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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.

Composition: Each 2ml solution contains 600mg Lincomycin Base (300mg/ml) (as Lincomycin Hydrochloride Monohydrate).

Pharmacological Classifications: Antibacterial drugs

Microbiology:

Lincomycin has been shown to be active against most strains of the following organisms both in vitro and in clinical infections

Staphylococcus aureus

Streptococcus pneumoniae

- Gram-positive bacteria: Corynebacterium diphtheria, Streptococcus pyogenes

Viridans group streptococci

- Anaerobic bacteria: Clostridium tetani, Clostridium perfringens

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.

Pharmacokinetics:

Intramuscular administration of a single dose of 600 mg of lincomycin produces peak serum levels of 11.6 μg/mL at 60 minutes and maintains therapeutic levels 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 levels of 15.9 μg/mL and yields therapeutic levels 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 impairment of renal function compared to patients with normal renal function. In patients with abnormal hepatic function, serum half-life may be two fold longer than in patients with normal hepatic function. Hemo dialysis and peritoneal dialysis are not effective in removing lincomycin from the serum.

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

Indications:

LINCODOM 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 antibacterial associated pseudo membranous colitis, before selecting LINCODOM the physician should consider the nature of the infection and the suitability of less toxic alternatives (e.g., erythromycin).

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

Contraindications:

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

Warnings And Precautions:

- LINCODOM should be used with caution in patients with a history of asthma or significant allergies. (See Warning Box)

Hypersensitivity: Serious hypersensitivity reactions, including anaphylaxis and erythema multiforme, have been reported with use of LINCODOM. If an allergic reaction to LINCOMYCIN occurs, discontinue the drug.

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.

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

Adverse Reactions:

Gastrointestinal disorders: Common: persistent diarrhea, nausea, vomiting.

Skin and subcutaneous tissue disorders: Uncommon: rash , urticaria .

Infections: Uncommon: vaginal infection.

Laboratory Tests: During prolonged therapy with LINCOMYCIN, periodic liver and kidney function tests and blood counts should be performed.

Pregnancy: Pregnancy Category C

LINCODOM Sterile Solution contains benzyl alcohol as a preservative, Benzyl alcohol can cross the placenta.

LINCODOM should only be used during pregnancy if strictly necessary.

Nursing Mothers:

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:

LINCODOM Sterile Solution contains benzyl alcohol as a preservative. Benzyl alcohol has been associated with a fatal "Gasping Syndrome" in premature infants.

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 LINCODOM 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

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.

Antagonism between lincomycin and erythromycin in vitro has been demonstrated.  Because of possible clinical significance, the two drugs should not be administered concurrently.

Dosage and administration:

Intramuscular

• Adults

Serious infections: 600 mg intramuscularly every 24 hours.

More severe infections: 600 mg intramuscularly every 12 hours or more often.

•  Children over 2 years of age:

Severe infections: 10 mg/kg/daily by intramuscular injection.

Very severe infections: 10 mg/kg/ every 12 hours or more frequently.

Intravenous:

-Adults

600 mg every 8 to 12 hours. For more severe infections these doses may have to be increased.

Intravenous doses are given on the basis of 1 gram of Lincomycin diluted in not less than 100 mL of appropriate solution and infused over a period of not less than one hour.

Dose	Vol. diluent	Time
600 mg	100 ml	1 hr
1 g	100 ml	1 hr
2 g	200 ml	2 hr
3 g	300 ml	3 hr
4 g	400 ml	4 hr

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:

 Children (over 2 years of age):

10-20 mg/kg/daily divided into 2-3 infusions every 12-8 hours.

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

Subconjunctival Injection:

75 mg injected subconjunctivally will result in ocular fluid levels of antibacterial (lasting for at least 5 hours) with MICs sufficient for most susceptible pathogens.

Patients with diminished renal function:

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

Overdosage:

Serum levels of Lincomycin are not appreciably affected by hemodialysis and peritoneal dialysis.