trimethoprim--sulfamethoxazole-drug-combination and Tremor

Topics: Adult; AIDS-Related Opportunistic Infections; Follow-Up Studies; Humans; Male; Pneumonia, Pneumocystis; Tremor; Trimethoprim, Sulfamethoxazole Drug Combination

: We describe a female patient who was an extensive metabolizer of cytochrome P450 isoenzyme (CYP) 2D6 and an intermediate metabolizer of CYP2C19 (genotype: CYP2C19 *1/*2). She exhibited high serum concentrations of venlafaxine and O-desmethylvenlafaxine and developed severe tremor after comedication with cotrimoxazole (sulfamethazole/trimethoprim). Venlafaxine is mainly metabolized by O- and N-demethylation. O-demethylation is catalyzed by the highly polymorphic CYP2D6 and N-demethylation by several enzymes, CYP2C19, CYP2C9, and CYP3A4. The observed overall pharmacokinetic effect was most probably the result of decreased N-demethylation of venlafaxine by (1) reduced expression of CYP2C19 due to a genetic deficit and (2) inhibition of CYP2C9 by cotrimoxazole.

Topics: Anti-Infective Agents; Aryl Hydrocarbon Hydroxylases; Cyclohexanols; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Depressive Disorder, Major; Drug Interactions; Female; Humans; Middle Aged; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Tremor; Trimethoprim, Sulfamethoxazole Drug Combination; Venlafaxine Hydrochloride

A 1.5-year-old girl developed high frequency tremors and chorea after receiving a dose of 120 mg/kg/d trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of Pneumocystis pneumonia. The child was human immunodeficiency virus-negative but immunocompromised because of prolonged immunosuppressive therapy. These symptoms disappeared 3 days after TMP-SMX was discontinued. Pediatricians should be aware of tremors and chorea among the potential adverse effects of high doses of TMP-SMX.

Topics: Anti-Infective Agents; Chorea; Female; Humans; Infant; Pneumonia, Pneumocystis; Tremor; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Arthritis; Chronic Disease; Diarrhea; Duodenum; Gastrointestinal Transit; Humans; Intestinal Mucosa; Male; Middle Aged; Tomography, X-Ray Computed; Treatment Outcome; Tremor; Trimethoprim, Sulfamethoxazole Drug Combination; Ultrasonography; Whipple Disease

Trimethoprim-sulfamethoxazole (TMP-SMX) is a widely administered antibiotic that is well tolerated by most patients. Hypersensitivity reactions and gastrointestinal intolerance are the most common adverse events associated with it. Central nervous system adverse effects such as tremors are less common and occur primarily in patients with acquired immune deficiency syndrome. A 29-year-old immunocompetent man developed a tremor while taking TMP-SMX. The tremor resolved within 2 days after the drug was discontinued.

Topics: Adult; Anti-Infective Agents; Enterobacteriaceae Infections; Humans; Immunocompetence; Male; Postoperative Complications; Tremor; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Tremor; Trimethoprim, Sulfamethoxazole Drug Combination

A child with dihydropteridine reductase (DHPR) deficiency developed signs of dopamine insufficiency after being given trimethoprim-sulfamethoxazole (TMP-SMX). She recovered function after the antibiotic was stopped, which suggests that it adversely influenced dopamine metabolism in the CNS. The authors speculate that TMP, a dihydrofolate reductase inhibitor, was the major cause of the patient's deterioration, and suggest that it and other dihydrofolate inhibitors, notably methotrexate, are contra-indicated for patients with DHPR deficiency.

Topics: Child, Preschool; Dopamine; Epinephrine; Female; Humans; NADH, NADPH Oxidoreductases; Norepinephrine; Phenylalanine; Phenylketonurias; Sinusitis; Tremor; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; Ataxia; Drug Combinations; Drug Eruptions; Emotions; Humans; Male; Pneumonia, Pneumocystis; Reflex, Abnormal; Sulfamethoxazole; Tremor; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination