Azithromycin Granules Instruction Manual

Main ingredient of this product: 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-lyxo-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-azacyclopentadecan-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 Streptococcus pyogenes.
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 Neisseria gonorrhoeae that are not multi-drug resistant.
5. Skin and soft tissue infections caused by sensitive bacteria.

 

0.1 g (100,000 units).

 

Pour this product into a cup, add an appropriate amount of cool boiled water, dissolve it thoroughly by shaking, and then take it orally. Take it 1 hour before or 2 hours after a meal.
Adult dosage:
1. For sexually transmitted diseases caused by Chlamydia trachomatis or susceptible Neisseria gonorrhoeae, a single oral dose of 1.0 g of this product is sufficient.
2. Treatment for Other Infections: The total dose is 1.5 g, to be taken in three divided doses—0.5 g of this product once daily. Alternatively, the total dose remains 1.5 g; on the first day, take 0.5 g, and then from days 2 to 5, take 0.25 g of this product orally once daily. Dosage for Children: 1. For the treatment of otitis media and pneumonia: On the first day, administer a single oral dose of 10 mg/kg based on body weight (maximum daily dose not exceeding 0.5 g). From days 2 to 5, administer a single oral dose of 5 mg/kg based on body weight daily (maximum daily dose not exceeding 0.25 g), or follow the dosing regimen below: Body Weight (kg) | First Day (Once Daily) | Days 2-5 (Once Daily) --- | --- | --- 15-25 | 0.2 g | 0.1 g 26-35 | 0.3 g | 0.15 g 36-45 | 0.4 g | 0.2 g 2. For the treatment of pharyngitis and tonsillitis in children: Administer a single oral dose of 12 mg/kg based on body weight daily (maximum daily dose not exceeding 0.5 g), for 5 consecutive days. Or follow the physician’s instructions.

 

This product is generally well-tolerated, with a low incidence of adverse reactions, most of which are mild to moderate and reversible.
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 difficulty breathing, etc.
2. The following adverse reactions, occurring at a rate of less than 1%, have also been observed in clinical practice: (1) Gastrointestinal system: dyspepsia, gastrointestinal bloating, mucositis, oral candidiasis, gastritis, etc.; (2) Nervous system: headache, somnolence, etc.; (3) Allergic reactions: bronchospasm, etc.; (4) Other reactions: abnormal taste sensation, etc.
3. Following market launch, the oral formulation has also been associated with the following adverse reactions, though their association with this product remains unclear: (1) Allergic reactions: joint pain, angioedema, urticaria, photosensitivity; (2) Cardiovascular system: arrhythmia, ventricular tachycardia; (3) Gastrointestinal tract: extremely rare cases of pseudomembranous colitis and tongue discoloration; (4) Urogenital system: interstitial nephritis, acute renal failure; (5) Hematopoietic system: thrombocytopenia; (6) Hepatobiliary system: there have been reports that azithromycin can cause hepatitis and cholestatic jaundice; occasionally, it may lead to hepatic necrosis and liver failure, though fatalities are rare, and the causal relationship has not yet been established; (7) Psychoneurological system: aggressive behavior, neurosis, anxiety, worry, headache, somnolence, dizziness, vertigo, seizures, hyperactivity; (8) Skin and appendages: rare but severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported; (9) Sensory organs: there have been reports that macrolide antibiotics can impair patients’ hearing. Some patients who took azithromycin experienced hearing impairment, including hearing loss, tinnitus, and/or deafness. According to investigative studies, this phenomenon appears to be associated with prolonged high-dose use of this product; follow-up of these patients revealed that most of them experienced recovery of their hearing. There have been rare reports of azithromycin causing changes in taste perception.
4. Abnormal laboratory findings: Elevated serum levels of ALT, AST, creatinine, LDH, bilirubin, and alkaline phosphatase; decreased counts of white blood cells, neutrophils, and platelets.

 

Do not use in patients allergic to azithromycin, erythromycin, or any other macrolide drug.

 

1. Food intake can affect the absorption of azithromycin; therefore, it should be taken orally 1 hour before or 2 hours after a meal.
2. Patients with mild renal impairment (creatinine clearance ≥ 40 ml/min) do not require dose adjustment. However, there is currently limited data on the use of azithromycin in patients with more severe renal impairment; therefore, caution should be exercised when administering azithromycin to such patients.
3. Since the hepatobiliary system is the primary route of azithromycin excretion, use with caution in patients with hepatic impairment; patients with severe liver disease should not use this medication. During treatment, regularly monitor liver function.
4. During medication, if an allergic reaction occurs (such as angioedema, skin reactions, Stevens-Johnson syndrome, or toxic epidermal necrolysis), the drug should be discontinued immediately, and appropriate measures should be taken.
5. During treatment, if the patient develops diarrhea, pseudomembranous colitis should be considered. If the diagnosis is confirmed, appropriate therapeutic measures should be taken, including maintaining fluid and electrolyte balance and supplementing protein.
6. During use of this product, if any adverse events and/or adverse reactions occur, please consult a doctor.
7. Please inform your doctor if you are taking other medications at the same time.
8. Please keep out of reach of children.

 

Animal studies have shown that this product has no adverse effects on the fetus; however, there is currently limited experience regarding its use in pregnant women. Therefore, when administering this product to pregnant women, a thorough risk-benefit assessment is essential. There is currently no data available indicating whether this product is excreted into breast milk; thus, caution should be exercised when using it in breastfeeding women.

 

For any type of infection, the total dose of azithromycin in children is recommended to not exceed 1,500 mg. The azithromycin dry suspension is intended for children weighing more than 45 kg; the dosage and administration regimen are the same as for adults. The efficacy and safety of azithromycin in treating otitis media in infants younger than 6 months, community-acquired pneumonia, and pharyngitis or tonsillitis in children younger than 2 years have not yet been established.

 

The experiment has not been conducted, and there are no reliable references.

 

According to data from overseas studies on drug interactions, the following information about this product has been obtained:
Antacids: In a pharmacokinetic study investigating the concurrent administration of antacids and azithromycin, the peak concentration of azithromycin was reduced by approximately 25%, but no effect on overall bioavailability was observed. Patients who need to take both azithromycin and antacids should not take these medications at the same time. Cetirizine: In healthy volunteers who orally administered azithromycin and cetirizine (20 mg) concurrently for 5 days, no pharmacokinetic interactions were observed between the two drugs at steady-state concentrations, nor were any significant changes in the QT interval noted. Didanosine (2',3'-dideoxyinosine): Compared with placebo, the concurrent daily administration of 1200 mg of azithromycin and 400 mg of didanosine to 6 HIV-positive patients did not affect the steady-state pharmacokinetics of didanosine. Digoxin: There have been reports that certain macrolide antibiotics can influence the intestinal metabolism of digoxin in some patients. Therefore, patients taking both azithromycin and digoxin should be monitored closely for potential increases in digoxin blood levels. Zidovudine: Single doses of 1000 mg and multiple doses of 1200 mg or 600 mg of azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, oral administration of azithromycin can increase the concentration of phosphorylated zidovudine in peripheral blood mononuclear cells, which is the clinically active metabolite. The clinical significance of these findings remains unclear, but they may be beneficial for patients. Azithromycin has no significant effect on the hepatic cytochrome P450 system. Unlike other macrolide antibiotics such as erythromycin, azithromycin does not alter the pharmacokinetics of other drugs, nor does it lose activity by inducing hepatic cytochrome P450 enzymes or by forming cytochrome-mediated metabolic complexes. Ergot: Due to the theoretical risk of ergotism, the concurrent use of azithromycin with ergot derivatives is not recommended. Pharmacokinetic studies have been conducted between azithromycin and the following drugs primarily metabolized by the hepatic cytochrome P450 system: Atorvastatin: Concurrent daily administration of 10 mg of atorvastatin with 500 mg of azithromycin had no effect on the blood concentrations of atorvastatin (HMG CoA-reductase inhibition assay). Carbamazepine: Pharmacokinetic studies in healthy volunteers showed that the concurrent use of carbamazepine and azithromycin had no significant impact on the blood concentrations of carbamazepine or its active metabolites. Cimetidine: In a single-dose pharmacokinetic study of cimetidine, when cimetidine was administered two hours before azithromycin, no changes in the pharmacokinetics of azithromycin were observed. Coumarin-based oral anticoagulants: In pharmacokinetic studies conducted in healthy volunteers, azithromycin did not affect the anticoagulant effect of a single 15-mg dose of warfarin. Since azithromycin was marketed, there have been reports that concurrent use of azithromycin and coumarin-based oral anticoagulants can enhance anticoagulant effects. Although the causal relationship has not been established, patients taking coumarin-based oral anticoagulants concurrently should be monitored regularly for prothrombin time. Cyclosporine: In pharmacokinetic studies conducted in healthy volunteers, after 3 consecutive days of oral administration of 500 mg of azithromycin daily followed by a single dose of cyclosporine at 10 mg/kg, the peak concentration and area under the curve of cyclosporine at 5 hours were significantly increased. Therefore, caution is required when these two drugs are used concurrently. If their concurrent use is necessary, cyclosporine blood concentrations should be monitored to adjust the dosage accordingly. Efavirenz: Concurrent administration of azithromycin (a single dose of 600 mg) and efavirenz (400 mg daily for 7 days) did not result in any pharmacokinetic changes of clinical significance. Fluconazole: Concurrent administration of a single dose of 800 mg of fluconazole with a single dose of 1200 mg of azithromycin did not significantly alter the pharmacokinetics of fluconazole; total exposure and half-life of azithromycin remained unchanged, although the peak blood concentration of azithromycin decreased by 18%, which was not considered clinically significant. Indinavir: Concurrent administration of a single dose of 1200 mg of azithromycin had no significant effect on the pharmacokinetics of indinavir (administered three times daily at 800 mg for 5 consecutive days). Methylprednisolone: In drug interaction studies conducted in healthy volunteers, azithromycin had no significant effect on the pharmacokinetic parameters of methylprednisolone. Midazolam: In healthy volunteers who simultaneously took azithromycin (500 mg daily for 3 days) and midazolam (a single dose of 15 mg), the pharmacokinetics and pharmacodynamics of the latter were not significantly altered. Nelfinavir: Concurrent administration of 1200 mg of azithromycin and nelfinavir (750 mg three times daily until steady-state blood concentrations were reached) did not result in any clinically significant drug interactions, so no dosage adjustments were necessary. Rifabutin: Co-administration of this product with rifabutin had no effect on the serum concentrations of either drug. When azithromycin is co-administered with rifabutin, neutropenia may occur. Although neutropenia is associated with rifabutin use, it remains inconclusive whether it is also associated with the co-administration of azithromycin. Sildenafil: In studies conducted in healthy male volunteers, there was no evidence that azithromycin (500 mg daily for 3 days) affected the peak blood concentration or area under the curve of sildenafil or its major N-desmethyl metabolite. Terfenadine: Pharmacokinetic studies indicated that there was no drug interaction between azithromycin and terfenadine. Although cases of interaction between these two drugs have rarely been reported, and the possibility of such an interaction cannot be completely ruled out, there is still no specific evidence indicating that such an interaction has occurred. Theophylline: In healthy volunteers, azithromycin did not interact with theophylline. Triazolam: Compared with placebo, 14 healthy volunteers who simultaneously took azithromycin (500 mg on day 1 and 250 mg on day 2) and triazolam (0.125 mg on day 2) showed no significant effects on the pharmacokinetics of triazolam. TMP/SMZ: Daily administration of TMP/SMZ 160 mg/800 mg for 7 consecutive days, followed by a single dose of 1200 mg of azithromycin on day 7, resulted in no significant changes in the blood concentrations, total exposure, or urinary clearance of TMP/SMZ. The blood concentrations of azithromycin were also similar to those observed in other studies.

 

The experiment has not been conducted, and there are no reliable references.

 

Pharmacological Action: Azithromycin is a macrolide antibiotic. Its mechanism of action involves binding to the 50S ribosomal subunit of susceptible microorganisms, thereby inhibiting protein synthesis (without affecting nucleic acid synthesis).
Both in vitro studies and clinical trials have demonstrated that azithromycin is effective against a variety of pathogenic bacteria, including: Gram-positive aerobic microorganisms: Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Streptococcus hemolyticus. Azithromycin exhibits cross-resistance to erythromycin-resistant Gram-positive bacteria. Most Enterococcus faecalis (enterococci) and methicillin-resistant Staphylococcus aureus are resistant to this drug. Gram-negative aerobic microorganisms: Haemophilus influenzae and Moraxella catarrhalis. Other microorganisms: Chlamydia trachomatis. In vitro studies and clinical trials suggest that this drug can prevent diseases caused by Mycobacterium avium complex (comprising Mycobacterium avium and Mycobacterium intracellulare). β-Lactamase produced by bacteria does not affect the activity of azithromycin. In vitro studies have been conducted on the following microorganisms, though their clinical significance remains unclear: Streptococcus species (C, F, G), viridans streptococci, Bordetella pertussis, Haemophilus ducreyi, Legionella pneumophila, Bacteroides species, Peptostreptococcus species, Borrelia burgdorferi, Mycoplasma pneumoniae, Treponema pallidum, Ureaplasma urealyticum, and others. Toxicological Effects: Genotoxicity: Results from human lymphocyte assays, mouse bone marrow micronucleus assays, and mouse in vitro lymphoma cell assays indicate that azithromycin does not exhibit mutagenic effects. Reproductive toxicity: Reproductive toxicity studies in rats and mice have shown that when azithromycin was administered orally at doses producing moderate maternal toxicity (i.e., 200 mg/kg/day, which, based on body surface area, is approximately 2–4 times the human therapeutic dose of 500 mg/kg/day), no teratogenic effects were observed. No adverse effects on fertility or fetal development have been identified thus far. Currently, there are no adequately designed and rigorously controlled clinical trials involving pregnant women. Since animal reproductive studies do not always predict human outcomes, this drug should be used during pregnancy only when absolutely necessary. It is currently unknown whether azithromycin is excreted in human breast milk; however, given that many drugs are secreted into breast milk, nursing mothers should exercise caution when using this medication. Carcinogenicity: There are currently no data available from long-term carcinogenicity studies in animals involving this drug.

 

After oral administration, the drug is rapidly absorbed, with a bioavailability of 37%. Following a single oral dose of 0.5 g, the time to peak plasma concentration (Tmax) is 2.5 to 2.6 hours, and the peak plasma concentration (Cmax) ranges from 0.4 to 0.45 mg/L. This drug exhibits extensive distribution throughout the body, with tissue concentrations reaching 10 to 100 times the corresponding plasma concentrations. It accumulates particularly high levels in macrophages and fibroblasts; the former can actively transport azithromycin to sites of inflammation. The terminal elimination half-life (t1/2β) after a single dose is 35 to 48 hours, and more than 50% of the administered dose is excreted unchanged via the biliary tract. Within 72 hours after administration, approximately 4.5% of the dose is excreted unchanged in the urine. The serum protein binding rate of this drug decreases as plasma drug concentrations increase: at a plasma concentration of 0.02 μg/mL, the serum protein binding rate is 15%; at a plasma concentration of 2 μg/mL, the serum protein binding rate drops to 7%. Foreign data indicate that in patients with mild to moderate renal impairment (glomerular filtration rate of 10–80 ml/min), pharmacokinetic parameters show no significant changes. However, in patients with severe renal impairment (glomerular filtration rate less than 10 ml/min), there are significant differences compared to healthy individuals, with a 33% increase in systemic exposure.

 

Seal and store in a dry place.

 

Broadcast: Paper-aluminum composite film bags, 9 bags per box.

 

24 months.

 

Volume II of the 2005 Edition of the Chinese Pharmacopoeia. ^[1]