GMP manufactured 

USP/BP 0.2g/100mL Levofloxacin lactate injection

Generic name: Levofloxacin Lactate Injection

The main ingredient of this product is levofloxacin lactate, its chemical name is: (S)-(-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl )-7-oxo-7H-pyrido[1,2,3-de]-[1,4]-benzoxazine-6-carboxylic acid lactate hemihydrate.

Molecular formula C18H20FN3O4·C3H6O3·1/2H2O

Molecular weight 460.41

[Properties] This product is a light yellow-green clear liquid.

Pharmacology and ToxicologyPharmacological effects

Levofloxacin is the L-body of ofloxacin. Its antibacterial activity is about twice that of ofloxacin. Its main mechanism of action is to inhibit bacterial DNA gyrase (bacterial topoisomerase) activity and hinder bacterial DNA replication To achieve antibacterial effect.

This product has the characteristics of wide antibacterial spectrum and strong antibacterial effect. It is against most Enterobacteriaceae bacteria, such as Escherichia coli, Klebsiella, Serratia, Proteus, Shigella, Salmonella, Citrobacter, Acinetobacter, Pseudomonas aeruginosa, Haemophilus influenzae, Neisseria gonorrhoeae and other gram-negative bacteria have strong antibacterial activity. It also has a good antibacterial effect on some methicillin-sensitive glucococcus, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus hemolyticus and other gram-positive bacteria, as well as Legionella, Mycoplasma, and Chlamydia, but it has a good antibacterial effect on anaerobic bacteria and enterococci. The effect is poor.

Toxicology

Repeated dosing toxicity: Rats were given levofloxacin doses of 50, 200, 800 mg/kg orally for 4 consecutive weeks, only the 800 mg/kg treatment group showed a decrease in neutrophils and an increase in bone marrow M/E; histopathology can be seen Mild degeneration of the joint surface of the limb. Rhesus monkeys were administered orally for 4 weeks, and the animals in the 100 mg/kg group showed salivation, diarrhea, mild body weight, and decreased urine pH. After oral administration of rats for 26 weeks, animals in the 80 and 320 mg/kg dose groups experienced salivation and increased urine pH. The amount of feces in the 320 mg/kg group increased, and the goblet cells of the cecal mucosa became enlarged. When rhesus monkeys were administered orally for 26 weeks, there were no obvious toxic reactions at the doses of 10, 25, and 62.5 mg/kg.

Effects on articular cartilage: young and 3-4 week old rats, 4-month-old harrier orally administered for 7 days, when the dose is above 300mg/kg for rats and 10mg/kg for harrier, joints appear Cartilage lesions, and joint toxicity is easily found in young and young harriers. A 13-month-old dog, orally administered for 7 days, showed very mild joint toxicity at a dose of 40 mg/kg. However, an 18-month-old dog was intravenously injected for 14 days at a dose of 30 mg/kg without joint toxicity.

Reproductive toxicity: When the oral dose reaches 360mg/kg before pregnancy and early pregnancy in rats, it has no effect on the reproductive ability of female and male animals and the fetus. When administered to rats during the organogenesis period, at a dose of 90 mg/kg, there is no significant effect on the fetus and newborn. When rabbits were administered 50mg/kg orally, there was no embryonic, fetal lethality, fetal growth retardation, and no teratogenic effects. When the oral administration of rats reached 360 mg/kg during the perinatal and lactation period, there was no significant effect on the delivery, lactation and birth of the animals.

Phototoxicity: Long-wavelength ultraviolet (320-400nm) irradiation was used to conduct a phototoxicity study with the change in the thickness of the mouse auricle as an indicator. As a result, no obvious abnormal changes were seen when the oral dose reached 200mg/kg.

[Pharmacokinetics] A constant rate of intravenous drip of levofloxacin lactate injection 0.2g (calculated as C18H20FN3O4) in healthy people in China, the drip time is 1 hour, and the peak blood concentration (Cmax) is 3.40 (2.8~4.0) μg/ml After 12 hours, the plasma concentration is 0.55(0.3~0.7)μg/ml, the elimination half-life (t1/2β) is about 5.2 hours, and the elimination rate (CL) is about 11.2L/h. There is still a lack of human pharmacokinetic data for intravenous infusion of levofloxacin lactate injection 0.3g.

According to foreign data, the pharmacokinetic parameters of a single intravenous injection of levofloxacin 300 mg and oral administration of the same dose are similar.

In the multi-dose study (300 mg twice a day intravenously for 6 days), the plasma concentration reached a steady state within 24-48 hours. The peak plasma concentrations after the first and last dose were 5.35 and 6.12μg/ml, respectively, indicating that there was no significant accumulation.

Levofloxacin is widely distributed in body tissues. The original drug is mainly excreted in the urine. Within 48 hours after oral administration, the urine excretion of the original drug accounts for about 87% of the dose; the excretion of the feces within 72 hours is less than 4% of the dose; About 5% of the drug is excreted in the urine in the form of inactive metabolites.

In patients with impaired renal function, the clearance rate of levofloxacin decreases and the elimination half-life is prolonged. To avoid accumulation of the drug, dosage adjustments should be made. Hemodialysis and continuous peritoneal dialysis (CAPD) do not affect the elimination of levofloxacin from the body.

[Indications] This product is suitable for the following moderate and severe infections caused by sensitive bacteria:

Respiratory system infection: acute bronchitis, acute exacerbation of chronic bronchitis, diffuse bronchiolitis, bronchiectasis combined infection, pneumonia, tonsillitis (peritonsillar abscess);

Urinary system infections: pyelonephritis, complicated urinary tract infections, etc.;

Reproductive system infections: acute prostatitis, acute epididymitis, uterine cavity infection, uterine adnexitis, pelvic inflammatory disease (metronidazole can be combined with suspected anaerobic infection);

Skin and soft tissue infections: infectious impetigo, cellulitis, lymphatic (nodular) inflammation, subcutaneous abscess, perianal abscess, etc.;

Intestinal infections: bacillary dysentery, infectious enteritis, Salmonella enteritis, typhoid fever and paratyphoid fever;

Various infections in patients with sepsis, neutropenia and immunocompromised;

Other infections: mastitis, trauma, burns and postoperative wound infections, abdominal cavity infections (with metronidazole if necessary), cholecystitis, cholangitis, bone and joint infections, and ENT infections.

Usage and DosageIntravenous drip. Adults 0.1~0.2g once, twice a day, or as directed by a doctor; severely infected patients and pathogenic bacteria that are less sensitive to this product (such as Pseudomonas aeruginosa), the maximum daily dose can be increased to 600mg, divided into 2 intravenous infusions .

[Adverse reactions] Nausea, vomiting, abdominal discomfort, diarrhea, loss of appetite, abdominal pain, bloating and other symptoms may occur during the medication; insomnia, dizziness, headache and other neurological symptoms; rash, itching, erythema and redness, itching or veins at the injection site Symptoms such as inflammation. There may also be an overdue abnormal liver function. Such as increased blood transaminase, increased serum total bilirubin and so on. Occasionally, blood urea nitrogen rises, fatigue, fever, heart palpitations, abnormal taste, and vascular irritation after injection, etc., are generally tolerated and will disappear after the course of treatment.

    [Contraindications] People who are allergic to quinolones, patients with epilepsy, pregnant and lactating women, and patients under 18 years old are contraindicated.

    Notes 1. Patients with renal insufficiency should reduce the dose or use it with caution.

    2. Use with caution in patients with central nervous system diseases.

    3. This preparation is for intravenous drip only, and the drip time is at least 60 minutes per 100ml intravenous drip rate. Too fast drip rate can easily cause venous irritation or central nervous system reaction. This preparation should not be mixed with other drugs for intravenous infusion in the same bottle, or intravenous infusion in the same intravenous infusion tube.

    4. Quinolones can still cause rare phototoxic reactions (incidence rate <0.1%). Avoid excessive sun exposure and artificial ultraviolet rays when receiving treatment with this product. If photosensitivity or skin damage occurs, this product should be stopped. In addition, there are occasional reports of follow-up inflammation or follow-up rupture after taking the medicine. Therefore, if the above symptoms occur, the drug should be stopped immediately, and exercise is strictly prohibited until the symptoms disappear.

5. When treating STD patients, syphilis serology should be performed to avoid delaying the treatment of syphilis.

   [Medication for pregnant women and breastfeeding women] 1. Because the safety of medication for pregnant women cannot be ensured, women who are pregnant or are likely to become pregnant are contraindicated.

2. Because the drug is excreted through breast milk, it is forbidden for breastfeeding women. If you must take this medicine, breastfeeding should be suspended.

Children's MedicationIt was found in animal experiments (puppies, puppies, puppies) that this product has abnormal damage to the weight-bearing joints, so patients under the age of 18 should not be used.

    [Medication for elderly patients] This product is mainly excreted through the kidneys (see "Pharmacokinetics"). Because most elderly patients have low renal function, persistent high blood drug concentrations may occur. Therefore, care should be taken to administer the dosage.

[Drug interactions] 1. This product cannot be used in the same infusion tube with solutions of multivalent metal ions such as magnesium and calcium.

2. This product is used in combination with benzoic acid, bifenbutyric acid, and non-steroidal anti-inflammatory and analgesics, which may cause convulsions, and should be avoided.

3. Avoid simultaneous use with theophylline. If simultaneous application is required, the blood concentration of theophylline should be monitored to adjust its dosage.

4. When using with warfarin or its derivatives, prothrombin time or other coagulation tests should be monitored.

5. It may cause hypoglycemia when used with oral hypoglycemic drugs at the same time, so care should be taken to monitor the blood glucose concentration during the medication process.

This product should be stopped immediately when hypoglycemia, and appropriate treatment should be given.

[Drug overdose] When quinolone drugs are overdose, the following symptoms may occur: nausea, vomiting, stomach pain, heartburn, diarrhea, thirst, stomatitis, staggering, dizziness, headache, general fatigue, numbness, chills, fever, cones Extracorporeal symptoms, excitement, hallucinations, convulsions, delirium, cerebellar ataxia, increased intracranial pressure (headache, vomiting, optic nerve head edema), metabolic acidosis, increased blood sugar, increased GOT/GPT/AL-P , Leukopenia, eosinophilia, thrombocytopenia, hemolytic anemia, hematuria, cartilage/joint disorders, cataracts, visual disturbances, abnormal color vision and diplopia.

First aid measures and antidote (1) Infusion (plus liver protection drugs): sodium bicarbonate injection for metabolic acidosis, sodium bicarbonate injection for urinary alkalization, to increase the excretion of this product by the kidneys; (2) Mandatory diuresis: give furanophenine injection; (3) symptomatic therapy: give diazepam intravenous injection repeatedly during convulsions; (4) severe disease: hemodialysis may be considered.

Since 2015, NINGBO VOICE BIOCHEMIC CO. LTD. is a professional company to offer one-package service for FPP (Finished Pharmaceutical Products ); APIs (Active Pharmaceutical Ingredients); Chemicals (Pharmaceutical Intermediates ); Veterinary Pharmaceuticals.that meet requirements of Standard GMP and current BP,USP version.

We will spare no efforts to meet your demands!