Levofloxacin hydrochloride tablets
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Details
Date of approval: January 29, 2007 Registered trademark
Date of revision: October 1, 2010
October 01, 2012
December 31, 2012
November 30, 2015
July 05, 2017
Levofloxacin hydrochloride tablets instructions
Please read the instructions carefully and use them under the guidance of a physician.
For food and feed processing
caveat:
In all age groups, fluoroquinolones, including levofloxacin hydrochloride, can increase the risk of tendonitis and tendon rupture. This risk is further increased in elderly patients over the age of 60, patients receiving glucocorticoid therapy, and patients receiving kidney transplantation, heart transplantation, or lung transplantation.
Serious adverse reactions, including tendinitis and tendon rupture, peripheral neuropathy, central nervous system effects, and increased myasthenia gravis.
• The use of fluoroquinolone drugs (including levofloxacin hydrochloride tablets) has been reported to have both disabling and potentially irreversible serious adverse effects (see [Precautions]), including:
o Tendinitis and tendon rupture (see [Precautions])
o Peripheral neuropathy (see [Precautions])
o The effects of the central nervous system (see [Notes])
When these serious adverse reactions occur (see [Precautions]), levofloxacin hydrochloride tablets should be discontinued immediately and fluoroquinolone drugs should be avoided.
• Fluoroquinolone drugs may aggravate myasthenia gravis in patients with myasthenia gravis. Patients with a history of myasthenia gravis should be advised to avoid levofloxacin hydrochloride tablets (see [Precautions]).
• Serious adverse reactions have been reported due to the use of fluoroquinolone drugs (including levofloxacin hydrochloride tablets) (see [Precautions]). For patients with the following indications, levofloxacin hydrochloride tablets should be used without other medications:
o Acute bacterial sinusitis (see [Indications] and [Usage and Dosage])
o Acute bacterial attack of chronic bronchitis (see [Indications] and [Usage and Dosage])
o Non-complex urinary tract infections (see [Indications] and [Usage and Dosage])
【Drug Name】
Common name: levofloxacin hydrochloride tablets
Product Name: Pito
English name: Levofloxacin Hydrochloride Tablets
Chinese Pinyin: Yansuan Zuoyangfushaxing Pian
[ingredients]
The main component of this product is: levofloxacin hydrochloride. Its chemical name is: (-)-(S)-3-methyl-9-fluoro-2,3-dihydro-10-(4-methyl-1-piperazinyl)-7-oxo-7H Pyrido[1,2,3-de]-[1,4]benzoxazine-6-carboxylic acid hydrochloride-hydrate.
Chemical Structure:
Molecular formula: C18H20FN3O4·HCl·H2O
Molecular weight: 415.85
【Properties】 This product is a film-coated tablet, which is white to pale yellow after removal of the coating.
[indications]
In order to reduce the production of drug-resistant bacteria and ensure the effectiveness of levofloxacin hydrochloride and other antibiotics, levofloxacin is only used to treat or prevent infections that have been proven or highly suspected to be caused by sensitive bacteria. The results of bacterial culture and susceptibility testing should be considered when selecting or modifying an antimicrobial treatment regimen. If there is no data for these trials, empirical treatment should be based on local epidemiology and pathogen sensitivity.
Bacterial culture and susceptibility testing should be performed prior to treatment to isolate and identify infectious pathogens and determine their sensitivity to levofloxacin hydrochloride. Levofloxacin can be used for treatment before the above test results are obtained, and the appropriate treatment is selected after the test results are obtained.
As with other drugs in this class, certain strains of P. aeruginosa can quickly develop resistance when treated with levofloxacin hydrochloride. Bacterial culture and drug susceptibility testing should be carried out regularly during treatment to see if the pathogen is continuously sensitive to antimicrobial agents and can be detected in time after bacterial resistance develops.
Oral formulations and injections of levofloxacin hydrochloride can be used to treat the following mild, moderate, and severe infections caused by sensitive strains of the following bacteria in adults (≥ 18 years old). If intravenous drip is more beneficial to the patient (eg, the patient cannot tolerate oral administration, etc.) levofloxacin hydrochloride injection can be used.
Hospital acquired pneumonia
Treatment of hospital acquired by methicillin-sensitive Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae or Streptococcus pneumoniae pneumonia. At the same time, other ancillary treatments should be taken according to clinical needs. If Pseudomonas aeruginosa infection has been proven or suspected, it is recommended to use anti-Pseudomonas β-lactam drugs for treatment.
2. Community acquired pneumonia
7 to 14 days of treatment: treatment of methicillin-sensitive Staphylococcus aureus, Streptococcus pneumoniae [including multi-drug resistant strains (MDRSP*)], Haemophilus influenzae, Haemophilus parainfluenzae, pneumonia Community-acquired pneumonia caused by Bacillus, Moraxella catarrhalis, Chlamydia pneumoniae, Legionella pneumoniae or Mycoplasma pneumoniae.
Note: MDRSP (multi-drug resistant pneumococci) refers to strains resistant to two or more of the following antibiotics: penicillin (MIC ≥ 2 μg/mL), second-generation cephalosporins (such as cefuroxime), large Cyclolactones, tetracycline and trimethoprim/sulfamethoxazole.
5-day treatment regimen: treatment of community-acquired pneumonia caused by S. pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae or Chlamydia pneumoniae.
3. Acute bacterial sinusitis
5-day treatment regimen: treatment of acute bacterial sinusitis caused by S. pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.
10 to 14 days of treatment: treatment of acute bacterial sinusitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.
Serious adverse reactions have been reported due to the use of fluoroquinolones (including levofloxacin hydrochloride tablets), and for some patients, acute bacterial sinusitis is self-limiting, and levofloxacin hydrochloride tablets should be used without other medications.
4. Acute bacterial attack of chronic bronchitis
Treatment of acute bacterial outbreaks of chronic bronchitis caused by methicillin-sensitive Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae or Moraxella catarrhalis.
Serious adverse reactions have been reported due to the use of fluoroquinolones (including levofloxacin hydrochloride tablets), and for some patients, the acute bacterial attack of chronic bronchitis is self-limiting, and levofloxacin hydrochloride should be used without other medications. sheet.
5. Complex skin and skin soft tissue infections
Treatment of complex skin and skin and soft tissue infections caused by methicillin-sensitive Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes or Proteus mirabilis.
6. Non-complex skin and skin soft tissue infections
Treatment of non-complex skin and soft tissue infections caused by methicillin-sensitive Staphylococcus aureus or Streptococcus pyogenes (mild to moderate), including abscesses, cellulitis, warts, impetigo, pyoderma ,Wound infection.
7. Chronic bacterial prostatitis
Treatment of chronic bacterial prostatitis caused by Escherichia coli, Enterococcus faecalis or methicillin-sensitive Staphylococcus epidermidis.
8. Complex urinary tract infections
5-day treatment regimen: treatment of complex urinary tract infections caused by Escherichia coli, Klebsiella pneumoniae or Proteus mirabilis.
10-day treatment regimen: treatment of complex urinary tract infections (mild to moderate) caused by Enterococcus faecalis, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis or Pseudomonas aeruginosa.
9. Acute pyelonephritis
5-day treatment regimen: treatment of acute pyelonephritis caused by Escherichia coli, including the name of the bacteremia.
10-day treatment regimen: treatment of acute pyelonephritis caused by Escherichia coli, including the name of the bacteremia.
10. Uncomplicated urinary tract infections:
Treatment of uncomplicated urinary tract infections (mild to moderate) caused by Escherichia coli, Klebsiella pneumoniae or Staphylococcus aureus.
Serious adverse reactions have been reported due to the use of fluoroquinolones (including levofloxacin hydrochloride tablets), and for some patients, non-complex urinary tract infections are self-limiting, and levofloxacin hydrochloride tablets should be used without other medications.
11. Inhalation anthrax (after exposure)
Suitable for inhalation anthrax (post-exposure) treatment, reducing the incidence of disease or slowing the progression of the disease after exposure to B. anthracis spray. The effectiveness of levofloxacin is based on the surrogate endpoint of human plasma concentrations to predict clinical outcomes.
The preventive effect of levofloxacin on inhalation exposure to anthrax has not been tested in humans. The safety of levofloxacin in more than 28 days of treatment in adults has not been studied. Long-term treatment with levofloxacin can only be used if the benefits outweigh the risks.
[Specifications] according to C18H20FN3O4 (1) 0.1g (2) 0.2g
【Dosage】
Oral formulations and injections of levofloxacin hydrochloride are used for the treatment of the above-mentioned infectious diseases (see Indications). The general usage and dosage are as follows, but must be determined by the clinician in combination with the severity of the disease.
1. Dosage and administration method
(1) Dose in patients with normal renal function
The usual dose of levofloxacin hydrochloride oral formulation is 250 mg or 500 mg or 750 mg, orally once every 24 hours. According to the infection, take it as shown in the table below (Table 1).
The usual dose of levofloxacin hydrochloride injection is 250 mg or 500 mg, slow infusion, infusion time of not less than 60 minutes, intravenous infusion every 24 hours; or 750 mg, slow infusion, time not less than 90 minutes, every 24 Intensively once every hour. According to the infection, it is used as shown in Table 1.
There is no need to adjust the amount of creatinine clearance ≥ 50 mL / min. When the creatinine clearance rate is <50 mL/min, the dosage should be adjusted.
Table 1: Dose in patients with normal renal function (creatinine clearance ≥ 50 mL/min)
Infection type 1 every 24 hours dose course (days) 2
Hospital pneumonia 750 mg 7～14
Community acquired pneumonia 3 500 mg 7-14
Community acquired pneumonia 4 750 mg 5
Acute bacterial sinusitis 750 mg 5
500 mg 10~14
Acute bacterial exacerbation of chronic bronchitis 500 mg 7
Complex skin and skin soft tissue infections (cSSSI) 750 mg 7 to 14
Non-complex skin and skin soft tissue infections (uSSSI) 500 mg 7-10
Chronic bacterial prostatitis 500 mg 28
Complex urinary tract infection (cUTI) or acute pyelonephritis (AP) 5 750 mg 5
Complex urinary tract infection (cUTI) or acute pyelonephritis (AP) 6 250 mg 10
Uncomplicated urinary tract infection 250 mg 3
Inhalation anthrax (after exposure), adult and pediatric patients >50 kg and ≥6 months 7,8
Pediatric patients <50 kg and ≥6 months 7,8 500 mg
See the table below (Table 2) 608
608
Note: 1 caused by specific pathogens (see indications).
2 physicians can use continuous treatment (intravenous or oral) at their own discretion.
3 by methicillin-sensitive Staphylococcus aureus, Streptococcus pneumoniae [including multi-drug resistant strains (MDRSP)], Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydia pneumoniae, Legionella pneumophila or Mycoplasma pneumoniae (see indications).
4 caused by Streptococcus pneumoniae [including multi-drug resistant strains (MDRSP)], Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae or Chlamydia pneumoniae (see indications).
5 This protocol is applicable to cUTI caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and acute pancreatitis caused by Escherichia coli, including the name of simultaneous bacteremia.
6 This protocol is applicable to cUTI caused by Enterococcus faecalis, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and acute pancreatitis caused by Escherichia coli.
7 should be administered as soon as possible after suspected or clear exposure to Bacillus anthracis spray. This indication is based on the surrogate endpoint. The plasma concentration of levofloxacin achieved in humans may predict clinical efficacy.
The safety of 8 levofloxacin hydrochloride in more than 28 days in adults and more than 14 days in pediatric patients has not been studied. An increased incidence of musculoskeletal adverse reactions was observed in pediatric patients compared to controls (see Warnings and Precautions for details). Long-term treatment with levofloxacin hydrochloride can only be used when the benefit exceeds the risk.
(2) Dose in pediatric patients (<18 years old)
The doses for pediatric patients (≥6 months) are described in the table below (Table 2).
Table 2: Dose of pediatric patients (≥6 months)
Infection type 1 dose per administration frequency course 2
Inhalation anthrax (after exposure) 3, 4
Pediatric patients >50 kg and ≥6 months 500 mg 24 hours 60 days 4
Pediatric patients <50 kg and ≥6 months 8 mg/kg (no more than 250 mg per dose) 12 hours 60 days 4
Note: 1 caused by Bacillus anthracis (see indications).
2 physicians can use continuous treatment (intravenous or oral) at their own discretion.
3 should be administered as soon as possible after suspected or clear exposure to B. anthracis spray. This indication is based on the surrogate endpoint. The plasma concentration of levofloxacin hydrochloride achieved in humans may predict clinical efficacy.
The safety of 4 levofloxacin hydrochloride in pediatric patients for more than 14 days has not been studied. An increased incidence of musculoskeletal adverse reactions was observed in pediatric patients compared to controls (see Warnings and Precautions). Long-term levofloxacin treatment can only be used when the benefit exceeds the risk.
(3) Dose adjustment in patients with renal insufficiency
If there is renal insufficiency, levofloxacin hydrochloride should be used with caution. Since the clearance of levofloxacin hydrochloride may be reduced, careful clinical observation and appropriate laboratory studies should be performed before and during the start of treatment.
There is no need for dose adjustment for patients with creatinine clearance ≥50 mL/min.
In patients with renal insufficiency (creatinine clearance <50 mL/min), due to decreased creatinine clearance, doses need to be adjusted to avoid accumulation of levofloxacin hydrochloride (see use in special populations).
The table below (Table 3) shows how to adjust the dose based on creatinine clearance.
Table 3: Dose adjustment in patients with renal insufficiency (creatinine clearance <50 mL/min)
Creatinine clearance per 24 hours in patients with normal renal function
20 to 49 mL/min creatinine clearance
10 to 19 mL/min hemodialysis or continuous ambulatory peritoneal dialysis (CAPD)
Since the drug does not contain a preservative or bacteriostatic agent, aseptic technique should be used in the preparation of the intravenous solution.
Care should be taken to see if the solution contains particulate impurities before use. Drugs containing visible particles should be discarded.
Stability of levofloxacin hydrochloride injection after dilution: Levofloxacin hydrochloride injection can be diluted to a concentration of 5 mg/mL with a compatible intravenous solution, and can be stored at 25 ° C (77 ° F) or below 25 ° C. For 72 hours, it can be stored in a plastic container for intravenous drip in a refrigerator at 5 ° C (41 ° F) for 14 days. The solution diluted with a compatible intravenous solution is frozen in a glass bottle or a plastic container for intravenous drip, stored at -20 ° C (-4 ° F), and stable for 6 months. The frozen solution was thawed at room temperature 25 ° C (77 ° F) or in a 8 ° C (46 ° F) refrigerator. Do not use a microwave or water bath to accelerate its dissolution. Do not freeze and melt again after melting once.
Injection instructions: Check the container for minor leaks before use. If there is a leak or the seal is incomplete, the solution should be discarded as the solution may not be sterile. Do not use if the solution is cloudy or precipitates. Sterile equipment should be used.
Caution: Do not connect containers together. This may result in air embolism due to the inhalation of residual air in the primary container prior to the completion of liquid in the secondary container.
【Adverse reactions】
This product is levofloxacin hydrochloride, the active ingredient of which is levofloxacin. The related cases of levofloxacin reported in the literature are as follows:
1. Serious and other important adverse reactions
Disabling and potentially irreversible serious adverse reactions, including tendinitis and tendon rupture, peripheral neuropathy, central nervous system effects
tendonitis and tendon rupture
Myasthenia gravis is aggravated
QT interval extension
Allergic reactions
Hypersensitivity
other serious and potentially fatal reactions
The influence of the central nervous system
Peripheral neuropathy
Clostridium difficile-associated diarrhea
Interference with blood sugar
Light sensitivity / phototoxicity
Hepatotoxicity
Musculoskeletal disorders in pediatric patients
Drug-resistant bacteria
The above adverse reactions are described in detail under [Precautions].
Cardiovascular system: prolonged QT interval, torsade de pointive ventricular tachycardia, ventricular arrhythmia
Central nervous system: convulsions, toxic psychosis, tremors, agitation, anxiety, dizziness, confusion, hallucinations, delusions, depression, nightmares, insomnia, seizures, and very few situations can lead to suicidal thoughts or actions
Peripheral neuropathy: feeling disorganized, feeling dull, feeling of touch, pain, burning, tingling, numbness, weakness, or light touch, pain, temperature, position and vibration abnormalities, polyneuritis
Skeletal muscle system: joint pain, myalgia, muscle weakness, tension hypertonic tendonitis, tendon rupture, worsening myasthenia gravis
Hypersensitivity reactions: urticaria, itching and other serious skin reactions (such as toxic epidermal necrolysis, erythema multiforme), dyspnea, angioedema (including tongue, throat, pharynx or facial edema/swelling), Cardiovascular collapse, hypotension, loss of consciousness, airway obstruction (including bronchospasm, shortness of breath and acute respiratory distress), hypersensitivity pneumonitis, anaphylactic shock
Hepatobiliary system: hepatitis, jaundice, acute hepatic necrosis or liver failure
Urinary system: acute renal insufficiency or renal failure
Blood system: anemia, including hemolytic anemia and aplastic anemia, thrombocytopenia, including thrombotic thrombocytopenic purpura, leukopenia, neutropenia, pancytopenia, and/or other blood diseases
Others: fever, vasculitis, serum disease, Clostridium difficile-associated diarrhea, blood glucose disorder, photosensitivity/phototoxicity
Rapid intravenous infusion or bolus injection of levofloxacin may result in hypotension. According to the dose, intravenous infusion should be no less than 60 to 90 minutes. The use of quinolones (including levofloxacin) has been reported to cause crystallized urine and tubular urine. Therefore, for patients receiving levofloxacin, proper hydration should be maintained to prevent the formation of highly concentrated urine.
2. Clinical trial experience
Since clinical trials are performed under different conditions, the adverse reaction rate of one drug observed in clinical trials cannot be directly compared with the adverse reaction rates of other drugs in clinical trials, and may not reflect adverse reactions in practical applications. rate.
The data described below reflects the combined exposure of levofloxacin to 7,537 patients in 29 phase III clinical trials. The average age of the study population was 50 years (about 74% of the population <65 years old), of which 50% were male, 71% were white, and 17% were black. Patients were treated with levofloxacin for a wide range of infectious diseases (see indications). The patient received levofloxacin at a dose of 750 mg once daily, 250 mg once daily, or 500 mg once or twice daily for a period of 3 to 14 days with an average course of 10 days.
The overall incidence, type, and distribution of adverse events were similar in patients who used levofloxacin 750 mg once daily, 250 mg once daily, or 500 mg once or twice daily. A total of 4.3% of patients discontinued levofloxacin due to adverse drug reactions, which was 3.8% in patients receiving 250 mg and 500 mg daily doses, and 5.4 in patients receiving 750 mg daily dose. %. The most common adverse drug reaction in patients receiving daily doses of 250 mg and 500 mg was gastrointestinal reactions (1.4%), mainly nausea (0.6%), vomiting (0.4%), and dizziness (0.3 %) and headache (0.2%). The most common adverse drug response in patients receiving a daily dose of 750 mg was gastrointestinal reactions (1.2%), mainly nausea (0.6%), vomiting (0.5%), dizziness (0.3%), and Headache (0.3%).
Adverse reactions occurring in ≥1% of patients receiving levofloxacin and adverse events occurring in 0.1 to <1% of patients receiving levofloxacin were listed in the following table (Tables 5 and 6), respectively. The most common adverse reactions (≥3%) were nausea, headache, diarrhea, insomnia, constipation and dizziness.
Table 5: Common (≥1%) adverse reactions reported in levofloxacin clinical trials
System/organ classification adverse reactions %(N=7537)
Infection and infections Candidiasis 1
Psychosis, insomnia 4 a
Various neurological diseases headaches 6
Dizziness 3
Respiratory, chest and mediastinal diseases Dyspnea 1
Gastrointestinal diseases, nausea 7
Diarrhea 5
Constipation 3
Gastrointestinal diseases, abdominal pain 2
Vomiting 2
Indigestion 2
Skin and subcutaneous tissue diseases
Itching 2
1
Reproductive system and breast disease Vaginitis 1b
Systemic diseases and various reactions at the site of administration
Various reactions at the injection site
Chest pain 1
1
1
Note: a. N = 7274;
b. N = 3758 (female).
Table 6: Less common (0.1 to 1%) adverse events reported in levofloxacin clinical trials (N=7537)
System/organ classification adverse reactions
Infection and infection genital candidiasis
Blood and lymphatic diseases, anemia, thrombocytopenia, neutropenia
Immune system disease
Metabolic and nutritional diseases Hyperglycemia, hypoglycemia, hyperkalemia
Psychiatry Anxiety, agitation, confusion, depression, hallucinations, nightmares, sleep disorders a, anorexia
Various neurological diseases, tremors, convulsions, confusion, dizziness, high tension, hyperkinesia, gait
Abnormal, lethargy a, syncope
Respiratory, chest and mediastinal diseases
Cardiac organ disease cardiac arrest, palpitations, ventricular tachycardia, ventricular arrhythmia
Vascular disease phlebitis
Gastrointestinal diseases Gastritis, stomatitis, pancreatitis, esophagitis, gastroenteritis, glossitis, pseudomembranous / Clostridium difficile colitis
Hepatobiliary diseases, abnormal liver function, increased liver enzymes, and increased alkaline phosphatase
Skin and skin soft tissue diseases urticaria
Various musculoskeletal and connective tissue diseases joint pain, tendonitis, myalgia, bone pain
Kidney and urinary system disorders renal dysfunction, acute renal failure
Note: a. N = 7274.
In clinical trials using multiple doses of therapy, it was noted that ophthalmologic abnormalities, including cataracts and multiple punctate patches of the lens, occurred in patients receiving quinolone antibiotics, including levofloxacin. The link between drugs and these events has not yet been established.
3. Post-marketing monitoring
The following table (Table 7) lists the adverse reactions identified in the use of levofloxacin after it has been approved for marketing. Because these responses are spontaneously reported from a variable population, it is sometimes impossible to reliably assess the incidence of these events or establish a causal relationship between drug exposure and these events.
Table 7: Report of adverse drug reactions after marketing
System/organ classification adverse reactions
Blood and lymphatic system diseases, whole blood cell reduction, aplastic anemia, leukopenia, hemolytic anemia, eosinophilia
Immune system diseases Allergic reactions, sometimes fatal, including: allergic reactions / allergic reactions, anaphylactic shock, angioedema, serum disease
Psychiatric psychiatry, paranoia, individual reported suicide attempts and suicidal thoughts
Various neurological diseases Deterioration of myasthenia gravis, olfactory loss, loss of taste, olfactory abnormalities, dysgeus, peripheral neuropathy, individual reported encephalopathy, abnormal electroencephalogram (EEG), difficulty in vocalization
Eye disease, visual impairment, including diplopia, decreased visual sensitivity, blurred vision, dark spots
Ear and labyrinth diseases, hearing loss, tinnitus
Cardiac organ diseases Individually reported torsades de pointes ventricular tachycardia, electrocardiogram QT interval prolongation, tachycardia
Vascular disease vasodilation
Respiratory, chest and mediastinal diseases Individually reported hypersensitivity pneumonitis
Hepatobiliary diseases liver failure (including fatal disease name), hepatitis, jaundice
Skin and skin soft tissue disorders Bullous rashes, including: Stevens-Johnson syndrome, toxic epidermal necrosis, erythema multiforme, photosensitivity/phototoxicity, leukocyte rupture vasculitis
Various musculoskeletal and connective tissue diseases tendon rupture, muscle damage, including rupture, rhabdomyolysis
Kidney and urinary system diseases interstitial nephritis
Systemic disease and site of administration Multiple organ failure, fever
Various types of tests prolonged prothrombin time and increased muscle enzymes
[taboo]
Those who are allergic to quinolones, pregnant and lactating women, and patients under 18 years of age are banned.
【Precautions】
This product is levofloxacin hydrochloride, the active ingredient of which is levofloxacin. The related cases of levofloxacin reported in the literature are as follows:
1. Disabling and potentially irreversible serious adverse reactions, including tendinitis and tendon rupture, peripheral neuropathy, central nervous system effects
The use of fluoroquinolone drugs has been reported to cause disabling and potentially irreversible serious adverse reactions in different organ systems of the same patient, usually including: tendonitis, tendon rupture, joint pain, myalgia, peripheral neuropathy and Central nervous system reactions (illusions, anxiety, depression, insomnia, severe headaches and confusion). These adverse reactions can occur from hours to weeks after the use of levofloxacin hydrochloride tablets. These adverse events have been reported in patients of any age without prior risk factors.
2. Tendinitis and tendon rupture
Fluoroquinolone drugs increase the risk of tendonitis and tendon rupture in patients of all ages. This adverse reaction most often occurs in the Achilles tendon, which may require surgical repair. There have also been reports of tendonitis and tendon rupture in the shoulders, hands, biceps, thumb and other tendon points. Tendinitis and tendon rupture can occur hours or days after the start of the levofloxacin hydrochloride tablets, or months after the end of treatment. Tendinitis and tendon rupture can occur bilaterally. This risk is further increased in elderly patients over 60 years of age, patients taking corticosteroids, and patients undergoing kidney, heart or lung transplants. In addition to age and the use of corticosteroids, factors that independently increase the risk of tendon rupture include severe physical activity, renal failure, and previous tendon diseases such as rheumatoid arthritis. Tendinitis and tendon rupture also occur in patients who use fluoroquinolone drugs without the above risk factors. Tendon rupture can occur during or after treatment; it is also reported that tendon rupture occurs several months after the end of treatment. This product should be discontinued after the patient has muscle pain, swelling, inflammation or breakage. After signs of tendonitis or tendon rupture, patients should be advised to rest and contact a physician for a non-quinolone. Patients with a history of tendon disease or who have had tendinitis and tendon rupture should avoid fluoroquinolone drugs.
3. Myasthenia gravis is aggravated
Fluoroquinolone drugs, which have neuromuscular blocking activity, may aggravate the symptoms of myasthenia gravis in patients with myasthenia gravis. Serious adverse events after marketing, including death and need for ventilatory support, and patients with myasthenia gravis are associated with the use of fluoroquinolones. Patients with myasthenia gravis should avoid the use of levofloxacin hydrochloride tablets.
4. QT interval extension
Some fluoroquinolone drugs can prolong the QT interval of the electrocardiogram, and a few patients can have arrhythmia. Patients with spontaneously reported fluoroquinolone therapy during the post-marketing surveillance period have a rare torsade ventricular tachycardia. Patients with known QT prolongation, uncorrected hypokalemia patients, and patients with antiarrhythmic drugs of class IA (quinidine, procainamide) and class III (amiodarone, sotalol) Levofloxacin hydrochloride tablets should be avoided. Elderly patients are more susceptible to drug-related QT intervals.
5. Allergic reactions
Serious allergic reactions have been reported using fluoroquinolone drugs. Some patients occur after the first dose, and some reactions can be accompanied by cardiovascular failure, loss of consciousness, tingling, swallowing or facial edema, difficulty breathing, urticaria, itching, and the like. Severe allergic reactions require emergency treatment with adrenaline. Levofloxacin hydrochloride tablets should be discontinued the first time there is a rash or any other signs of allergies. If necessary, oxygen can be delivered, intravenous steroids, airway treatment, including intubation and other measures.
6. Hypersensitivity
Patients who are treated with fluoroquinolone antibiotics including levofloxacin occasionally develop severe, sometimes fatal, hypersensitivity and/or allergic reactions that occur after the first dose. Some reactions may be associated with cardiovascular collapse, hypotension/shock, seizures, loss of consciousness, tingling, angioedema (including tongue, throat, pharynx or facial edema/swelling), airway obstruction (including bronchospasm) , shortness of breath and acute respiratory distress), difficulty breathing, urticaria, itching and other serious skin reactions. Levofloxacin should be discontinued immediately when the first rash or any other symptom of hypersensitivity occurs. Severe acute hypersensitivity reactions require treatment with adrenaline, and other resuscitation measures such as oxygen inhalation, intravenous rehydration, antihistamines, corticosteroids, vasopressamines, and airway treatment are used depending on clinical needs.
7. Other serious and potentially fatal reactions
Other serious and potentially fatal incidents have been reported using fluoroquinolone drugs. Some of these events are due to allergies and some are unknown. These events can be severe and usually occur after multiple doses. Clinical manifestations may include one or more of the following symptoms: fever, rash, severe skin reaction (eg, toxic epidermal necrolysis, Stevens-Johnson syndrome); vasculitis; joint pain; myalgia; 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 thrombocytopenia Purpura; leukopenia; agranulocytosis; pancytopenia and/or other hematological abnormalities. The drug should be discontinued and measures taken immediately on the first occurrence of a rash, jaundice or any other allergic manifestation.
8. The influence of the central nervous system
The use of fluoroquinolone drugs, including levofloxacin hydrochloride tablets, has been reported to increase the risk of adverse central nervous system adverse reactions, including convulsions and increased intracranial pressure (including pseudo-brain tumors) and psychosis caused by poisoning. The use of fluoroquinolone drugs may cause central nervous system reactions including anxiety, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and suicidal thoughts or behaviors. These reactions may occur after the first dose. If these reactions occur when the patient is taking levofloxacin hydrochloride tablets, the administration should be stopped and appropriate measures taken. As with all fluoroquinolone drugs, patients with known or suspected central nervous system disorders (such as severe cerebral arteriosclerosis, epilepsy) or patients with other risk factors (if there is a tendency to attack or a lower threshold for seizures) should be obtained. Levofloxacin hydrochloride tablets are used when the risk exceeds the risk.
9. Peripheral neuropathy
Patients have been reported to use fluoroquinolone drugs to produce a rare sensory or sensorimotor axonal neuropathy that affects small and/or large axons, causing skin paresthesia, sensation of dullness, sensation of touch and weakness. For some patients, symptoms may occur soon after administration of levofloxacin hydrochloride tablets and may be irreversible. If the patient has symptoms of peripheral neuropathy, including pain, burning sensation, tingling, numbness and/or weakness, or other sensations, including changes in light touch, pain, temperature, position, and vibration, stop the drug immediately. Patients with a history of peripheral neuropathy should avoid the use of fluoroquinolone antibiotics.
10. C. difficile-associated diarrhea
Nearly all antibacterial drugs have been reported for C. difficile-associated diarrhea (CDAD), including levofloxacin hydrochloride tablets, ranging from mild diarrhea to severe colitis. Antimicrobial treatment changes the normal flora of the colon, resulting in overgrowth of C. difficile.
Toxins A and B produced by C. difficile are responsible for Clostridium difficile-associated diarrhea. The morbidity and mortality caused by highly toxic Clostridium are elevated, and these infections are ineffective and may require colectomy. After receiving antibiotics, the possibility of CDAD should be considered in the presence of diarrhea. Because CDAD may occur two months after treatment with antibacterial drugs, careful medical history is necessary.
If you suspect or confirm C. difficile-associated diarrhea, you may need to stop the antibiotics currently used against C. difficile. Appropriate supplementation of fluids and electrolytes, protein supplementation, antibiotic treatment for C. difficile should be performed, and surgical evaluation should be performed when clinical indications appear.
11. Interference with blood sugar
There have been reports of fluoroquinolone antibiotics causing blood glucose disorders (such as symptomatic hyperglycemia and hypoglycemia), which often occur in patients with simultaneous oral hypoglycemic agents (such as glibenclamide/glibenclamide) or insulin using insulin. . Therefore, for such patients, it is recommended that their blood glucose changes be closely monitored. If the patient has hypoglycemia when receiving levofloxacin hydrochloride tablets, discontinue the drug immediately and take appropriate treatment.
12. Light sensitivity / phototoxicity
Moderate to severe photosensitivity/phototoxicity after exposure to sunlight or UV light after exposure to fluoroquinolone antibiotics
The reaction, which may exhibit excessive sunburn reactions (eg, burning sensation, erythema, blisters, exudation, edema), often occurs in areas exposed to light (usually the "V"-shaped area of the neck, the forearm extensor surface The back of the hand). Therefore, excessive exposure to light sources should be avoided. The drug should be discontinued when a phototoxic reaction occurs.
13. Hepatotoxicity
Post-marketing reports of severe hepatotoxicity (including acute hepatitis and fatal events) in patients receiving levofloxacin have been received. No evidence of severe drug-related hepatotoxicity was found in clinical trials of more than 7,000 patients. Severe hepatotoxicity usually occurs within 14 days of starting treatment, and in most cases, it occurs within 6 days of starting treatment. Most cases of severe hepatotoxicity have nothing to do with allergies. Most of the fatal liver toxicity reports are seen in patients >65 years of age, most of which are not related to hypersensitivity. Levofloxacin should be discontinued immediately if the patient has signs and symptoms of hepatitis.
14. Musculoskeletal diseases in pediatric patients and joint disease effects in animals
In pediatric patients (≥6 months), levofloxacin is only suitable for the protection of anthrax inhalation (after exposure). Increased incidence of musculoskeletal disorders (joint pain, arthritis, tendon disorder, and gait abnormalities) was observed in pediatric patients receiving levofloxacin compared to controls.
In juvenile rats and dogs, oral and intravenous administration of levofloxacin resulted in an increase in osteochondrosis. Histopathological examination of the weighted joints of juvenile dogs receiving levofloxacin showed continued damage to the cartilage. Other quinolones can also produce similar weight-bearing joint erosions in juvenile animals of multiple species, as well as other signs of joint disease.
15. Drug-resistant bacteria production
Opening levofloxacin prescriptions without a diagnosis or a high degree of suspected bacterial infection and non-compliance with preventive indications does not benefit patients and increases the risk of developing resistant bacteria.
16. It is strictly forbidden to be used in food and feed processing.
[Pregnant women and lactating women]
This product is levofloxacin hydrochloride, the active ingredient of which is levofloxacin. The related cases of levofloxacin reported in the literature are as follows:
Pregnancy
Pregnancy medication grade C. Levofloxacin was not teratogenic when administered orally in rats at doses up to 810 mg/kg/day, which is equivalent to 9.4 times the maximum recommended dose for humans with the same body surface area. At an intravenous infusion dose of 160 mg/kg/day, levofloxacin also had no teratogenic effects, which corresponds to 1.9 times the maximum recommended dose for humans with the same body surface area. Rat oral dose of 810 mg / kg / day can reduce fetal weight and increase mortality. Levofloxacin was not observed to have teratogenic effects when administered orally in rabbits at 50 mg/kg/day, which corresponds to 1.1 times the maximum recommended dose for humans with the same body surface area. At an intravenous infusion dose of 25 mg/kg/day, levofloxacin also had no teratogenic effects, which corresponds to 0.5 times the maximum recommended dose for humans with the same body surface area.
However, there are not enough well-controlled trials for pregnant women to ensure the safety of pregnant women, so women who are pregnant or likely to be pregnant are prohibited. Levofloxacin can only be used in pregnant women when the potential benefit to the fetus is greater than the potential risk.
Lactating woman
Based on limited data from other fluoroquinolones and levofloxacin, it is speculated that levofloxacin should be secreted into human breast milk. Lactating women are banned because levofloxacin may cause serious adverse reactions in breastfed babies. Levofloxacin can be used in lactating women only when the potential benefit to lactating women is greater than the potential risk, but breastfeeding should be suspended.
[Children's medication]
This product is levofloxacin hydrochloride, the active ingredient of which is levofloxacin. The related cases of levofloxacin reported in the literature are as follows:
Quinolone antibiotics, including levofloxacin, can cause joint disease and bone/cartilage lesions in larvae of certain species of animals. The safety of children has not been established and is therefore prohibited for patients younger than 18 years of age, except for the protection of anthrax (after exposure).
Inhalation anthrax (after exposure)
Levofloxacin is indicated for use in pediatric inhaled anthrax (after exposure). Risk-benefit assessment suggests that levofloxacin is appropriate in pediatric patients. The safety of levofloxacin treatment for more than 14 days has not been studied in pediatric patients. The pharmacokinetics of a single intravenous levofloxacin was studied in pediatric patients between the ages of 6 months and 16 years. In children, levofloxacin is cleared faster than adults, so at a specific mg/kg dose, the resulting plasma exposure is lower than in adults.
Adverse reactions
In clinical trials, 1,534 children (aged 6 months to 16 years) received oral and intravenous levofloxacin treatment. Children aged 6 months to 5 years receive levofloxacin 10 mg/kg twice daily, children over 5 years old receive levofloxacin 10 mg/kg once daily (maximum dose is 500 mg daily), total course of treatment It is 10 days.
In a clinical trial, a subgroup of children (1340 receiving levofloxacin and 893 receiving non-fluoroquinolones) participated in a prospective long-term monitoring study to evaluate the first dose of study drug for 60 days and 1 year. The incidence of musculoskeletal disorders (joint pain, arthritis, tendon disorders, gait abnormalities) as defined by the subsequent protocol. The incidence of musculoskeletal disorders in children treated with levofloxacin was significantly higher than in children treated with non-fluoroquinolones, as shown in the following table (Table 8).
Table 8: Incidence of musculoskeletal diseases in pediatric clinical trials
Follow-up period levofloxacin
N = 1340 non-fluoroquinolone a
N = 893 p value b
60 days 28 (2.1%) 8 (0.9%) p = 0.038
1 year c 46 (3.4%) 16 (1.8%) p = 0.025
Note: a. Non-fluoroquinolones: ceftriaxone, amoxicillin/clavulanic acid, clarithromycin.
b. Bilateral Fisher's accuracy test.
c. A one-year evaluation visit was conducted on 1199 levofloxacin-treated children and 804 non-fluoroquinolones-treated children. However, the incidence of musculoskeletal disorders was calculated using all reported events for all participating children during the specified period, regardless of whether they completed a one-year evaluation visit.
Joint pain is the most common musculoskeletal disorder in both treatment groups. In both groups, the vast majority of musculoskeletal diseases involve multiple weight-bearing joints. The disease was moderate in 8/46 (17%) levofloxacin-treated children and mild in 35/46 (76%) levofloxacin-treated children, most of whom received analgesic treatment. The median remission time was 7 days in the levofloxacin-treated group and 9 days in the non-fluoroquinolone-treated group (in both groups, approximately 80% of patients resolved within 2 months). No serious or major illnesses in children, and all musculoskeletal disorders are relieved without sequelae.
Vomiting and diarrhea were the most frequently reported adverse events, with similar rates in the levofloxacin-treated and non-fluoroquinolone-treated groups.
In addition to events reported in clinical trials in pediatric patients, events reported in clinical trials or after-sales monitoring in adult patients may also occur in pediatric patients.
[Geriatric Use]
This product is levofloxacin hydrochloride, the active ingredient of which is levofloxacin. The related cases of levofloxacin reported in the literature are as follows:
Older patients have an increased risk of serious adverse events, including tendon rupture, during the course of receiving fluoroquinolones, such as levofloxacin. This risk is further increased in patients receiving a combination of glucocorticoids. Tendonitis or tendon rupture can affect the ankle, hand, shoulder or other tendon and can occur during or after treatment. The names of the diseases that occurred several months after the end of the fluoroquinolone treatment were reported. Levofloxacin must be used with caution in elderly patients, especially those receiving glucocorticoid therapy. These potential side effects must be communicated to the patient, and if any symptoms of tendinitis or tendon rupture occur, it is recommended to stop levofloxacin treatment and get in touch with healthcare providers.
In phase III clinical trials, 1,945 patients receiving levofloxacin (26%) were ≥ 65 years old, 1081 (14%) were between 65 and 74 years old, and 864 (12%) were equal to or greater than 75 years old. year old. There is no significant difference in the safety and efficacy of these patients and younger patients, but it does not rule out that some older patients may be more sensitive.
In the listing report, there have been serious, even fatal, hepatotoxicities associated with levofloxacin. The main fatal hepatotoxicity reported occurred in the age of 65 or older, and most of them did not have an allergic reaction. Levofloxacin should be discontinued immediately if the patient has symptoms or symptoms of hepatitis.
Elderly patients may be more sensitive to drug-related effects in the QT interval. Therefore, both levofloxacin and certain drugs that cause QT prolongation (such as IA or III antiarrhythmic drugs) or the presence of torsades de pointes (such as known QT interval prolongation, refractory hypokalemia) are used. Patients should be cautious when using levofloxacin.
If the difference in creatinine clearance is considered, there is no significant difference in the pharmacokinetic profile of levofloxacin between young and elderly subjects. However, since levofloxacin is mostly excreted from the kidneys, patients with impaired renal function have a higher risk of drug toxicity. Older patients are more likely to have renal dysfunction, so caution should be exercised when selecting doses, and renal function needs to be monitored simultaneously.
【medicine interactions】
This product is levofloxacin hydrochloride, the active ingredient of which is levofloxacin. The related cases of levofloxacin reported in the literature are as follows:
1. Chelating agents: antacids, sucralfate, metal cations, multivitamin preparations
Levofloxacin oral preparation
Although the chelation of levofloxacin with divalent cations is weaker than other fluoroquinolone antibiotics, it also uses levofloxacin.
Oral preparations of Shaxing and antacids such as magnesium or aluminum and sucralfate, metal cations such as iron and zinc-containing multivitamin preparations can still affect the gastrointestinal absorption of levofloxacin, resulting in a systemic drug concentration significantly lower than the expected concentration. Drugs containing antacids such as magnesium or aluminum and sucralfate, metal cations such as iron and zinc-containing multivitamin preparations or didanosine can significantly affect the gastrointestinal absorption of levofloxacin, resulting in a systemic drug concentration that is significantly lower than expected. These medications should be taken at least two hours before levofloxacin or two hours after taking the drug.
Levofloxacin injection
There are no data on the interaction between intravenous quinolone antibiotics and oral antacids, sucralfate, multivitamin preparations, didanosine or metal cations. However, the quinolone antibiotic should not be instilled through the same intravenous infusion channel with any solution containing a multivalent cation such as magnesium.
7. Other serious and potentially fatal reactions
Other serious and potentially fatal incidents have been reported using fluoroquinolone drugs. Some of these events are due to allergies and some are unknown. These events can be severe and usually occur after multiple doses. Clinical manifestations may include one or more of the following symptoms: fever, rash, severe skin reaction (eg, toxic epidermal necrolysis, Stevens-Johnson syndrome); vasculitis; joint pain; myalgia; 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 thrombocytopenia Purpura; leukopenia; agranulocytosis; pancytopenia and/or other hematological abnormalities. The drug should be discontinued and measures taken immediately on the first occurrence of a rash, jaundice or any other allergic manifestation.
8. The influence of the central nervous system
The use of fluoroquinolone drugs, including levofloxacin hydrochloride tablets, has been reported to increase the risk of adverse central nervous system adverse reactions, including convulsions and increased intracranial pressure (including pseudo-brain tumors) and psychosis caused by poisoning. The use of fluoroquinolone drugs may cause central nervous system reactions including anxiety, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and suicidal thoughts or behaviors. These reactions may occur after the first dose. If these reactions occur when the patient is taking levofloxacin hydrochloride tablets, the administration should be stopped and appropriate measures taken. As with all fluoroquinolone drugs, patients with known or suspected central nervous system disorders (such as severe cerebral arteriosclerosis, epilepsy) or patients with other risk factors (if there is a tendency to attack or a lower threshold for seizures) should be obtained. Levofloxacin hydrochloride tablets are used when the risk exceeds the risk.
9. Peripheral neuropathy
Patients have been reported to use fluoroquinolone drugs to produce a rare sensory or sensorimotor axonal neuropathy that affects small and/or large axons, causing skin paresthesia, sensation of dullness, sensation of touch and weakness. For some patients, symptoms may occur soon after administration of levofloxacin hydrochloride tablets and may be irreversible. If the patient has symptoms of peripheral neuropathy, including pain, burning sensation, tingling, numbness and/or weakness, or other sensations, including changes in light touch, pain, temperature, position, and vibration, stop the drug immediately. Patients with a history of peripheral neuropathy should avoid the use of fluoroquinolone antibiotics.
10. C. difficile-associated diarrhea
Nearly all antibacterial drugs have been reported for C. difficile-associated diarrhea (CDAD), including levofloxacin hydrochloride tablets, ranging from mild diarrhea to severe colitis. Antimicrobial treatment changes the normal flora of the colon, resulting in overgrowth of C. difficile.
Toxins A and B produced by C. difficile are responsible for Clostridium difficile-associated diarrhea. The morbidity and mortality caused by highly toxic Clostridium are elevated, and these infections are ineffective and may require colectomy. After receiving antibiotics, the possibility of CDAD should be considered in the presence of diarrhea. Because CDAD may occur two months after treatment with antibacterial drugs, careful medical history is necessary.
If you suspect or confirm C. difficile-associated diarrhea, you may need to stop the antibiotics currently used against C. difficile. Appropriate supplementation of fluids and electrolytes, protein supplementation, antibiotic treatment for C. difficile should be performed, and surgical evaluation should be performed when clinical indications appear.
11. Interference with blood sugar
There have been reports of fluoroquinolone antibiotics causing blood glucose disorders (such as symptomatic hyperglycemia and hypoglycemia), which often occur in patients with simultaneous oral hypoglycemic agents (such as glibenclamide/glibenclamide) or insulin using insulin. . Therefore, for such patients, it is recommended that their blood glucose changes be closely monitored. If the patient has hypoglycemia when receiving levofloxacin hydrochloride tablets, discontinue the drug immediately and take appropriate treatment.
12. Light sensitivity / phototoxicity
Moderate to severe photosensitivity/phototoxicity after exposure to sunlight or UV light after exposure to fluoroquinolone antibiotics
The reaction, which may exhibit excessive sunburn reactions (eg, burning sensation, erythema, blisters, exudation, edema), often occurs in areas exposed to light (usually the "V"-shaped area of the neck, the forearm extensor surface The back of the hand). Therefore, excessive exposure to light sources should be avoided. The drug should be discontinued when a phototoxic reaction occurs.
13. Hepatotoxicity
Post-marketing reports of severe hepatotoxicity (including acute hepatitis and fatal events) in patients receiving levofloxacin have been received. No evidence of severe drug-related hepatotoxicity was found in clinical trials of more than 7,000 patients. Severe hepatotoxicity usually occurs within 14 days of starting treatment, and in most cases, it occurs within 6 days of starting treatment. Most cases of severe hepatotoxicity have nothing to do with allergies. Most of the fatal liver toxicity reports are seen in patients >65 years of age, most of which are not related to hypersensitivity. Levofloxacin should be discontinued immediately if the patient has signs and symptoms of hepatitis.
14. Musculoskeletal diseases in pediatric patients and joint disease effects in animals
In pediatric patients (≥6 months), levofloxacin is only suitable for the protection of anthrax inhalation (after exposure). Increased incidence of musculoskeletal disorders (joint pain, arthritis, tendon disorder, and gait abnormalities) was observed in pediatric patients receiving levofloxacin compared to controls.
In juvenile rats and dogs, oral and intravenous administration of levofloxacin resulted in an increase in osteochondrosis. Histopathological examination of the weighted joints of juvenile dogs receiving levofloxacin showed continued damage to the cartilage. Other quinolones can also produce similar weight-bearing joint erosions in juvenile animals of multiple species, as well as other signs of joint disease.
15. Drug-resistant bacteria production
Opening levofloxacin prescriptions without a diagnosis or a high degree of suspected bacterial infection and non-compliance with preventive indications does not benefit patients and increases the risk of developing resistant bacteria.
16. It is strictly forbidden to be used in food and feed processing.
[Pregnant women and lactating women]
This product is levofloxacin hydrochloride, the active ingredient of which is levofloxacin. The related cases of levofloxacin reported in the literature are as follows:
Pregnancy
Pregnancy medication grade C. Levofloxacin was not teratogenic when administered orally in rats at doses up to 810 mg/kg/day, which is equivalent to 9.4 times the maximum recommended dose for humans with the same body surface area. At an intravenous infusion dose of 160 mg/kg/day, levofloxacin also had no teratogenic effects, which corresponds to 1.9 times the maximum recommended dose for humans with the same body surface area. Rat oral dose of 810 mg / kg / day can reduce fetal weight and increase mortality. Levofloxacin was not observed to have teratogenic effects when administered orally in rabbits at 50 mg/kg/day, which corresponds to 1.1 times the maximum recommended dose for humans with the same body surface area. At an intravenous infusion dose of 25 mg/kg/day, levofloxacin also had no teratogenic effects, which corresponds to 0.5 times the maximum recommended dose for humans with the same body surface area.
However, there are not enough well-controlled trials for pregnant women to ensure the safety of pregnant women, so women who are pregnant or likely to be pregnant are prohibited. Levofloxacin can only be used in pregnant women when the potential benefit to the fetus is greater than the potential risk.
Lactating woman
Based on limited data from other fluoroquinolones and levofloxacin, it is speculated that levofloxacin should be secreted into human breast milk. Lactating women are banned because levofloxacin may cause serious adverse reactions in breastfed babies. Levofloxacin can be used in lactating women only when the potential benefit to lactating women is greater than the potential risk, but breastfeeding should be suspended.
[Children's medication]
This product is levofloxacin hydrochloride, the active ingredient of which is levofloxacin. The related cases of levofloxacin reported in the literature are as follows:
Quinolone antibiotics, including levofloxacin, can cause joint disease and bone/cartilage lesions in larvae of certain species of animals. The safety of children has not been established and is therefore prohibited for patients younger than 18 years of age, except for the protection of anthrax (after exposure).
Inhalation anthrax (after exposure)
Levofloxacin is indicated for use in pediatric inhaled anthrax (after exposure). Risk-benefit assessment suggests that levofloxacin is appropriate in pediatric patients. The safety of levofloxacin treatment for more than 14 days has not been studied in pediatric patients. The pharmacokinetics of a single intravenous levofloxacin was studied in pediatric patients between the ages of 6 months and 16 years. In children, levofloxacin is cleared faster than adults, so at a specific mg/kg dose, the resulting plasma exposure is lower than in adults.
Adverse reactions
In clinical trials, 1,534 children (aged 6 months to 16 years) received oral and intravenous levofloxacin treatment. Children aged 6 months to 5 years receive levofloxacin 10 mg/kg twice daily, children over 5 years old receive levofloxacin 10 mg/kg once daily (maximum dose is 500 mg daily), total course of treatment It is 10 days.
In a clinical trial, a subgroup of children (1340 receiving levofloxacin and 893 receiving non-fluoroquinolones) participated in a prospective long-term monitoring study to evaluate the first dose of study drug for 60 days and 1 year. The incidence of musculoskeletal disorders (joint pain, arthritis, tendon disorders, gait abnormalities) as defined by the subsequent protocol. The incidence of musculoskeletal disorders in children treated with levofloxacin was significantly higher than in children treated with non-fluoroquinolones, as shown in the following table (Table 8).
Table 8: Incidence of musculoskeletal diseases in pediatric clinical trials
Follow-up period levofloxacin
N = 1340 non-fluoroquinolone a
N = 893 p value b
60 days 28 (2.1%) 8 (0.9%) p = 0.038
1 year c 46 (3.4%) 16 (1.8%) p = 0.025
Note: a. Non-fluoroquinolones: ceftriaxone, amoxicillin/clavulanic acid, clarithromycin.
b. Bilateral Fisher's accuracy test.
c. A one-year evaluation visit was conducted on 1199 levofloxacin-treated children and 804 non-fluoroquinolones-treated children. However, the incidence of musculoskeletal disorders was calculated using all reported events for all participating children during the specified period, regardless of whether they completed a one-year evaluation visit.
Joint pain is the most common musculoskeletal disorder in both treatment groups. In both groups, the vast majority of musculoskeletal diseases involve multiple weight-bearing joints. The disease was moderate in 8/46 (17%) levofloxacin-treated children and mild in 35/46 (76%) levofloxacin-treated children, most of whom received analgesic treatment. The median remission time was 7 days in the levofloxacin-treated group and 9 days in the non-fluoroquinolone-treated group (in both groups, approximately 80% of patients resolved within 2 months). No serious or major illnesses in children, and all musculoskeletal disorders are relieved without sequelae.
Vomiting and diarrhea were the most frequently reported adverse events, with similar rates in the levofloxacin-treated and non-fluoroquinolone-treated groups.
In addition to events reported in clinical trials in pediatric patients, events reported in clinical trials or after-sales monitoring in adult patients may also occur in pediatric patients.
[Geriatric Use]
This product is levofloxacin hydrochloride, the active ingredient of which is levofloxacin. The related cases of levofloxacin reported in the literature are as follows:
Older patients have an increased risk of serious adverse events, including tendon rupture, during the course of receiving fluoroquinolones, such as levofloxacin. This risk is further increased in patients receiving a combination of glucocorticoids. Tendonitis or tendon rupture can affect the ankle, hand, shoulder or other tendon and can occur during or after treatment. The names of the diseases that occurred several months after the end of the fluoroquinolone treatment were reported. Levofloxacin must be used with caution in elderly patients, especially those receiving glucocorticoid therapy. These potential side effects must be communicated to the patient, and if any symptoms of tendinitis or tendon rupture occur, it is recommended to stop levofloxacin treatment and get in touch with healthcare providers.
In phase III clinical trials, 1,945 patients receiving levofloxacin (26%) were ≥ 65 years old, 1081 (14%) were between 65 and 74 years old, and 864 (12%) were equal to or greater than 75 years old. year old. There is no significant difference in the safety and efficacy of these patients and younger patients, but it does not rule out that some older patients may be more sensitive.
In the listing report, there have been serious, even fatal, hepatotoxicities associated with levofloxacin. The main fatal hepatotoxicity reported occurred in the age of 65 or older, and most of them did not have an allergic reaction. Levofloxacin should be discontinued immediately if the patient has symptoms or symptoms of hepatitis.
Elderly patients may be more sensitive to drug-related effects in the QT interval. Therefore, both levofloxacin and certain drugs that cause QT prolongation (such as IA or III antiarrhythmic drugs) or the presence of torsades de pointes (such as known QT interval prolongation, refractory hypokalemia) are used. Patients should be cautious when using levofloxacin.
If the difference in creatinine clearance is considered, there is no significant difference in the pharmacokinetic profile of levofloxacin between young and elderly subjects. However, since levofloxacin is mostly excreted from the kidneys, patients with impaired renal function have a higher risk of drug toxicity. Older patients are more likely to have renal dysfunction, so caution should be exercised when selecting doses, and renal function needs to be monitored simultaneously.
【medicine interactions】
This product is levofloxacin hydrochloride, the active ingredient of which is levofloxacin. The related cases of levofloxacin reported in the literature are as follows:
1. Chelating agents: antacids, sucralfate, metal cations, multivitamin preparations
Levofloxacin oral preparation
Although the chelation of levofloxacin with divalent cations is weaker than other fluoroquinolone antibiotics, it also uses levofloxacin.
Oral preparations of Shaxing and antacids such as magnesium or aluminum and sucralfate, metal cations such as iron and zinc-containing multivitamin preparations can still affect the gastrointestinal absorption of levofloxacin, resulting in a systemic drug concentration significantly lower than the expected concentration. Drugs containing antacids such as magnesium or aluminum and sucralfate, metal cations such as iron and zinc-containing multivitamin preparations or didanosine can significantly affect the gastrointestinal absorption of levofloxacin, resulting in a systemic drug concentration that is significantly lower than expected. These medications should be taken at least two hours before levofloxacin or two hours after taking the drug.
Levofloxacin injection
There are no data on the interaction between intravenous quinolone antibiotics and oral antacids, sucralfate, multivitamin preparations, didanosine or metal cations. However, the quinolone antibiotic should not be instilled through the same intravenous infusion channel with any solution containing a multivalent cation such as magnesium....
【Pharmacology and Toxicology】
This product is levofloxacin hydrochloride, the active ingredient of which is levofloxacin. The related cases of levofloxacin reported in the literature are as follows:
Pharmacological action
Mechanism of action: Levofloxacin is the left-handed body of ofloxacin (racemate), a quinolone antibacterial. The antibacterial effect of ofloxacin is mainly produced by the left-handed body. The mechanism of action of levofloxacin and other fluoroquinolone antibacterial drugs is topoisomerase IV and DNA gyrase (which is topoisomerase II) required for inhibition of bacterial DNA replication, transcription, repair and recombination.
Drug resistance: Fluoroquinolone resistance is caused by mutations in specific regions of DNA gyrase or topoisomerase IV, also known as quinolone resistance determining regions (ORDRs), or changes in the drug efflux system.
Fluoroquinolone antibiotics, including levofloxacin, have different chemical structures and modes of action than aminoglycosides, macrolides, and beta-lactam antibiotics (including penicillin). Therefore, fluoroquinolones may still be effective against the above-mentioned antibiotic-resistant bacteria.
Levofloxacin resistance due to spontaneous variation in in vitro conditions is less (range: 10-9 to 10-10). Although cross-resistance between levofloxacin and some other fluoroquinolones has been observed, bacteria resistant to other fluoroquinolone species may still be sensitive to levofloxacin.
In vitro and in vivo antibacterial activity:
Levofloxacin has antibacterial activity against a variety of Gram-negative and Gram-positive bacteria in vitro, and has bactericidal activity at a concentration equal to or slightly higher than the inhibitory concentration.
In vitro studies and clinical infections have demonstrated that levofloxacin has an antibacterial effect on the following microorganisms:
Gram-positive aerobic bacteria: Enterococcus faecalis (multiple strains are only moderately sensitive), Staphylococcus aureus (methicillin-sensitive strain), Staphylococcus epidermidis (methicillin-sensitive strain), Staphylococcus aureus, Streptococcus pneumoniae [Including multi-drug resistant strains (MDRSP)*], S. pyogenes.
Note: MDRSP (multi-drug resistant pneumococci) refers to strains resistant to two or more of the following antibiotics: penicillin (MIC ≥ 2 μg/mL), second-generation cephalosporins (such as cefuroxime), large Cyclolactones, tetracycline and trimethoprim/sulfamethoxazole.
Gram-negative aerobic bacteria: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Legionella pneumoniae, Moraxella catarrhalis, Proteus mirabilis, patina Cytobacteria*, Serratia marcescens.
Note: * As with other drugs in this category, certain strains of P. aeruginosa can quickly develop resistance when treated with levofloxacin.
Other microorganisms: Chlamydia pneumoniae, Mycoplasma pneumoniae.
Levofloxacin has an antibacterial effect on Bacillus anthracis in the macaque anthrax (post-exposure) model and in vitro conditions using plasma concentrations as surrogate markers.
The following data are in vitro test results, but their clinical significance is unknown:
The minimum inhibitory concentration (MIC) of levofloxacin to most strains (≥90%) of the following microorganisms in vitro was 2 μg/mL or lower; however, the safety and efficacy of levofloxacin in the treatment of clinical infections caused by these microorganisms No adequate, well-controlled trial studies have been conducted.
Gram-positive aerobic bacteria: hemolytic staphylococci, β-hemolytic streptococci (C/F group), β-hemolytic streptococcus (group G), Streptococcus agalactiae, Streptococcus mutans, Streptococcus viridans.
Gram-negative aerobic bacteria: Acinetobacter baumannii, Acinetobacter baumannii, Bordetella pertussis, Citrobacter erecta (different Citrobacter), Citrobacter freundii, Enterobacter aerogenes, Enterobacter sakazakii, Klebsiella, K. faecalis, Enterobacter agglomerans, Proteus vulgaris, Providencia serrata, Providencia striata, Pseudomonas fluorescens.
Gram-positive anaerobic bacteria: Clostridium perfringens.
2. Non-clinical toxicology
Carcinogenicity, mutagenicity, reproductive function damage: Bioassay results in the whole life of rats showed that taking levofloxacin daily for 2 years did not show any carcinogenic effects. The highest dose used (100 mg/kg/day) was 1.4 times the recommended maximum dose (750 mg) for humans (based on relative body surface area). Any dose of levofloxacin did not shorten the progression time of UV-induced albino nude mouse (Skh-1) skin tumors, and therefore did not have photocarcinogenicity under the conditions of this test. In the photocarcinogenicity test, the levofloxacin concentration in nude mice ranged from 25 to 42 μg/g at the maximum dose of levofloxacin (300 mg/kg/day). At a dose of 750 mg, the Cmax of the levofloxacin skin concentration in human subjects averaged about 11.8 μg/g.
The following tests indicate that levofloxacin does not have mutagenic effects: Ames bacterial mutation analysis (S. typhimurium and Escherichia coli), CHO/HGPRT forward mutation detection, mouse micronucleus test, mouse dominant lethal test, rat non-procedure Sex DNA synthesis assay, mouse sister chromatid exchange test. Positive in in vitro chromosomal aberrations (CHL cell line) and sister chromatid exchange test (CHL/IU cell line).
Levofloxacin has no damage to its ability to reproduce when the oral dose is as high as 360 mg/kg/day. This dose is equivalent to 4.2 times the maximum recommended dose for humans with the same body surface area. At an intravenous infusion dose of 100 mg/kg/day, levofloxacin did not impair its ability to reproduce, which corresponds to 1.2 times the maximum recommended dose for humans with the same body surface area.
Animal Toxicology and/or Pharmacodynamics: Levofloxacin and other quinolone antibiotics have been shown to cause joint lesions in juvenile experimental animals of most species. Juvenile dogs (4 to 5 months old) orally administered levofloxacin at a dose of 10 mg/kg/day for 7 consecutive days, or intravenously, at a dose of 4 mg/kg/day for 14 consecutive days. Joint damage. The oral dose of juvenile rats is 300 mg/kg/day, continuous administration for 7 days, or intravenous administration, the dose is 60 mg/kg/day, and continuous administration for 4 weeks can cause joint lesions. The 3-month-old beagle was orally administered with a regular dose of levofloxacin 40 mg/kg/day for 14 consecutive days, and severe joint toxicity occurred on the 8th day. At doses ≥ 2.5 mg/kg (based on a comparison of plasma AUC, approximately 0.2 times the amount of children), clinical manifestations of mild musculoskeletal injury may occur, but gross pathology and histopathological damage are not present. Synovitis and articular cartilage damage can be caused by doses of 10 and 40 mg/kg (about 0.7 and 2.4 times, respectively, for children). After 18 weeks of recovery, the gross pathology and histopathology of articular cartilage still exist.
The mouse ear swelling test showed that the phototoxicity of levofloxacin was similar to that of ofloxacin, but weaker than other quinolones.
Although crystallized urine was found in certain intravenously administered rat tests, crystallization was not formed in the bladder but was formed after urination and therefore did not mean that levofloxacin was nephrotoxic.
Simultaneous use with non-steroidal anti-inflammatory drugs can aggravate the stimulating effect of quinolones on mouse CNS.
When the dose of levofloxacin is 6 mg/kg or higher, rapid intravenous injection can cause hypotension in dogs. This effect may be related to the release of histamine.
In vitro and in vivo experiments in animals have shown that levofloxacin is neither an enzyme inducer nor an enzyme inhibitor in the range of plasma concentrations in which the body functions as a therapeutic agent, and therefore, there is no drug-metabolizing enzyme-related interaction with other drugs or agents.
【Pharmacokinetics】
This product is levofloxacin hydrochloride, its active ingredient is levofloxacin. The pharmacokinetics of levofloxacin reported in the literature are as follows:
The pharmacokinetic parameters of levofloxacin tablets, oral liquid or intravenous administration and levofloxacin after steady-state administration were determined as Mean±SD, which are summarized in the following table (Table 9).
Table 9: Mean±SD of levofloxacin PK parameters
Treatment plan Cmax
(μg/mL) Tmax
(h) AUC
(μg·h/mL) CL/F1
(mL/min) Vd/F2
(L) t1/2
(h) CLR
(mL/min)
Single dose
250 mg p.o. Tablet 3 2.8 ± 0.4 1.6 ± 1.0 27.2 ± 3.9 156 ± 20 ND 7.3 ± 0.9 142 ± 21
500 mg p.o. Tablet 3* 5.1 ± 0.8 1.3 ± 0.6 47.9 ± 6.8 178 ± 28 ND 6.3 ± 0.6 103 ± 30
500 mg oral solution 12 5.8 ± 1.8 0.8 ± 0.7 47.8 ± 10.8 183 ± 40 112 ± 37.2 7.0 ± 1.4 ND
500 mg i.v.3 6.2 ± 1.0 1.0 ± 0.1 48.3 ± 5.4 175 ± 20 90 ± 11 6.4 ± 0.7 112 ± 25
750 mg p.o. Tablet 5* 9.3 ± 1.6 1.6 ± 0.8 101 ± 20 129 ± 24 83 ± 17 7.5 ± 0.9 ND
750 mg i.v.5 11.5 ± 4.04 ND 110 ± 40 126 ± 39 75 ± 13 7.5 ±1.6 ND
Multiple doses
500 mg q24h p.o. Tablet 3 5.7 ± 1.4 1.1 ± 0.4 47.5 ± 6.7 175 ± 25 102 ± 22 7.6 ± 1.6 116 ± 31
500 mg q24h i.v. 3 6.4 ± 0.8 ND 54.6 ± 11.1 158 ± 29 91 ± 12 7.0 ± 0.8 99 ± 28
500 mg or 250 mg q24h i.v. 8.7 ± 4.07 ND 72.5 ± 51.27 154 ± 72 111 ± 58 ND ND
Bacterial infection patients 6
750 mg q24h p.o. tablets 5 8.6 ± 1.9 1.4 ± 0.5 90.7 ± 17.6 143 ± 29 100 ± 16 8.8 ± 1.5 116 ± 28
750 mg q24h i.v. 5 12.1 ± 4.14 ND 108 ± 34 126 ± 37 80 ± 27 7.9 ± 1.9 ND
500 mg p.o. tablets, single dose, sex and age factors:
Male 8 5.5 ± 1.1 1.2 ± 0.4 54.4 ± 18.9 166 ± 44 89 ± 13 7.5 ± 2.1 126 ± 38
Female 9 7.0 ± 1.6 1.7 ± 0.5 67.7 ± 24.2 136 ± 44 62 ± 16 6.1 ± 0.8 106 ± 40
Young people 10 5.5 ± 1.0 1.5 ± 0.6 47.5 ± 9.8 182 ± 35 83 ± 18 6.0 ± 0.9 140 ± 33
Older people 11 7.0 ± 1.6 1.4 ± 0.5 74.7 ±23.3 121 ± 33 67 ± 19 7.6 ±2.0 91 ± 29
500 mg p.o. Single dose, tablet, renal insufficiency:
CLCR50-80 mL/min 7.5 ± 1.8 1.5 ± 0.5 95.6 ± 11.8 88 ± 10 ND 9.1 ± 0.9 57 ± 8
CLCR20-49 mL/min 7.1 ± 3.1 2.1 ± 1.3 182.1 ± 62.6 51 ± 19 ND 27 ± 10 26 ± 13
CLCR<20 mL/min 8.2 ± 2.6 1.1 ± 1.0 263.5 ± 72.5 33 ± 8 ND 35 ± 5 13 ± 3
Hemodialysis 5.7 ± 1.0 2.8 ± 2.2 ND ND ND 76 ±42 ND
CAPD 6.9 ± 2.3 1.4 ± 1.1 ND ND ND 51 ± 24 ND
Note: 1 clearance rate / bioavailability.
2 Distribution volume / bioavailability.
3 healthy men, aged 18 to 53 years old.
4 When the dose is 250 mg and 500 mg, instill for 60 minutes, and when the dose is 750 mg, instill for 90 minutes.
5 Healthy male and female subjects, aged 18 to 54 years.
6 Patients with moderate renal impairment and patients with respiratory or skin infections were given 500 mg (CLCR 20-50 mL/min) every 48 hours.
7 Dose standard values (500 mg dose) estimated according to the population pharmacokinetic model.
8 healthy men, aged 22 to 75 years old.
9 healthy women, aged 18 to 80 years old.
10 Healthy young male and female subjects, aged 18 to 36 years.
11 Healthy elderly male and female subjects, aged 66 to 80 years.
12 Healthy men and women, aged 19 to 55 years.
13 Absolute bioavailability; 500 mg tablets, F = 0.99 ± 0.08; 750 mg tablets, F = 0.99 ± 0.06;
ND = not detected.
absorb
After oral administration of levofloxacin, the absorption is rapid and complete, usually peaking in plasma drug concentration 1 to 2 hours after oral administration. The absolute bioavailability of levofloxacin 500 mg tablets and 750 mg tablets was approximately 99%, indicating complete absorption of levofloxacin after oral administration. A single intravenous dose of healthy volunteers was given at a dose of 500 mg. When the infusion time was greater than 60 minutes, the peak plasma concentration of Mean±SD was 6.2 ± 1.0 μg/mL; the dose was 750 mg, and the infusion time was greater than 90 minutes. The Mean±SD of the peak plasma concentration was 11.5 ± 4.0 μg/mL. Levofloxacin oral solutions and tablets are bioequivalent.
After single or multiple oral or injections of levofloxacin, the pharmacokinetics is linear and predicts changes in pharmacokinetics. Take the drug once a day, when the dose is 500 mg or 750 mg, reach steady state after 48 hours. Take 500 mg once a day orally, and the Mean±SD of plasma peak concentration and trough concentration after multiple administrations are 5.7 ± 1.4 and 0.5 ± 0, respectively.
.2 μg/mL; and oral administration once a day, once 750 mg, Mean ± SD of peak and trough concentrations after multiple administrations were 8.6 ± 1.9 and 1.1 ± 0.4 μg / mL, respectively. Intravenous infusion, once daily, at a dose of 500 mg, the Mean±SD of peak and trough concentrations after multiple administrations were 6.4 ± 0.8 and 0.6 ± 0.2 μg/mL, respectively, at a dose of 750 mg. Mean±SD of plasma peak concentration and trough concentration after multiple administrations were 12.1 ± 4.1 and 1.3 ± 0.71 μg/mL, respectively.
Taking oral levofloxacin 500 mg while eating will delay the peak time by about 1 hour, and reduce the peak concentration, the tablet is reduced by about 14%, and the oral solution is reduced by about 25%. Therefore, taking levofloxacin tablets has nothing to do with eating or not. However, it is recommended that levofloxacin oral solution should be taken 1 hour before meals or 2 hours after meals. The time course (AUC) of plasma drug concentration change after levofloxacin injection administration was similar to the time curve after oral administration of the same dose (mg/mg) tablet. Therefore, both oral and injectable routes of administration can be substituted for each other.
distributed
Levofloxacin is administered single or multiple times at a dose of 500 mg or 750 mg, with an average volume of 74 to 112 L, which means that levofloxacin can be widely distributed in various tissues of the body. Healthy subjects peaked in drug concentrations in the skin and body fluids approximately 3 hours after administration.
Healthy subjects were orally administered once daily at doses of 750 mg and 500 mg. After multiple doses, the ratio of skin to plasma AUC was about 2, and the ratio of body fluid to plasma AUC was about 1. Levofloxacin also has good permeability to lung tissue. For a single oral administration, at a dose of 500 mg, the drug concentration in the lungs after 24 hours is usually 2 to 5 times higher than the plasma concentration, and the concentration range is about 2.4 to 11.3 μg/g.
In the case of ex vivo, equilibrium dialysis was used to measure approximately 82% to 38% of levofloxacin and serum in the range of levofloxacin clinically relevant serum/plasma concentrations (1–10 μg/mL). Protein binding. In humans, levofloxacin is primarily associated with serum albumin. The binding of levofloxacin to serum proteins was independent of drug concentration.
metabolism
Levofloxacin has a stable stereochemical structure in plasma and urine and is not metabolized to its optical isomer, D-oxaloxacin. The body's metabolism to levofloxacin is very low, and it is mainly excreted in the urine in its original form. After oral administration, approximately 87% of the drug was excreted in the form of urine in 48 hours, and less than 4% of the drug was excreted in the feces within 72 hours. Less than 5% of the drug is excreted in the urine in the form of demethylated metabolites and N-oxidized metabolites, which are the only two metabolites in humans. The pharmacological activities of these two metabolites are weak.
excretion
Levofloxacin is mainly excreted in the urine in its original form. After oral or intravenous single or multiple administration, the average terminal plasma elimination half-life is about 6 to 8 hours. The mean apparent clearance and renal clearance were approximately 144-226 mL/min and 96-142 mL/min, respectively.
Renal clearance exceeds glomerular filtration rate, indicating that levofloxacin is not only filtered through the glomerulus, but can also be secreted through the renal tubules. Simultaneous administration of cimetidine or probenecid reduced the renal clearance of levofloxacin by approximately 24% and 35%, respectively, indicating that levofloxacin secretion occurs mainly in the proximal convoluted tubules of the kidney. No levofloxacin crystals were found in fresh urine samples from subjects who received levofloxacin.
Elderly
There was no significant difference in the pharmacokinetics of levofloxacin between young and elderly subjects if the difference in creatinine clearance was considered in the subjects. Healthy elderly subjects (aged 66-80 years) received levofloxacin orally at a dose of 500 mg, with an average terminal plasma elimination half-life of about 7.6 hours, compared to about 6 hours for young adults. The reason for this difference is that the subject's renal function is different and is considered to be of no clinical significance. Age also has no effect on drug absorption. Therefore, it is not necessary to adjust the dosage of levofloxacin based solely on age.
child
The pharmacokinetics of a single intravenous administration of 7 mg/kg levofloxacin was studied in children between 6 months and 16 years of age. Levofloxacin is cleared faster in children than in adults. Leading to plasma exposure is lower than the corresponding dose for adults. 8 months to 17 years old children 8mg/kg, once every 12 hours (no more than 250mg each time) can fully reach steady-state plasma exposure (AUC0-24 and Cmax), while adults need 500mg every 24 hours 1 The second-time steady-state plasma exposure.
gender
There was no significant difference in the pharmacokinetics of levofloxacin between male and female subjects if the difference in creatinine clearance was considered in the subjects. Healthy male subjects received oral levofloxacin at a dose of 500 mg with an average terminal plasma elimination half-life of approximately 7.5 hours compared to approximately 6.1 hours for women. The reason for this difference is that male and female subjects have different renal functional status and are considered to be of no clinical significance. Subject gender had no effect on drug absorption. There is no need to adjust the dose of levofloxacin based solely on gender.
race
Data from 72 subjects were analyzed by covariance analysis to investigate the effects of ethnic factors on levofloxacin pharmacokinetics, including 48 Caucasians and 24 non-whites. The subject's race had no effect on apparent clearance and apparent volume of distribution.
Kidney damage
In patients with impaired renal function (creatinine clearance <50 mL/min), the clearance of levofloxacin was significantly reduced, and the half-life of plasma clearance was significantly prolonged. Therefore, the dosage of these patients needs to be adjusted to avoid drug accumulation.
Neither hemodialysis nor continuous ambulatory peritoneal dialysis (CAPD) can effectively remove levofloxacin in the body, indicating that levofloxacin should not be taken after hemodialysis and CAPD.
Liver damage
The pharmacokinetics of patients with liver damage were not studied. Due to the low metabolism of levofloxacin, liver function damage may not affect the pharmacokinetics of levofloxacin.
Bacterial infections
The pharmacokinetic profile of levofloxacin in patients with severe community-acquired bacterial infections is similar to the pharmacokinetic profile of healthy subjects.
medicine interactions
The interaction between levofloxacin and theophylline, warfarin, cyclosporine, digoxin, probenecid, cimetidine, sucralfate and antacids was studied (see medicine interactions).
[Storage] shading, sealed (10 ~ 30 ° C) preservation.
[Packing] Aluminum-plastic packaging, 6 pieces per box; 10 pieces per box; 12 pieces per box.
[Validity Period] 24 months
[Executive Standards] "Chinese Pharmacopoeia" 2015 Edition 2
【Approval Number】
(1) National Drug Standard H19990053 (0.1g according to C18H20FN3O4)
(2) National medicine standard word H20067901 (0.2g according to C18H20FN3O4)
【manufacturer】
Company Name: Guangdong Pi Di Pharmaceutical Co., Ltd.
Production address: No. 66, Pidi Avenue, Yueshan Town, Kaiping City, Guangdong Province
Postal code: 529331
Phone number: (0750) 2789348
400-8899-328 (National Service Phone)
Fax number: (0750) 2789348
Website: http://www.pdpharm.com
Registered trademark
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