caspofungin acetate Pharmacologic classification: glucan synthesis inhibitor
Therapeutic classification: antifungal
Pregnancy risk category C
Lyophilized powder for injection: 50-mg and 70-mg single-use vials
Indications and dosages
Invasive aspergillosis in patients refractory to or intolerant of other therapies (such as amphotericin B, lipid forms of
amphotericin B, itraconazole). Adults: A single 70-mg loading dose on day 1, followed by 50 mg daily thereafter. Administer by slow I.V. infusion over about 1 hour.
Duration of treatment based on severity of patient’s underlying disease, recovery from immunosuppression, and clinical response.
≡ Dosage adjustment. For patients with moderate hepatic insufficiency (Child-Pugh score 7 to 9), give 35 mg daily after the first 70-mg loading
dose. There’s no clinical experience in patients with severe hepatic insufficiency (Child-Pugh score above 9).
Antifungal action: Caspofungin inhibits synthesis of b(1,3)-D-glucan, an integral component of the cell walls of susceptible filamentous fungi
that isn’t found in mammal cells. Caspofungin has in vitro activity against Aspergillus fumigatus, Aspergillus flavus, and Aspergillus terreus. Development of resistance to caspofungin by Aspergillus species in vitro hasn’t been studied.
Absorption: Administered I.V.
Distribution: Distribution, rather than excretion or biotransformation, is the dominant mechanism influencing plasma clearance. Caspofungin
is extensively bound to albumin (about 97%), and distribution into RBCs is minimal. There’s little excretion or biotransformation
of caspofungin during the first 30 hours after administration. There are three phases of decline in serum levels; the first
is rapid, and the half-lives of the last two phases are 9 to 11 hours and 40 to 50 hours respectively.
Metabolism: Caspofungin is slowly metabolized by hydrolysis and N-acetylation. It also undergoes spontaneous chemical degradation to
an open-ring peptide compound.
Excretion: After single-dose I.V. administration of caspofungin acetate, about 35% of drug and metabolites is excreted in feces and
41% in urine. Renal clearance of parent drug is very low.
Contraindications and precautions
Contraindicated in patients hypersensitive to drug or its components.
Drug-drug. Carbamazepine, dexamethasone, efavirenz, nelfinavir, nevirapine, phenytoin, rifampin: May decrease caspofungin levels. Consider increasing caspofungin dosage if patient fails to respond.
Cyclosporine: Significantly increases caspofungin and ALT levels. Use together isn’t recommended unless potential benefit outweighs potential risk.
Tacrolimus: Decreases tacrolimus levels. Monitor tacrolimus levels and adjust tacrolimus dosage as needed.
CNS: headache, paresthesia, fever.
CV: tachycardia, phlebitis.
GI: nausea, vomiting, diarrhea, abdominal pain, anorexia.
GU: proteinuria, hematuria.
Hematologic: eosinophilia, anemia.
Musculoskeletal: pain, myalgia.
Skin: histamine-mediated symptoms, including rash, facial swelling, pruritus, or sensation of warmth, sweating.
Other: infused vein complications, chills.
Effects on lab test results
May increase alkaline phosphatase level. May decrease potassium level.
May increase eosinophil count. May decrease hemoglobin and hematocrit.
Overdose and treatment
No overdoses have been reported.
Caspofungin isn’t dialyzable.
ALERT Never mix or dilute caspofungin with dextrose solution. Don’t mix or infuse it with other drugs.
Caspofungin usually should be diluted in 250 ml of normal saline solution for all (70-mg, 50-mg, 35-mg) doses. In patients
with fluid restrictions, the 50-mg and 35-mg doses may be diluted in 100 ml of normal saline solution.
Refer to the manufacturer’s instructions for specific reconstitution and I.V. dose preparation guidelines.
Caspofungin should be administered by slow I.V. infusion over about 1 hour.
Reconstituted vials should be used within 1 hour or discarded.
Observe patient for histamine-mediated reactions: rash, facial swelling, pruritus, sensation of warmth.
Monitor I.V. site carefully for phlebitis.
Patients with hepatic insufficiency may require dosage reduction.
Duration of treatment should be based on the severity of the patient’s underlying disease, recovery from immunosuppression,
The efficacy of a 70-mg dose regimen in patients who don’t respond to 50-mg dose isn’t known, but the increase seems to be
well tolerated. The safety of treatment lasting longer than 2 weeks is unclear, but such longer courses seem to be well tolerated.
It isn’t known whether drug appears in breast milk. Use cautiously in breast-feeding women.
Safety and effectiveness in patients younger than age 18 are unknown.
Instruct patient to report signs and symptoms of phlebitis.
Reactions may be common, uncommon, life-threatening, or
COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use