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Lincomycin Hydrochloride

Lincomycin is an antibiotic that is structurally related to clindamycin.

Uses

Staphylococcal and Streptococcal Infections

Lincomycin is used in the treatment of serious infections caused by susceptible strains of staphylococci, Streptococcus pneumoniae, and other streptococci; however, lincomycin is not considered the drug of choice in infections caused by gram-positive cocci and its use in these infections should be reserved for penicillin-allergic patients or other patients for whom less toxic alternatives (e.g., erythromycin) are contraindicated.

Lincomycin should be not used for the treatment of minor bacterial infections or for nonbacterial infections. Because of poor CNS penetration, lincomycin should not be used in the treatment of meningitis. In general, lincomycin appears to be less effective than clindamycin in the treatment of infections caused by susceptible organisms because of lesser activity and slower and less complete absorption following oral administration. Prior to initiation of lincomycin therapy, the causative organism should be cultured and in vitro susceptibility tests conducted. Use of lincomycin therapy does not preclude surgical procedures as needed.

Dosage and Administration

Administration

Lincomycin hydrochloride is administered orally, by IM injection, or by slow IV infusion. Lincomycin hydrochloride also has been administered by subconjunctival injection. Oral lincomycin should be administered at least 1-2 hours before or after ingestion of food. Prior to IV administration, each gram of lincomycin should be diluted in 100 mL or more of compatible IV solution. The appropriate dose should then be infused over a period of at least 1 hour.

Dosage

Dosage of lincomycin hydrochloride is expressed in terms of lincomycin and depends on the severity of the infection and the susceptibility of the infecting organism. The duration of lincomycin therapy is dependent on the type of infection. If lincomycin is used in infections caused by group A b-hemolytic streptococci, therapy should be continued for at least 10 days. Oral Dosage The usual adult oral dosage of lincomycin is 500 mg 3 times daily (500 mg approximately every 8 hours) for the treatment of serious infections and 500 mg or more 4 times daily (500 mg or more approximately every 6 hours) for the treatment of more severe infections.

Children older than 1 month of age should receive oral lincomycin in a dosage of 30 mg/kg daily given in 3 or 4 equally divided doses for the treatment of serious infections or a dosage of 60 mg/kg daily given in 3 or 4 equally divided doses for the treatment of more severe infections.

Parenteral Dosage

The usual adult IM dosage of lincomycin is 600 mg given once every 24 hours for the treatment of serious infections or every 12 hours (or more frequently) for more severe infections. IM dosage for children older than 1 month of age is 10 mg/kg given once every 24 hours for serious infections or every 12 hours (or more frequently) for more severe infections. The usual adult IV dosage of lincomycin is 600 mg to 1 g every 8-12 hours for the treatment of serious infections.

More severe infections may require increased dosage; in the treatment of life-threatening infections, adult IV dosage may be increased to a maximum of 8 g daily. IV lincomycin dosage for children older than 1 month of age is 10-20 mg/kg daily (depending on the severity of infection) administered in 2 or 3 equally divided doses.

Dosage in Renal and Hepatic Impairment

The manufacturer states that patients with severe renal impairment may receive 25-30% of the usual lincomycin dose. The drug should be used with caution in these patients and serum lincomycin concentrations should be monitored during high-dose therapy.

Although the manufacturer does not make specific dosage recommendations for use of lincomycin in patients with impaired hepatic function, the drug should be used with caution in these patients and serum lincomycin concentrations should be monitored during high-dose therapy.

Drug Interactions

Erythromycin

Because of reported in vitro antagonism between lincomycin and erythromycin, the drugs should not be used concomitantly.

Kaolin

When administered concomitantly, kaolin reduces the GI absorption of lincomycin by as much as 90%, resulting in decreased plasma concentrations of the antibiotic. If administration of both drugs is necessary, patients should receive kaolin at least 2 hours before lincomycin.

Neuromuscular Blocking Agents

Lincomycin has been shown to have neuromuscular blocking properties that may enhance the neuromuscular blocking action of other agents (e.g., ether, tubocurarine, pancuronium). Lincomycin should be used with caution in patients receiving such agents.

Mechanism of Action

Lincomycin may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. Lincomycin appears to inhibit protein synthesis in susceptible organisms by binding to 50S ribosomal subunits; the primary effect is inhibition of peptide bond formation. The site of action appears to be the same as that of clindamycin, erythromycin, chloramphenicol, oleandomycin, and troleandomycin. Spectrum Lincomycin and clindamycin have similar spectra of activity; however, lincomycin is generally less active against susceptible organisms than is clindamycin.

Lincomycin is active against most aerobic gram-positive cocci including staphylococci, Streptococcus pneumoniae, and other streptococci (except Enterococcus faecalis [formerly S. faecalis]).

Lincomycin is also active against several anaerobic and microaerophilic gram-negative and gram-positive organisms including Actinomyces, Bacteroides, Eubacterium, Fusobacterium, Propionibacterium, microaerophilic streptococci, Peptococcus, Peptostreptococcus, and Veillonella. Clostridium perfringens, C. tetani, Corynebacterium diphtheriae and Mycoplasma are also inhibited by lincomycin. Haemophilus and Neisseria are not generally inhibited by lincomycin.Lincomycin is inactive against Enterobacteriaceae, Plasmodium, fungi, and most strains of C. difficile. In vitro, lincomycin concentrations of 0.02-3.1 mcg/mL inhibit most susceptible strains of staphylococci, streptococci, Corynebacterium diphtheriae, and Actinomyces. In vitro, the minimum inhibitory concentration (MIC) of lincomycin for most susceptible anaerobic and microaerophilic bacteria is 0.1-6.2 mcg/mL.

Resistance

Staphylococcal resistance to lincomycin has been induced in vitro and has been shown to be acquired in a stepwise manner. Natural and acquired resistance to the antibiotic has been demonstrated in vitro and in vivo in strains of staphylococci, streptococci, and B. fragilis.

Complete cross-resistance occurs between clindamycin and lincomycin, and there is evidence of partial cross-resistance between the lincomycin and erythromycin. In vitro, bacteria resistant to erythromycin and susceptible to lincomycin may exhibit a dissociated type of resistance to lincomycin during susceptibility testing if erythromycin is also present.

This phenomenon may be the result of competition between erythromycin and lincomycin for the ribosomal binding site.

Pharmacokinetics

Absorption

Approximately 20-30% of an oral dose of lincomycin hydrochloride is rapidly absorbed from the GI tract. Food delays and decreases the extent of absorption of the drug. Lincomycin is not inactivated by gastric acidity. Following oral administration of a single 500-mg dose of lincomycin hydrochloride to healthy fasting adults, peak plasma concentrations of the drug average 1.8-5.3 mcg/mL and are attained within 2-4 hours; plasma concentrations of lincomycin average 1.4 mcg/mL at 6 hours and 0.3 mcg/mL at 12 hours.

Lincomycin Hydrochloride

Lincomycin hydrochloride, when administered orally in one group of children in single lincomycin doses of 22-33 mg/kg, produced mean peak lincomycin plasma concentrations of 4-9 mcg/mL. Following IM administration of 600 mg of lincomycin hydrochloride in healthy adults, peak plasma concentrations of the drug occur in 30 minutes and range from 9.3-18. mcg/mL; plasma concentrations of lincomycin range from 1.3-3.2 mcg/mL at 12 hours and detectable concentrations may persist for up to 24 hours. Following IV infusion of 600 mg of lincomycin hydrochloride over a period of 2 hours, postinfusion plasma concentrations of the drug average 15.9-20.9 mcg/mL.

Distribution

Lincomycin is distributed into many body tissues and fluids including peritoneal fluid, pleural fluid, synovial fluid, bone, bile, and the aqueous humor of the eye. The manufacturer states that subconjunctival injection of 0.25 mL of a solution containing 300 mg of lincomycin per mL will result in inhibitory ocular fluid concentrations of the drug for most susceptible organisms for at least 5 hours.

The drug diffuses poorly into the CSF; however, in the presence of inflamed meninges, low concentrations of the drug (18% of concurrent plasma concentration) have been attained. The concentration of lincomycin in bone is reported to be 20-33% of concurrent plasma concentrations of the drug.

Lincomycin readily crosses the placenta, and cord blood concentrations of the drug have been reported to be 25% of concurrent maternal blood concentrations. Lincomycin is distributed into milk, and concentrations of the drug in milk may be equal to maternal plasma concentrations. At a plasma concentration of 5 mcg/mL, lincomycin is approximately 72% bound to plasma proteins; at a concentration of 1 mcg/mL, the drug is approximately 57% bound to plasma proteins.

Elimination

The plasma half-life of lincomycin is 4-6. hours in patients with normal renal function. The plasma half-life is increased in proportion to the degree of impairment in patients with reduced renal or hepatic function. Plasma half-lives as high as 3 times normal have been reported in patients with severe renal impairment. Plasma concentrations of lincomycin are not appreciably affected by hemodialysis, peritoneal dialysis, or prolonged administration in patients with normal renal function.

Lincomycin is partially metabolized in the liver and both drug and metabolites are excreted in urine, bile, and feces. Following oral administration of 500 mg of lincomycin hydrochloride, 1-31% of the dose is excreted in urine and as much as 40% of the dose is excreted in feces. Following parenteral administration of 600 mg of lincomycin hydrochloride, 1.8-30.3% of the dose is excreted in urine and 4-14% of the dose is excreted in feces.

Chemistry and Stability

Chemistry

Lincomycin is an antibiotic obtained from cultures of Streptomyces lincolnensis. Lincomycin is commercially available as the hydrochloride monohydrate. The drug occurs as a white to off-white, crystalline powder, which may have a faint odor and is freely soluble in water.

The pKa of lincomycin is 7.6. Lincomycin hydrochloride injection is a clear, colorless to slightly yellow solution; hydrochloric acid and/or sodium hydroxide may be added during manufacture to adjust the pH to 3-5.5.

Stability

Lincomycin hydrochloride capsules and injection should be stored at 20-25°C; freezing of the injection should be avoided, and the capsules should be stored in tight containers. Lincomycin hydrochloride is reported to be physically compatible for 24 hours at room temperature in the following IV infusion fluids: 5% or 10% dextrose in water or 0.9% sodium chloride, Ringer’s, 1/6 M sodium lactate, 6% dextran in 0.9% sodium chloride, and Travert® 10% Electrolyte No. 1.100 Lincomycin hydrochloride has been reported to be incompatible with various drugs, but the compatibility depends on several factors (e.g., concentration of the drugs, specific diluents used, resulting pH, temperature). Specialized references should be consulted for specific compatibility information.

Preparations

Lincomycin Hydrochloride Oral Capsules 500 mg (of lincomycin) Lincocin®,Pfizer Parenteral Injection 300 mg (of lincomycin) per Lincocin®, (with benzyl mL alcohol 9.45 mg/mL) Pfizer Bactramycin®, Clint Lincomycin Hydrochloride Injection, Compumed Hyrex Keene Radford Raway

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