Levaquin (Levofloxacin) - Indications and Dosage

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of LEVAQUIN® (levofloxacin) and other antibacterial drugs, LEVAQUIN 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.

LEVAQUIN Tablets/Injection are indicated for the treatment of adults (>/=18 years of age) with mild, moderate, and severe infections caused by susceptible strains of the designated microorganisms in the conditions listed below. LEVAQUIN Injection is indicated when intravenous administration offers a route of administration advantageous to the patient (e.g., patient cannot tolerate an oral dosage form). Please see DOSAGE AND ADMINISTRATION for specific recommendations.

Acute maxillary sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.

Acute bacterial exacerbation of chronic bronchitis due to Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis.

Nosocomial pneumonia due to methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, or Streptococcus pneumoniae. Adjunctive therapy should be used as clinically indicated. Where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an anti-pseudomonal (beta)-lactam is recommended. (See CLINICAL STUDIES.)

Community-acquired pneumonia due to Staphylococcus aureus, Streptococcus pneumoniae (including penicillin-resistant strains, MIC value for penicillin >/=2 µg/mL), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydia pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae. (See CLINICAL STUDIES.)

Complicated skin and skin structure infections due to methicillin-susceptible Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes, or Proteus mirabilis.

Uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections, due to Staphylococcus aureus or Streptococcus pyogenes.

Chronic bacterial prostatitis due to Escherichia coli, Enterococcus faecalis, or Staphylococcus epidermidis.

Complicated urinary tract infections (mild to moderate) due to Enterococcus faecalis, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa.

Acute pyelonephritis (mild to moderate) caused by Escherichia coli.

Uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus.

Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to levofloxacin. Therapy with levofloxacin may be initiated before results of these tests are known; once results become available, appropriate therapy should be selected.

As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with levofloxacin. Culture and susceptibility testing performed periodically during therapy will provide information about the continued susceptibility of the pathogens to the antimicrobial agent and also the possible emergence of bacterial resistance.

DOSAGE AND ADMINISTRATION

LEVAQUIN Injection should only be administered by intravenous infusion. It is not for intramuscular, intrathecal, intraperitoneal, or subcutaneous administration.

CAUTION:   RAPID OR BOLUS INTRAVENOUS INFUSION MUST BE AVOIDED. Levofloxacin Injection should be infused intravenously slowly over a period of not less than 60 or 90 minutes, depending on the dosage. (See PRECAUTIONS.)

Single-use vials require dilution prior to administration. (See PREPARATION FOR ADMINISTRATION.)

The usual dose of LEVAQUIN Tablets or Injection is 250 mg or 500 mg administered orally or by slow infusion over 60 minutes every 24 hours or 750 mg administered orally or by slow infusion over 90 minutes every 24 hours, as indicated by infection and described in the following dosing chart. These recommendations apply to patients with normal renal function (i.e., creatinine clearance > 80 mL/min). For patients with altered renal function see the Patients with Impaired Renal Function subsection. Oral doses should be administered at least two hours before or two hours after antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or Videx® (didanosine), chewable/buffered tablets or the pediatric powder for oral solution.

When only the serum creatinine is known, the following formula may be used to estimate creatinine clearance.

The serum creatinine should represent a steady state of renal function.

PREPARATION OF LEVOFLOXACIN INJECTION FOR ADMINISTRATION

LEVAQUIN Injection in Single-Use Vials:    LEVAQUIN Injection is supplied in single-use vials containing a concentrated levofloxacin solution with the equivalent of 500 mg (20 mL vial) and 750 mg (30 mL vial) of levofloxacin in Water for Injection, USP. The 20 mL and 30 mL vials each contain 25 mg of levofloxacin/mL. THESE LEVAQUIN INJECTION SINGLE-USE VIALS MUST BE FURTHER DILUTED WITH AN APPROPRIATE SOLUTION PRIOR TO INTRAVENOUS ADMINISTRATION. (See COMPATIBLE INTRAVENOUS SOLUTIONS.) The concentration of the resulting diluted solution should be 5 mg/mL prior to administration.

This intravenous drug product should be inspected visually for particulate matter prior to administration.

This intravenous drug product should be inspected visually for particulate matter prior to administration. Samples containing visible particles should be discarded.

Since no preservative or bacteriostatic agent is present in this product, aseptic technique must be used in preparation of the final intravenous solution. Since the vials are for single-use only, any unused portion remaining in the vial should be discarded. When used to prepare two 250 mg doses from the 20 mL vial containing 500 mg of levofloxacin, the full content of the vial should be withdrawn at once using a single-entry procedure, and a second dose should be prepared and stored for subsequent use. (See Stability of LEVAQUIN Injection Following Dilution.)

Since only limited data are available on the compatibility of levofloxacin intravenous injection with other intravenous substances, additives or other medications should not be added to LEVAQUIN Injection in single-use vials or infused simultaneously through the same intravenous line. If the same intravenous line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of LEVAQUIN Injection with an infusion solution compatible with LEVAQUIN Injection and with any other drug(s) administered via this common line.

Prepare the desired dosage of levofloxacin according to the following chart:

For example, to prepare a 500 mg dose using the 20 mL vial (25 mg/mL), withdraw 20 mL and dilute with a compatible intravenous solution to a total volume of 100 mL.

Compatible Intravenous Solutions:   Any of the following intravenous solutions may be used to prepare a 5 mg/mL levofloxacin solution with the approximate pH values:

LEVAQUIN Injection Premix in Single-Use Flexible Containers:    LEVAQUIN Injection is also supplied in flexible containers containing a premixed, ready-to-use levofloxacin solution in D₅ W for single-use. The fill volume is either 50 or 100 mL for the 100 mL flexible container or 150 mL for the 150 mL container. NO FURTHER DILUTION OF THESE PREPARATIONS ARE NECESSARY. Consequently each 50 mL, 100 mL, and 150 mL premix flexible container already contains a dilute solution with the equivalent of 250 mg, 500 mg, and 750 mg of levofloxacin, respectively (5 mg/mL) in 5% Dextrose (D₅ W).

This parenteral drug product should be inspected visually for particulate matter prior to administration. Samples containing visible particles should be discarded.

Since the premix flexible containers are for single-use only, any unused portion should be discarded.

Since only limited data are available on the compatibility of levofloxacin intravenous injection with other intravenous substances, additives or other medications should not be added to LEVAQUIN Injection in flexible containers or infused simultaneously through the same intravenous line. If the same intravenous line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of LEVAQUIN Injection with an infusion solution compatible with LEVAQUIN Injection and with any other drug(s) administered via this common line.

Instructions for the Use of LEVAQUIN Injection Premix in Flexible Containers

To open:

1. Tear outer wrap at the notch and remove solution container.
2. Check the container for minute leaks by squeezing the inner bag firmly. If leaks are found, or if the seal is not intact, discard the solution, as the sterility may be compromised.
3. Do not use if the solution is cloudy or a precipitate is present.
4. Use sterile equipment.
5. WARNING:   Do not use flexible containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Preparation for administration:

1. Close flow control clamp of administration set.
2. Remove cover from port at bottom of container.
3. Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated. NOTE: See full directions on administration set carton.
4. Suspend container from hanger.
5. Squeeze and release drip chamber to establish proper fluid level in chamber during infusion of LEVAQUIN Injection in Premix Flexible Containers.
6. Open flow control clamp to expel air from set. Close clamp.
7. Regulate rate of administration with flow control clamp.

STABILITY OF LEVAQUIN INJECTION AS SUPPLIED

When stored under recommended conditions, LEVAQUIN Injection, as supplied in 20 mL and 30 mL vials, or 100 mL and 150 mL flexible containers, is stable through the expiration date printed on the label.

STABILITY OF LEVAQUIN INJECTION FOLLOWING DILUTION

LEVAQUIN Injection, when diluted in a compatible intravenous fluid to a concentration of 5 mg/mL, is stable for 72 hours when stored at or below 25°C (77°F) and for 14 days when stored under refrigeration at 5°C (41°F) in plastic intravenous containers. Solutions that are diluted in a compatible intravenous solution and frozen in glass bottles or plastic intravenous containers are stable for 6 months when stored at -20°C (-4°F). THAW FROZEN SOLUTIONS AT ROOM TEMPERATURE 25°C (77°F) OR IN A REFRIGERATOR 8°C (46°F). DO NOT FORCE THAW BY MICROWAVE IRRADIATION OR WATER BATH IMMERSION. DO NOT REFREEZE AFTER INITIAL THAWING.

HOW SUPPLIED

LEVAQUIN TABLETS

LEVAQUIN (levofloxacin) Tablets are supplied as 250, 500, and 750 mg capsule-shaped, coated tablets. LEVAQUIN Tablets are packaged in bottles and in unit-dose blister strips in the following configurations:

250 mg tablets are terra cotta pink and are imprinted: "LEVAQUIN" on one side and "250" on the other side.

bottles of 50 (NDC 0045-1520-50)

unit-dose/100 tablets (NDC 0045-1520-10)

500 mg tablets are peach and are imprinted: "LEVAQUIN" on one side and "500" on the other side.

bottles of 50 (NDC 0045-1525-50)

unit-dose/100 tablets (NDC 0045-1525-10)

750 mg tablets are white and are imprinted: "LEVAQUIN" one side and "750" the other side.

bottles of 20 (NDC 0045-1530-20)

unit-dose/100 tablets (NDC 0045-1530-10)

LEVA-Pak 5 tablets (NDC 0045-1530-05)

LEVAQUIN Tablets should be stored at 15° to 30°C (59° to 86°F) in well-closed containers.

LEVAQUIN Tablets are manufactured for OMP DIVISION, ORTHO-McNEIL PHARMACEUTICAL, INC. by Janssen Ortho LLC, Gurabo, Puerto Rico 00778.

LEVAQUIN INJECTION

Single-Use Vials:    LEVAQUIN (levofloxacin) Injection is supplied in single-use vials. Each vial contains a concentrated solution with the equivalent of 500 mg of levofloxacin in 20 mL vials and 750 mg of levofloxacin in 30 mL vials.

25 mg/mL, 20 mL vials (NDC 0045-0069-51)

25 mg/mL, 30 mL vials (NDC 0045-0065-55)

LEVAQUIN Injection in Single-Use Vials should be stored at controlled room temperature and protected from light.

LEVAQUIN Injection in Single-Use Vials is manufactured for OMP DIVISION, ORTHO-McNEIL PHARMACEUTICAL, INC. by OMJ Pharmaceuticals, Inc., San German, Puerto Rico 00683.

Premix in Flexible Containers:    LEVAQUIN (levofloxacin in 5% dextrose) Injection is supplied as a single-use, premixed solution in flexible containers. Each bag contains a dilute solution with the equivalent of 250, 500, or 750 mg of levofloxacin, respectively, in 5% Dextrose (D₅ W).

5 mg/mL (250 mg), 50 mL flexible container (NDC 0045-0067-01)

5 mg/mL (500 mg), 100 mL flexible container (NDC 0045-0068-01)

5 mg/mL (750 mg), 150 mL flexible container (NDC 0045-0066-01)

LEVAQUIN Injection Premix in Flexible Containers should be stored at or below 25°C (77°F); however, brief exposure up to 40°C (104°F) does not adversely affect the product. Avoid excessive heat and protect from freezing and light.

LEVAQUIN Injection Premix in Flexible Containers is manufactured for OMP DIVISION, ORTHO-McNEIL PHARMACEUTICAL, INC. by ABBOTT Laboratories, North Chicago, IL 60064.