Dosing and uses of Cancidas (caspofungin)
Adult dosage forms and strengths
powder for injection
- 50mg/vial
- 70mg/vial
Candida Infections
Includes candidemia and other Candida infections including intra-abdominal abscesses, peritonitis, and pleural space infections
Day 1 loading dose: 70 mg IV infused over 1 hr (as a single dose)
Maintenance: 50 mg IV qDay infused over 1 hr
Continue antifungal therapy for at least 14 days after last positive culture; patients who remain persistently neutropenic may warrant longer course of therapy pending resolution of neutropenia
Esophageal Candidiasis
Indicated for treatment of esophageal candidiasis
50 mg IV qDay infused over 1 hr, continue for 7-14 days after symptom resolution
Loading dose not necessary, has not been studied with this indication
May consider suppressive oral therapy in patients with HIV infection because of the risk of oropharyngeal candidiasis relapse
Invasive Aspergillosis
Indicated for invasive aspergillosis in patients refractory to or intolerant of other therapies (eg, amphotericin B, itraconazole)
Day 1 loading dose: 70 mg IV infused over 1 hr (as a single dose)
Maintenance: 50 mg IV qDay infused over 1 hr
Duration of treatment should be based upon the severity of the underlying disease, recovery from immunosuppression, and clinical response.
Febrile Neutropenia
Empirical therapy for presumed fungal infections in febrile, neutropenic patients
Day 1 loading dose: 70 mg IV infused over 1 hr
Maintenance: 50 mg IV qDay infused over 1 hour; if well tolerated but not achieving adequate response, may increase to 70 mg IV qDay
Duration of treatment should be based on clinical response; continue empirical therapy until resolution of neutropenia
If fungal infection is confirmed, continue therapy for a minimum of 14 days; treatment should continue for at least 7 days after both neutropenia and clinical symptoms are resolved
Dosage modifications
Coadministration with strong CYP inducers (rifampin): 70 mg IV qDay
Coadministration with other drug clearance inducers: Consider increasing to 70 mg IV qDay
Hepatic Impairment
Mild Child-Pugh 5-6: No dosage adjustment necessary
Moderate Child-Pugh 7-9: Load 70 mg IV, then 35 mg IV qDay
Severe Child-Pugh >9: Safety and efficacy not established
Pediatric dosage forms and strengths
powder for injection
- 50mg/vial
- 70mg/vial
Candida Infections
Includes candidemia and other Candida infections including intra-abdominal abscesses, peritonitis, and pleural space infections
Dosing based on patient’s body surface area
<3 months: Safety and efficacy not established; limited data suggest off-label dose of 25 mg/m²/dose IV once daily
≥3 months
- Day 1 loading dose: 70 mg/m² IV infused over 1 hr
- Maintenance: 50 mg/m² IV qDay infused over 1 hr
- If well tolerated but not achieving adequate response, may increase to 70 mg/m² IV qDay
- Not to exceed 70 mg qDay
- Continue antifungal therapy for at least 14 days after last positive culture; patients who remain persistently neutropenic may warrant longer course of therapy pending resolution of neutropenia
Esophageal Candidiasis
Dosing based on patient’s body surface area
<3 months: Safety and efficacy not established
≥3 months
- Day 1 loading dose: 70 mg/m² IV infused over 1 hr
- Maintenance: 50 mg/m² IV qDay infused over 1 hr
- If well tolerated but not achieving adequate response, may increase to 70 mg/m² IV qDay
- Not to exceed 70 mg qDay
- Continue antifungal therapy for 7-14 days after symptoms resolution
Invasive Aspergillosis
Dosing based on patient’s body surface area
<3 months: Safety and efficacy not established
≥3 months
- Day 1 loading dose: 70 mg/m² IV infused over 1 hr
- Maintenance: 50 mg/m² IV qDay infused over 1 hr
- If well tolerated but not achieving adequate response, may increase to 70 mg/m² IV qDay
- Not to exceed 70 mg qDay
- Duration of treatment should be based upon the severity of the underlying disease, recovery from immunosuppression, and clinical response
Febrile Neutropenia
Empirical therapy for presumed fungal infections in febrile, neutropenic patients
Dosing based on patient’s body surface area
<3 months: safety and efficacy not established
≥3 months
- Day 1 loading dose: 70 mg/m² IV infused over 1 hr
- Maintenance: 50 mg/m² IV qDay infused over 1 hr
- If well tolerated but not achieving adequate response, may increase to 70 mg/m² IV qDay
- Not to exceed 70 mg qDay
Duration of treatment should be based on clinical response; continue empirical therapy until resolution of neutropenia
If fungal infection is confirmed, continue therapy for a minimum of 14 days; treatment should continue for at least 7 days after both neutropenia and clinical symptoms are resolved
Dosage modifications
Coadministration with CYP inducers (eg rifampin): Consider 70 mg/m² IV qDay, not to exceed 70 mg qDay
Hepatic Impairment
Safety and efficacy not established
Cancidas (caspofungin) adverse (side) effects
Varies with condition
Anaphylaxis reported during administration of Cancidas
>10%
Infused vein complications/ phlebitis (20-35%)
Fever (6-30%)
Diarrhea (6-27%)
Shivering (9-23%)
Rash (4-23%)
Incr serum alk phos (9-22%)
Hypotension (3-20%)
Respiratory failure (2-20%)
Incr transaminases (2-18%)
Septic shock (11% to 14% )
1-10% (selected)
Pleural effusion (9%)
Respiratory distress (up to 8%)
Abdominal pain
Nausea
Vomiting
Anemia
Decreased HgB
Neutropenia
Chills
Hypokalemia
Dizziness
Erythema
Facial edema, flushing
Hematuria
Hyperbilirubinemia
Increased serum creatinine
Induration
Myalgia
Pain
Paresthesia
Pruritus
Sepsis
Tachycardia
<1%
Erythema multiforme
Stevens-Johnson syndrome
Pancreatitis
Hepatic necrosis
Liver failure
Anaphylaxis
Nephrotoxicity
Renal impairment
Postmarketing Reports
Blood and lymphatic system disorders: Anemia, coagulopathy, febrile neutropenia, neutropenia, thrombocytopenia
Cardiac disorders: Arrhythmia, atrial fibrillation, bradycardia, cardiac arrest, myocardial infarction, tachycardia
Gastrointestinal disorders: Abdominal distension, abdominal pain upper, constipation, dyspepsia
General disorders and administration site conditions: Asthenia, fatigue, infusion site pain/pruritus/swelling, mucosal inflammation, edema
Hepatobiliary disorders: Hepatic failure, hepatomegaly, hepatotoxicity, hyperbilirubinemia, jaundice
Infections and infestations: Bacteremia, sepsis, urinary tract infection Metabolic and nutrition disorders: Anorexia, decreased appetite, fluid overload, hypomagnesemia, hypercalcemia, hyperglycemia, hypokalemia
Musculoskeletal, connective tissue, and bone disorders: Arthralgia, back pain, pain in extremity
Nervous system disorders: Convulsion, dizziness, somnolence, tremor
Psychiatric disorders: Anxiety, confusional state, depression, insomnia
Renal and urinary disorders: Hematuria, renal failure
Respiratory, thoracic, and mediastinal disorders: Dyspnea, epistaxis, hypoxia, tachypnea
Skin and subcutaneous tissue disorders: Erythema, petechiae, skin lesion, urticaria; toxic epidermal necrolysis
Vascular disorders: Flushing, hypertension, phlebitis
Warnings
Contraindications
Hypersensitivity
Cautions
Anaphylaxis reported, discontinue and administer appropriate treatment; possible histamine-mediated adverse reactions, including rash, facial swelling, angioedema, pruritus, sensation of warmth or bronchospasm
Do not use dextrose diluents
Do not use with cyclosporine (unless benefits outweigh risks)
Not for bolus administration
Can cause abnormalities in hepatic enzyme levels
Cyclosporine may increase AUC of caspofungin by approximately 35%
Hepatic effects: Abnormalities in LFTs and isolated cases of clinically significant hepatic dysfunction, hepatitis, or hepatic failure
Pregnancy and lactation
Pregnancy category: C
Lactation: not known if excreted in breast milk, use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Cancidas (caspofungin)
Mechanism of action
Echinocandin; inhibits fungal cell wall synthesis
Distribution
Protein Bound: 97% to albumin
Metabolism
Slowly, via hydrolysis and N-acetylation as well as by spontaneous degradation with subsequent metabolism to component amino acids
Elimination
Half-life: 9-11 hr (beta phase); 40-50 hr (gamma phase)
Excretion: 41% urine; 35% feces
Administration
IV Incompatibilities
Do not mix with dextrose-containing solutions or coadminister with other medications
IV Preparation
Reconstitute vial (70 mg for loading dose or 50 mg for daily dose) with 10.5 mL NS, SWI or BWI-may be stored for up to 1 hr at 25°C (or less)
Mix gently to obtain clear soln-discard if particulate or discolored
Transfer 10 mL of reconstituted solution to 250 mL NS, 1/2NS 1/4NS or Lr
Use infusion soln within 24 hr if stored at room temp or within 48 hr if refrigerated at 2-8°C
If 70 mg vials are not available for preparation of the loading dose, reconstitute two 50 mg vials & transfer 14 mL to 250 mL NS, 1/2NS, 1/4NS or Lr
For 35 mg, reconstitute a 50 mg vial w/ 10 mL & transfer 7 mL to 250 mL (or 100 mL if medically necessary) infusion soln
IV Administration
Infuse IV slowly over 1 hr
Storage
Store vials at 2-8°C (36-46°F)
