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Pronunciation
(kas poe FUN jin)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of invasive Aspergillus infections in patients who are refractory or intolerant of other therapy; treatment of candidemia and other Candida infections (intra-abdominal abscesses, esophageal, peritonitis, pleural space); empirical treatment for presumed fungal infections in febrile neutropenic patient
Use: Dental
Management of angular cheilitis
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events have been observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Should be used during pregnancy only if potential benefit justifies the potential risk to the fetus.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to caspofungin or any component of the formulation
Warnings/Precautions
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; increased transaminases and rare cases of liver impairment have been reported in pediatric and adult patients. Dosage reduction required in adults with moderate hepatic impairment; safety and efficacy have not been established in children with any degree of hepatic impairment and adults with severe hepatic impairment.
Concurrent drug therapy issues:
• Cyclosporine: Concurrent use of cyclosporine should be limited to patients for whom benefit outweighs risk, due to a high frequency of hepatic transaminase elevations observed during concurrent use.
Adverse Reactions
>10%:
Cardiovascular: Hypotension (3% to 20%), peripheral edema (6% to 11%), tachycardia (4% to 11%)
Central nervous system: Fever (6% to 30%), chills (9% to 23%), headache (5% to 15%)
Dermatologic: Rash (4% to 23%)
Endocrine & metabolic: Hypokalemia (5% to 23%)
Gastrointestinal: Diarrhea (6% to 27%), vomiting (6% to 17%), nausea (4% to 15%)
Hematologic: Hemoglobin decreased (18% to 21%), hematocrit decreased (13% to 18%), WBC decreased (12%), anemia (2% to 11%)
Hepatic: Serum alkaline phosphatase increased (9% to 22%), transaminases increased (2% to 18%), bilirubin increased (5% to 13%)
Local: Phlebitis/thrombophlebitis (18%)
Renal: Serum creatinine increased (3% to 11%)
Respiratory: Respiratory failure (2% to 20%), cough (6% to 11%), pneumonia (4% to 11%)
Miscellaneous: Infusion reactions (20% to 35%), septic shock (11% to 14%)
5% to 10%:
Cardiovascular: Hypertension (5% to 6%; children 9% to 10%)
Dermatologic: Erythema (4% to 9%), pruritus (6% to 7%)
Endocrine & metabolic: Hypomagnesemia (7%), hyperglycemia (6%)
Gastrointestinal: Mucosal inflammation (4% to 10%), abdominal pain (4% to 9%)
Hepatic: Albumin decreased (7%)
Local: Infection (1% to 9%, central line)
Renal: Hematuria (10%), blood urea nitrogen increased (4% to 9%)
Respiratory: Dyspnea (9%), pleural effusion (9%), respiratory distress (≤8%), rales (7%)
Miscellaneous: Sepsis (5% to 7%)
<5%, postmarketing. and/or case reports: Abdominal distention, anaphylaxis, anorexia, anxiety, appetite decrease, arrhythmia, arthralgia, atrial fibrillation, back pain, bacteremia, bradycardia, cardiac arrest, coagulopathy, confusion, constipation, depression, dizziness, dyspepsia, dystonia, edema, epistaxis, erythema multiforme, fatigue, febrile neutropenia, fluid overload, flushing, hematuria, hepatic necrosis, hepatomegaly, hepatotoxicity, hypercalcemia, hyperkalemia, hypoxia, infusion site reactions (pain/pruritus/swelling), insomnia, jaundice, liver failure, MI, nephrotoxicity (serum creatinine ≥2 x baseline value or ≥1 mg/dL in patients with serum creatinine above ULN range), pain (extremities), pancreatitis, petechiae, pulmonary edema, renal failure/insufficiency, seizure, skin exfoliation, skin lesion, somnolence, stridor, Stevens-Johnson syndrome, tachypnea, thrombocytopenia, tremor, urinary tract infection, urticaria, weakness; histamine-mediated reactions (including facial swelling, bronchospasm, sensation of warmth) have been reported
Metabolism/Transport Effects
None known.
Drug Interactions
CycloSPORINE: May enhance the adverse/toxic effect of Caspofungin. CycloSPORINE may increase the serum concentration of Caspofungin. Management: Weigh potential benefits of caspofungin against a possible elevated risk of hepatotoxicity. Monitor liver function and re-evaluate treatment in patients with abnormal values. Mild transaminase elevations may occur relatively commonly. Risk D: Consider therapy modification
CycloSPORINE (Systemic): May enhance the adverse/toxic effect of Caspofungin. CycloSPORINE (Systemic) may increase the serum concentration of Caspofungin. Management: Weigh potential benefits of caspofungin against a possible elevated risk of hepatotoxicity. Monitor liver function and re-evaluate treatment in patients with abnormal values. Mild transaminase elevations may occur relatively commonly. Risk D: Consider therapy modification
Inducers of Drug Clearance: May decrease the serum concentration of Caspofungin. Management: Consider using an increased caspofungin dose of 70 mg daily in adults (or 70 mg/m2, up to a maximum of 70 mg, daily in pediatric patients) when coadministered with known inducers of drug clearance. Risk D: Consider therapy modification
Rifampin: May decrease the serum concentration of Caspofungin. Management: Caspofungin prescribing information recommends using a dose of 70 mg daily in adults (or 70 mg/m2, up to a maximum of 70 mg, daily in pediatric patients) who are also receiving rifampin. Risk D: Consider therapy modification
Saccharomyces boulardii: Antifungal Agents may diminish the therapeutic effect of Saccharomyces boulardii. Risk D: Consider therapy modification
Tacrolimus: Caspofungin may decrease the serum concentration of Tacrolimus. Risk C: Monitor therapy
Tacrolimus (Systemic): Caspofungin may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Storage
Store vials at 2°C to 8°C (36°F to 46°F). Reconstituted solution may be stored at ≤25°C (≤77°F) for 1 hour prior to preparation of infusion solution. Infusion solutions may be stored at ≤25°C (≤77°F) and should be used within 24 hours; up to 48 hours if stored at 2°C to 8°C (36°F to 46°F).
Reconstitution
Bring refrigerated vial to room temperature. Reconstitute vials using 0.9% sodium chloride for injection, SWFI, or bacteriostatic water for injection. Mix gently until clear solution is formed; do not use if cloudy or contains particles. Solution should be further diluted with 0.9%, 0.45%, or 0.225% sodium chloride or LR (do not exceed final concentration of 0.5 mg/mL).
Compatibility
Stable in NS, 1/2NS, 1/4NS, LR.
Y-site administration: Compatible: Amikacin, amiodarone, azithromycin, aztreonam, bumetanide, carboplatin, cisplatin, cyclosporine, daptomycin, daunorubicin, diltiazem, diphenhydramine, dobutamine, dolasetron, dopamine, doripenem, doxorubicin, epinephrine, etoposide phosphate, famotidine, fentanyl, fluconazole, ganciclovir, gentamicin, hydralazine, hydrocortisone sodium succinate, hydromorphone, ifosfamide, imipenem/cilastatin, insulin (regular), linezolid, lorazepam, magnesium sulfate, melphalan, meperidine, meropenem, metronidazole, midazolam, milrinone, mitomycin, morphine, mycophenolate, norepinephrine, ondansetron, phenylephrine, potassium chloride, quinupristin/dalfopristin, tacrolimus, telavancin, tobramycin, vancomycin, vasopressin, vincristine, voriconazole. Incompatible: Amphotericin B, amphotericin B lipid complex, amphotericin B liposomal, ampicillin, cefazolin, cefepime, ceftazidime, ceftriaxone, clindamycin, cytarabine, ertrapenem, furosemide, heparin, methylpredisolone sodium succinate, nafcillin, piperacillin/tazobactam, potassium phosphate, sulfamethoxazole/trimethoprim. Variable (consult detailed reference): Acyclovir, ciprofloxacin, levofloxacin, pantoprazole.
Compatibility in syringe: Incompatible:Ceftriaxone.
Mechanism of Action
Inhibits synthesis of β(1,3)-D-glucan, an essential component of the cell wall of susceptible fungi. Highest activity in regions of active cell growth. Mammalian cells do not require β(1,3)-D-glucan, limiting potential toxicity.
Pharmacodynamics/Kinetics
Protein binding: ~97% to albumin
Metabolism: Slowly, via hydrolysis and N-acetylation as well as by spontaneous degradation, with subsequent metabolism to component amino acids. Overall metabolism is extensive.
Half-life elimination: Beta (distribution): 9-11 hours; Terminal: 40-50 hours
Excretion: Urine (41%; primarily as metabolites, ~1% of total dose as unchanged drug); feces (35%; primarily as metabolites)
Dosage
I.V.:
Children: 3 months to 17 years: Initial dose: 70 mg/m2 on day 1, subsequent dosing: 50 mg/m2 once daily, if clinical response inadequate, may increase to 70 mg/m2 once daily if tolerated, but increased efficacy not demonstrated (maximum dose: 70 mg/day)
Adults: Note: Duration of caspofungin treatment should be determined by patient status and clinical response. Empiric therapy should be given until neutropenia resolves. In patients with positive cultures, treatment should continue until 14 days after last positive culture. In neutropenic patients, treatment should be given at least 7 days after both signs and symptoms of infection and neutropenia resolve.
Aspergillosis, invasive: Initial dose: 70 mg on day 1; subsequent dosing: 50 mg/day. If clinical response inadequate, may increase up to 70 mg/day if tolerated, but increased efficacy not demonstrated. Note: Duration of therapy should be a minimum of 6-12 weeks or throughout period of immunosuppression.
Candidiasis: Initial dose: 70 mg on day 1; subsequent dosing: 50 mg/day; higher doses (150 mg once daily infused over ~2 hours) compared to the standard adult dosing regimen (50 mg once daily) have not demonstrated additional benefit or toxicity in patients with invasive candidiasis (Betts, 2009)
Esophageal: 50 mg/day; Note: The majority of patients studied for this indication also had oropharyngeal involvement.
Empiric therapy: Initial dose: 70 mg on day 1; subsequent dosing: 50 mg/day; if clinical response inadequate, may increase up to 70 mg/day if tolerated, but increased efficacy not demonstrated
Concomitant use of an enzyme inducer:
Children: Patients receiving carbamazepine, dexamethasone, efavirenz, nevirapine, phenytoin, or rifampin (and possibly other enzyme inducers): Consider 70 mg/m2 once daily (maximum: 70 mg/day)
Adults:
Patients receiving rifampin: 70 mg caspofungin daily
Patients receiving carbamazepine, dexamethasone, efavirenz, nevirapine, or phenytoin (and possibly other enzyme inducers) may require an increased daily dose of caspofungin (70 mg/day).
Elderly: The number of patients >65 years of age in clinical studies was not sufficient to establish whether a difference in response may be anticipated.
Dosage adjustment in renal impairment: No dosage adjustment required in renal impairment.
Poorly dialyzed; no supplemental dose or dosage adjustment necessary, including patients on intermittent hemodialysis, peritoneal dialysis, or continuous renal replacement therapy (eg, CVVHD).
Dosage adjustment in hepatic impairment:
Children: Mild-to-severe hepatic insufficiency: No clinical experience
Adults:
Mild hepatic insufficiency (Child-Pugh score 5-6): No adjustment necessary
Moderate hepatic insufficiency (Child-Pugh score 7-9): 70 mg on day 1 (where recommended), followed by 35 mg once daily
Severe hepatic insufficiency (Child-Pugh score >9): No clinical experience
Administration: I.V.
Infuse slowly, over 1 hour
Administration: I.V. Detail
Monitor during infusion. Isolated cases of possible histamine-related reactions have occurred during clinical trials (rash, flushing, pruritus, facial edema).
Monitoring Parameters
Liver function
Patient Education
This medication can only be administered by infusion. Report immediately any pain, burning, or swelling at infusion site or any signs of allergic reaction (eg, respiratory difficulty or swallowing, back pain, chest tightness, rash, hives, swelling of lips or mouth). Report gastrointestinal upset (nausea, vomiting, abdominal pain, diarrhea), swelling of extremities, chest pain or palpations, or unusual cough.
Geriatric Considerations
The number of patients >65 years of age in clinical studies was not sufficient to establish whether a difference in response may be anticipated.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness and insomnia
Mental Health: Effects on Psychiatric Treatment
Carbamazepine may decrease serum concentration of caspofungin
Nursing: Physical Assessment/Monitoring
Use caution in presence of hepatic impairment.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as acetate:
Cancidas®: 50 mg [contains sucrose 39 mg]
Cancidas®: 70 mg [contains sucrose 54 mg]
References
Betts RF, Nucci M, Talwar D, et al, “A Multicenter, Double-Blind Trial of a High-Dose Caspofungin Treatment Regimen Versus a Standard Caspofungin Treatment Regimen for Adult Patients With Invasive Candidiasis,” Clin Infect Dis, 2009, 48(12):1676-84.
Gould FK, Denning DW, Elliott TS, et al, “Guidelines for the Diagnosis and Antibiotic Treatment of Endocarditis in Adults: A Report of the Working Party of the British Society for Antimicrobial Chemotherapy,” J Antimicrob Chemother, 2012, 67(2):269-89.
Mora-Duarte J, Betts R, Rotstein C, et al, “Comparison of Caspofungin and Amphotericin B for Invasive Candidiasis,” N Engl J Med, 2002, 347(25):2020-9.
Pappas PG, Kauffman CA, Andes D, et al, “Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious Diseases Society of America,” Clin Infect Dis, 2009, 48(5):503-35.
Stone EA, Fung HB, and Kirschenbaum HL, “Caspofungin: An Echinocandin Antifungal Agent,” Clin Ther, 2002, 24(3):351-77.
Walsh TJ, Anaissie EJ, Denning DW, et al, “Treatment of Aspergillosis: Clinical Practice Guidelines of the Infectious Diseases Society of America,” Clin Infect Dis, 2008, 46(3):327-60.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
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