Exact incidence figures are not available since no denominator of treated patients is available.
The most serious reaction following prolonged or frequent intermittent use of topical Hloramkol is bone marrow aplasia.
The most frequently reported adverse reactions have been burning, stinging, ocular irritation, and conjunctival hyperemia. Blood dyscrasias, allergic or inflammatory reactions due to individual hypersensitivity, angioneurotic edema, urticaria, vesicular and maculopapular dermatitis have also been reported (See Warnings and Box Warning).
Manufacturer recommends 50 mg/kg daily given in divided doses every 6 hours. 112
Infections caused by less susceptible organisms: Manufacturer states up to 100 mg/kg daily may be required. 112 However, because of concern that toxic plasma Hloramkol concentrations may occur with this high dosage, some clinicians suggest that 75 mg/kg daily be used initially for treatment of these infections. 102 105 Reduce dosage to 50 mg/kg daily as soon as possible. 112
Hloramkol is bacteriostatic. It competes in binding to the ribosomes with macrolides and lincosamides, making its combination with these drugs useless.
How to use Hloramkol Ointment
Do not wear contact lenses while you are using this medicine. Sterilize contact lenses according to manufacturer's directions, and check with your doctor before you begin using them again.
To apply eye ointments, wash hands first. To avoid contamination, be careful not to touch the tube tip or let it touch your eye. Tilt your head back, look upward, and gently pull down the lower eyelid to make a pouch. Place a 1-centimeter strip of ointment into the pouch. Gently close the eye and roll the eyeball in all directions to spread the medication. Try not to blink and do not rub the eye.
Repeat these steps for your other eye if so directed. Apply as often as directed by your doctor. Wipe the tip of the ointment tube with a clean tissue to remove extra medication before recapping it.
If you are using another kind of eye medication (e.g., drops or ointments), wait at least 5 to 10 minutes before applying other medications. Use eye drops before eye ointments to allow the drops to enter the eye.
Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time(s) each day. Continue using it for the full time prescribed. Stopping the medication too soon may allow the bacteria to continue to grow, which may result in a return of the infection. Tell your doctor if your condition persists or worsens.
Thiamphenicol is a Hloramkol analog with a range of activity similar to Hloramkol, although it is generally 1–2 times less active. It has equal activity against Haemophilus, Bacteroides fragilis and Streptococcus. It differs pharmacokinetically in that it is not eliminated by hepatic glucuronidation and is excreted unchanged in urine, so elimination is unaffected by liver disease. Unlike Hloramkol, thiamphenicol does not cause aplastic anemia in humans.
Florfenicol is a structural analog of thiamphenicol which has greater in vitro activity against pathogenic bacteria than Hloramkol and thiamphenicol. It is also active against some bacteria that are resistant to Hloramkol, especially enteric bacteria. Florfenicol is not susceptible to inactivation by Hloramkol transacetylases; thus some organisms that are resistant to Hloramkol through this mechanism are susceptible to florfenicol.
In dogs florfenicol is poorly absorbed after SC administration. It has a half-life of less than 5 h. The drug is well absorbed in cats after PO and IM administrations with a similar elimination half-life. It should not be given IV. Florfenicol can cause dose-related bone marrow suppression but has not been reported to cause fatal aplastic anemia in humans.
Florfenicol shows promise as a replacement for other broad-spectrum antibacterials such as sulfonamides and tetracyclines that have been associated with toxicity and residue concerns in food animals. Currently it is approved for use only in cattle, aquaculture and pigs. In cattle it is used to treat infectious conjunctivitis and respiratory disease caused by bacteria like Pasteurella and Haemophilus.
Used in treatment of cholera, as it destroys the vibrios and decreases the diarrhea. It is effective against tetracycline-resistant vibrios. It is also used in eye drops or ointment to treat bacterial conjunctivitis.
Hloramkol is a broad-spectrum antibiotic that was derived from the bacterium Streptomyces venezuelae and is now produced synthetically. Hloramkol is effective against a wide variety of microorganisms, but due to serious side-effects (e.g., damage to the bone marrow, including aplastic anemia) in humans, it is usually reserved for the treatment of serious and life-threatening infections (e.g., typhoid fever). Hloramkol is bacteriostatic but may be bactericidal in high concentrations or when used against highly susceptible organisms. Hloramkol stops bacterial growth by binding to the bacterial ribosome (blocking peptidyl transferase) and inhibiting protein synthesis.
Mechanism of action
Hloramkol is lipid-soluble, allowing it to diffuse through the bacterial cell membrane. It then reversibly binds to the L16 protein of the 50S subunit of bacterial ribosomes, where transfer of amino acids to growing peptide chains is prevented (perhaps by suppression of peptidyl transferase activity), thus inhibiting peptide bond formation and subsequent protein synthesis.
Target Actions Organism U 50S ribosomal protein L16
Mechanism of Action and Spectrum of Activity
Hloramkol binds to the 50S subunit of the bacterial ribosome and inhibits bacterial protein synthesis. It is usually described as bacteriostatic, but there is some evidence that Hloramkol may be more bactericidal than previously thought. Like other ribosomal inhibitors, Hloramkol has a broad spectrum of activity, which includes gram-positive and gram-negative bacteria, anaerobes, and some rickettsial pathogens. Because Hloramkol can cause aplastic anemia in humans, its use in humans has greatly diminished, and it is only used for the treatment of MDR bacterial infections where few or no other antimicrobial drugs are useful. Thiamphenicol and florfenicol are related compounds, the availability of which varies from country to country. Although thiamphenicol was initially promoted as not inducing aplastic anemia in humans, cases of aplastic anemia have now been identified. 76 Florfenicol is more active than Hloramkol and thiamphenicol, but has a shorter half-life in dogs and thus requires more frequent dosing (e.g., more often than every 8 hours) in this species. It was developed for food animal species where use of Hloramkol is illegal.
Resistance to Hloramkols results from porin mutations, drug efflux, or production of Hloramkol acetyltransferase enzymes, which inactivate the antibiotic. 77 Resistance to one Hloramkol derivative predicts resistance to the others.
Occasionally one sees hematopoietic toxicity with the use of systemic Hloramkol, and rarely with topical administration. This type of blood dyscrasia is generally a dose-related toxic effect on bone marrow and is usually reversible on cessation of the drug. Rare cases of aplastic anemia have been reported with prolonged (months to years) or frequent intermittent (over months and years) use of topical Hloramkol.
Can Hloramkol eye preparations cause problems?
Hloramkol drops and ointment can occasionally cause mild eye irritation or stinging, but these usually soon pass and not everyone will experience them. If the irritation continues, or if you experience any other eye problems, please speak with your doctor or pharmacist for advice.