Amphotericin dosage

Potassium Iodide. When potassium iodide [7681-11-0] is adrninistered orally for several (6—8) weeks, a therapeutic effect may be obtained ia the subcutaneous form of sporotrichosis. Amphotericin B is used iatravenously to treat systemic sporotrichosis. The KI dosage is usually a saturated solution ia water (1 g/mL). The usual oral dose is 30 mg/kg/d. Children should receive five droplets, three times a day (after meals) the dose may be iacreased to 15—20 droplets. Side effects iaclude digestive disorders, swelling of the saUvary glands, and lacrimation. Thyroid function tests may be disturbed. 

A patient weighs 140 pounds. If amphotericin B 1.5 mg/kg per day is prescribed, what is the total daily dosage of amphotericin B for this 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... 

Specific antifungals (and their usual dosages) for the treatment of coccidioidomycosis include amphotericin B IV (0.5 to 1.5 mg/kg/day), ketocona-zole (400 mg orally daily), IV or oral fluconazole (usually 400 to 800 mg daily, although dosages as high as 1,200 mg/day have been utilized without complications), and itraconazole (200 to 300 mg orally twice daily as either capsules or solution). If itraconazole is used, measurement of serum concentrations may be helpful to ascertain whether oral bioavailability is adequate. 

The use of intrathecal amphotericin B is not recommended for the treatment of cryptococcal meningitis except in very ill patients or in those with recurrent or progressive disease despite aggressive IV amphotericin B therapy. The dosage of amphotericin B employed is usually 0.5 mg administered via the lumbar, cisternal, or intraventricular (via an Ommaya reservoir) route two or three times weekly. 

Remove existing central venous catheters when feasible, plus Amphotericin B IV 0.7-1 m k day (total dosages 0.5-1 g)... 

Suggested Indication-Specific Dosage Regimens for Amphotericin B... 

To decrease dose-related toxicity by using reduced doses of one or more components of the drug regimen. The use of flucytosine in combination with amphotericin for the treatment of cryptococcal meningitis in non-HIV-infected patients allows for a reduction in amphotericin dosage with decreased amphotericin -induced nephrotoxicity. 

This important antifungal drug (see Chapter 48) is an alternative therapy for visceral leishmaniasis, especially in parts of India with high-level resistance to sodium stibogluconate. Liposomal amphotericin has shown excellent efficacy at a dosage of 3 mg/kg/d intravenously on days 1-5, 14, and 21. Nonliposomal amphotericin (1 mg/kg intravenously every other day for 30 days) is much less expensive, also efficacious, and widely used in India. Amphotericin is also used for cutaneous leishmaniasis in some areas. The use of amphotericin, and especially liposomal preparations, is limited in developing countries by difficulty of administration, cost, and toxicity. 

Paromomycin sulfate is an aminoglycoside antibiotic that until recently was used in parasitology only for oral therapy of intestinal parasitic infections (see previous text). It has recently been developed for the treatment of visceral leishmaniasis. A phase 3 trial in India showed excellent efficacy for this disease, with a daily intramuscular dosage of 11 mg/kg for 21 days yielding a 95% cure rate, and noninferiority compared with amphotericin. The drug was registered for the treatment of visceral leishmaniasis in India in 2006. In initial studies, paromomycin was well tolerated, with common mild injection pain, uncommon ototoxicity and reversible liver enzyme elevations, and no nephrotoxicity. Paromomycin is much less expensive than liposomal amphotericin or miltefosine, the other promising new therapies for visceral leishmaniasis. 

Amphotericin (Fungizone) is available for topical use in cream and lotion form. The recommended dosage in the treatment of paronychial and intertriginous candidiasis is application two to four times daily to the affected area. 

For treatment of systemic fungal disease, amphotericin B is given by slow intravenous infusion at a dosage of 0.5-1 mg/kg/d. It is usually continued to a defined total dose (eg, 1-2 g), rather than a defined time span, as used with other antimicrobial drugs. 

All patients receiving amphotericin intravenously suffer from nephrotoxicity. In nonconventional dosage forms, such as liposomal formulations, the adverse effects are similar but less toxic when compared with conventional dosage. 

Amphotericin is highly effective in the treatment of visceral leishmaniasis (18). In a prospective study of 938 patients from Bihar, India, who received the drug in a dosage of 1 mg/kg/day infused over 2 hours for 20 days, serum creatinine values over 177 pmol/l were noted in 6.3%, and acute renal insufficiency developed in three patients. Two patients died, possibly related to amphotericin, one with renal insufficiency and one with hypokalemia and cardiac arrest. Infnsion-related chills occurred in 92% and fever in 40% of patients. The parasitological cure rate (no relapse within 6 months) exceeded 99%. 

Liposomal amphotericin and ABLC have been compared in an open randomized study in 75 adults with leukemia and 82 episodes of suspected or documented mycosis (48). The median durations of treatment and dosages were 15 days at 4 mg/kg/day for liposomal amphotericin and 10 days at 3 mg/kg/day for ABLC. Acute but not dose-limiting infusion-related adverse events occurred in 36 versus 70%. Bilirubin increased to over 1.5 times baseline in 59 versus 38%. There was no difference in the effects of either agent on renal function and drug-related withdrawals. The overall response rate to therapy in documented fungal infections (29 and 30% respectively) was not different between the two drugs. 

This case shows that, regardless of the formulation of amphotericin, severe neurological adverse effects can occur, in particular in patients who receive large dosages of amphotericin after cranial irradiation. A clinical syndrome of akinetic mutism, incontinence, and parkinsonism has been described in patients who received large doses of amphotericin deoxycholate in association with central nervous system irradiation or infection (67). 

In a retrospective analysis, 5 of 31 children with cancers, who had received liposomal amphotericin in dosages of 1-3 mg/kg/day, had an isolated transient rise in the serum hpase activity during or shortly after therapy with liposomal amphotericin (96). Three of these patients had signs of pancreatitis. While the exact pathogenesis is unclear, the authors proposed fat overload or toxic damage to the pancreas by the liposomes or amphotericin itself as potential mechanisms. 

There has been a retrospective comparison of the renal effects of ABLC with amphotericin deoxycholate in the treatment of invasive candidiasis and cryptococcosis in dosages of 0.6-5 mg/kg/day most patients received 5 mg/kg/day (115). Changes in serum creatinine were evaluated in three ways doubling of the baseline value, an increase from below 132 pmol/l (1.5 mg/dl) at baseline to over 132 pmol/l, and an increase from below 132 pmol/l at baseline to at least 177 pmol/l (2.0 mg/dl). These endpoints were achieved significantly more often with amphotericin deoxycholate than with ABLC, and the time needed to reach each of the endpoints was significantly shorter with amphotericin deoxycholate. An increased serum creatinine concentration was reported as an adverse event more often in patients receiving amphotericin deoxycholate than in patients receiving ABLC (24 versus 43%). 

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