Cipro (ciprofloxacin) Side Effects, Warnings, and Interactions

Cipro (ciprofloxacin) is a fluoroquinolone antibiotic used to treat bacterial infections including infections of the skin, lung or airways; for example:

• TB (tuberculosis);
• pneumonic and septicemic plague due to Yersinia pestis (Y. pestis);
• lower respiratory tract infections;
• chronic bronchitis;
• Infections of bones and joints;
• urinary tract infections caused by certain bacteria such as E. coli;
• diarrheas (caused by E. coli, Campylobacter jejuni, and Shigella bacteria);
• anthrax patients with fever, low white blood cell counts, and intra-abdominal infections;
• typhoid fever;
• cervical and urethral gonorrhea due to Neisseria gonorrhoeae;
• chronic bacterial prostatitis; and
• acute uncomplicated cystitis.

Common side effects of Cipro and Cipro XR include

• nausea,
• vomiting,
• diarrhea,
• abdominal pain,
• rash,
• headache, and
• restlessness.

Serious side effects of Cipro and Cipro XR include

• peripheral neuropathy,
• central nervous system effects
  • (for example, toxic psychosis, nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, tremors, depression, and hallucinations),
• high blood sugar (hyperglycemia),
• Clostridium difficile-associated diarrhea (CDAD),
• abnormal heartbeats,
• liver dysfunction,
• stroke,
• convulsions,
• toxic epidermal necrolysis,
• Stevens-Johnson syndrome,
• vasculitis,
• allergic pneumonitis,
• interstitial nephritis,
• acute kidney failure,
• hepatitis,
• yellowing skin and eyes (jaundice),
• liver failure,
• anemia,
• tendinopathy, and
• low white blood cell counts (leukopenia).

Anaphylaxis, or shock, is a rare allergic reaction and a medical emergency. Seek medical immediately if you experience symptoms of shock including cardiovascular collapse, facial or throat swelling, shortness of breath, hives, or itching.

Drug interactions of Cipro and Cipro XR include theophylline, tizanidine, iron salts (for example, ferrous sulfate), warfarin, sevelamer, diabetic medications, sildenafil, and sulfonylureas.

Milk, orange juice, and antacids may reduce the absorption of ciprofloxacin.

Use of Cipro and Cipro XR is not recommended if you are pregnant or breastfeeding because it is unknown if it is safe.

Cipro and Cipro XR as well as other antibiotics in the fluoroquinolone class of antibiotics has been associated with tendonitis and even tendon rupture, particularly the Achilles tendon. Some doctors and other medical professionals recommend that their patients discontinue vigorous exercise while they are taking fluoroquinolone antibiotics.

Fluoroquinolones have neuromuscular blocking activity and can worsen muscle weakness in individuals with myasthenia gravis.

The most common side effects of Cipro, Cipro XR are:

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Rash
• Headache
• Restlessness

Anaphylaxis, or shock, is a rare allergic reaction to this drug. This allergic reaction is a medical emergency and you are experiencing these symptoms seek medical immediately.

Symptoms of shock include:

• Cardiovascular collapse
• Facial or throat swelling
• Shortness of breath
• Hives
• Itching

Other possible serious side effects of Cipro, Cipro XR include:

• Peripheral neuropathy
• Central nervous system effects (CNS), for example,
  • toxic psychosis,
  • nervousness,
  • agitation,
  • insomnia,
  • anxiety,
  • nightmares,
  • paranoia,
  • dizziness,
  • tremors,
  • depression, and
  • hallucinations.
• Hyperglycemia
• Clostridiumdifficile-associated diarrhea (CDAD)
• Abnormal heartbeats
• Liver dysfunction
• Stroke
• Convulsions
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Vasculitis
• Allergic pneumonitis
• Interstitial nephritis
• Acute kidney failure
• Hepatitis
• Jaundice
• Liver failure
• Anemia
• Leukopenia
• Cardiac arrest
• Respiratory failure

Other serious side effects and adverse events of Cipro, Cipro XR include:

Cipro, Cipro XR should be used with caution in patients with central nervous system diseases such as seizures, because rare seizures have been reported in patients receiving Cipro, Cipro XR.

Cipro, Cipro XR should be avoided in children and adolescents less than 18 years of age, as safe use in these patients has not been established.

Many antibiotics, including Cipro, Cipro XR, can alter the normal bacteria in the colon and encourage overgrowth of a bacterium responsible for the development of inflammation of the colon, (C. difficile or pseudomembranous colitis). Patients who develop signs of pseudomembranous colitis after starting Cipro, Cipro XR (diarrhea, fever, abdominal pain, and possibly shock) should contact their doctor immediately.

The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:

• Disabling and Potentially Irreversible Serious Adverse Reactions
• Tenditits and Tendon Rupture
• Peripheral Neuropathy
• Central Nervous System Effects
• Exacerbation of Myasthenia Gravis
• Other Serious and Sometimes Fatal Adverse Reactions
• Hypersensitivity Reactions
• Hepatotoxicity
• Serious Adverse Reactions with Concomitant Theophylline
• Clostridium difficile-Associated Diarrhea
• Prolongation of the QT Interval
• Musculoskeletal Disorders in Pediatric Patients
• Photosensitivity/Phototoxicity
• Development of Drug Resistant Bacteria

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical trials in patients with urinary tract infections enrolled 961 patients treated with 500 mg or 1000 mg CIPRO XR. The overall incidence, type and distribution of adverse reactions were similar in patients receiving both 500 mg and 1000 mg of CIPRO XR. The adverse reaction information from clinical studies does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

In the clinical trial of uncomplicated UTIs, CIPRO XR (500 mg once daily) in 444 patients was compared to ciprofloxacin immediate-release tablets (250 mg twice daily) in 447 patients for 3 days. Discontinuations due to adverse reactions thought to be drug-related occurred in 0.2% (1/444) of patients in the CIPRO XR arm and in 0% (0/447) of patients in the control arm.

In the clinical trial of cUTI and acute uncomplicated pyelonephritis (AUP) defined as infections occurring in premenopausal, non-pregnant women with no known urological abnormalities or comorbidities, CIPRO XR (1000 mg once daily) in 517 patients was compared to ciprofloxacin immediate-release tablets (500 mg twice daily) in 518 patients for 7 to 14 days. Discontinuations due to adverse reactions thought to be drug-related occurred in 3.1% (16/517) of patients in the CIPRO XR arm and in 2.3% (12/518) of patients in the control arm. The most common reasons for discontinuation in the CIPRO XR arm were nausea/vomiting (4 patients) and dizziness (3 patients). In the control arm the most common reason for discontinuation was nausea/vomiting (3 patients).

In these clinical trials, the following events occurred in ≥ 2% of all CIPRO XR patients: nausea (4%), headache (3%), dizziness (2%), diarrhea (2%), vomiting (2%) and vaginal moniliasis (2%).

Adverse reactions, judged by investigators to be at least possibly drug-related, occurring in greater than or equal to 1% of all CIPRO XR treated patients were: nausea (3%), diarrhea (2%), headache (1%), dyspepsia (1%), dizziness (1%), and vaginal moniliasis (1%). Vomiting (1%) occurred in the 1000 mg group.

Postmarketing Experience

The following adverse reactions have been reported from worldwide marketing experience with fluoroquinolones, including CIPRO XR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure (Table 3).

Adverse Laboratory Changes

Changes in laboratory parameters while on CIPRO are listed below:

Hepatic – Elevations of ALT (SGPT), AST (SGOT), alkaline phosphatase, LDH, serum bilirubin.

Hematologic – Eosinophilia, leukopenia, decreased blood platelets, elevated blood platelets, pancytopenia.

Renal – Elevations of serum creatinine, BUN, crystalluria, cylindruria, and hematuria have been reported.

Other changes occurring were: elevation of serum gammaglutamyl transferase, elevation of serum amylase, reduction in blood glucose, elevated uric acid, decrease in hemoglobin, anemia, bleeding diathesis, increase in blood monocytes, and leukocytosis.

Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. Co-administration of CIPRO XR with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the co-administered drug.