Microbiology

Mechanism of Action

Lincomycin inhibits bacterial protein synthesis by binding to the 23S RNA of the 50S subunit of the bacterial ribosome. Lincomycin is predominantly bacteriostatic in vitro.

Resistance

Cross resistance has been demonstrated between clindamycin and lincomycin. Resistance is most often due to methylation of specific nucleotides in the 23S RNA of the 50S ribosomal subunit, which can determine cross resistance to macrolides and streptogramins B (MLSB phenotype). Macrolide-resistant isolates of these organisms should be tested for inducible resistance to lincomycin/clindamycin using the D-zone test or other appropriate method.

Antimicrobial Activity

Lincomycin has been shown to be active against most strains of the following bacteria both in vitroand in clinical infections (see INDICATIONS AND USAGE):

Staphylococcus aureus
Streptococcus
pneumoniae

The following in vitrodata are available, but their clinical significance is unknown.
Lincomycin has been shown to be active in vitroagainst the following microorganisms; however, the safety and efficacy of lincomycin in treating clinical infections due to these organisms have not been established in adequate and well controlled trials.

Gram-positive bacteria:

Corynebacterium
diphtheriae Streptococcus
pyogenes Viridans group

Anaerobic bacteria:

Clostridium tetani
Clostridium
perfringens

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

Clostridium difficileassociated diarrhea

Clostridium difficileassociated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Lincomycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficileproduces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficilecause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficilemay need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Hypersensitivity

Severe hypersensitivity reactions, including anaphylactic reactions and severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and erythema multiforme (EM) have been reported in patients receiving lincomycin injection therapy. If an anaphylactic reaction or severe skin reaction occurs, lincomycin injection should be discontinued and appropriate therapy should be initiated (see ADVERSE REACTIONS).

Benzyl Alcohol Toxicity in Pediatric Patients (Gasping Syndrome)

This product contains benzyl alcohol as a preservative.

The preservative benzyl alcohol has been associated with serious adverse events, including the “gasping syndrome”, and death in pediatric patients. Although normal therapeutic doses of this product ordinarily deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. The risk of benzyl alcohol toxicity depends on the quantity administered and the liver and kidneys’ capacity to detoxify the chemical. Premature and low-birth weight infants may be more likely to develop toxicity.

Use in Meningitis

Although lincomycin appears to diffuse into cerebrospinal fluid, concentrations of lincomycin in the CSF may be inadequate for the treatment of meningitis.

General

Review of experience to date suggests that a subgroup of older patients with associated severe illness may tolerate diarrhea less well. When lincomycin injection is indicated in these patients, they should be carefully monitored for change in bowel frequency.

Lincomycin injection should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Lincomycin injection should be used with caution in patients with a history of asthma or significant allergies.

Certain infections may require incision and drainage or other indicated surgical procedures in addition to antibacterial therapy.

The use of lincomycin injection may result in overgrowth of nonsusceptible organisms— particularly yeasts. Should superinfections occur, appropriate measures should be taken as indicated by the clinical situation. When patients with pre-existing monilial infections require therapy with lincomycin injection, concomitant antimonilial treatment should be given.

The serum half-life of lincomycin may be prolonged in patients with severe renal impairment compared to patients with normal renal function. In patients with hepatic impairment, serum half-life may be twofold longer than in patients with normal hepatic function.

Patients with severe renal impairment and/or hepatic impairment should be dosed with caution and serum lincomycin concentrations monitored during high-dose therapy (see DOSAGE AND ADMINISTRATION).

Lincomycin should not be injected intravenously undiluted as a bolus, but should be infused over at least 60 minutes as directed in the DOSAGE AND ADMINISTRATIONsection.
Prescribing lincomycin injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Information for Patients

Patients should be counseled that antibacterial drugs including lincomycin injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When lincomycin injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness
of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by lincomycin injection or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibacterial which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterial, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial. If this occurs, patients should contact their physician as soon as possible.

Laboratory Test

During prolonged therapy with lincomycin injection, periodic liver and kidney function tests and blood counts should be performed.

Drug Interactions

Lincomycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be used in caution in patients receiving such agents.

Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenic potential of lincomycin has not been evaluated.

Lincomycin was not found to be mutagenic in the Ames Salmonellareversion assay or the V79 Chinese hamster lung cells at the HGPRT locus. It did not induce DNA strand breaks in V79 Chinese hamster lung cells as measured by alkaline elution or chromosomal abnormalities in cultured human lymphocytes. In vivo, lincomycin was negative in both the rat and mouse micronucleus assays and it did not induce sex-linked recessive lethal mutations in the offspring of male Drosophila. However, lincomycin did cause unscheduled DNA syntheses in freshly isolated rat hepatocytes.

Impairment of fertility was not observed in male or female rats given oral 300 mg/kg doses of lincomycin (0.36 times the highest recommended human dose based on mg/m 2).

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Lincomycin injection sterile solution contains benzyl alcohol as a preservative. Benzyl alcohol can cross the placenta (see WARNINGS). Lincomycin should be used during pregnancy only if clearly needed.

Teratogenic Effects
In a study with 60 pregnant women, cord serum concentrations were approximately 25% of the maternal serum concentrations, indicating that lincomycin crosses the placenta, and no substantial accumulation occurred in the amniotic fluid. Experience with 345 obstetrical patients receiving lincomycin revealed no ill effects related to pregnancy.

There was no evidence of teratogenicity when lincomycin was administered in diet or via oral gavage to pregnant Sprague Dawley rats during the period of major organogenesis at doses up to 5,000 mg/kg and 100 mg/kg (approximately 6 times and 0.12 times the maximum recommended human dose [MRHD], respectively, based on body surface area comparison).

Nonteratogenic Effects
However, reproduction studies performed in rats administered oral lincomycin in diet for 2 weeks prior to mating, throughout pregnancy and lactation, revealed no adverse effects on survival of offspring from birth to weaning at doses up to 1,000 mg/kg (1.2 times the MRHD based on body surface area comparison) up to 2 generations.

Nursing Mothers

Lincomycin has been reported to appear in human milk in concentrations of 0.5 to 2.4 mcg/mL. Because of the potential for serious adverse reactions in nursing infants from lincomycin injection, a decision should be made whether to discontinue nursing, or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Lincomycin injection sterile solution contains benzyl alcohol as a preservative. Benzyl alcohol has been associated with a fatal “Gasping Syndrome” in premature infants (see WARNINGS). Safety and effectiveness in pediatric patients below the age of one month have not been established (see DOSAGE AND ADMINISTRATION).

Storage Conditions

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Sterile, Nonpyrogenic.
The container closure is not made with natural rubber latex.