Antibiotics (Other)

Renal dosing: 
[CRCL >30 ml/min]: no change.  
[10-30 ml/min]: Loading dose: 1-2 grams x 1, then give 50% of the usual dose (e.g. 0.5 - 1 gm) q6-12h. 
[<10 ml/min]: 1-2 grams x 1, then 25% of usual dose (e.g. 250-500 mg) q6-12 hours.

Hemodialysis: 1 - 2 grams x 1, then 25% of usual dose q6-12h. (e.g., 250-500 mg q6-12 hours). 
 For serious or life-threatening infections, give an additional 125mg after each hemodialysis session (1/8th of the usual dose).  PD: 1 - 2 grams x 1, then 25% of usual dose q6-12h. (e.g., 250-500 mg q6-12 hours).  

Renal Dosing: 
[>30 ml/min]: no change .  
 [15-30] 50% of usual regimen.

Alternatively: 8-10mg/kg/day divided q12h x 1-2 days, then 4-6mg/kg q24h.   
[<15] not recommended by manufacturer.   

Alternatively: Non PCP: 8-12 mg/kg/dose q48h (or 4-6 mg/kg/day divided q12-24h) .  
PCP: 15-20 mg/kg/dose q48h (or 7-10 mg/kg/day divided q12-24h).  

Hemodialysis: Not recommended by manufacturer.

INDICATIONS:
 In accord with the concepts in the Warning Box and this INDICATIONS AND USAGE section, chloramphenicol must be used only in those serious infections for which less potentially dangerous drugs are ineffective or contraindicated. However, chloramphenicol may be chosen to initiate antibiotic therapy on the clinical impression that one of the conditions below is believed to be present; in vitro sensitivity tests should be performed concurrently so that the drug may be discontinued as soon
as possible if less potentially dangerous agents are indicated by such tests. The decision to continue use of chloramphenicol rather than another antibiotic when both are suggested by in vitro studies to be effective against a specific pathogen should be based upon severity of the infection, susceptibility of the pathogen to the various antimicrobial drugs, efficacy of the various drugs in the infection, and the important additional concepts contained in the Warning Box above.

1. Acute infections caused by Salmonella typhi*
It is not recommended for the routine treatment of the typhoid carrier state.

2. Serious infections caused by susceptible strains in accordance with the concepts expressed above:
a) Salmonella species
b) H. influenzae, specially meningeal infections
c) Rickettsia
d) Lymphogranuloma-psittacosis group
e) Various gram-negative bacteria causing bacteremia, meningitis, or other serious gram-negative infections
f) Other susceptible organisms which have been demonstrated to be resistant to all other appropriate antimicrobial agents.

3. Cystic fibrosis regimens
*In treatment of typhoid fever some authorities recommend that chloramphenicol be administered at therapeutic levels for 8 to 10 days after the patient has become afebrile to lessen the possibility of relapse.

DOSAGE AND ADMINISTRATION
Chloramphenicol, like other potent drugs, should be prescribed at recommended doses known to have therapeutic activity. Administration of 50 mg/kg/day in divided doses will produce blood levels of the magnitude to which the majority of susceptible microorganisms will respond.

As soon as feasible an oral dosage form of another appropriate antibiotic should be substituted for intravenous chloramphenicol sodium succinate.

The following method of administration is recommended:
Intravenously as a 10% (100 mg/mL) solution to be injected over at least a one-minute interval. This is prepared by the addition of 10 mL of an aqueous diluent such as water for injection or 5% dextrose injection.

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Adults
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Adults should receive 50 mg/kg/day in divided doses at 6-hour intervals. In exceptional cases patients with infections due to moderately resistant organisms may require increased dosage up to 100 mg/kg/day to achieve blood levels inhibiting the pathogen, but these high doses should be decreased as soon as possible. Adults with impairment of hepatic or renal function or both may have reduced ability to metabolize and excrete the drug. In instances of impaired metabolic processes, dosages should be adjusted accordingly. 

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Children
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Dosage of 50 mg/kg/day divided into 4 doses at 6-hour intervals yields blood levels in the range effective against most susceptible organisms. Severe infections (eg, bacteremia or meningitis), especially when adequate cerebrospinal fluid concentrations are desired, may require dosage up to 100 mg/kg/day; however, it is recommended that dosage be reduced to 50 mg/kg/day as soon as possible. Children with impaired liver or kidney function may retain excessive amounts of the drug.

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Newborn Infants
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(See section titled “Gray Syndrome” under ADVERSE REACTIONS (package insert.)
A total of 25 mg/kg/day in 4 equal doses at 6-hour intervals usually produces and maintains concentrations in blood and tissues adequate to control most infections for which the drug is indicated. Increased dosage in these individuals, demanded by severe infections, should be given only to maintain the blood concentration within a therapeutically effective range. After the first two weeks of life, full-term neonates ordinarily may receive up to a total of 50 mg/kg/day equally divided into 4 doses at 6-hour intervals. These dosage recommendations are extremely important because blood concentration in all premature and full-term neonates under two weeks of age differs from that of other infants neonates. This difference is due to variations in the maturity of the metabolic functions of the liver and the kidneys. When these functions are immature (or seriously impaired in adults), high concentrations of the drug are found which tend to increase with succeeding doses.

Infants and Children with Immature Metabolic Processes
In young infants and other pediatric patients in whom immature metabolic functions are suspected, a dose of 25 mg/kg/day will usually produce therapeutic concentrations of the drug in the blood. In this group particularly, the concentration of the drug in the blood should be carefully followed by microtechniques. (Information available on request.)

Renal Dosing: No adjustments needed.  Hemodialysis:   No adjustments needed.

Microbiology:
Clindamycin inhibits bacterial protein synthesis by binding to the 50S subunit of the ribosome. It has activity against Gram-positive aerobes and anaerobes, as well as some Gram-negative anaerobes. Clindamycin is bacteriostatic. Cross-resistance between clindamycin and lincomycin is complete. Antagonism in vitro has been demonstrated between clindamycin and erythromycin. Clindamycin inducible resistance has been identified in macrolide-resistant staphylococci and beta-hemolytic streptococci. Macrolide-resistant isolates of these organisms should be screened for clindamycin inducible resistance using the D-zone test.

Clindamycin has been shown to be active against most of the isolates of the following microorganisms, both in vitro and in clinical infections, as described in the INDICATIONS AND USAGE section.

Gram-positive Aerobes
Staphylococcus aureus (methicillin-susceptible strains)
Streptococcus pneumoniae (penicillin-susceptible strains)
Streptococcus pyogenes

Anaerobes
Prevotella melaninogenica
Fusobacterium necrophorum
Fusobacterium nucleatum
Peptostreptococcus anaerobius
Clostridium perfringens

At least 90% of the microorganisms listed below exhibit in vitro minimum inhibitory concentrations (MICs) less than or equal to the clindamycin susceptible MIC breakpoint for organisms of a similar type. However, the efficacy of clindamycin in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.

Gram-positive aerobes
Staphylococcus epidermidis (methicillin-susceptible strains)
Streptococcus agalactiae
Streptococcus anginosus
Streptococcus oralis
Streptococcus mitis

Anaerobes
Prevotella intermedia
Prevotella bivia
Propionibacterium acnes
Micromonas ("Peptostreptococcus") micros
Finegoldia ("Peptostreptococcus") magna
Actinomyces israelii
Clostridium clostridioforme
Eubacterium lentum

INDICATIONS AND USAGE:
CLEOCIN PHOSPHATE products are indicated in the treatment of serious infections caused by susceptible anaerobic bacteria.

CLEOCIN PHOSPHATE products are also 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 antibiotic-associated pseudomembranous colitis, as described in the WARNING box, before selecting clindamycin the physician should consider the nature of the infection and the suitability of less toxic alternatives (e.g., erythromycin).

Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to clindamycin.

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

CLEOCIN PHOSPHATE is indicated in the treatment of serious infections caused by susceptible strains of the designated organisms in the conditions listed below:

Lower respiratory tract infections including pneumonia, empyema, and lung abscess caused by anaerobes, Streptococcus pneumoniae, other streptococci (except E. faecalis), and Staphylococcus aureus.

Skin and skin structure infections caused by Streptococcus pyogenes, Staphylococcus aureus, and anaerobes.

Gynecological infections including endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis, and postsurgical vaginal cuff infection caused by susceptible anaerobes.

Intra-abdominal infections including peritonitis and intra-abdominal abscess caused by susceptible anaerobic organisms.

Septicemia caused by Staphylococcus aureus, streptococci (except Enterococcus faecalis), and susceptible anaerobes.

Bone and joint infections including acute hematogenous osteomyelitis caused by Staphylococcus aureus and as adjunctive therapy in the surgical treatment of chronic bone and joint infections due to susceptible organisms.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of CLEOCIN PHOSPHATE and other antibacterial drugs, CLEOCIN PHOSPHATE 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.

DOSAGE AND ADMINISTRATION:
If diarrhea occurs during therapy, this antibiotic should be discontinued (see WARNING box).

Clindamycin phosphate IM administration should be used undiluted.
Clindamycin phosphate IV administration should be diluted (See Dilution for IV use and IV infusion rates below)

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PARENTERAL (IV)
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Adults
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Parenteral (IM or IV Administration): Serious infections due to aerobic gram-positive cocci and the more susceptible anaerobes (NOT generally including Bacteroides fragilis, Peptococcus species and Clostridium species other than Clostridium perfringens):

600-1200 mg/day in 2, 3 or 4 equal doses.

More severe infections, particularly those due to proven or suspected Bacteroides fragilis, Peptococcus species, or Clostridium species other than Clostridium perfringens:

1200-2700 mg/day in 2, 3 or 4 equal doses.

For more serious infections, these doses may have to be increased. In life-threatening situations due to either aerobes or anaerobes these doses may be increased. Doses of as much as 4800 mg daily have been given intravenously to adults. See Dilution for IV use and IV Infusion Rates section below.

Single intramuscular injections of greater than 600 mg are not recommended.

Alternatively, drug may be administered in the form of a single rapid infusion of the first dose followed by continuous IV infusion as follows:

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Neonates (less than 1 month)
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15 to 20 mg/kg/day in 3 to 4 equal doses. The lower dosage may be adequate for small prematures.

Pediatric patients 1 month of age to 16 years

Parenteral (IM or IV) Administration: 20 to 40 mg/kg/day in 3 or 4 equal doses. The higher doses would be used for more severe infections. As an alternative to dosing on a body weight basis, pediatric patients may be dosed on the basis of square meters body surface: 350 mg/m2/day for serious infections and 450 mg/m2/day for more severe infections.

Parenteral therapy may be changed to oral CLEOCIN PEDIATRIC® Flavored Granules (clindamycin palmitate hydrochloride) or CLEOCIN HCl® Capsules (clindamycin hydrochloride) when the condition warrants and at the discretion of the physician.

In cases of beta-hemolytic streptococcal infections, treatment should be continued for at least 10 days.

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Dilution for IV use and IV Infusion Rates
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The concentration of clindamycin in diluent for infusion should not exceed 18 mg per mL. Infusion rates should not exceed 30 mg per minute. The usual infusion dilutions and rates are as follows:

Administration of more than 1200 mg in a single 1-hour infusion is not recommended.

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

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Dilution and Compatibility
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Physical and biological compatibility studies monitored for 24 hours at room temperature have demonstrated no inactivation or incompatibility with the use of CLEOCIN PHOSPHATE Sterile Solution (clindamycin phosphate) in IV solutions containing sodium chloride, glucose, calcium or potassium, and solutions containing vitamin B complex in concentrations usually used clinically. No incompatibility has been demonstrated with the antibiotics cephalothin, kanamycin, gentamicin, penicillin or carbenicillin.

The following drugs are physically incompatible with clindamycin phosphate: ampicillin sodium, phenytoin sodium, barbiturates, aminophylline, calcium gluconate, and magnesium sulfate.

The compatibility and duration of stability of drug admixtures will vary depending on concentration and other conditions. For current information regarding compatibilities of clindamycin phosphate under specific conditions, please contact the Medical and Drug Information Unit, Pharmacia & Upjohn Company (Division of Pfizer Inc).

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ORAL
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If significant diarrhea occurs during therapy, this antibiotic should be discontinued (see WARNING box).

Adults: Serious infections - 150 to 300 mg every 6 hours. More severe infections - 300 to 450 mg every 6 hours. Pediatric Patients: Serious infections - 8 to 16 mg/kg/day (4 to 8 mg/lb/day) divided into three or four equal doses. More severe infections - 16 to 20 mg/kg/day (8 to 10 mg/lb/day) divided into three or four equal doses.

To avoid the possibility of esophageal irritation, CLEOCIN HCl Capsules should be taken with a full glass of water.

Serious infections due to anaerobic bacteria are usually treated with CLEOCIN PHOSPHATE® Sterile Solution. However, in clinically appropriate circumstances, the physician may elect to initiate treatment or continue treatment with CLEOCIN HCl Capsules.

In cases of beta-hemolytic streptococcal infections, treatment should continue for at least 10 days.

Renal Dosing:
Dosage schedules need not be modified in the presence of mild or moderate renal or hepatic disease.

SUPPLIED:
IV:
Each mL of CLEOCIN PHOSPHATE Sterile Solution contains clindamycin phosphate equivalent to 150 mg clindamycin, 0.5 mg disodium edetate,; 9.45 mg benzyl alcohol added as preservative. When necessary, pH is adjusted with sodium hydroxide and/or hydrochloric acid. CLEOCIN PHOSPHATE is available in the following packages:
1-2 mL vial NDC 0009-0302-02
1-4 mL vial NDC 0009-0602-04
1-6 mL vial NDC 0009-0901-06
25-2 mL vials NDC 0009-0302-25
25-4 mL vials NDC 0009-0602-25
25-6 mL vials NDC 0009-0901-25

Oral:
CLEOCIN HCl Capsules are available in the following strengths, colors and sizes:
75 mg Green
Bottles of 100 NDC 0009-0331-02
150 mg Light Blue and Green
Bottles of 100 NDC 0009-0225-02
Unit dose package of 100 NDC 0009-0225-03
300 mg Light Blue
Bottles of 100 NDC 0009-0395-14
Unit dose package of 100 NDC 0009-0395-02

Store at controlled room temperature 20° to 25° C (68° to 77° F) [see USP].

SOURCE:
Package insert data:

WARNINGS
The patient should be warned to respond to the presence of clinical signs such as sore throat, fever, pallor, purpura or jaundice. Deaths associated with the administration of Dapsone have been reported from agranulocytosis, aplastic anemia and other blood dyscrasias. Complete blood counts should be done frequently in patients receiving Dapsone. The FDA Dermatology Advisory Committee recommended that, when feasible, counts should be done weekly for the first month, monthly for six months and semi-annually thereafter. If a significant reduction in leucocytes, platelets or hemopoiesis is noted, Dapsone should be discontinued and the patient followed intensively. Folic acid antagonists have similar effects and may increase the incidence of hematologic reactions; if co-administered with Dapsone the patient should be monitored more frequently. Patients on weekly pyrimethamine and Dapsone have developed agranulocytosis during the second and third month of therapy.

Severe anemia should be treated prior to initiation of therapy and hemoglobin monitored. Hemolysis and methemoglobin may be poorly tolerated by patients with severe cardiopulmonary disease.

Cutaneous reactions, especially bullous, include exfoliative dermatitis and are probably one of the most serious, though rare, complications of sulfone therapy. They are directly due to drug sensitization. Such reactions include toxic erythema, erythema multiforme, toxic epidermal necrolysis, morbilliform and scarlatiniform reactions, urticaria and erythema nodosum. If new or toxic dermatologic reactions occur, sulfone therapy must be promptly discontinued and appropriate therapy instituted. Leprosy reactional states, including cutaneous, are not hypersensitivity reactions to Dapsone and do not require discontinuation. See special section.

DOSAGE AND ADMINISTRATION
Dosing: 100 mg po qd.
[PCP]: 100mg po qd.
[Dermatitis herpetiformis]: 50-300 mg qd.

Dermatitis herpetiformis:
The dosage should be individually titrated starting in adults with 50 mg daily and correspondingly smaller doses in children. If full control is not achieved within the range of 50-300 mg daily, higher doses may be tried. Dosage should be reduced to a minimum maintenance level as soon as possible. In responsive patients there is a prompt reduction in pruritus followed by clearance of skin lesions. There is no effect on the gastrointestinal component of the disease. Dapsone levels are influenced by acetylation rates. Patients with high acetylation rates, or who are receiving treatment affecting acetylation may require an adjustment in dosage.

A strict gluten free diet is an option for the patient to elect, permitting many to reduce or eliminate the need for Dapsone; the average time for dosage reduction is 8 months with a range of 4 months to 2 1/2 years and for dosage elimination 29 months with a range of 6 months to 9 years.

Leprosy:
In order to reduce secondary Dapsone resistance, the WHO Expert Committee on Leprosy and the USPHS at Carville, LA, recommended that Dapsone should be commenced in combination with one or more anti-leprosy drugs. In the multidrug program Dapsone should be maintained at the full dosage of 100 mg daily without interruption (with corresponding smaller doses for children) and provided to all patients who have sensitive organisms with new or recrudescent disease or who have not yet completed a two year course of Dapsone monotherapy. For advice and other drugs, the USPHS at Carville, LA (1-800-642-2477) should be contacted. Before using other drugs consult appropriate product labeling.

In bacteriologically negative tuberculoid and indeterminate disease, the recommendation is the coadministration of Dapsone 100 mg daily with six months of Rifampin 600 mg daily. Under WHO, daily Rifampin may be replaced by 600 mg Rifampin monthly, if supervised. The Dapsone is continued until all signs of clinical activity are controlled - usually after an additional six months. Then Dapsone should be continued for an additional three years for tuberculoid and indeterminate patients and for five years for borderline tuberculoid patients.

In lepromatous and borderline lepromatous patients, the recommendation is the co-administration of Dapsone 100 mg daily with two years of Rifampin 600 mg daily. Under WHO daily Rifampin may be replaced by 600 mg Rifampin monthly, if supervised. One may elect the concurrent administration of a third anti-leprosy drug, usually either Clofazamine 50-100 mg daily or Ethionamide 250-500 mg daily. Dapsone 100 mg daily is continued 3-10 years until all signs of clinical activity are controlled with skin scrapings and biopsies negative for one year. Dapsone should then be continued for an additional 10 years for borderline patients and for life for lepromatous patients.

Secondary Dapsone resistance should be suspected whenever a lepromatous or borderline lepromatous patient receiving Dapsone treatment relapses clinically and bacteriologically, solid staining bacilli being found in the smears taken from the new active lesions. If such cases show no response to regular and supervised Dapsone therapy within three to six months or good compliance for the past 3-6 months can be assured, Dapsone resistance should be considered confirmed clinically. Determination of drug sensitivity using the mouse footpad method is recommended and, after prior arrangement, is available without charge from the USPHS, Carville, LA. Patients with proven Dapsone resistance should be treated with other drugs.

LEPROSY REACTIONAL STATES
Abrupt changes in clinical activity occur in leprosy with any effective treatment and are known as reactional states. The majority can be classified into two groups. The “Reversal” reaction (Type 1) may occur in borderline or tuberculoid leprosy patients often soon after chemotherapy is started. The mechanism is presumed to result from a reduction in the antigenic load: the patient is able to mount an enhanced delayed hypersensitivity response to residual infection leading to swelling (“Reversal”) of existing skin and nerve lesions. If severe, or if neuritis is present, large doses of steroids should always be used. If severe, the patient should be hospitalized. In general anti-leprosy treatment is continued and therapy to suppress the reaction is indicated such as analgesics, steroids, or surgical decompression of swollen nerve trunks. USPHS at Carville, LA should be contacted for advice in management.

Erythema nodosum leprosum (ENL) (lepromatous reaction) (Type 2 reaction) occurs mainly in lepromatous patients and small numbers of borderline patients. Approximately 50% of treated patients show this reaction in the first year. The principal clinical features are fever and tender erythematous skin nodules sometimes associated with malaise, neuritis, orchitis, albuminuria, joint swelling, iritis, epistaxis or depression. Skin lesions can become pustular and/or ulcerate. Histologically there is a vasculitis with an intense polymorphonuclear infiltrate. Elevated circulating immune complexes are considered to be the mechanism of reaction. If severe, patients should be hospitalized. In general, anti-leprosy treatment is continued. Analgesics, steroids, and other agents available from USPHS, Carville, LA, are used to suppress the reaction.

Renal Dosing:  
Specific guidelines are not available

Daptomycin exhibits rapid, concentration-dependent bactericidal activity against Gram-positive bacteria in vitro. This has been demonstrated both by time-kill curves and by MBC/MIC (minimum bactericidal concentration/minimum inhibitory concentration) ratios using broth dilution methodology. Daptomycin maintained bactericidal activity in vitro against stationary phase S. aureus in simulated endocardial vegetations. The clinical significance of this is not known.

Mechanism of Action
The mechanism of action of daptomycin is distinct from that of any other antibacterial. Daptomycin binds to bacterial cell membranes and causes a rapid depolarization of membrane potential. This loss of membrane potential causes inhibition of DNA, RNA, and protein synthesis, which results in bacterial cell death.

Mechanism of Resistance
The mechanism(s) of daptomycin resistance is not fully understood. Currently, there are no known transferable elements that confer resistance to daptomycin.

Complicated Skin and Skin Structure Infection (cSSSI) Trials
The emergence of daptomycin non-susceptible isolates occurred in 2 infected patients across the set of Phase 2 and pivotal Phase 3 clinical trials of cSSSI. In one case, a non-susceptible S. aureus was isolated from a patient in a Phase 2 trial who received CUBICIN at less than the protocol-specified dose for the initial 5 days of therapy. In the second case, a non-susceptible Enterococcus faecalis was isolated from a patient with an infected chronic decubitus ulcer who was enrolled in a salvage trial.

S. aureus Bacteremia/Endocarditis and Other Post-Approval Trials
In subsequent clinical trials, non-susceptible isolates were recovered. S. aureus was isolated from a patient in a compassionate-use trial and from 7 patients in the S. aureus bacteremia/endocarditis trial [see Clinical Trials (14.2)]. An E. faecium was isolated from a patient in a vancomycin-resistant enterococci trial.

Interactions with Other Antibacterials
In vitro studies have investigated daptomycin interactions with other antibacterials. Antagonism, as determined by kill curve studies, has not been observed. In vitro synergistic interactions of daptomycin with aminoglycosides, ß-lactam antibacterials, and rifampin have been shown against some isolates of staphylococci (including some methicillin-resistant isolates) and enterococci (including some vancomycin-resistant isolates).

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Activity In Vitro and In Vivo
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Daptomycin has been shown to be active against most isolates of the following Gram-positive bacteria both in vitro and in clinical infections, as described in Indications and Usage.

Gram-Positive Bacteria
Enterococcus faecalis (vancomycin-susceptible isolates only)
Staphylococcus aureus (including methicillin-resistant isolates)
Streptococcus agalactiae
Streptococcus dysgalactiae subsp. equisimilis
Streptococcus pyogenes

The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following Gram-positive bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for daptomycin versus the bacterial genus. However, the efficacy of CUBICIN in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials.

Gram-Positive Bacteria
Corynebacterium jeikeium
Enterococcus faecalis (vancomycin-resistant isolates)
Enterococcus faecium (including vancomycin-resistant isolates)
Staphylococcus epidermidis (including methicillin-resistant isolates)
Staphylococcus haemolyticus

INDICATIONS AND USAGE
CUBICIN is indicated for the treatment of the infections listed below.

Complicated Skin and Skin Structure Infections
Complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of the following Gram-positive bacteria: Staphylococcus aureus (including methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subsp. equisimilis, and Enterococcus faecalis (vancomycin-susceptible isolates only).

Staphylococcus aureus Bloodstream Infections (Bacteremia), Including Those with Right-Sided Infective Endocarditis, Caused by Methicillin-Susceptible and Methicillin-Resistant Isolates

Limitations of Use
CUBICIN is not indicated for the treatment of pneumonia.

CUBICIN is not indicated for the treatment of left-sided infective endocarditis due to S. aureus. The clinical trial of CUBICIN in patients with S. aureus bloodstream infections included limited data from patients with left-sided infective endocarditis; outcomes in these patients were poor [see Clinical Trials (14.2)]. CUBICIN has not been studied in patients with prosthetic valve endocarditis.

Usage
Appropriate specimens for microbiological examination should be obtained in order to isolate and identify the causative pathogens and to determine their susceptibility to daptomycin.

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

When culture and susceptibility information is available, it 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. Empiric therapy may be initiated while awaiting test results.

DOSAGE AND ADMINISTRATION

Administration Duration
CUBICIN should be administered intravenously either by injection over a two (2) minute period or by infusion over a thirty (30) minute period.

Complicated Skin and Skin Structure Infections
CUBICIN 4 mg/kg should be administered intravenously in 0.9% sodium chloride injection once every 24 hours for 7 to 14 days.

Staphylococcus aureus Bloodstream Infections (Bacteremia), Including Those with Right-Sided Infective Endocarditis, Caused by Methicillin-Susceptible and Methicillin-Resistant Isolates
CUBICIN 6 mg/kg should be administered intravenously in 0.9% sodium chloride injection once every 24 hours for 2 to 6 weeks. There are limited safety data for the use of CUBICIN for more than 28 days of therapy. In the Phase 3 trial, there were a total of 14 patients who were treated with CUBICIN for more than 28 days.

Renal Dosing:   Crcl <30 mL/min: 4-6 mg/kg every 48 hours depending on indication.
Hemodialysis (administer after hemodialysis) and/or CAPD: 4-6 mg/kg every 48 hours. 

The recommended dosage regimen for patients with creatinine clearance (CLCR) <30 mL/min, including patients on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), is 4 mg/kg (cSSSI) or 6 mg/kg (S. aureus bloodstream infections) once every 48 hours (Table 1). When possible, CUBICIN should be administered following the completion of hemodialysis on hemodialysis days.

Table 1. Recommended Dosage of CUBICIN in Adult Patients

*When possible, administer CUBICIN following the completion of hemodialysis on hemodialysis days.

Preparation of CUBICIN for Administration
CUBICIN is supplied in single-use vials, each containing 500 mg daptomycin as a sterile, lyophilized powder. The contents of a CUBICIN vial should be reconstituted, using aseptic technique, to 50 mg/mL as follows:
Note: To minimize foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.
1] Remove the polypropylene flip-off cap from the CUBICIN vial to expose the central portion of the rubber stopper.

2] Slowly transfer 10 mL of 0.9% sodium chloride injection through the center of the rubber stopper into the CUBICIN vial, pointing the transfer needle toward the wall of the vial.

3] Ensure that all of the CUBICIN powder is wetted by gently rotating the vial.

4] Allow the wetted product to stand undisturbed for 10 minutes.

5] Gently rotate or swirl the vial contents for a few minutes, as needed, to obtain a completely reconstituted solution.

For intravenous (IV) injection over a period of 2 minutes, administer the appropriate volume of the reconstituted CUBICIN (concentration of 50 mg/mL).

For IV infusion over a period of 30 minutes, the appropriate volume of the reconstituted CUBICIN (concentration of 50 mg/mL) should be further diluted, using aseptic technique, into a 50 mL IV infusion bag containing 0.9% sodium chloride injection.

Parenteral drug products should be inspected visually for particulate matter prior to administration.

No preservative or bacteriostatic agent is present in this product. Aseptic technique must be used in the preparation of final IV solution. Stability studies have shown that the reconstituted solution is stable in the vial for 12 hours at room temperature and up to 48 hours if stored under refrigeration at 2 to 8°C (36 to 46°F).

The diluted solution is stable in the infusion bag for 12 hours at room temperature and 48 hours if stored under refrigeration. The combined storage time (reconstituted solution in vial and diluted solution in infusion bag) should not exceed 12 hours at room temperature or 48 hours under refrigeration.
CUBICIN vials are for single use only.

Compatible Intravenous Solutions
CUBICIN is compatible with 0.9% sodium chloride injection and lactated Ringer's injection.

Supplied:  250 mg, 500 mg  (Injection - powder for reconstitution)

DOSAGE AND ADMINISTRATION
One 200 mg tablet orally twice daily for 10 days with or without food .

HOW SUPPLIED
Film-coated tablets: 200 mg

Uncomplicated skin and skin structure infections: Oral: 400 mg every 12 hours for 10-14 days.

Renal Dosing: no adjustment necessary.
(Two primary metabolites of linezolid may accumulate in patients with renal insufficiency- more studies are needed to determine the clinical significance). 
Hemodialysis:   No adjustment necessary. On dialysis days, schedule dose after dialysis. (~30% extraction).

Seven-day course of treatment - 250 mg three times daily for seven consecutive days. There is some indication from controlled comparative studies that cure rates as determined by vaginal smears and signs and symptoms, may be higher after a seven-day course of treatment than after a one-day treatment regimen.

The dosage regimen should be individualized. Single-dose treatment can assure compliance, especially if administered under supervision, in those patients who cannot be relied on to continue the seven-day regimen. A seven-day course of treatment may minimize reinfection by protecting the patient long enough for the sexual contacts to obtain appropriate treatment. Further, some patients may tolerate one treatment regimen better than the other.

Pregnant patients should not be treated during the first trimester (see PACKAGE INSERT FOR CONTRAINDICATIONS). In pregnant patients for whom alternative treatment has been inadequate, the one-day course of therapy should not be used, as it results in higher serum levels which can reach the fetal circulation.

When repeat courses of the drug are required, it is recommended that an interval of four to six weeks elapse between courses and that the presence of the trichomonad be reconfirmed by appropriate laboratory measures. Total and differential leukocyte counts should be made before and after re-treatment.

In the Male
Treatment should be individualized as it is for the female.

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Amebiasis
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Adults
For acute intestinal amebiasis (acute amebic dysentery): 750 mg orally three times daily for 5 to 10 days.

For amebic liver abscess: 500 mg or 750 mg orally three times daily for 5 to 10 days.

Pediatric patients: 35 to 50 mg/kg/24 hours, divided into three doses, orally for 10 days.

==================
Anaerobic Bacterial Infections
==================
In the treatment of most serious anaerobic infections, intravenous metronidazole is usually administered initially.

The usual adult oral dosage is 7.5 mg/kg every six hours (approx. 500 mg for a 70-kg adult). A maximum of 4 g should not be exceeded during a 24-hour period.

The usual duration of therapy is 7 to 10 days; however, infections of the bone and joint, lower respiratory tract, and endocardium may require longer treatment.

Renal Dosing:
[CRCL > 10]: no changes.   
[<10]: 500mg q8-12h or (50% of usual dose at same interval). 

Hemodialysis: 500mg q8-12h (usually q12h) or (50% of usual dose at same interval). On dialysis days, schedule dose after dialysis.  

Mechanism of Action
The mechanism of the antimicrobial action of nitrofurantoin is unusual among antibacterials.

Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates which inactivate or alter bacterial ribosomal proteins and other acromolecules. As a result of such inactivations, the vital biochemical processes of protein synthesis, aerobic energy metabolism, DNA synthesis, RNA synthesis, and cell wall synthesis are inhibited. Nitrofurantoin is bactericidal in urine at therapeutic doses. The broad-based nature of this mode of action may explain the lack of acquired bacterial resistance to nitrofurantoin, as the necessary multiple and simultaneous mutations of the target macromolecules would likely be lethal to the bacteria.

Interactions with Other Antibiotics
Antagonism has been demonstrated in vitro between nitrofurantoin and quinolone antimicrobials. The clinical significance of this finding is unknown.

Development of Resistance
Development of resistance to nitrofurantoin has not been a significant problem since its introduction in 1953. Cross-resistance with antibiotics and sulfonamides has not been observed, and transferable resistance is, at most, a very rare phenomenon.

Nitrofurantoin has been shown to be active against most strains of the following bacteria both in vitro and in clinical infections [see Indications and Usage):

Aerobic and facultative Gram-positive microorganisms:
Staphylococcus aureus
Enterococci (e.g. Enterococcus faecalis)

Aerobic and facultative Gram-negative microorganisms:
Escherichia coli

NOTE: While nitrofurantoin has excellent activity against Enterococcus faecalis, the majority of Enterococcus faecium isolates are not susceptible to nitorfurantoin.

At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for nitrofurantoin. However, the efficacy of nitrofurantoin in treating clinical infections due to these

microorganisms has not been established in adequate and well-controlled trials.

Aerobic and facultative Gram-positive microorganisms:
Coagulase-negative staphylococci (including Staphylococcus epidermidis and Staphylococcus saprophyticus)
Streptococcus agalactiae
Group D streptococci
Viridans group streptococci

Aerobic and facultative Gram-negative microorganisms:
Citrobacter amalonaticus
Citrobacter diversus
Citrobacter freundii
Klebsiella oxytoca
Klebsiella ozaenae

NOTE: Some strains of Enterobacter species and Klebsiella species are resistant to nitrofurantoin.

INDICATIONS AND USAGE
Macrodantin is specifically indicated for the treatment of urinary tract infections when due to susceptible strains of Escherichia coli, enterococci, Staphylococcus aureus, and certain susceptible strains of Klebsiella and Enterobacter species.

Nitrofurantoin is not indicated for the treatment of pyelonephritis or perinephric abscesses.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Macrodantin and other antibacterial drugs, Macrodantin 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.

Nitrofurantoins lack the broader tissue distribution of other therapeutic agents approved for urinary tract infections. Consequently, many patients who are treated with Macrodantin are predisposed to persistence or reappearance of bacteriuria. Urine specimens for culture and susceptibility testing should be obtained before and after completion of therapy. If persistence or reappearance of bacteriuria occurs after treatment with Macrodantin, other therapeutic agents with broader tissue distribution should be selected. In considering the use of Macrodantin, lower eradication rates should be balanced against the increased potential for systemic toxicity and for the development of antimicrobial resistance when agents with broader tissue distribution are utilized.

CONTRAINDICATIONS
Anuria, oliguria, or significant impairment of renal function (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine) are contraindications. Treatment of this type of patient carries an increased risk of toxicity because of impaired excretion of the drug.

Because of the possibility of hemolytic anemia due to immature erythrocyte enzyme systems (glutathione instability), the drug is contraindicated in pregnant patients at term (38-42 weeks’ gestation), during labor and delivery, or when the onset of labor is imminent. For the same reason, the drug is contraindicated in neonates under one month of age.

Macrodantin is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin.

Macrodantin is also contraindicated in those patients with known hypersensitivity to nitrofurantoin.

DOSAGE AND ADMINISTRATION
Dosing: 50-100 mg q6h.
Macrobid: 100 mg q12h.

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MACROBID (nitrofurantoin monohydrate/macrocrystalline) capsule
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Macrobid capsules should be taken with food.

Adults and Pediatric Patients Over 12 Years: One 100 mg capsule every 12 hours for seven days.

HOW SUPPLIED
Macrobid is available as 100 mg opaque black and yellow capsules imprinted “(Band) Macrobid (Band)” on one half and “52427-285” on the other.
NDC 52427-285-01 bottle of 100

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NITROFURANTOIN MACROCRYSTALS capsule
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DOSAGE AND ADMINISTRATION

Nitrofurantoin macrocrystals should be given with food to improve drug absorption and, in some patients, tolerance.
Adults
50 to 100 mg four times a day - the lower dosage level is recommended for uncomplicated urinary tract infections.

Pediatric Patients
5 to 7 mg/kg of body weight per 24 hours, given in four divided doses (contraindicated under one month of age).

Therapy should be continued for one week or for at least 3 days after sterility of the urine is obtained. Continued infection indicates the need for reevaluation.

For long-term suppressive therapy in adults, a reduction of dosage to 50 to 100 mg at bedtime may be adequate. For long-term suppressive therapy in pediatric patients, doses as low as 1 mg/kg per 24 hours, given in a single dose or in two divided doses, may be adequate.

Renal Dosing:
[CRCL >50]: Normal dose.  
[0-49]: Avoid use.  
Hemo: Avoid use.

Complicated skin and skin structure infections caused by Staphylococcus aureus (methicillin susceptible) or Streptococcus pyogenes.

CONTRAINDICATIONS
Synercid is contraindicated in patients with known hypersensitivity to Synercid, or with prior hypersensitivity to other streptogramins (e.g., pristinamycin or virginiamycin).

DOSAGE AND ADMINISTRATION
Synercid should be administered by intravenous infusion in 5% Dextrose in Water solution over a 60-minute period.  An infusion pump or device may be used to control the rate of infusion. If necessary, central venous access (e.g., PICC) can be used to administer Synercid to decrease the incidence of venous irritation.
The recommended dosage for the treatment of complicated skin and skin structure infections is 7.5 mg/kg q12h. The minimum recommended treatment duration for complicated skin and skin structure infections is seven days.

--------------------------
Special Populations
--------------------------
Elderly: No dosage adjustment of Synercid is required for use in the elderly.

Renal Insufficiency: No dosage adjustment of Synercid is required for use in patients with renal impairment or patients undergoing peritoneal dialysis.

Hepatic Insufficiency: Data from clinical trials of Synercid suggest that the incidence of adverse effects in patients with chronic liver insufficiency or cirrhosis was comparable to that in patients with normal hepatic function. Pharmacokinetic data in patients with hepatic cirrhosis (Child Pugh A or B) suggest that dosage reduction may be necessary but exact recommendations cannot be made at this time.

Pediatric Patients: The recommended dose of Synercid for pediatric patients (12 to <18 years of age) is 7.5 mg/kg q12h. No dosing recommendations are available in pediatric patients less than 12 years of age.

--------------------------
Preparation and administration of solution:
--------------------------
1] Reconstitute the 500 mg single dose vial by slowly adding 5 mL of 5% Dextrose in Water or Sterile Water for injection.

2] GENTLY swirl the vial by manual rotation without shaking to ensure dissolution of contents while LIMITING FOAM FORMATION.

3] Allow the solution to sit for a few minutes until all the foam has disappeared. The resulting solution should be clear. Vials reconstituted in this manner will give a solution of 100 mg/mL. CAUTION: FURTHER DILUTION REQUIRED BEFORE INFUSION.

4] According to the patient's weight, the reconstituted Synercid solution should be added to 250 mL of 5% Dextrose solution. An infusion volume of 100 mL may be used for central line infusions.

5] If moderate to severe venous irritation occurs following peripheral administration of Synercid diluted in 250 mL of Dextrose 5% in water, consideration should be given to increasing the infusion volume to 500 or 750 mL, changing the infusion site, or infusing by a peripherally inserted central catheter (PICC) or a central venous catheter.

6]  The desired dose should be administered by intravenous infusion over 60 minutes.

NOTE: As for other parenteral drug products, Synercid should be inspected visually for particulate matter prior to administration.

Renal Dosing: No adjustment necessary.

Travelers’ Diarrhea
XIFAXAN 200 mg is indicated for the treatment of patients (≥12 years of age) with travelers’ diarrhea caused by noninvasive strains of Escherichia coli.

Limitations of Use
XIFAXAN should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli.

Hepatic Encephalopathy
XIFAXAN 550 mg is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in
patients ≥ 18 years of age.

In the trials of XIFAXAN for HE, 91% of the patients were using lactulose concomitantly. Differences in the treatment effect of those patients not using lactulose concomitantly could not be assessed.

XIFAXAN has not been studied in patients with MELD (Model for End-Stage Liver Disease) scores > 25, and only 8.6% of patients in the controlled trial had MELD scores over 19. There is increased systemic exposure in patients with more severe hepatic dysfunction [see Warnings and Precautions].

WARNINGS AND PRECAUTIONS
--Travelers’ Diarrhea Not Caused by E. coli: XIFAXAN was not effective in diarrhea complicated by fever and/or blood in the stool or diarrhea due to pathogens other than E. coli. If diarrhea symptoms get worse or persist for more than 24-48 hours, discontinue XIFAXAN and consider alternative antibiotics.
--Clostridium difficile-Associated Diarrhea: Evaluate if diarrhea occurs after therapy or does not improve or worsens during therapy.
--Hepatic Impairment: Use with caution in patients with severe (Child-Pugh C) hepatic impairment.
--Concomitant P-glycoprotein inhibitor: Caution should be exercised when concomitant use of rifaximin and a P-glycoprotein inhibitor is needed.

USE IN SPECIFIC POPULATIONS
--Pregnancy: Based on animal data, may cause fetal harm.
--Nursing Mothers: Discontinue nursing or drug, taking into account the importance of the drug to the mother.

=======================================
DOSAGE AND ADMINISTRATION:
=======================================

----------------------------
Dosage for Travelers’ Diarrhea
----------------------------
The recommended dose of XIFAXAN is one 200 mg tablet taken orally three times a day for 3 days. XIFAXAN can be administered orally, with or without food.

----------------------------
Dosage for Hepatic Encephalopathy
----------------------------
The recommended dose of XIFAXAN is one 550 mg tablet taken orally two times a day, with or without food.

Renal Dosing:
The pharmacokinetics of rifaximin in patients with impaired renal function has not been studied.

SUPPLIED:
XIFAXAN is a pink-colored biconvex tablet and is available in the following strengths:

200 mg - a round tablet debossed with “Sx” on one side.
550 mg - an oval tablet debossed with “rfx” on one side.

INDICATIONS AND USAGE
TYGACIL is a tetracycline-class antibacterial drug indicated for the treatment of infections caused by susceptible isolates of the designated microorganisms in the conditions listed below for patients 18 years of age and older:
Complicated Skin and Skin Structure Infections
Complicated skin and skin structure infections caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes, Enterobacter cloacae, Klebsiella pneumoniae, and Bacteroides fragilis.

Complicated Intra-abdominal Infections
Complicated intra-abdominal infections caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros.

Community-Acquired Bacterial Pneumonia
Community-acquired bacterial pneumonia caused by Streptococcus pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, Haemophilus influenzae (beta-lactamase negative isolates), and Legionella pneumophila.
-------------------------------
Limitations of Use
-------------------------------
TYGACIL is not indicated for the treatment of diabetic foot infections. A clinical trial failed to demonstrate non-inferiority of TYGACIL for treatment of diabetic foot infections.

TYGACIL is not indicated for the treatment of hospital-acquired or ventilator-associated pneumonia. In a comparative clinical trial, greater mortality and decreased efficacy were reported in TYGACIL-treated patients.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of TYGACIL and other antibacterial drugs, TYGACIL 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.

Appropriate specimens for bacteriological examination should be obtained in order to isolate and identify the causative organisms and to determine their susceptibility to tigecycline. TYGACIL may be initiated as empiric monotherapy before results of these tests are known.

DOSAGE AND ADMINISTRATION
---------------------------------------------------
General Dosage and Administration
---------------------------------------------------
The recommended dosage regimen for TYGACIL is an initial dose of 100 mg, followed by 50 mg every 12 hours. Intravenous infusions of TYGACIL should be administered over approximately 30 to 60 minutes every 12 hours.

The recommended duration of treatment with TYGACIL for complicated skin and skin structure infections or for complicated intra-abdominal infections is 5 to 14 days. The recommended duration of treatment with TYGACIL for community-acquired bacterial pneumonia is 7 to 14 days. The duration of therapy should be guided by the severity and site of the infection and the patient's clinical and bacteriological progress.

---------------------------------------------------
Patients With Hepatic Impairment
---------------------------------------------------
No dosage adjustment is warranted in patients with mild to moderate hepatic impairment (Child Pugh A and Child Pugh B). In patients with severe hepatic impairment (Child Pugh C), the initial dose of TYGACIL should be 100 mg followed by a reduced maintenance dose of 25 mg every 12 hours. Patients with severe hepatic impairment (Child Pugh C) should be treated with caution and monitored for treatment response.

---------------------------------------------------
Pediatric Patients
---------------------------------------------------
The safety and efficacy of the proposed pediatric dosing regimens have not been evaluated due to the observed increase in mortality associated with tigecycline in adult patients. Tigecycline should not be used in pediatric patients unless no alternative antibacterial drugs are available. Under these circumstances, the following doses are suggested:

Pediatric patients aged 8 to 11 years should receive 1.2 mg/kg of tigecycline every 12 hours intravenously to a maximum dose of 50 mg of tigecycline every 12 hours.
Pediatric patients aged 12 to 17 years should receive 50 mg of tigecycline every 12 hours,

The proposed pediatric doses of tigecycline were chosen based on exposures observed in pharmacokinetic trials, which included small numbers of pediatric patients.

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Preparation and Handling
---------------------------------------------------
Each vial of TYGACIL should be reconstituted with 5.3 mL of 0.9% Sodium Chloride Injection, USP, 5% Dextrose Injection, USP, or Lactated Ringer's Injection, USP to achieve a concentration of 10 mg/mL of tigecycline. (Note: Each vial contains a 6% overage. Thus, 5 mL of reconstituted solution is equivalent to 50 mg of the drug.) The vial should be gently swirled until the drug dissolves. Withdraw 5 mL of the reconstituted solution from the vial and add to a 100 mL intravenous bag for infusion (for a 100 mg dose, reconstitute two vials; for a 50 mg dose, reconstitute one vial). The maximum concentration in the intravenous bag should be 1 mg/mL. The reconstituted solution should be yellow to orange in color; if not, the solution should be discarded. Parenteral drug products should be inspected visually for particulate matter and discoloration (e.g., green or black) prior to administration. Once reconstituted, TYGACIL may be stored at room temperature (not to exceed 25°C/77°F) for up to 24 hours (up to 6 hours in the vial and the remaining time in the intravenous bag). If the storage conditions exceed 25°C (77°F) after reconstitution, tigecycline should be used immediately. Alternatively, TYGACIL mixed with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP may be stored refrigerated at 2° to 8°C (36° to 46°F) for up to 48 hours following immediate transfer of the reconstituted solution into the intravenous bag.

TYGACIL may be administered intravenously through a dedicated line or through a Y-site. If the same intravenous line is used for sequential infusion of several drugs, the line should be flushed before and after infusion of TYGACIL with 0.9% Sodium Chloride Injection, USP, 5% Dextrose Injection, USP or Lactated Ringer's Injection, USP. Injection should be made with an infusion solution compatible with tigecycline and with any other drug(s) administered via this common line.

Compatibilities
Compatible intravenous solutions include 0.9% Sodium Chloride Injection, USP, 5% Dextrose Injection, USP, and Lactated Ringer's Injection, USP. When administered through a Y-site, TYGACIL is compatible with the following drugs or diluents when used with either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP: amikacin, dobutamine, dopamine HCl, gentamicin, haloperidol, Lactated Ringer's, lidocaine HCl, metoclopramide, morphine, norepinephrine, piperacillin/tazobactam (EDTA formulation), potassium chloride, propofol, ranitidine HCl, theophylline, and tobramycin.

Renal Dosing: No adjustment necessary.

Supplied:  Each single-dose 5 mL glass vial and 10 mL glass vial contain 50 mg of tigecycline as an orange lyophilized powder for reconstitution.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of KETEK and other antibacterial drugs, KETEK should be used only to treat 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.

3. MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates known as PRSP (penicillin-resistant Streptococcus pneumoniae), and are isolates resistant to two or more of the following antibiotics: penicillin, 2nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole.

CONTRAINDICATIONS
KETEK is contraindicated in patients with myasthenia gravis. Exacerbations of myasthenia gravis have been reported in patients and sometimes occurred within a few hours of the first dose of telithromycin. Reports have included fatal and life-threatening acute respiratory failure with a rapid onset and progression.

KETEK is contraindicated in patients with previous history of hepatitis and/or jaundice associated with the use of KETEK tablets, or any macrolide antibiotic.

KETEK is contraindicated in patients with a history of hypersensitivity to telithromycin and/or any components of KETEK tablets, or any macrolide antibiotic.

Concomitant administration of KETEK with cisapride or pimozide is contraindicated.

Concomitant administration of KETEK and colchicine is contraindicated in patients with renal or hepatic impairment.

DOSAGE AND ADMINISTRATION
Dosing (Adults): 
The dose of KETEK tablets is 800 mg (2 tablets of 400 mg) taken orally once every 24 hours, for 7–10 days. KETEK tablets can be administered with or without food.

KETEK may be administered without dosage adjustment in the presence of hepatic impairment.

Renal Dosing: 
In the presence of severe renal impairment (CLCR < 30 mL/min), including patients who need dialysis, the dose should be reduced to KETEK 600 mg once daily. In patients undergoing hemodialysis, KETEK should be given after the dialysis session on dialysis days.

In the presence of severe renal impairment (CLCR < 30 mL/min), with coexisting hepatic impairment, the dose should be reduced to KETEK 400 mg once daily.
 
Hemodialysis: Administer dose following dialysis.

Supplied:  300 mg, 400mg tab.

INDICATIONS AND USAGE
Trichomoniasis:   Tinidazole is indicated for the treatment of trichomoniasis caused by Trichomonas vaginalis. The organism should be identified by appropriate diagnostic procedures. Because trichomoniasis is a sexually transmitted disease with potentially serious sequelae, partners of infected patients should be treated simultaneously in order to prevent re-infection.

Giardiasis:  Tinidazole is indicated for the treatment of giardiasis caused by Giardia duodenalis (also termed G. lamblia) in both adults and pediatric patients older than three years of age.

Amebiasis:  Tinidazole is indicated for the treatment of intestinal amebiasis and amebic liver abscess caused by Entamoeba histolytica in both adults and pediatric patients older than three years of age. It is not indicated in the treatment of asymptomatic cyst passage.

Bacterial Vaginosis:  Tinidazole is indicated for the treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, or anaerobic vaginosis) in non-pregnant women.

Other pathogens commonly associated with vulvovaginitis such as Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, Candida albicans and Herpes simplex virus should be ruled out.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tindamax and other antibacterial drugs, Tindamax 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.

CONTRAINDICATIONS
The use of tinidazole is contraindicated:

In patients with a previous history of hypersensitivity to tinidazole or other nitroimidazole derivatives. Reported reactions have ranged in severity from urticaria to Stevens-Johnson syndrome.

During first trimester of pregnancy.

In nursing mothers: Interruption of breast-feeding is recommended during tinidazole therapy and for 3
days following the last dose.

DOSAGE AND ADMINISTRATION
Dosing Instructions
It is advisable to take tinidazole with food to minimize the incidence of epigastric discomfort and other gastrointestinal side-effects. Food does not affect the oral bioavailability of tinidazole.

Alcoholic beverages should be avoided when taking tinidazole and for 3 days afterwards.

Compounding of the Oral Suspension
For those unable to swallow tablets, tinidazole tablets may be crushed in artificial cherry syrup to be taken with food.

Procedure for Extemporaneous Pharmacy Compounding of the Oral Suspension: Pulverize four 500 mg oral tablets with a mortar and pestle. Add approximately 10 mL of cherry syrup to the powder and mix until smooth. Transfer the suspension to a graduated amber container. Use several small rinses of cherry syrup to transfer any remaining drug in the mortar to the final suspension for a final volume of 30 mL. The suspension of crushed tablets in artificial cherry syrup is stable for 7 days at room temperature. When this suspension is used, it should be shaken well before each administration.

Dosing (Adults):
Amebiasis, intestinal: Oral: 2 g/day for 3 days.  
Amebiasis, liver abscess: Oral: 2 g/day for 3-5 days. 
Giardiasis: Oral: 2 g as a single dose. 
Trichomoniasis: Oral: 2 g as a single dose; sexual partners should be treated at the same time. 

-------------------------
Trichomoniasis
-------------------------
The recommended dose in both females and males is a single 2 g oral dose taken with food. Since trichomoniasis is a sexually transmitted disease, sexual partners should be treated with the same dose and at the same time.

-------------------------
Giardiasis
-------------------------
The recommended dose in adults is a single 2 g dose taken with food. In pediatric patients older than three years of age, the recommended dose is a single dose of 50 mg/kg (up to 2 g) with food.

-------------------------
Amebiasis
-------------------------
Intestinal: The recommended dose in adults is a 2 g dose per day for 3 days taken with food. In pediatric patients older than three years of age, the recommended dose is 50 mg/kg/day (up to 2 g per day) for 3 days with food.

Amebic Liver Abscess: The recommended dose in adults is a 2 g dose per day for 3-5 days taken with food. In pediatric patients older than three years of age, the recommended dose is 50 mg/kg/day (up to 2 g per day) for 3-5 days with food. There are limited pediatric data on durations of therapy exceeding 3 days, although a small number of children were treated for 5 days without additional reported adverse reactions. Children should be closely monitored when treatment durations exceed 3 days.

-------------------------
Bacterial Vaginosis
-------------------------
The recommended dose in non-pregnant females is a 2 g oral dose once daily for 2 days taken with food or a 1 g oral dose once daily for 5 days taken with food. The use of tinidazole in pregnant patients has not been studied for bacterial vaginosis.

Renal Dosing:   no adjustment necessary.

Supplied: 250 mg, 500 mg tab.  
250 mg tablets are pink, round, scored tablets, with TM debossed on one side and 250 on the other
500 mg tablets are pink, oval, scored tablets, with TM debossed on one side and 500 on the other