Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Orthoclone OKT3 (Ortho Biotech Inc, Raritan, NJ) is a potent immunosuppressive agent effective in the therapy of acute renal allograft rejection. Following the first one or two doses, patients often exhibit a "flu-like" illness ascribed to OKT3-induced release of cytokines. Systemic reactions resulting from the cytokines include pyrexia, pulmonary edema, bronchospasm, photophobia, headache, hypotension, rigors, hypertension, gastrointestinal disturbances, and arthralgias/myalgias. The cyclooxygenase inhibitor indomethacin has been shown to ameliorate the pyrexia associated with OKT3 administration. We conducted a retrospective analysis with the purposes of (1) confirming that indomethacin reduces pyrexia and (2) determining the effect of indomethacin on the other aforementioned adverse side effects. Group 1 patients (n = 28) received indomethacin during the initial 48 hours of OKT3 antirejection therapy. Group 2 patients (n = 28) received OKT3 without indomethacin. The incidence of fever (P < 0.0001), headache (P < 0.030), and gastrointestinal disturbances (P < 0.030), and the number of adverse effects (P < 0.0001) were significantly less in the indomethacin-treated group. There were no differences between the groups in pre- and post-OKT3 serum creatinine levels. The indomethacin was well tolerated. We conclude that the widely available and relatively inexpensive cyclooxygenase inhibitor indomethacin safely and significantly reduces adverse effects associated with OKT3 therapy of acute renal allograft rejection.
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PMID:A retrospective analysis of the effect of indomethacin on adverse reactions to orthoclone OKT3 in the therapy of acute renal allograft rejection. 807 74

Muromonab CD3 (OKT3), the murine anti-CD3 monoclonal antibody (mAb) of the IgG-2a class, directed against the CD3 molecule on the surface of human T cells, has proven to be a powerful immunosuppressive agent in solid organ transplantation and has been shown to be superior to high-dose steroids as first-line treatment of acute allograft rejection. It is comparable to antithymocyte globulin (ATG) in treating steroid-resistant rejection and it is also effective as rescue treatment in ATG-resistant rejection. However, OKT3 treatment is followed by a substantial percentage of re-rejections, most of which respond well to steroids. In the early post-transplant period, a prophylactic course of OKT3 can delay the onset of acute rejection, in particular in immunologically high-risk patients. First-dose-related adverse effects (pyrexia, dyspnoea, headache, nausea, vomiting and diarrhoea) of OKT3 are severe, but usually transient and seldom life-threatening, provided overhydration has been corrected and steroids have been given before the first administration. These adverse effects are partly attributed to the release of cytokines as a result of mononuclear cell activation. In addition, complement activation and subsequent activation of neutrophils may play a role in their pathogenesis. After exposure of patients to OKT3 an increased incidence of infections and malignancies has been reported. However, most likely this merely reflects the total burden of immunosuppression. Xenosensitisation represents an important limitation to OKT3 treatment, although a second or third course can still be effective in patients with low antibody titres. In practice, the initiation of OKT3 treatment should be preceded by correction of overhydration, if necessary by means of dialysis or ultrafiltration. According to the instructions from the manufacturer the first dose of OKT3 is preceded by paracetamol (acetaminophen), an antihistamine and intravenous (IV) corticosteroids, in an attempt to mitigate the first dose-related symptoms. A regimen consisting of administration of 2 IV doses of 250mg methylprednisolone, given 6 hours and 1 hour before the first OKT3 injection, followed by a 2-hour infusion of OKT3, is most effective in diminishing OKT3-induced adverse effects.
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PMID:Guidelines for the optimal use of muromonab CD3 in transplantation. 1803 Nov 37