Caspofungin Acetate (caspofungin acetate)

Dosage of caspofungin acetate is expressed in terms of the salt.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Caspofungin/Cyclosporine

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The exact mechanism is unknown.

CLINICAL EFFECTS: The concurrent use of caspofungin and cyclosporine may result in elevated levels of caspofungin, as well as increases in alanine transaminase (ALT) and aspartate transaminase (AST) levels.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Caspofungin and cyclosporine should only be used concurrently if the potential benefits outweigh the potential risk to the patient. Patients receiving concurrent therapy who develop elevated liver function tests should be monitored and the risk/benefit of continuing concurrent therapy should be evaluated.(1)

DISCUSSION: In a clinical study, four subjects received two 3 mg/kg doses of cyclosporine on Day 10 of caspofungin (70 mg daily). Three of the four subjects developed transient elevations of ALT on Day 11 that were 2-3 times the upper limit of normal. AST levels were also elevated, but to a lesser magnitude. Eight subjects received cyclosporine (3 mg/kg) twice on Day 1 of caspofungin (35 mg daily for 3 days). Two of these subjects had a small increase in ALT (slightly above the upper limit of normal) and a slight elevation in AST. Cyclosporine (one 4 mg/kg dose or two 3 mg/kg doses) has been shown to increase the area-under-curve (AUC) of caspofungin by 35%.(1) In a study in 40 immunocompromised patients, subjects received concurrent caspofungin and cyclosporine from 1 to 290 days (median 17.5 days). Of these, 14 (35%) developed transaminase elevations greater than 5 times the upper limit of normal or greater than 3 times baseline during concurrent therapy or the 14 days afterwards. Five were considered possibly related to concurrent therapy. None developed clinical evidence of hepatotoxicity or serious hepatic events. Discontinuation of therapy because of abnormalities in hepatic enzymes from any cause occurred in 4 patients, 2 were considered related to concurrent therapy.(1) In prospective invasive aspergillosis and compassionate use studies, there were 4 patients who received concurrent therapy for 2 to 56 days. None developed increased hepatic enzymes.(1)

Myelosuppressives; Immunomodulators/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)

CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)

DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Caspofungin/Carbamazepine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Carbamazepine may induce the metabolism of caspofungin by CYP3A4.(1)

CLINICAL EFFECTS: The concurrent administration of caspofungin with carbamazepine may result in decreased levels and clinical effectiveness of caspofungin.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: In adult patients receiving concurrent therapy with carbamazepine, the US manufacturer of caspofungin recommends that an increase in the daily dose of caspofungin to 70 mg (following the usual 70 mg loading dose) be considered.(1) In pediatric patients receiving concurrent therapy with carbamazepine, the US manufacturer of caspofungin recommends that an increase in the daily dose of caspofungin to 70 mg/m2 (to a maximum of 70 mg daily, following the usual 70 mg/m2 loading dose) be considered.(1)

DISCUSSION: Regression analyses of patient pharmacokinetic data suggests that administration of caspofungin with inducers and or mixed inducers/ inhibitors of drug clearance may result in clinically significant decreases in caspofungin concentrations. Therefore, the manufacturer of caspofungin recommends that an increase in the daily dose of caspofungin to 70 mg (following the usual 70 mg loading dose) be considered. The efficacy of a 70 mg daily dose in patients who are not responding to the 50 mg daily dose is not known, but limited safety data suggests that it is well tolerated.(1)

Caspofungin/Dexamethasone

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Dexamethasone may induce the metabolism of caspofungin by CYP3A4.(1)

CLINICAL EFFECTS: The concurrent administration of caspofungin with dexamethasone may result in decreased levels and clinical effectiveness of caspofungin.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: In adult patients receiving concurrent therapy with dexamethasone, the US manufacturer of caspofungin recommends that an increase in the daily dose of caspofungin to 70 mg (following the usual 70 mg loading dose) be considered.(1) In pediatric patients receiving concurrent therapy with dexamethasone, the US manufacturer of caspofungin recommends that an increase in the daily dose of caspofungin to 70 mg/m2 (to a maximum of 70 mg daily, following the usual 70 mg/m2 loading dose) be considered.(1)

DISCUSSION: Regression analyses of patient pharmacokinetic data suggests that administration of caspofungin with inducers and or mixed inducers/ inhibitors of drug clearance may result in clinically significant decreases in caspofungin concentrations. Therefore, the manufacturer of caspofungin recommends that an increase in the daily dose of caspofungin to 70 mg (following the usual 70 mg loading dose) be considered in patients receiving concurrent therapy with dexamethasone. The efficacy of a 70 mg daily dose in patients who are not responding to the 50 mg daily dose is not known, but limited safety data suggests that it is well tolerated.(1)

Caspofungin/Efavirenz; Nevirapine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Efavirenz and nevirapine may induce the metabolism of caspofungin via induction of unspecified hepatic CYP enzymes.(1)

CLINICAL EFFECTS: The concurrent administration of caspofungin with either efavirenz or nevirapine may result in decreased levels and clinical effectiveness of caspofungin.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: In adult patients receiving concurrent therapy with efavirenz or nevirapine, the US manufacturer of caspofungin recommends that an increase in the daily dose of caspofungin to 70 mg (following the usual 70 mg loading dose) be considered.(1) In pediatric patients receiving concurrent therapy with efavirenz or nevirapine, the US manufacturer of caspofungin recommends that an increase in the daily dose of caspofungin to 70 mg/m2 (to a maximum of 70 mg daily, following the usual 70 mg/m2 loading dose) be considered.(1)

DISCUSSION: Regression analyses of patient pharmacokinetic data suggests that administration of caspofungin with inducers and or mixed inducers/ inhibitors of drug clearance may result in clinically significant decreases in caspofungin concentrations. Therefore, the manufacturer of caspofungin recommends that an increase in the daily dose of caspofungin to 70 mg (following the usual 70 mg loading dose) be considered in patients receiving concurrent therapy with efavirenz or nevirapine. The efficacy of a 70 mg daily dose in patients who are not responding to the 50 mg daily dose is not known, but limited safety data suggests that it is well tolerated.(1)

Caspofungin/Fosphenytoin; Phenytoin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Phenytoin may induce the metabolism of caspofungin by CYP3A4.(1)

CLINICAL EFFECTS: The concurrent administration of caspofungin with phenytoin may result in decreased levels and clinical effectiveness of caspofungin.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: In adult patients receiving concurrent therapy with phenytoin, the US manufacturer of caspofungin recommends that an increase in the daily dose of caspofungin to 70 mg (following the usual 70 mg loading dose) be considered.(1) In pediatric patients receiving concurrent therapy with phenytoin, the US manufacturer of caspofungin recommends that an increase in the daily dose of caspofungin to 70 mg/m2 (to a maximum of 70 mg daily, following the usual 70 mg/m2 loading dose) be considered.(1)

DISCUSSION: Regression analyses of patient pharmacokinetic data suggests that administration of caspofungin with inducers and or mixed inducers/ inhibitors of drug clearance may result in clinically significant decreases in caspofungin concentrations. Therefore, the manufacturer of caspofungin recommends that an increase in the daily dose of caspofungin to 70 mg (following the usual 70 mg loading dose) be considered in patients receiving concurrent therapy with phenytoin. The efficacy of a 70 mg daily dose in patients who are not responding to the 50 mg daily dose is not known, but limited safety data suggests that it is well tolerated.(1)

Caspofungin/Rifampin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Rifampin may induce the metabolism of caspofungin by CYP3A4.(1)

CLINICAL EFFECTS: The concurrent administration of caspofungin with rifampin may result in decreased levels and clinical effectiveness of caspofungin.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: In adult patients receiving concurrent therapy with rifampin, the US manufacturer of caspofungin states that a daily dose of 70 mg of caspofungin should be used.(1) In pediatric patients receiving concurrent therapy with rifampin, the US manufacturer of caspofungin recommends that an increase in the daily dose of caspofungin to 70 mg/m2 (to a maximum of 70 mg daily, following the usual 70 mg/m2 loading dose) be considered.(1)

DISCUSSION: In a study in healthy volunteers, rifampin decreased caspofungin trough concentrations by 30%.(1)

Caspofungin/Tacrolimus

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The mechanism of the interaction is unknown.

CLINICAL EFFECTS: Concurrent use of caspofungin may result in decreased levels and effectiveness of tacrolimus.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Tacrolimus levels should be closely monitored in patients receiving concurrent caspofungin. The dosage of tacrolimus may need to be adjusted during and after caspofungin.(1,2)

DISCUSSION: In a placebo-controlled, randomized, parallel panel study in healthy subjects, caspofungin (70 mg daily for 10 days) decreased the area-under-curve (AUC), maximum concentration, (Cmax) and minimum concentration (Cmin) of tacrolimus (2 doses of 0.1 mg/kg 12 hours apart) by 20%, 16%, and 26%, respectively.(1,2) There were no significant effects on caspofungin levels.(1)

Caspofungin acetate is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis) to the drug or any ingredient in the formulation.

There are no contraindication contraindications for this drug.

• Child-pugh class B hepatic impairment
• Disease of liver

There are no moderate contraindications for this drug.

Adverse effects reported in 5% or more of patients receiving caspofungin include pyrexia, diarrhea, chills, decreased potassium, increased alkaline phosphatase, decreased hemoglobin, hypotension, respiratory failure, increased ALT, fever, decreased hematocrit, phlebitis, vomiting, rash, increased AST, nausea, headache, increased bilirubin, septic shock, decreased leukocyte count, peripheral edema, cough, pneumonia, increased creatinine, anemia, abdominal pain, dyspnea, increased blood urea, pleural effusion, increased conjugated bilirubin, tachycardia, decreased albumin, decreased magnesium, rales, and sepsis.

More Frequent

• Abnormal hepatic function tests
• Anemia
• Hypokalemia
• Increased alanine transaminase
• Increased alkaline phosphatase
• Increased aspartate transaminase

Less Frequent

• Dyspnea
• Injection site sequelae
• Neutropenic disorder
• Peripheral edema

Rare or Very Rare

• Acute myocardial infarction
• Anaphylaxis
• Angioedema
• Atrial fibrillation
• Bradycardia
• Bronchospastic pulmonary disease
• Erythema multiforme
• Exfoliative dermatitis
• Hematuria
• Hepatic necrosis
• Hepatitis
• Hyperbilirubinemia
• Hypercalcemia
• Hypomagnesemia
• Hypoxia
• Jaundice
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Pancreatitis
• Renal failure
• Seizure disorder
• Stevens-johnson syndrome
• Thrombocytopenic disorder
• Toxic epidermal necrolysis

More Frequent

• Acute abdominal pain
• Chills
• Diarrhea
• Fever
• Nausea
• Vomiting

Less Frequent

• Abdominal distension
• Anorexia
• Body fluid retention
• Constipation
• Cough
• Dizziness
• Drowsy
• Erythema
• Fatigue
• Flushing
• General weakness
• Headache disorder
• Hyperglycemia
• Hypertension
• Hypotension
• Phlebitis after infusion
• Pruritus of skin
• Skin rash
• Stomatitis
• Tachycardia

Rare or Very Rare

• Acute cognitive impairment
• Arthralgia
• Back pain
• Depression
• Dyspepsia
• Epistaxis
• Facial edema
• Insomnia
• Petechiae
• Sensation of warmth
• Symptoms of anxiety
• Tremor
• Urinary tract infection
• Urticaria

No enhanced messaging available.

Safety and efficacy of caspofungin have not been established in neonates and infants younger than 3 months of age. Although limited pharmacokinetic data are available for this age group, the manufacturer states that data are insufficient to date to establish a safe and effective dosage for treatment of neonatal candidiasis. In addition, invasive candidiasis in neonates has a higher rate of CNS and multi-organ involvement than do such infections in older patients, and data are insufficient to date regarding distribution of caspofungin into the CNS or regarding efficacy in the treatment of meningitis and endocarditis.

Caspofungin has not been evaluated in pediatric patients for the treatment of endocarditis, osteomyelitis, or meningitis caused by Candida or for initial therapy of invasive aspergillosis. The drug also has not been evaluated for use in pediatric patients with hepatic impairment.

Safety and efficacy of caspofungin for use in infants and children 3 months to 17 years of age for treatment of invasive aspergillosis in those refractory to or intolerant of other antifungals; for treatment of candidemia and certain other invasive Candida infections (intra-abdominal abscesses, peritonitis, pleural space infections) or esophageal candidiasis; and for empiric treatment of presumed fungal infections in febrile neutropenic patients is based on adequate and well-controlled studies in adults, pharmacokinetic data in pediatric patients, and additional data from prospective studies in this age group.

The manufacturer states that the overall safety profile of caspofungin in pediatric patients is comparable to that in adults. Adverse effects reported in 7% or more of pediatric patients receiving caspofungin include pyrexia, rash, decreased potassium, increased AST, diarrhea, increased ALT, chills, hypotension, vomiting, tachycardia, mucosal inflammation, hypertension, headache, erythema, central line infection, cough, respiratory distress, hypokalemia, abdominal pain, and pruritus.

Although data are limited, some experts state that caspofungin can be considered for first-line treatment of invasive candidiasis or for alternative treatment of esophageal candidiasis in children with human immunodeficiency virus (HIV) infection.

Category C. (See Users Guide.)

There are no adequate and well-controlled studies of caspofungin acetate in pregnant women, and the manufacturer states that the drug should be used during pregnancy only if potential benefits justify potential risks to the fetus.

In animals, embryofetal toxicity (increased resorptions, increased peri-implantation loss, incomplete ossification at multiple fetal sites) has been reported with caspofungin dosages about 2 times the recommended human dosage (based on body surface area comparisons).

Caspofungin is distributed into milk in rats; it is not known whether the drug is distributed into milk in humans.

Caspofungin should be used with caution in nursing women.

Dosage adjustments are not necessary in patients 65 years of age or older.

Clinical studies of caspofungin did not include a sufficient number of patients 65 years of age or older to determine whether they respond differently than younger individuals. Although no overall differences in efficacy or safety were observed between geriatric and younger adults, the possibility that some older patients may have increased sensitivity to the drug cannot be ruled out.

Although caspofungin plasma concentrations are increased slightly in men and women 65 years of age and older compared with young healthy males, dosage adjustments are not necessary in geriatric patients.