CIPRO IV® (ciprofloxacin) injection

CIPRO IV® (ciprofloxacin) injection

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CIPRO IV® (ciprofloxacin) injection

CIPRO IV (ciprofloxacin) is a synthetic antimicrobial agent for intravenous (IV) administration. Ciprofloxacin, a fluoroquinolone, is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1piperazinyl)-3-quinolinecarboxylic acid. Its empirical formula is C17H18FN3O3

Indications

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

  • Skin and Skin structure Infections: CIPRO IV is indicated in adult patients for treatment of skin and skin structure infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, Providencia stuartii, Morganella morganii, Citrobacter freundii, Pseudomonas aeruginosa, methicillin-susceptible Staphylococcus aureus, methicillinsusceptible Staphylococcus epidermidis, or Streptococcus pyogenes.
  • Bone and Joint infections: CIPRO IV is indicated in adult patients for treatment of bone and joint infections caused by Enterobacter cloacae, Serratia marcescens, or Pseudomonas aeruginosa.
  • Complicated Intra-Abdominal infections: CIPRO IV is indicated in adult patients for treatment of complicated intra-abdominal infections (used in combination with metronidazole) caused by Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, or Bacteroides fragilis.
  • Nosocomial Pneumonia: CIPRO IV is indicated in adult patients for treatment of nosocomial pneumonia caused by Haemophilus influenzae or Klebsiella pneumoniae.
  • Empirical Therapy for Febrile Neutropenic Patients
  • Inhalational Anthrax Post-Exposure in Adult and Pediatric Patients: CIPRO IV is indicated in adults and pediatric patients from birth to 17 years of age for treatment of inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis.
  • Plague in adult and pediatric patients: CIPRO IV is indicated for treatment of plague, including pneumonic and septicemic plague, due to Yersinia pestis (Y. pestis) and prophylaxis for plague in adults and pediatric patients from birth to 17 years of age. Efficacy studies of ciprofloxacin could not be conducted in humans with plague for feasibility reasons. Therefore this indication is based on an efficacy study conducted in animals only
  • Chronic Bacterial Prostatitis: CIPRO IV is indicated in adult patients for treatment of chronic bacterial prostatitis caused by Escherichia coli or Proteus mirabilis.
  • Lower respiratory tract infections: CIPRO IV is indicated in adult patients for treatment of lower respiratory tract infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus parainfluenzae, or Streptococcus pneumoniae CIPRO IV is not a drug of first choice in the treatment of presumed or confirmed pneumonia secondary to Streptococcus pneumonia.

Acute Exacerbation of Chronic Bronchitis: CIPRO IV is indicated for the treatment of acute exacerbations of chronic bronchitis (AECB) caused by Moraxella catarrhalis.

  • Urinary Tract Infections:

Urinary Tract Infections (UTI): CIPRO IV is indicated in adult patients for treatment of urinary tract infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus mirabilis, Providencia rettgeri, Morganella morganii, Citrobacter koseri, Citrobacter freundii, Pseudomonas aeruginosa, methicillin-susceptible Staphylococcus epidermidis, Staphylococcus saprophyticus, or Enterococcus faecalis.

Complicated UTI and Pyelonephritis in Pediatric Patients: CIPRO IV is indicated in pediatric patients one to 17 years of age for treatment of complicated urinary tract infections (cUTI) and pyelonephritis due to Escherichia coli

  • Acute Sinusitis: CIPRO IV is indicated in adult patients for treatment of acute sinusitis caused by Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis.

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of CIPRO IV and other antibacterial drugs, CIPRO IV 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

ADULT

InfectionDoseFrequencyDuration
Skin and Skin Structure400 mgevery 8 to 12 hours7–14 days
Bone and Joint400 mgevery 8 to 12 hours4 to 8 weeks
Complicated Intra-Abdominal400 mgevery 12 hours7–14 days
Nosocomial Pneumonia400 mgevery 8 hours10–14 days
Empirical Therapy In Febrile Neutropenic Patients400 mg and
Piperacillin 50 mg/kg
every 8 hours
every 4 hours
7-14 days
Inhalational anthrax(post-exposure)400 mgevery 12 hours60 days
Plague400 mgevery 8 to 12 hours14 days
Chronic Bacterial prostatitis400 mgevery 12 hours28 days
Lower Respiratory Tract400 mgevery 8 to 12 hours7–14 days
Urinary Tract200 to 400 mgevery 8 to 12 hours7–14 days
Acute Sinusitis400 mgevery 12 hours10 days

Adults with creatinine clearance 5–29 mL/min 250–500 mg q 18 h

Pediatric Intravenous Dosing Guidelines

InfectionDoseFrequencyDuration
Complicated UTI and Pyelonephritis (patients from 1 to 17 years of age)6 mg/kg to 10 mg/kg (maximum 400 mg per dose)Every 8 hours10–21 days
Inhalational Anthrax (Post-Exposure)10 mg/kg (maximum 400 mg per dose)Every 12 hours60 days
Plague10 mg/kg (maximum 400 mg per dose)Every 8 to 12 hours10–21 days

Contraindications

Hypersensitivity: Ciprofloxacin is contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antibacterials, or any of the product components

Tizanidine: Concomitant administration with tizanidine is contraindicated

Warnings and precautions

Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects

Fluoroquinolones, including CIPRO IV, have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). These reactions can occur within hours to weeks after starting CIPRO IV. Patients of any age or without pre-existing risk factors have experienced these adverse reactions

Discontinue CIPRO IV immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including CIPRO IV, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones.

Tendinitis and Tendon Rupture: Fluoroquinolones, including CIPRO IV, have been associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and has also been reported with the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendons. Tendinitis or tendon rupture can occur, within hours or days of starting CIPRO IV, or as long as several months after completion of fluoroquinolone therapy. Tendinitis and tendon rupture can occur bilaterally.

Peripheral Neuropathy: Discontinue CIPRO IV immediately if the patient experiences symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness, or other alterations in sensations including light touch, pain, temperature, position sense and vibratory sensation, and/or motor strength in order to minimize the development of an irreversible condition. Avoid fluoroquinolones, including CIPRO IV, in patients who have previously experienced peripheral neuropathy

Central Nervous System Effects: Fluoroquinolones, including CIPRO IV, have been associated with an increased risk of central nervous system (CNS) effects, including convulsions, increased intracranial pressure (including pseudotumor cerebri), and toxic psychosis CIPRO IV may also cause central nervous system (CNS) events including: nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and, psychotic reactions have progressed to suicidal ideations/thoughts and self-injurious behavior such as attempted or completed suicide. These reactions may occur following the first dose. Advise patients receiving CIPRO IV to inform their healthcare provider immediately if these reactions occur, discontinue the drug, and institute appropriate care.

Exacerbation of Myasthenia Gravis: Fluoroquinolones, including CIPRO IV, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. Postmarketing serious adverse reactions, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Avoid CIPRO IV in patients with known history of myasthenia gravis

Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving fluoroquinolone therapy, including CIPRO IV. 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 hypersensitivity reactions. Serious anaphylactic reactions require immediate emergency treatment with epinephrine and other resuscitation measures, including oxygen, intravenous fluids, intravenous antihistamines, corticosteroids, pressor amines, and airway management, including intubation, as indicated.

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Hepatotoxicity: Cases of severe hepatotoxicity, including hepatic necrosis, life-threatening hepatic failure, and fatal events, have been reported with CIPRO IV. Acute liver injury is rapid in onset (range 1–39 days), and is often associated with hypersensitivity. The pattern of injury can be hepatocellular, cholestatic or mixed. Most patients with fatal outcomes were older than 55 years old. In the event of any signs and symptoms of hepatitis (such as anorexia, jaundice, dark urine, pruritus, or tender abdomen), discontinue treatment immediately.

Serious Adverse Reactions with Concomitant Theophylline: Serious and fatal reactions have been reported in patients receiving concurrent administration of Intravenous CIPRO and theophylline. These reactions have included cardiac arrest, seizure, status epilepticus, and respiratory failure. Instances of nausea, vomiting, tremor, irritability, or palpitation have also occurred.

Clostridium difficile-Associated Diarrhea: Clostridium difficile (C. difficile)-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including CIPRO IV, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

Prolongation of the QT Interval: Avoid CIPRO IV in patients with known prolongation of the QT interval, risk factors for QT prolongation or torsade de pointes (for example, congenital long QT syndrome, uncorrected electrolyte imbalance, such as hypokalemia or hypomagnesemia and cardiac disease, such as heart failure, myocardial infarction, or bradycardia), and patients receiving Class IA antiarrhythmic agents (quinidine, procainamide), or Class III antiarrhythmic agents (amiodarone, sotalol), tricyclic antidepressants, macrolides, and antipsychotics. Elderly patients may also be more susceptible to drug-associated effects on the QT interval

Photosensitivity/Phototoxicity: Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (for example, burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, “V” area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of quinolones, including CIPRO IV, after sun or UV light exposure. Therefore, avoid excessive exposure to these sources of light. Discontinue CIPRO IV if phototoxicity occurs.

Development of Drug Resistant Bacteria: Prescribing CIPRO IV in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Potential Risks with Concomitant Use of Drugs Metabolized by Cytochrome P450 1A2 Enzymes: Ciprofloxacin is an inhibitor of the hepatic CYP1A2 enzyme pathway. Co-administration of CIPRO IV and other drugs primarily metabolized by CYP1A2 (for example, theophylline, methylxanthines, caffeine, tizanidine, ropinirole, clozapine, olanzapine, and zolpidem) results in increased plasma concentrations of the co-administered drug and could lead to clinically significant pharmacodynamic adverse reactions of the co-administered drug.

Crystalluria: Crystals of ciprofloxacin have been observed rarely in the urine of human subjects but more frequently in the urine of laboratory animals, which is usually alkaline. Crystalluria related to ciprofloxacin has been reported only rarely in humans because human urine is usually acidic. Avoid alkalinity of the urine in patients receiving CIPRO IV. Hydrate patients well to prevent the formation of highly concentrated urine.

Drug interactions

Tizanidine: Concomitant administration of tizanidine and CIPRO IV is contraindicated due to the potentiation of hypotensive and sedative effects of tizanidine

Theophylline: Concurrent administration of CIPRO IV 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 IV 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: Glucose-lowering effect potentiated Hypoglycemia sometimes severe has been reported when CIPRO IV 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 ciprofloxacin 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 IV discontinuation in patients receiving both agents, monitor phenytoin therapy, including phenytoin serum concentration during and shortly after co-administration of CIPRO IV with phenytoin.

Cyclosporine: Monitor renal function (in particular serum creatinine) when ciprofloxacin is co-administered with cyclosporine.

Use in specific populations

Pregnancy: Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. CIPRO IV should not be used during pregnancy unless the potential benefit justifies the potential risk to both fetus and mother.

Nursing Mothers: Ciprofloxacin is excreted in human milk. The amount of ciprofloxacin absorbed by the nursing infant is unknown. Because of the potential risk of serious adverse reactions (including articular damage) in infants nursing from mothers taking CIPRO IV, 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:

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

CIPRO IV 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 IV 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 IV. 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 IV 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.

Overdosage

In the event of acute overdosage, reversible renal toxicity has been reported in some cases. Observe the patient carefully and give supportive treatment, including monitoring of renal function, urinary pH and acidify, if required, to prevent crystalluria. Adequate hydration must be maintained. Only a small amount of ciprofloxacin (less than 10%) is removed from the body after hemodialysis or peritoneal dialysis.

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