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Florfenicol
Florfenicol 327
Regulatory Information Withdrawal time is not established for food animals, but 26 days for slaughter has been used for calves in other countries. Do not administer to horses that are used for human consumption. In racing horses, it is not permitted to be used 12 hours prior to competition.
Florfenicol flore-fen’ih-kole
Trade and other names: Nuflor, Nuflor Gold, Resflor (flunixin and florfenicol) Aquaflor (fish formulation) Functional classification: Antibacterial
Pharmacology and Mechanism of Action Florfenicol is a thiamphenicol derivative with the same mechanism of action as chloramphenicol (inhibition of protein synthesis). However, it is more active than either chloramphenicol or thiamphenicol, and may be more bactericidal than previously thought against some pathogens (e.g., BRD pathogens). Florfenicol has a broad spectrum of antibacterial activity that includes all organisms sensitive to chloramphenicol, gram-negative bacilli, gram-positive cocci, and other atypical bacteria such as mycoplasma. Florfenicol is highly lipophilic, which provides high enough concentrations to treat intracellular pathogens and cross some anatomic barriers (penetration across the blood–brain barrier in cattle is 46%). The half-life of florfenicol is 2-3 hours in cattle after IV administration, but it is prolonged (18 hours) after IM injection, and 27 hours after 40 mg/kg subcutaneously. In dogs, the half-life is shorter, with values of 1.1 and 1.2 after IV and oral administration, respectively. The half-life in cats is approximately 4 hours and 7.8 hours after IV and oral administration, respectively.
Indications and Clinical Uses Because florfenicol is a derivative of chloramphenicol, it has been used in situations in which chloramphenicol is unavailable or illegal. (Chloramphenicol is illegal to use in food animals in the US.) Florfenicol has been shown to be effective for treatment of bovine respiratory disease (BRD) in cattle associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni (formerly Haemophilus somnus). Administration of florfenicol (40 mg/kg once SQ) at time of arrival to the feedlot decreased the incidence of BRD. It also is used for treatment of bovine interdigital phlegmon (foot rot, acute interdigital necrobacillosis, and infectious pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus and for treatment of infectious bovine keratoconjunctivitis caused by Moraxella bovis. Resflor Gold contains both florfenicol and flunixin. It is used for the same BRD pathogens and provides anti-inflammatory activity with the addition of flunixin meglumine, including BRD-associated pyrexia in beef and nonlactating dairy cattle. In pigs, it is used for treatment of swine respiratory disease (SRD) caused by Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, and Streptococcus suis. In cats, effective concentrations can be achieved with twice-daily administration. In dogs, the half-life is short, and frequent administration is necessary to produce effective concentrations. Florfenicol also has been administered to fish. There is a feedadditive formulation that also has been approved for catfish (10 mg/kg).
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328 Florfenicol
Precautionary Information Adverse Reactions and Side Effects Use in dogs and cats has been limited; therefore adverse effects have not been reported. Chloramphenicol has been linked to dose-dependent bone marrow depression, and similar reactions may be possible with florfenicol. However, there does not appear to be a risk of aplastic anemia as for chloramphenicol. At high doses, florfenicol may cause testicular degeneration. In horses, doses of 20 mg/kg q48h IM changed the bacterial flora and increased risk of diarrhea. Contraindications and Precautions Long-term use in animals may cause bone marrow suppression. Administration to horses has caused diarrhea, colitis, and elevations in bilirubin. Administration to horses is not recommended. Do not administer more than 10 mL in a single site. Drug Interactions No drug interactions are reported for animals. However, chloramphenicol is well known to inhibit cytochrome P450 enzymes and decrease metabolism of other drugs (see Appendix I). Therefore it is possible, but not documented, that florfenicol could cause drug interactions.
Instructions for Use Dose form is only approved for use in cattle and pigs, and doses listed have not been thoroughly evaluated in small animals. Doses listed are derived from pharmacokinetic studies. Sustained effect in cattle from IM and SQ administration does not appear to be long lasting in dogs. Injectable formulation for cattle has been administered orally to small animals, if necessary, but the taste is bitter.
Patient Monitoring and Laboratory Tests Monitor CBC for evidence of bone marrow depression. Susceptibility testing: laboratories have used chloramphenicol to test for susceptibility to florfenicol. Clinical and Laboratory Standards Institute (CLSI) break points for susceptible organisms are #4 mcg/mL for streptococci and #8 mcg/mL for other organisms.
Formulations • Florfenicol is available in 300-mg/mL injectable solution (cattle) or 23-mg/mL solution to be added to drinking water for pigs (400 mg per gallon). Medicated feed formulation contains 500 g/kg to be added to fish feed. Flunixin is combined with florfenicol in Resflor Gold, which has 300 mg florfenicol and 16.5 mg flunixin per mL with vehicles of 2-pyrrolidone, 35 mg malic acid, and triacetin.
Stability and Storage Store in a tightly sealed container, protected from light, and at room temperature. Light yellow or straw color does not affect potency. Stability of compounded formulations has not been evaluated.
Small Animal Dosage Dogs • 20 mg/kg q6h IM or PO.
Cats • 22 mg/kg q8h IM or PO.
Large Animal Dosage Cattle, BRD • 20 mg/kg q48h SQ or IM (in the neck). • 40 mg/kg SQ as a single injection or q72h SQ in the neck region (also combined with flunixin at 2.2 mg/kg and Nuflor Gold at 40 mg/kg single injection).
Fluconazole 329
Horses • Although florfenicol has been administered, some references cite adverse effects after administration. Until more safety data become available, it is suggested to avoid use of florfenicol in horses. Pigs • 15 mg/kg IM in the neck q48h. • Administer in drinking water at 400 mg per gallon (100 parts per million) for 5 consecutive days.
Regulatory Information Cattle withdrawal time (meat): 28 days if administered IM; 38 days if administered SQ. Nuflor Gold withdrawal time (40 mg/kg SQ) is 44 days. A withdrawal period has not been established in preruminating calves. Do not use in calves to be processed for veal; not to be used in dairy cattle 20 months of age or older or in veal calves younger than 1 month. Pig withdrawal time: 16 days after last treatment when administered in water; 13 days after last treatment when administered with feed.
Fluconazole floo-kahn’ah-zole
Trade and other names: Diflucan and generic brands Functional classification: Antifungal
Pharmacology and Mechanism of Action Azole antifungal drug. Fungistatic. Fluconazole inhibits ergosterol synthesis in fungal cell membrane and has activity against dermatophytes, systemic fungi, and yeasts, including Candida, Coccidioides, and Cryptococcus spp. However, it has weak activity against molds such as Aspergillus or Zygomycetes. The two triazolel rings on fluconazole make it less lipophilic and more water soluble than other azole antifungal agents. It is less protein bound than other azole antifungal drugs. Compared to other oral azole antifungals, fluconazole is absorbed more predictably and completely, even on an empty stomach. The half-life in dogs, cats, and horses is approximately 14-15, 13-25, and 38 hours, respectively.
Indications and Clinical Uses Fluconazole is effective against dermatophytes, yeasts, and a variety of systemic fungi. In dogs, cats, horses, and exotic animals, it is used to treat systemic fungal infections, yeast infections, and dermatophytes, including Malassezia dermatitis. In cats, it has been used to treat Cryptococcus and histoplasmosis. In dogs, it is not as active against coccidioidomycosis as other azole antifungal drugs, but it has been effective in some patients. Higher doses may be needed (e.g., 10 mg/kg q12h) for coccidioidomycosis. It has been as effective as for treatment of blastomycosis in dogs with efficacy similar to itraconazole. Because it is water soluble, it has been used to treat fungal cystitis.
Precautionary Information Adverse Reactions and Side Effects Adverse effects have not been reported from fluconazole administration. Compared to ketoconazole, it has less effect on endocrine function. However, increased liver enzyme concentrations and hepatopathy are possible.
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Regulatory Information Withdrawal time is not established for food animals, but 26 days for slaughter has been used for calves in other countries. Do not administer to horses that are used for human consumption. In racing horses, it is not permitted to be used 12 hours prior to competition.
Florfenicol flore-fen’ih-kole
Trade and other names: Nuflor, Nuflor Gold, Resflor (flunixin and florfenicol) Aquaflor (fish formulation) Functional classification: Antibacterial
Pharmacology and Mechanism of Action Florfenicol is a thiamphenicol derivative with the same mechanism of action as chloramphenicol (inhibition of protein synthesis). However, it is more active than either chloramphenicol or thiamphenicol, and may be more bactericidal than previously thought against some pathogens (e.g., BRD pathogens). Florfenicol has a broad spectrum of antibacterial activity that includes all organisms sensitive to chloramphenicol, gram-negative bacilli, gram-positive cocci, and other atypical bacteria such as mycoplasma. Florfenicol is highly lipophilic, which provides high enough concentrations to treat intracellular pathogens and cross some anatomic barriers (penetration across the blood–brain barrier in cattle is 46%). The half-life of florfenicol is 2-3 hours in cattle after IV administration, but it is prolonged (18 hours) after IM injection, and 27 hours after 40 mg/kg subcutaneously. In dogs, the half-life is shorter, with values of 1.1 and 1.2 after IV and oral administration, respectively. The half-life in cats is approximately 4 hours and 7.8 hours after IV and oral administration, respectively.
Indications and Clinical Uses Because florfenicol is a derivative of chloramphenicol, it has been used in situations in which chloramphenicol is unavailable or illegal. (Chloramphenicol is illegal to use in food animals in the US.) Florfenicol has been shown to be effective for treatment of bovine respiratory disease (BRD) in cattle associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni (formerly Haemophilus somnus). Administration of florfenicol (40 mg/kg once SQ) at time of arrival to the feedlot decreased the incidence of BRD. It also is used for treatment of bovine interdigital phlegmon (foot rot, acute interdigital necrobacillosis, and infectious pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus and for treatment of infectious bovine keratoconjunctivitis caused by Moraxella bovis. Resflor Gold contains both florfenicol and flunixin. It is used for the same BRD pathogens and provides anti-inflammatory activity with the addition of flunixin meglumine, including BRD-associated pyrexia in beef and nonlactating dairy cattle. In pigs, it is used for treatment of swine respiratory disease (SRD) caused by Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, and Streptococcus suis. In cats, effective concentrations can be achieved with twice-daily administration. In dogs, the half-life is short, and frequent administration is necessary to produce effective concentrations. Florfenicol also has been administered to fish. There is a feedadditive formulation that also has been approved for catfish (10 mg/kg).
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328 Florfenicol
Precautionary Information Adverse Reactions and Side Effects Use in dogs and cats has been limited; therefore adverse effects have not been reported. Chloramphenicol has been linked to dose-dependent bone marrow depression, and similar reactions may be possible with florfenicol. However, there does not appear to be a risk of aplastic anemia as for chloramphenicol. At high doses, florfenicol may cause testicular degeneration. In horses, doses of 20 mg/kg q48h IM changed the bacterial flora and increased risk of diarrhea. Contraindications and Precautions Long-term use in animals may cause bone marrow suppression. Administration to horses has caused diarrhea, colitis, and elevations in bilirubin. Administration to horses is not recommended. Do not administer more than 10 mL in a single site. Drug Interactions No drug interactions are reported for animals. However, chloramphenicol is well known to inhibit cytochrome P450 enzymes and decrease metabolism of other drugs (see Appendix I). Therefore it is possible, but not documented, that florfenicol could cause drug interactions.
Instructions for Use Dose form is only approved for use in cattle and pigs, and doses listed have not been thoroughly evaluated in small animals. Doses listed are derived from pharmacokinetic studies. Sustained effect in cattle from IM and SQ administration does not appear to be long lasting in dogs. Injectable formulation for cattle has been administered orally to small animals, if necessary, but the taste is bitter.
Patient Monitoring and Laboratory Tests Monitor CBC for evidence of bone marrow depression. Susceptibility testing: laboratories have used chloramphenicol to test for susceptibility to florfenicol. Clinical and Laboratory Standards Institute (CLSI) break points for susceptible organisms are #4 mcg/mL for streptococci and #8 mcg/mL for other organisms.
Formulations • Florfenicol is available in 300-mg/mL injectable solution (cattle) or 23-mg/mL solution to be added to drinking water for pigs (400 mg per gallon). Medicated feed formulation contains 500 g/kg to be added to fish feed. Flunixin is combined with florfenicol in Resflor Gold, which has 300 mg florfenicol and 16.5 mg flunixin per mL with vehicles of 2-pyrrolidone, 35 mg malic acid, and triacetin.
Stability and Storage Store in a tightly sealed container, protected from light, and at room temperature. Light yellow or straw color does not affect potency. Stability of compounded formulations has not been evaluated.
Small Animal Dosage Dogs • 20 mg/kg q6h IM or PO.
Cats • 22 mg/kg q8h IM or PO.
Large Animal Dosage Cattle, BRD • 20 mg/kg q48h SQ or IM (in the neck). • 40 mg/kg SQ as a single injection or q72h SQ in the neck region (also combined with flunixin at 2.2 mg/kg and Nuflor Gold at 40 mg/kg single injection).
Fluconazole 329
Horses • Although florfenicol has been administered, some references cite adverse effects after administration. Until more safety data become available, it is suggested to avoid use of florfenicol in horses. Pigs • 15 mg/kg IM in the neck q48h. • Administer in drinking water at 400 mg per gallon (100 parts per million) for 5 consecutive days.
Regulatory Information Cattle withdrawal time (meat): 28 days if administered IM; 38 days if administered SQ. Nuflor Gold withdrawal time (40 mg/kg SQ) is 44 days. A withdrawal period has not been established in preruminating calves. Do not use in calves to be processed for veal; not to be used in dairy cattle 20 months of age or older or in veal calves younger than 1 month. Pig withdrawal time: 16 days after last treatment when administered in water; 13 days after last treatment when administered with feed.
Fluconazole floo-kahn’ah-zole
Trade and other names: Diflucan and generic brands Functional classification: Antifungal
Pharmacology and Mechanism of Action Azole antifungal drug. Fungistatic. Fluconazole inhibits ergosterol synthesis in fungal cell membrane and has activity against dermatophytes, systemic fungi, and yeasts, including Candida, Coccidioides, and Cryptococcus spp. However, it has weak activity against molds such as Aspergillus or Zygomycetes. The two triazolel rings on fluconazole make it less lipophilic and more water soluble than other azole antifungal agents. It is less protein bound than other azole antifungal drugs. Compared to other oral azole antifungals, fluconazole is absorbed more predictably and completely, even on an empty stomach. The half-life in dogs, cats, and horses is approximately 14-15, 13-25, and 38 hours, respectively.
Indications and Clinical Uses Fluconazole is effective against dermatophytes, yeasts, and a variety of systemic fungi. In dogs, cats, horses, and exotic animals, it is used to treat systemic fungal infections, yeast infections, and dermatophytes, including Malassezia dermatitis. In cats, it has been used to treat Cryptococcus and histoplasmosis. In dogs, it is not as active against coccidioidomycosis as other azole antifungal drugs, but it has been effective in some patients. Higher doses may be needed (e.g., 10 mg/kg q12h) for coccidioidomycosis. It has been as effective as for treatment of blastomycosis in dogs with efficacy similar to itraconazole. Because it is water soluble, it has been used to treat fungal cystitis.
Precautionary Information Adverse Reactions and Side Effects Adverse effects have not been reported from fluconazole administration. Compared to ketoconazole, it has less effect on endocrine function. However, increased liver enzyme concentrations and hepatopathy are possible.
F