CIPROFLOXACIN TABLETS USP, Rx only

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Prescription Drug Name:

ID:

6150bd37-2019-48fa-8dde-5b361f61cedc

Code:

34391-3

DESCRIPTION

id: 3ee568dc-041d-463e-8c65-57032783517c
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Ciprofloxacin hydrochloride USP is a synthetic broad-spectrum antimicrobial agent for oral administration. Ciprofloxacin hydrochloride USP, a fluoroquinolone, is the monohydrochloride monohydrate salt of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. It is a faintly yellowish to light yellow crystalline substance that has the following chemical structure: C₁₇H₁₈FN₃O₃•HCl•H₂O M.W. 385.8 Each Ciprofloxacin Tablet USP, for oral administration, is available in 250 mg, 500 mg or 750 mg strengths. In addition, each tablet also contains the following inactive ingredients: colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, pregelatinized starch, sodium starch glycolate, talc, titanium dioxide and triacetin.

INDICATIONS AND USAGE

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displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Ciprofloxacin Tablets USP are indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions and patient populations listed below. Please see DOSAGE AND ADMINISTRATION for specific recommendations.

CONTRAINDICATIONS

id: 6ee064de-2e52-4b07-9ef1-2a2137fc6200
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Ciprofloxacin hydrochloride is contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components. Concomitant administration with tizanidine is contraindicated (see PRECAUTIONS, Drug
Interactions).

OVERDOSAGE

id: 69228052-dd77-44b9-bd61-e8c0d8a716f8
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

In the event of acute overdosage, reversible renal toxicity has been reported in some cases. The stomach should be emptied by inducing vomiting or by gastric lavage. The patient should be carefully observed and given supportive treatment, including monitoring of renal function and administration of magnesium, aluminum, or calcium containing antacids which can reduce the absorption of ciprofloxacin. Adequate hydration must be maintained. Only a small amount of ciprofloxacin (< 10%) is removed from the body after hemodialysis or peritoneal dialysis. Single doses of ciprofloxacin were relatively non-toxic via the oral route of administration in mice, rats, and dogs. No deaths occurred within a 14-day post treatment observation period at the highest oral doses tested; up to 5000 mg/kg in either rodent species, or up to 2500 mg/kg in the dog. Clinical signs observed included hypoactivity and cyanosis in both rodent species and severe vomiting in dogs. In rabbits, significant mortality was seen at doses of ciprofloxacin > 2500 mg/kg. Mortality was delayed in these animals, occurring 10 to 14 days after dosing. In mice, rats, rabbits and dogs, significant toxicity including tonic/clonic convulsions was observed at intravenous doses of ciprofloxacin between 125 and 300 mg/kg.

DOSAGE AND ADMINISTRATION -ADULTS

id: 25366db9-2ce0-4b81-bfb4-954f610ed89f
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Ciprofloxacin tablets should be administered orally to adults as described in the Dosage Guidelines table. The determination of dosage for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative organism, the integrity of the patient’s host-defense mechanisms, and the status of renal function and hepatic function. The duration of treatment depends upon the severity of infection. The usual duration is 7 to 14 days; however, for severe and complicated infections more prolonged therapy may be required. Ciprofloxacin should be administered at least 2 hours before or 6 hours after magnesium/aluminum antacids, or sucralfate, Videx^® (didanosine) chewable/buffered tablets or pediatric powder for oral solution, other highly buffered drugs, or other products containing calcium, iron or zinc.

ADULT DOSAGE GUIDELINES
^used in conjunction with metronidazole ^†Generally ciprofloxacin should be continued for at least 2 days after the signs and symptoms of infection have disappeared, except for inhalational anthrax (post-exposure). ^*Drug administration should begin as soon as possible after suspected or confirmed exposure. This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit.⁵ For a discussion of ciprofloxacin serum concentrations in various human populations, see INHALATIONAL ANTHRAX – ADDITIONAL INFORMATION.
Infection	Severity	Dose	Frequency	Usual Durations ^†
Urinary Tract	Acute Uncomplicated	250 mg	q 12 h	3 days
	Mild/Moderate	250 mg	q 12 h	7 to 14 days
	Severe/Complicated	500 mg	q 12 h	7 to 14 days
Chronic Bacterial Prostatitis	Mild/Moderate	500 mg	q 12 h	28 days
Lower Respiratory Tract	Mild/Moderate	500 mg	q 12 h	7 to 14 days
Lower Respiratory Tract	Severe/Complicated	750 mg	q 12 h	7 to 14 days
Acute Sinusitis	Mild/Moderate	500 mg	q 12 h	10 days
Skin and Skin Structure	Mild/Moderate	500 mg	q 12 h	7 to 14 days
Skin and Skin Structure	Severe/Complicated	750 mg	q 12 h	7 to 14 days
Bone and Joint	Mild/Moderate	500 mg	q 12 h	≥ 4 to 6 weeks
Bone and Joint	Severe/Complicated	750 mg	q 12 h	≥ 4 to 6 weeks
Intra-Abdominal^*	Complicated	500 mg	q 12 h	7 to 14 days
Infectious Diarrhea	Mild/Moderate/Severe	500 mg	q 12 h	5 to 7 days
Typhoid Fever	Mild/Moderate	500 mg	q 12 h	10 days
Urethral and Cervical Gonococcal Infections	Uncomplicated	250 mg	single dose	single dose
Inhalational anthrax (post-exposure)^**		500 mg	q 12 h	60 days

DOSAGE AND ADMINISTRATION – PEDIATRICS

id: b8f41596-4301-445f-8c3c-c9a566ea4e56
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Ciprofloxacin tablets should be administered orally as described in the Dosage Guidelines table. An increased incidence of adverse events compared to controls, including events related to joints and/or surrounding tissues, has been observed (see ADVERSE REACTIONS and CLINICAL STUDIES). Dosing and initial route of therapy (i.e., I.V. or oral) for complicated urinary tract infection or pyelonephritis should be determined by the severity of the infection. In the clinical trial, pediatric patients with moderate to severe infection were initiated on 6 to 10 mg/kg I.V. every 8 hours and allowed to switch to oral therapy (10 to 20 mg/kg every 12 hours), at the discretion of the physician.

PEDIATRIC DOSAGE GUIDELINES
Infection	Route of Administration	Dose (mg/kg)	Frequency	Total Duration
Complicated Urinary Tract or Pyelonephritis (patients from 1 to 17 years of age)	Intravenous	6 to 10 mg/kg (maximum 400 mg per dose; not to be exceeded even in patients weighing > 51 kg)	Every 8 hours	10 to 21 days^*
	Oral	10 mg/kg to 20 mg/kg (maximum 750 mg per dose; not to be exceeded even in patients weighing > 51 kg)	Every 12 hours	10 to 21 days^*
Inhalational Anthrax (Post- Exposure)^**	Intravenous	10 mg/kg (maximum 400 mg per dose)	Every 12 hours	60 days
Inhalational Anthrax (Post- Exposure)^**	Oral	15 mg/kg (maximum 500 mg per dose)	Every 12 hours	60 days

* The total duration of therapy for complicated urinary tract infection and pyelonephritis in the clinical trial was determined by the physician. The mean duration of treatment was 11 days (range 10 to 21 days). ** Drug administration should begin as soon as possible after suspected or confirmed exposure to Bacillus anthracis spores. This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit.⁵ For a discussion of ciprofloxacin serum concentrations in various human populations, see INHALATIONAL ANTHRAX – ADDITIONAL INFORMATION. Pediatric patients with moderate to severe renal insufficiency were excluded from the clinical trial of complicated urinary tract infection and pyelonephritis. No information is available on dosing adjustments necessary for pediatric patients with moderate to severe renal insufficiency (i.e., creatinine clearance of < 50 mL/min/1.73m²).

HOW SUPPLIED

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displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Ciprofloxacin Tablets USP, 250 mg are available as white to off white, oval, biconvex, unscored, film-coated tablets, debossed “TEVA” on one side and “5311” on the other side containing ciprofloxacin hydrochloride USP equivalent to 250 mg ciprofloxacin, packaged in bottles of 100 tablets and unit-dose boxes of 100 tablets. Ciprofloxacin Tablets USP, 500 mg are available as white to off white, oval, biconvex, unscored, film-coated tablets, debossed “TEVA” on one side and “5312” on the other side containing ciprofloxacin hydrochloride USP equivalent to 500 mg ciprofloxacin, packaged in bottles of 100 and 500 tablets and unit-dose boxes of 100 tablets. Ciprofloxacin Tablets USP, 750 mg are available as white to off white, oval, biconvex, unscored, film-coated tablets, debossed “TEVA” on one side and “5313” on the other side containing ciprofloxacin hydrochloride USP equivalent to 750 mg ciprofloxacin, packaged in bottles of 100 tablets and unit-dose boxes of 100 tablets. Dispense in a well-closed container as defined in the USP, with a child-resistant closure (as required). Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN

ANIMAL PHARMACOLOGY

id: 1bf4a5ea-5dff-47fd-809d-4fda5939042d
displayName: ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION
FDA Article Code: 34091-9

Ciprofloxacin and other quinolones have been shown to cause arthropathy in immature animals of most species tested (see WARNINGS). Damage of weight bearing joints was observed in juvenile dogs and rats. In young beagles, 100 mg/kg ciprofloxacin, given daily for 4 weeks, caused degenerative articular changes of the knee joint. At 30 mg/kg, the effect on the joint was minimal. In a subsequent study in young beagle dogs, oral ciprofloxacin doses of 30 mg/kg and 90 mg/kg ciprofloxacin (approximately 1.3 and 3.5 times the pediatric dose based upon comparative plasma AUCs) given daily for 2 weeks caused articular changes which were still observed by histopathology after a treatment-free period of 5 months. At 10 mg/kg (approximately 0.6-times the pediatric dose based upon comparative plasma AUCs), no effects on joints were observed. This dose was also not associated with arthrotoxicity after an additional treatment-free period of 5 months. In another study, removal of weight bearing from the joint reduced the lesions but did not totally prevent them. Crystalluria, sometimes associated with secondary nephropathy, occurs in laboratory animals dosed with ciprofloxacin. This is primarily related to the reduced solubility of ciprofloxacin under alkaline conditions, which predominate in the urine of test animals; in man, crystalluria is rare since human urine is typically acidic. In rhesus monkeys, crystalluria without nephropathy was noted after single oral doses as low as 5 mg/kg (approximately 0.07 times the highest recommended therapeutic dose based upon mg/m²). After 6 months of intravenous dosing at 10 mg/kg/day, no nephropathological changes were noted; however, nephropathy was observed after dosing at 20 mg/kg/day for the same duration (approximately 0.2 times the highest recommended therapeutic dose based upon mg/m²). In dogs, ciprofloxacin at 3 and 10 mg/kg by rapid IV injection (15 sec.) produces pronounced hypotensive effects. These effects are considered to be related to histamine release, since they are partially antagonized by pyrilamine, an antihistamine. In rhesus monkeys, rapid IV injection also produces hypotension but the effect in this species is inconsistent and less pronounced. In mice, concomitant administration of non-steroidal anti-inflammatory drugs such as phenylbutazone and indomethacin with quinolones has been reported to enhance the CNS stimulatory effect of quinolones. Ocular toxicity seen with some related drugs has not been observed in ciprofloxacin-treated animals.

INHALATIONAL ANTHRAX IN ADULTS AND PEDIATRICS – ADDITIONAL INFORMATION

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displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5

The mean serum concentrations of ciprofloxacin associated with a statistically significant improvement in survival in the rhesus monkey model of inhalational anthrax are reached or exceeded in adult and pediatric patients receiving oral and intravenous regimens (see DOSAGE AND ADMINISTRATION). Ciprofloxacin pharmacokinetics have been evaluated in various human populations. The mean peak serum concentration achieved at steady-state in human adults receiving 500 mg orally every 12 hours is 2.97 mcg/mL, and 4.56 mcg/mL following 400 mg intravenously every 12 hours. The mean trough serum concentration at steady state for both of these regimens is 0.2 mcg/mL. In a study of 10 pediatric patients between 6 and 16 years of age, the mean peak plasma concentration achieved is 8.3 mcg/mL and trough concentrations range from 0.09 to 0.26 mcg/mL, following two 30-minute intravenous infusions of 10 mg/kg administered 12 hours apart. After the second intravenous infusion patients switched to 15 mg/kg orally every 12 hours achieve a mean peak concentration of 3.6 mcg/mL after the initial oral dose. Long-term safety data, including effects on cartilage, following the administration of ciprofloxacin to pediatric patients are limited. (For additional information, see PRECAUTIONS, Pediatric Use.) Ciprofloxacin serum concentrations achieved in humans serve as a surrogate endpoint reasonably likely to predict clinical benefit and provide the basis for this indication⁵. A placebo-controlled animal study in rhesus monkeys exposed to an inhaled mean dose of 11 LD₅
₀ (~5.5 × 10⁵ spores (range 5 to 30 LD₅
₀) of B. anthracis was conducted. The minimal inhibitory concentration (MIC) of ciprofloxacin for the anthrax strain used in this study was 0.08 mcg/mL. In the animals studied, mean serum concentrations of ciprofloxacin achieved at expected T_max (1 hour post-dose) following oral dosing to steady state ranged from 0.98 to 1.69 mcg/mL. Mean steady state trough concentrations at 12 hours post-dose ranged from 0.12 to 0.19 mcg/mL⁶. Mortality due to anthrax for animals that received a 30 day regimen of oral ciprofloxacin beginning 24 hours post-exposure was significantly lower (1/9), compared to the placebo group (9/10) [p = 0.001]. The one ciprofloxacin-treated animal that died of anthrax did so following the 30 day drug administration period⁷. More than 9300 persons were recommended to complete a minimum of 60 days of antibiotic prophylaxis against possible inhalation exposure to B. anthracis during 2001. Ciprofloxacin was recommended to most of those individuals for all or part of the prophylaxis regimen. Some persons were also given anthrax vaccine or were switched to alternative antibiotics. No one who received ciprofloxacin or other therapies as prophylactic treatment subsequently developed inhalational anthrax. The number of persons who received ciprofloxacin as all or part of their post-exposure prophylaxis regimen is unknown. Among the persons surveyed by the Centers for Disease Control and Prevention, over 1000 reported receiving ciprofloxacin as sole post-exposure prophylaxis for inhalational anthrax. Gastrointestinal adverse events (nausea, vomiting, diarrhea, or stomach pain), neurological adverse events (problems sleeping, nightmares, headache, dizziness or lightheadedness) and musculoskeletal adverse events (muscle or tendon pain and joint swelling or pain) were more frequent than had been previously reported in controlled clinical trials. This higher incidence, in the absence of a control group, could be explained by a reporting bias, concurrent medical conditions, other concomitant medications, emotional stress or other confounding factors, and/or a longer treatment period with ciprofloxacin. Because of these factors and limitations in the data collection, it is difficult to evaluate whether the reported symptoms were drug-related.

REFERENCES

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displayName: REFERENCES SECTION
FDA Article Code: 34093-5

1. National Committee for Clinical Laboratory Standards, Methods for Dilution Antimicrobial
Susceptibility Tests for Bacteria That Grow Aerobically – Fifth Edition. Approved Standard NCCLS Document M7-A5, Vol. 20, No. 2, NCCLS, Wayne, PA, January, 2000. 2. Clinical and Laboratory Standards Institute, Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria; Approved Guideline., CLSI Document M45-A, Vol. 26, No. 19, CLSI, Wayne, PA, 2006. 3. National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disk Susceptibility Tests – Seventh Edition. Approved Standard NCCLS Document M2-A7, Vol. 20, No. 1, NCCLS, Wayne, PA, January, 2000. 4. Report presented at the FDA’s Anti-Infective Drug and Dermatological Drug Product’s Advisory Committee meeting, March 31, 1993, Silver Spring, MD. Report available from FDA, CDER, Advisors and Consultants Staff, HFD-21, 1901 Chapman Avenue, Room 200, Rockville, MD 20852, USA. 5. 21 CFR 314.510 (Subpart H – Accelerated Approval of New Drugs for Life-Threatening Illnesses). 6. Kelly DJ, et al. Serum concentrations of penicillin, doxycycline, and ciprofloxacin during prolonged therapy in rhesus monkeys. J Infect Dis 1992; 166: 1184-7. 7. Friedlander AM, et al. Postexposure prophylaxis against experimental inhalational anthrax. J Infect Dis 1993; 167: 1239-42. 8. Friedman J, Polifka J. Teratogenic effects of drugs: a resource for clinicians (TERIS). Baltimore, Maryland: Johns Hopkins University Press, 2000: 149-195. 9. Loebstein R, Addis A, Ho E, et al. Pregnancy outcome following gestational exposure to fluoroquinolones: a multicenter prospective controlled study. Antimicrob Agents Chemother. 1998; 42(6): 1336-1339. 10. Schaefer C, Amoura-Elefant E, Vial T, et al. Pregnancy outcome after prenatal quinolone exposure. Evaluation of a case registry of the European network of teratology information services (ENTIS). Eur J Obstet Gynecol Reprod Biol. 1996;69:83-89. Manufactured In Croatia By: PLIVA HRVATSKA d.o.o. Zagreb, Croatia Manufactured For: TEVA PHARMACEUTICALS USA Sellersville, PA 18960 Rev. D 3/2011 All trademarks are the property of their respective owners.