CIPROKANT-500 (Ciprofloxacin)

CIPRO® (ciprofloxacin hydrochloride)

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CIPRO® (ciprofloxacin hydrochloride)

CIPRO (ciprofloxacin hydrochloride) Tablets and CIPRO (ciprofloxacin) Oral Suspension are synthetic antimicrobial agents 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 with a molecular weight of 385.8. Its empirical formula is C17H18FN3O3•HCl•H2O

Ciprofloxacin is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. Its empirical formula is C17H18FN3O3 and its molecular weight is 331.4. It is a faintly yellowish to light yellow crystalline substance

Indications and usage

CIPRO is a fluoroquinolone antibacterial indicated in adults (18 years of age and older) with the following infections caused by designated, susceptible bacteria and in pediatric patients where indicated:

  • Skin and Skin Structure Infections
  • Bone and Joint Infections
  • Complicated Intra-Abdominal Infections
  • Infectious Diarrhea
  • Typhoid Fever (Enteric Fever)
  • Uncomplicated Cervical and Urethral Gonorrhea
  • Inhalational Anthrax post-exposure in adult and pediatric patients
  • Plague in adult and pediatric patients
  • Chronic Bacterial Prostatitis

Lower Respiratory Tract Infections

  • Acute Exacerbation of Chronic Bronchitis

Urinary Tract Infections

  • Urinary Tract Infections (UTI)
  • Acute Uncomplicated Cystitis
  • Complicated UTI and Pyelonephritis in Pediatric Patients
  • Acute Sinusitis

To reduce the development of drug-resistant bacteria and maintain the effectiveness of CIPRO and other antibacterial drugs, CIPRO should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Mechanism of Action

The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination.

Mechanism of Resistance

The mechanism of action of fluoroquinolones, including ciprofloxacin, is different from that of penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines; therefore, microorganisms resistant to these classes of drugs may be susceptible to ciprofloxacin. Resistance to fluoroquinolones occurs primarily by either mutations in the DNA gyrases, decreased outer membrane permeability, or drug efflux. In vitro resistance to ciprofloxacin develops slowly by multiple step mutations. Resistance to ciprofloxacin due to spontaneous mutations occurs at a general frequency of between < 10-9 to 1×10-6 .

Dosage and administration

Dosage in Adults: The determination of dosage and duration for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative microorganism, the integrity of the patient’s host-defense mechanisms, and the status of renal and hepatic function. CIPRO Tablets or Oral Suspension may be administered to adult patients when clinically indicated at the discretion of the physician. Administer CIPRO for Oral Suspension using the co-packaged graduated spoon

InfectionDoseFrequencyUsual Durations1
Skin and Skin Structure500–750 mgevery 12 hours7 to 14 days
Bone and Joint500–750 mgevery 12 hours4 to 8 weeks
Complicated Intra–Abdominal2500 mgevery 12 hours7 to 14 days
Infectious Diarrhea500 mgevery 12 hours5 to 7 days
Typhoid Fever500 mgevery 12 hours10 days
Uncomplicated Urethral and Cervical Gonococcal Infections250 mgsingle dosesingle dose
Inhalational anthrax (post exposure)3500 mgevery 12 hours60 days
Plague3500–750 mgevery 12 hours14 days
Chronic Bacterial Prostatitis500 mgevery 12 hours28 days
Lower Respiratory Tract Infections500–750 mgevery 12 hours7 to 14 days
Urinary Tract Infections250–500 mgevery 12 hours7 to 14 days
Acute Uncomplicated Cystitis250 mgevery 12 hours3 days
Acute Sinusitis500 mgevery 12 hours10 days
  1. 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).
  2. Used in conjunction with metronidazole.
  3. Begin drug administration as soon as possible after suspected or confirmed exposure.

Dosage in Pediatric Patients

Dosing and initial route of therapy (that is, IV or oral) for cUTI or pyelonephritis should be determined by the severity of the infection. CIPRO should be administered as described in Table 3. Administer CIPRO for Oral Suspension using the co-packaged graduated spoon

InfectionDoseFrequencyUsual Durations1
Complicated Urinary Tract or Pyelonephritis (patients from 1 to 17 years of age)10 mg/kg to 20 mg/kg (maximum 750 mg per dose; not to be exceeded even in patients weighing more than 51 kg).every 12 hours10–21 days1
Inhalational Anthrax (Post Exposure)215 mg/kg (maximum 500 mg per dose)every 12 hours60 days
Plague2,315 mg/kg (maximum 500 mg per dose)Every 8 to 12 hours14 days
  1. The total duration of therapy for cUTI and pyelonephritis in the clinical trial was determined by the physician. The mean duration of treatment was 11 days (range 10 to 21 days).
  2. Begin drug administration as soon as possible after suspected or confirmed exposure.
  3. Begin drug administration as soon as possible after suspected or confirmed exposure to Y. pestis.

Contraindications

  • Known hypersensitivity to CIPRO or other quinolones
  • Concomitant administration with tizanidine

Warnings and precautions

Hypersensitivity and other serious reactions: Serious and sometimes fatal reactions (for example, anaphylactic reactions) may occur after the first or subsequent doses of CIPRO. Discontinue CIPRO at the first sign of skin rash, jaundice or any sign of hypersensitivity.

Hepatotoxicity: Discontinue immediately if signs and symptoms of hepatitis occur.

Clostridioides difficile-associated diarrhea: Evaluate if colitis occurs.

QT Prolongation: Prolongation of the QT interval and isolated cases of torsade de pointes have been reported. Avoid use in patients with known prolongation, those with hypokalemia, and with other drugs that prolong the QT interval.

Fluoroquinolones, including CIPRO®, have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together, including:

  • Tendinitis and tendon rupture
  • Peripheral neuropathy
  • Central nervous system effects

Discontinue CIPRO immediately and avoid the use of fluoroquinolones, including CIPRO, in patients who experience any of these serious adverse reactions

Fluoroquinolones, including CIPRO, may exacerbate muscle weakness in patients with myasthenia gravis. Avoid CIPRO in patients with known history of myasthenia gravis

Because fluoroquinolones, including CIPRO, have been associated with serious adverse reactions, reserve CIPRO for use in patients who have no alternative treatment options for the following indications:

  • Acute exacerbation of chronic bronchitis
  • Acute uncomplicated cystitis
  • Acute sinusitis

Adverse reactions

The most common adverse reactions ≥1% were nausea, diarrhea, liver function tests abnormal, vomiting, and rash.

Drug interactions

  • Tizanidine: Concomitant administration of tizanidine and CIPRO is contraindicated due to the potentiation of hypotensive and sedative effects of tizanidine
  • Theophylline: Concurrent administration of CIPRO with theophylline may result in increased risk of a patient developing central nervous system (CNS) or other adverse reactions. If concomitant use cannot be avoided, monitor serum levels of theophylline and adjust dosage as appropriate
  • Drugs Known to Prolong QT Interval: CIPRO may further prolong the QT interval in patients receiving drugs known to prolong the QT interval (for example, class IA or III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics)
  • Oral antidiabetic drugs: Hypoglycemia sometimes severe has been reported when CIPRO and oral antidiabetic agents, mainly sulfonylureas (for example, glyburide, glimepiride), were co-administered, presumably by intensifying the action of the oral antidiabetic agent. Fatalities have been reported. Monitor blood glucose when CIPRO is co-administered with oral antidiabetic drugs
  • Phenytoin: To avoid the loss of seizure control associated with decreased phenytoin levels and to prevent phenytoin overdose-related adverse reactions upon CIPRO discontinuation in patients receiving both agents, monitor phenytoin therapy, including phenytoin serum concentration during and shortly after coadministration of CIPRO with phenytoin.
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  • Cyclosporine: Monitor renal function (in particular serum creatinine) when CIPRO is co-administered with cyclosporine.
  • Anti-coagulant drugs: The risk may vary with the underlying infection, age and general status of the patient so that the contribution of CIPRO to the increase in INR (international normalized ratio) is difficult to assess. Monitor prothrombin time and INR frequently during and shortly after co-administration of CIPRO with an oral anti-coagulant (for example, warfarin).
  • Methotrexate: Potential increase in the risk of methotrexate associated toxic reactions. Therefore, carefully monitor patients under methotrexate therapy when concomitant CIPRO therapy is indicated.
  • Ropinirole: Monitoring for ropinirole-related adverse reactions and appropriate dose adjustment of ropinirole is recommended during and shortly after coadministration with CIPRO
  • Clozapine: Careful monitoring of clozapine associated adverse reactions and appropriate adjustment of clozapine dosage during and shortly after co-administration with CIPRO are advised.
  • NSAIDs: Non-steroidal anti-inflammatory drugs (but not acetyl salicylic acid) in combination of very high doses of quinolones have been shown to provoke convulsions in pre-clinical studies and in postmarketing.
  • Sildenafil: Two-fold increase in exposure Monitor for sildenafil toxicity
  • Duloxetine: If unavoidable, monitor for duloxetine toxicity
  • Caffeine/Xanthine Derivatives: CIPRO inhibits the formation of paraxanthine after caffeine administration (or pentoxifylline containing products). Monitor for xanthine toxicity and adjust dose as necessary.
  • Zolpidem: Co-administration with ciprofloxacin may increase blood levels of zolpidem, concurrent use is not recommended
  • Multivalent cationcontaining products including antacids, metal cations or didanosine: Decreased CIPRO absorption. Take CIPRO 2 hours before or 6 hours after administration of multivalent cation containing drugs

Use in specific populations

Pregnancy: Prolonged experience with ciprofloxacin in pregnant women over several decades, based on available published information from case reports, case control studies and observational studies on ciprofloxacin administered during pregnancy, have not identified any drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

Lactation: Published literature reports that ciprofloxacin is present in human milk following intravenous and oral administration. There is no information regarding effects of CIPRO on milk production or the breastfed infant. Because of the potential risk of serious adverse reactions in breastfed infants, including arthropathy shown in juvenile animal studies, for most indications a lactating woman may consider pumping and discarding breast milk during treatment with CIPRO and an additional two days (five half-lives) after the last dose. Alternatively, advise a woman that breastfeeding is not recommended during treatment with CIPRO and for an additional two days (five half-lives) after the last dose.

Ciprofloxacin may cause intestinal flora alteration of the breastfeeding infant. Advise a woman to monitor the breastfed infant for loose or bloody stools and candidiasis (thrush, diaper rash).

Pediatric Use: Although effective in clinical trials, CIPRO is not a drug of first choice in the pediatric population due to an increased incidence of adverse reactions compared to controls. Quinolones, including CIPRO, cause arthropathy (arthralgia, arthritis), in juvenile animals

CIPRO is indicated for the treatment of cUTI and pyelonephritis due to Escherichia coli in pediatric patients 1 to 17 years of age. Although effective in clinical trials, CIPRO is not a drug of first choice in the pediatric population due to an increased incidence of adverse reactions compared to the controls, including events related to joints and/or surrounding tissues.

CIPRO is indicated in pediatric patients from birth to 17 years of age, for inhalational anthrax (post-exposure). The riskbenefit assessment indicates that administration of ciprofloxacin to pediatric patients is appropriate.

CIPRO is indicated in pediatric patients from birth to 17 years of age, for treatment of plague, including pneumonic and septicemic plague due to Yersinia pestis (Y. pestis) and prophylaxis for plague. Efficacy studies of CIPRO could not be conducted in humans with pneumonic plague for feasibility reasons. Therefore, approval of this indication was based on an efficacy study conducted in animals. The risk-benefit assessment indicates that administration of CIPRO to pediatric patients is appropriate.

Geriatric Use: Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as CIPRO. This risk is further increased in patients receiving concomitant corticosteroid therapy. Tendinitis or tendon rupture can involve the Achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported. Caution should be used when prescribing CIPRO to elderly patients especially those on corticosteroids. Patients should be informed of this potential adverse reaction and advised to discontinue CIPRO and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur.

Renal Impairment: Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and partially cleared through the biliary system of the liver and through the intestine. These alternative pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. Nonetheless, some modification of dosage is recommended, particularly for patients with severe renal dysfunction

Hepatic Impairment: In preliminary studies in patients with stable chronic liver cirrhosis, no significant changes in ciprofloxacin pharmacokinetics have been observed. The pharmacokinetics of ciprofloxacin in patients with acute hepatic insufficiency, have not been studied.

Overdosage

In the event of acute overdosage, reversible renal toxicity has been reported in some cases. Empty the stomach by inducing vomiting or by gastric lavage. Observe the patient carefully and give supportive treatment, including monitoring of renal function, urinary pH and acidify, if required, to prevent crystalluria 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 (less than 10%) is removed from the body after hemodialysis or peritoneal dialysis.

Storage and handling

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Store microcapsules and diluent below 25°C (77°F); excursions are permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from freezing.

The reconstituted product may be stored at 25°C (77°F) for 14 days; excursions are permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from freezing.

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