FDA Label for Lincomycin

Other

To reduce the development of drug-resistant bacteria and maintain the effectiveness of lincomycin and other antibacterial drugs, lincomycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Warning

Clostridium difficile associated 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.

Because lincomycin therapy has been associated with severe colitis which may end fatally, it should be reserved for serious infections where less toxic antimicrobial agents are inappropriate, as described in the  INDICATIONS AND USAGE  section. It should not be used in patients with nonbacterial infections such as most upper respiratory tract infections.

C. diffficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause 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. difficile may 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.

Description

Lincomycin Sterile Solution contains lincomycin hydrochloride which is the monohydrated salt of lincomycin, a substance produced by the growth of a member of the lincolnensis group of Streptomyces lincolnensis (Fam. Streptomycetaceae). The chemical name for lincomycin hydrochloride is Methyl 6,8-dideoxy-6-(1-methyl-trans-4-propyl-L­-2-pyrolidinecarboxamido)-1-thio-D-erythro-α-D-galacto-octopyranoside monohydrochloride monohydrate. The molecular formula of lincomycin hydrochloride is C ₁₈H ₃₄N ₂O ₆S.HCl.H ₂O and the molecular weight is 461.01.

The structural formula is represented below:

strc - lincomycin structure

Lincomycin hydrochloride is a white or practically white, crystalline powder. Its solutions are acid and are dextrorotary. Lincomycin hydrochloride is freely soluble in water and soluble in dimethylformamide, insoluble in acetone.

Clinical Pharmacology

Intramuscular administration of a single dose of 600 mg of lincomycin produces average peak serum concentrations of 11.6 mcg/mL at 60 minutes and maintains therapeutic concentrations for 17 to 20 hours for most susceptible gram-positive organisms. Urinary excretion after this dose ranges from 1.8 to 24.8 percent (mean: 17.3 percent).

A two hour intravenous infusion of 600 mg of lincomycin achieves average peak serum concentrations of 15.9 mcg/mL and maintains therapeutic concentrations for 14 hours for most susceptible gram-positive organisms. Urinary excretion ranges from 4.9 to 30.3 percent (mean: 13.8 percent).

The biological half-life after intramuscular or intravenous administration is 5.4 ± 1.0 hours. 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. Hemodialysis and peritoneal dialysis are not effective in removing lincomycin from the serum.

Tissue distribution studies indicate that bile is an important route of excretion. Significant concentrations have been demonstrated in most body tissues. Although lincomycin appears to diffuse into cerebrospinal fluid (CSF), concentrations of lincomycin in the CSF appear inadequate for the treatment of meningitis.

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 vitro and in clinical infections: (see INDICATIONS AND USAGE).

Staphylococcus aureus

Streptococcus pneumoniae

The following in vitro data are available, but their clinical significance is unknown.

Lincomycin has been shown to be active in vitro against 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 streptococci

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.

Indications And Usage

Lincomycin Sterile Solution is indicated in the treatment of serious infections due to susceptible strains of streptococci, pneumococci, and staphylococci. Its use should be reserved for penicillin-allergic patients or other patients for whom, in the judgment of the physician, a penicillin is inappropriate. Because of the risk of CDAD, as described in the BOXED WARNING, before selecting lincomycin the physician should consider the nature of the infection and the suitability of other alternatives.

Indicated surgical procedures should be performed in conjunction with antibacterial therapy.

The drug may be administered concomitantly with other antimicrobial agents when indicated.

Lincomycin is not indicated in the treatment of minor bacterial infections or viral infections.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of lincomycin and other antibacterial drugs, lincomycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Contraindications

This drug is contraindicated in patients previously found to be hypersensitive to lincomycin or clindamycin.

Warnings

See BOXED WARNING.

Clostridium difficile associated diarrhea

Clostridium difficile associated 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. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause 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. difficile may 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 therapy. If an anaphylactic reaction or severe skin reaction occurs, lincomycin 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 is indicated in these patients, they should be carefully monitored for change in bowel frequency.

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

Lincomycin 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 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, 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 l 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 ADMINISTRATION  Section.

Prescribing lincomycin 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 should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When lincomycin 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 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 Tests

During prolonged therapy with lincomycin, 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 Salmonella reversion 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 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 5000 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 1000 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, 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 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)

Adverse Reactions

The following adverse reactions have been reported with the use of lincomycin.

Gastrointestinal disorders

Diarrhea, nausea, vomiting, glossitis, stomatitis, abdominal pain, abdominal discomfort†, anal pruritus

Skin and subcutaneous tissue disorders

Toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, dermatitis bullous, dermatitis exfoliative, erythema multiforme (see WARNINGS), rash, urticaria, pruritus

Infections and infestations

Vaginal infection, pseudomembranous colitis, Clostridium difficile colitis (see   WARNINGS)

Blood and lymphatic system disorders

Pancytopenia, agranulocytosis, aplastic anemia, leukopenia, neutropenia, thrombocytopenic purpura

Immune system disorders

Anaphylactic reaction (see WARNINGS), angioedema, serum sickness

Hepatobiliary disorders

Jaundice, liver function test abnormal, transaminases increased

Renal and urinary disorders

Renal impairment, oliguria, proteinuria, azotemia

Cardiac disorders

Cardio-respiratory arrest (see DOSAGE AND ADMINISTRATION)

Vascular disorders

Hypotension (see DOSAGE AND ADMINISTRATION), thrombophlebitis†

Ear and labyrinth disorders

Vertigo, tinnitus

Neurologic disorders

Headache, dizziness, somnolence

General disorders and administration site conditions

Injection site abscess sterile‡, injection site induration‡, injection site pain‡, injection site irritation‡

†Event has been reported with intravenous injection.

‡Reported with intramuscular injection.

To report SUSPECTED ADVERSE REACTIONS, contact Micro Labs USA, Inc. at 1-855-839-8195 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Overdosage

Serum concentrations of lincomycin are not appreciably affected by hemodialysis and peritoneal dialysis.

Dosage And Administration

If  significant diarrhea occurs during therapy, this antibacterial should be discontinued. (see BOXED WARNING)

INTRAMUSCULAR - Adults: Serious infections—600 mg (2 mL) intramuscularly every 24 hours. More severe infections—600 mg (2 mL) intramuscularly every 12 hours or more often. Pediatric patients over 1 month of age: Serious infections—one intramuscular injection of 10 mg/kg (5 mg/lb) every 24 hours. More severe infections— one intramuscular injection of 10 mg/kg (5 mg/lb) every 12 hours or more often.

INTRAVENOUS - Adults: The intravenous dose will be determined by the severity of the infection. For serious infections doses of 600 mg of lincomycin (2 mL of lincomycin) to 1 gram are given every 8 to 12 hours. For more severe infections these doses may have to be increased. In life-threatening situations daily intravenous doses of as much as 8 grams have been given. Intravenous doses are given on the basis of 1 gram of lincomycin diluted in not less than 100 mL of appropriate solution (see PHYSICAL COMPATIBILITIES) and infused over a period of not less than one hour.

These doses may  be repeated as often as required to the limit of the maximum recommended daily dose of 8 grams of lincomycin.

Pediatric patients over 1 month of age: 10 to 20 mg/kg/day (5 to 10 mg/lb/day) depending on the severity of the infection may be infused in divided doses as described above for adults.

NOTE: Severe cardiopulmonary reactions have occurred when this drug has been given at greater than the recommended concentration and rate.

SUBCONJUNCTIVAL INJECTION - 0.25 mL (75 mg) injected subconjunctivally will result in ocular fluid concentrations of antibacterial (lasting for at least 5 hours) sufficient for most susceptible pathogens.

Patients with diminished renal function: When therapy with lincomycin is required in individuals with severe renal impairment, an appropriate dose is 25 to 30% of that recommended for patients with normally functioning kidneys.

How Supplied

Lincomycin Injection, USP is clear, colorless to slightly yellow solution, having a slight odor. Free from any visible particles available in the following strength and package sizes:

300 mg

2 mL Multiple-dose Vial                                    NDC 42571-374-75

10 mL  Multiple-dose Vial                                  NDC 42571-374-88

Each mL of Lincomycin Injection, USP contains lincomycin hydrochloride equivalent to lincomycin 300 mg; also benzyl alcohol, 9.45 mg added as preservative.

Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP].

Animal Pharmacology

In vivo experimental animal studies demonstrated the effectiveness of lincomycin preparations (lincomycin) in protecting animals infected with Streptococcus viridans, β- hemolytic Streptococcus, Staphylococcus aureus, Streptococcus pneumoniae and Leptospira pomona. It was ineffective in Klebsiella, Pasteurella, Pseudomonas, Salmonella and Shigella infections .

Physical Compatibilities

Physically compatible for 24 hours at room temperature unless otherwise indicated.

Infusion Solutions

5% Dextrose Injection

10% Dextrose Injection

5% Dextrose and 0.9% Sodium Chloride Injection 10% Dextrose and 0.9% Sodium Chloride Injection Ringer’s Injection

1/6 M Sodium Lactate Injection Travert 10%-Electrolyte No. 1

Dextran in Saline 6% w/v

Vitamins in Infusion Solutions

B-Complex

B-Complex with Ascorbic Acid

Antibacterial in Infusion Solutions

Penicillin G Sodium (Satisfactory for 4 hours)

Cephalothin

Tetracycline HCl

Cephaloridine

Colistimethate (Satisfactory for 4 hours)

Ampicillin

Methicillin

Chloramphenicol

Polymyxin B Sulfate

Physically Incompatible with:

Novobiocin

Kanamycin

IT SHOULD BE EMPHASIZED THAT THE COMPATIBLE AND INCOMPATIBLE DETERMINATIONS ARE PHYSICAL OBSERVATIONS ONLY, NOT CHEMICAL DETERMINATIONS. ADEQUATE CLINICAL EVALUATION OF THE SAFETY AND EFFICACY OF THESE COMBINATIONS HAS NOT BEEN PERFORMED.

Rx only

Manufactured by:

Micro Labs Limited

Bangalore-560099, INDIA.

Manufactured for:

Micro Labs USA, Inc. 

Somerset, NJ 08873

Rev.11/2021

Package Label.Principal Display Panel

2 mL Vial Label

NDC-42571-374-75

Rx Only
Lincomycin Injection, USP
600 mg/ 2 mL
(300 mg/mL)
For Intramuscular Use or
Intravenous Use
2 mL Multiple-dose Vial
Micro Labs Limited

2 mL Vial-Carton Label

NDC-42571-374-75

Lincomycin Injection, USP
600 mg/ 2 mL*
(300 mg/mL)
For Intramuscular Use or
Intravenous Use

Rx only
2 mL Multiple-dose Vial 
Micro Labs Limited

10 mL Vial Label

NDC-42571-374-88
Lincomycin Injection, USP

Rx only
3,000 mg/ 10 mL*
(300 mg/mL)
For Intramuscular Use or
Intravenous Use
10 mL Multiple-dose Vial
Micro Labs Limited

10 mL Vial-Carton Label

NDC-42571-374-88

Lincomycin Injection, USP
3,000 mg/ 10 mL*
(300 mg/mL)
For Intramuscular Use or
Intravenous Use

Rx only
10 mL Multiple-dose Vial
Micro Labs Limited