Caspofungin is an antifungal medication used to treat a variety of fungal infections. It belongs to a class of drugs called echinocandins, which work by inhibiting the synthesis of beta-(1,3)-D-glucan, an essential component of the fungal cell wall. By disrupting cell wall synthesis, caspofungin weakens the fungal cell wall, leading to cell death.

This medication is primarily used to treat invasive aspergillosis, candidemia, and other serious fungal infections caused by Candida species (such as Candida albicans and Candida glabrata). It's typically administered intravenously, and its usage is usually reserved for cases where other antifungal medications have been ineffective or cannot be used due to resistance or intolerance.

An antifungal medication called capsofungin (cancidas) prevents the production of (1,3)-D-glucan, which is necessary for the creation of fungal cell walls. These conditions are treated with it:

• Treatment of invasive Aspergillosis in patients older than 3 months who are resistant to or intolerable to alternative treatments such itraconazole and amphotericin B.
• Esophageal Candidiasis Treatment (Not approved for oropharyngeal candidiasis).
• Treatment for candida infections that cause pleural space infections, peritonitis, and intra-abdominal abscesses. Meningitis, endocarditis, and osteomyelitis brought on by candida have not been examined.
• Empiric treatment for patients with febrile neutropenia who have fungal infections

Off-Label Use of Caspofungin in Adults include:

• Candidiasis of the articular bones
• Invasive candidiasis prevention in high-risk ICU patients
• In non-neutropenic ICU patients with candidiasis as the first course of treatment
• Patients with oesophagal candidiasis who are HIV-positive
• prevention of Candida infection in cancer patients with neutropenia who are at high risk
• persistent, widespread candidiasis (such as hepatosplenic candidiasis);
• Candida infections that induce intravascular infections
• Oropharyngeal Candidiasis Is Refractory

Caspofungin Dose in Adult

Doctors decide how long someone should take caspofungin based on how they're doing and how the infection is responding.

Caspofungin As a last resort for treating invasive aspergillosis, capofungin

• Through intravenous (IV) therapy, the typical starting dose is 70 mg on the first day, followed by 50 mg once daily for subsequent doses.
• The duration of treatment usually spans from 6 to 12 weeks, but it may vary based on factors like the location and severity of the infection, as well as the level and duration of immunosuppression in the patient.

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Caspofungin dose in the treatment of Candidemia and other Candida infections:  

• Through intravenous (IV) therapy, the typical starting dose is 70 mg on the first day, followed by 50 mg once daily for subsequent doses.
• This treatment regimen is usually continued for at least 14 days after the last positive culture, or longer if the patient is experiencing neutropenia.
• It's worth noting that higher doses (150 mg once daily) haven't shown additional benefits or risks compared to the standard dosing.
• According to the IDSA Candidiasis guidelines, clinically stable patients with fluconazole-susceptible isolates and negative repeat cultures may transition to fluconazole, usually after 5 to 7 days.

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Caspofungin off-label usage as prevention in cancer patients with neutropenia who are at high risk for Candida infection:

• Caspofungin is administered intravenously at a dose of 50 mg once daily.

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Caspofungin off-label usage to treat hepatosplenic candidiasis that has spread throughout the body:

• Caspofungin is typically administered intravenously.
• The initial dose is 70 mg on the first day, followed by 50 mg daily for several weeks.
• After the initial intravenous therapy, patients may transition to oral fluconazole therapy.
• This treatment approach is based on guidelines provided by the Infectious Diseases Society of America (IDSA) in 2016, as outlined by Pappas and colleagues.
• Off-label use indicates that the medication is being used in a manner not specified in the FDA-approved prescribing information but may still be recommended based on clinical evidence and judgment.

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Caspofungin off label use as empiric therapy in the treatment of non-neutropenic ICU patients with Candidiasis:  

• Caspofungin is administered intravenously.
• The initial dose is 70 mg on the first day, followed by 50 mg once daily for subsequent doses.
• Clinicians should consider discontinuing treatment after 4 to 5 days if there is no clinical improvement.
• However, if patients respond positively to antifungal therapy, treatment should be continued for a total duration of 2 weeks, as recommended by the Infectious Diseases Society of America (IDSA) guidelines.

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Caspofungin dose in the treatment of esophageal Candidiasis:

• Caspofungin is administered intravenously.
• The initial dose is 70 mg on the first day, followed by 50 mg daily for subsequent doses.
• Patients may transition to oral fluconazole therapy once they can tolerate oral intake.
• If the disease is refractory to fluconazole, caspofungin should be continued for 14 to 21 days, as recommended by the Infectious Diseases Society of America (IDSA) guidelines provided by Pappas and colleagues in 2016.
• However, according to the manufacturer's labeling, the dosing information may differ, suggesting 50 mg once daily.

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Caspofungin off label use as an alternative agent in the treatment of Esophageal Candidiasis in HIV-infected patients:

• Caspofungin can be used as an alternative agent, albeit off-label.
• The recommended intravenous dose is 50 mg once daily, continued for a duration of 14 to 21 days.
• It's worth noting that echinocandins like caspofungin may have a higher relapse rate compared to fluconazole, as indicated by the Department of Health and Human Services (HHS) guidelines for opportunistic infections in adults in 2017.

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Caspofungin off label use in the treatment of Candidiasis and intravascular infections (native or prosthetic valve endocarditis, infection of implantable cardiac devices, and suppurative thrombophlebitis):  

• Caspofungin is used off-label with an intravenous dose of 150 mg daily.
• For native or prosthetic valve endocarditis, therapy should continue for at least 6 weeks after valve replacement surgery, with longer durations in patients with complications.
• For implantable cardiac devices, therapy should last 4 to 6 weeks after surgery, depending on the extent of infection.
• For suppurative thrombophlebitis, treatment should continue for at least 2 weeks after clearing of candidemia.
• Clinically stable patients with fluconazole-susceptible isolates and negative repeat cultures may transition to fluconazole therapy, as recommended by the Infectious Diseases Society of America (IDSA) guidelines provided by Pappas and colleagues in 2016.

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Caspofungin off label use as an alternative agent in the treatment of Candidiasis and osteoarticular infections like osteomyelitis or septic arthritis:  

• Caspofungin can serve as an alternative therapy, though off-label.
• The recommended intravenous dose ranges from 50 to 70 mg daily for a minimum of 14 days.
• After this initial treatment period, patients may transition to fluconazole therapy, as advised by the Infectious Diseases Society of America (IDSA) guidelines provided by Pappas and colleagues in 2016.

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Caspofungin off label use as an alternative therapy in the treatment of Candidiasis and prophylaxis against invasive candidiasis in high-risk ICU patients:

• Caspofungin can be used as an alternative therapy, although off-label.
• The recommended intravenous dose includes a loading dose of 70 mg on the first day, followed by 50 mg daily thereafter, as indicated by the Infectious Diseases Society of America (IDSA) guidelines provided by Pappas and colleagues in 2016.

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Caspofungin off label use as an alternative therapy in the treatment of refractory oropharyngeal Candidiasis:

• Caspofungin can be considered as an alternative therapy, though off-label.
• The recommended intravenous dose is 70 mg on the first day, followed by 50 mg once daily for subsequent doses, as advised by the Infectious Diseases Society of America (IDSA) guidelines provided by Pappas and colleagues in 2016.

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Caspofungin dose in the empiric treatment of neutropenic patients with Fungal infections:

• Caspofungin is administered intravenously.
• The initial dose is 70 mg on the first day, followed by 50 mg once daily for subsequent doses.
• Treatment should continue until resolution of neutropenia.
• If a fungal infection is confirmed, therapy should be maintained for a minimum of 14 days, extending for at least 7 days after both neutropenia and clinical symptoms have resolved.
• In cases where the clinical response is inadequate, the dosage may be increased up to 70 mg once daily if tolerated.

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Dosage adjustment with concomitant use of an enzyme inducer:

• When patients are receiving rifampin concurrently, the usual dosage of caspofungin is increased to 70 mg once daily.
• Similarly, if patients are taking enzyme inducers such as carbamazepine, dexamethasone, efavirenz, nevirapine, phenytoin, or possibly other enzyme inducers, they may also require an increased dose of caspofungin to 70 mg once daily. This adjustment compensates for the potential reduction in caspofungin levels caused by the induction of drug-metabolizing enzymes by these medications.

Caspofungin (cancidas) Dose in Children

Caspofungin dose in the treatment of invasive Aspergillosis:  

In infants aged 3 months and older, children, and adolescents under 18 years:

• Caspofungin is administered intravenously.
• The initial dose is 70 mg per square meter of body surface area on the first day, followed by 50 mg per square meter once daily.
• If the clinical response is inadequate, the dosage may be increased to 70 mg per square meter once daily.
• The maximum dose should not exceed 70 mg per dose.
• It's important to note that caspofungin is recommended for salvage therapy or when other antifungals are contraindicated, rather than for routine use as primary treatment, according to guidelines provided by the Infectious Diseases Society of America (IDSA) by Patterson and colleagues in 2016.

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Caspofungin dose in the empiric treatment of Fungal infections in neutropenic patients:

In infants aged 3 months and older, children, and adolescents under 18 years

• Caspofungin is administered intravenously.
• The initial dose is 70 mg per square meter of body surface area on the first day, followed by 50 mg per square meter once daily.
• If the clinical response is inadequate, the dosage may be increased to 70 mg per square meter once daily.
• The maximum dose should not exceed 70 mg per dose.
• This dosing regimen is designed to address fungal infections in neutropenic patients and provides flexibility for dose adjustments based on individual clinical responses.

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Caspofungin dose in the treatment of Candida infections:

For non-HIV-exposed/-positive patients, including infants, children, and adolescents:

• Infants <3 months:
  • Limited data suggest an initial intravenous dose of 25 mg per square meter of body surface area once daily.
  • This dosing regimen is based on pharmacokinetic studies showing similar serum concentrations to standard adult doses, with slightly elevated trough concentrations not correlated with increased adverse events.
• Infants ≥3 months, Children, and Adolescents <18 years:
  • The recommended initial intravenous dose is 70 mg per square meter of body surface area on the first day, followed by 50 mg per square meter once daily.
  • If the clinical response is inadequate, the dosage may be increased to 70 mg per square meter once daily.
  • The maximum dose should not exceed 70 mg per dose.
  • For esophageal disease, treatment should continue for 7 to 14 days after symptom resolution, while for candidemia, treatment should be continued until 2 weeks after the last positive blood culture.

For HIV-exposed/-positive patients, the treatment duration varies based on the site of infection:

• Infants <3 months:
  • Limited data suggest an initial intravenous dose of 25 mg per square meter of body surface area once daily.
• Infants ≥3 months, Children, and Adolescents ≤17 years:
  • The recommended initial intravenous dose is 70 mg per square meter of body surface area on the first day, followed by 50 mg per square meter once daily.
  • The maximum dose should not exceed 70 mg per dose.
• Adolescents ≥18 years:
  • The recommended initial intravenous dose is 70 mg on the first day, followed by 50 mg once daily.

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Dosing adjustment for concomitant administration:

• For patients receiving rifampin concurrently, including infants aged 3 months and older, children, and adolescents, the usual dosage of caspofungin is increased to 70 mg per square meter of body surface area once daily. The maximum dose should not exceed 70 mg per dose.

• Similarly, for patients receiving enzyme inducers such as carbamazepine, dexamethasone, phenytoin, nevirapine, or efavirenz, including infants aged 3 months and older, children, and adolescents, an increase in caspofungin dose to 70 mg per square meter of body surface area once daily may be required. The maximum dose should not exceed 70 mg per dose. These adjustments compensate for potential reductions in caspofungin levels caused by the induction of drug-metabolizing enzymes by these medications.

Pregnancy Risk Factor D

• Caspofungin might harm babies if they're exposed to it while still in the womb, because of how it works.
• If a pregnant person needs treatment for invasive Aspergillus or Candida infections, doctors usually prefer using different medications instead, according to guidelines from the Department of Health and Human Services (HHS) and the Infectious Diseases Society of America (IDSA).

Caspofungin use during breastfeeding:

• The presence of caspofungin in breast milk isn't known for certain.
• The decision on whether to breastfeed while undergoing therapy with caspofungin should carefully weigh the risk of the baby being exposed to the medication, the benefits of breastfeeding for the infant's health, and the benefits of treatment for the mother.

Caspofungin Dose adjustment in renal disease:

• Dose adjustment in renal disease is not required.
• In patients with end-stage renal disease (ESRD) who require dialysis, including those undergoing intermittent hemodialysis (IHD), peritoneal dialysis, or continuous renal replacement therapy (such as CVVHD), no supplemental dose or dosage adjustment is usually necessary for caspofungin. This applies even if dialysis is poorly effective. These recommendations are supported by studies from Aronoff in 2007 and Heintz in 2009.

Caspofungin Dose adjustment in patients with Liver disease:

• For patients with mild impairment, specifically Child-Pugh class A, no dosage adjustment is necessary for caspofungin.
• For those with moderate impairment (Child-Pugh class B), the recommended initial dose is 70 mg on the first day, followed by 35 mg once daily. It's important to note that recent pharmacokinetic data suggest that this reduced dose may result in suboptimal drug exposure.
• As for severe impairment (Child-Pugh class C), the manufacturer's labeling doesn't provide specific dosage adjustments. However, recent pharmacokinetic data indicate that the degree of impairment, whether moderate or severe, doesn't further decrease the clearance of caspofungin. Therefore, patients with severe impairment can be dosed the same as those with moderate impairment, following the initial dosing regimen of 70 mg on the first day and 35 mg once daily thereafter. These adjustments are based on studies by Mistry in 2007 and Gustot in 2018.

Common Side Effects of Caspofungin Include:

• Cardiovascular:
  • Hypotension
  • Peripheral edema
  • Tachycardia
• Central nervous system:
  • Chills
  • Headache
• Dermatologic:
  • Skin rash
• Gastrointestinal:
  • Diarrhea
  • Vomiting
  • Nausea
• Hematologic & oncologic:
  • Decreased hemoglobin
  • Decreased hematocrit
  • Decreased white blood cell count
  • Anemia
• Hepatic:
  • Increased serum alkaline phosphatase
  • Increased serum ALT
  • Increased serum AST
  • Increased serum bilirubin
• Local:
  • Localized phlebitis
• Renal:
  • Increased serum creatinine
• Respiratory:
  • Respiratory failure
  • Cough
  • Pneumonia
• Miscellaneous:
  • Infusion-related reaction
  • Fever
  • Septic shock

Less Common Side Effects of Caspofungin Include:

• Cardiovascular:
  • Hypertension
  • Atrial fibrillation
  • Bradycardia
  • Cardiac arrhythmia
  • Edema
  • Flushing
  • Myocardial infarction
• Central nervous system:
  • Anxiety
  • Confusion
  • Depression
  • Dizziness
  • Drowsiness
  • Fatigue
  • Insomnia
  • Seizure
• Dermatologic:
  • Erythema
  • Pruritus
  • Skin lesion
  • Urticaria
• Endocrine & metabolic:
  • • Hypomagnesemia
    • Hyperglycemia
    • Hypokalemia
    • Hypercalcemia
    • Hypervolemia
• Gastrointestinal:
  • Abdominal pain
  • Mucosal inflammation
  • Abdominal distention
  • Anorexia
  • Constipation
  • Decreased appetite
  • Dyspepsia
  • Upper abdominal pain
• Genitourinary:
  • Urinary tract infection
  • Nephrotoxicity
• Hematologic & oncologic:
  • Blood coagulation disorder
  • Febrile neutropenia
  • Neutropenia
  • Petechia
  • Thrombocytopenia
• Hepatic:
  • Decreased serum albumin
  • Hepatic failure
  • Hepatomegaly
  • Hepatotoxicity
  • Hyperbilirubinemia
  • Jaundice
• Infection:
  • Sepsis
  • Bacteremia
• Local:
  • Catheter infection
  • Infusion site reaction
• Neuromuscular & skeletal:
  • Arthralgia
  • Back pain
  • Limb pain
  • Tremor
  • Weakness
• Renal:
  • Hematuria
  • Increased blood urea nitrogen
  • Renal failure
• Respiratory:
  • Dyspnea
  • Pleural effusion
  • Respiratory distress
  • Rales
  • Epistaxis
  • Hypoxia
  • Tachypnea

Contraindication to Caspofungin include:

• Individuals who have a known hypersensitivity to caspofungin or any component of its formulation should avoid its use.
• While there is limited documentation regarding allergenic cross-reactivity among echinocandin antifungals, such as caspofungin, it's important to note that similarities in chemical structure and pharmacologic actions may potentially lead to cross-sensitivity reactions.
• Therefore, even though it's not conclusively established, the possibility of cross-sensitivity cannot be entirely ruled out.

Warnings and Precautions

Hepatic effects

• Caspofungin can sometimes affect the liver, causing increased levels of liver enzymes (transaminases) and, rarely, significant liver problems like hepatitis or liver failure in both children and adults.
• It's important to monitor liver function tests during caspofungin therapy.

Hypersensitivity

• Hypersensitivity reactions to caspofungin can range from mild symptoms like rash or facial swelling to severe reactions such as anaphylaxis or Stevens-Johnson syndrome, which can be life-threatening.
• If any signs of a hypersensitivity reaction appear, like difficulty breathing, swelling, rash, or severe skin reactions, it's crucial to stop the medication immediately and seek medical attention.
• Supportive treatment may be necessary depending on the severity of the reaction.
• Being vigilant and responsive to any signs of hypersensitivity is essential for ensuring patient safety during caspofungin therapy.

Hepatic impairment

• Caspofungin should be used cautiously in patients with hepatic impairment.
• In adults with moderate impairment (Child-Pugh class B), dosage reduction may be necessary.
• However, the safety and effectiveness of caspofungin have not been established in children with any degree of hepatic impairment or in adults with severe impairment (Child-Pugh class C).

Caspofungin: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor D (Consider therapy modifications)
CycloSPORINE Systemic	Caspofungin may have an adverse or toxic effect. Caspofungin can increase serum CycloSPORINE Systemic concentrations. CycloSPORINE (Systemic) may increase the serum concentration of Caspofungin. Management: Consider the potential benefits and risks of caspofungin versus the possible increased risk of hepatotoxicity. Patients with abnormal liver function should be monitored and treated accordingly. It is possible to experience mild transaminase elevations quite often.
Inducers for Drug Clearance	Caspofungin serum concentration may be decreased. Management: Increase caspofungin dosage to 70 mg per day for adults, or 70 mg/m for children, when administered with known drug clearance inducers.
RifAMPin	Caspofungin serum concentration may be decreased. Management: Caspofungin prescribing instructions recommend a daily dose of 70mg for adults and 70mg/m for children. Children who also receive rifampin should take 70 mg/day.
Risk Factor X (Avoid Combination)
Saccharomyces boulardii	Antifungal Agents (Oral, Systemic) can reduce the therapeutic effects of Saccharomyces boulardii.

Monitor:

Liver Function:

• Caspofungin can affect how your liver works.
• Your doctor may check your liver function with tests during treatment.
• If these tests show any problems or get worse, your doctor may stop the medication.

Anaphylaxis, Skin Rash, or Histamine-Related Reactions:

• Some people may have allergic reactions to caspofungin.
• These reactions can range from mild, like a skin rash or facial swelling, to severe, like anaphylaxis.
• If you experience difficulty breathing, swelling, rash, or severe skin reactions, stop taking the medication immediately and seek medical help.
• Treatment may be needed depending on the severity of the reaction.

How to administer Caspofungin:

IV Administration:

• Caspofungin should be given slowly through an intravenous (IV) infusion.
• It should be infused over approximately one hour.
• It's important not to administer caspofungin as an IV bolus injection.
• This slow infusion helps ensure safety and effectiveness of the medication.

Mechanism of action Caspofungin (Cancidas):

• Caspofungin works by inhibiting the synthesis of a substance called β(1,3)-D-glucan, which is crucial for building the cell wall of certain fungi.
• This action disrupts the growth of these fungi, particularly in areas where cells are actively multiplying.
• Importantly, mammalian cells, which make up our bodies, don't rely on β(1,3)-D-glucan for their cell structure.
• This means that caspofungin's effects are specific to fungi, reducing the likelihood of harming human cells and minimizing potential side effects.

Distribution:

• Caspofungin concentrations in the cerebrospinal fluid (CSF) are very low, typically nondetectable at less than 10 ng/mL based on available data.
• The medication binds to albumin in the blood, with approximately 97% of it being bound to this protein.

Metabolism:

• Caspofungin is metabolized slowly in the body through processes like hydrolysis, N-acetylation, and spontaneous degradation.
• These metabolic processes eventually break caspofungin down into its component amino acids.
• Overall, caspofungin undergoes extensive metabolism in the body.

Elimination:

• The elimination half-life of caspofungin is around 9 to 11 hours during the distribution phase and 40 to 50 hours during the terminal phase.
• In children under 12 years old, the distribution phase half-life is shorter, approximately 8 hours, compared to adults.

Excretion:

• Caspofungin is primarily excreted from the body through urine (about 41% of the total dose, primarily as metabolites) and feces (about 35% of the total dose, also primarily as metabolites).
• Only a very small percentage, approximately 1%, of the total dose is excreted unchanged in the urine.

Caspofungin International brands:

• BDCASPO
• Cancidas
• Mymicyas

Caspofungin (cancidas) Brands in Pakistan:

Update soon.