Cipro
  Ciprofloxacin
  Bayer A. G. as well as Generic Manufacturers
  NDA  019537, 019847, 020780
  Latest Package Insert
  Cipro 2000,  2004
  Safety Profile

  DO NOT USE 

Listed  as a DO NOT USE drug
Numerous other, safer antibiotics are approved to treat the same infections as this drug

There are numerous FATAL adverse reactions associated with this drug. (Read More)

BLACK BOX WARNINGS TO BE ADDED (Read More)
 FDA is notifying the makers of fluoroquinolone antimicrobial
 drugs for systemic use of the need to add a boxed warning to
 the prescribing information about the increased risk of developing
 tendinitis and tendon rupture in patients taking fluoroquinolones
 and to develop a Medication Guide for patients.

In view of the potentially fatal consequences of anaphylactic reactions to Ciprofloxacin and other quinolones doctors should take care when prescribing these drugs.

Peripheral Neuropathy
Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving quinolones.

QUINOLONES MAY HAVE THE POTENTIAL TO PROLONG THE QTc INTERVAL OF THE ELECTROCARDIOGRAM IN SOME PATIENTS. DUE TO THE LACK OF CLINICAL EXPERIENCE, QUINOLONES SHOULD BE AVOIDED IN PATIENTS WITH KNOWN PROLONGATION OF THE QTc INTERVAL, PATIENTS WITH UNCORRECTED HYPOKALEMIA, AND PATIENTS RECEIVING CLASS IA (E.G. QUINIDINE, PROCAINAMIDE) OR CLASS III (E.G. AMIODARONE, SOTALOL) ANTIARRHYTHMIC AGENTS.

Ruptures of the shoulder, hand, and Achilles tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones. Tendon rupture can occur during or after therapy with quinolones.

Quinolones may cause central nervous system (CNS) events including nervousness, agitation, insomnia, anxiety, nightmares, or paranoia.

As with other quinolones, disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic (e. g., glyburide) or with insulin. In these patients, the monitoring of blood glucose is recommended.

In 2004 new warning labels added to all of the Fluoroquinolones regarding Peripheral Neuropathy (irreversible nerve damage), Tendon Damage, Heart Problems (prolonged QT Interval / Torsades de pointes), Pseudomembranous colitis, Rhabdomyolysis (muscle wasting), Steven Johnson Syndrome, as well as concurrent usage of NSAIDs contributing to the severity of these reactions.
.
Although such events have been reported since the mid sixties, the FDA waited almost forty years to add such warnings to the package inserts.  These new warnings again fail to adequately warn either the patient or the physician.

"Drug companies write the package inserts of all drugs, carefully including the information they choose and
omitting information they want to avoid. Drug companies underwrite a large percentage of continuing
education courses for doctors. In doing so, they make sure that the speakers represent the company view.
Drug companies design studies that are meant to produce favorable results and then publish the studies in
medical journals. Studies with unfavorable results are not published. Drug reps typically bring stacks of
studies, all favorable, which impress doctors, who no longer have the time or motivation to search  the
medical literature themselves. Drug reps do not include independent studies with less favorable
conclusions. Many doctors never see these." 

Source:   THE MEDICAL PROFESSION AND THE CULTURE OF CORRUPTION

http://www.fda.gov/cder/foi/label/2004/

Ciprofloxacin
Brand Names: Cipr, Ci[proHC, Ciloxan Opht, Baycip, Cetraxal, Ciflox, Cifran, Ciplox, Ciprobay, Quintor
BAYER CIPROFLOXACIN HYDROCHLORIDE FDA Approval Date: OCT 22, 1987 CIPRO

Public Citizen list this drug for LIMITED USEAGE

Limited Use
Generic drug name: ciprofloxacin (sip roe FLOX a sin) 
Brand name(s): CILOXAN; CIPRO (Bayer Pharmaceuticals Corp.)
GENERIC: not available    FAMILY: Fluoroquinolones

Recent Changes to the package insert:
July 2004 Cipro Warnings:

Changes made to the package insert for Cipro IV:

WARNINGS
Pseudomembranous Colitis: After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against C. difficile colitis. Drugs that inhibit peristalsis should be avoided.

Peripheral Neuropathy: Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving quinolones, including Ciprofloxacin. Ciprofloxacin should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness, and/or weakness, or is found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength in order to prevent the development of an irreversible condition.

Tendon Effects: Ciprofloxacin should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon. Patients should rest and refrain from exercise until the diagnosis of tendinitis or tendon rupture has been excluded. Tendon rupture can occur during or after therapy with quinolones, including Ciprofloxacin. {notice the lack of warning regarding the use of steroids}

Changes made to the package insert for Cipro Tab:

WARNINGS

Peripheral Neuropathy: Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving quinolones, including Ciprofloxacin. Ciprofloxacin should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness, and/or weakness, or is found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength in order to prevent the development of an irreversible condition

Tendon Effects: Ciprofloxacin should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon. Patients should rest and refrain from exercise until the diagnosis of tendinitis or tendon rupture has been excluded. Tendon rupture can occur during or after therapy with quinolones, including Ciprofloxacin. {notice the lack of warning regarding the use of steroids}


Changes made to the package insert for Cipro XR:

WARNINGS

Pseudomembranous Colitis: After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against C. difficile colitis. Drugs that inhibit peristalsis should be avoided.

Peripheral Neuropathy: Rare cases of sensory or sensorimotor axonal polyneuropathy hypoesthesias, dysesthesias and weakness have been reported in patients receiving quinolones, including Ciprofloxacin. Ciprofloxacin should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness, and/or weakness, or is found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength in order to prevent the development of an irreversible condition.

Tendon Effects: Ruptures of the shoulder, hand, Achilles tendon or other tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones, including Ciprofloxacin. Post-marketing surveillance reports indicate that this risk may be increased in patients receiving concomitant corticosteroids, especially the elderly. Ciprofloxacin should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon. Patients should rest and refrain from exercise until the diagnosis of tendinitis or tendon rupture has been excluded. Tendon rupture can occur during or after therapy with quinolones, including Ciprofloxacin.


April 2004 Cipro Warnings
http://www..univgraph.com/bayer/inserts/ciprotab.pdf.

PERIPHERAL NEUROPATHY: Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and or large axons resulting in paresthesias, hypoaesthesias, dysesthesias, and weakness have been reported in patients taking quinolones including ciprofloxacin. Ciprofloxacin should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness and or weakness or is found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and or motor strength in order to prevent the development of an irreversible condition.

Concomitant steroid warning added to Cipro March 2004.

PERIPHERAL NEUROPATHY (as noted above)
Achilles and other tendon ruptures that required surgical repair or resulted in prolonged disability.
Convulsions, increased intracranial pressure, and toxic psychosis.
Central nervous system (CNS) events including: dizziness, confusion, tremors, hallucinations, depression, and, rarely, suicidal thoughts or acts. These reactions may occur following the first dose.
Severe hypersensitivity reactions characterized by rash, fever, eosinophilia, jaundice, and hepatic necrosis with fatal outcome
Pseudomembranous colitis and may range in severity from mild to life-threatening.
Lameness in immature dogs with permanent lesions of the cartilage.
Central nervous system (CNS) events, including nervousness, agitation, insomnia, anxiety, nightmares or paranoia.
Crystalluria
Moderate to severe photoxicity

Additional adverse events reported, regardless of relationship to the drug:

Body as a Whole: Change in serum phenytoin.

Cardiovascular: Palpitation, atrial flutter, ventricular ectopy, syncope, hypertension, angina pectoris, myocardial infarction, cardiopulmonary arrest, cerebral thromobosis. Cardiovascular collapse, cardiopulmonary arrest, myocardial infarction, arrhythmia, tachycardia, palpitation, cerebral thrombosis, syncope, cardiac murmur, hypertension, hypotension, angina pectoris. Postural hypotension, vasculitis.

Central Nervous System: Dizziness, lightheadedness, insomnia, nightmares, hallucinations, manic reaction, irritability, tremor, ataxia, convulsive seizures, lethargy, drowsiness, weakness, malaise, anorexia, phobia, depersonalization, depression, paresthesia. Convulsive seizures, paranoia, toxic psychosis, depression, dysphasia, phobia, depersonalization, manic reaction, unresponsiveness, ataxia, confusion, hallucinations, dizziness, lightheadedness, paresthesia, anxiety, tremor, insomnia, nightmares, weakness, drowsiness, irritability, malaise, lethargy Agitation, confusion, delirium, dysphasia, myoclonus, nystagmus, toxic psychosis.
.
Gastrointestinal: Painful oral mucosa, oral candidiasis, dysphagia, intestinal perforation, gastrointestinal bleeding. Cholestatic jaundice has been reported. Ileus, jaundice, gastrointestinal bleeding, C. difficle associated diarrhea, pseudomembranous colitis, pancreatitis, hepatic necrosis, intestinal perforation, dyspepsia, epigastric or abdominal pain, vomiting, constipation, oral ulceration, oral candidiasis, mouth dryness, anorexia, dysphagia, flatulence Constipation, dyspepsia, flatulence, hepatic necrosis, jaundice, pancreatitis, pseudomembranous colitis. (The onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment.)

Hemic/Lymphatic: Agranulocytosis, hemolytic anemia, methemaglobinemia, prolongation of prothrombin time

Metabolic/Nutritional: Elevation of serum triglycerides, cholesterol, blood glucose, serum potassium.

Musculoskeletal: Arthralgia or back pain, joint stiffness, achiness, neck or chest pain, flare up of gout. Arthralgia, jaw, arm or back pain, joint stiffness, neck and chest pain, achiness, flare up of gout Myalgia, possible exacerbation of myasthenia gravis, tendinitis/tendon rupture.

Renal/Urogenital: Interstitial nephritis, nephritis, renal failure, polyuria, urinary retention, urethral bleeding, vaginitis, acidosis. Renal failure, intarstitial nephritis, hemorrhagic cystitis, renal calcuti, frequent urination, acidosis, urethral bleeding, polyuria, urinary retention, gynecomastia, candiduria, vaginitis. Crystalluria, cylindruria, hematuria, and albuminutia have also been reported.
Albuminuria, candiduria, renal calculi, vaginal candidiasis.

Respiratory: Dyspnea, epistaxis, laryngeal or pulmonary edema, hiccough, hemophysis, bronchospasm, pulmonary embolism. Respiratory arrest, pulmonary embolism, dyspnea, pulmonary edema, respiratory distress, pleural effusion, hemoptysis, epistaxis, hiccough

Skin/Hypersensitivity: Pruritus, urticaria, photosensitivity, flushing, fever, chills, angioedema, edema of the face, neck, lips, conjunctivae or hands, cutaneous candidiasis, hyperpigmentation, erytherna nodosum. Allergic reactions ranging from urticaria to anaphylactic reactions have been reported. Anaphylactic reactions, erythema multiforme/Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, vasculitis, angioedema, edema of the lips, face, neck, conjunctivae, hands or lower extremities, purpura, fever, chills, flushing, pruritus, urtigaria, cutaneous candidiasis, vesicles, increased perspiration, hyperpigmentation, erythema nodosum, photosensitivity. Allergic reactions ranging from urticaria to anaphylactic reactions have been reported. Anaphylactic reactions, erythema multiforme/Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis.

Special Senses: Blurred vision, disturbed vision (change in color perception, overbrightness of lights), decreased visual acuity, diplopia, eye pain, tinnitus, hearing loss, bad taste. Decreased visual acuity, blurred vision, disturbed vision (flashing lights, change in color perception, overbrightness of lights, diplopia), eye pain, anosmia, hearing loss, tinnitus, nystagmus, a bad taste Also reported were agranulocytosis, prolongation of prothrombin time, and possible exacerbation of myasthenia gravis. Anosmia, taste loss.
 

Adverse Laboratory Changes

Oral

Changes in Laboratory Parameters Listed as Adverse Events Without Regard to Drug Relationship:

Other changes occurring rarely during administration of ciprofloxacin were: elevation of serum amylase, decrease of blood glucose, pancytopenia, leukocytosis, elevated sedimentation rate, change in serum phenytoin, decreased prothrombin time, hemolytic anemia, and bleeding diathesis.
 

ANIMAL PHARMACOLOGY
Oral and I.V.