Anfogen

Uses

Aspergillosis, Bacterial endocarditis, Candida albicans, Candidal cystitis, Candidemia, Candidiasis, Coccidioidomycosis, Cryptococcal meningitis, Cryptococcosis, Echinococcosis, Endocarditis, Fungal keratitis, Histoplasmosis, Intestinal or oropharyngeal candidiasis, Invasive aspergillosis, Leishmaniasis, Primary amoebic meningoencephalitis, Pulmonary eosinophilia, Sepsis, Systemic fungal infections, Thrush, Visceral leishmaniasis

Anfogen is also used to associated treatment for these conditions: Coccidioidomycosis, Histoplasmosis, Infections, Fungal, Invasive Aspergillosis, Invasive Fungal Infections, Leishmaniasis, Meningitis, Cryptococcal, Meningitis, Fungal, Mucocutaneous Leishmaniasis, Penicillium marneffei infection, Visceral Leishmaniasis, Candidal cystitis, Disseminated Cryptococcosis, Fungal endophthalmitis, Fungal osteoarticular infections, Ocular aspergillosis, Refractory aspergillosis, Severe Coccidioidomycosis, Severe Cryptococcosis, Severe Fungal infection caused by Basidiobolus spp., Severe Fungal infection caused by Conidiobolus spp., Severe Fungal infection caused by sporotrichosis spp., Severe Histoplasmosis, Severe Mucocutaneous leishmaniasis, Severe North American blastomycosis, Severe Systemic candidiasis

How Anfogen works

Anfogen is fungistatic or fungicidal depending on the concentration obtained in body fluids and the susceptibility of the fungus. The drug acts by binding to sterols (ergosterol) in the cell membrane of susceptible fungi. This creates a transmembrane channel, and the resultant change in membrane permeability allowing leakage of intracellular components. Ergosterol, the principal sterol in the fungal cytoplasmic membrane, is the target site of action of amphotericin B and the azoles. Anfogen, a polyene, binds irreversibly to ergosterol, resulting in disruption of membrane integrity and ultimately cell death.

Dosage

Anfogen dosage

Intrathecal (Adult):

Severe meningitis:Using conventional amphotericin B: If needed, test dose of 1 mg infused over 20-30 minutes. Initially, 25 mcg increased gradually to the max that can be tolerated without excessive discomfort. Usual dose: 0.25-1 mg 2-4 times a wk.

Intravenous(Adult):

Aspergillosis, disseminated:Using conventional amphotericin B: If needed, test dose of 1 mg infused over 20-30 minutes. 0.6-0.7 mg/kg daily for 3-6 mth.

Intravenous(Adult):

Endocarditis:Using conventional amphotericin B: If needed, test dose of 1 mg infused over 20-30 minutes. 0.6-1 mg/kg/day for 1 wk, then 0.8 mg/kg/day every other day for 6-8 wk post-operatively.

Intravenous(Adult):

Severe systemic fungal infections:Using conventional amphotericin B: If needed, test dose of 1 mg infused over 20-30 minutes. Initial dose: 250 mcg/kg daily, increased gradually to a max of 1 mg/kg/day. For seriously ill patients, up to 1.5 mg/kg may be given daily or on alternate days may be needed. Daily dose is infused over 2-4 hr at a concentration of 100 mcg/ml in glucose 5%. If treatment is interrupted for more than 7 days, then restart at 250 mcg/kg daily and increase slowly.

Irrigation(Adult):

Candiduria:Using conventional amphotericin B: 50 mg daily in 1000 ml of sterile water by continuous bladder irrigation for 5-10 days or until cultures are clear.

For conventional amphotericin B: Reconstitute with sterile water for inj (without preservatives), then further dilute with glucose inj 5% (with a pH>4.2) to a final concentration not exceeding 0.1 mg/ml for peripheral infusion or 0.25 mg/ml for central infusion.

Side Effects

IV infusion: Fever, chills, convulsions, malaise; nausea, vomiting, diarrhoea, anorexia; tinnitus, vertigo, hearing loss; hypotension, hypertension, cardiac arrhythmias; peripheral neuropathy; phloebitis, pain at Inj site, disturbances in renal function and renal toxicity.

Toxicity

Oral, rat: LD₅₀ = >5 gm/kg. Anfogen overdoses can result in cardio-respiratory arrest.

Precaution

Renal and hepatic impairment; pregnancy; monitor renal and liver function changes.

Interaction

Increased toxicity with flucytosine. Drug induced renal toxicity enhanced in presence of other nephrotoxic medications. Antagonises effects of azole antifungals.

Food Interaction

Elimination Route

Bioavailability is 100% for intravenous infusion.

Half Life

An elimination half-life of approximately 15 days follows an initial plasma half-life of about 24 hours.

Clearance

• 39 +/- 22 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 1 mg/kg/day at Day 1]
• 17 +/- 6 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 1 mg/kg/day 3-20 days later]
• 51 +/- 44 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 2.5 mg/kg/day at Day 1]
• 22 +/- 15 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 2.5 mg/kg/day 3-20 days later]
• 21 +/- 14 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 5 mg/kg/day at Day 1]
• 11 +/- 6 mL/hr/kg [febrile neutropenic cancer and bone marrow transplant patients receiving infusion of 5 mg/kg/day 3-20 days later]

Pregnancy & Breastfeeding use

Pregnancy Category B. Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

Contraindication

Hypersensitivity; lactation; do not give to patients receiving antineoplastics.

Acute Overdose

May result in cardiac arrest.

Storage Condition

Store at 2-8° C. Reconstituted vials: If protected from light, stable for 24 hr at room temperature and 1 wk if refrigerated. Parenteral admixtures: If protected from light, stable for 24 hr at room temperature and 2 days if refrigerated.

Innovators Monograph

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