ADVERSE REACTIONS SECTION.

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 pruritusSkin 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 disordersPancytopenia, agranulocytosis, aplastic anemia, leukopenia, neutropenia, thrombocytopenic purpuraImmune system disorders Anaphylactic reaction (see WARNINGS), angioedema, serum sickness Hepatobiliary disorders Jaundice, liver function test abnormal, transaminases increasedRenal and urinary disorders Renal impairment, oliguria, proteinuria, azotemiaCardiac disorders Cardio-respiratory arrest (see DOSAGE AND ADMINISTRATION) Vascular disorders Hypotension (see DOSAGE AND ADMINISTRATION), thrombophlebitis+ Ear and labyrinth disorders Vertigo, tinnitusNeurologic disorders Headache, dizziness, somnolenceGeneral 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.

BOXED WARNING SECTION.

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 and 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.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. Intramuscular administration of 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 ActionLincomycin inhibits bacterial protein synthesis by binding to the 23S RNA of the 50S subunit of the bacterial ribosome. Lincomycin is predominantly bacteriostatic in vitro. ResistanceCross 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 (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 ActivityLincomycin 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 pneumoniaeThe 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 streptococciAnaerobic bacteria:Clostridium tetaniClostridium perfringensSusceptibility TestingFor 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.

DOSAGE & ADMINISTRATION SECTION.

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 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 gram are given every 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 grams have been given. Intravenous doses are given on the basis of gram of lincomycin diluted in not less than 100 mL of appropriate solution (see PHYSICAL COMPATIBILITIES) and infused over period of not less than one hour. DoseVol. DiluentTime600 mg 100 mL hr gram 100 mL hr grams 200 mL hr grams 300 mL hr grams 400 mL hr These doses may be repeated as often as required to the limit of the maximum recommended daily dose of grams of lincomycin.Pediatric patients over 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 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.

GENERAL PRECAUTIONS SECTION.

General. Review of experience to date suggests that 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 history of gastrointestinal disease, particularly colitis.Lincomycin should be used with caution in patients with 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 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 bolus, but should be infused over at least 60 minutes as directed in the DOSAGE AND ADMINISTRATION Section. Prescribing lincomycin in the absence of proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

INDICATIONS & USAGE SECTION.

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, 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.

INFORMATION FOR PATIENTS SECTION.

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 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 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.

PRECAUTIONS SECTION.

PRECAUTIONS. General. Review of experience to date suggests that 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 history of gastrointestinal disease, particularly colitis.Lincomycin should be used with caution in patients with 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 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 bolus, but should be infused over at least 60 minutes as directed in the DOSAGE AND ADMINISTRATION Section. Prescribing lincomycin in the absence of proven or strongly suspected bacterial infection or 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 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 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 preservative. Benzyl alcohol can cross the placenta. See WARNINGS. Lincomycin should be used during pregnancy only if clearly needed. Teratogenic Effects:In 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 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 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 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, 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 preservative. Benzyl alcohol has been associated with 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).

PREGNANCY SECTION.

Pregnancy. There are no adequate and well-controlled studies in pregnant women. Lincomycin Sterile Solution contains benzyl alcohol as preservative. Benzyl alcohol can cross the placenta. See WARNINGS. Lincomycin should be used during pregnancy only if clearly needed. Teratogenic Effects:In 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 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 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 generations.

WARNINGS SECTION.

WARNINGS. See BOXED WARNING. Clostridium difficile associated diarrheaClostridium 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 and 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 againstC. 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 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.