Linco-Sol

La solution stérile de Linco-SolCIN est indiquée dans le traitement des infections graves dues à des souches sensibles de streptocoques, de pneumocoques et de staphylocoques. Son utilisation doit être réservée aux patients allergiques à la pénicilline ou à d'autres patients pour lesquels, de l'avis du médecin, une pénicilline est inappropriée. En raison du risque de colite pseudomembraneuse associée aux antibactériens, comme décrit dans le Boîte AVERTISSEMENT, avant de sélectionner la linco-solmycine, le médecin doit tenir compte de la nature de l'infection et de l'adéquation des alternatives moins toxiques (par ex., érythromycine).

Les procédures chirurgicales indiquées doivent être effectuées en association avec un traitement antibactérien.

Le médicament peut être administré en concomitance avec d'autres agents antimicrobiens lorsqu'il est indiqué.

La linco-solmycine n'est pas indiquée dans le traitement des infections bactériennes mineures ou des infections virales.

Pour réduire le développement de bactéries résistantes aux médicaments et maintenir l'efficacité de Linco-SolCIN et d'autres médicaments antibactériens, Linco-SolCIN ne doit être utilisé que pour traiter ou prévenir les infections prouvées ou fortement suspectées d'être causées par des bactéries sensibles. Lorsque des informations sur la culture et la sensibilité sont disponibles, elles doivent être prises en compte lors de la sélection ou de la modification du traitement antibactérien. En l'absence de telles données, l'épidémiologie locale et les schémas de sensibilité peuvent contribuer à la sélection empirique de la thérapie.

If significant diarrhea occurs during therapy, this antibacterial should be discontinued. (see BOX 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 Linco-Solmycin (2 mL of Linco-SolCIN) 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 Linco-Solmycin diluted in not less than 100 mL of appropriate solution (see Physical Compatibities) 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 Linco-Solmycin.

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.

Reported with intramuscular injection.

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 levels of antibacterial (lasting for at least 5 hours) with MICs sufficient for most susceptible pathogens.

Patients With Diminished Renal Function

When therapy with Linco-SolCIN 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.

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.

Ce médicament est contre-indiqué chez les patients précédemment jugés hypersensibles à la linco-solmycine ou à la clindamycine.

WARNINGS

see BOX WARNING.

Clostridium Difficile Associated Diarrhea

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Linco-Solmycin, 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

Serious hypersensitivity reactions, including anaphylaxis and erythema multiforme, have been reported with use of Linco-SolCIN. If an allergic reaction to Linco-SolCIN occurs, discontinue the drug. (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 Linco-Solmycin appears to diffuse into cerebrospinal fluid, levels of Linco-Solmycin in the CSF may be inadequate for the treatment of meningitis.

PRECAUTIONS

General

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

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

Linco-SolCIN 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 Linco-SolCIN 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 Linco-SolCIN, concomitant antimonilial treatment should be given.

The serum half-life of Linco-Solmycin 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 twofold longer than in patients with normal hepatic function.

Patients with severe impairment of renal function and/or abnormal hepatic function should be dosed with caution and serum Linco-Solmycin levels monitored during high-dose therapy. (see DOSAGE AND ADMINISTRATION)

Linco-Solmycin 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 Linco-SolCIN 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.

Laboratory Tests

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

Carcinogenesis, Mutagenesis, Impairment Of Fertility

The carcinogenic potential of Linco-Solmycin has not been evaluated.

Linco-Solmycin 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, Linco-Solmycin 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, Linco-Solmycin 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 Linco-Solmycin (0.36 times the highest recommended human dose based on mg/m² ).

Pregnancy

Pregnancy Category C

Linco-SolCIN Sterile Solution contains benzyl alcohol as a preservative. Benzyl alcohol can cross the placenta. See WARNINGS.

Teratogenic Effects

There are no studies on the teratogenic potential of Linco-Solmycin in animals or adequate and wellcontrolled studies of pregnant women.

Nonteratogenic Effects

Reproduction studies have been performed in rats using oral doses of Linco-Solmycin up to 1000 mg/kg (1.2 times the maximum daily human dose based on mg/m² ) and have revealed no adverse effects on survival of offspring from birth to weaning.

Nursing Mothers

Linco-Solmycin has been reported to appear in human milk in concentrations of 0.5 to 2.4 μg/mL. Because of the potential for serious adverse reactions in nursing infants from Linco-SolCIN, 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

Linco-SolCIN 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)

Les réactions suivantes ont été rapportées avec l'utilisation de la linco-solmycine et sont répertoriées par classe de systèmes d'organes.

Troubles gastro-intestinaux

Diarrhée, nausées, vomissements, glossite, stomatite, douleurs abdominales, gêne abdominale¹ , prurit anal

¹Un événement a été signalé par injection intraveineuse.

Troubles de la peau et des tissus sous-cutanés

Éruption cutanée, urticaire, prurit, syndrome de Stevens-Johnson, érythème polymorphe (voir AVERTISSEMENTS), dermatite bulleuse, dermatite exfoliative

Infections et infestations

Infection vaginale, colite pseudomembraneuse , Clostridium difficile colite (voir AVERTISSEMENTS)

Troubles du sang et du système lymphatique

Pancytopénie, agranulocytose, anémie aplasique, leucopénie, neutropénie, purpura thrombocytopénique

Troubles du système immunitaire

Réaction anaphylactique (voir AVERTISSEMENTS), œdème de Quincke, maladie sérique

Troubles hépatobiliaires

Jaunisse, test de la fonction hépatique anormal, transaminases augmentées

Troubles rénaux et urinaires

Insuffisance rénale, oligurie, protéinurie, azotémie

Troubles cardiaques

Arrêt cardio-respiratoire (voir DOSAGE ET ADMINISTRATION)

Troubles vasculaires

Hypotension (voir DOSAGE ET ADMINISTRATION), thrombophlébite¹

Troubles de l'oreille et du labyrinthe

Vertige, acouphènes

Troubles neurologiques

Maux de tête, vertiges, somnolence

Troubles généraux et conditions du site d'administration

Abcès au site d'injection stérile² , induration du site d'injection² , douleur au site d'injection² , irritation au site d'injection²

² Signalé par injection intramusculaire.

Les taux sériques de Linco-Solmycine ne sont pas sensiblement affectés par l'hémodialyse et la dialyse péritonéale.