia in patients administered with MTX. The incidence of cytopenia did not significantly differ between the MTX group and MTX + TMP-SMX group (5.0 vs 5.7%, p > 0.999). According to the Cox proportional hazards model, chronic liver disease (hazard ratio [HR] 5.829, 95% confidence interval [CI] 1.211–28.063, p = 0.028) was associated with an increased risk of cytopenia. However, the concomitant use of a prophylactic dose of TMP-SMX (HR 1.717, 95% CI 0.352–8.371, p = 0.504) was not significantly associated with an increased risk of cytopenia. Compared with the use of MTX alone, the concomitant use of MTX with a prophylactic dose of TMP-SMX was not significantly associated with an increased risk of cytopenia. Thus, a prophylactic dose of TMP-SMX can be safely used with MTX.
Similar content being viewed by others
References
Braun J, Rau R (2009) An update on methotrexate. Curr Opin Rheumatol 21(3):216–223. https://doi.org/10.1097/BOR.0b013e328329c79d
Kelley WN (1997) Textbook of rheumatology, 9th edn. Saunders, Philadelphia
Smolen JS, Landewe R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M et al (2017) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 76(6):960–977. https://doi.org/10.1136/annrheumdis-2016-210715
Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC et al (2016) 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken) 68(1):1–25. https://doi.org/10.1002/acr.22783
Manger B, Rech J, Schett G (2010) Use of methotrexate in adult-onset Still’s disease. Clin Exp Rheumatol 28(5 Suppl 61):S168–S171
Yates M, Watts RA, Bajema IM, Cid MC, Crestani B, Hauser T, Hellmich B, Holle JU, Laudien M, Little MA, Luqmani RA, Mahr A, Merkel PA, Mills J, Mooney J, Segelmark M, Tesar V, Westman K, Vaglio A, Yalçındağ N, Jayne DR, Mukhtyar C (2016) EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 75(9):1583–1594. https://doi.org/10.1136/annrheumdis-2016-209133
Masters PA, O’Bryan TA, Zurlo J, Miller DQ, Joshi N (2003) Trimethoprim-sulfamethoxazole revisited. Arch Intern Med 163(4):402–410. https://doi.org/10.1001/archinte.163.4.402
Gutierrez-Urena S, Molina JF, Garcia CO, Cuellar ML, Espinoza LR (1996) Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis. Arthritis Rheum 39(2):272–276. https://doi.org/10.1002/art.1780390214
Poe M (1976) Antibacterial synergism: a proposal for chemotherapeutic potentiation between trimethoprim and sulfamethoxazole. Science 194(4264):533–535. https://doi.org/10.1126/science.788154
Sosin M, Handa S (2003) Low dose methotrexate and bone marrow suppression. BMJ 326(7383):266–267. https://doi.org/10.1136/bmj.326.7383.266
Ng HW, Macfarlane AW, Graham RM, Verbov JL (1987) Near fatal drug interactions with methotrexate given for psoriasis. Br Med J (Clin Res Ed) 295(6601):752–753. https://doi.org/10.1136/bmj.295.6601.752
Maricic M, Davis M, Gall EP (1986) Megaloblastic pancytopenia in a patient receiving concurrent methotrexate and trimethoprim-sulfamethoxazole treatment. Arthritis Rheum 29(1):133–135
al-Awadhi A, Dale P, RJ MK (1993) Pancytopenia associated with low dose methotrexate therapy. A regional survey. J Rheumatol 20(7):1121–1125
Salliot C, van der Heijde D (2009) Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 68(7):1100–1104. https://doi.org/10.1136/ard.2008.093690
Al-Quteimat OM, Al-Badaineh MA (2013) Methotrexate and trimethoprim-sulphamethoxazole: extremely serious and life-threatening combination. J Clin Pharm Ther 38(3):203–205. https://doi.org/10.1111/jcpt.12060
Groenendal H, Rampen FH (1990) Methotrexate and trimethoprim-sulphamethoxazole—a potentially hazardous combination. Clin Exp Dermatol 15(5):358–360. https://doi.org/10.1111/j.1365-2230.1990.tb02113.x
Shimada T, Nishimura Y, Funada Y, Takenaka K, Kobayashi K, Urata Y et al (2004) A case of pneumocystis carinii pneumonia associated with low dose methotrexate treatment for rheumatoid arthritis and trimethoprim-sulphamethoxazole induced pancytopenia. Arerugi 53(6):575–581
Thomas CF Jr, Limper AH (2004) Pneumocystis pneumonia. N Engl J Med 350(24):2487–2498. https://doi.org/10.1056/NEJMra032588
Yale SH, Limper AH (1996) Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc 71(1):5–13. https://doi.org/10.4065/71.1.5
Nicolle LE, Harding GK, Thomson M, Kennedy J, Urias B, Ronald AR (1988) Efficacy of five years of continuous, low-dose trimethoprim-sulfamethoxazole prophylaxis for urinary tract infection. J Infect Dis 157(6):1239–1242. https://doi.org/10.1093/infdis/157.6.1239
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The Institutional Review Board of the Asan Medical Center, Seoul, South Korea, approved this study (IRB No.: 2017-0623).
Disclosures
None.
Rights and permissions
About this article
Cite this article
Kwon, O.C., Lee, J.S., Kim, YG. et al. Safety of the concomitant use of methotrexate and a prophylactic dose of trimethoprim-sulfamethoxazole. Clin Rheumatol 37, 3215–3220 (2018). https://doi.org/10.1007/s10067-018-4005-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-018-4005-6