Caspofungin

Caspofungin belongs to the pharmacological class of Echinocandins.

Caspofungin has been approved to relieve symptoms and also for treating and maintaining Aspergillosis, invasive, Candidiasis, Neutropenic fever, empiric antifungal therapy, and Prophylaxis against invasive fungal infections.

Regarding the absorption of caspofungin, approximately 92% of the administered dose is distributed to various tissues within 36 to 48 hours following intravenous infusion. The volume of distribution for caspofungin is not available. The drug is highly bound to proteins, with approximately 97% of it being bound. Caspofungin is metabolized slowly through processes of hydrolysis and N-acetylation. In terms of elimination, after a single intravenous dose of [3H] caspofungin acetate, approximately 35% of the dose is excreted in feces and 41% in urine, indicating a combination of renal and fecal elimination.

The common side effects involved in using Caspofungin are Diarrhea, Fever, Chills, Abnormal liver function tests, Skin rash, Dizziness, Lightheadedness.

Caspofungin is available in the form of Powder for injection .

Caspofungin is approved in Germany, Japan, Malaysia, India, the U.K., the U.S., and China.

Caspofungin belongs to the pharmacological class of Echinocandins.

Caspofungin, a semi-synthetic lipopeptide belonging to the echinocandin family, exhibits a distinct mechanism of action compared to other antifungal agents. It targets 1,3-β-D-glucan synthesis, a crucial process involved in the formation of the structural cell wall in certain pathogenic fungi, including Candida albicans and Aspergillus fumigatus. By inhibiting the enzymatic transfer of glucose from UDP-glucose into 1,3-β-D-glucan, caspofungin disrupts the synthesis of this key component in the membrane fractions of A. fumigatus and C. albicans. The inhibitory concentration 50% values for caspofungin against these fungi are 9.6 nM and 0.6 nM, respectively. However, a direct correlation between enzyme inhibition and antifungal activity in vitro or in vivo has not yet been established. Importantly, the absence of 1,3-β-D-glucan in mammalian cells indicates that caspofungin specifically targets fungal cells, enhancing its selectivity of action.

Caspofungin has been approved to relieve symptoms and also for the treatment and maintenance of Aspergillosis, invasive, Candidiasis, Neutropenic fever, empiric antifungal therapy, Prophylaxis against invasive fungal infections.

The elimination half-life of caspofungin ranges from 9 to 11 hours.

Caspofungin is found to be available in the form of Powder for injection .

Caspofungin can be used in the following treatment:

• Aspergillosis, invasive
• Candidiasis
• Neutropenic fever, empiric antifungal therapy
• Prophylaxis against invasive fungal infections

Caspofungin can help to relieve symptoms and also for the treatment and maintenance of Aspergillosis, invasive, Candidiasis, Neutropenic fever, empiric antifungal therapy, Prophylaxis against invasive fungal infections.

Caspofungin is approved for use in the following clinical indications:

• Aspergillosis, invasive
• Candidiasis
• Neutropenic fever, empiric antifungal therapy
• Prophylaxis against invasive fungal infections

• Aspergillosis, Invasive (including disseminated and extrapulmonary) - Alternative Agent:

Please note that caspofungin is typically reserved for salvage therapy or when other antifungals are contraindicated. Monotherapy is further reserved for patients who are intolerant of or refractory to azoles and polyenes. In combination with voriconazole, some experts use caspofungin as initial therapy for severe or progressive infection.

Dosage:

• Intravenous (IV): 70 mg on day 1, followed by 50 mg once daily. If the clinical response is inadequate, the dose may be increased to 70 mg once daily.

Duration:

• Monotherapy: The minimum duration is 6 to 12 weeks, depending on the degree and duration of immunosuppression, disease site, and response to therapy. Prolonged treatment may be required for immunosuppressed patients.
• Combination regimen: The optimal duration is uncertain. Some experts have used caspofungin in combination with voriconazole for approximately 2 weeks before transitioning to voriconazole monotherapy.
• Candidiasis:

Candidemia (neutropenic and nonneutropenic patients), including disseminated candidiasis:

• IV: 70 mg on day 1, followed by 50 mg once daily. The total duration, including oral step-down therapy, is at least 14 days after the first negative blood culture and continues until signs/symptoms of candidemia and neutropenia, if present, have resolved. Metastatic complications may require a longer duration.

Cardiac device infection (including implantable cardiac defibrillator, pacemaker, ventricular assist device) - Off-label use:

• IV: 150 mg once daily. Caspofungin is typically stepped down to azole therapy in clinically stable patients with susceptible isolates and negative repeat cultures. The total antifungal duration is at least 4 weeks after device removal for isolated generator pocket infection and at least 6 weeks after device removal for wire infection.

• Powder for injection : 50mg/vial , 70mg/vial

Powder for injection.

Dosage Adjustments in Kidney Patients:

• Altered Kidney Function: No adjustment in dosage is necessary for any degree of kidney dysfunction.
• Hemodialysis, Intermittent (Thrice Weekly): For patients who are poorly dialyzed, no supplemental dose or adjustment in dosage is required.
• Peritoneal Dialysis: Due to the high protein binding of caspofungin, it is unlikely to be significantly removed during peritoneal dialysis. Therefore, no dosage adjustment is necessary.
• CRRT (Continuous Renal Replacement Therapy): Similar to patients undergoing hemodialysis, poorly dialyzed patients on CRRT do not require a dosage adjustment.
• Note: There is significant variability in caspofungin pharmacokinetics observed in critically ill patients and those receiving renal replacement therapies. Results from a Monte Carlo simulation suggest that an alternative dosing regimen, such as a larger loading dose (e.g., 100 mg) followed by a maintenance dose of 50 mg once daily for patients weighing less than 80 kg or 70 mg once daily for patients weighing more than 80 kg, increases the likelihood of achieving pharmacodynamic targets.
• PIRRT (Sustained, Low-Efficiency Diafiltration): Caspofungin is unlikely to be significantly removed during PIRRT, and thus no dosage adjustment is necessary.
• Note: Similar to CRRT, significant variability in caspofungin pharmacokinetics has been observed in critically ill patients and those on renal replacement therapies. The results of the Monte Carlo simulation suggest that the alternative dosing regimen mentioned earlier increases the probability of achieving pharmacodynamic targets in patients on CRRT. These results are likely applicable to critically ill patients receiving PIRRT therapies as well.

Dosage Adjustments in Hepatic Impairment Patients:

Mild Impairment (Child-Pugh class A): No adjustment in dosage is necessary for caspofungin.

Moderate Impairment (Child-Pugh class B): On day 1, a dose of 70 mg is recommended, followed by 35 mg once daily. However, it is important to note that pharmacokinetic data suggest that this dose reduction may lead to suboptimal drug exposure.

Severe Impairment (Child-Pugh class C): The manufacturer's labeling does not provide specific dosage adjustments for severe impairment (Child-Pugh class C). However, subsequent pharmacokinetic data indicate that the degree of impairment (whether moderate or severe) does not significantly affect caspofungin clearance. Therefore, patients with severe impairment can be dosed similarly to patients with moderate impairment.

Dosage Adjustments in Pediatric Patients:

• Treatment of Invasive Aspergillosis:

Note: Caspofungin is recommended for salvage therapy or when other antifungals are contraindicated. It is not routinely recommended for primary treatment.

• Infants ≥3 months, Children, and Adolescents <18 years: Intravenous (IV) administration. Initial dose of 70 mg/m2 on day 1, followed by 50 mg/m2 once daily. The dose may be increased to 70 mg/m2 once daily if the clinical response is inadequate. Maximum dose: 70 mg/dose.

Empiric Therapy for Fungal Infections in Neutropenic Patients:

• Infants ≥3 months, Children, and Adolescents <18 years: IV administration. Initial dose: 70 mg/m2 on day 1, followed by 50 mg/m2 once daily. The dose may be increased to 70 mg/m2 once daily if the clinical response is inadequate. Maximum dose: 70 mg/dose.
• Prophylaxis for Fungal Infections in Patients with Acute Myeloid Leukemia:

Limited data available.

• Infants ≥3 months, Children, and Adolescents: IV administration. Initial dose: 70 mg/m2 on day 1 (maximum dose: 70 mg/dose), followed by 50 mg/m2 once daily (maximum dose: 50 mg/dose). Start therapy 24 to 72 hours after completion of each chemotherapy cycle and continue until absolute neutrophil count (ANC) reaches 100 to 500/µL following nadir or until the next chemotherapy cycle, whichever occurs first.
• Prophylaxis for Fungal Infections in Allogeneic Hematopoietic Stem Cell Transplantation Recipients:

Limited data available.

• Infants ≥8 months, Children, and Adolescents: IV administration. 50 mg/m2 once daily. Maximum dose: 50 mg/dose. Some studies have used a loading dose. Guidelines recommend administering antifungal prophylaxis from the start of conditioning through engraftment.

Treatment of Candida Infections (independent of HIV status):

• Infants <3 months: Limited data available. IV administration. 25 mg/m2 once daily. Dosing based on a pharmacokinetic study in infants (≤12 weeks) that showed similar serum concentrations to standard adult doses (50 mg/day). Slightly elevated trough concentrations were observed but not correlated with increased adverse events.
• Infants ≥3 months, Children, and Adolescents <18 years: IV administration. Initial dose: 70 mg/m2 on day 1, followed by 50 mg/m2 once daily. The dose may be increased to 70 mg/m2 once daily if the clinical response is inadequate. Maximum dose: 70 mg/dose. Treat esophageal disease for 14 to 21 days and candidemia until 2 weeks after the last positive blood culture.

• Adolescents ≥18 years: IV administration. Initial dose: 70 mg on day 1, followed by 50 mg once daily. Treat candidemia until 2 weeks after the last positive blood culture and symptom resolution. Treat esophageal disease for 14 to 21 days. A higher rate of relapse has been reported with echinocandins compared to fluconazole for esophageal disease. Transition to fluconazole is recommended in clinically stable patients with fluconazole-susceptible isolates and negative repeat cultures.

There are no specific dietary restrictions associated with the use of caspofungin. Caspofungin can be administered with or without food, and no specific foods or beverages are known to interact with caspofungin.

Caspofungin may be contraindicated under the following conditions:

• Caspofungin is contraindicated in patients who have demonstrated hypersensitivity to the drug.

Hypersensitivity:

• Anaphylaxis has been reported during the administration of caspofungin. In the event of anaphylaxis, caspofungin should be discontinued, and appropriate treatment should be administered.

Possible Histamine-Mediated Adverse Reactions:

• Adverse reactions caused by histamine, such as rash, facial swelling, angioedema, pruritus, sensation of warmth, or bronchospasm, had been reported. These reactions may require the discontinuation of caspofungin and/or appropriate treatment.

Hepatic Effects:

• Laboratory abnormalities in liver function tests had been observed in healthy volunteers, as well as adult and pediatric patients treated with caspofungin. In some cases, clinically significant hepatic dysfunction, hepatitis, and hepatic failure have been reported in adult as well as pediatric patients with serious underlying conditions who were receiving multiple concomitant medications along with caspofungin. However, a causal relationship between caspofungin and these hepatic effects has not been established. Patients who develop abnormal liver function tests during caspofungin therapy should be monitored for worsening hepatic function, and the risk versus benefit of continuing caspofungin therapy should be evaluated.

Elevated Liver Enzymes during Concomitant Use with Cyclosporine:

• Elevated liver enzymes have been observed in patients receiving caspofungin and cyclosporine concurrently. The use of caspofungin and cyclosporine should only be considered in patients where the potential benefits outweigh the potential risks. Patients who experience abnormal liver enzymes during concomitant therapy should be closely monitored, and the risk versus benefit of continuing therapy should be evaluated.

Information regarding the presence of caspofungin in human milk, its impact on breastfed infants, and its influence on milk production is currently unavailable. However, studies conducted on lactating rats that received caspofungin revealed its presence in their milk.

When considering the use of Caspofungin in breastfeeding mothers, it is important to weigh the developmental and health advantages of breastfeeding against the clinical necessity for Caspofungin in the mother and any potential adverse effects it may have on the breastfed child. Additionally, the effects of the underlying maternal condition should also be taken into account.

Pregnancy:

Teratogenic Effects - Category C

Risk Summary:

It is uncertain whether using Caspofungin during pregnancy increases the likelihood of major birth defects, miscarriage, or adverse effects on the mother or fetus as there is insufficient human data available. However, animal studies suggest that administering Caspofungin intravenously during the organogenesis phase to pregnant rats and rabbits at doses up to 0.8 and 2 times the clinical dose, respectively, may result in embryofetal toxicity, including increased resorptions, higher peri-implantation loss, and incomplete ossification at multiple fetal sites. Patients should be advised of the possible risk to the fetus.

The background risk of major birth defects and miscarriage in the relevant population is unknown, but all pregnancies come with inherent risks of adverse outcomes. In the general U.S. population, the estimated background risk of major birth defects is between 2% to 4%, while the estimated background risk of miscarriage in clinically recognized pregnancies is between 15% to 20%.

Data:

Animal Data:

During animal studies, pregnant rats and rabbits were given intravenous caspofungin during organogenesis, which resulted in various effects on their offspring. The rats that received doses up to 5 mg/kg/day experienced increased resorptions and peri-implantation losses at the highest dose. The offspring born to these rats showed incomplete ossification of the skull and torso, as well as a higher incidence of cervical rib. Similarly, pregnant rabbits treated with caspofungin at doses up to 6 mg/kg/day had increased fetal resorptions and an increased incidence of incomplete ossification of the talus/calcaneus in their offspring at the highest dose. It was found that caspofungin crossed the placenta in both rats and rabbits and was detected in fetal plasma.

However, in a peri- and postnatal development study in rats, intravenous administration of caspofungin at doses of 0.5, 2, or 5 mg/kg/day from Day 6 of gestation through Day 20 of lactation did not result in adverse effects on reproductive performance, the subsequent development of first-generation (F1) offspring, or malformations in second-generation (F2) offspring.

No specific food restrictions or dietary modifications are required when using caspofungin. Caspofungin can be administered with or without food.

The adverse reactions related to Caspofungin can be categorized as follows:

Common:

• Diarrhea
• Fever
• Chills
• Abnormal liver function tests
• Skin rash
• Dizziness
• Lightheadedness

Less common:

• Hives
• Burning in your eyes
• Difficulty breathing
• Swelling of the face, lips, tongue, or throat
• Fever
• Sore throat
• Skin pain
• Red or purple skin rash that spreads as well as causes blistering and peeling
• Pain, swelling, or vein irritation around the IV needle
• Chills
• Body aches
• Flu-like symptoms
• Swelling in hands or feet
• Weakness
• Muscle cramps
• Pounding or uneven heartbeats
• Confusion
• Extreme thirst
• Increased urination
• Leg discomfort
• Muscle weakness or limp feeling
• Nausea
• Upper stomach pain
• Itching
• Tired feeling
• Loss of appetite
• Dark urine
• Clay-colored stools
• Yellowing of the skin or eyes (jaundice)

Rare:

• None

• Cyclosporine Interaction:
• Influence on Caspofungin Pharmacokinetics:

In two adult clinical studies, the administration of cyclosporine (either a single 4 mg/kg dose or two 3 mg/kg doses) resulted in an increase in the AUC (area under the concentration-time curve) of Caspofungin. However, Caspofungin did not have a significant effect on the plasma levels of cyclosporine. When Caspofungin and cyclosporine were co-administered, there were transient elevations in liver ALT and AST levels. It is recommended to monitor patients who experience abnormal liver enzyme levels during concomitant therapy and carefully evaluate the risk versus benefit of continuing treatment .

• Tacrolimus Interaction:

For patients receiving both Caspofungin and tacrolimus, it is advised to perform standard monitoring of tacrolimus trough whole blood concentrations and make appropriate dosage adjustments for tacrolimus.

• Inducers of Hepatic CYP Enzymes:
• Interaction with Rifampin:

Rifampin is a potent inducer of the CYP3A4 enzyme, which is expected to decrease the plasma concentrations of Caspofungin when administered together. Therefore, adult patients taking rifampin should be given a daily dose of 70 mg of Caspofungin, while pediatric patients on rifampin should receive 70 mg/m2 of Caspofungin per day (with a maximum daily dose of 70 mg) .

• Interaction with Other Inducers of Hepatic CYP Enzymes:

In Adult Patients:

When Caspofungin is co-administered with other inducers of hepatic CYP enzymes such as efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine in adult patients, a daily dose of 70 mg of Caspofungin should be considered .

For pediatric patients receiving Caspofungin along with other inducers of hepatic CYP enzymes like efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, a daily dose of 70 mg/m2 of Caspofungin should be considered (not exceeding an actual daily dose of 70 mg).

The following are the side effects involving Caspofungin:

• Diarrhea
• Fever
• Chills
• Abnormal liver function tests
• Skin rash
• Dizziness
• Lightheadedness

Pregnancy:

Teratogenic Effects - Category C

Risk Summary:

It is uncertain whether using Caspofungin during pregnancy increases the likelihood of major birth defects, miscarriage, or adverse effects on the mother or fetus as there is insufficient human data available. However, animal studies suggest that administering Caspofungin intravenously during the organogenesis phase to pregnant rats and rabbits at doses up to 0.8 and 2 times the clinical dose, respectively, may result in embryofetal toxicity, including increased resorptions, higher peri-implantation loss, and incomplete ossification at multiple fetal sites. Patients should be advised of the possible risk to the fetus.

The background risk of major birth defects and miscarriage in the relevant population is unknown, but all pregnancies come with inherent risks of adverse outcomes. In the general U.S. population, the estimated background risk of major birth defects is between 2% to 4%, while the estimated background risk of miscarriage in clinically recognized pregnancies is between 15% to 20%.

Data:

Animal Data:

During animal studies, pregnant rats and rabbits were given intravenous caspofungin during organogenesis, which resulted in various effects on their offspring. The rats that received doses up to 5 mg/kg/day experienced increased resorptions and peri-implantation losses at the highest dose. The offspring born to these rats showed incomplete ossification of the skull and torso, as well as a higher incidence of cervical rib. Similarly, pregnant rabbits treated with caspofungin at doses up to 6 mg/kg/day had increased fetal resorptions and an increased incidence of incomplete ossification of the talus/calcaneus in their offspring at the highest dose. It was found that caspofungin crossed the placenta in both rats and rabbits and was detected in fetal plasma.

However, in a peri- and postnatal development study in rats, intravenous administration of caspofungin at doses of 0.5, 2, or 5 mg/kg/day from Day 6 of gestation through Day 20 of lactation did not result in adverse effects on reproductive performance, the subsequent development of first-generation (F1) offspring, or malformations in second-generation (F2) offspring.

Lactation:

Information regarding the presence of caspofungin in human milk, its impact on breastfed infants, and its influence on milk production is currently unavailable. However, studies conducted on lactating rats that received caspofungin revealed its presence in their milk.

When considering the use of Caspofungin in breastfeeding mothers, it is important to weigh the developmental and health advantages of breastfeeding against the clinical necessity for Caspofungin in the mother and any potential adverse effects it may have on the breastfed child. Additionally, the effects of the underlying maternal condition should also be taken into account.

Pediatric:

Caspofungin has been proven to be safe and effective for pediatric patients aged 3 months to 17 years through well-controlled adult studies and pharmacokinetic data analysis in pediatric patients. Additional evidence from prospective studies in pediatric patients within the same age range further support its use for the following indications:

● Empirical therapy for presumed fungal infections in neutropenic patients with fever; treatment of candidemia and various Candida infections such as intra-abdominal abscesses, peritonitis, and pleural space infections

● Treatment of esophageal candidiasis; and

● Treatment of invasive aspergillosis in patients who cannot tolerate or are unresponsive to other treatments like amphotericin B, lipid formulations of amphotericin B, and itraconazole.

However, clinical trials involving neonates and infants under 3 months of age have not adequately investigated the efficacy and safety of Caspofungin. Although pharmacokinetic data were collected in neonates and infants below 3 months of age, they are insufficient to establish a safe and effective dose of caspofungin for the treatment of neonatal candidiasis. In neonates, invasive candidiasis often involves the central nervous system (CNS) and multiple organs, and the ability of Caspofungin to penetrate the blood-brain barrier and effectively treat patients with meningitis and endocarditis remains unknown.

Caspofungin has not been specifically studied in pediatric patients with endocarditis, osteomyelitis, and meningitis caused by Candida. Additionally, it has not been evaluated as initial therapy for invasive aspergillosis in pediatric patients.

In clinical trials, a total of 171 pediatric patients (ranging from 0 months to 17 years of age), including 18 patients below 3 months of age, received intravenous Caspofungin. Pharmacokinetic studies involved 66 pediatric patients, and an additional 105 pediatric patients were enrolled in safety and efficacy studies. The majority of pediatric patients received a once-daily maintenance dose of 50 mg/m2 of Caspofungin for an average duration of 12 days (median 9 days, range 1-87 days). Safety assessments were conducted by the investigator throughout the treatment period and for 14 days after the completion of therapy. The most commonly reported adverse reactions in pediatric patients treated with Caspofungin were pyrexia (29%), decreased blood potassium (15%), diarrhea (14%), increased aspartate aminotransferase (12%), rash (12%), increased alanine aminotransferase (11%), hypotension (11%), and chills (11%).

Cases of hepatobiliary adverse reactions have been reported in pediatric patients with underlying serious medical conditions in postmarketing reports.

Geriatric Use:

The clinical studies conducted on Caspofungin did not include an adequate number of patients aged 65 and above to establish whether they exhibit different responses compared to younger patients. Although the number of elderly patients was insufficient for a statistical analysis, no notable discrepancies in safety or effectiveness were observed between this age group and younger patients. In healthy older men and women (aged 65 years and above), plasma concentrations of caspofungin exhibited a slight increase (approximately 28% in AUC) compared to young healthy men. Similar effects of age on pharmacokinetics were observed in patients with candidemia or other Candida infections, such as intra-abdominal abscesses, peritonitis, or pleural space infections. No dose adjustment has been recommended for the elderly population; however, it is important to acknowledge that certain older individuals may potentially be more sensitive to the medication, although this cannot be definitively determined.

Physicians should be knowledgeable as well as vigilant about the treatment and identification of overdosage of Caspofungin.

In a group of 6 healthy individuals who were administered a single dose of 210 mg, no significant adverse reactions were observed. However, the effects of multiple doses exceeding 150 mg per day have not been investigated. Caspofungin is not removed through dialysis.

During clinical trials, a single pediatric patient (16 years old) inadvertently received a dose of 113 mg on Day 1, followed by a daily dose of 80 mg for 7 additional days. No clinically significant adverse reactions were reported in this case.

Pharmacodynamics:

Caspofungin, an antifungal medication, is classified as an echinocandin and is utilized for the treatment of Aspergillus and Candida infections. Its mechanism of action involves the inhibition of cell wall synthesis. Echinocandins, a novel class of antifungals, impede the synthesis of glucan in the cell wall, likely through the enzyme 1,3-beta glucan synthase. While there is a possibility of resistance development, studies on in vitro resistance development to Caspofungin by Aspergillus species have not been conducted.

Pharmacokinetics:

Absorption:

● In rats, oral absorption of caspofungin was extremely poor, resulting in oral bioavailability of less than 0.2% after doses of 50 mg/kg.

● In rats receiving single intravenous doses ranging from 0.5 to 5 mg/kg, a nearly linear relationship was observed between the dose and the area under the concentration-time curve (AUC).

● The AUC values were comparable between single doses (4813 ± 451 μg x min/ml) and multiple doses (4061 ± 398 μg x min/ml on day 10) of 2 mg/kg over a period of up to 21 days.

● In monkeys, the terminal half-life of caspofungin appeared to increase over time, and after receiving multiple doses (5 mg/kg) for 14 days, there was evidence of drug accumulation as indicated by an increase in the minimum concentration (Cmin) from 2.4 μg/ml on day 2 to 5.6 μg/ml on day 10.

● It appeared that steady state levels of caspofungin were achieved within 10 days in monkeys.

Distribution:

● Following single 1-hour IV infusions, plasma concentrations of caspofungin decline in a polyphasic manner.

● The decline consists of a short α-phase immediately after infusion, a β-phase (with a half-life of 9 to 11 hours) from 6 to 48 hours post-dose, and a longer γ-phase (with a half-life of 40-50 hours).

● Plasma clearance of caspofungin is primarily influenced by distribution rather than excretion or biotransformation.

● Caspofungin is highly bound to albumin (~97%), and its distribution into red blood cells is minimal.

● Mass balance results indicate that approximately 92% of the administered radioactivity is distributed to tissues within 36 to 48 hours after a single 70-mg dose of [3H] Caspofungin.

● During the first 30 hours after administration, there is limited excretion or biotransformation of caspofungin.

Metabolism:

● Caspofungin undergoes slow metabolism through hydrolysis and N-acetylation.

● It also undergoes spontaneous chemical degradation to form an open-ring peptide compound called L-747969.

● At later time points (≥5 days post-dose), there is a low level of covalent binding of radiolabel in plasma, possibly due to reactive intermediates formed during the chemical degradation of caspofungin.

● Additional metabolism involves hydrolysis into constituent amino acids and their degradates, including dihydroxyhomotyrosine and N-acetyl-dihydroxyhomotyrosine, which are found only in urine, suggesting rapid clearance by the kidneys.

Excretion:

● Two radiolabeled pharmacokinetic studies were conducted, and they showed similar plasma concentrations of radioactivity and caspofungin during the first 24 to 48 hours post-dose.

● Plasma concentrations of caspofungin fell below the limit of quantitation after 6 to 8 days post-dose, while radiolabel fell below the limit of quantitation at 22.3 weeks post-dose.

● After a single intravenous administration of [3H] Caspofungin, approximately 35% of the dose was excreted in feces and 41% in urine as caspofungin and its metabolites.

● A small amount of caspofungin is found to be excreted unchanged in urine (~1.4% of the dose).

● Renal clearance of the parent drug is low (~0.15 mL/min), and the total clearance of caspofungin is 12 mL/min.

1. https://reference.medscape.com/drug/Caspofungin-caspofungin-342584
2. https://go.drugbank.com/drugs/DB00520
3. https://medlineplus.gov/druginfo/meds/a615001.html
4. https://www.webmd.com/drugs/2/drug-20428/caspofungin-intravenous/details
5. https://www.merck.com/product/usa/pi_circulars/c/Caspofungin/Caspofungin_pi.pdf
6. https://www.ema.europa.eu/en/documents/scientific-discussion/Caspofungin-epar-scientific-discussion_en.pdf
7. https://www.medicines.org.uk/emc/product/2226/smpc#gref
8. https://www.rxlist.com/caspofungin/generic-drug.htm
9. https://www.fresenius-kabi.com/en-ca/documents/caspofungin-pm-eng-pristine-022421.pdf