AMPHOTERICIN B LIPID-BASED

AMPHOTERICIN B LIPID-BASED Abelcet, Amphotec, AmBisome Classifications: antifungal; Therapeutic: antifungal Prototype: AMPHOTERICIN B Pregnancy Category: B; C (oral suspension)

Availability

Abelcet: 100 mg/20 mL suspension for injection;

Amphotec: 50 mg, 100 mg powder for injection;

AmBisome: 50 mg powder for injection

Action

Fungistatic antibiotic produced by Streptomyces nodosus. Exerts antifungal action on both resting and growing cells at least in part by selectively binding to sterols in fungus cell membrane. This results in fungal cell death.

Therapeutic Effect

Fungicidal at higher concentrations, depending on sensitivity of fungus.

Uses

Used intravenously for a wide spectrum of potentially fatal systemic fungal (mycotic) infections.

Unlabeled Uses

Treatment of candiduria, fungal endocarditis, meningitis, septicemia; fungal infections of urinary bladder and urinary tract; amebic meningoencephalitis, and paracoccidioidomycosis.

Contraindications

Hypersensitivity to amphotericin; lactation.

Cautious Use

Severe bone marrow depression; renal function impairment; anemia; pregnancy (category B).

Route & Dosage

Systemic Infections [Abelcet] Adult/Child: IV 5 mg/kg/d [Amphotec] Adult/Child: IV Test Dose 10 mL (1.6–8.3 mg) of initial dose infused over 10–30 min IV Maintenance Dose 3–4 mg/kg/d (max: 7.5 mg/kg/d) infused at 1 mg/kg/h [AmBisome] Adult/Child: IV 3–5 mg/kg/d infused over 1–2 h Cryptococcal Meningitis in HIV [AmBisome] Adult: IV 6 mg/kg/d infused over 2 h Leishmaniasis [AmBisome] Adult: IV Immunocompetent patient: 3 mg/kg/d days 1–5, 14, and 21; may repeat if necessary  Immunocompromised: 4 mg/kg/d on days 1–5, 10, 17, 24, 31, and 38

Administration

Oral

• Instruct patient not to swallow drug immediately, but swish carefully to coat lesions.
• Store according to manufacturer's recommendations.

Topical Application

• Do not cover with plastic wrap, plastic cloth, rubber, or other occlusive dressings. Ask physician to specify when and how lesions are to be washed.
• Discontinue topical treatment promptly if signs of hypersensitivity, irritation, or worsening of lesions occurs.
• Store topical forms in well-closed containers at room temperature, 15°–30° C (59°–86° F), unless otherwise directed.

Intravenous PREPARE: Each brand of amphotericin is prepared differently according to manufacturer's directions. Refer to specific manufacturer's guidelines for preparation of IV solutions.   ADMINISTER: Abelcet Intermittent: • Flush existing IV line with D5W before infusion.• Use 5 micron in-line filter. Infuse total daily dose at 2.5 mg/kg/h.• Shake IV bag at least q2h to evenly mix solution. Amphotec Intermittent: •  Do not use an in-line filter.• Infuse total daily dose at 1 mg/kg/h. Infusion time may be shortened but should never be <2 h. Infusion time may also be extended for better tolerance. AmBisome Intermittent: • Do not use an in-line filter.• Infuse total daily dose over 2 h. Infusion time may be shortened but should never be <1 h.• Alert: Rapid infusion of any amphotericin can cause cardiovascular collapse. If hypotension or arrhythmias develop interrupt infusion and notify physician.• Protect IV solution from light during administration.• Note incompatibilities. When given through an existing IV line, flush before and after with D5W.• Initiate therapy using the most distal vein possible and alternate sites with each dose if possible to reduce the risk of thrombophlebitis.• Check IV site frequently for patency.  INCOMPATIBILITIES Solution/additive: Any saline-containing solution (precipitate will form), parenteral nutrition solutions. Y-site: aminoglycosides, penicillins, phenothiazines, alfentanil, amikacin, ampicillin, ampicillin/sulbactam, atenolol, aztreonam, bretylium, buprenorphine, butorphanol, calcium salts, carboplatin, cefazolin, cefepime, ceftazidime, ceftriaxone, chlorpromazine, cimetidine, cisatracurium, cyclophosphamide, cyclosporine, cytarabine, diazepam, digoxin, diphenhydramine, dobutamine, dopamine, doxorubicin, doxorubicin liposome, droperidol, enalaprilat, esmolol, etoposide, famotidine, fluconazole, fluorouracil, haloperidol, heparin (flush lines with D5W, not NS), hetastartch, hydromorphone, hydroxy-zine, imipenem/cilastatin, labetalol, leucovorin, lidocaine, magnesium sulfate, meperidine, mesna, metoclopramide, midazolam, mitoxantrone, morphone, nalbuphine, naloxone, netilmicin, ofloxacin, ondansetron, paclitaxel, phenytoin, piperacillin, piperacillin/tazobactam, potassium chloride, prochlorperazine, promethazine, propranolol, ranitidine, remifentanil, sodium bicarbonate, ticarcillin/clavulanate, vecuronium, verapamil, vinorelbine. Do not mix Abelcet or Amphotec with any other drugs.

• Store according to manufacturer's recommendations for reconstituted and unopened vials.

Adverse Effects (≥1%)

Body as a Whole: Hypersensitivity (pruritus, urticaria, skin rashes, fever, dyspnea, anaphylaxis); fever, chills. CNS: Headache, sedation, muscle pain, arthralgia, weakness. CV: Hypotension, cardiac arrest. Special Senses: Ototoxicity with tinnitus, vertigo, loss of hearing. GI: nausea, vomiting, diarrhea, epigastric cramps, anorexia, weight loss. Hematologic: Anemia, thrombocytopenia. Metabolic: Hypokalemia, hypomagnesemia. Urogenital: Nephrotoxicity, urine with low specific gravity. Skin: Dry, erythema, pruritus, burning sensation; allergic contact dermatitis, exacerbation of lesions. Other: Pain; arthralgias, thrombophlebitis (IV site), superinfections.

Interactions

Drug: aminoglycosides, capreomycin, cisplatin, carboplatin, colistin, cyclosporine, mechlorethamine, furosemide, vancomycin increase the possibility of nephrotoxicity; corticosteroids potentiate hypokalemia; with digitalis glycosides, hypokalemia increases the risk of digitalis toxicity.

Pharmacokinetics

Peak: 1–2 h after IV infusion. Duration: 20 h. Distribution: Minimal amounts enter CNS, eye, bile, pleural, pericardial, synovial, or amniotic fluids; similar plasma and urine concentrations. Elimination: Excreted renally; can be detected in blood up to 4 wk and in urine for 4–8 wk after discontinuing therapy. Half-Life: 24–48 h.

Nursing Implications

Assessment & Drug Effects

• Lab tests: Baseline C&S tests prior to initiation of therapy; start drug pending results. Baseline and periodic BUN, serum creatinine, creatinine clearance; during therapy periodic CBC, serum electrolytes (especially K⁺, Mg⁺⁺, Na⁺, Ca⁺⁺), and liver function tests.
• Monitor for S&S of local inflammatory reaction or thrombosis at injection site, particularly if extravasation occurs.
• Monitor cardiovascular and respiratory status and observe patient closely for adverse effects during initial IV therapy. If a test dose (1 mg over 20–30 min) is given, monitor vital signs every 30 min for at least 4 h. Febrile reactions (fever, chills, headache, nausea) occur in 20–90% of patients, usually 1–2 h after beginning infusion, and subside within 4 h after drug is discontinued. The severity of this reaction usually decreases with continued therapy. Keep physician informed.
• Monitor I&O and weight. Report immediately oliguria, any change in I&O ratio and pattern, or appearance of urine [e.g., sediment, pink or cloudy urine (hematuria)], abnormal renal function tests, unusual weight gain or loss. Generally, renal damage is reversible if drug is discontinued when first signs of renal dysfunction appear.
• Report to physician and withhold drug, if BUN exceeds 40 mg/dL or serum creatinine rises above 3 mg/dL. Dosage should be reduced or drug discontinued until renal function improves.
• Consult physician about the appearance of mild erythema surrounding topical application to skin lesions. This may be an indication to reduce frequency of topical application.
• Consult physician for guidelines on adequate hydration and adjustment of daily dose as a possible means of avoiding or minimizing nephrotoxicity.
• Report promptly any evidence of hearing loss or complaints of tinnitus, vertigo, or unsteady gait. Tinnitus may not be a complaint in older adults or the very young. Other signs of ototoxicity (i.e., vertigo or hearing loss) are more reliable indicators of ototoxicity in these age groups.

Patient & Family Education

• Notify physician if improvement does not occur within 1–2 wk or if lesions appear to worsen. Nail infections usually require several months or longer to improve.
• Wash towels and clothing that were in contact with affected areas after each treatment.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug