Is it Safe to Use Azithromycin in Pregnancy?

Azithromycin for injection, the indication is applicable to the following infections caused by sensitive pathogens. Azithromycin recommends different dosages, courses of treatment and different targets when treating various infections. For specific drug regimens, please refer to [Usage and Dosage]. Community-acquired pneumonia is caused by pathogens such as Chlamydia pneumoniae, Haemophilus influenzae, Legionella pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae, Staphylococcus aureus, or Streptococcus pneumoniae, and initial treatment requires intravenous administration . Pelvic inflammatory diseases are caused by Chlamydia trachomatis, Neisseria gonorrhoeae, or Mycoplasma hominis, and are initially treated for patients requiring intravenous administration. If it is suspected that anaerobic infection may be combined, an anti-anaerobic drug should be added in combination with this drug. If necessary, after stopping Cismet® injection (azithromycin for injection), sequential treatment with oral Cismet® can be followed (see [Dosage and Administration] for details). Bacterial culture and drug sensitivity tests should be performed before administration to identify pathogenic bacteria and their sensitivity to azithromycin. After collecting the specimen, you can start the treatment with cismemet®, and then adjust accordingly after knowing the result of drug sensitivity. In order to reduce the production of resistant bacteria and maintain the effect of this product (azithromycin) and other antibacterial drugs, this product (azithromycin) should only be used to treat or prevent infections caused by confirmed or highly suspected sensitive bacteria. If culture and susceptibility data are available, they should be considered when selecting or adjusting antimicrobial treatment. Without these data, local epidemiological and drug sensitivity models can help select empirical treatments.

Drug Name: Azithromycin for injection

Drug type: Prescription drugs, medicines for medical workers' injuries
Use classification: Antibiotics

Azithromycin for injection

The main ingredient of this product is azithromycin.
Chemical name: (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R) -13-[(2,6-dideoxy-3-C-methyl-3-O-methyl- -L-Nuclear-hexapyranosyl) oxy] -2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11- [ [3,4,6-trideoxy-3- (dimethylamino) --D-xylopyranosyl] oxy] -1-oxa-6-azacyclopentadecan-15-one Chemical Structure:

Molecular formula: C ₃₈ H ₇₂ N ₂ O ₁₂ · 2H ₂ O
Molecular weight: 785.0
The auxiliary materials contained in this product are: anhydrous citric acid, sodium hydroxide

Azithromycin properties for injection

This product is white to off-white block powder.

Azithromycin indications for injection

This product is suitable for the following infections caused by sensitive pathogens. Azithromycin treats various infections with different recommended dosages, courses of treatment and applicable objects. Please refer to [Usage and Dosage] for specific drug regimens.
Community-acquired pneumonia < br is caused by pathogens such as Chlamydia pneumoniae, Haemophilus influenzae, Legionella pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae, Staphylococcus aureus, or Streptococcus pneumoniae, and initial treatment requires intravenous Patient administration.
Pelvic inflammatory disease caused by Chlamydia trachomatis, Neisseria gonorrhoeae, or Mycoplasma humanis, and initially treated for intravenous administration. If it is suspected that anaerobic infection may be combined, an anti-anaerobic drug should be added in combination with this drug.
If necessary, after stopping Cismet® injection (azithromycin for injection), sequential treatment with oral Cismet® can be followed (see [Dosage and Administration] for details).
Bacterial culture and drug sensitivity tests should be performed before administration to identify pathogenic bacteria and their sensitivity to azithromycin. After collecting the specimen, you can start the treatment with cismemet®, and then adjust accordingly after knowing the result of drug sensitivity.
In order to reduce the production of resistant bacteria and maintain the effect of this product (azithromycin) and other antibacterial drugs, this product (azithromycin) should only be used to treat or prevent infections caused by confirmed or highly suspected sensitive bacteria. If culture and susceptibility data are available, they should be considered when selecting or adjusting antimicrobial treatment. Without these data, local epidemiological and drug sensitivity models can help select empirical treatments.

Azithromycin specifications for injection

Each bottle contains azithromycin 0.5g.

Azithromycin for injection

(See [Indications] and [Pharmacokinetics] )
When this product is used to treat community-acquired pneumonia caused by a specific pathogen, the recommended dose is 500 mg per day for a single intravenous administration for at least 2 days. After intravenous administration, sequential oral treatment with azithromycin is required. 500 mg (two tablets of 250 mg) is administered once a day for a total of 7-10 days. The time from intravenous administration to oral administration should be determined by the doctor based on clinical efficacy.
For the treatment of pelvic inflammatory diseases caused by specific pathogens, the recommended dose is 500 mg daily, once a day, intravenously, followed by oral sequential treatment with azithromycin after 1-2 days, 250 mg once daily , Intravenous and oral treatment for 7 days. When to change to oral is determined by the doctor based on clinical efficacy. If anaerobic infection is suspected, anti-anaerobic drugs should be added.
Renal insufficiency:
For patients with impaired renal function (GFR 80 mL / min), no dose adjustment is recommended. Patients with GFR 10 to 80 mL / min had an average AUC0 to 120 similar to those with normal renal function, while patients with GFR <10 mL / min increased 35% compared with patients with normal renal function. Azithromycin should be used with caution in patients with severe renal impairment (see [Pharmacokinetics], Specific Populations-Renal Insufficiency).
Liver insufficiency:
The pharmacokinetics of azithromycin in patients with liver damage has not been determined. For patients with impaired liver function, no dose adjustment is recommended (see [Pharmacokinetics], Specific Populations-Hepatic Insufficiency).
There is no need to adjust the dose according to age or sex (see [Pharmacokinetics], special populations).
Concentration and speed of administration of this product: When the concentration of the drug solution is 1 mg / ml, the infusion time should be 3 hours or the infusion time should be 1 hour when the concentration is 2 mg / ml. This product cannot be injected intravenously or intramuscularly.
According to the results of domestic clinical trials, the intravenous infusion of this product should not be too fast, and the infusion time per 500mg / 500ml should be 4 hours.
To prepare a solution for intravenous administration:
Dissolving < br Preparation of drug stock solution: Add 4.8 ml of sterile water for injection to a 500 mg Histomet® (azithromycin for injection) bottle and shake until the drug is completely dissolved. Because Insulin® (azithromycin for injection) is vacuum packed, it is recommended to use a standard 5 ml syringe (non-automatic) to ensure accurate extraction of 4.8 ml of sterile water for injection. Make 100 mg of azithromycin per ml of solution. The solution can be stored for 24 hours below 30 ° C (or 86 ° F).
Parenteral administration must be observed with the naked eye for particulate matter before use. If there are obvious particulate matter in the solution, the drug solution should be discarded.
Before use, dilute the drug solution as follows: Dilute <br Add 5 ml of a 100 mg / ml azithromycin solution to any of the following solutions. ml of azithromycin solution.
Normal saline (0.9% sodium chloride)
1/2 saline (0.45% sodium chloride)
5% glucose solution sodium lactate Ringer's solution 5% glucose + 1/2 saline (0.45% sodium chloride) containing 20 mmol / l potassium chloride 5% gluconate sodium lactate Ringer's solution 5% glucose + 1/3 saline (0.3% sodium chloride)
5% glucose + 1/2 saline (0.45% sodium chloride)
Normosol®-M5% Glucose Solution Normosol®-R5% Glucose Solution If using a Vial-Mate drug dissolution device, please refer to the assembly and dissolution instructions of Vial-Mate®.
[u] Final infusion concentration (mg / mL) [/ u] [u] Amount of dilution (mL) [/ u]
1.0 mg / mL 500 mL
2.0 mg / mL 250 mL
It is recommended that the infusion time of 500mg of this product after dilution according to the above method is not less than 60 minutes.
This product cannot be injected intravenously or intramuscularly. Other intravenous infusions, additives, drugs cannot be added to this product, nor can it be infused into the same intravenous access at the same time.

Azithromycin adverse reactions for injection

In the clinical trial of azithromycin intravenous preparation for community-acquired pneumonia, 2-5 doses were administered intravenously, and most of the reported adverse reactions were mild to moderate, and they could be recovered after stopping the drug. Most patients in these clinical trials have more than one comorbid condition and require other drugs. Approximately 1.2% of patients receiving Cismet® intravenous medication discontinued medication, and 2.4% of patients treated with intravenous or oral azithromycin discontinued medication due to symptoms of adverse reactions or laboratory abnormalities.
In clinical trials conducted in patients with pelvic inflammatory diseases, 2% of patients discontinued due to clinical adverse reactions after intravenous administration of 1-2 doses of azithromycin monotherapy. Among patients who received azithromycin combined with metronidazole 4% of patients discontinued treatment due to adverse reactions.
In the above studies, the most common adverse reactions leading to drug withdrawal were gastrointestinal reactions (abdominal pain, nausea, vomiting, diarrhea, etc.) and rashes. The abnormal laboratory tests leading to drug withdrawal were mainly serum transaminase and / or alkaline phosphatase. high.
Clinical aspects:
In the study of community-acquired pneumonia, the most common adverse reaction of adult patients after receiving cismet [sup] ® [/ sup] intravenous / oral preparations was gastrointestinal reactions, of which diarrhea or loose stools (4.3%), Nausea (3.9%), abdominal pain (2.7%), and vomiting (1.4%). About 12% of patients experienced intravenous-related adverse reactions, the most common being pain at the injection site (6.5%) and local inflammatory reactions (3.1%).
In clinical trials of patients with pelvic inflammatory diseases, adult female patients were treated with cismet [sup] ® [/ sup] intravenous / oral preparations. The most common adverse reactions related to treatment are also gastrointestinal reactions, of which diarrhea (8.5 %), Nausea (6.6%), vaginitis (2.8%), abdominal pain (1.9%), anorexia (1.9%), rash and pruritus (1.9%). When azithromycin was combined with metronidazole in these studies, adverse reactions such as nausea (10.3%), abdominal pain (3.7%), vomiting (2.8%), site-of-administration reactions, gastritis, dizziness, and dyspnea (1.9% in total) occurred. Rate is higher.
The other adverse reactions caused by Cismet [sup] ® [/ sup] intravenous / oral multi-dose treatment regimen are not more than 1%.
Adverse reactions with an incidence of less than 1% are:
Gastrointestinal reactions : indigestion, bloating, mucositis, oral candidiasis and gastritis.
Nervous system : headache, drowsiness.
Allergic reaction : bronchospasm.
Special sensation : abnormal taste.
Post-market application experience :
Oral azithromycin preparations are used in adult and / or pediatric patients after marketing. The following adverse events have been reported, but it is not certain whether they are caused by azithromycin:
Allergic reactions : joint pain, edema, urticaria, angioedema.
Cardiovascular : Arrhythmias include ventricular tachycardia and hypotension.
Gastrointestinal tract : anorexia, constipation, indigestion, bloating, vomiting / diarrhea but rarely cause dehydration, pseudomembranous enteritis, pancreatitis, oral candidiasis, and rare reports of discoloration of the tongue.
Systemic reactions : fatigue, paresthesia, and allergies (rarely life-threatening).
Urogenital system : interstitial nephritis, acute renal insufficiency, candidiasis, vaginitis.
Hematopoietic system : thrombocytopenia.
Liver / Bile : Hepatic abnormalities include hepatitis and cholestatic jaundice, as well as liver cell necrosis and liver failure, some of which may be fatal.
Nervous system : convulsions, dizziness / vertigo, headache, drowsiness, hyperactivity, nervousness, and agitation.
Spirit : Aggressive response and anxiety.
Skin and accessories : itching, severe skin reactions including erythema polymorpha, Stevens Johnson syndrome, and toxic epidermolysis and necrosis are rare.
Special sensations : Hearing impairments include hearing loss, deafness and / or tinnitus, and occasional reports of taste disorders.
Laboratory inspection abnormalities:
Significant abnormal laboratory tests (whether drug-related or not) seen in clinical trials are:
Incidence rate 4-6%: ALT (SGPT), AST (SGOT), creatinine increase.
Incidence rate 1-3%: LDH, bilirubin increased.
Incidence rate is less than 1%: Leukopenia, thrombocytopenia, elevated serum alkaline phosphatase.
Follow-up found that the laboratory abnormalities mentioned above were reversible.
In more than 750 patients participating in this drug intravenous / oral multi-dose clinical trial, no more than 2% of patients discontinued azithromycin due to treatment-related liver enzyme abnormalities.

Azithromycin for injection contraindications

Cisumeb is contraindicated in patients known to be allergic to azithromycin, erythromycin, or other macrolides.
Warning Severe reports of severe allergic reactions, including angioedema, anaphylactic shock-like reactions, Stevens Johnson syndrome, and toxic epidermal necrolysis, are rare. Although very few deaths have been reported. When allergic symptoms occur in some patients, symptomatic treatment is effective at first. If treatment is stopped prematurely, allergic symptoms can quickly return even if azithromycin is not used. For such patients, the time for symptomatic treatment and observation needs to be extended. It is unknown whether these events are related to the long half-life of azithromycin in the tissues and the longer exposure of the body to the antigen.
If an allergic reaction occurs, the drug should be discontinued immediately and appropriate treatment given. Doctors should be aware that after stopping symptomatic treatment, allergic symptoms may recur.
Hepatotoxicity There have been reports of liver dysfunction, hepatitis, cholestatic jaundice, liver necrosis, and liver failure, some of which may be fatal. If you have signs and symptoms of hepatitis, you should stop using this product immediately.
Clostridium difficile-associated diarrhea < br Almost all antibacterial applications have reports of Clostridium difficile-associated diarrhea (CDAD), including this product, which can range in severity from mild diarrhea to lethal colon inflammation. Antimicrobial treatment can cause changes in the normal flora in the colon, resulting in the overproduction of Clostridium difficile.
Clostridium difficile toxin A and toxin B are related to the pathogenesis of CDAD. Highly toxic Clostridium difficile causes increased morbidity and mortality. These infections may be difficult to treat with antimicrobials and may require colectomy. For all patients with diarrhea after antibiotic use, the possibility of CDAD must be considered. Since there have been reports of CDAD occurring more than 2 months after antimicrobial treatment, a careful medical history is required.
If CDAD is suspected or diagnosed, antibiotics not being used against C. difficile may need to be discontinued. Water, electrolytes, and proteins must be appropriately supplemented according to clinical needs, antibiotics effective for Clostridium difficile must be given, and surgical evaluations must be performed if necessary.

Azithromycin for injection

General matters: As azithromycin is mainly eliminated by the liver, patients with hepatic impairment should use azithromycin with caution. There is no data on the use of azithromycin in patients with impaired renal function. Such patients should also be used with caution.
This product should be dissolved and diluted according to the instructions, the intravenous drip time should not be less than 60 minutes (see [Dosage and Administration] for details).
It has been reported that local adverse reactions may occur during intravenous application of azithromycin. 500 mg of azithromycin was given and formulated at a concentration of 2 mg / mL. A 250 mL solution was dropped within 1 hour or a 1 mg / mL solution was prepared. A 500 mL solution was dropped within 3 hours. The incidence and severity of local adverse reactions during injection were similar (see [Adverse Reactions] for details). All volunteers who received azithromycin solution with a concentration greater than 2.0 mg / mL experienced local injection reactions, so the concentration of the solution during intravenous infusion should not be too high.
It has been reported that the application of other macrolide antibiotics can lead to prolonged cardiac repolarization duration and QT interval, thereby risking arrhythmia and torsional ventricular tachycardia. When patients are at increased risk for prolonged cardiac repolarization, azithromycin cannot be completely ruled out.
Exacerbation of myasthenia gravis or new onset of myasthenic syndrome has been reported in patients treated with azithromycin.
In the case of undiagnosed or highly suspected bacterial infections, or without indications for prevention, the use of this product may not benefit patients and increase the risk of drug-resistant bacteria.
Patients need to know:
When any signs of allergy appear, azithromycin should be stopped immediately and contact your doctor.
Patients should be informed that antibacterials, including azithromycin, can only be used to treat bacterial infections and not viral infections (such as the common cold). When using this product (azithromycin) to treat bacterial infections, patients must be informed that although they usually feel better in the early stages of treatment, they should still take the medicine accurately according to the instructions of the physician. Missing or not completing the entire course of treatment may: (1) reduce the efficacy of the current treatment, and (2) increase the possibility of bacterial resistance, which will cause azithromycin or other antibacterial drugs to fail to treat these resistant bacteria in the future.
Antibiotic treatment often causes diarrhea, which usually recovers after stopping antibiotics. Sometimes after antibiotic administration, patients develop watery or bloody stools (with or without stomach cramps and fever) even 2 months or more after the last antibiotic. If this happens, the patient should contact a doctor as soon as possible.

Azithromycin for injections for pregnant and lactating women

Pregnancy : teratogenic effects. This product belongs to Class B in the pregnancy drug classification, and the dose reached the mother's moderate poisoning level in the fertility study conducted in rats and mice (ie, oral 200 mg / kg / d). These doses are calculated on the basis of body surface area mg / m ² , which are approximately two and four times the human daily oral 500 mg dose, respectively. Azithromycin has not been found to have any damaging effects on embryos in animal experiments. However, there are not enough controlled studies in pregnant women. Since animal fertility studies cannot fully predict human response, azithromycin should be used with precise indications during pregnancy.
Lactating women: It is not known whether azithromycin is secreted by milk. Because many drugs are secreted by milk, lactating women should pay attention to azithromycin.

Azithromycin for children

The efficacy and safety of azithromycin for injection in children and adolescents under 16 years of age have not been proven. Oral azithromycin has been used in pediatric patients from 6 months to 16 years in controlled clinical trials. For information about cismel® (azithromycin dry suspension) for pediatric patients, see 100mg / 5ml
[Indications] and [Dosage and Administration] sections of the bottled Histimax® (azithromycin dry suspension) instructions.

Azithromycin for injection

The pharmacokinetics of azithromycin for intravenous administration have not been performed in elderly volunteers. The pharmacokinetic characteristics of azithromycin for 5 days in elderly volunteers (65-85 years) were similar to those of young volunteers (18-40 years).
In a clinical trial of azithromycin multiple-dose intravenous treatment of community-acquired pneumonia, 45% of patients (188/414) were over 65 years of age and 22% (91/414) were over 75 years of age. In terms of adverse events, laboratory abnormalities, and withdrawal trials, there was no overall difference in safety between these patients and younger patients. It was found that as the patient's age increased, the decrease in clinical efficacy was similar between the azithromycin treatment group and the control drug treatment group.
Cishomex® (azithromycin for injection) contains 114 mg (4.96 mEq) of sodium in each bottle. At the usual recommended dose, patients will receive 114 mg of sodium (4.96 mEq). For sodium load, urinary sodium excretion decreases in the elderly. Total dietary and non-dietary sodium intake is of clinical significance for specific diseases (eg, congestive heart failure).

Azithromycin drug interactions for injection

In the steady state of nafinavir, a single dose of azithromycin taken orally can increase the serum concentration of azithromycin. Although it is not necessary to adjust the dose of azithromycin when used with nafinavir, the known side effects of azithromycin such as liver enzyme abnormalities and hearing impairment must be closely monitored (see Adverse Reactions).
Although in a study of 22 healthy men, a 5-day course of azithromycin had no effect on subsequent prothrombin time after warfarin administration, spontaneous post-marketing reports suggest that combined use of azithromycin may enhance oral anticoagulants. effect. When patients use azithromycin in combination with oral anticoagulants, the prothrombin time should be closely monitored.
The drug interactions between azithromycin and other drugs that may be combined were studied (see [Pharmacokinetics]-Drug Interactions). Azithromycin is used against atorvastatin, carbamazepine, cetirizine, didanosine, efavirenz, fluconazole, indinavir, midazolam, rifabutin, xibuterol when used in therapeutic dose The pharmacokinetics of dinafil, theophylline (intravenous and oral administration), triazolam, trimethoprim / sulfamethoxazole, or zidovudine have little effect. When combined, efavirenz or fluconazole have little effect on the pharmacokinetics of azithromycin. When azithromycin is used in combination with any of the above drugs, there is no need to adjust the dose of any one drug.
Azithromycin has not been reported in clinical trials to interact with the following drugs. However, no special studies have been conducted to evaluate the potential interactions of azithromycin with these drugs. However, these situations have occurred when using other macrolides. Therefore, when new research data are not available, azithromycin should be closely observed when used in combination with:
Digoxin-Digoxin concentration increased.
Ergotamine or dihydroergotamine-acute ergot poisoning, manifested by severe peripheral vasospasm and feeling dull.
Terfenadine, cyclosporine, histobitum, and phenytoin-increased in concentration.
Impact on laboratory tests: No reports have been found to have an impact on laboratory results.

Azithromycin overdose for injection

There is no relevant research data.

Azithromycin clinical trials for injection

[u] Clinical research [/ u]
Community-acquired pneumonia < br In a controlled study of community-acquired pneumonia in the United States, azithromycin (500 mg intravenously once daily for 2-5 days followed by oral administration of 500 mg / d for a total course of 7 -10 days) compared with cefuroxime (2 250 mg / d, divided into 3 intravenous administrations for 2-5 days, then 1000 mg / d, divided into 2 oral administrations, the total course of treatment is 7-10 days). Furulin group was added with or without erythromycin. A total of 291 patients can be evaluated for clinical efficacy. The clinical outcomes of 277 patients who were followed up for 10-14 days after treatment, that is, cured, improved and effective (cured + improved) are shown in the table below:
Clinical Outcome Azithromycin Control 46% 44% Cure
32% 30% improvement
Effective (cure + improvement) 78% 74%
Another trial in the United States, without a control, was designed to evaluate clinical and microbial efficacy. 94 patients with community-acquired pneumonia who received the same azithromycin treatment plan could be evaluated clinically. Follow-up was performed in 84 cases from 10-14 days after treatment. The cure, improvement, and effectiveness (cure + improvement) were as follows:
Clinical Outcome Azithromycin 60% cure
29% improvement
Effective (cure + improvement) 89%
During the follow-up before treatment, microbiological examination was performed on the patients in the above two trials, and if possible, re-examination will be performed at subsequent follow-up. Serological tests were performed before treatment and at the last follow-up. Calculate total bacterial clearance based on data from evaluable cases:
Total bacterial clearance by azithromycin treatment:
(At the last follow-up after the end of the trial) Azithromycin Streptococcus pneumoniae 64/67 (96%) [sup] a [/ sup]
Haemophilus influenzae 41/43 (95%)
Moraxella catarrhalis
Staphylococcus aureus
[sup] a [/ sup] Of the 24 patients with a blood culture of Streptococcus pneumoniae, 19 (79%) were cured and the pathogens were cleared (ITT).
In the above two trials, there were cases of atypical pathogen infection (serology and / or culture), and the pathogen examination results of these cases on days 10-14 after azithromycin treatment were:
Pathogens Total number of cases Cure Cure Cure + Cure Mycoplasma pneumoniae 18 11 (61%) 5 (28%) 16 (89%)
Chlamydia pneumoniae 34 15 (44%) 13 (38%) 28 (82%)
Legionella pneumophila 16 5 (31%) 8 (50%) 13 (81%)

Azithromycin Pharmacology and Toxicology for Injection

Azithromycin is an aza compound and belongs to a macrolide antibiotic. It is derived by chemically inserting a nitrogen atom into the erythromycin A lactone ring.
Microbiology : The antibacterial mechanism of azithromycin is that it binds to the 50S ribosomal subunit of sensitive bacteria and affects the protein synthesis of bacteria. Its nucleic acid synthesis is not affected.
In vitro culture showed that azithromycin was concentrated in phagocytes and fibroblasts. With in vitro culture, the ratio of intracellular and extracellular drug concentrations measured after 1 hour was greater than 30. In vivo studies have suggested that high concentrations of drugs in phagocytic cells may help drug distribution to inflammatory tissues.
Azithromycin has antibacterial activity against most of the following strains, including in vitro effects and clinical efficacy, see the [Indications] section of this product's package insert:
Aerobic gram-positive bacteria < br Staphylococcus aureus pneumococcus Note: Azithromycin is cross-resistant to erythromycin-resistant gram-positive bacteria. Most Enterococcus faecalis and methicillin-resistant Staphylococci are resistant to azithromycin.
Aerobic gram-negative bacteria < br Haemophilus influenza catarrhalis Neisseria gonorrhoeae <br Other microorganisms < br Chlamydia pneumoniae Chlamydia trachomatis pneumophila Legionella pneumoniae human mycoplasma pneumoniae mycoplasma bacteria Beta-lactamase had no effect on azithromycin activity.
Azithromycin has antibacterial activity against most of the following strains, including in vitro effects and clinical efficacy, see the [Indications] section of the package instructions for cisme (azithromycin tablets) and cisme (kids).
Aerobic Gram-positive bacteria < br Staphylococcus aureus Streptococcus pneumoniae Streptococcus pyogenes <br Aerobic Gram-negative bacteria < br Hemophilus ducrei Haemophilus influenzae Catalmo Neisseria gonorrhoeae Neisseria gonorrhoeae <br Other microorganisms < br The following are in vitro test data for Chlamydia pneumoniae, Chlamydia trachomatis, and Mycoplasma pneumoniae, but their clinical significance is unknown [/ u] .
Azithromycin has the lowest in vitro inhibitory concentration (MIC) of most Streptococcus strains (90%) 0.5 ug / mL; for most of the following other bacteria (90%), the MIC is 2.0 ug / mL. However, there is no comprehensive clinical controlled trial data to confirm the safety and efficacy of azithromycin in the treatment of infections caused by these pathogens.
Aerobic Gram-positive bacteria Streptococcus spp. (Groups C, F and G)
Streptococcus green group Other microorganisms Ureaplasma urealyticum Test method for drug sensitivity <br If possible, the results of in vitro drug sensitivity tests for antibacterial drugs used in hospital wards should be provided to doctors as a description in the hospital and in the community Periodic reports on susceptibility to sexually transmitted pathogens. These reports may differ from the sensitivity data obtained from the clinic, but help doctors choose the most effective antimicrobials.
[u] Dilution technology [/ u] :
Quantitative determination of the minimum inhibitory concentration (MIC) of antibacterials. MIC can estimate the susceptibility of bacteria to antibacterials. To determine MIC, a standardized method must be used. The standard method is based on the dilution method (broth dilution method or agar dilution method) or equivalent method. Concentration of azithromycin. The significance of the MIC value is judged according to the following criteria:
There is no established susceptibility standard for Neisseria gonorrhoeae, and susceptibility tests for Neisseria gonorrhoeae are not routine.
The standardized drug sensitivity test method requires the use of laboratory quality control strains to ensure the consistency of experimental operation techniques. Using azithromycin standard powder, the drug sensitivity results of each quality control strain should be:
Diffusion method < br The diameter of the zone of inhibition can also be used to estimate the susceptibility of bacteria to antibacterials, and the test results are reproducible. Standardized test methods require standardized inoculum. This method uses 15 g azithromycin-containing paper to detect bacterial sensitivity to azithromycin. The laboratory report of the paper drug sensitivity test should be interpreted according to Table 1:
Table 1. Criteria for interpretation of azithromycin sensitivity results

Due to the lack of information on drug-resistant strains, there are no criteria for delineating other categories other than the "sensitive" category. If the MIC value is outside the "sensitive" range, the strain should be sent to a reference laboratory for further testing.
The susceptibility of Streptococcus, including Streptococcus pneumoniae, to azithromycin and other macrolides can be predicted by testing erythromycin.
There is no established susceptibility standard for Neisseria gonorrhoeae, and susceptibility tests for Neisseria gonorrhoeae are not routine.
Reporting "sensitivity" means that pathogenic bacteria may be inhibited if the concentration of the antimicrobial drug reaches a commonly achievable concentration. The report "Medium Sensitivity" indicates that the treatment results are uncertain, and if the bacteria are not completely sensitive to other available drugs, the drug sensitivity test needs to be repeated. The clinical significance of this type of result is that azithromycin can be used in both cases where the concentration of the drug at the infection site is high or the dosage can be increased. This result provides a buffering range that can avoid significant differences in interpretation of results caused by tiny uncontrolled technical factors. The report "resistance" indicates that when the antibacterial drug reaches the commonly achievable concentration, the pathogenic bacteria cannot be inhibited, and other treatment drugs should be selected.
[u] Quality Control [/ u]
Standardized drug sensitivity test methods require the use of quality control strains to control the technical aspects of the test. Using azithromycin standard powder, the range of drug sensitivity results of each quality control strain is shown in Table 2. Quality control strains are specific strains with inherent biological characteristics. Quality control strains are very stable and can provide standard, repeatable drug sensitivity results. The specific strain used for microbiological quality control has no clinical significance.
Table 2. Acceptable quality control ranges for azithromycin

Toxicology studies <br Repeated administration toxicity < br After multiple administrations of azithromycin in mice, rats, and dogs, phospholipidosis (intracellular phospholipid accumulation) can occur in some tissues. It has been confirmed that in terms of body surface area mg / m ² , azithromycin equivalent to an adult dose is given to dogs, and azithromycin equivalent to one-sixth of an adult dose to rats, this change can occur in many organs, such as eyes, ganglia Dorsal root, liver, gallbladder, kidney, spleen and pancreas. This change can be restored after azithromycin is discontinued. Neonatal rats and dogs were given azithromycin once a day, and 10 to 30 days later, phospholipidosis also occurred in the tissues to the same extent. According to pharmacokinetic data, after azithromycin was administered to rats at 30 mg / kg, the Cmax value was observed to be 1.3 g / ml when phospholipidosis occurred (this value is 0.216 g / ml at a dose of 10 mg / kg for children). 6 times). Similarly, dogs given 10 mg / kg azithromycin had a Cmax value of 1.5 g / ml when phospholipidosis occurred (this value is 7 times the Cmax value and dose administered in the child population studied). Based on mg / m ^{2 of} body surface area, the dose of 30 mg / kg in newborn rats (135 mg / m ² ) and the dose of 10 mg / kg in dogs (79 mg / m ² ) are approximately the recommended doses for children with an average body weight of 25 kg. 0.45 times and 0.3 times. This effect was reversible after azithromycin was discontinued, similar to that observed in adult animals. What these findings mean for animals and humans is unclear.
Genotoxicity < br Azithromycin has not been found to have potential mutagenic effects in standard laboratory tests such as mouse lymphoma test, human lymphocyte test, and mouse bone marrow micronucleus test.
Reproductive toxicity < br Reproductive toxicity tests in rats and mice have shown that when azithromycin is administered at a dose level that produces a moderate degree of maternal toxicity (ie, 200 mg / kg / day, calculated based on body surface area, approximately the dose for human use) 500 mg / kg / day (2 to 4 times), no teratogenic effect was found. No damage to fertility and fetuses was found.
Carcinogenicity < br Long-term animal tests have not been conducted to determine whether azithromycin is potentially carcinogenic.

Azithromycin Pharmacokinetics for Injection

Inpatients with community-acquired pneumonia received an intravenous infusion of 500 mg azithromycin at a concentration of 2 mg / mL once daily for 1 hour each time. After 2-5 days of administration, the concentration of azithromycin was 2 mg / mL The average Cmax ± SD was 3.63 ± 1.60 ug / mL, the 24-hour trough concentration level was 0.20 ± 0.15 ug / mL, and the AUC24 was 9.60 ± 4.80 ug / h / mL.
Normal volunteers inject 500 mg azithromycin intravenously for 3 hours, the concentration of the drug solution is 1 mg / mL, and the average Cmax, 24-hour trough concentration, and AUC24 values are 1.14 ± 0.14 ug / mL and 0.18 ± 0.02 ug / mL and 8.03 ± 0.86 ug / h / mL. Inpatients with community-acquired pneumonia use the same dosing regimen. After 2-5 days of administration, their pharmacokinetic parameters are similar to the above-mentioned indicators of normal people.

a = Patients with community-acquired pneumonia receive azithromycin 500 mg (2 mg / mL) intravenously for 2-5 days.
b = 500 mg (1 mg / mL) intravenous drip of azithromycin in healthy people for 5 days.
The average CLt and Vd values of 18 normal volunteers after intravenous drip of 1000-4000 mg (1 mg / mL) azithromycin within 2 hours were 10.18 mL / min / kg and 33.3 L / kg, respectively.
Comparing the daily pharmacokinetic parameters of azithromycin 500 mg once a day by intravenous infusion, the first day and the fifth day after drug administration, it was found that after the fifth day of administration, Cmax increased by only 8%, but AUC24 increased by 61%, indicating that The C24 valley concentration increased three-fold.
After 12 healthy volunteers took 500 mg of azithromycin in a single dose, the Cmax, trough concentration, and AUC24 were 0.41 ug / mL, 0.05 ug / mL, and 2.6 ug / h / mL, respectively. The parameters after oral administration were approximately 38%, 83%, and 52% of a single-dose intravenous infusion of 500 mg (infusion time of 3 hours) (Cmax: 1.08 ug / mL after intravenous infusion; trough concentration: 0.06 ug / mL; AUC24). : 5.0 ug / h / mL). As a result, plasma concentrations are higher for intravenous administration every 24 hours. Healthy adults (18-40 years old) take a 500 mg loading dose of azithromycin capsules, followed by 250 mg orally daily. The pharmacokinetic parameters on day 5 are as follows: Cmax = 0.24 ug / mL, AUC24 = 2.1 ug / h / mL. When taking the drug on an empty stomach, azithromycin 250 mg tablets are bioequivalent to taking 250 mg capsules on an empty stomach.
Twelve healthy volunteers took azithromycin once daily for 5 days (2 250 mg tablets on the first day, followed by 1 250 mg tablet on the 2nd to 5th days) or 3 days (500mg per day on the 1st to 3rd days). After a dose of 1500 mg, the median exposures of azithromycin (AUC0 to 288) in monocytes (MN) and polymorphonuclear (PMN) leukocytes were 1000 and 800 times higher than those in serum, respectively.
distributed:
The serum protein binding rate of azithromycin changes with changes in blood drug concentration. In humans, the protein binding rate is 51% when the blood drug concentration is 0.02 g / ml. When the blood drug concentration increases to 2 g / ml, the protein binding rate decreases 7%.
The exact tissue concentration after intravenous infusion of azithromycin is not yet known. The partial tissue (or body fluid) concentration and the ratio of tissue (body fluid) and plasma / serum concentration after oral azithromycin administration are shown in the table below:

1 High tissue concentration is not necessarily proportional to clinical efficacy. The antibacterial activity of azithromycin is related to pH. Azithromycin has a concentration phenomenon in the lysosome, and the pH value in the lysosome is low, so the activity of the drug in the lysosome is reduced. However, the large distribution of drugs in tissues may be related to their clinical efficacy.
* Specimens taken 2-4 hours after the first dose.
** Specimens taken 10-12 hours after the first dose.
*** The dosage regimen is 250 mg orally every 12 hours, twice.
**** Specimens collected 19 hours after a single 500 mg dose.
Tissue concentration was determined in 7 gynecological and obstetric patients after a single oral dose of 500 mg azithromycin. About 17 hours after taking the drug, the concentration in the ovarian tissue was 2.7 g / g, the concentration in the uterine tissue was 3.5 g / g, and the concentration in the fallopian tube tissue was 3.3 g / g. In the absence of inflammation of the meninges, 500 mg was administered on the first day, followed by 250 mg once daily on the second day, and after a 4-day regimen, the concentration in the cerebrospinal fluid was less than 0.01 g / mL.
Metabolism < br No in vitro and in vivo studies evaluating the metabolism of azithromycin have been conducted.
Elimination < br After a single 500 mg oral and intravenous administration, the plasma concentration of azithromycin decreases in a heterogeneous pattern, with an average apparent plasma clearance of 630 ml / min and a terminal elimination half-life of 68 hours. It is generally believed that prolonged terminal half-life is due to widespread tissue uptake followed by drug release.
In a multi-dose study of 12 normal volunteers, the dosage regimen was azithromycin 500 mg (1 mg / ml) intravenous infusion, the infusion time was 1 hour, and the continuous use was 5 days. The amount of urine excreted in the urine 24 hours after the first administration was about 11% of the administered dose, and the amount of urine excreted in the urine 24 hours after the fifth administration was about 14%. After oral administration of azithromycin, 6% of the dose was excreted from the urine in the original form, and the amount of urine excreted after intravenous infusion was higher than that of oral administration. After oral administration, bile secretion is the main route of excretion of the original drug.
Special populations < br Renal insufficiency The pharmacokinetics of azithromycin was studied in 42 adults (aged 21 to 85 years) with varying degrees of renal impairment. After taking a single dose of azithromycin 1000 mg orally, the average Cmax in patients with mild to moderate renal impairment (GFR 10-80 mL / min) compared with subjects with normal renal function (GFR> 80 mL / min) And AUC0 120 increased by 5.1% and 4.2%, respectively. Compared with subjects with normal renal function (GFR> 80 mL / min), patients with severe renal impairment (GFR <10 mL / min) had an average Cmax and AUC0 to 120 increase of 61% and 35%, respectively. (See [Usage and dosage]).
Hepatic dysfunction The pharmacokinetics of azithromycin in patients with hepatic impairment has not been determined.
Gender < br Azithromycin has no significant difference in the in vivo processes of male and female subjects. It is not recommended to adjust the dose according to gender.
Elderly patients < br The pharmacokinetics of intravenous administration of azithromycin have not been performed in elderly volunteers.
The pharmacokinetics of 5-day oral azithromycin treatment for elderly volunteers (65-85 years) was similar to that of young volunteers (18-40 years).
Pediatric patients . Pharmacokinetic studies of azithromycin intravenously have not been performed in children.
Drug Interactions < br Drug interaction studies were performed on oral azithromycin and other drugs that may be combined. Table 3 shows the effects of combined azithromycin on the pharmacokinetics of other drugs, and the effects of other drugs on the pharmacokinetics of azithromycin are shown in Table 4.
The combination of azithromycin at the therapeutic dose has little effect on the pharmacokinetics of the drugs in Table 3. When combined with azithromycin, it is recommended that the dosage of the drugs in Table 3 not be adjusted.
Azithromycin in combination with efavirenz or fluconazole has little effect on the pharmacokinetics of azithromycin. Nafinavir significantly increased the Cmax and AUC of azithromycin. When combined with the drugs in Table 4, it is recommended that the dose of azithromycin not be adjusted. (See [Drug Interactions]).
Table 3. Drug interactions: pharmacokinetic parameters of drugs used in combination with azithromycin

NA-Not obtained *-No 90% confidence interval was reported with azithromycin. The mean concentration of rifabutin was 60 ng / mL half a day after the last dose, and 71 ng / mL with placebo.
Table 4 Drug interactions: Pharmacokinetic parameters of Azithromycin when combined with other drugs (see [Drug Interactions])

NA-Not obtained *-No reported 90% confidence interval when combined with rifabutin 300 mg daily, 1 day after the last dose, the average concentration of azithromycin was 53 ng / mL, and 49 ng / mL when combined with placebo .

Azithromycin for injection storage

Keep tightly closed in a dry place.
If diluted to a concentration of 1.0mg / mL-2.0 mg / mL according to the instructions, cisme [sup] ® [/ sup] (azithromycin for injection) can be stored at room temperature (30 ° C or 86 ° F) for 24 hours. Medium (5 ° C or 41 ° F) can be stored for 7 days.

Azithromycin for injection

Molded antibiotic bottle.
1 stick / box, 10 sticks / box.

Azithromycin for injection

36 months

Azithromycin for injection

Import drug registration standard JX20090226. ^[1]

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