Dilution Levofloxacin

Levofloxacin (Levaquin ® )

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Usual Diluents

D5W, NS

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]

Primary: (Used commercially available premixed bags - 5 mg/ml): Premix in Single-Use Flexible Containers, for intravenous infusion (5 mg/mL in 5% Dextrose)

1] Premixed 50 mL solution - (equivalent to 250 mg levofloxacin)

2] Premixed 100 mL solution - (equivalent to 500 mg levofloxacin)

3] Premixed 150 mL solution -(equivalent to 750 mg levofloxacin)

Secondary:
If premixed bags are NOT available, use single use vials of levofloxacin:
[250 mg (10 ml)] [40 ml] [60 min] (Total volume: 50 ml)
[500 mg (20 ml)] [80 ml] [60 min] (Total volume: 100 ml)
[750 mg (30 ml)] [120 ml] [90 min] (Total volume: 150 ml)

Stability / Miscellaneous

EXP: 3 DAYS (RT) /14 DAYS (REF)
Label: Refrigerate.DOSAGE AND ADMINISTRATION
Dosage in Adult Patients with Normal Renal Function
The usual dose of LEVAQUIN® Injection is 250 mg or 500 mg administered by slow infusion over 60 minutes every 24 hours or 750 mg administered by slow infusion over 90 minutes every 24 hours, as indicated by infection and described in Table 1.

These recommendations apply to patients with creatinine clearance ≥ 50 mL/min. For patients with creatinine clearance <50 mL/min, adjustments to the dosing regimen are required.

Table 1: Dosage in Adult Patients with Normal Renal Function (creatinine clearance ≥ 50 mL/min)

Type of Infection	Dosed Every 24 hours	Duration (days)
Nosocomial Pneumonia	750 mg	7–14
Community Acquired Pneumonia‡	500 mg	7–14
Community Acquired Pneumonia§	750 mg	5
Acute Bacterial Sinusitis	750 mg	5
Acute Bacterial Sinusitis	500 mg	10–14
Acute Bacterial Exacerbation of Chronic Bronchitis	500 mg	7
Complicated Skin and Skin Structure Infections (SSSI)	750 mg	7–14
Uncomplicated SSSI	500 mg	7–10
Chronic Bacterial Prostatitis	500 mg	28
Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)¶	750 mg	5
Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)#	250 mg	10
Uncomplicated Urinary Tract Infection	250 mg	3
Inhalational Anthrax (Post-Exposure), adult and pediatric patients > 50 kg and ≥ 6 months of age Þ,ß Pediatric patients < 50 kg and ≥ 6 months of age Þ,ß	500 mg see Table 3 below (2.2)	60ß 60ß
Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. ‡ - Due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multi-drug-resistant strains [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae §- Due to Streptococcus pneumoniae (excluding multi-drug-resistant strains [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae ¶ - This regimen is indicated for cUTI due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and AP due to E. coli, including cases with concurrent bacteremia. # - This regimen is indicated for cUTI due to Enterococcus faecalis, Enterococcus cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa; and for AP due to E. coli. Þ- Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit ß-The safety of LEVAQUIN® in adults for durations of therapy beyond 28 days or in pediatric patients for durations beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients. Prolonged LEVAQUIN® therapy in adults should only be used when the benefit outweighs the risk.

Dosage Adjustment in Adults with Renal Impairment
Administer LEVAQUIN® with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced.

No adjustment is necessary for patients with a creatinine clearance ≥ 50 mL/min.

In patients with impaired renal function (creatinine clearance<50 mL/min), adjustment of the dosage regimen is necessary to avoid the accumulation of levofloxacin due to decreased clearance.

Table 3 shows how to adjust dose based on creatinine clearance.
Table 3: Dosage Adjustment in Patients with Renal Impairment (creatinine clearance <50 mL/min)

Dosage in Normal Renal Function Every 24 hours	Creatinine Clearance 20 to 49 mL/min	Creatinine Clearance 10 to 19 mL/min	Hemodialysis or Chronic Ambulatory Peritoneal Dialysis (CAPD)
750 mg	750 mg every 48 hours	750 mg initial dose, then 500 mg every 48 hours	750 mg initial dose, then 500 mg every 48 hours
500 mg	500 mg initial dose, then 250 mg every 24 hours	500 mg initial dose, then 250 mg every 48 hours	500 mg initial dose, then 250 mg every 48 hours
250 mg	No dosage adjustment required	250 mg every 48 hours. If treating uncomplicated UTI, then no dosage adjustment is required	No information on dosing adjustment is available

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

Because only limited data are available on the compatibility of LEVAQUIN® Injection with other intravenous substances, additives or other medications should not be added to LEVAQUIN® Injection Premix in Single-Use Flexible Containers and 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.

LEVAQUIN ® Injection in Single-Use Vials

Single-use vials require dilution prior to administration.

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 Table 4]. The concentration of the resulting diluted solution should be 5 mg/mL prior to administration.

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:
Table 4: Compatible Intravenous Solutions

Intravenous Fluids	Final pH of LEVAQUIN® Solution
0.9% Sodium Chloride Injection, USP	4.71
5% Dextrose Injection, USP	4.58
5% Dextrose/0.9% NaCl Injection	4.62
5% Dextrose in Lactated Ringers	4.92
Plasma-Lyte® 56/5% Dextrose Injection	5.03
5% Dextrose, 0.45% Sodium Chloride, and 0.15% Potassium Chloride Injection	4.61
Sodium Lactate Injection (M/6)	5.54

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] .

Prepare the desired dosage of levofloxacin according to Table 5:
Table 5: Preparation of LEVAQUIN® Intravenous Solution

Desired Dosage Strength	From Appropriate Vial, Withdraw Volume	Volume of Diluent	Infusion Time
250 mg	10 mL (20 mL Vial)	40 mL	60 min
500 mg	20 mL (20 mL Vial)	80 mL	60 min
750 mg	30 mL (30 mL Vial)	120 mL	90 min

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.

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

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.

DOSAGE FORMS AND STRENGTHS
INJECTION, Single-Use Vials of concentrated solution for dilution for intravenous infusion, clear yellow to clear greenish-yellow in appearance

* 20 mL vial of 25 mg/mL levofloxacin solution, equivalent to 500 mg of levofloxacin
* 30 mL vial of 25 mg/mL levofloxacin solution, equivalent to 750 mg of levofloxacin

INJECTION (5 mg/mL in 5% Dextrose) Premix in Single-Use Flexible Containers, for intravenous infusion
* 100 mL container, fill volume 50 mL (equivalent to 250 mg levofloxacin)
* 100 mL container, fill volume 100 mL (equivalent to 500 mg levofloxacin)
* 150 mL container, fill volume 150 mL (equivalent to 750 mg levofloxacin)

Source: [package insert]