Proquin XR

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

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Proquin XR (ciprofloxacin hydrochloride) extended-release tablets contain ciprofloxacin hydrochloride, a synthetic broad-spectrum fluoroquinolone antimicrobial agent for oral administration.

Ciprofloxacin hydrochloride is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid hydrochloride. The molecular weight of the monohydrate is 385.82. It is a faintly yellowish to light yellow crystalline substance and its chemical structure is as follows:

Proquin XR is available as 500 mg (ciprofloxacin equivalent) tablets, utilizing AcuForm™ delivery technology. Proquin XR tablets are blue film-coated and oval-shaped. The inactive ingredients are povidone, magnesium stearate, polyethylene oxide, and film coating (Opadry® Blue).

General

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. (See ANIMAL PHARMACOLOGY). Crystalluria related to ciprofloxacin has been reported only rarely in humans because human urine is usually acidic. Alkalinity of the urine should be avoided in patients receiving ciprofloxacin. Patients should be well hydrated to prevent the formation of highly concentrated urine.

Quinolones, including ciprofloxacin, may also cause CNS events, including nervousness, agitation, insomnia, anxiety, nightmares, or paranoia. (See WARNINGS)

Moderate to severe photosensitivity/ phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (e.g., 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 quinolone antibiotics after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if phototoxicity occurs (See ADVERSE REACTIONS and ADVERSE REACTIONS/ Post-Marketing Adverse Events).

Prescribing Proquin XR in the absence of a strongly suspected bacterial infection is unlikely to benefit the patient and increases the risk of the development of drug-resistant bacteria.

Information for Patients

Patients should be advised:

• to contact their healthcare provider if they experience pain, swelling, or inflammation of a tendon, or weakness or inability to use one of their joints; rest and refrain from exercise; and discontinue Proquin XR treatment. The risk of severe tendon disorders with fluoroquinolones is higher in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants.
• that antibacterial drugs, including Proquin XR, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Proquin XR is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Proquin XR or other antibacterial drugs in the future.
• that Proquin XR should only be used to treat uncomplicated urinary tract infections (also known as bladder infections). The safety and efficacy of Proquin XR to treat other urinary tract or non-urinary tract infections have not been studied.
• that Proquin XR should be taken with a main meal of the day, preferably the evening meal. The patient should not take more than one Proquin XR tablet per day, even if the patient misses a dose.
• that Proquin XR tablets should be taken whole and never split, crushed, or chewed.
• that concomitant administration of Proquin XR with aluminum or magnesium-containing antacids, sucralfate, VIDEX® (didanosine) chewable buffered tablets or pediatric powder, metal cations such as iron and calcium, and multivitamin preparations containing zinc should be avoided. Proquin XR should be administered at least 4 hours before or 2 hours after these products. (See CLINICAL PHARMACOLOGY: Drug Interactions, DOSAGE AND ADMINISTRATION, and PRECAUTIONS: Drug Interactions)
• that Proquin XR should not be taken with dairy products (like milk or yogurt) or calcium-fortified juices alone, since the absorption of ciprofloxacin may be significantly reduced. However, Proquin XR may be taken with a meal that contains these products. (See CLINICAL PHARMACOLOGY: Drug Interactions and PRECAUTIONS: Drug Interactions)
• that ciprofloxacin may be associated with hypersensitivity reactions, even following a single dose, and to discontinue Proquin XR at the first sign of a skin rash or other allergic reaction and contact their physician.
• that photosensitivity/ phototoxicity has been reported in patients receiving quinolone antibiotics. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while taking quinolones. If patients need to be outdoors while using quinolones, they should wear loose-fitting clothes that protect the skin from sun exposure and discuss other sun protection measures with their physician. If a sunburn-like reaction or skin eruption occurs, patients should contact their physician;
• that peripheral neuropathies have been associated with ciprofloxacin use. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness and/or weakness develop, patients should discontinue treatment and contact their physician.
• to contact their doctor if they do not feel better or if they develop fever and back pain while or after taking Proquin XR.
• that Proquin XR may cause dizziness and lightheadedness; therefore, patients should know how they react to this drug before they operate an automobile or machinery or engage in activities requiring mental alertness or coordination.
• that Proquin XR may increase the effects of theophylline and caffeine. There is a possibility of caffeine accumulation when products containing caffeine are consumed while taking quinolones.
• that convulsions have been reported in patients receiving quinolones, including ciprofloxacin, and to notify their physician before taking this drug if there is a history of this condition.
• that diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Drug Interactions

Caffeine: Some quinolones, including ciprofloxacin, have also been shown to interfere with the metabolism of caffeine. This may lead to reduced clearance of caffeine and a prolongation of its serum half-life.

Cyclosporine: Some quinolones, including ciprofloxacin, have been associated with transient elevations in serum creatinine in patients receiving cyclosporine concomitantly.

Glyburide: The concomitant administration of ciprofloxacin with the sulfonylurea glyburide has, on rare occasions, resulted in severe hypoglycemia.

Histamine H2-receptor antagonists: Histamine H2-receptor antagonists appear to have no significant effect on the bioavailability of ciprofloxacin.

Methotrexate: Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin, potentially leading to increased plasma levels of methotrexate. This might increase the risk of methotrexate toxic reactions. Therefore, patients under methotrexate therapy should be carefully monitored when concomitant ciprofloxacin therapy is indicated.

Multivalent cation-containing products: Concurrent administration of a quinolone, including ciprofloxacin, with multivalent cation-containing products such as magnesium or aluminum antacids, sucralfate, VIDEX® chewable/buffered tablets or pediatric powder, or products containing calcium, iron, or zinc may substantially decrease the absorption of ciprofloxacin, resulting in serum and urine levels considerably lower than desired. Proquin XR should be administered at least 4 hours before or 2 hours after these products. This time window is different than for other oral formulations of ciprofloxacin, which are usually administered 2 hours before or 6 hours after antacids. (See CLINICAL PHARMACOLOGY: Drug Interactions, PRECAUTIONS: Information for Patients, and DOSAGE AND ADMINISTRATION)

Non-steroidal anti-inflammatory drugs (but not aspirin): These drugs in combination with very high doses of quinolones have been shown to provoke convulsions in pre-clinical studies.

Omeprazole: The rate and extent of absorption of ciprofloxacin was bioequivalent when Proquin XR was given alone or when Proquin XR was given 2 hours after omeprazole at the dose that maximally suppresses gastric acid secretion. Omeprazole should be taken as directed and Proquin XR should be taken with a main meal of the day, preferably the evening meal. (See CLINICAL PHARMACOLOGY: Drug Interactions and Information for Patients).

Phenytoin: Altered serum levels of phenytoin (increased and decreased) have been reported in patients receiving concomitant ciprofloxacin.

Probenecid: Probenecid interferes with renal tubular secretion of ciprofloxacin and produces an increase in the level of ciprofloxacin in serum.

Theophylline: As with some other quinolones, concurrent administration of ciprofloxacin with theophylline may lead to elevated serum concentrations of theophylline and prolongation of its elimination half-life. This may result in increased risk of theophylline-related adverse reactions. (See WARNINGS) If concomitant use cannot be avoided, serum levels of theophylline should be monitored and dosage adjustments made as appropriate.

Warfarin: Quinolones have been reported to enhance the effects of the oral anticoagulant warfarin or its derivatives. When these products are administered concomitantly, prothrombin time or other suitable coagulation tests should be monitored.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Rodent carcinogenicity studies were not required. Two in vitro mutagenicity tests were conducted with ciprofloxacin:

• Bacterial Reverse Mutation Assay; negative for mutagenicity in the presence and absence of an S-9 metabolic activation system.
• Chinese Hamster Ovary (CHO) Chromosomal Aberration Assay; positive for inducing chromosomal aberrations.

In addition to the in vitro genotoxicity assays, an in vivo rat micronucleus study with ciprofloxacin was negative.

Fertility studies performed with male and female rats at oral doses of ciprofloxacin up to 600 mg/kg/day (approximately 10-fold the recommended 500 mg therapeutic dose based upon body surface area) revealed no evidence of impairment.

Pregnancy: Teratogenic Effects. Pregnancy Category C

There are no adequate and well-controlled studies of Proquin XR in pregnant women. An expert review of published data on experiences with ciprofloxacin use during pregnancy by TERIS - the Teratogen Information System - concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (quantity and quality of data = fair), but the data are insufficient to state that there is no risk.

A controlled prospective observational study followed 200 women exposed to fluoroquinolones (52.5% exposed to ciprofloxacin and 68% first trimester exposures) during gestation. In utero exposure to fluoroquinolones during embryogenesis was not associated with increased risk of major malformations. The reported rates of major congenital malformations were 2.2% for the fluoroquinolone group and 2.6% for the control group (background incidence of major malformations is 1-5%). Rates of spontaneous abortions, prematurity and low birth weight did not differ between the groups and there were no clinically significant musculoskeletal dysfunctions up to one year of age in the ciprofloxacin exposed children.

Another prospective follow up study reported on 549 pregnancies with fluoroquinolone exposure (93% first trimester exposures). There were 70 ciprofloxacin exposures, all within the first trimester. The malformation rates among live-born babies exposed to ciprofloxacin and to fluoroquinolones overall were both within background incidence ranges. No specific patterns of congenital abnormalities were found. The study did not reveal any clear adverse reactions due to in utero exposure to ciprofloxacin.

No differences in the rates of prematurity, spontaneous abortions, or birth weight were seen in women exposed to ciprofloxacin during pregnancy. However, these small postmarketing epidemiology studies, of which most experience is from short term first semester exposure, are insufficient to evaluate the risk for less common defects or to permit reliable and definitive conclusions regarding the safety of ciprofloxacin in pregnant women and their developing fetuses. Ciprofloxacin should not be used during pregnancy unless the potential benefit justifies the potential risk to both fetus and mother (see WARNINGS).

Embryo/fetal developmental toxicity studies were conducted in pregnant rats and rabbits using oral doses up to 600 mg/kg/day in rats and 30 mg/kg/day in rabbits. Fetal development (skeletal variation) was affected in rats at the maternally toxic dose of 600 mg/kg/day (approximately 1.8-fold the recommended 500 mg therapeutic dose based upon plasma AUC measure of systemic exposure). The maternally toxic 30 mg/kg/day dose to pregnant rabbits resulted in abortions and body weight gain depression; embryo/fetal lethality and skeletal developmental effects were observed at this dose level (approximately 1.2-fold the recommended therapeutic dose based upon body surface area). The 10 mg/kg/day dose level, although maternally toxic, did not induce embryo/fetal developmental effects. A peri/postnatal developmental toxicity study with pregnant/lactating female rats exhibited no developmental effects to the F1 pups at the highest dose level of 600 mg/kg/day; the 300 and 600 mg/kg/day dose levels were maternally toxic to the pregnant dams based upon slight body weight gain reduction. No evidence of compound-related fetal malformation was observed in any of the reproductive toxicity studies.

Nursing Mothers

Ciprofloxacin is excreted in human milk. The amount of ciprofloxacin absorbed by the nursing infant is unknown. Because of the potential for serious adverse reactions in infants nursing from mothers taking ciprofloxacin, a decision should be made whether to discontinue nursing or to discontinue ciprofloxacin taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of Proquin XR in pediatric patients and adolescents less than 18 years of age have not been established. Quinolones, including ciprofloxacin, cause arthropathy in juvenile animals. (See WARNINGS)

Geriatric Use

Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as Proquin XR. 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 Proquin XR to elderly patients especially those on corticosteroids. Patients should be informed of this potential side effect and advised to discontinue Proquin XR and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur (See Boxed Warning, WARNINGS, and ADVERSE REACTIONS/ Post-Marketing Adverse Event Reports).

Clinical experience with Proquin XR did not include sufficient number of subjects 65 years of age or older to determine whether they respond differently than younger subjects. Reported clinical experience with other formulations of ciprofloxacin has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals on any drug therapy cannot be ruled out. Ciprofloxacin is substantially excreted by the kidney and the risk of adverse reactions may be greater in patients with impaired renal function. No alteration of dosage is necessary for patients greater than 65 years of age with normal renal function. (See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION)

In general, elderly patients may be more susceptible to drug-associated effects on the QT interval. Therefore, precaution should be taken when using Proquin XR with concomitant drugs that can result in prolongation of the QT interval (e.g. class IA or class III antiarrhythmics) or in patients with risk factors for torsades de pointes (e.g., known QT prolongation, uncorrected hypokalemia).

Proquin XR and other oral formulations of ciprofloxacin are not interchangeable. Proquin XR should be administered orally once daily for 3 days with a main meal of the day, preferably the evening meal. Proquin XR should be administered at least 4 hours before or 2 hours after antacids containing magnesium or aluminum, sucralfate, VIDEX® (didanosine) chewable/buffered tablets or pediatric powder, metal cations such as iron, and multivitamin preparations containing zinc.

Proquin XR tablets should be taken whole and never split, crushed, or chewed. (See CLINICAL PHARMACOLOGY: Drug Interactions)

Impaired Renal Function:

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 alternate pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. No dosage adjustment is required for patient with uUTI and mild to moderate renal impairment. The efficacy of Proquin XR has not been studied in patients with severe renal impairment. (See CLINICAL PHARMACOLOGY: Special Populations and PRECAUTIONS: Geriatric Use)

Impaired Liver Function:

No dosage adjustment is required with Proquin XR in patients with stable chronic cirrhosis. However, the pharmacokinetics of ciprofloxacin in patients with acute hepatic insufficiency have not been fully elucidated. (See CLINICAL PHARMACOLOGY: Special Populations)

You should not use Proquin XR if you are also taking tizanidine.

You may not be able to use Proquin XR if you have a muscle disorder. Tell your doctor if you have a history of myasthenia gravis.

Proquin XR may cause swelling or tearing of a tendon (the fiber that connects bones to muscles in the body), especially in the Achilles' tendon of the heel. This effect may be more likely to occur if you are over 60, if you use steroid medication, or if you have had a kidney, heart, or lung transplant.

Call your doctor at once if you have sudden pain, swelling, bruising, tenderness, stiffness, or movement problems in any of your joints. Rest the joint until you receive medical care or instructions.

Proquin XR is usually taken every 12 hours. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take Proquin XR with water, and drink extra fluids to keep your kidneys working properly.

Proquin XR may be taken with or without food, but take it at the same time each day.

Do not crush, chew, or break an extended-release Proquin XR tablet. Swallow the tablet whole.

Use this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Ciprofloxacin will not treat a viral infection such as the flu or a common cold.

Do not share Proquin XR with another person, even if they have the same symptoms you have.

Store at room temperature away from moisture and heat. Do not allow the liquid medicine to freeze. Throw away any unused liquid after 14 days.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Get emergency medical help if you have signs of an allergic reaction to Proquin XR: hives, or the first sign of a skin rash; fast heartbeat, difficult breathing; swelling of your face, lips, tongue, or throat.

Ciprofloxacin may cause swelling or tearing of (rupture) a tendon. Ciprofloxacin can also have serious effects on your nerves, and may cause permanent nerve damage. Stop using Proquin XR and call your doctor at once if you have:

• signs of tendon rupture - sudden pain, swelling, bruising, tenderness, stiffness, movement problems, or a snapping or popping sound in any of your joints (rest the joint until you receive medical care or instructions); or

• nerve symptoms - numbness, tingling, burning pain, or being more sensitive to temperature, light touch, or the sense of your body position.

Also, stop using Proquin XR and call your doctor at once if you have:

• severe stomach pain, diarrhea that is watery or bloody;

• a headache with chest pain and severe dizziness and fast or pounding heartbeats;

• the first sign of any skin rash, no matter how mild;

• confusion, hallucinations, nightmares, paranoia, depression, thoughts about hurting yourself;

• muscle weakness or trouble breathing;

• ongoing headaches (sometimes with blurred vision);

• tremors, anxiety, trouble sleeping, feeling restless or nervous;

• a light-headed feeling, like you might pass out;

• increased pressure inside the skull - severe headaches, ringing in your ears, dizziness, vision problems, pain behind your eyes;

• liver problems - nausea, vomiting, loss of appetite, upper stomach pain, itching, fever, tiredness, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

• severe skin reaction - fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common Proquin XR side effects may include:

• nausea, vomiting, diarrhea;

• rash; or

• abnormal liver function tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Applies to ciprofloxacin: intravenous solution, oral powder for reconstitution, oral tablet, oral tablet extended release

General

The most common side effects (from clinical trials of all formulations, doses, durations of therapy, and indications) were nausea, diarrhea, abnormal liver function tests, vomiting, and rash. The most common side effects reported with the IV formulation were nausea, diarrhea, vomiting, injection and infusion site reactions, rash, and increased transaminases (transient).[Ref]

Gastrointestinal

Antibiotic-associated colitis with possible fatal outcome was reported very rarely.

The onset of pseudomembranous colitis symptoms has been reported during or after antimicrobial treatment.[Ref]

Common (1% to 10%): Nausea, diarrhea, vomiting, dyspepsia
Uncommon (0.1% to 1%): Abdominal pains/discomfort, gastrointestinal (GI) pains, flatulence
Rare (0.01% to 0.1%): Elevated amylase, antibiotic-associated colitis, pancreatitis
Frequency not reported: Clostridium difficile-associated diarrhea, constipation, GI bleeding, ileus, intestinal perforation, dry mouth, oral ulceration, epigastric pain, dysphagia, elevated lipase, painful oral mucosa, heartburn, acid reflux, aggravated irritable bowel syndrome, lower abdominal pain
Postmarketing reports: GI candidiasis, oral candidiasis, pseudomembranous colitis[Ref]

Dermatologic

Photosensitivity was seen most often when patients were exposed to intense sun (e.g., as when used to treat or prevent travelers' diarrhea).

A 27-year-old woman with mild systemic erythematosus developed toxic epidermal necrolysis (TEN) after starting a second oral course of this drug after a prior 5-day course. She developed a rash, high fever, and diarrhea after taking the 2nd dose and presented with diffuse rash, epidermal sloughing of 60% of the skin, desquamation of the lips, shock, and respiratory distress. She died on the 28th hospital day of TEN, right ventricular failure, and acute respiratory distress syndrome. As of 2003, 9 cases of TEN, including 5 fatalities, had been reported in the literature.

Erythema nodosum, Stevens-Johnson syndrome (potentially life-threatening), and TEN (potentially life-threatening) have also been reported during postmarketing experience.[Ref]

Common (1% to 10%): Rash
Uncommon (0.1% to 1%): Pruritus, urticaria
Rare (0.01% to 0.1%): Angioedema, photosensitivity reactions, sweating/hyperhidrosis, petechiae, blistering
Very rare (less than 0.01%): Erythema multiforme, erythema nodosum, Stevens-Johnson syndrome (potentially life-threatening), toxic epidermal necrolysis (potentially life-threatening)
Frequency not reported: Exfoliative dermatitis, purpura, burning, phototoxicity reaction, dry skin, maculopapular rash, skin disorder, vesiculobullous rash, erythema, hyperpigmentation, cutaneous candidiasis, bullous pemphigoid, vesicles, lobular panniculitis, photoinduced acute exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS)
Postmarketing reports: Acute generalized exanthematous pustulosis, fixed eruption[Ref]

Nervous system

Seizures have been reported in 2 patients given this drug and foscarnet. The temporal association between the onset of seizures and drug administration suggests a possible drug interaction; causal relationship was not established in either case. Both drugs are individually epileptogenic; concurrent use may potentiate risk of seizures.

Cases of sensory or sensorimotor axonal polyneuropathy (affecting small and/or large axons) resulting in paresthesias, hypoesthesias, dysesthesias, and weakness have been reported.

One survey reported 11 cases of peripheral neuropathy associated with this drug. The severity ranged from mild and reversible to severe and persistent. In 1 case, a 44-year-old female developed numbness, allodynia, hypoesthesia, tremors, electrical and diffuse burning sensations, twitching, disorientation, visual impairment, nausea, temperature intolerance, rash, and palpitations; she remained disabled after 29 months.

Nystagmus, anosmia, hyperesthesia, hypoesthesia, hypertonia, intracranial hypertension, and exacerbation of myasthenia gravis have also been reported during postmarketing experience.[Ref]

Common (1% to 10%): Headache, dizziness/lightheadedness, central nervous system disturbance
Uncommon (0.1% to 1%): Sleep disorders, taste disorders, seizures (including status epilepticus), dysesthesia, paresthesia, vertigo, hearing loss
Rare (0.01% to 0.1%): Syncope, hypoesthesia, tremor, tinnitus, migraine, olfactory nerve disorders, smell disorders, hearing impaired
Very rare (less than 0.01%): Disturbed coordination, intracranial hypertension, benign intracranial hypertension/pseudotumor cerebri, exacerbation of myasthenia gravis, hyperesthesia
Frequency not reported: Unresponsiveness, ataxia, hypertonia, anosmia, nystagmus, taste perversion/bad taste, somnolence/drowsiness, incoordination, disturbance in attention, dyskinesia, myasthenia gravis, paresis, aseptic meningitis, cerebral thrombosis, grand mal convulsion, dysphasia, lethargy, sensory axonal polyneuropathy, sensorimotor axonal polyneuropathy
Postmarketing reports: Taste loss, peripheral neuropathy (may be irreversible), polyneuropathy[Ref]

Hematologic

Pancytopenia (life-threatening or fatal outcome) and bone marrow depression (life-threatening) were reported very rarely; also reported during postmarketing experience.

Increased INR was reported in patients treated with vitamin K antagonists.[Ref]

Common (1% to 10%): Eosinophilia
Uncommon (0.1% to 1%): Thrombocytopenia, thrombocythemia
Rare (0.01% to 0.1%): Leukopenia, anemia, neutropenia, leukocytosis, pancytopenia, bone marrow depression, abnormal prothrombin level
Very rare (less than 0.01%): Hemolytic anemia, agranulocytosis
Frequency not reported: Decreased hematocrit, decreased platelet counts, increased platelet counts, prolonged prothrombin time, decreased prothrombin, bleeding diathesis, decreased hemoglobin, decreased leukocyte count, increased atypical lymphocyte count, immature WBCs, increased blood monocytes, elevated sedimentation rate, elevated eosinophil counts, lymphadenopathy
Postmarketing reports: Methemoglobinemia, increased INR, prothrombin time prolonged or decreased[Ref]

Hepatic

Liver necrosis very rarely progressed to life-threatening hepatic failure. Liver necrosis and hepatic failure (including fatal cases) have also been reported during postmarketing experience.[Ref]

Common (1% to 10%): Abnormal liver function tests, increased transaminases
Uncommon (0.1% to 1%): Elevated bilirubin, hepatic impairment, cholestatic icterus/cholestatic jaundice, jaundice
Rare (0.01% to 0.1%): Hepatitis, liver necrosis
Very rare (less than 0.01%): Hepatic failure
Frequency not reported: Elevated AST, elevated ALT, elevated GGT[Ref]

Psychiatric

Common (1% to 10%): Restlessness
Uncommon (0.1% to 1%): Psychomotor hyperactivity/agitation, confusion, disorientation, hallucinations
Rare (0.01% to 0.1%): Anxiety reaction, abnormal dreams, depression, psychotic reactions
Frequency not reported: Depersonalization, insomnia, manic reaction, nightmares, paranoia, phobia, toxic psychosis, nervousness, self-injurious behavior, suicidal ideations/thoughts, attempted suicide, completed suicide, catatonia, mania (including hypomania)
Postmarketing reports: Delirium[Ref]

Depression and psychotic reactions (both potentially culminating in self-injurious behavior such as suicidal ideations/thoughts and attempted or completed suicide) have been reported.

Agitation, confusion, and toxic psychosis have also been reported during postmarketing experience.[Ref]

Genitourinary

Crystalluria has been reported in patients with alkaline urine and did not necessarily lead to nephrotoxicity. At physiological urinary pH, the risk of crystalluria was considered minor.

Vaginal candidiasis has also been reported during postmarketing experience.[Ref]

Common (1% to 10%): Vaginal candidiasis
Rare (0.01% to 0.1%): Hematuria, crystalluria
Frequency not reported: Albuminuria, cylindruria, frequent urination, hemorrhagic cystitis, vaginitis, dysmenorrhea, candiduria, polyuria, urethral bleeding, urinary retention, urinary tract infection, fungal vaginosis, bacterial vaginitis, dysuria, abnormal urine odor, female genital pruritus, vaginal infection, urinary frequency, micturition urgency, vaginal pruritus[Ref]

Local

Local IV site reactions occurred more often if the infusion time was 30 minutes or less. These reactions have appeared as local skin reactions and resolved quickly when infusion was completed.

Injection site irritation and induration have been reported with IV infusion time 30 minutes or less (instead of the recommended 1 hour) or when a small vein in the back of the hand was used.[Ref]

Common (1% to 10%): Local IV site reactions, injection and infusion site reactions (e.g., phlebitis, thrombophlebitis)
Frequency not reported: Injection site irritation and induration with IV infusion[Ref]

Musculoskeletal

Uncommon (0.1% to 1%): Musculoskeletal pain (e.g., extremity pain, back pain, chest pain), arthralgia
Rare (0.01% to 0.1%): Myalgia, arthritis, increased muscle tone and cramping, tendon rupture (mainly Achilles tendon)
Very rare (less than 0.01%): Tendinitis, muscular weakness
Frequency not reported: Arthropathy (including suspected reversible cases), joint stiffness, elevated serum creatine phosphokinase, abnormal joint exam, joint sprains, arthrosis, bone pain, decreased range of motion in a joint (knee, elbow, ankle, hip, wrist, shoulder), jaw pain, neck pain, gout flare-up, joint swelling, muscle spasms, night cramps, knee inflammation
Postmarketing reports: Myoclonus, myasthenia, twitching[Ref]

Arthropathy has primarily been a concern in pediatric patients; however, at least 1 case was described in an adult cystic fibrosis patient receiving this drug. Although cystic fibrosis arthropathy and hypertrophic pulmonary osteoarthropathy typically occur in 7% to 8% of cystic fibrosis adults and adolescents, the arthropathy exhibited in this patient did not resemble either. Several elements in its presentation strongly supported the diagnosis of ciprofloxacin-induced arthropathy, such as: a consistent time of onset with other reported cases of suspected quinolone-induced arthropathy (usually 3 weeks after starting therapy); a lack of history of arthralgia in the patient; reoccurrence upon rechallenge; and resolution of symptoms upon discontinuation of therapy (usually 2 weeks after therapy stopped).

Tendinitis with subsequent tendon rupture has been documented in numerous case reports. One patient with chronic renal failure developed bilateral Achilles tendon rupture after 4 days of ciprofloxacin therapy. Although renal transplant patients and those with end-stage renal disease tend to have an increased risk of Achilles tendinitis and rupture over the general population, quinolone use has been shown to further increase that risk (12% in quinolone-treated patients versus 7% in nonquinolone-treated patients).

As of October 1994, 25 cases of Achilles tendon rupture had been reported to the US FDA. Some ruptures have also occurred in the hand or shoulder. Other risk factors identified included age and corticosteroid use.

There had been 23 reports of tendinitis submitted to the Australian Adverse Drug Reactions Committee (ADRAC) between 2006 and 2008, including reports of Achilles tendinitis, tendon rupture, and tendon pain and swelling. The reports were primarily in male patients (15 cases) older than 56 years who used this drug for 2 to 14 days. In 19 of the reported cases, a fluoroquinolone (generally ciprofloxacin) was the primary suspect; however, details of concomitant serious medical conditions were not documented in most of the reports.

Musculoskeletal side effects reported in pediatric patients included arthralgia, abnormal gait, abnormal joint exam, joint sprains, leg pain, back pain, arthrosis, bone pain, pain, myalgia, arm pain, and decreased range of motion in a joint (knee, elbow, ankle, hip, wrist, shoulder).

Myalgia, tendinitis, and tendon rupture have also been reported during postmarketing experience.[Ref]

Cardiovascular

Uncommon (0.1% to 1%): Tachycardia, vasodilatation, hypotension
Rare (0.01% to 0.1%): Vasculitis
Frequency not reported: Angina pectoris, cardiopulmonary arrest, myocardial infarction, hypertension, palpitation, bradycardia, arrhythmia, atrial flutter, cardiac murmur, cardiovascular collapse, ventricular ectopy, ventricular bigeminy, abdominal aortic bruit, postural hypotension
Postmarketing reports: QT prolongation/ECG QT prolonged, torsade de pointes, ventricular arrhythmia[Ref]

Torsade de pointes was reported mainly in patients with risk factors for QT prolongation.

Vasculitis has also been reported during postmarketing experience.[Ref]

Other

Elevated serum theophylline has been reported in patients receiving theophylline concomitantly.

Gait disturbance and elevated serum potassium have also been reported during postmarketing experience.[Ref]

Uncommon (0.1% to 1%): Candida infections, mycotic superinfections, pain, fever, malaise/feeling unwell, asthenia, edema
Very rare (less than 0.01%): Gait disturbance/abnormal gait
Frequency not reported: Irritability, flushing, thirst, elevated serum calcium, elevated serum potassium, elevated triglycerides, decreased serum albumin, decreased serum potassium, decreased total serum protein, elevated serum theophylline, serum phenytoin altered, chills, swelling, breast pain, achiness, weakness, fatigue, suprapubic pain, rigors, tenderness, fungal infection, increased body temperature
Postmarketing reports: Elevated serum cholesterol[Ref]

Metabolic

Quinolone class antibiotics have been associated with symptomatic hypoglycemia.[Ref]

Uncommon (0.1% to 1%): Elevated blood alkaline phosphatase, decreased appetite/anorexia, decreased food intake
Rare (0.01% to 0.1%): Hyperglycemia, hypoglycemia
Frequency not reported: Elevated LDH, elevated uric acid, elevated blood glucose, decreased uric acid, decreased blood glucose, acidosis, symptomatic hypoglycemia[Ref]

Renal

Uncommon (0.1% to 1%): Renal impairment, renal failure
Rare (0.01% to 0.1%): Tubulointerstitial nephritis
Frequency not reported: Elevated serum creatinine, renal calculi, elevated BUN, decreased BUN, abnormal kidney function, allergic interstitial nephritis, nephritis, myoglobin-associated acute kidney injury/failure[Ref]

Allergic interstitial nephritis resulting in nonoliguric renal failure has been described in numerous case reports. Several cases included symptoms of rash, fever, and arthralgia and were accompanied by eosinophilia and eosinophiluria. Cases of allergic interstitial nephritis often responded to short courses of corticosteroid therapy.[Ref]

Ocular

Uncommon (0.1% to 1%): Visual disturbances (e.g., chromatopsia, diplopia, photopsia)
Very rare (less than 0.01%): Visual color distortions
Frequency not reported: Decreased visual acuity, blurred vision, cataracts, multiple punctate lenticular opacities, eye pain[Ref]

Quinolone class antibiotics have been associated with cataracts and multiple punctate lenticular opacities.[Ref]

Hypersensitivity

Rare (0.01% to 0.1%): Allergic reactions, anaphylactic shock (life-threatening), allergic edema
Very rare (less than 0.01%): Anaphylactic reaction, serum sickness-like reaction
Frequency not reported: Anaphylactoid reactions, necrotizing vasculitis, cutaneous vasculitis[Ref]

Allergic reactions ranged from urticaria to anaphylactic reactions, including life-threatening anaphylactic shock.

At least 2 cases have been reported of patients developing a cutaneous vasculitis related to use of this drug. The vasculitis resolved without medical intervention after the drug was discontinued.

Serum sickness-like reaction and anaphylactic shock (life-threatening) have also been reported during postmarketing experience.[Ref]

Respiratory

Rare (0.01% to 0.1%): Dyspnea (including asthmatic condition)
Frequency not reported: Bronchospasm, hemoptysis, laryngeal edema, respiratory arrest, epistaxis, hiccough, pulmonary edema, pleural effusion, pulmonary embolism, respiratory distress, wheeze, cough, upper respiratory tract infection, pharyngitis, nasopharyngitis[Ref]

Endocrine

Frequency not reported: Gynecomastia[Ref]

Immunologic

Frequency not reported: Jarisch-Herxheimer reaction[Ref]

Oral ciprofloxacin has been associated with a case of Jarisch-Herxheimer reaction (characterized by hypotension, tachycardia, and disseminated intravascular coagulation) in a 14-year-old female with tickborne relapsing fever.[Ref]

Some side effects of Proquin XR may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.