Caspofungin

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications:

• Empirical therapy for presumed fungal infections in febrile, neutropenic patients
• Invasive candidiasis, including candidaemia
• Oesophageal candidiasis (where IV antifungal therapy is appropriate)
• Oropharyngeal candidiasis (where IV antifungal therapy is appropriate)
• Invasive Aspergillosis in patients who are refractory to or intolerant of other therapies, including amphotericin B, lipid formulations of amphotericin B and itraconazole

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Severe hepatic insufficiency, as caspofungin has not been studied in these patients

Cautions

• Pregnancy
• Breastfeeding
• Moderate (Child-Pugh Score 7-9) hepatic impairment
• Less common non-Candida yeasts and non-Aspergillus moulds
• Patients with serious underlying conditions receiving multiple concomitant medications with caspofungin
• History of allergic skin reaction
• Coadministration with ciclosporin

Forms avail. in SA and covered in this monograph: inj

Dosages below include:

• General dosing range
• International manufacturer recommendations
• South African manufacturer recommendations

Infections caused by: Candida albicans, Candida dubliniensis, Candida glabrata, Candida tropicalis, Candida krusei, Aspergillus sp.

General dosing range

• IV: Initial: Day 1: 70mg; Then: 50mg, dly

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

International manufacturer recommendations

Treatment of invasive candidiasis 
Treatment of invasive aspergillosis in patients refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B and/or itraconazole 
- Progression of infection or failure to improve after a minimum of 7 days of prior therapeutic doses of effective antifungal therapy
Empirical therapy for presumed fungal infections (such as Candida or Aspergillus) in febrile, neutropenic patients 

• IV: Loading dose: Day 1: 70mg, as an infusion over 1hr; Then: 50mg, dly, as an infusion over 1hr; Treatment duration: Empirical therapy: Based on patient's response and continued up to 72hrs after resolution of neutropenia; Confirmed fungal infection: ≥14 days and continued for ≥7 days after both neutropenia and clinical symptoms are resolved

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In patients weighing >80kg, after the initial 70mg loading dose, caspofungin 70mg daily is recommended

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Duration of empirical therapy should be based on the patient's clinical response. Therapy should be continued until up to 72 hours after resolution of neutropaenia (ANC≥500). Patients found to have a fungal infection should be treated for a minimum of 14 days and treatment should continue for at least 7 days after both neutropaenia and clinical symptoms are resolved

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Duration of treatment of invasive candidiasis should be based upon the patient's clinical and microbiological response. After signs and symptoms of invasive candidiasis have improved and cultures have become negative, a switch to oral antifungal therapy may be considered. In general, antifungal therapy should continue for at least 14 days after the last positive culture

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Duration of treatment of invasive aspergillosis is determined on a case by case basis and should be based upon the severity of the patient's underlying disease, recovery from immunosuppression, and clinical response. In general, treatment should continue for at least 7 days after resolution of symptoms

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The safety information on treatment durations longer than 4 weeks is limited. However, available data suggest that caspofungin continues to be well tolerated with longer courses of therapy (up to 162 days in adult patients)

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After reconstitution and dilution, the solution should be administered by slow IV infusion over approximately 1hr  

See additional prescribing points

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South African manufacturer recommendations

Empirical therapy for presumed fungal infections in febrile, neutropenic patients

• IV: Loading dose: Day 1: 70mg, as an infusion over 1hr; Then: 50mg, dly, as an infusion over 1hr; Treatment duration: Based on the patient's clinical response; Empirical therapy: Continue until resolution of neutropenia; Confirmed fungal infection: ≥14 days and continued for ≥7 days after both neutropenia and clinical symptoms are resolved

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If the 50mg dose is well tolerated but does not provide an adequate clinical response, the daily dose can be increased to 70mg. Although an increase in efficacy with 70mg daily has not been demonstrated, safety data suggest that an increase in dose to 70mg daily is well tolerated

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Invasive candidiasis, including candidaemia 

• IV: Loading dose: Day 1: 70mg, as an infusion over 1hr; Then: 50mg, dly, as an infusion over 1hr; Treatment duration: Continue dictated by the patient’s clinical and microbiological response, generally ≥14 days after last positive culture

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Patients who remain persistently neutropenic may warrant a longer course of therapy pending resolution of the neutropenia

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The safety and efficacy of multiple doses up to 150mg daily (range: 1 to 51 days; median: 14 days) have been studied in 100 adult patients with invasive candidiasis. Caspofungin was generally well tolerated in these patients receiving caspofungin at this higher dose; however, the efficacy of caspofungin at this higher dose was generally similar to patients receiving the 50mg daily dose of caspofungin

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Oesophageal and oropharyngeal candidiasis (where IV antifungal therapy is appropriate)

• IV: 50mg, dly, as an infusion over 1hr

Invasive aspergillosis
- In patients who are refractory to or intolerant of other therapies, including amphotericin B, lipid formulations of amphotericin B and itraconazole

• IV: Loading dose: Day 1: 70mg, as an infusion over 1hr; Then: 50mg, dly, as an infusion over 1hr; Treatment duration: based upon the severity of the patient’s underlying disease, recovery from immunosuppression, and clinical response

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The efficacy of a 70mg dose regimen in patients who are not clinically responding to the 50mg daily dose is not known. Safety data suggests that an increase in dose to 70mg daily is well tolerated. The efficacy of doses above 70mg has not been adequately studied in patients with invasive aspergillosis

Paed. forms avail. in SA and covered in this monograph: inj

Paed. dosages below include:

• General dosing range
• International manufacturer recommendations
• South African manufacturer recommendations

Infections caused by: Candida albicans, Candida dubliniensis, Candida glabrata, Candida tropicalis, Candida krusei, Aspergillus sp.

General dosing range

• IV: Initial: Day 1: 70mg/m²; Then: 50mg/m², dly; Max: 70mg/24hrs

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

International manufacturer recommendations

Treatment of invasive candidiasis
Treatment of invasive aspergillosis in patients refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B and/or itraconazole
- Progression of infection or failure to improve after a minimum of 7 days of prior therapeutic doses of effective antifungal therapy
Empirical therapy for presumed fungal infections (such as Candida or Aspergillus) in febrile, neutropenic patients 

Younger than 12 months

• Not established for use

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The safety and efficacy of caspofungin have not been sufficiently studied in clinical trials involving neonates and infants below 12 months of age. Caution is advised when treating this age group

Limited data suggest that caspofungin at 25 mg/m² daily in neonates and infants (<3 months of age) and 50 mg/m² daily in young children (3-11 months of age) can be considered

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Between 12 months-17 years

• IV: Loading dose: Day 1: 70mg/m², as an infusion over 1hr; Max single dose: 70mg; Then: 50mg/m², dly, as an infusion over 1hr; Max single dose: 70mg; Treatment duration: Empirical therapy: Based on patient's response and continued up to 72hrs after resolution of neutropenia; Confirmed fungal infection: ≥14 days and continued for ≥7 days after both neutropenia and clinical symptoms are resolved

---

If the 50mg/m² daily dose is well-tolerated but does not provide an adequate clinical response, the daily dose can be increased to 70mg/m²; Max: 70mg/24hrs

---

Duration of empirical therapy should be based on the patient's clinical response. Therapy should be continued until up to 72 hours after resolution of neutropaenia (ANC≥500). Patients found to have a fungal infection should be treated for a minimum of 14 days and treatment should continue for at least 7 days after both neutropaenia and clinical symptoms are resolved

---

Duration of treatment of invasive candidiasis should be based upon the patient's clinical and microbiological response. After signs and symptoms of invasive candidiasis have improved and cultures have become negative, a switch to oral antifungal therapy may be considered. In general, antifungal therapy should continue for at least 14 days after the last positive culture

---

Duration of treatment of invasive aspergillosis is determined on a case by case basis and should be based upon the severity of the patient's underlying disease, recovery from immunosuppression, and clinical response. In general, treatment should continue for at least 7 days after resolution of symptoms

---

The safety information on treatment durations longer than 4 weeks is limited. However, available data suggest that caspofungin continues to be well tolerated with longer courses of therapy (up to 87 days in paediatric patients)

---

After reconstitution and dilution, the solution should be administered by slow IV infusion over approximately 1hr 

See additional prescribing points

---

South African manufacturer recommendations

Empirical therapy for presumed fungal infections in febrile, neutropenic patients
Invasive candidiasis, including candidaemia
Oesophageal or oropharyngeal candidiasis (where IV antifungal therapy is appropriate)
Invasive aspergillosis
- In patients who are refractory to or intolerant of other therapies, including amphotericin B, lipid formulations of amphotericin B and itraconazole

Younger than 3 months

• Not established for use

Between 3 months - 17 years

• IV: Loading dose: Day 1: 70mg/m², as an infusion over 1hr; Max single dose: 70mg; Then: 50mg/m², dly, as an infusion over 1hr; Max single dose: 70mg

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Duration of treatment should be individualised to the indication, as described for each indication in adults:
- Empirical therapy: Continue until resolution of neutropenia
- Confirmed fungal infection: ≥14 days and continued for ≥7 days after both neutropenia and clinical symptoms are resolved
- Invasive candidiasis: Continue dictated by the patient’s clinical and microbiological response, generally ≥14 days after last positive culture
- Oesophageal and oropharyngeal candidiasis: No information available
- Invasive aspergillosis: Based upon the severity of the patient’s underlying disease, recovery from immunosuppression, and clinical response

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If the 50mg/m² daily dose is well tolerated but does not provide an adequate clinical response, the daily dose can be increased to 70mg/m² daily (not to exceed an actual daily dose of 70mg).
Although an increase in efficacy with 70mg/m² daily has not been demonstrated, limited safety data suggest that an increase in dose to 70mg/m² daily is well tolerated

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Older than 17 years

• See adult dosage

Pregnancy

• Caution
• There are no or limited data from the use of caspofungin in pregnant women
• Caspofungin should not be used during pregnancy unless clearly necessary. Animal studies have shown developmental toxicity. Caspofungin has been shown to cross the placental barrier in animal studies

Breastfeeding

• Caution; not recommended
• It is unknown whether caspofungin is excreted in human milk
• Available pharmacodynamic/ toxicological data in animals have shown excretion of caspofungin in milk. Women receiving caspofungin should not breastfeed

Fertility

• For caspofungin, there were no effects on fertility in studies conducted in male and female rats
• There are no clinical data for caspofungin to assess its impact on fertility

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Mild (Child-Pugh Score 5-6): No dose adjustment recommended
• Moderate (Child-Pugh Score 7-9): Caution; dose adjustment recommended
  IV: Loading dose: Day 1: 70mg; Then: 35mg, dly
• Severe (Child-Pugh Score >9): Contraindicated
• Paediatric patients: Caution; no information available

Elderly

• Caution; no dose adjustment recommended 
  In elderly patients (≥65 years), the area under the curve (AUC) is increased by approximately 30%. However, no systematic dosage adjustment is required
  There is limited treatment experience in patients ≥65 years of age

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Anxiety
• Disorientation
• Insomnia
• Headache
• Dizziness
• Paraesthesia
• Somnolence
• Tremor
• Hypoaesthesia
• Fatigue

Cardiovascular Disorders

• Palpitations
• Tachycardia
• Arrhythmia
• Atrial fibrillation
• Congestive cardiac failure
• Thrombophlebitis
• Phlebitis
• Hot flush
• Hypertension
• Hypotension

Respiratory Disorders

• Dyspnoea
• Nasal congestion
• Pharyngolaryngeal pain
• Tachypnoea
• Bronchospasm
• Cough
• Paroxysmal nocturnal dyspnoea
• Hypoxia
• Rales
• Wheezing
• Abnormal breath sounds

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Abdominal pain
• Dry mouth
• Dyspepsia
• Stomach discomfort
• Abdominal distension
• Ascites
• Constipation
• Dysphagia
• Flatulence

Hepatobiliary Disorders

• Elevated hepatic enzymes (alanine aminotransferase, aspartate aminotransferase, blood alkaline phosphatase, bilirubin conjugated, blood bilirubin)
• Cholestasis
• Hepatomegaly
• Hyperbilirubinaemia
• Jaundice
• Abnormal hepatic function
• Hepatotoxicity
• Hepatic disorder
• Increased gamma-glutamyltransferase  

Genitourinary Disorders

• Acute renal failure
• Increased blood creatinine
• Increased urea
• Urinary casts
• Positive white blood cells in urine  
• Increased urine pH  
• Blood present in urine
• Protein present in urine

Endocrine and Metabolic Disorders

• Hypokalemia
• Fluid overload
• Hypomagnesaemia
• Anorexia
• Electrolyte imbalance
• Hyperglycaemia
• Hypocalcaemia
• Metabolic acidosis
• Decreased blood potassium  
• Decreased blood albumin  
• Urine positive for red blood cells  
• Decreased total protein
• Decreased blood sodium  
• Increased blood sodium
• Decreased blood calcium  
• Increased blood calcium
• Decreased blood chloride  
• Increased blood glucose  
• Decreased blood magnesium  
• Decreased blood phosphorus  
• Increased blood phosphorus  
• Decreased blood bicarbonate
• Increased blood chloride
• Increased blood potassium  
• Decreased blood uric acid  
• Decreased carbon dioxide

Musculoskeletal Disorders

• Back pain
• Pain in extremity
• Bone pain
• Muscular weakness
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Flushing
• Rash
• Pruritus
• Erythema
• Hyperhidrosis
• Erythema multiforme
• Macular rash  
• Maculo-papular rash  
• Pruritic rash
• Urticaria
• Allergic dermatitis  
• Generalised pruritus
• Erythematous rash
• Generalised rash
• Morbiliform rash
• Skin lesion
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Fever
• Chills
• Infusion site pruritus
• Infusion site erythema
• Infusion site induration
• Infusion site pain
• Infusion site swelling
• Injection site phlebitis
• Peripheral oedema  
• Tendernessat administration site
• Induration
• Infusion site extravasation
• Infusion site irritation
• Infusion site phlebitis
• Infusion site rash
• Infusion site urticaria
• Injection site erythema
• Injection site oedema
• Injection site pain
• Injection site swelling
• Oedema

Immune, Blood and Lymphatic System Disorders

• Decreased haemoglobin
• Decreased haematocrit
• Decreased white blood cell count
• Anaemia
• Thrombocytopaenia
• Coagulopathy
• Leukopaenia
• Increased eosinophil count
• Decreased/ increased platelet count
• Decreased lymphocyte count
• Increased white blood cell count
• Decreased neutrophil count
• Prolonged activated partial thromboplastin time  
• Increased international normalised ratio  
• Prolonged prothrombin time
• Shortened prothrombin time  

Sensory Disorders

• Dysgeusia
• Ocular icterus
• Blurred vision  
• Eyelid oedema
• Increased lacrimation

Other

• Pain
• Catheter site pain
• Feeling hot/ cold
• Increased immunosuppressant drug level

• Ciclosporin
• Tacrolimus
• Rifampicin
• Metabolic enzyme inducers (See additional prescribing points)
• Dexamethasone (in children)

None routine. Specific cases may require

• Hepatic function

Additional observations

• Anaphylaxis
• Skin rash
• Histamine-related reactions
  - Facial swelling
  - Bronchospasm
  - Sensation of warmth

Reconstitution directions

• DO NOT use any diluents containing glucose, as caspofungin is not stable in diluents containing glucose. DO NOT mix or co-infuse caspofungin with ANY other medicines, as there are no data available on its compatibility with other IV substances, additives or medicinal products
• Visually inspect the infusion solution for particulate matter or discolouration

Coadministration with metabolic enzyme inducers 

• Limited data suggest that an increase in the daily dose of caspofungin to 70mg, following the 70mg loading dose, should be considered when coadministering caspofungin in adult patients with certain inducers of metabolic enzymes. When caspofungin is coadministered to paediatric patients (12 months to 17 years of age) with these same inducers of metabolic enzymes, a caspofungin dose of 70mg/m² daily (not to exceed an actual daily dose of 70mg) should be considered

Caspofungin acetate is a semi-synthetic lipopeptide (echinocandin) compound synthesised from a fermentation product of Glarea lozoyensis. Caspofungin acetate inhibits the synthesis of beta (1,3)-D-glucan, an essential component of the cell wall of many filamentous fungi and yeast. Beta (1,3)-D-glucan is not present in mammalian cells. Fungicidal activity with caspofungin has been demonstrated against Candida yeasts. Studies in vitro and in vivo demonstrate that exposure of Aspergillus to caspofungin results in lysis and death of hyphal apical tips and branch points where cell growth and division occur.

Spectrum of activity: Candida albicans, Candida dubliniensis, Candida glabrata, Candida tropicalis, Candida krusei, Aspergillus sp.

 

Injection (per vial) 50mg

• Cancidas (MSD) originator
• Casfolred 50 (Dr Reddy's Lab)
• Caspex 50 (Acino Pharma)
• Caspofungin 50mg Aspen (Pharmacare Limited)
• Cascagin 50 (Activo Health)
• Fungiject 50 IV (Abex Pharmaceutica)
• Ivecas 50 IV (Pharma Dynamics)
• MSD Caspofungin (MSD)

Injection (per vial) 70mg

• Cancidas (MSD) originator
• Casfolred 70 (Dr Reddy's Lab)
• Caspex 70 (Acino Pharma)
• Caspofungin 70mg Aspen (Pharmacare Limited)
• Cascagin 70 (Activo Health)
• Fungiject 70 IV (Abex Pharmaceutica)
• Ivecas 70 IV (Pharma Dynamics)
• MSD Caspofungin (MSD)