Ciprofloxacin Oral Suspension

• If you have an allergy to ciprofloxacin or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Long QTc on ECG or other heartbeat that is not normal, slow heartbeat, or low potassium or magnesium levels.
• If you have kidney problems.
• If you have heart failure (weak heart).
• If you have had a recent heart attack.
• If you have ever had any of these health problems: Nerve problems or tendon problems.
• If you have had tendons get irritated or torn when taking ciprofloxacin oral suspension or an alike drug in the past.
• If you have been taking any drugs to treat a heartbeat that is not normal.
• If you are taking any drugs that can cause a certain type of heartbeat that is not normal (prolonged QT interval). There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.
• If you are taking any of these drugs: Duloxetine, theophylline, tizanidine, or zolpidem.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take ciprofloxacin oral suspension with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Chest pain or pressure.
• Feeling very tired or weak.
• Shortness of breath.
• Any unexplained bruising or bleeding.
• Shakiness.
• Trouble walking.
• Vaginal itching or discharge.
• White patches in mouth.
• Sunburn.
• Fever or chills.
• Sore throat.
• Ringing in ears.
• Muscle pain or weakness.
• Very bad and sometimes deadly liver problems have happened with this medicine. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
• It is common to have diarrhea when taking ciprofloxacin oral suspension. Rarely, a very bad form of diarrhea called Clostridium difficile (C diff)–associated diarrhea (CDAD) may occur. Sometimes, this has led to a deadly bowel problem (colitis). CDAD may happen while you are taking this medicine or within a few months after you stop taking it. Call your doctor right away if you have stomach pain or cramps, very loose or watery stools, or bloody stools. Do not try to treat loose stools without first checking with your doctor.

Skin and Skin Structure Infections

Ciprofloxacin for oral suspension 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, methicillin-susceptible Staphylococcus epidermidis, or Streptococcus pyogenes.

Bone and Joint Infections

Ciprofloxacin for oral suspension 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

Ciprofloxacin for oral suspension 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.

Infectious Diarrhea

Ciprofloxacin for oral suspension is indicated in adult patients for treatment of infectious diarrhea caused by Escherichia coli (enterotoxigenic isolates), Campylobacter jejuni, Shigella boydii †, Shigella dysenteriae, Shigella flexneri or Shigella sonnei †when antibacterial therapy is indicated.

†Although treatment of infections due to this organism in this organ system demonstrated a clinically significant outcome, efficacy was studied in fewer than 10 patients.

Typhoid Fever (Enteric Fever)

Ciprofloxacin for oral suspension is indicated in adult patients for treatment of typhoid fever (enteric fever) caused by Salmonella typhi. The efficacy of ciprofloxacin in the eradication of the chronic typhoid carrier state has not been demonstrated.

Uncomplicated Cervical and Urethral Gonorrhea

Ciprofloxacin for oral suspension is indicated in adult patients for treatment of uncomplicated cervical and urethral gonorrhea due to Neisseria gonorrhoeae [see WARNINGS AND PRECAUTIONS (5.16)].

Inhalational Anthrax (Post-Exposure)

Ciprofloxacin for oral suspension is indicated in adults and pediatric patients from birth to 17 years of age for inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis.

Ciprofloxacin serum concentrations achieved in humans served as a surrogate endpoint reasonably likely to predict clinical benefit and provided the initial basis for approval of this indication.1Supportive clinical information for ciprofloxacin for anthrax post-exposure prophylaxis was obtained during the anthrax bioterror attacks of October 2001 [see CLINICAL STUDIES (14.2)].

Plague

Ciprofloxacin for oral suspension 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 [see CLINICAL STUDIES (14.3)].

Chronic Bacterial Prostatitis

Ciprofloxacin for oral suspension is indicated in adult patients for treatment of chronic bacterial prostatitis caused by Escherichia coli or Proteus mirabilis.

Lower Respiratory Tract Infections

Ciprofloxacin for oral suspension 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.

Ciprofloxacin for oral suspension is not a drug of first choice in the treatment of presumed or confirmed pneumonia secondary to Streptococcus pneumoniae

Ciprofloxacin for oral suspension is indicated for the treatment of acute exacerbations of chronic bronchitis (AECB) caused by Moraxella catarrhalis.

Because fluoroquinolones, including Ciprofloxacin for oral suspension, have been associated with serious adverse reactions [see WARNINGS AND PRECAUTIONS (5.1 to 5.15)] and for some patients AECB is self-limiting, reserve Ciprofloxacin for oral suspension for treatment of AECB in patients who have no alternative treatment options.

Urinary Tract Infections

Urinary Tract Infections in Adults

Ciprofloxacin for oral suspension 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.

Acute Uncomplicated Cystitis

Ciprofloxacin for oral suspension is indicated in adult female patients for treatment of acute uncomplicated cystitis caused by Escherichia coli or Staphylococcus saprophyticus.

Because fluoroquinolones, including ciprofloxacin for oral suspension, have been associated with serious adverse reactions [see WARNINGS AND PRECAUTIONS (5.1 to 5.15)] and for some patients acute uncomplicated cystitis is self-limiting, reserve ciprofloxacin for oral suspension for treatment of acute uncomplicated cystitis in patients who have no alternative treatment options.

Complicated Urinary Tract Infection and Pyelonephritis in Pediatric Patients

Ciprofloxacin for oral suspension is indicated in pediatric patients aged one to 17 years of age for treatment of complicated urinary tract infections (cUTI) and pyelonephritis due to Escherichia coli [see USE IN SPECIFIC POPULATIONS (8.4)].

Although effective in clinical trials, ciprofloxacin for oral suspension is not a drug of first choice in the pediatric population due to an increased incidence of adverse reactions compared to controls, including reactions related to joints and/or surrounding tissues. Ciprofloxacin for oral suspension, like other fluoroquinolones, is associated with arthropathy and histopathological changes in weight-bearing joints of juvenile animals [see WARNINGS AND PRECAUTIONS (5.12), ADVERSE REACTIONS (6.1), USE IN SPECIFIC POPULATIONS (8.4) and NONCLINICAL TOXICOLOGY (13.2)].

Acute Sinusitis

Ciprofloxacin for oral suspension is indicated in adult patients for treatment of acute sinusitis caused by Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis.

Because fluoroquinolones, including ciprofloxacin for oral suspension, have been associated with serious adverse reactions [see WARNINGS AND PRECAUTIONS (5.1 to 5.15)] and for some patients acute sinusitis is self-limiting, reserve ciprofloxacin for oral suspension for treatment of acute sinusitis in patients who have no alternative treatment options.

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ciprofloxacin for oral suspension and other antibacterial drugs, ciprofloxacin for oral suspension 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.

If anaerobic organisms are suspected of contributing to the infection, appropriate therapy should be administered. Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to ciprofloxacin. Therapy with ciprofloxacin for oral suspension may be initiated before results of these tests are known; once results become available appropriate therapy should be continued.

As with other drugs, some isolates of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with ciprofloxacin. Culture and susceptibility testing performed periodically during therapy will provide information not only on the therapeutic effect of the antimicrobial agent but also on the possible emergence of bacterial resistance.

Ciprofloxacin for oral suspension should be administered orally as described in the appropriate Dosage Guidelines tables.

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.

Conversion of IV to Oral Dosing in Adults

Patients whose therapy is started with CIPRO IV may be switched to ciprofloxacin for oral suspension when clinically indicated at the discretion of the     physician (Table 2) [see CLINICAL PHARMACOLOGY (12.3)].

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. Ciprofloxacin should be administered as described in Table 3.

Dosage Modifications in Patients with 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. Dosage guidelines for use in patients with renal impairment are shown in Table 4.

When only the serum creatinine concentration is known, the following formulas may be used to estimate creatinine clearance:

Men - Creatinine clearance (mL/min) = Weight (kg) x (140–age)

                                                            72 x serum creatinine (mg/dL)

Women - 0.85 x the value calculated for men.

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

In patients with severe infections and severe renal impairment, a unit dose of 750 mg may be administered at the intervals noted above. Patients should be carefully monitored.

Pediatric patients with moderate to severe renal insufficiency were excluded from the clinical trial of cUTI and pyelonephritis. No information is available on dosing adjustments necessary for pediatric patients with moderate to severe renal insufficiency (that is, creatinine clearance of < 50 mL/min/1.73m2).

Important Administration Instructions

With Multivalent Cations

Administer ciprofloxacin for oral suspension at least 2 hours before or 6 hours after magnesium/aluminum antacids; polymeric phosphate binders (for example, sevelamer, lanthanum carbonate) 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.

With Dairy Products

Concomitant administration of ciprofloxacin for oral suspension with dairy products (like milk or yogurt) or calcium-fortified juices alone should be avoided since decreased absorption is possible; however, ciprofloxacin for oral suspension may be taken with a meal that contains these products.

Hydration of Patients Receiving Ciprofloxacin for Oral Suspension

Assure adequate hydration of patients receiving ciprofloxacin for oral suspension to prevent the formation of highly concentrated urine. Crystalluria has been reported with quinolones.

Instruct the patient of the appropriate ciprofloxacin for oral suspension administration [see PATIENT COUNSELING INFORMATION (17)].

Directions for Reconstitution of the Ciprofloxacin Granular Blend for Oral Suspension

Ciprofloxacin for oral suspension is supplied in 5% (5 g ciprofloxacin in 100 mL) and 10% (10 g ciprofloxacin in 100 mL) strengths. Ciprofloxacin for oral suspension is composed of two components (granular blend and diluent) that must be combined prior to dispensing.

Preparation of the suspension

Step1:

The small bottle contains the diluent, which is clear to yellow oil. Sometimes, you may observe yellow droplets (of one of the component of diluent i.e. polysorbate -20), which should disappear on vigorous shaking. The large bottle contains the ciprofloxacin granular blend.

Step 2:

Open both bottles. Child-proof cap: Press down according to instructions on the cap while turning to the left.

Step 3:

Pour the diluent completely into the larger bottle of granular blend. Do not add water to the suspension.

Step 4:

Remove the top layer of the granular blend bottle label (to reveal the Ciprofloxacin for Oral Suspension label). Close the large bottle completely according to the directions on the cap and shake vigorously for about 30 seconds. The suspension is ready for use.

Step 5:

Write the expiration date of the re-constituted oral suspension on the bottle label.

Reconstituted product may be stored below 30°C (86°F) for 14 days. Protect from freezing.

No additions should be made to the mixed final ciprofloxacin suspension. Ciprofloxacin for oral suspension should not be administered through feeding or NG (nasogastric) tubes due to its physical characteristics.

Oral Suspension

• 5% Oral Suspension: 250 mg ciprofloxacin per 5 mL after reconstitution
• 10% Oral Suspension: 500 mg ciprofloxacin per 5 mL after reconstitution

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.

Complicated Urinary Tract Infection and Pyelonephritis–Efficacy in Pediatric Patients

Ciprofloxacin administered intravenously and/or orally was compared to a cephalosporin for treatment of cUTI and pyelonephritis in pediatric patients 1 to 17 years of age (mean age of 6 ± 4 years). The trial was conducted in the US, Canada, Argentina, Peru, Costa Rica, Mexico, South Africa, and Germany. The duration of therapy was 10 to 21 days (mean duration of treatment was 11 days with a range of 1 to 88 days). The primary objective of the study was to assess musculoskeletal and neurological safety.

Patients were evaluated for clinical success and bacteriological eradication of the baseline organism(s) with no new infection or superinfection at 5 to 9 days post-therapy (Test of Cure or TOC). The Per Protocol population had a causative organism(s) with protocol specified colony count(s) at baseline, no protocol violation, and no premature discontinuation or loss to follow-up (among other criteria).

The clinical success and bacteriologic eradication rates in the Per Protocol population were similar between ciprofloxacin and the comparator group as shown below.

Inhalational Anthrax in Adults and Pediatrics

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. 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 mcg/mL 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. Ciprofloxacin serum concentrations achieved in humans serve as a surrogate endpoint reasonably likely to predict clinical benefit and provide the basis for this indication.1

A placebo-controlled animal study in rhesus monkeys exposed to an inhaled mean dose of 11 LD50 (~5.5 x 105spores (range 5 to 30 LD50) 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 Tmax (1 hour post-dose) following oral dosing to steady-state ranged from 0.98 mcg/mL to 1.69 mcg/mL. Mean steady-state trough concentrations at 12 hours post-dose ranged from 0.12 mcg/mL to 0.19 mcg/mL.10Mortality 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 period.11

More than 9300 persons were recommended to complete a minimum of 60 days of antibacterial prophylaxis against possible inhalational 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 antibacterial drugs. 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.

Plague

A placebo-controlled animal study in African green monkeys exposed to an inhaled mean dose of 110 LD50 (range 92 to 127 LD50) of Yersinia pestis (CO92 strain) was conducted. The minimal inhibitory concentration (MIC) of ciprofloxacin for the Y. pestis strain used in this study was 0.015 mcg/mL. Mean peak serum concentrations of ciprofloxacin achieved at the end of a single 60 minute infusion were 3.49 ± mcg/mL 0.55 mcg/mL, 3.91 mcg/mL ± 0.58 mcg/mL and 4.03 mcg/mL ± 1.22 mcg/mL on Day 2, Day 6 and Day 10 of treatment in African green monkeys, respectively All trough concentrations (Day 2, Day 6 and Day 10) were <0.5 mcg /mL. Animals were randomized to receive either a 10-day regimen of intravenous ciprofloxacin 15 mg/kg, or placebo beginning when animals were found to be febrile (a body temperature greater than 1.5oC over baseline for two hours), or at 76 hours post-challenge, whichever occurred sooner. Mortality in the ciprofloxacin group was significantly lower (1/10) compared to the placebo group (2/2) [difference: -90.0%, 95% exact confidence interval: -99.8% to -5.8%]. The one ciprofloxacin-treated animal that died did not receive the proposed dose of ciprofloxacin due to a failure of the administration catheter. Circulating ciprofloxacin concentration was below 0.5 mcg/mL at all timepoints tested in this animal. It became culture negative on Day 2 of treatment, but had a resurgence of low grade bacteremia on Day 6 after treatment initiation. Terminal blood culture in this animal was negative.12

Side effects that you should report to your doctor or health care professional as soon as possible:

• allergic reactions like skin rash or hives, swelling of the face, lips, or tongue
• anxious
• confusion
• depressed mood
• diarrhea
• fast, irregular heartbeat
• hallucination, loss of contact with reality
• joint, muscle, or tendon pain or swelling
• pain, tingling, numbness in the hands or feet
• suicidal thoughts or other mood changes
• sunburn
• unusually weak or tired

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

• dry mouth
• headache
• nausea
• trouble sleeping