Fluconazole

By M. Younus, BVSc, MVSc, SKUAST-K

Fluconazole (triazole).

Key features:

• First-generation triazole antifungal medication
• Extra label drug.
• Fungistatic used to treat serious fungal or yeast infections.
• Avoid combining with Erythromycin, as it may raise serum levels of Erythromycin.
• Can be taken with or without food as it doesn’t depend on pH for absorption.

MOA:

• Fluconazole stops enzymes that make ergosterol, a key part of the fungal cell wall.
• This weakens the cell, making it leaky, and eventually the fungus dies.

Effects:

• Fungal growth is inhibited.

Side effects:

• GIT upset including vomiting and diarrhea.
• long term use can cause liver toxicity.

Spectrum:

• Dermatophytosis (ringworm).
• Blastomycosis.
• Cryptococcosis (window washer’s disease).
• Histoplasmosis.
• Candidiasis.
• Coccidioidomycosis (Valley Fever).
• Usually reserved for more serious fungal disease.
• Malassezia dermatitis (yeast infection of the skin).

Species:

• Dog, Cat and Birds.

Indications:

• Fungal infections of skin , toenail, brain spinal cord and bone.

Dose:

• 2.5-5 mg/kg PO OD x 8-12 weeks in dog.
• 2.5-10 mg/kg PO BD in cat.
• 5-10 mg/kg PO OD X 6 weeks in birds.

Contraindication:

• Pregnancy.
• Lactation.

Brands:

Human brands in India.

• Fluka-150 ( Fluconazole 150mg) tab(Cipla India).

• Af-150 ( Fluconazole 150mg) tab (Systopic India).

• Gocan 150 ( Fluconazole 150mg) tab( Hetero Drugs India).

• Fungid best 150 ( Fluconazole 150mg)tab (Hegde and Hegde Pharmaceuticals India).

Flucytosine

By M. Younus, BVSc, MVSc, SKUAST-K

Flucytosine (fluorinated pyrimidine).

Key Features:

• Absorption is good and enters the CNS in high concentration.
• well absorbed and enters the CNS in high concentrations.
• Used in combination with amphotercin B to treat cryptococcal meningitis.
• The use is mainly for treating cryptococcosis in cats because it can be harmful to dogs.

MOA:

• Flucytosine interfers with purine and pyrimidine uptake.
• Flucytosine deaminated to 5-fluorouracil (5-FU) and then converted to 5-fluorodeoxyuridylic acid monophosphate.
• The 5-fluorodeoxyuridylic acid monophosphate is noncompetitive inhibitor of thymidylate synthetase which interferes with DNA synthesis.

Effects:

• Flucytosine is either fungistatic or fungicidal depending on the concentration of drug.

Side effects:

• Vomiting, diarrhea, and anorexia.
• Bone marrow suppression leading to anemia, leukopenia, and thrombocytopenia
• Skin problems like depigmentation, ulceration, exudation, and crust formation( most advers effects).

Drug combinbation:

• Flucytosine combined with amphotercin B for the treatment of cryptococcosis.

Species :

• Dog and Cat.

Indication:

• Cryptococcal meningitis.

Dose:

• 25–50 mg/kg, PO TID for 6 weeks in dog and cat.

Contraindication:

• Use cautiously in dogs as it cause toxic reaction in them.
• Bone marrow disease.

Brands:

Human brands in India:

• Cytorx 500mg (Flucytosine 500mg ) tab ( Cipla India).
• Fcfung 500mg (Flucytosine 500mg ) tab ( Glenmark Pharmaceuticals India).
• Flucyto 500mg (Flucytosine 500mg ) tab ( Aureate Healthcare India).
• Cytobuz 500mg (Flucytosine 500mg ) tab ( Alniche Life Sciences India).
• Cytoflu 500mg (Flucytosine 500mg ) tab ( Jolly Healthcare India).

Griseofulvin

By M. Younus, BVSc, MVSc, SKUAST-K

Griseofulvin

Key features:

• Fungistatic, FDA-approved for horses but used off label in dogs and cats.
• Verify FIV status in cats before administering this drug.
• Solubility is very low water.
• Absorption improves with a fatty meal and polyethylene glycol.
• Micronization helps absorption, with ultramicrsized forms being nearly 100% absorbed.
• Griseofulvin accumulates in the skin (mainly the outer layer), hair, nails, fat, muscles, and liver. It shows up in the skin within 4 hours after taking it.

MOA:

• Griseofulvin builds up in keratin precursor cells and effectively targets diseased tissue. It binds to new keratin, making it resistant to fungal infections.
• When it reaches the skin, the keratin-Griseofulvin complex connects to fungal microtubules (tubulin), and disrupts fungal cell division.

Effects:

• It is Fungistatic in actin and is effective only against dermatophytes (eg, Microsporum, Trichophyton, and Epidermophyton).

Side effects:

• Vomiting, diarrhea and increased liver enzyme activity.
• Decreased appetite.
• Depression.
• Incoordination.

Species:

• Horse, Rabbit, Dog and Cat.

Indication:

• Ring worm infection.
• Advanced dermatophytosisin rabbits.

Dose:

• 5–10 mg/kg OD PO for 3–6 weeks in adult horses.
• 15 mg/kg OD PO, for 2-4 weeks in dog .
• Ultramicrosize 6.25 mg/kg PO BD for 4–6 weeks and Microsize: 25 mg/kg PO OD/BD for one month Rabbit.
• 10–50 (up to 130) mg/kg OD PO in dog and cat if drug is in microsized form.
• 5–20 (up to 50) mg/kg OD, PO in dog and cat if drug is in ultramicrosized form.

Contraindication:

• Feline immunodeficiency virus (FIV)-positive cats.
• Pregnant animals.
• Kittens < 8 weeks old

Brands:

Human brands in India:

• Grisovin-FP 500(Griseofulvin 500mg) tab( Glaxo SmithKline Pharmaceuticals India).
• Grisovin-FP 250(Griseofulvin 250mg) tab( Glaxo SmithKline Pharmaceuticals India).
• Ecovin 500(Griseofulvin 500mg) tab ( Brinton Pharmaceuticals India).
• Ecovin 250(Griseofulvin 250mg) tab ( Brinton Pharmaceuticals India).
• Ulvin 500(Griseofulvin 500mg) tab (Seagull Pharmaceutical India ).
• Fulvinem 500(Griseofulvin 500mg) tab ( Medopharm India).
• Fulvinem 250(Griseofulvin 250mg) tab ( Medopharm India).
• Grisofline 500(Griseofulvin 500mg) ( Shalina Laboratories India).
• Grisofline 250 Griseofulvin 250mg) ( Shalina Laboratories India).
• Dermonorm 500(Griseofulvin 500mg) tab ( Glaxo SmithKline PharmaceuticalsIndia)

Iodides

By M. Younus, BVSc, MVSc, SKUAST-K

Iodides ( Salts of Iodine).

Key features:

• Commonly used Iodides are Sodium Iodide and Potassium Iodide
• Are used against infections caused by bacteria, actinomycetes, and fungi.
• Sodium Iodide is preferred over Potassium Iodide.

MOA:

• Iodide break down important proteins, nucleotides, and fatty acids in fungal cell, ultimately causing cell death.

Effects:

• Fungicidal action.

Side effects:

• Vomiting, diarrhea and inappetence in small animals
• Ocular and nasal discharge, scaling, and a dry coat in small animals.
• Seromucoid discharge, lacrimation, cough, invariable appetite, joint pain, and seborrhea sicca with partial alopecia in large animals.

Species:

• Horse, Cow, dog and Cat.

Indication:

• Zygomycosis, and Sporothrix schenckii.
• Sporotrichosis.
• Actinomycosis.
• Actinobcilosis.
• Necrotic stomatitis.

Dose:

• Potassium Iodide: 40 mg/kg, PO, OD for two months in dogs.
• Potassium Iodide : 20 mg/kg, PO OD for two months in cat.
• Potassium Iodide : 5-10 gm /day PO for 7-10 days in cow.
• Potassium Iodide : 8gm/day PO in horse.
• Sodium iodide : 60 mg /kg IV repeated weekly in cows.
• Sodium iodide: 60 mg/kg IV once daily. Administer this for 3 days. Then follow with 30 g orally, once daily for 30 days in a horse.
• Sodium iodide : 44 mg/kg/day, PO, for dogs, and 22 mg/kg/day, PO, for cats.

Contraindication:

• Systemic iodide may also cause abortion and should not be used in pregnant or lactating animals.
• Potassium Iodide should not be given IV.

Brands:

• Potassium Iodide 20gm powder ( Zenley Animal Health India).

Itraconazole

By M. Younus, BVSc, MVSc, SKUAST-K

Itraconazole ( N-arylpiperazine )

Key features:

• A broad-spectrum antifungal drug from the imidazole family.
• Used in the treatment of systemic and superficial fungal infections.
• Drug of choice for blastomycosis and histoplasmosis
• Absorbs better at lower pH; take with food.
• Oral solution is better absorbed than capsules in horses.
• less effective for oral, CNS, eye, and prostate infections due to limited penetration. However, many fungal infections in these areas can be effectively treated with itraconazole.
• Interact with cholinergics , busulfan and antacids . 

MOA:

• Itraconazole is a Cytochrome P450 3A4 and P-Glycoprotein inhibitor. It prevents the synthesis of ergosterol, a key component of fungal cell membranes, leading to the rupture of fungal cells.

Effects:

• Fungal growth is inhibited.

Side effects:

• Loss of appetite, vomiting, and weight loss.
• Ulcerate dermatitis.
• leg swelling.
• Excessive a saliva production
• Liver toxicity and inflammation of the blood vessels.

Drug combination:

• Itraconazole + Amphotericin B for rapidly progressing fungal infections.

Species:

• Dog and Cat.

Indication:

• Fungal infections caused by dermatophytes, Malassezia , Candida, Histoplasma , Blastomyces and Sporothrix.
• Infection from the protozoans Leishmania and Trypanosoma.

Dose:

• 5–10 mg/kg, PO OD for 60 days in dogs.
• 5/kg, PO OD for 7 days in cats. Follow with a one week break. Then use the same dosage for another 7 days. Take another one week break. Repeat the 7 days dosage regime in cats.
• Dogs given more than 10 mg/kg of itraconazole can develop severe skin ulcers.

Contraindication:

• Concurrent administration of antacids, H₂-blockers, and cholinergics.
• Hepatic impairment or achlorhydria (or hypochlorhydria).

Brands:

• Itopet 60 ml( 10mg Itraconazole/ml) oral suspension( Medilogy Biotech india).
• Izopet 100ml ( 10mg Itraconazole/ml) oral solution ( Intas India).
• Vetconazole 100mg ( 100mg Itraconazole Capsule( Vetina India).
• Vetconazole 200mg ( 200mg Itraconazole Capsule( Vetina India).
• SUBAvet IT 50 (50mg Itraconazole Capsule( Vivaldis India).
• Itrpet 100ml ( 20mg Itraconazole/ml) oral solution ( PCD India).

Miconazole

By M. Younus, BVSc, MVSc, SKUAST-K

Miconazole(azole derivative)

Key Features:

• Wide antifungal range effective against many fungi and yeasts that cause skin infections in cats and dogs.
• Oral absorption is poor and clearance is rapid.
• Formulated as a cream ,ointment or spray for treating skin infections.
• Effective against yeasts complicating canine otitis externa.
• Effective against Staphylococcus intermedius, the main bacteria that causes skin infections in small animals.

MOA:

1 ). Miconazole blocks the enzyme CYP450 14α-lanosterol demethylase. This disruption affects ergosterol production. It impacts cell membrane structure and permeability. As a result, it causes leakage of cations, phosphate, and small proteins.

2). Miconazole inhibits fungal peroxidase and catalase. It does not affect NADH oxidase activity. This leads to increased production of reactive oxygen species (ROS). Increased intracellular ROS leads to downstream pleiotropic effects and eventual apoptosis

3). Miconazole causes a rise in intracellular levels of farnesol. Farnesol is a quorum sensing agent in Candida. It is also an inhibitor of drug efflux ABC transporters, namely Candida CaCdr1p and CaCdr2p. Thus preventing the transition from yeast to mycelial forms and thereby the formation of biofilms, which are more resistant to antibiotics.

Effects:

• At low concentrations, miconazole stops fungus growth, while at high concentrations, it can kill fungus.

Side effects:

• Redness, itching, and/or irritation at site of application.
• Allergic reactions exhibiting irregular breathing, rash, fever, and swelling around the face. Contact a veterinarian under such circumstances.

Drug combination:

• A formulation containing chlorhexidine and miconazole potentiates treatment effect.
• Combinatin of Miconazole , Ofloxacin Miconazole , Clobetasol and Zinc Sulphate enhance the antimicrobial spectrum.

Species:

• Dog , and Cat.

Indication:

• Ring worm infection.
• Fungal infections caused by Microsporum canis, Microsporum gypseum, and Trichophyton mentagrophytes.
• Otitis externa.
• Skin infection caused by Staphylococcus intermedius.

Dose:

• Apply as per direction of product label.

Contraindication:

• Burn wounds and ulcerated wounds.
• Use cautiously in animals on warfarin treatment.
• Pregnancy.

Brands:

• Easotic 10 ml ( 1.1 mg Hydrocortisone aceponate, 1505 iu Gentamicin and 15.1 mg Miconazole /ml) suspension (Verbac India).
• Wokazole Plus 30 gm(Ofloxacin 0.1% w/v, Miconazole2% w/v , Clobetasol 0.025% w/v Zinc Sulphate 3% w/v) lotion ( Vetoquinol India).
• Wokazole Plus 100 gm(Ofloxacin 0.1% w/v, Miconazole2% w/v , Clobetasol 0.025% w/v Zinc Sulphate 3% w/v) lotion ( Vetoquinol India).
• Kiskin 30ml (Ofloxacin 0.1% w/v, Miconazole2% w/v , Clobetasol 0.025% w/v Zinc Sulphate 3% w/v) lotion ( Intas India).
• Kiskin 100ml (Ofloxacin 0.1% w/v, Miconazole2% w/v , Clobetasol 0.025% w/v Zinc Sulphate 3% w/v) lotion ( Intas India).
• Micodin 200ml (Chlorhexidine Gluconate 2% & Miconazole 2%) Shampoo ( Intas India).
• Mecopet 200ml ( Miconazole nitrate 20.0 gm & chlorhexidine gluconate solution 20.0%) shampoo ( Medilogy Biotech India).
• Ichvet 20gm ( (Ofloxacin 0.1% w/v, Miconazole 2% w/v , Clobetasol 0.025% w/v Zinc Sulphate 3% w/v) cream ( PCD pharma India).