Usage
- Anidulafungin is prescribed for the treatment of candidemia (a bloodstream infection caused by Candida species), other forms of invasive candidiasis (such as intra-abdominal abscesses and peritonitis), and esophageal candidiasis (a Candida infection of the esophagus). It has not been sufficiently studied in patients with endocarditis, osteomyelitis, or meningitis due to Candida. It is also associated with high relapse rates in esophageal candidiasis, especially in patients with HIV infection.
- Pharmacological Classification: Echinocandin antifungal agent.
- Mechanism of Action: Anidulafungin inhibits the synthesis of 1,3-β-D-glucan, a vital component of the fungal cell wall. This leads to cell wall instability and ultimately fungal cell death.
Alternate Names
- International Nonproprietary Name (INN): Anidulafungin
- Brand Names: Eraxis, Ecalta
How It Works
- Pharmacodynamics: Anidulafungin exerts its antifungal effect by disrupting the fungal cell wall. It is fungicidal against most Candida species, including Candida glabrata and isolates resistant to azoles and polyenes.
- Pharmacokinetics:
- Absorption: Administered intravenously; thus, 100% bioavailability.
- Distribution: Distributes extensively into tissues.
- Metabolism: Undergoes slow, nonenzymatic chemical degradation in plasma; not metabolized by CYP450 enzymes.
- Elimination: Primarily eliminated via slow chemical degradation; negligible renal clearance.
- Mode of Action: Anidulafungin noncompetitively inhibits 1,3-β-D-glucan synthase, an enzyme complex responsible for synthesizing 1,3-β-D-glucan, an essential polysaccharide in the fungal cell wall. Inhibition results in cell wall stress, lysis, and fungal cell death.
- Receptor Binding, Enzyme Inhibition: Anidulafungin specifically targets the fungal enzyme 1,3-β-D-glucan synthase. It’s not known to bind to human receptors or significantly inhibit human enzymes.
- Elimination Pathways: Undergoes slow chemical degradation in plasma with negligible renal excretion.
Dosage
Standard Dosage
Adults:
- Candidemia and Invasive Candidiasis: 200 mg loading dose on Day 1, followed by 100 mg once daily.
- Esophageal Candidiasis: 100 mg loading dose on Day 1, followed by 50 mg once daily.
Children (1 month and older):
- Candidemia and Invasive Candidiasis: 3 mg/kg (not to exceed 200 mg) loading dose on Day 1, followed by 1.5 mg/kg (not to exceed 100 mg) once daily.
- Esophageal Candidiasis: Not approved.
Special Cases:
- Elderly Patients: No dose adjustment is required.
- Patients with Renal Impairment: No dose adjustment is required.
- Patients with Hepatic Dysfunction: No dose adjustment is required.
- Patients with Comorbid Conditions: Close monitoring is recommended, especially in patients with pre-existing liver disease.
Clinical Use Cases
- Intubation: Dose as per standard recommendations for the underlying Candida infection.
- Surgical Procedures (prophylaxis): Not indicated for surgical prophylaxis.
- Mechanical Ventilation: Dose as per the standard recommendations for the underlying Candida infection.
- Intensive Care Unit (ICU) Use: Dose as per the standard recommendations for the underlying Candida infection.
- Emergency Situations: Dose as per standard recommendations.
Dosage Adjustments
- No dose adjustments are generally needed for renal or hepatic impairment, elderly patients, or those with most comorbid conditions.
Side Effects
Common Side Effects
- Diarrhea
- Nausea
- Vomiting
- Hypokalemia
- Headache
- Rash
- Liver function test abnormalities
- Hypoglycemia
Rare but Serious Side Effects
- Hepatotoxicity (hepatitis, hepatic failure)
- Anaphylaxis (including shock)
- Infusion-related reactions (fever, chills, hypotension)
Contraindications
- Hypersensitivity to anidulafungin or other echinocandins.
- Known or suspected hereditary fructose intolerance (due to the fructose content in the formulation).
Drug Interactions
- Clinically significant interactions are uncommon due to anidulafungin’s non-CYP450 mediated metabolism.
- No dose adjustments are required for concomitant administration with ciclosporin, voriconazole, tacrolimus, amphotericin B, or rifampicin.
- Rifampicin might decrease anidulafungin exposure, though clinical significance is not established.
Pregnancy and Breastfeeding
- Pregnancy: Based on animal data, anidulafungin may cause fetal harm. Use only if the potential benefit outweighs the risk to the fetus.
- Breastfeeding: Anidulafungin is present in rat milk. It’s unknown if it’s present in human milk. The decision to breastfeed should consider the potential risk to the infant.
Drug Profile Summary
- Mechanism of Action: Inhibits 1,3-β-D-glucan synthase, disrupting fungal cell wall synthesis.
- Side Effects: Diarrhea, nausea, vomiting, hypokalemia, elevated liver enzymes, rash, anaphylaxis (rare).
- Contraindications: Hypersensitivity, hereditary fructose intolerance.
- Drug Interactions: Few clinically significant interactions.
- Pregnancy & Breastfeeding: Use with caution; potential fetal risk; unknown if present in human milk.
- Dosage: See dosage section above.
- Monitoring Parameters: Liver function tests, serum potassium, signs of hypersensitivity or infusion reactions.
Popular Combinations
- Often used as monotherapy.
- May be used in conjunction with other antifungals in cases of severe or refractory infections, though data is limited.
Precautions
- Monitor liver function.
- Observe for hypersensitivity reactions, particularly during infusion.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Anidulafungin?
A: See dosage section above.
Q2: How is Anidulafungin administered?
A: Administered intravenously as a slow infusion (over 1-2 hours).
Q3: What are the most common side effects?
A: Diarrhea, nausea, vomiting, hypokalemia, rash, and headache are among the more commonly observed side effects.
Q4: Is Anidulafungin safe for patients with renal impairment?
A: Yes, no dose adjustment is necessary for patients with renal impairment, including those on dialysis.
Q5: Are there any significant drug interactions I should be aware of?
A: Clinically significant drug interactions are uncommon. No dose adjustments are needed for concomitant administration with ciclosporin, voriconazole, tacrolimus, amphotericin B, or rifampicin. Rifampicin may decrease anidulafungin exposure, although the clinical significance is not yet fully understood.
Q6: Can Anidulafungin be used during pregnancy?
A: Anidulafungin should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus, as suggested by animal studies. There are no controlled studies in pregnant humans.
Q7: Can Anidulafungin be used in breastfeeding mothers?
A: Anidulafungin’s presence in human milk is unknown, although it has been detected in rat milk. The decision to continue/discontinue breastfeeding should consider the potential risks to the neonate and the mother’s clinical need for the drug.
Q8: Is Anidulafungin effective against all Candida species?
A: While Anidulafungin exhibits fungicidal activity against most Candida species, including C. glabrata, individual susceptibility patterns can vary. It is crucial to consider species-specific susceptibility data where available.
Q9: How long should treatment with Anidulafungin typically last?
A: The duration of Anidulafungin therapy should be guided by the patient’s clinical response and the specific type of Candida infection being treated. Typically, treatment continues for at least 14 days after the last positive culture for candidemia and other invasive Candida infections. For esophageal candidiasis, treatment continues for at least 14 days and at least 7 days following the resolution of symptoms.
