CIDAFLOX® TABLETS

Levofloxacin Tablets 500 mg

DRUG DESCRIPTION

CIDAFLOX® is a synthetic broad-spectrum quinolone antibacterial agent for oral administration.

INDICATIONS

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

CIDAFLOX® Tablets are indicated for the treatment of adults ( ≥ 18 years of age) with mild, moderate, and severe infections caused by susceptible isolates of the designated microorganisms in the conditions listed:

  • Nosocomial Pneumonia

  • Community-Acquired Pneumonia

  • Acute Bacterial Sinusitis

  • Acute Bacterial Exacerbation of Chronic Bronchitis (AECB)

  • Complicated Skin and Skin Structure Infections

  • Uncomplicated Skin and Skin Structure Infections

  • Chronic Bacterial Prostatitis

  • Complicated Urinary Tract Infections: 5-day Treatment Regimen

  • Complicated Urinary Tract Infections: 10-day Treatment Regimen

  • Acute Pyelonephritis: 5 or 10-day Treatment Regimen

  • Uncomplicated Urinary Tract Infections

  • Inhalational Anthrax (Post-Exposure)

  • Plague

DOSAGE AND ADMINISTRATION:

Dosage in Adult Patients with Normal Renal Function

The usual dose of CIDAFLOX® Tablets is 250 mg, 500 mg, or 750 mg administered orally every 24 hours.

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.

Drug Interaction With Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins

CIDAFLOX® Tablets 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 didanosine chewable/buffered tablets or the pediatric powder for oral solution.

Administration Instructions

Food and CIDAFLOX® Tablets

CIDAFLOX® Tablets can be administered without regard to food

Hydration for Patients Receiving CIDAFLOX® Tablets

Adequate hydration of patients receiving CIDAFLOX® Tablets should be maintained to prevent the formation of highly concentrated urine. Crystalluria and cylindruria have been reported with quinolones.

 

CLINICAL PHARMACOLOGY

Mechanism of Action

Levofloxacin is a member of the fluoroquinolone class of antibacterial agents.

Regimen

Cmax (mcg/mL)

Tmax (h)

AUC (mcg·h/mL)

CL/F1 (mL/min)

Vd/F2 (L)

t½ (h)

CLR (mL/min)

Single dose

250 mg oral tablet3

2.8 ± 0.4

1.6 ± 1.0

27.2 ± 3.9

156 ± 20

ND

7.3 ± 0.9

142 ± 21

500 mg oral tablet3*

5.1 ± 0.8

1.3 ± 0.6

47.9 ± 6.8

178 ± 28

ND

6.3 ± 0.6

103 ± 30

500 mg oral solution12

5.8 ± 1.8

0.8 ± 0.7

47.8 ± 10.8

183 ± 40

112 ± 37.2

7.0 ± 1.4

ND

500 mg IV3

6.2 ± 1.0

1.0 ± 0.1

48.3 ± 5.4

175 ± 20

90 ± 11

6.4 ± 0.7

112 ± 25

750 mg oral tablet5*

9.3 ± 1.6

1.6 ± 0.8

101 ± 20

129 ± 24

83 ± 17

7.5 ± 0.9

ND

750 mg IV5

11.5 ± 4.04

ND

110 ± 40

126 ± 39

75 ± 13

7.5 ± 1.6

ND

Multiple dose

500 mg every 24h oral tablet3

5.7 ± 1.4

1.1 ± 0.4

47.5 ± 6.7

175 ± 25

102 ± 22

7.6 ± 1.6

116 ± 31

500 mg every 24h IV3

6.4 ± 0.8

ND

54.6 ± 11.1

158 ± 29

91 ± 12

7.0 ± 0.8

99 ± 28

500 mg or 250 mg every 24h IV, patients with bacterial infection6

8.7± 4.07

ND

72.5 ± 51.27

154 ± 72

111 ± 58

ND

ND

750 mg every 24h oral tablet5

8.6 ± 1.9

1.4 ± 0.5

90.7 ± 17.6

143 ± 29

100 ± 16

8.8 ± 1.5

116 ± 28

750 mg every 24h IV5

12.1 ± 4.14

ND

108 ± 34

126 ± 37

80 ± 27

7.9 ± 1.9

ND

500 mg oral tablet single dose, effects of gender and age:

Male8

5.5 ± 1.1

1.2 ± 0.4

54.4 ± 18.9

166 ± 44

89 ± 13

7.5 ± 2.1

126 ± 38

Female9

7.0 ± 1.6

1.7 ± 0.5

67.7 ± 24.2

136 ± 44

62 ± 16

6.1 ± 0.8

106 ± 40

Young10

5.5 ± 1.0

1.5 ± 0.6

47.5 ± 9.8

182 ± 35

83 ± 18

6.0 ± 0.9

140 ± 33

Elderly11

7.0 ± 1.6

1.4 ± 0.5

74.7 ± 23.3

121 ± 33

67 ± 19

7.6 ± 2.0

91 ± 29

500 mg oral single dose tablet, patients with renal insufficiency:

CLCR 50–80 mL/min

7.5 ± 1.8

1.5 ± 0.5

95.6 ± 11.8

88 ± 10

ND

9.1 ± 0.9

57 ± 8

CLCR 20–49 mL/min

7.1 ± 3.1

2.1 ± 1.3

182.1 ± 62.6

51 ± 19

ND

27 ± 10

26 ± 13

CLCR <20 mL/min

8.2 ± 2.6

1.1 ± 1.0

263.5 ± 72.5

33 ± 8

ND

35 ± 5

13 ± 3

Hemodialysis

5.7 ± 1.0

2.8 ± 2.2

ND

ND

ND

76 ± 42

ND

CAPD

6.9 ± 2.3

1.4 ± 1.1

ND

ND

ND

51 ± 24

ND

1clearance/bioavailability

2volume of distribution/bioavailability

3healthy males 18–53 years of age

460 min infusion for 250 mg and 500 mg doses, 90 min infusion for 750 mg dose

5healthy male and female subjects 18–54 years of age

6500 mg every 48h for patients with moderate renal impairment (CLCR 20–50 mL/min) and infections of the respiratory tract or skin

7dose-normalized values (to 500 mg dose), estimated by population pharmacokinetic modeling

8healthy males 22–75 years of age

9healthy females 18–80 years of age

10young healthy male and female subjects 18–36 years of age

11healthy elderly male and female subjects 66–80 years of age

12healthy males and females 19–55 years of age.

* Absolute bioavailability; F=0.99 ± 0.08 from a 500 mg tablet and F=0.99 ± 0.06 from a 750 mg tablet; ND=not determined.

Absorption

Levofloxacin is rapidly and essentially completely absorbed after oral administration. Peak plasma concentrations are usually attained one to two hours after oral dosing. The absolute bioavailability of levofloxacin from a 500 mg tablet is approximately 99%, demonstrating complete oral absorption of levofloxacin.

Oral administration of a 500 mg dose of CIDAFLOX® with food prolongs the time to peak concentration by approximately 1 hour and decreases the peak concentration by approximately 14% following administration. Therefore, CIDAFLOX® Tablets can be administered without regard to food.

Microbiology

Mechanism of Action

Levofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone antimicrobial agent. The antibacterial activity of ofloxacin resides primarily in the L-isomer. The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination.

CONTRAINDICATIONS:

Levofloxacin is contraindicated in persons with a history of hypersensitivity to Levofloxacin, quinolone antimicrobial agents, or any other components of this product.

ADVERSE EFFECTS:

The most frequently reported side events are nausea or vomiting (1 out of every 12 persons), diarrhea (1 out 20), headache (1 out 20), and constipation (1 out of 30). Less common side effects include difficulty in sleeping, dizziness, abdominal pain, rash, abdominal gas, and itching.

 

DRUG INTERACTION:

While the chelation by divalent cations is less marked than with other quinolones, concurrent administration of Levofloxacin Tablets with antacids containing magnesium, or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc may interfere with the gastrointestinal absorption of levofloxacin, resulting in systemic levels considerably lower than desired.

OVERDOSAGE:

Levofloxacin exhibits a low potential for acute toxicity. Mice, rats, dogs and monkeys exhibited the following clinical signs after receiving a single high dose of Levofloxacin: ataxia, ptosis, decreased locomotor activity, dyspnea, prostration, tremors, and convulsions. Doses in excess of 1500 mg/kg orally and 250 mg/kg I. V. produced significant mortality in rodents. In the event of an acute overdosage, the stomach should be emptied. The patient should be observed and appropriate hydration maintained.

STORAGE:

Store at a temperature not exceeding 30°C. Protect from light.

Keep medicine out of reach of children.

PRESENTATION:

Alu Alu blister of 10 tablets.

CIDAFLOX® is a registered trademark of FilGap Healthcare Limited