Frademicina

Overdose

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

Contraindications

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

Undesirable effects

The following reactions have been reported with the use of Frademicinamycin and are listed by System Organ Class.

Gastrointestinal Disorders

Diarrhea, nausea, vomiting, glossitis, stomatitis, abdominal pain, abdominal discomfort1 , anal pruritus

1Event has been reported with intravenous injection.

Skin And Subcutaneous Tissue Disorders

Rash, urticaria, pruritus, Stevens-Johnson syndrome, erythema multiforme (see WARNINGS), dermatitis bullous, dermatitis exfoliative

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), thrombophlebitis1

Ear And Labyrinth Disorders

Vertigo, tinnitus

Neurologic Disorders

Headache, dizziness, somnolence

General Disorders And Administration Site Conditions

Injection site abscess sterile2 , injection site induration2 , injection site pain2 , injection site irritation2

2 Reported with intramuscular injection.

Therapeutic indications

FrademicinaCIN 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 antibacterial associated pseudomembranous colitis, as described in the WARNING box, before selecting Frademicinamycin the physician should consider the nature of the infection and the suitability of less toxic alternatives (e.g., erythromycin).

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

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

Frademicinamycin 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 FrademicinaCIN and other antibacterial drugs, FrademicinaCIN 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.

Name of the medicinal product

Frademicina

Qualitative and quantitative composition

Lincomycin

Special warnings and precautions for use

WARNINGS

see BOX WARNING.

Clostridium Difficile Associated Diarrhea

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Frademicinamycin, 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 FrademicinaCIN. If an allergic reaction to FrademicinaCIN 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 Frademicinamycin appears to diffuse into cerebrospinal fluid, levels of Frademicinamycin 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 FrademicinaCIN is indicated in these patients, they should be carefully monitored for change in bowel frequency.

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

FrademicinaCIN 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 FrademicinaCIN 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 FrademicinaCIN, concomitant antimonilial treatment should be given.

The serum half-life of Frademicinamycin 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 Frademicinamycin levels monitored during high-dose therapy. (see DOSAGE AND ADMINISTRATION)

Frademicinamycin 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 FrademicinaCIN 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 FrademicinaCIN, periodic liver and kidney function tests and blood counts should be performed.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

The carcinogenic potential of Frademicinamycin has not been evaluated.

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

Pregnancy Pregnancy Category C

FrademicinaCIN 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 Frademicinamycin in animals or adequate and wellcontrolled studies of pregnant women.

Nonteratogenic Effects

Reproduction studies have been performed in rats using oral doses of Frademicinamycin 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

Frademicinamycin 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 FrademicinaCIN, 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

FrademicinaCIN 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)

Dosage (Posology) and method of administration

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 Frademicinamycin (2 mL of FrademicinaCIN) 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 Frademicinamycin diluted in not less than 100 mL of appropriate solution (see Physical Compatibities) and infused over a period of not less than one hour.

Dose	Vol. Diluent	Time
600 mg	100 mL	1 hr
1 gram	100 mL	1 hr
2 grams	200 mL	2 hr
3 grams	300 mL	3 hr
4 grams	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 Frademicinamycin.

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 FrademicinaCIN 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.