caspofungin

REMS

Invasive aspergillosis refractory to, or intolerant of, other therapies.
Candidemia and associated serious infections (intra-abdominal abscesses, peritonitis, pleural space infections).
Esophageal candidiasis.
Suspected fungal infections in febrile neutropenic patients.

Action ⬆ ⬇

Inhibits the synthesis of β (1, 3)-D-glucan, a necessary component of the fungal cell wall.

Therapeutic effects:

Death of susceptible fungi.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Protein Binding: 97%.

Metabolism/Excretion: Slowly and extensively metabolized; <1.5% excreted unchanged in urine.

Half-Life: Polyphasic: βphase: 9–11 hr; γphase: 40–50 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
IV	unknown	end of infusion	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
OB: Pregnancy.

Use Cautiously in:

Moderate hepatic impairment (↓ maintenance dose recommended);
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: flushing, pruritus, rash, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS

GI: ↑liver enzymes, diarrhea, nausea, vomiting

GU: ↑serum creatinine

Local: venous irritation at injection site

Neuro: headache

Resp: bronchospasm

Misc: chills, fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

↑risk of hepatotoxicity with Cyclosporine; closely monitor liver enzymes during concurrent therapy.
May ↓ levels and effectiveness of tacrolimus.
Rifampin may ↓ levels and effectiveness; maintenance dose should be ↑ to 70 mg/day (in patients with normal hepatic function).
Efavirenz, nelfinavir, nevirapine, phenytoin, dexamethasone, or carbamazepine may ↓ levels and effectiveness; an ↑ in the maintenance dose to 70 mg/day should be considered in patients who are not clinically responding.

Route/Dosage ⬆ ⬇

IV (Adults ): 70 mg initially followed by 50 mg once daily; duration determined by clinical situation and response; Esophageal candidiasis: 50 mg once daily; duration determined by clinical situation and response.
IV (Children ≥3 mo): 70 mg/m² (max = 70 mg) initially followed by 50 mg/m² once daily (max = 70 mg/day); duration determined by clinical situation and response.
IV (Infants 1 to <3 mo and Neonates): 25 mg/m² once daily.

Hepatic Impairment

IV (Adults ): Moderate hepatic impairment: 70 mg initially followed by 35 mg once daily; duration determined by clinical situation and response.

Availability ⬆ ⬇

(Generic available)

Powder for injection: 50 mg/vial; 70 mg/vial

Assessment ⬆ ⬇

Assess patient for signs and symptoms of fungal infections prior to and periodically during therapy.
Assess for skin rash frequently during therapy. Discontinue at first sign of rash; may be life-threatening. SJS may develop. Treat symptomatically; may recur once treatment is stopped.
Monitor patient for signs of anaphylaxis (rash, dyspnea, stridor, facial swelling, angioedema, pruritus, sensation of warmth, bronchospasm) during therapy.

Lab Test Considerations:

May cause ↑ serum alkaline phosphatase, serum creatinine, AST, ALT, eosinophils, and urine protein and RBCs. May also cause ↓ serum potassium, hemoglobin, hematocrit, and WBCs.

Implementation ⬆ ⬇

IV Administration:

Intermittent Infusion: Allow refrigerated vial to reach room temperature. For 70-mg or 50-mg dose: Reconstitute vials with 10.8 mL of 0.9% NaCl, sterile water for injection, bacteriostatic water for injection with methylparaben and propylparaben, or bacteriostatic water for injection with 0.9% benzyl alcohol. Use preservative-free diluents for neonates. Do not dilute with dextrose solutions. Reconstituted solution is stable for 1 hr at room temperature. Diluent: Withdraw 10 mL from vial and add to 250 mL of 0.9% NaCl, 0.45% NaCl, 0.225% NaCl, or LR. The 50-mg dose also can be diluted in 100 mL when volume restriction is necessary. Infusion is stable for 24 hr at room temperature or 48 hr if refrigerated. For 35-mg dose: Reconstitute a 50-mg or 70-mg vial as per the directions above. Remove the volume of drug equal to the calculated loading dose or calculated maintenance dose based on a concentration of 7 mg/mL (if reconstituted from the 70-mg vial) or a concentration of 5 mg/mL (if reconstituted from the 50-mg vial). White cake should dissolve completely. Mix gently until a clear solution is obtained. Do not use a solution that is cloudy, discolored, or contains precipitates.Concentration: 0.14–0.47 mg/mL.
Rate: Infuse over 1 hr.

Patient/Family Teaching ⬆ ⬇

Explain the purpose of caspofungin to patient and family.
Advise patient to notify health care professional immediately if symptoms of allergic reactions (rash, facial swelling, pruritus, sensation of warmth, difficulty breathing) occur.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇