R S Slavik1, M J Rybak, S A Lerner. 1. College of Pharmacy and Allied Health, Wayne State University, Detroit, MI, USA.
Abstract
OBJECTIVE: To report a case of trimethoprim/sulfamethoxazole (TMP/SMX)-induced tremor responsive to a reduction in dosage. CASE SUMMARY: A 55-year-old white man with AIDS and Pneumocystis carinii pneumonia (PCP) developed a tremor after receiving 5 days of therapy with TMP/SMX 19.4 mg/kg/d (TMP). The tremor resolved completely 3 days after a dosage reduction to TMP/SMX 15.1 mg/kg/d. DISCUSSION: Central nervous system adverse reactions to TMP/SMX have been reported in both the AIDS and non-AIDS populations. To our knowledge, this is the first reported case of TMP/SMX-induced tremor responsive to a reduction in dosage. Pharmacokinetic and clinical data suggest a concentration-dependent etiology for various adverse effects, including tremor. The mechanism of the tremor is unknown; however, toxic metabolites of SMX and disruptions of biogenic amine neurotransmission by TMP have been hypothesized. CONCLUSIONS: TMP/SMX remains the drug of first choice for treating PCP, but it is clearly not well tolerated by patients with AIDS. Concentration-dependent toxicities such as tremor may lead to premature discontinuation of proven, effective TMP/SMX therapy. Using the lower end of the recommended dosing range for TMP/SMX (TMP 15 mg/kg/d) may reduce the incidence of these toxicities while still achieving acceptable TMP concentrations and antimicrobial efficacy.
OBJECTIVE: To report a case of trimethoprim/sulfamethoxazole (TMP/SMX)-induced tremor responsive to a reduction in dosage. CASE SUMMARY: A 55-year-old white man with AIDS and Pneumocystis carinii pneumonia (PCP) developed a tremor after receiving 5 days of therapy with TMP/SMX 19.4 mg/kg/d (TMP). The tremor resolved completely 3 days after a dosage reduction to TMP/SMX 15.1 mg/kg/d. DISCUSSION: Central nervous system adverse reactions to TMP/SMX have been reported in both the AIDS and non-AIDS populations. To our knowledge, this is the first reported case of TMP/SMX-induced tremor responsive to a reduction in dosage. Pharmacokinetic and clinical data suggest a concentration-dependent etiology for various adverse effects, including tremor. The mechanism of the tremor is unknown; however, toxic metabolites of SMX and disruptions of biogenic amine neurotransmission by TMP have been hypothesized. CONCLUSIONS:TMP/SMX remains the drug of first choice for treating PCP, but it is clearly not well tolerated by patients with AIDS. Concentration-dependent toxicities such as tremor may lead to premature discontinuation of proven, effective TMP/SMX therapy. Using the lower end of the recommended dosing range for TMP/SMX (TMP 15 mg/kg/d) may reduce the incidence of these toxicities while still achieving acceptable TMP concentrations and antimicrobial efficacy.