Cinobac

Capsules

250 mg orange and green, imprinted with "OCL 55" on the cap and "CINOBAC (cinoxacin) 250 mg" on the body, (UC 5355)-(40s) NDC 55515-055-02

500 mg orange and green, imprinted with "OCL 56" on the cap and "CINOBAC (cinoxacin) 500 mg" on the body, (UC 5356)-(50s) NDC 55515-056-04

Storage: Store at controlled room temperature, 59° to 86° F (15° to 30° C).

REFERENCES

1. National Committee for Clinical Laboratory Standards, Performance standards for antimicrobial disk susceptibility tests- 5th ed. Appoved Standard NCCLS Document M2-A5, Vol 13, No 24, NCCLS, Villanova, PA 1993.

2. National Committee for Clinical Laboratory Standards, Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically- 3rd ed. Approved Standard NCCLS Document M7-A3, Vol 13, No 25, NCCLS, Villanova, PA, 1993.

CAUTION: Federal (USA) law prohibits dispensing without prescription.

Cinobac (cinoxacin) is indicated for the treatment of initial and recurrent urinary tract infections in adults caused by the following susceptible microorganisms: Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species (including K.pneumoniae), and Enterobacter species.

Cinobac (cinoxacin) is effective in preventing urinary tract infections for up to 5 months in women with a history of recurrent urinary tract infections.

In vitro susceptibility testing should be performed prior to administration of the drug and, when clinically indicated, during treatment.

The usual adult dosage for the treatment of urinary tract infections is 1 g daily, administered orally in 2 or 4 divided doses (500 mg b.i.d. or 250 mg q.i.d. respectively) for 7 to 14 days. Doses should be administered at least 2 hours before or 2 hours after antacids containing magnesium or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or Videx (didanosine) chewable tablets or the pediatric powder for oral solution. Although susceptible organisms may be eradicated within a few days after therapy has begun, the full treatment course is recommended.

Impaired Renal Function: When renal function is impaired, a reduced dosage must be employed. After an initial dose of 500 mg, a maintenance dosage schedule should be used (see table).

Administration of Cinobac (cinoxacin) to anuric patients is not recommended.

When only serum creatinine is available, the following formula (based on sex, weight and age of patient) may be used to convert this value into creatinine clearance.

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

Preventive Therapy: A single dose of 250 mg at bedtime for up to 5 months has been shown to be effective in women with a history of recurrent urinary tract infections.

Cinobac (cinoxacin) is contraindicated in patients with a history of hypersensitivity to cinoxacin or other quinolones.

WARNINGS

THE SAFETY AND EFFECTIVENESS OF CINOXACIN IN PEDIATRIC PATIENTS, PREGNANT WOMEN, AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED (SEE PEDIATRIC USE, PREGNANCY, AND NURSING MOTHERS SUBSECTIONS IN THE

PRECAUTIONS

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving quinolone class antimicrobials. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching. Only a few patients had a history of previous hypersensitivity reactions. If an allergic reaction to cinoxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures, including oxygen, intravenous fluids, intravenous antihistamines, corticosteroids, pressor amines, and airway management as clinically indicated.

Convulsions and abnormal electroencephalograms have been reported in a few patients receiving quinolone class antimicrobials. No causal relationship has been established. Convulsions, increased intracranial pressure, and toxic psychoses have also been reported in patients receiving other drugs in this class.

Quinolones may also cause central nervous system (CNS) stimulation with tremors, restlessness, light-headedness, confusion, or hallucinations. If these reactions occur in patients receiving cinoxacin, the drug should be discontinued and appropriate measures instituted. As with all quinolones cinoxacin should be used with caution in patients with known or suspected CNS disorders, such as severe cerebral arteriosclerosis, epilepsy, and other factors that predispose to seizures (see ADVERSE REACTIONS).

Achilles and other tendon ruptures that require surgical repair or resulted in prolonged disability have been reported with quinolones. Cinoxacin should be discontinued if the patient experiences pain, inflammation, or tendon rupture.

PRECAUTIONS

General

Since Cinobac (cinoxacin) is eliminated primarily by the kidney, the usual dosage should be lower in patients with reduced renal function (see DOSAGE AND ADMINISTRATION). Administration of Cinobac (cinoxacin) is not recommended for anuric patients.

In clinical trials with large doses of quinolones, crystalluria was reported in some volunteers. Although crystalluria is not expected to occur with the usually recommended dosages of cinoxacin, patients should be well hydrated, and alkalinization of urine should be avoided.

Moderate to severe phototoxicity reactions have been observed in patients who were exposed to direct sunlight while receiving some members of this drug class. Excessive sunlight should be avoided. Therapy should be discontinued if phototoxicity occurs.

As with any potent drug, periodic assessment of organ system function, including renal, hepatic, and hematopoietic function, is advisable during prolonged therapy.

Information for Patients

See PATIENT INFORMATION section.

Drug Interactions

See DRUG INTERACTIONS section.

Pregnancy

Teratogenic Effects: Pregnancy Category C: Reproduction studies have been performed in rats and rabbits at doses up to 10 times the daily human dose and have revealed no evidence of impaired fertility or harm to the fetus due to cinoxacin. There are, however, no adequate and well-controlled studies in pregnant women. Cinoxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus (see

WARNINGS

Nursing Mothers

It is not known whether cinoxacin is excreted in human milk. Because other drugs in this class are excreted in human milk and because of the potential for serious adverse reactions from cinoxacin in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of cinoxacin in pediatric patients and adolescents less than 18 years of age have not been established. Cinoxacin causes arthropathy in juvenile animals (see

WARNINGS

Geriatric Use

Following a single 500 mg dose of cinoxacin, peak serum concentrations in geriatric patients were similar to those in all adults. With repeated administration of cinoxacin, no accumulation of drug was found in the twenty patients ages 70-89 (see Geriatric under Clinical Pharmacology). No dosage adjustment is required based on age alone. In geriatric patients with reduced renal function, the dosage should be reduced (see Impaired Renal Function under Dosage and Administration).

Clinical studies of cinoxacin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

SIDE EFFECTS

In clinical studies involving 1,118 patients, the following adverse effects were considered to be related to cinoxacin therapy:

Gastrointestinal: Nausea was reported most commonly and occurred in less than 3 in 100 patients. Other side effects, occurring less frequently (1 in 100), were anorexia, vomiting, abdominal cramps/pain, perverse taste, and diarrhea.

Central Nervous System: The most frequent side effects were headache and dizziness, reported by 1 in 100 patients. Other adverse reactions possibly related to Cinobac (cinoxacin) include insomnia, drowsiness, tingling sensation, perineal burning, photophobia, and tinnitus. These were reported by less than 1 in 100 patients.

Hypersensitivity: Rash, urticaria, pruritus, edema, angioedema, and eosinophilia were reported by less than 3 in 100 patients. Rare cases of anaphylactic reactions have been reported. Toxic epidermal necrolysis has been reported very rarely. Erythema multiforme and Stevens-Johnson syndrome have been reported with cinoxacin and other drugs in this class.

Hematologic: Rare reports of thrombocytopenia.

Laboratory values reported to be abnormal were, in descending order of frequency, elevation of BUN (1 in 100), AST (SGOT), ALT (SGPT), serum creatinine, and alkaline phosphatase; and reduction in hematocrit/hemoglobin (each less than 1 in 100).

Although not observed in the 1,118 patients treated with cinoxacin the following side effects have been reported for other drugs in the same pharmacologically active and chemically related class: restlessness nervousness, change in color perception, difficulty in focusing, decrease in visual acuity, double vision, weakness, constipation, erythema and bullae feelings of disorientation or agitation or acute anxiety, palpitation, soreness of the gums, joint stiffness, swelling of the extremities, and toxic psychosis or convulsions (rare). All adverse reactions observed with drugs in this class were reversible.

The most frequently reported adverse events in post marketing surveillance of cinoxacin have been rash and anaphylactic reactions. Other frequently reported reactions have been pruritus, urticaria, allergic reactions, nausea, abdominal pain, and headache.

DRUG INTERACTIONS

Elevated plasma levels of theophylline have been reported with concomitant use of some quinolones. There have been reports of theophylline-related side-effects in patients on concomitant theophylline-quinolone therapy. Therefore, monitoring of theophylline plasma levels should be considered and dosage of theophylline adjusted as required.

Quinolones have also been shown to interfere with the metabolism of caffeine. This may lead to reduced clearance of caffeine and a prolongation of its plasma half-life. Although this interaction has not been reported with cinoxacin, caution should be exercised when cinoxacin is given concomitantly with caffeine-containing products.

Antacids or sucralfate substantially interfere with the absorption of some quinolones, resulting in low urine levels. Also, concomitant administration of quinolones with products containing iron, multivitamins containing zinc, or Videx (didanosine) chewable/buffered tablets or the pediatric powder for oral solution may result in low urine levels.

Quinolones, including cinoxacin, may enhance the effects of oral anticoagulants, such as warfarin or its derivatives. When these products are administered concomitantly, prothrombin time or other suitable coagulation tests should be closely monitored.

Seizures have been reported in patients taking another quinolone class antimicrobial and the nonsteroidal anti-inflammatory drug fenbufen concurrently. Animal studies also suggest an increased potential for seizures when these 2 drugs are given concomitantly. Fenbufen is not approved in the United States at this time. Physicians are provided this information to increase awareness of the potential for serious interactions when cinoxacin and certain nonsteroidal anti-inflammatory agents are administered concomitantly.

Elevated cyclosporine serum levels have been reported with the concomitant use of quinolones and cyclosporine.

In clinical studies involving 1,118 patients, the following adverse effects were considered to be related to cinoxacin therapy:

Gastrointestinal: Nausea was reported most commonly and occurred in less than 3 in 100 patients. Other side effects, occurring less frequently (1 in 100), were anorexia, vomiting, abdominal cramps/pain, perverse taste, and diarrhea.

Central Nervous System: The most frequent side effects were headache and dizziness, reported by 1 in 100 patients. Other adverse reactions possibly related to Cinobac (cinoxacin) include insomnia, drowsiness, tingling sensation, perineal burning, photophobia, and tinnitus. These were reported by less than 1 in 100 patients.

Hypersensitivity: Rash, urticaria, pruritus, edema, angioedema, and eosinophilia were reported by less than 3 in 100 patients. Rare cases of anaphylactic reactions have been reported. Toxic epidermal necrolysis has been reported very rarely. Erythema multiforme and Stevens-Johnson syndrome have been reported with cinoxacin and other drugs in this class.

Hematologic: Rare reports of thrombocytopenia.

Laboratory values reported to be abnormal were, in descending order of frequency, elevation of BUN (1 in 100), AST (SGOT), ALT (SGPT), serum creatinine, and alkaline phosphatase; and reduction in hematocrit/hemoglobin (each less than 1 in 100).

Although not observed in the 1,118 patients treated with cinoxacin the following side effects have been reported for other drugs in the same pharmacologically active and chemically related class: restlessness nervousness, change in color perception, difficulty in focusing, decrease in visual acuity, double vision, weakness, constipation, erythema and bullae feelings of disorientation or agitation or acute anxiety, palpitation, soreness of the gums, joint stiffness, swelling of the extremities, and toxic psychosis or convulsions (rare). All adverse reactions observed with drugs in this class were reversible.

The most frequently reported adverse events in post marketing surveillance of cinoxacin have been rash and anaphylactic reactions. Other frequently reported reactions have been pruritus, urticaria, allergic reactions, nausea, abdominal pain, and headache.

Signs and Symptoms

Symptoms following an overdose of cinoxacin may include anorexia, nausea, vomiting, epigastric distress, and diarrhea. The severity of the epigastric distress and the diarrhea are dose related. Headache, dizziness, insomnia, photophobia, tinnitus, and a tingling sensation have been reported in some patients. If other symptoms are present, they are probably secondary to an underlying disease state, an allergic reaction, or the ingestion of a second medication with toxicity.

Treatment

In all cases of suspected overdosage, call your regional Poison Control Center to obtain the most up-to-date information about the treatment of overdose. This recommendation is made because, in general, information regarding the treatment of overdosage may change more rapidly than do package inserts.

In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.

Patients who have ingested an overdose of cinoxacin should be kept well hydrated to prevent crystalluria.

Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which in many cases, is more effective than emesis or lavage; consider charcoal instead of, or in addition to, gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal.

Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of cinoxacin.