Azithromycin Granules Instructions

Main ingredient: Azithromycin.
Chemical Name: (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecane-15-one.
Molecular Formula: C38H72N2O12
Molecular Weight: 749.00

 

This product is a white or off-white granule.

 

1. Acute pharyngitis and acute tonsillitis caused by pyogenic streptococci.
2. Sinusitis, otitis media, acute bronchitis, and acute exacerbation of chronic bronchitis caused by sensitive bacteria.
3. Pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae.
4. Urethritis and cervicitis caused by Chlamydia trachomatis and non-multidrug-resistant Neisseria gonorrhoeae.
5. Skin and soft tissue infections caused by sensitive bacteria.

 

0.1g (100,000 units).

 

Pour this product into a cup, add an appropriate amount of cool boiled water, dissolve and shake well before oral administration. Take 1 hour before or 2 hours after meals.
Adult Dosage:
1. For sexually transmitted diseases caused by Chlamydia trachomatis or sensitive Neisseria gonorrhoeae, a single oral dose of 1.0g is sufficient.
2. Treatment of other infections: Total dose 1.5g, divided into three doses, 0.5g once daily; or the same total dose, still 1.5g, 0.5g on the first day, then 0.25g once daily on days 2-5. Pediatric Dosage: 1. For otitis media and pneumonia, on the first day, 10mg/kg body weight once daily (maximum daily dose not exceeding 0.5g), on days 2-5, 5mg/kg body weight once daily (maximum daily dose not exceeding 0.25g) or according to the following method: Weight (kg) Day 1 (once daily) Days 2-5 (once daily) 15-25 0.2g 0.1g 26-35 0.3g 0.15g 36-45 0.4g 0.2g 2. For pharyngitis and tonsillitis in children, 12mg/kg body weight once daily (maximum daily dose not exceeding 0.5g) for 5 consecutive days. Or as directed by a physician.

 

This product is generally well-tolerated, with a low incidence of adverse reactions, mostly mild to moderate reversible reactions.
1. Common adverse reactions include: (1) Gastrointestinal reactions: diarrhea, nausea, abdominal pain, loose stools, vomiting, etc.; (2) Skin reactions: rash, itching, etc.; (3) Other reactions: such as anorexia, vaginitis, dizziness, or dyspnea, etc.
2. The following adverse reactions <1% have also been observed in clinical practice. (1) Digestive system: dyspepsia, gastrointestinal bloating, mucositis, oral candidiasis, gastritis, etc.; (2) Nervous system: headache, somnolence, etc.; (3) Allergic reactions: bronchospasm, etc.; (4) Other reactions: taste disorders, etc.
3. The following adverse reactions have also been observed in post-marketing oral formulations, and their relationship to this product is unclear. (1) Allergic reactions: arthralgia, angioneurotic edema, urticaria, photosensitivity; (2) Cardiovascular system: arrhythmia, ventricular tachycardia; (3) Gastrointestinal: very rare pseudomembranous colitis, tongue discoloration; (4) Genitourinary system: interstitial nephritis, acute renal failure; (5) Hematopoietic system: thrombocytopenia; (6) Hepatobiliary system: there have been reports of azithromycin causing hepatitis and cholestatic jaundice, occasionally causing liver necrosis and liver failure, but rarely fatal, and the causal relationship has not been determined; (7) Psychoneurological system: aggressive reactions, nervousness, anxiety, worry, headache, somnolence, dizziness, vertigo, convulsions, hyperactivity; (8) Skin/appendages: rare serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported; (9) Sensory organs: there are reports that macrolide antibiotics can damage patients' hearing. Some patients have experienced hearing impairment after taking azithromycin, including hearing loss, tinnitus, and/or deafness. Investigations have shown that this phenomenon is related to the patient's continued use of large doses of this product. Follow-up of these patients showed that most patients' hearing recovered. There are rare reports of azithromycin causing taste changes.
4. Abnormal laboratory tests: elevated serum ALT, AST, creatinine, LDH, bilirubin, and alkaline phosphatase; decreased white blood cells, neutrophils, and platelets.

 

Contraindicated in patients allergic to azithromycin, erythromycin, or any other macrolide antibiotics.

 

1. Food can affect the absorption of azithromycin, so it should be taken orally 1 hour before or 2 hours after meals.
2. No dose adjustment is needed for patients with mild renal insufficiency (creatinine clearance ≥40ml/min), but there is no data on the use of azithromycin in patients with more severe renal insufficiency. Caution should be exercised when using azithromycin in these patients.
3. Since the hepatobiliary system is the main excretion pathway of azithromycin, it should be used with caution in patients with hepatic insufficiency, and should not be used in patients with severe liver disease. Liver function should be monitored regularly during medication.
4. If allergic reactions (such as angioneurotic edema, skin reactions, Stevens-Johnson syndrome, and toxic epidermal necrolysis) occur during medication, the medication should be stopped immediately, and appropriate measures should be taken.
5. During treatment, if the patient experiences diarrhea, pseudomembranous colitis should be considered. If the diagnosis is confirmed, appropriate treatment measures should be taken, including maintaining water and electrolyte balance, and supplementing protein.
6. If any adverse events and/or adverse reactions occur during the use of this product, please consult a doctor.
7. Please inform your doctor if you are using other medications concurrently.
8. Please keep out of reach of children.

 

Animal experiments have shown that this product has no effect on the fetus, but there is a lack of experience in its use in pregnant women, so its use in pregnant women requires careful consideration of the benefits and risks. There is no data to show whether this product can be secreted into breast milk, so its use in lactating women should be considered cautiously.

 

Regardless of the type of infection, the total dose of azithromycin in children is recommended not to exceed 1500mg. Azithromycin dry suspension is used for children weighing more than 45kg, and the dosage is the same as for adults. The efficacy and safety of treating otitis media, community-acquired pneumonia in children under 6 months of age, and pharyngitis or tonsillitis in children under 2 years of age have not been established.

 

No such experiment has been conducted and there are no reliable references.

 

Based on the information from foreign drug interaction studies, the following information on this product is obtained:
Antacids: In pharmacokinetic studies exploring the co-administration of antacids and azithromycin, the peak concentration of azithromycin was reduced by approximately 25%, with no observed effect on total bioavailability. Patients taking azithromycin who also need to take antacids should not take these medications at the same time. Cetirizine: In healthy volunteers who orally co-administered azithromycin and cetirizine (20mg) for 5 days, there was no pharmacokinetic interaction between the two at steady-state concentrations, and no significant changes in QT interval were observed. Deoxyguanosine (dideoxyinosine): Compared with placebo, co-administration of 1200mg azithromycin and 400mg deoxyguanosine daily in 6 HIV-positive patients did not affect the steady-state pharmacokinetics of deoxyguanosine. Digoxin: It has been reported that some macrolide antibiotics affect the intestinal metabolism of digoxin in some patients. Therefore, patients taking azithromycin and digoxin should be aware of the possibility of increased digoxin blood concentrations. Zidovudine: Single doses of 1000mg and multiple doses of 1200mg or 600mg of azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolites. However, oral azithromycin can increase the concentration of phosphorylated zidovudine in peripheral blood mononuclear cells, which is a clinically active metabolite. The clinical significance of these findings is unclear, but it may be beneficial to patients. Azithromycin has no significant effect on the hepatic cytochrome P450 system. Unlike other macrolide antibiotics such as erythromycin, azithromycin does not affect the pharmacokinetics of other drugs, and does not lose its activity by inducing hepatic cytochrome P450 or by forming cytochrome metabolic complexes. Ergot: Due to the theoretical possibility of ergot poisoning, the simultaneous use of azithromycin and ergot derivatives is not recommended. Pharmacokinetic studies have been conducted on azithromycin and the following drugs that are primarily metabolized by the hepatic cytochrome P450 system. Atorvastatin: Co-administration of 10mg atorvastatin daily and 500mg azithromycin daily had no effect on atorvastatin blood concentrations (HMG CoA-reductase inhibition assay). Carbamazepine: Pharmacokinetic studies in healthy volunteers showed that the co-administration of carbamazepine and azithromycin had no significant effect on the blood concentrations of carbamazepine and its active metabolites. Cimetidine: In a pharmacokinetic study of a single dose of cimetidine, administration two hours before azithromycin did not alter the pharmacokinetics of azithromycin. Oral coumarin anticoagulants: In pharmacokinetic studies in healthy volunteers, azithromycin did not affect the anticoagulant effect of a single oral dose of 15mg warfarin. After the launch of azithromycin, there have been reports that the co-administration of azithromycin and oral coumarin anticoagulants can enhance the anticoagulant effect. Although the causal relationship has not been established, patients who are co-administering oral coumarin anticoagulants should have their prothrombin time monitored frequently. Cyclosporine: In a pharmacokinetic study in healthy volunteers, a single oral dose of 10mg/kg cyclosporine was administered after 3 days of oral azithromycin 500mg daily, resulting in a significant increase in the peak concentration and area under the curve at 5 hours of cyclosporine. Therefore, caution must be exercised when using the two together. If they must be used together, the blood concentration of cyclosporine should be monitored so that the dose can be adjusted accordingly. Efavirenz: Co-administration of azithromycin (single dose 600mg) and efavirenz (400mg daily for 7 days) did not reveal any clinically significant pharmacokinetic changes. Fluconazole: Co-administration of a single dose of 800mg fluconazole and a single dose of 1200mg azithromycin did not show any significant changes in the pharmacokinetics of fluconazole, and the total exposure and half-life of azithromycin were also unchanged, while the peak blood concentration was reduced by 18%, but without significant clinical significance. Indinavir: Co-administration of a single dose of 1200mg azithromycin had no significant effect on the pharmacokinetics of indinavir (800mg three times daily for 5 days). Methylprednisolone: In a drug interaction study in healthy volunteers, azithromycin had no significant effect on the pharmacokinetic parameters of methylprednisolone. Midazolam: In healthy volunteers who co-administered azithromycin (500mg/day for 3 days) and midazolam (single dose 15mg), there were no significant changes in the pharmacokinetics and pharmacodynamics of the latter. Nelfinavir: Co-administration of 1200mg azithromycin and nelfinavir (750mg three times daily until steady-state blood concentration was reached) did not result in clinically significant drug interactions, so no dose adjustment is needed. Rifabutin: Co-administration with rifabutin had no effect on the serum concentrations of either drug. Co-administration of azithromycin and rifabutin can cause neutropenia. Although neutropenia is associated with the use of rifabutin, whether it is related to the co-administration of azithromycin is still inconclusive. Sildenafil: In studies in healthy male volunteers, there is no evidence that azithromycin (500mg daily for 3 days) affects the peak blood concentration or area under the curve of sildenafil or its major N-oxide metabolite. Terfenadine: Pharmacokinetic studies have shown no drug interaction between azithromycin and terfenadine. Although there have been rare reports of interactions between the two, and the possibility of such interaction cannot be completely ruled out, there is still no specific evidence that such interaction has occurred. Theophylline: There was no interaction between azithromycin and theophylline in healthy volunteers. Triazolam: Compared with placebo, co-administration of azithromycin (500mg on day 1, 250mg on day 2) and triazolam (0.125mg on day 2) in 14 healthy volunteers had no significant effect on the pharmacokinetics of triazolam. TMP/SMZ: Daily administration of 160mg/800mg TMP/SMZ for 7 days, and co-administration of a single dose of 1200mg azithromycin on day 7, showed no significant changes in the blood concentration, total exposure, and urinary clearance of TMP/SMZ. The blood concentration of azithromycin was also similar to that in other studies.

 

No such experiment has been conducted and there are no reliable references.

 

Pharmacological effects Azithromycin is an azalide antibiotic. Its mechanism of action is to interfere with protein synthesis (without affecting nucleic acid synthesis) by binding to the 50s ribosomal subunit of susceptible microorganisms.
Both in vitro and clinical studies have shown that azithromycin is effective against a variety of pathogens, including: Gram-positive aerobic microorganisms: Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and hemolytic streptococci. Azithromycin has cross-resistance to erythromycin-resistant Gram-positive bacteria. Most enterococci (enterococci) and methicillin-resistant Staphylococcus aureus are resistant to this product. Gram-negative aerobic microorganisms: Haemophilus influenzae, Moraxella catarrhalis. Other microorganisms: Chlamydia trachomatis. In vitro and clinical studies suggest that this product can prevent diseases caused by the Mycobacterium avium complex (consisting of Mycobacterium avium and Mycobacterium intracellulare). Bacterial β-lactamases do not affect the activity of azithromycin. In vitro studies have been conducted on the following microorganisms, but their clinical significance is unclear, including Streptococcus spp. (C, F, G), viridans streptococci, Bordetella pertussis, Haemophilus ducreyi, Legionella pneumophila, Bacteroides spp., Streptococcus anginosus group, Treponema pallidum, Mycoplasma pneumoniae, Treponema pallidum, Ureaplasma urealyticum, etc. Toxicological effects Genotoxicity: Azithromycin did not show mutagenic effects in human lymphocyte tests, mouse bone marrow micronucleus tests, and in vitro mouse lymphoma cell tests. Reproductive toxicity: Reproductive toxicity tests in rats and mice showed that when azithromycin (oral administration) was administered at doses that produced moderate maternal toxicity (i.e., 200 mg/kg/day, calculated by body surface area, approximately 2-4 times the human dose of 500 mg/kg/day), no teratogenic effects were found. No harm to fertility and fetuses has been found. There are currently no adequate and well-controlled clinical trials in pregnant women. Because the results of animal reproductive studies do not always predict human outcomes, this product should only be used in pregnant women if absolutely necessary. It is unknown whether this product is secreted in human milk. Since many drugs are secreted in human milk, nursing mothers should be cautious when using it. Carcinogenicity: There is no data on the carcinogenicity of this product in long-term animal studies.

 

Rapidly absorbed after oral administration, with a bioavailability of 37%. After a single oral dose of 0.5 g, the peak time is 2.5-2.6 hours, and the peak blood concentration (Cmax) is 0.4-0.45 mg/L. This product is widely distributed in the body, and the concentration in various tissues can reach 10-100 times the blood concentration at the same time. The concentration is high in macrophages and fibroblasts, and the former can transport azithromycin to the site of inflammation. The blood elimination half-life (t1/2β) after a single dose is 35-48 hours, more than 50% of the dose is excreted in the bile in its original form, and about 4.5% is excreted in the urine in its original form within 72 hours after administration. The serum protein binding rate decreases with increasing blood drug concentration. When the blood drug concentration is 0.02 μg/ml, the serum protein binding rate is 15%; when the blood drug concentration is 2 μg/ml, the serum protein binding rate is 7%. Foreign data show that there is no significant change in pharmacokinetic parameters in patients with mild to moderate renal insufficiency (glomerular filtration rate of 10-80 ml/min), while those with severe renal insufficiency (glomerular filtration rate of less than 10 ml/min) have significant differences from normal individuals, with a 33% increase in systemic exposure.

 

Seal and store in a dry place.

 

Paper-aluminum composite film bag, 9 bags/box.

 

24 months.

 

2005 edition, Part II of the Chinese Pharmacopoeia. ^[1]