High-dose intravenous

Empirical therapy for postoperative infections in neurosurgical patients (including patients with CSF shunts) should include vancomycin in combination with either cefepime, ceftazidime, or meropenem. Linezolid has been reported to reach adequate CSF concentrations and resolve cases of meningitis refractory to vancomycin.35 However, data with linezolid are limited. The addition of rifampin should be considered for treatment of shunt infections. When culture and sensitivity data are available, pathogen-directed antibiotic therapy should be administered. Removal of infected devices is desirable aggressive antibiotic therapy (including high-dose intravenous antibiotic therapy plus intraventricular vancomycin and/or tobramycin) may be effective for patients in whom hardware removal is not possible.36... 

Based on patient-specific data, local resistance patterns, and other relevant data, design an appropriate empirical antimicrobial regimen directed at the most likely pathogens empirical regimens should consist of high-dose intravenous cidal therapy. 

TesarGE, Murray GB, Cassem NH. Use of high-dose intravenous haloperidol in the treatment of agitated cardiac patients. J Clin Psychopharmacol 1985 5 344-347. 

LePage GA, Whitecar JP. Pharmacology of 6-thioguaninc in man. Cancer Res 1971 31 1627-1631. Konits PH, Egorin MJ, Van Echo DA et al. Phase II evaluation and plasma pharmacokinetics of high-dose intravenous 6-thioguanine in patients with colorectal carcinoma. Cancer Chemother Pharmacol 1982 8 199-203. 

Costedoat-Chalumeau N, Amoura Z, Aymard G, Sevin O, Wechsler B, Du Cacoub PLT, Diquet B, Ankri A, Piette JC. Potentiation of vitamin K antagonists by high-dose intravenous methylprednisolone. Ann Intern Med 2000 132(8) 631-5. 

Hisamatsu H, Sakai H, Kanetake H. High-dose intravenous diethylstilbestrol diphosphate (DES-DP) in the treatment of prostatic cancer during relapse. Nioshinihon J Urol 2002 64 199-202. 

Michinaga S, Ariyoshi A. High-dose intravenous diethylstilbestrol diphosphate therapy for hormone-refractory prostate cancer. Nishinihon J Urol 2002 64 203-5. 

Sensky PR, Olczak SA. High-dose intravenous glucagon in severe tricyclic poisoning. Postgrad Med J 1999 75(888) 611-2. 

Oral verapamil has been shown to increase peak plasma levels, prolong the terminal half-life, and increase the volume of distribution at steady state of doxorubicin (282). Gigante et al. (283) performed similar studies in which the pharmacokinetics of doxorubicin in combination with verapamil given at high doses intravenously were followed for 17 patients with advanced neoplasms. The steady-state concentration and systemic and renal clearances were found to be statistically similar for various doses of verapamil and doxorubicin, and for doxorubicin administered alone. 

Lithium gamolenate, a compound with in vitro antitumor activity, given intravenously or orally, was ineffective in treating advanced pancreatic adenocarcinoma (n = 278) (52). Adverse effects attributed to lithium (type unspecified) were reported in two of 93 in the oral group (mean serum lithium 0.15 mmol/1), five of 90 with low-dose intravenous administration (mean serum lithium 0.4 mmol/1), and seven of 95 with the high-dose intravenous administration (mean serum lithium 0.8 mmol/1). 

Manfredi PL, Gonzales GR, Payne R. Reversible spastic paraparesis induced by high-dose intravenous methadone. J Pain 2001 2(l) 77-9. 

SLE appears to be steroid responsive only in the early coiu se of the disease. Optic atrophy occiu s in untreated cases, with the development of permanent visual field defects. Therapy includes high-dose intravenous methyl-prednisolone, oral prednisone, or steroid-sparing medications such as mycophenolate mofetil (CellCept). A rheumatology referral is also advised. 

Theis JG, Liau-Chu M, Chan HS, Doyle J, Greenberg ML, Koren G. Anaphylactoid reactions in children receiving high-dose intravenous cyclosporine for reversal of tumor resistance The causative role of improper dissolution of Cremophor EL. J Clin Oncol 1995 13 2508-16. 

Brown RH Jr, Hauser SL, Harrington H, Weiner HL (1986) Failure of immunosuppression widi a ten- to 14-day course of high-dose intravenous cyclophosphamide to alter die progression of amyotrophic lateral sclerosis. Arch Neurol 43 383—384. 

The frequencies of severe adverse effects of aldesleukin (7) are listed in Table 1 and the most frequent reasons for withdrawal of high-dose intravenous aldesleukin in Table 2. 

Table 2 The most frequent reasons for withdrawal of high-dose intravenous aldesleukin...

Among 199 patients with metastatic melanoma or renal cell carcinoma treated with high-dose intravenous bolus aldesleukin, there was severe respiratory distress in 3.2% of treatment courses, but intubation was required in only one (24). This is far less common than earlier estimates... 

Hematological toxicity was analysed in 199 patients treated with a high-dose intravenous bolus aldesleukin regimen for metastatic melanoma or renal cell carcinoma (60). Anemia requiring transfusions was noted in 14% of all treatment courses and severe thrombocytopenia occurred in 2.2%, with three patients suffering from serious hemorrhages. Severe leukopenia was infrequent and not associated with infectious episodes. Early transient lymphopenia (93% reduction) was followed by rebound lymphocytosis up to 198% above baseline values. Except for severe thrombocytopenia, treatment withdrawal was... 

Choy EH, Panayi GS, Emery P, Madden S, Breedveld EC, Kraan MC, Kalden JR, Rascu A, Brown JC, Rapson N, Johnston JM. Repeat-cycle study of high-dose intravenous 4162W94 anti-CD4 humanized monoclonal antibody in rheumatoid arthritis. A randomized placebo-controUed trial. Rheumatology (Oxford) 2002 41(10) 1142-8. 

Scheule AM, Beierlein W, Wendel HP, Jurmann MJ, Eckstein FS, Ziemer G. Aprotinin in fibrin tissue adhesives induces specific antibody response and increases antibody response of high-dose intravenous application. J Thorac Cardiovasc Surg 1999 118(2) 348-53. 

While in large series of several thousands of patients, neutropenia has generally been reported as an adverse effect in under 0.1-1.0% (SEDA-13, 212), an overview in 1985 estimated that neutropenia (neutrophil count below 1.0 X 10 /1) occurs in up to 15% of all patients treated with high-dose intravenous beta-lactam antibiotics for more than 10 days (26). In subsequent series of patients treated for several weeks with various beta-lactam antibiotics, up to 25% developed neutropenia (5,21,67-69). 

Varescon I, Vidal-Trecan G, Nabet N, Boissonnas A. Substitution et mesusage I injection intraveineuse de buprenorphine haut dosage. [Buprenorphine abuse high dose intravenous administration of buprenorphine.] Encephale 2002 28(5 Pt 1) 397 02. 

During a Phase I/II trial of high-dose intravenous ciclosporin, there was a high incidence of anaphylactoid reactions associated with improper mixing during preparation of the infusions, perhaps due to large initial bolus infusions of the vehicle, Cremophor EL (174). 

Liau-Chu M, Theis JG, Koren G. Mechanism of anaphylactoid reactions improper preparation of high-dose intravenous cyclosporine leads to bolus infusion of Cremophor EL and cyclosporine Ann Pharmacother 1997 31(11) 1287-91. 

Potentiation of the effects of vitamin K antagonists by high-dose intravenous methylprednisolone has been prospectively studied in 10 consecutive patients and 5 controls after the observation of a sharp increase in the International Normalized Ratio (INR) in a patient taking oral anticoagulation after concomitant administration of methylprednisolone (1 g/day for 3 days) (262). The mean INR was 2.8 (range 2.0-3.8) at baseline and increased to 8.0 (5.3-20). The maximum increase in INR occurred after a mean of 93 (29-156) hours. The coumarins taken by these patients were fluindione in eight and acenocoumarol in two. The prothrombin time in the controls... 

Baker DL, Manno CS. Rapid excretion of gaUium-67 isotope in an iron-overloaded patient receiving high-dose intravenous deferoxamine. Am J Hematol 198829(4) 230-2. 

Erythromycin has antidysrhythmic properties similar to those of Class lA antidysrhythmic drugs, and causes an increase in atrial and ventricular refractory periods. This is only likely to be a problem in patients with heart disease or in those who are receiving drugs that delay ventricular repolarization (5). High-doses intravenously have caused ventricular fibrillation and torsade de pointes (6). Each episode of dysrhythmia, QT interval prolongation, and myocardial dysfunction occurred 1-1.5 hours after erythromycin infusion and resolved after withdrawal. 

Emanuel D, Cunningham 1, Jules-Elysee K, Brochstein JA, Kernan NA, Laver J, Stover D, White DA, Fels A, Polsky B, et al. Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin. Ann Intern Med I988 I09(I0) 777-82. 

Lame GA, Hossain SM, Solis RT, Adams SC. Polyethylene glycol nephrotoxicity secondary to prolonged high-dose intravenous lorazepam. Ann Pharmacother 1995 29(11) 1110-14. 

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