Lincomycin Injection, USP

Clostridioides 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.

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, USP therapy. If an anaphylactic reaction or severe skin reaction occurs, Lincomycin Injection, USP should be discontinued and appropriate therapy should be initiated. (See ADVERSE REACTIONS)

Lincomycin injection 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.

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

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 Candida infections require therapy with Lincomycin, concomitant antifungal 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 levels monitored during high-dose therapy. (See DOSAGE AND ADMINISTRATION)

Lincomycin MUST be diluted prior to intravenous infusion. For intravenous infusion, infuse over at least 60 minutes as directed in the DOSAGE AND ADMINISTRATION Section. Do NOT administer as an intravenous bolus. Severe cardiopulmonary reactions have occurred at greater than the recommended concentration and rate.

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.

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 an antibacterial, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after taking the last dose of the antibacterial. If this occurs, patients should contact their physician as soon as possible

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

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

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).

There are no adequate and well-controlled studies in pregnant women. Lincomycin Injection, USP Sterile Solution contains benzyl alcohol as a preservative. Benzyl alcohol can cross the placenta. See WARNINGS. Lincomycin for Injection, USP should be used during pregnancy only if clearly needed.

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.

Lincomycin Injection, USP 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)

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.

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 Injection) 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 Lincomycin injection has been given at greater than the recommended concentration and rate (see PRECAUTIONS).

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.

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 (see PRECAUTIONS).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.