ABELCET: Package Insert and Label Information (Page 2 of 3)

PRECAUTIONS

General:

As with any amphotericin B-containing product, during the initial dosing of ABELCET ® , the drug should be administered under close clinical observation by medically trained personnel.

Acute reactions including fever and chills may occur 1 to 2 hours after starting an intravenous infusion of ABELCET ®. These reactions are usually more common with the first few doses of ABELCET ® and generally diminish with subsequent doses. Infusion has been rarely associated with hypotension, bronchospasm, arrhythmias, and shock.

Laboratory Tests:

Serum creatinine should be monitored frequently during ABELCET ® therapy (see ADVERSE REACTIONS). It is also advisable to regularly monitor liver function, serum electrolytes (particularly magnesium and potassium), and complete blood counts.

Drug Interactions:

No formal clinical studies of drug interactions have been conducted with ABELCET ®. However, when administered concomitantly, the following drugs are known to interact with amphotericin B; therefore, the following drugs may interact with ABELCET ®:

Antineoplastic agents: Concurrent use of antineoplastic agents and amphotericin B may enhance the potential for renal toxicity, bronchospasm, and hypotension. Antineoplastic agents should be given concomitantly with ABELCET ® with great caution.

Corticosteroids and corticotropin (ACTH): Concurrent use of corticosteroids and corticotropin (ACTH) with amphotericin B may potentiate hypokalemia which could predispose the patient to cardiac dysfunction. If used concomitantly with ABELCET ® , serum electrolytes and cardiac function should be closely monitored.

Cyclosporin A: Data from a prospective study of prophylactic ABELCET ® in 22 patients undergoing bone marrow transplantation suggested that concurrent initiation of cyclosporin A and ABELCET ® within several days of bone marrow ablation may be associated with increased nephrotoxicity.

Digitalis glycosides: Concurrent use of amphotericin B may induce hypokalemia and may potentiate digitalis toxicity. When administered concomitantly with ABELCET ® , serum potassium levels should be closely monitored.

Flucytosine: Concurrent use of flucytosine with amphotericin B-containing preparations may increase the toxicity of flucytosine by possibly increasing its cellular uptake and/or impairing its renal excretion. Flucytosine should be given concomitantly with ABELCET ® with caution.

Imidazoles (e.g., ketoconazole, miconazole, clotrimazole, fluconazole, etc.): Antagonism between amphotericin B and imidazole derivatives such as miconazole and ketoconazole, which inhibit ergosterol synthesis, has been reported in both in vitro and in vivo animal studies. The clinical significance of these findings has not been determined.

Leukocyte transfusions: Acute pulmonary toxicity has been reported in patients receiving intravenous amphotericin B and leukocyte transfusions. Leukocyte transfusions and ABELCET ® should not be given concurrently.

Other nephrotoxic medications: Concurrent use of amphotericin B and agents such as aminoglcosides and pentamidine may enhance the potential for drug-induced renal toxicity. Aminoglycosides and pentamidine should be used concomitantly with ABELCET ® only with great caution. Intensive monitoring of renal function is recommended in patients requiring any combination of nephrotoxic medications.

Skeletal muscle relaxants: Amphotericin B-induced hypokalemia may enhance the curariform effect of skeletal muscle relaxants (e.g., tubocurarine) due to hypokalemia. When administered concomitantly with ABELCET ® , serum potassium levels should be closely monitored.

Zidovudine: Increased myelotoxicity and nephrotoxicity were observed in dogs when either ABELCET ® (at doses 0.16 or 0.5 times the recommended human dose) or amphotericin B desoxycholate (at 0.5 times the recommended human dose) were administered concomitantly with zidovudine for 30 days. If zidovudine is used concomitantly with ABELCET ® , renal and hematologic function should be closely monitored.

Carcinogenesis, Mutagenesis, and Impairment of Fertility:

No long-term studies in animals have been performed to evaluate the carcinogenic potential of ABELCET ®. The following in vitro (with and without metabolic activation) and in vivo studies to assess ABELCET ® for mutagenic potential were conducted: bacterial reverse mutation assay, mouse lymphoma forward mutation assay, chromosomal aberration assay in CHO cells, and in vivo mouse micronucleus assay. ABELCET ® was found to be without mutagenic effects in all assay systems. Studies demonstrated that ABELCET ® had no impact on fertility in male and female rats at doses up to 0.32 times the recommended human dose (based on body surface area considerations).

Pregnancy:

There are no reports of pregnant women having been treated with ABELCET ®. Teratogenic Effects. Reproductive studies in rats and rabbits at doses of ABELCET ® up to 0.64 times the human dose revealed no harm to the fetus. Because animal reproductive studies are not always predictive of human response, and adequate and well-controlled studies have not been conducted in pregnant women, ABELCET ® should be used during pregnancy only after taking into account the importance of the drug to the mother.

Nursing Mothers:

It is not known whether ABELCET ® is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in breast-fed infants from ABELCET ® , a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use:

One hundred eleven children (2 were enrolled twice and counted as separate patients), age 16 years and under, of whom 11 were less than 1 year, have been treated with ABELCET ® at 5 mg/kg/day in two open-label studies and one small, prospective, single-arm study. In one single-center study, 5 children with hepatosplenic candidiasis were effectively treated with 2.5 mg/kg/day of ABELCET ®. No serious unexpected adverse events have been reported.

Geriatric Use:

Forty-nine elderly patients, age 65 years or over, have been treated with ABELCET ® at 5 mg/kg/day in two open-label studies and one small, prospective, single-arm study. No serious unexpected adverse events have been reported.

ADVERSE REACTIONS

The total safety data base is composed of 921 patients treated with ABELCET ® (5 patients were enrolled twice and counted as separate patients), of whom 775 were treated with 5 mg/kg/day. Of these 775 patients, 194 patients were treated in four comparative studies; 25 were treated in open-label, non-comparative studies; and 556 patients were treated in an open-label, emergency-use program. Most had underlying hematologic neoplasms, and many were receiving multiple concomitant medications. Of the 556 patients treated with ABELCET ® , 9% discontinued treatment due to adverse events regardless of presumed relationship to study drug.

In general, the adverse events most commonly reported with ABELCET ® were transient chills and/or fever during infusion of the drug.

Adverse Events a with an Incidence of ≥3% (N=556)

Adverse Event

Percentage (%) of Patients

Chills

18

Fever

14

Increased Serum Creatinine

11

Multiple Organ Failure

11

Nausea

9

Hypotension

8

Respiratory Failure

8

Vomiting

8

Dyspnea

7

Sepsis

7

Diarrhea

6

Headache

6

Cardiac Arrest

6

Hypertension

5

Hypokalemia

5

Infection

5

Kidney Failure

5

Pain

5

Thrombocytopenia

5

Anemia

4

Hyperbilirubinemia

4

Gastrointestinal Hemorrhage

4

Leukopenia

4

Rash

4

Respiratory Disorder

4

Chest Pain

3

Nausea and Vomiting

3

a The causal association between these adverse events and ABELCET ® is uncertain.

The following adverse events have also been reported in patients using ABELCET ® in open-label, uncontrolled clinical studies. The causal association between these adverse events and ABELCET ® is uncertain.

Body as a whole: malaise, weight loss, deafness, injection site reaction including inflammation

Allergic: bronchospasm, wheezing, asthma, anaphylactoid and other allergic reactions

Cardiopulmonary: cardiac failure, pulmonary edema, shock, myocardial infarction, hemoptysis, tachypnea, thrombophlebitis, pulmonary embolus, cardiomyopathy, pleural effusion, arrhythmias including ventricular fibrillation.

Dermatological: maculopapular rash, pruritus, exfoliative dermatitis, erythema multiforme

Gastrointestinal: acute liver failure, hepatitis, jaundice, melena, anorexia, dyspepsia, cramping, epigastric pain, veno-occlusive liver disease, diarrhea, hepatomegaly, cholangitis, cholecystitis

Hematologic: coagulation defects, leukocytosis, blood dyscrasias including eosinophilia

Musculoskeletal: myasthenia, including bone, muscle, and joint pains

Neurologic: convulsions, tinnitus, visual impairment, hearing loss, peripheral neuropathy, transient vertigo, diplopia, encephalopathy, cerebral vascular accident, extrapyramidal syndrome and other neurologic symptoms

Urogenital: oliguria, decreased renal function, anuria, renal tubular acidosis, impotence, dysuria

Serum electrolyte abnormalities: hypomagnesemia, hyperkalemia, hypocalcemia, hypercalcemia

Liver function test abnormalities: increased AST, ALT, alkaline phosphatase, LDH

Renal function test abnormalities: increased BUN

Other test abnormalities: acidosis, hyperamylasemia, hypoglycemia, hyperglycemia, hyperuricemia, hypophosphatemia

To report SUSPECTED ADVERSE REACTIONS, contact Leadiant Biosciences, Inc. at 1-888-393-4584 or by email at drugsafety@leadiant.com or contact the FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch.

OVERDOSAGE

Amphotericin B desoxycholate overdose has been reported to result in cardio-respiratory arrest. Fifteen patients have been reported to have received one or more doses of ABELCET ® between 7-13 mg/kg. None of these patients had a serious acute reaction to ABELCET ®. If an overdose is suspected, discontinue therapy, monitor the patient’s clinical status, and administer supportive therapy as required. ABELCET ® is not hemodialyzable.

DOSAGE AND ADMINISTRATION

The recommended daily dosage for adults and children is 5 mg/kg given as a single infusion. ABELCET ® should be administered by intravenous infusion at a rate of 2.5 mg/kg/h. If the infusion time exceeds 2 hours, mix the contents by shaking the infusion bag every 2 hours.

Renal toxicity of ABELCET ® , as measured by serum creatinine levels, has been shown to be dose dependent. Decisions about dose adjustments should be made only after taking into account the overall clinical condition of the patient.

Preparation of Admixture for Infusion: Shake the vial gently until there is no evidence of any yellow sediment at the bottom. Withdraw the appropriate dose of ABELCET ® from the required number of vials into one or more sterile syringes using an 18-gauge needle. Remove the needle from each syringe filled with ABELCET ® and replace with the 5-micron filter needle supplied with each vial. Each filter needle may be used to filter the contents of up to four 100 mg vials. Insert the filter needle of the syringe into an IV bag containing 5% Dextrose Injection USP, and empty the contents of the syringe into the bag. The final infusion concentration should be 1 mg/mL. For pediatric patients and patients with cardiovascular disease the drug may be diluted with 5% Dextrose Injection to a final infusion concentration of 2 mg/mL. Before infusion, shake the bag until the contents are thoroughly mixed. Do not use the admixture after dilution with 5% Dextrose Injection if there is any evidence of foreign matter. Vials are for single use. Unused material should be discarded. Aseptic technique must be strictly observed throughout handling of ABELCET ® , since no bacteriostatic agent or preservative is present.

DO NOT DILUTE WITH SALINE SOLUTIONS OR MIX WITH OTHER DRUGS OR ELECTROLYTES as the compatibility of ABELCET ® with these materials has not been established. An existing intravenous line should be flushed with 5% Dextrose Injection before infusion of ABELCET ® , or a separate infusion line should be used. DO NOT USE AN IN-LINE FILTER.

The diluted ready-for-use admixture is stable for up to 48 hours at 2° to 8°C (36° to 46°F) and an additional 6 hours at room temperature.

DrugInserts.com provides trustworthy package insert and label information about marketed drugs as submitted by manufacturers to the US Food and Drug Administration. Package information is not reviewed or updated separately by DrugInserts.com. Every individual package label entry contains a unique identifier which can be used to secure further details directly from the US National Institutes of Health and/or the FDA.

As the leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. Our material is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2023. All Rights Reserved.