Gatifloxacin Mesylate for Injection

Pharmacological action Gatifloxacin is a racemic compound of 8-methoxyfluoroquinolone, which has a broad spectrum of activity against Gram-negative and Gram-positive microorganisms in vitro, and its R- and S-enantiomers have the same antibacterial activity. The antibacterial effect of this product is through inhibiting bacterial DNA gyrase and topoisomerase IV, thereby inhibiting bacterial DNA replication, transcription and repair processes. In vitro tests and clinical use results have shown that this product has antibacterial activity against most strains of the following microorganisms: 1. Gram-positive bacteria: Staphylococcus aureus (limited to strains sensitive to methicillin), Streptococcus pneumoniae (strains sensitive to penicillin). 2. Gram-negative bacteria: Escherichia coli, Haemophilus influenzae and parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Neisseria gonorrhoeae, Proteus mirabilis. 3. Other microorganisms: Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae. Toxicological studies: Genotoxicity: In the Ames test, this product has no mutagenic effect on a variety of strains, but it has a mutagenic effect on Salmonella strain TA102 in vitro. The results of gene mutation tests in Chinese hamster V79 cells and genetic tests in Chinese hamster CHL/IU cells were both positive. Similar results can also be seen in other quinolone drugs, which may be due to the inhibitory effect of this product on type II DNA topoisomerase in eukaryotes at high concentrations. The results of the mouse micronucleus test, rat oral cytogenetic test, and rat oral DNA repair test of this product were all negative. Reproductive toxicity: The oral dose of rats was up to 200 mg/kg (equivalent to the maximum recommended dose for humans based on daily systemic exposure [AUC]), and there was no adverse reaction to rat fertility and reproduction. The oral doses of rats and rabbits reached 150 mg/kg and 50 mg/kg, respectively (based on AUC, approximately 0.7 and 1.9 times the maximum recommended dose for humans in clinical practice), and no teratogenic effect was observed. However, during the period of organogenesis, oral or intravenous administration of 200 mg/kg and 60 mg/kg, respectively, can cause fetal skeletal malformations in rats; oral or intravenous administration of ≥150 mg/kg and ≥30 mg/kg, respectively, can cause delayed fetal skeletal ossification, including the appearance of wavy ribs. This suggests that at this dose, there is mild fetal toxicity. This toxicity can also be seen in other quinolones. Rats were given oral doses of 200 mg/kg in the initial stage of late pregnancy and continued to be administered until lactation. Increased post-implantation embryo loss and increased mortality in newborn rats and perinatal periods were observed. These findings also suggest the fetal toxicity of this product. Carcinogenicity: B6C3F1 mice were administered with the drug by mixing it with food for 18 months, with the doses for female and male animals being 90 mg/kg and 81 mg/kg respectively (based on AUC, it is approximately 0.13 and 0.18 times the maximum recommended dose for humans in clinical practice); Fischer344 rats were administered with the drug by mixing it with food for 2 years, with the doses for female and male animals being 139 mg/kg and 47 mg/kg respectively (based on AUC, it is approximately 0.81 and 0.36 times the maximum recommended dose for humans in clinical practice). The results did not indicate that this product has the effect of promoting tumor growth. However, when the dose of male animals reached 100 mg/kg (based on AUC, it is approximately 0.74 times the maximum recommended dose for humans), the incidence of giant granulocyte lymphoblastic (LGL) leukemia was increased compared with the control group. Although this increase was slightly higher than the range of historical controls, it cannot be considered that these findings at high doses in male animals will affect the safety of this product in clinical use.

The active ingredient of this product is gatifloxacin mesylate. Chemical name: (±) 1-cyclopropyl-6-fluoro-7-(3-methyl-1-piperazinyl)-8-methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid methanesulfonate. Chemical structure: Molecular formula: C19H22FN3O4·CH3SO3H Molecular weight: 471.51

This product is white to light yellow loose lumps and powder.

This product is suitable for the following moderate and severe infections caused by sensitive bacteria: 1. Respiratory system infections: acute bronchitis, acute exacerbation of chronic bronchitis, diffuse bacterial bronchitis, bronchiectasis and infection, pneumonia, tonsillitis (peritonsillar abscess); 2. Urinary system infections: pyelonephritis, complicated urinary tract infection, etc.; 3. Reproductive system infections: acute prostatitis, acute epididymitis, intrauterine infection, adnexitis, pelvic inflammatory disease (metronidazole can be used in combination when anaerobic infection is suspected); 4. Skin and soft tissue infections: infectious impetigo, cellulitis, lymphangiitis (adenitis), subcutaneous abscess, perianal abscess, etc.; 5. Intestinal infections: bacillary dysentery, infectious enteritis, salmonella enteritis, typhoid and paratyphoid; sepsis, granulocytopenia

Intravenous drip, 400 mg each time, once a day, refer to the table below (Table 1) for details. This product is a powder injection, which can be used after being diluted to 2 mg/ml with 5% glucose injection or 0.9% sodium chloride injection. This product is bioequivalent to oral tablets. During the course of treatment, it can be changed from intravenous administration to oral tablets according to the doctor's decision, and no dosage adjustment is required. Table 1 Dosage Guide Gatifloxacin is mainly excreted through the kidneys. Patients with creatinine clearance less than 40 ml/min, including hemodialysis and long-term peritoneal dialysis patients, should adjust the dose of this product. Hemodialysis patients should take the drug after each hemodialysis. For renal insufficiency, refer to the table below (Table 2) for usage and dosage. Table 2 Recommended dose of this product for patients with renal insufficiency Patients with renal insufficiency do not need to adjust the dose of this product when using a single dose of 400 mg to treat simple urinary tract infection or gonorrhea, and 200 mg daily for 3 days to treat simple urinary tract infection.

Adverse reactions seen in clinical trials are mostly mild, mainly seen in the intravenous administration site and the gastrointestinal tract and nervous system, including phlebitis, nausea, vomiting, diarrhea, headache and dizziness. Other rare clinically relevant adverse events include: Systemic reactions: allergic reactions, chills, fever, back pain, chest pain, weakness and facial edema. Cardiovascular system: hypertension, palpitations. Digestive system: abdominal pain, constipation, indigestion, glossitis, candidal stomatitis, stomatitis, oral ulcers, vomiting, loss of appetite, gastritis and flatulence. Metabolic and nutritional system: peripheral edema, hyperglycemia and thirst. Musculoskeletal system: joint pain, painful cramps in the lower limbs. Nervous system: dreaminess, insomnia, paresthesia, tremor, vasodilation, dizziness, agitation, anxiety, confusion and tension. Respiratory system: dyspnea, pharyngitis. Skin and skin soft tissue: rash, sweating, dry skin and itching. Special senses: visual abnormalities, taste abnormalities, tinnitus. Urogenital system: dysuria. Rare related adverse events include: abnormal thinking, alcohol intolerance, arthritis, weakness, asthma (bronchospasm), ataxia, bone pain, bradycardia, chest pain, cheilitis, colitis, confusion, convulsions, cyanosis, depersonalization, depression, diabetes, dysphagia, ear pain, ecchymosis, edema, epistaxis, euphoria, eye pain, photosensitivity, generalized edema, gastrointestinal bleeding, gingivitis, halitosis, hallucinations, hematemesis, hematuria, hostility, hyperesthesia, hyperglycemia, increased muscle tension, hyperventilation, hypoglycemia, lymphadenopathy, maculopapular rash, uterine bleeding, migraine, oral edema, myalgia, muscle weakness, neck pain, panic, paranoia, smell perversion, photophobia, pseudomembranous enterocolitis, psychosis, ptosis, rectal bleeding, tension, substernal chest pain, tachycardia, loss of taste, tongue swelling, herpes, etc. The incidence of abnormal changes in laboratory tests is low, including: leukopenia, neutropenia, decreased hemoglobin, increased ALT and/or AST, as well as alkaline phosphatase, total bilirubin, blood sugar, serum amylase and electrolyte disorders.

This product is contraindicated for patients who are allergic to gatifloxacin or quinolones. It is contraindicated for patients with diabetes.

Precautions for children: The efficacy and safety of this product for children and adolescents (under 18 years old) have not been established, and it is recommended that this product be prohibited. Precautions for pregnancy and lactation: The efficacy and safety of gatifloxacin for pregnant and lactating women have not been established. Pregnant women should avoid using this product, and lactating women should suspend breastfeeding when using it. Precautions for the elderly: Elderly patients are more likely to suffer from reduced renal function and may also be at greater risk of toxic reactions. Therefore, caution should be exercised when selecting the dosage, and monitoring renal function will be helpful. After gatifloxacin was launched, it has been reported that elderly patients treated with gatifloxacin had significant abnormal blood sugar. Elderly patients may have undetected diabetes, age-related reduced renal function, underlying diseases, and/or are taking concomitant medications that affect glucose metabolism, which may pose a special risk for abnormal blood sugar. When preparing to use gatifloxacin for patients, it is recommended that doctors discuss with patients who may be at risk of hypoglycemia and/or hyperglycemia (abnormal blood sugar metabolism events) so that patients know how to monitor their blood sugar changes and what measures should be taken when such changes occur.

1. This product can be used in combination with probenecid to slow down the elimination of gatifloxacin through the kidney. 2. When this product is used simultaneously with digoxin, no significant changes in the pharmacokinetics of gatifloxacin are observed, but increased digoxin blood concentrations are found in some subjects. Therefore, patients taking digoxin should be monitored for symptoms and signs of digoxin toxicity. For patients showing toxic symptoms and signs, the blood concentration of digoxin should be measured and the digoxin dose should be adjusted appropriately. However, it is not recommended to adjust the doses of the two drugs in advance. 3. The simultaneous use of gatifloxacin and drugs that affect glucose metabolism can increase the risk of abnormal blood glucose metabolism in patients (see Contraindications and Warnings: Abnormal Blood Glucose). Antidiabetic drugs: Pharmacodynamic changes that affect glucose metabolism have been observed after the combined use of glibenclamide and other hypoglycemic drugs. No significant pharmacokinetic interactions were observed when glibenclamide was administered concomitantly with gatifloxacin.

Keep in a dark, sealed and dry place.

0.2g (based on gatifloxacin)

24 months