Chloramphenicol dosage

Two children, aged 2 and 5 years, with Haemophilus influenzae meningitis, were given chloramphenicol 100 mg/kg per day in four divided doses by infusion over 30 minutes. Within 3 days of starting rifampicin (rifampin) 20 mg/kg per day their peak serum chloramphenicol levels were reduced by 86 and 64%, respectively, and only returned to the therapeutic range when the chloramphenicol dosage was increased to 125 mg/kg per day. ... 

Two other children, of 5 and 18 months, with Haemophilus influenzae infections, are also reported to have shown reductions of 75% and 94%, respectively, in serum chloramphenicol levels when given rifampicin 20 mg/kg daily for 4 days. These reductions occurred despite 20 to 25% increases in the chloramphenicol dosage. ... 

So far only four cases of an interaction between rifampicin and chloramphenicol appear to have been reported. However, the evidence is of good quality and in line with the way rifampicin interacts with other drugs, so this interaction should be taken seriously. There is a risk that serum chloramphenicol levels will become subtherapeutic. The authors of the second report point out that raising the chloramphenicol dosage may possibly expose the patient to a greater risk of bone marrow aplasia. They suggest delaying rifampicin prophylaxis in patients with invasive Haemophilus influenzae infections until the end of chloramphenicol treatment. 

Erythromycin is considered the optimal drug for treatment of Campylobacter infections. The rate of resistance of Campylobacter to erythromycin remains low. Other advantages of this drug include ease of administration, low cost, lack of major toxicity, and narrow spectrum of activity.14 The recommended dosage for adults is 250 mg orally four times daily or 500 mg orally twice daily for 5 to 7 days. For very ill patients, treatment with gentamicin, imipenem, cefotaxime, or chloramphenicol is indicated, but susceptibility tests should be performed. 

IV administration Chloramphenicol sodium succinate is intended for IV use only it is ineffective when given IM. Administer IV as a 10% solution injected over at least 1 minute. Substitute oral dosage as soon as feasible. 

Only a few well-documented drug combinations with phenytoin may necessitate dosage adjustment. Coadministration of the following drugs can result in elevations of plasma phenytoin levels in most patients cimetidine, chloramphenicol, disulfiram, sulthiame, and isoniazid (in slow acetylators). Phenytoin often causes a decline in plasma carbamazepine levels if these two drugs are given concomitantly. 

Chloramphenicol also is widely used for the topical treatment of eye infections. It is a very effective agent because of its extremely broad spectrum of activity and its ability to penetrate ocular tissue. The availability of safer, less irritating instilled ophthalmic antibiotics and the increase in fatal aplastic anemia associated with the use of this dosage form suggest that this agent might best be withdrawn. 

The usual dosage of chloramphenicol is 50-100 mg/kg/d. After oral administration, crystalline chloramphenicol is rapidly and completely absorbed. A 1-g oral dose produces blood levels between 10 and 15 mcg/mL. Chloramphenicol palmitate is a prodrug that is hydrolyzed in the intestine to yield free chloramphenicol. The parenteral formulation is a prodrug, chloramphenicol succinate, which hydrolyzes to yield free chloramphenicol, giving blood levels somewhat lower than those achieved with orally administered drug. Chloramphenicol is widely distributed to virtually all tissues and body fluids, including the central nervous system and cerebrospinal fluid, such that the concentration of chloramphenicol in brain tissue may be equal to that in serum. The drug penetrates cell membranes readily. 

Most of the drug is inactivated either by conjugation with glucuronic acid (principally in the liver) or by reduction to inactive aryl amines. Active chloramphenicol (about 10% of the total dose administered) and its inactive degradation products (about 90% of the total) are eliminated in the urine. A small amount of active drug is excreted into bile and feces. The systemic dosage of chloramphenicol need not be altered in renal insufficiency, but it must be reduced markedly in hepatic failure. Newborns less than a week old and premature infants also clear chloramphenicol less well, and the dosage should be reduced to 25 mg/kg/d. 

Because of potential toxicity, bacterial resistance, and the availability of many other effective alternatives, chloramphenicol is rarely used. It may be considered for treatment of serious rickettsial infections such as typhus and Rocky Mountain spotted fever. It is an alternative to a B-lactam antibiotic for treatment of meningococcal meningitis occurring in patients who have major hypersensitivity reactions to penicillin or bacterial meningitis caused by penicillin-resistant strains of pneumococci. The dosage is 50-100 mg/kg/d in four divided doses. 

Chloramphenicol commonly causes a dose-related reversible suppression of red cell production at dosages exceeding 50 mg/kg/d after 1-2 weeks. Aplastic anemia, a rare consequence (1 in 24,000 to 40,000 courses of therapy) of chloramphenicol administration by any route, is an idiosyncratic reaction unrelated to dose, although it occurs more frequently with prolonged use. It tends to be irreversible and can be fatal. 

Chloramphenicol Prevents bacterial protein synthesis by binding to the 50S ribosomal subunit Bacteriostatic activity against susceptible bacteria Use is rare in the developed world because of serious toxicities Oral, IV hepatic clearance (half-life 2.5 h) dosage is 50-100 mg/kg/d in four divided doses Toxicity Dose-related anemia, idiosyncratic aplastic anemia, gray baby syndrome... 

Chloramphenicol is a highly active antibiotic that was first isolated from cultures of Streptomyces venezuelae but is now produced synthetically. It is unique among natural compounds in that it contains a nitrobenzene moiety. Chloramphenicol has been used both in treatment and prophylactically in food-producing animals for over 40 years, administered orally with the feed or drinking water to poultry, veal calves, swine, sheep, and lambs, and intramuscularly or intravenously to sheep, goats, pigs, and calves at a dosage of 2-4 mg/kg bw. In several countries, chloramphenicol has been also used in fish for the treatment of furunculoses on salmonids (22). 

The resulting disease is fatal in approximately 70% of the cases and those who recover experience a high incidence of acute leukemia (31). It has been reported that a 6-year-old girl died after receiving only 2 g chloramphenicol (32), while a 73-year-old woman died following an estimated total dose of only 82 mg chloramphenicol received as an ophthalmic drug (33). These total dosages have the potential to be present in human food it has been confirmed in a report in which chloramphenicol residues were found in 13 of 3020 calves tested (31). Ten muscle samples had levels above 1 ppm, while one was reported to contain about 12 ppm chloramphenicol. 

A reduction in particle size results in an increase in the surface area, which facilitates an increase in the dissolution rate and therefore, also, an increase in the rate of absorption. Drugs administered as suspension are generally rapidly absorbed because of the large available surface area of the dispersed solid. For solid dosage forms such as tablets and capsules, decreasing the particle size facilitates dissolution and thus absorption. Figure 6.8 shows the effect of particle size on absorption and resultant blood levels after oral administration of chloramphenicol in rabbits. Peak blood levels occurred much faster with the smaller... 

Examples of some drugs whose activity is increased in liver disease include oral anticoagulants, metformin, chloramphenicol, NSAIDs and sulphonylureas. It is well known that drugs such as opioids should be used in reduced dosage in patients with hepatic dysfunction doses need to be titrated, Therefore, if adverse drug interactions with opioids occur in patients with liver dysfunction, the consequences such as respiratory depression could be life-threatening,... 

Most cases of optic neuritis associated with chloramphenicol therapy have occurred in children with cystic fibrosis who were treated with large daily dosages of the... 

Drugs that meet one or more of the criteria given above and have been shown to exhibit significant differences in the bioavailability of marketed dosage forms include digoxin, quinidine, furosemide, nitrofurantoin, prednisone, chloramphenicol, theophylline, chlorpromazine, phenytoin, amitriptyline, and phenylbutazone. 

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