Amphotericin follow

A 50-year-old male heroin user developed Candida parapsilosis infection and was given amphotericin followed by long-term oral voriconazole 200 mg bd after 5 months he developed a non-pruritic, non-tender, erythematous, macular eruption on sun-exposed skin areas, particularly on the face, neck, and hands [47 ]. The photosensitivity reaction resolved over 6 weeks after fluconazole was substituted for voriconazole. 

The final stages of the successful drive towards amphotericin B (1) are presented in Scheme 19. Thus, compound 9 is obtained stereoselectively by sodium borohydride reduction of heptaenone 6a as previously described. The formation of the desired glycosida-tion product 81 could be achieved in dilute hexane solution in the presence of a catalytic amount PPTS. The by-product ortho ester 85 was also obtained in approximately an equimolar amount. Deacetylation of 81 at C-2, followed sequentially by oxidation and reduction leads, stereoselectively, to the desired hydroxy compound 83 via ketone 82. The configuration of each of the two hydroxylbearing stereocenters generated by reduction of carbonyls as shown in Scheme 19 (6—>9 and 82->83) were confirmed by conversion of 83 to amphotericin B derivative 5 and comparison with an... 

Mr. Carr is receiving amphotericin B for a systemic fungal infection. Which of the following would most likely indicate to tiie nurse that Mr. Carr is experiencing an adverse reaction to amphotericin B ... 

Kullberg BJ, Sobel JD, Ruhnke M, et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients a randomised non-inferiority trial. Lancet 2005 366 1435-1442. 

Due to the high relapse rate following acute therapy for C. neoformans, AIDS patients require lifelong maintenance or suppressive therapy. The standard of care for AIDS-associated cryptococcal meningitis is primary therapy, generally using amphotericin B with or without flucytosine followed by maintenance therapy with fluconazole for the fife of the patient. 

Disseminated histoplasmosis Acute (Infantile) Subacute Progressive histoplasmosis (immunocompetent patients and immunosuppressed patients without AIDS) 0.02-0.05 Disseminated histoplasmosis Untreated mortality 83% to 93% relapse 5% to 23% in non-AIDS patients therapy is recommended tor all patients Nonimmunosuppressedpatients Ketoconazole 400 mj day orally x 6-12 months or amphotericin B 35 mg/kg IV Immunosuppressed patients (non-AIDS) or endocarditis or CNS disease Amphotericin B >35 mg/kg x 3 months followed by fluconazole or itraconazole 200 mg orally twice daily x 12 months Life-threatening disease Amphotericin B 0.7-1 mg/kg/day IV for a total dosage of 35 mj kg over 2-4 months once the patient is afebrile, able to take oral medications, and no longer requires blood pressure or ventilatory support therapy can be changed to itraconazole 200 mg orally twice daily for 6-18 months Non-life-threatening disease Itraconazole 200-400 mg orally daily for 6-18 months fluconazole therapy 400-800 mg daily should be reserved for patients intolerant to itraconazole, and the development of resistance can lead to relapses... 

Progressive disease of AIDS 25-50e Amphotericin B 15-30 mg/kg (1 -2 g over 4-10 weeks/ or itraconazole 200 mg three times daily for 3 days then twice daily for 12 weeks, followed by lifelong suppressive therapy wilh ihaconazole 200-400 mg orally daily. Although patients receiving secondary prophylaxis (chronic maintenance therapy) might be at low risk for recurrence of systemic mycosis when their CD4+ T-lymphocyte counts increase to >100 cells/ microliter in response to HAART, the number of patents who have been evaluated is insufficient to warrant a recommendation to discontinue prophylaxis. 

The combination of amphotericin B with flucytosine for 6 weeks is often used for treatment of cryptococcal meningitis. An alternative is amphotericin B for 2 weeks followed by fluconazole for an additional 8 to 10 weeks. Suppressive therapy with fluconazole 200 mg/day for 6 to 12 months is optional. 

Cryptococcemia wilh positive serum antigen titer (>1 8), cutaneous infection, a positive urine culture, or prostatic disease Recurrent or progressive disease not responsive to amphotericin B Isolated pulmonary disease (without evidence of CNS infection) Clinician must decide whether to follow the pulmonary therapeutic regimen or the CNS (disseminated) regimen Amphotericin Brf IV 0.5-0.75 mj kj day intrathecal amphotericin B 0.5 mg 2-3 times weekly Mild to moderate symptoms or asymptomatic with a positive pulmonary specimen Fluconazole 200-400 mg orally daily x lifelong or Itraconazole 200-400 mg orally daily x lifelong or... 

CNS disease acute (induction/con-solidation therapy) (follow all regimens with suppressive therapy) Fluconazole 400 mg orally daily + flucytosine 100-150 mg/kg/ day orally x l o weeks Severe disease Amphotericin B until symptoms are controlled, followed by fluconazole Amphotericin Brf IV 0.7-1 mg/kj day orally x >2 weeks, then fluconazole 400 mg orally daily x >8 weekse or Amphotericin Brf IV 0.7-1 mg/kg/day + flucytosine 100 mg/kg/ day orally x 6-I0weekse or Amphotericin Brf IV 0.7-1 mg/kg/day x 6-10 weekse or Fluconazole 400-800 mg orally daily x 10-12 weeks or Itraconazole 400-800 mg orally daily x 10-12 weeks or Fluconazole 400-800 mg orally daily + flucytosine 100-150 mg/ kg/day orally x 6 weekse or... 

Amphotericin IV 0.7-1 mg/kg/day x 2 weeks, followed by fluconazole 400-800 mg orally daily 8-10 weeks, followed by fluconazole 200 mg orally daily x 6-12 months (in patients intolerant to fluconazole, substitute itraconazole 200-400 mg orally daily)... 

Amphotericin B 0.7 mg/kg/day IV for a minimum of 2 weeks with or without flucytosine 100 m kg/day orally in four divided doses (Al) followed by... 

Other drugs that may interact with cardiac glycosides include the following Albuterol, amphotericin B, beta-blockers, calcium, disopyramide, loop diuretics, nondepolarizing muscle relaxants, potassium-sparing diuretics, succinylcholine, sympathomimetics, thiazide diuretics, thioamines, and thyroid hormones. 

Incompatibilities Do not mix IV minocycline before or during administration with any solutions containing the following Adrenocorticotropic hormone (ACTH), aminophylline, amobarbital sodium, amphotericin B, bicarbonate infusion mixtures, calcium gluconate or chloride, carbenicillin, cephalothin sodium, cefazolin sodium, chloramphenicol succinate, colistin sulfate, heparin sodium, hydrocortisone sodium succinate, iodine sodium, methicillin sodium, novobiocin, penicillin, pentobarbital, phenytoin sodium, polymyxin, prochlorperazine, sodium ascorbate, sulfadiazine, sulfisoxazole, thiopental sodium, vitamin K (sodium bisulfate or sodium salt), whole blood. 

Admixture Incompatibilities Physical incompatibilities resulted when linezolid IV injection was combined with the following drugs during simulated Y-site administration amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isothionate, erythromycin lactobionate, phenytoin sodium, and trimethoprim-sulfamethoxazole. Additionally, chemical incompatibility resulted when linezolid IV injection was combined with ceftriaxone sodium. 

Rhinocerebral p/iycomycos/s A cumulative dose of at least 3 g amphotericin B is recommended. Although a total dose of 3 to 4 g will infrequently cause lasting renal impairment, it is a reasonable minimum where there is clinical evidence of deep tissue invasion. Rhinocerebral phycomycosis usually follows a rapidly fatal course therapy must be more aggressive than that for more indolent mycoses. 

Metabolism/Excretion — Amphotericin B has a relatively short initial serum half-life of 24 hours, followed by a second elimination phase with a half-life of approximately 15 days. The drug is slowly excreted by the kidneys with 2% to 5% as the biologically active form. 

The following table presents pharmacokinetic parameters at steady-state for lipid-based formulations of amphotericin B the assay used to measure serum levels did not distinguish between free and complex amphotericin B. 

Renai function impairment Use amphotericin B desoxycholate with care in patients with reduced renal function frequent monitoring is recommended (see Precautions). Lipid formulations have been reported to overcome most problems of chronic nephrotoxicity, even in patients with impaired renal function following previous treatment with amphotericin B desoxycholate. 

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