Approved on.
Date of revision.
Norfloxacin Tablets Instructions
Please read the instructions carefully and use under the guidance of your physician
WARNING: Serious adverse reactions, including tendonitis and tendon rupture, peripheral neuropathy, central nervous system effects, and exacerbation of myasthenia gravis.
With fluoroquinolones (including norfloxacin tablets), both disabling and potentially irreversible serious adverse reactions (see [Precautions]), including:
Tendonitis and tendon rupture (see [Precautions])
Peripheral neuropathy (see [Precautions])
Central nervous system effects (see [Precautions])
When these serious adverse reactions occur (see [Precautions]), discontinue Norfloxacin tablets immediately and avoid fluoroquinolones.
Fluoroquinolone drugs may exacerbate symptoms of muscle weakness in patients with myasthenia gravis. Norfloxacin tablets should be avoided in patients with a known history of myasthenia gravis (see [Precautions]).
Serious adverse reactions have been reported with fluoroquinolones (including norfloxacin tablets) (see [Precautions]), norfloxacin tablets should be used only in the absence of other drug therapy for patients with the following indications:
Simple urinary tract infection (see [Indications] and [Dosage])Simple urinary tract infection (see [Indications] and [Dosage])[Drug Name]
Generic name: Norfloxacin Tablets
English name: Norfloxacin Tablets
Hanyu Pinyin: NuofushaxingPian
The main ingredient of this product is Norfloxacin.
Chemical name: 1-Ethyl-6- Fluorine-1,,4-dihydro-4-oxo-7-(1-Piperazine base)-3-quinolinecarboxylic acid.
Chemical structure formula.
Molecular Formula: C16H18FN3O3
Molecular weight: 319.24
[Properties]
This product is a film-coated tablet, which appears off-white to light yellow after removing the coating.
[Indications
It is indicated for urinary tract infections, gonorrhea, prostatitis, intestinal infections and typhoid and other Salmonella infections caused by sensitive bacteria. Because serious adverse reactions have been reported with fluoroquinolones, including norfloxacin tablets, and because for some patients, simple urinary tract infections are self-limiting, norfloxacin tablets should be used only in the absence of other drug therapy.
[Specifications]0.1g
[Dosage].
To be taken orally with 250 ml of water. should be taken at least 1 hour before or at least 2 hours after eating a meal or consuming milk and/or other dairy products.
Acute simple lower urinary tract infection due to Escherichia coli, Klebsiella pneumoniae, and Acinetobacter chimaera, 400 mg (4 tablets) twice a day for 3 days.
Simple urinary tract infections due to other pathogens at the same dose as above for 7 to 10 days.
Complex urinary tract infections at the same dose as above for 10 to 21 days.
Simple gonococcal urethritis single dose of 800 (8 tablets).
Acute and chronic prostatitis, 400 mg (4 tablets) twice a day for 28 days.
For intestinal infections, 300-400mg (3-4 tablets) twice a day for 5 to 7 days.
Salmonella typhi infection, 800-1200 mg (8-12 tablets) twice or three times a day for 14-21 days.
[Adverse effects
Serious and other important adverse reactions
Disabling and potentially irreversible serious adverse reactions. including tendonitis and tendon rupture, peripheral neuropathy, central nervous system effects
Tendinopathy and tendon rupture
QTProlonged interval
Allergic reaction
Other severe and sometimes fatal reactions
Central nervous system effects
Clostridium difficile-associated diarrhea
Peripheral neuropathy
Interference with blood glucose
Light sensitivity/Phototoxicity
The above adverse reactions are described in detail under [Precautions].
Cardiovascular system:Prolonged QT interval, tip-twist ventricular tachycardia, ventricular arrhythmias
Central nervous system: convulsions, ataxia, toxic psychosis, tremor, agitation, anxiety, dizziness, headache, drowsiness, confusion, hallucinations, delusions, depression, nightmares, insomnia, seizures, rare cases can lead to suicidal thoughts or actions
Peripheral neuropathy: sensory confusion, dullness, painful sensation to touch, pain, burning, tingling, numbness, weakness, or abnormalities in light touch, pain, temperature, position and vibration sensation, polyneuritis
Skeletal Muscular System: arthralgia, myalgia, muscle weakness, hypertonic tendonitis, tendon rupture, worsening of myasthenia gravis, creatine kinase (CK) elevation, muscle spasm
Hypersensitivity reactions: urticaria, pruritus, and other severe skin reactions (e.g., toxic epidermal necrolysis relaxation[Lyellsyndrome], cutaneous mucocutaneous eye syndrome[Stevens-Jonhnson syndrome], erythema multiforme, exfoliative dermatitis, drug reaction with eosinophilia and systemic symptoms[DRESS syndrome ]), dyspnea, angioneurotic edema (including edema of the tongue, throat, pharynx, or face/swelling), cardiovascular deficit, hypotension, loss of consciousness, airway obstruction (including bronchospasm, shortness of breath, and acute respiratory distress), allergic pneumonia, anaphylaxis
Digestive tract: pseudomembranous colitis, abdominal discomfort or pain, diarrhea, nausea, vomiting, loss of appetite, indigestion, bloating, constipation, stomatitis, labyrinthitis, stomatitis, pancreatitis
Hepatobiliary system: hepatitis, jaundice, acute hepatic necrosis or liver failure
Urologic: acute renal insufficiency or renal failure, interstitial nephritis, crystalluria (mostly seen with high dose application)
Hematologic: anemia, including hemolytic anemia and aplastic anemia, thrombocytopenia, including thrombotic thrombocytopenic purpura, leukopenia, granulocytopenia, eosinophilia, pancytopenia, and/or other blood disorders
Other: fatigue, chills, fever, vasculitis, serum sickness, Clostridium difficile-associated diarrhea, dysglycemia, photosensitivity// =”font-family:equine”>phototoxicity, palpitations, chest pain, hearing loss, tinnitus, diplopia, taste disturbance
[Contraindications
It is contraindicated in patients with hypersensitivity to this product and fluoroquinolones.
It is contraindicated in patients whose use of this product or fluoroquinolones has caused tendonitis or tendon rupture.
[Precautions].
1.Disabling and potentially irreversible serious adverse reactions, including tendonitis and tendon rupture, peripheral neuropathy, and central nervous system effects
Disabling and potentially irreversible serious adverse reactions have been reported with fluoroquinolones in different organ systems of the body in the same patient at the same time, often including: tendonitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and Central nervous system reactions (hallucinations, anxiety, depression, insomnia, severe headaches and confusion). These adverse reactions can occur hours to weeks after the use of norfloxacin tablets. These adverse reactions have been reported in patients of any age with no prior associated risk factors.
2.Tendinopathy and tendon rupture
Fluoroquinolones, which increase the risk of tendinopathy and tendon rupture in patients of all ages. This adverse reaction most often occurs in the Achilles tendon, which may require surgical repair for rupture. Tendonitis and tendon rupture have also been reported in the shoulder, hand, biceps, thumb, and other tendon points. Tendonitis and tendon rupture can occur hours or days after starting norfloxacin tablets, or months after finishing treatment. Tendonitis and tendon rupture can occur bilaterally. This risk is further increased in older patients over 60 years of age, in patients taking corticosteroid medications and in patients undergoing kidney, heart or lung transplantation. In addition to age and corticosteroid use, other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disease, such as rheumatoid arthritis. Tendonitis and tendon rupture also occur in patients using fluoroquinolones without these risk factors. Tendon ruptures can occur during or after the end of treatment; they have also been reported several months after the end of treatment. This product should be discontinued after a patient develops tendon pain, swelling, inflammation, or rupture. After signs of tendonitis or tendon rupture, patients should be advised to rest and contact their physician to switch to a non-quinolone drug. Patients with a history of tendon disease or who have experienced tendonitis and tendon rupture should avoid fluoroquinolone medications.
3.Exacerbation of myasthenia gravis
Fluoroquinolones, which have neuromuscular blocking activity, may exacerbate symptoms of myasthenia gravis in patients with myasthenia gravis. Postmarketing serious adverse events, including death and the need for ventilatory support, and patients with myasthenia gravis have been associated with the use of fluoroquinolones. Norfloxacin tablets should be avoided in patients with myasthenia gravis.
4. Prolonged QT interval
Some fluoroquinolones can prolong the ECG’sQTinterval is prolonged, and a few patients can develop arrhythmias. Spontaneous reports of tip-twist ventricular tachycardia in patients treated with fluoroquinolones during postmarketing surveillance are rare. Patients with knownprolonged QTintervals, patients with uncorrected hypokalemia, and patients onIAclass (quinidine, procainamide) and class III (amiodarone, sotalol) antiarrhythmic drugs should be avoided in patients with norfloxacin tablets. Elderly patients are more susceptible to drug-relatedQTintervals.
5.Allergic reactions
Severe allergic reactions have been reported with the use of fluoroquinolones. Some patients experience them after the first dose, and some reactions may be accompanied by cardiovascular system failure, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and pruritus. Severe allergic reactions require emergency treatment with epinephrine. Norfloxacin tablets should be discontinued at the first sign of rash or any other signs of allergy. Oxygen administration, intravenous steroids, and airway management, including intubation, may be indicated if necessary.
6.Other severe and potentially fatal reactions
Other serious and potentially fatal events have been reported with the use of fluoroquinolones. Some of these events are due to allergy and others are of unknown etiology. These events may be severe and usually occur after multiple dose administration. Clinical manifestations may include one or more of the following symptoms: fever, rash, severe skin reactions (e.g., toxic epidermal necrolysis relaxation,Stevens-Johnsonsyndrome); vasculitis; arthralgia; myalgia; serum sickness; allergic pneumonia; interstitial nephritis; acute renal insufficiency or renal failure; hepatitis, jaundice, acute hepatic necrosis or liver failure; anemia, including hemolytic anemia and aplastic anemia; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; granulocytic deficiency; allocytopenia and/ or other hematologic abnormalities. The drug should be discontinued and action taken immediately at the first appearance of rash, jaundice, or any other manifestation of allergy.
7.Central nervous system effects
The use of fluoroquinolones, including norfloxacin tablets, has been reported to increase the risk of central nervous system adverse effects, including convulsions and increased intracranial pressure (including pseudotumor cerebri) and psychosis due to toxicity. Use of fluoroquinolones may cause CNS reactions including agitation, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and suicidal thoughts or behaviors. These reactions may occur after the first dose of the drug. If these reactions occur while the patient is using norfloxacin tablets, dosing should be discontinued and appropriate action taken. As with all fluoroquinolones, norfloxacin tablets should be used when the benefit outweighs the risk in patients with known or suspected CNS disease (eg, severe cerebral atherosclerosis, epilepsy) or in patients with other risk factors (eg, a tendency to seizures or a lowered seizure threshold).
8.Peripheral neuropathy
Rare sensory or sensorimotor axonal neuropathies have been reported in patients using fluoroquinolones, affecting small and/or large axons, resulting in abnormal skin sensation, dullness of sensation, painful sensation to touch, and debilitation. For some patients, symptoms may occur soon after norfloxacin tablets are administered and may be irreversible. If a patient develops peripheral neuropathy symptoms, including pain, burning, tingling, numbness and / or weakness, or other sensations, including light touch, pain, warmth, position The medication should be discontinued immediately if there is a change in sensation, including light touch, pain, temperature, position, and vibration. Fluoroquinolone antibiotics should be avoided in patients with a history of peripheral neuropathy.
9.Clostridium difficile-associated diarrhea
Clostridium difficile-associated diarrhea has been seen with almost all antibacterial drugs (CDAD) reports, including norfloxacin tablets, ranging in severity from mild diarrhea to severe colitis. Antimicrobial drug therapy alters the normal flora of the colon, leading to Clostridium difficile overgrowth.
Toxins produced by C. difficileAandB, are the causes of Clostridium difficile-associated diarrhea. Highly virulent Clostridium difficile causes increased morbidity and mortality, and these infections are ineffective with antimicrobial therapy and may require colectomy. The possibility of CDAD should be considered in all cases of diarrhea after antibiotic therapy. BecauseCDAD may occur up to two months after treatment with antimicrobial drugs, careful history taking is necessary.
If C. difficile-associated diarrhea is suspected or confirmed, it may be necessary to discontinue current antibiotics that do not target C. difficile. Appropriate fluid and electrolyte replacement, protein supplementation, treatment with C. difficile-specific antibiotics, and surgical evaluation should be performed when clinically indicated.
10.Interference with blood glucose
Disruption of blood glucose (e.g., symptomatic hyperglycemia and hypoglycemia) has been reported with fluoroquinolone antibiotics, which mostly occurs with concomitant oral hypoglycemic agents (e.g., euglycemia/glibenclamide) or in diabetic patients using insulin. Therefore, for such patients, it is recommended that their blood glucose changes should be closely monitored. If a patient develops hypoglycemic reactions while receiving norfloxacin tablets, the drug should be discontinued immediately and appropriate therapeutic measures should be taken.
11.Photosensitivity/Phototoxicity
Moderate to severe photosensitivity occurs after exposure to sunlight or ultraviolet radiation following the use of fluoroquinolone antibiotics/phototoxic reactions, the latter may manifest as excessive sunburn reactions (e.g., burning sensation, erythema, blistering, oozing, edema), often in areas exposed to light (usually the neck “V “type area, the surface of the forearm extensors, and the back of the hand). Therefore, overexposure to light sources should be avoided. The drug should be discontinued in case of phototoxic reactions.
12.Safety in children, adolescents, nursing mothers and during pregnancy
Children, adolescents (18years of age), pregnant women, and nursing mothers The safety and efficacy of oral norfloxacin has not been established.
Norfloxacin has not been shown to be effective in the treatment of syphilis. Treatment of gonorrhea with high doses of antimicrobial agents over a short period of time may mask or delay the symptoms of latent syphilis. All patients with gonorrhea should be tested for syphilis serology at the time of diagnosis. Patients treated with norfloxacin should undergo follow-up serologic testing for syphilis after three months.
14.Crystalluria may occur with high dose of this product or with urinary pH above 7. To avoid crystalluria, it is advisable to drink more water and maintain urinary output above 1200 ml in 24 hours.
15.In patients with decreased renal function, the dose should be adjusted according to renal function.
16.In patients with glucose-6-phosphate dehydrogenase deficiency, hemolytic reactions may occur in rare cases.
17.Because of the high prevalence of E. coli resistance to flunofloxacin, urine specimens should be obtained for culture prior to administration and dosing should be adjusted with reference to bacterial drug sensitivity results. Use of this product in the absence of a confirmed or not highly suspected bacterial infection, or in the absence of an indication for prophylaxis, may not be beneficial to the patient and may increase the risk of development of drug-resistant organisms.
19. Organ system function, including renal, hepatic, and hematopoietic function, should be evaluated periodically during long-term therapy.
20. Use in food and feed processing is strictly prohibited.
[For Pregnant and Lactating Women
Norfloxacin was found to cause abortion in monkeys when administered at 10 times the maximum daily human dose (based on mg/kg). At this dose, the peak plasma concentration (Cmax) in monkeys was approximately twice that in humans. No teratogenic effects were demonstrated in test animals (rats, rabbits, mice, monkeys) at doses 6-50 times the maximum daily human dose (based on mg/kg). However, adequate, well-controlled studies have not been performed in pregnant women, and therefore this product is not recommended for use in pregnant women.
There is a lack of information on whether this product is secreted through breast milk. When 200 mg of norfloxacin was administered to a pregnant woman, the drug was not detectable in breast milk; however, because of the small doses studied and the secretion of other species of this drug through breast milk, as well as the potential for adverse effects in newborns and infants, pregnant women should avoid this product or discontinue breastfeeding at the time of application.
[Pediatric use
The safety and efficacy of oral norfloxacin in children and adolescents under 18 years of age have not been established. Norfloxacin can cause joint lesions when used in several species of young animals. It should not be used in children and adolescents younger than 18 years of age.
[Geriatric Use
Elderly patients are at increased risk of severe tendon disease, including tendon rupture, when treated with fluoroquinolones such as norfloxacin. This risk is further increased if concomitant corticosteroid therapy is received. Tendonitis or tendon rupture may occur in the Achilles tendon, hand, shoulder, or other tendon sites and can occur during or after treatment is completed. Cases have been reported that occurred several months after fluoroquinolone therapy. This product should be used with caution in elderly patients (especially those who are taking corticosteroids). Patients should be informed of this adverse reaction and advised to discontinue use of this product and seek prompt medical attention if they develop any symptoms of tendonitis or tendon rupture.
In a large foreign clinical study of norfloxacin for the treatment of urinary tract infections involving 340 subjects, 103 patients were 65 years of age and older and 77 patients were 70 years of age and older, and there were no significant differences in safety and efficacy between these subjects and younger subjects. In clinical practice, there were no differences in the types of adverse reactions reported by older and younger patients, except that older patients treated with concomitant corticosteroids may have an increased risk of tendon rupture. In addition, an increased risk of other adverse reactions in some older adults cannot be excluded.
The product is primarily excreted by the kidneys, and patients with impaired renal function may be at greater risk for toxic reactions. Because elderly patients often have decreased renal function and require reduced dose application, renal function monitoring may be required.
In general, older patients are more susceptible to drug-related QT intervals. Therefore, precautions should be taken when taking this product with concomitant medications that cause prolongation of the QTc interval (eg, class IA and class III antiarrhythmics) or in patients with risk factors for tip-twist ventricular tachycardia (eg, patients with known QT interval prolongation, uncorrected hypokalemia).
[Drug Interactions].
Quinolones, including norfloxacin, have been shown to inhibit CYP1A2 in in vitro trials. Use can result in increased drug concentrations.
Urinary alkalinizing agents may reduce the solubility of this product in urine, leading to crystalluria and nephrotoxicity.
The combination of this product with theophyllines may result in a marked decrease in hepatic clearance of theophyllines, prolonged blood clearance half-life (t1/2β), increased blood levels, and symptoms of theophylline toxicity due to competitive inhibition of the binding site with cytochrome P450, such as nausea, Vomiting, tremor, restlessness, agitation, convulsions, palpitations, etc. Therefore, theophylline blood concentration should be measured and dose adjusted when combined.
Cyclosporine in combination with this product may increase the blood concentration of the former, and the cyclosporine blood concentration must be monitored and the dose adjusted.
The anticoagulant effect of the latter may be enhanced when this product is used with the anticoagulant warfarin, and the patient’s prothrombin time should be closely monitored when combined.
Probenecid may reduce the secretion of this product from the renal tubules by approximately 50%, and may be toxic due to increased blood concentrations of this product when used in combination.
Probenecid is antagonistic to furantoin and is not recommended for combination use.
Multivitamins, or other preparations containing iron or zinc ions, and acid-control agents containing aluminum or magnesium may reduce the absorption of this product, and it is recommended to avoid combining them, or if not, to take them 2 hours before or 6 hours after the dose of this product.
Desoxymyxin may reduce the oral absorption of this product and should not be combined because its formulation contains aluminum and magnesium, which can chelate with fluoroquinolones.
This product interferes with the metabolism of caffeine, resulting in decreased clearance of caffeine, prolonged blood elimination half-life (t1/2β), and possible central nervous system toxicity.
Concomitant administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with quinolones, including norfloxacin, may increase the risk of central nervous system stimulation and convulsive seizures.
The combination of quinolones, including norfloxacin, with glibenclamide (sulfonylurea) has, in rare cases, led to severe hypoglycemia.
[Drug overdose].
No lethal effects were observed in mice and rats with single oral doses of this product up to 4 g/kg. Acute overdose requires emetic or gastric lavage to induce gastric emptying, careful observation of changes in condition, symptomatic management and supportive therapy. It is important to maintain appropriate rehydration levels.
[Pharmacologic Toxicology]
The product is a fluoroquinolone antibacterial agent with broad-spectrum antibacterial effect, especially high antibacterial activity against gram-negative bacilli. It has good antibacterial effect in vitro against the following bacteria: most bacteria of the Enterobacteriaceae family, including Enterobacter citri, Enterobacter cloacae, Enterobacter aerogenes and other Enterobacter spp, Escherichia coli, Klebsiella spp, Aspergillus spp. Salmonella, Shigella, Vibrio, Yersinia, etc. Norfloxacin also has antibacterial effect on many drug-resistant bacteria in vitro. Norfloxacin is a bactericidal agent that causes bacterial death by acting on the A subunit of bacterial DNA helicase, which inhibits DNA synthesis and replication.
[Pharmacokinetics
Blood levels
Blood concentrations and pharmacokinetic parameters for a single oral dose of norfloxacin 200 mg in healthy adults are as follows.
Figure: Blood concentration (healthy adults)
Pharmacokinetic Parameters
Dose (mg)Tmax(hr)Cmax(μg/ml)T1/2(hr)AUC(μg.hr/ml)2001.31.152.744.29
2. Distribution: The concentrations in tissues of adult patients receiving a single oral dose of norfloxacin 200 mg are as follows.
In a single oral dose of 200 mg of norfloxacin in healthy adult subjects, approximately 80% was excreted in urine as the prototype, and five other metabolites were observed.
4. Excretion
A single oral dose of 200 mg of norfloxacin in healthy adult subjects resulted in a peak concentration of 348 μg/mL in urine from 0 to 2 hours, with an 8-hour urinary drug recovery of 42.6%.
In addition, excretion in urine was significantly reduced in patients with severe renal insufficiency with creatinine clearance ≤29 ml/min.
Food and/or dairy products may reduce absorption.
In healthy elderly volunteers (age 65-75 years with normal renal function), norfloxacin was eliminated more slowly due to a slight decrease in renal function. After a single 400 mg norfloxacin dose, mean (±SD) AUC and Cmax of 9.8 (2.83) μg-hr/mL and 2.02 (0.77) μg/mL, respectively, were observed in healthy elderly volunteers. systemic exposure was slightly higher than in younger adults (AUC 6.4 μg-hr/mL and Cmax 1.5 μg/ml). Drug absorption was not affected. However, the half-life of norfloxacin in these elderly subjects was 4 hours.
No accumulation of multiple doses of norfloxacin was observed in elderly patients. Therefore, no separate dose adjustment based on age is required. In elderly patients with decompensated renal function, the dose should be adjusted according to other patients with renal insufficiency.
[Storage] Store under shade and seal.
[Packaging] This product is packaged in an aluminum-plastic package (polyvinyl chloride solid pharmaceutical rigid tablets and pharmaceutical aluminum foil) with a polyester/aluminum/polyethylene pharmaceutical laminated film bag and a built-in bag of silica gel desiccant; 12 tablets/plate, 2 plates/bag, 1 bag/box.
[Expiration date] 12 months
[Execution Standard
[Approval number] 国药准字H13022772
[Drug Marketing Authorization Holder
Name: Shiyang Group Ouyi Pharmaceutical Co.
Registered Address: No. 88 Yangzi Road, Shijiazhuang Economic and Technological Development Zone
Postal Code: 052165
Tel: 0311-87886158, 0311-67163660
Fax number: 0311-87171665
[Manufacturer
Company name: Shiyang Group Ouyi Pharmaceutical Co.
Production Address: No. 88 Yangzi Road, Shijiazhuang Economic and Technological Development Zone
Postal Code: 052165
Tel: 0311-87886158, 0311-67163660
Fax number: 0311-87171665