Pyrrolidone

 Active 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-threo-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-lyxo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one.  
Molecular Formula: C38H72N2O12  
Molecular Weight: 749.00 

This product is a white or off-white granular substance.

1. Acute pharyngitis and acute tonsillitis caused by Streptococcus pyogenes.
2. Sinusitis, otitis media, acute bronchitis, and acute exacerbations of chronic bronchitis caused by susceptible 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.

0.1 g (100,000 units).

Pour this product into a cup, add an appropriate amount of cooled boiled water, dissolve and shake well before taking it orally. Consume 1 hour before meals or 2 hours after meals.
Adult dosage:
1. For sexually transmitted infections 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: - Total dose: 1.5 g, divided into three doses. Take 0.5 g of this medication once daily. - Alternatively, maintain the same total dose of 1.5 g, administering 0.5 g on the first day, followed by 0.25 g orally once daily from days 2 through 5. Pediatric Dosage: 1. For treating otitis media or pneumonia: On the first day, administer a single dose of 10 mg/kg based on body weight (maximum daily dose not exceeding 0.5 g). From days 2 to 5, give a single daily dose of 5 mg/kg based on body weight (maximum daily dose not exceeding 0.25 g). Alternatively, follow this dosing regimen: - Body Weight (kg): - Day 1 (once daily): 0.2 g - Days 2–5 (once daily): 0.1 g - Body Weight (kg): - Day 1 (once daily): 0.3 g - Days 2–5 (once daily): 0.15 g - Body Weight (kg): - Day 1 (once daily): 0.4 g - Days 2–5 (once daily): 0.2 g 2. For treating pharyngitis or tonsillitis in children: Administer a single daily dose of 12 mg/kg based on body weight (maximum daily dose not exceeding 0.5 g), taken for 5 consecutive days. Alternatively, follow your doctor’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 symptoms: diarrhea, nausea, abdominal pain, loose stools, vomiting, etc.; (2) Skin reactions: rash, itching, and other such symptoms; (3) Other reactions: such as loss of appetite, vaginitis, dizziness, or difficulty breathing, among others.
2. The following adverse reactions, occurring in less than 1% of cases, have also been observed in clinical practice: (1) Digestive system: Indigestion, gastrointestinal bloating, mucositis, oral candidiasis, gastritis, etc.; (2) Nervous system: Headache, drowsiness, etc.; (3) Allergic reactions: Bronchospasm, among others; (4) Other reactions: Abnormal taste perception, etc.
3. The following adverse reactions have also been observed in oral formulations after marketing, though their association with this product remains unclear: (1) Allergic reactions: joint pain, angioedema, urticaria, and photosensitivity; (2) Cardiovascular system: arrhythmias and ventricular tachycardia; (3) Gastrointestinal tract: rare cases of pseudomembranous colitis and tongue discoloration; (4) Urogenital system: interstitial nephritis and acute renal failure; (5) Hematopoietic system: thrombocytopenia; (6) Hepatobiliary system: there have been reports of azithromycin causing hepatitis and cholestatic jaundice, with occasional instances of hepatic necrosis and liver failure—though fatalities are extremely rare—and causality has yet to be definitively established; (7) Psychoneurological system: aggressive behavior, nervousness, anxiety, worry, headache, drowsiness, dizziness, vertigo, seizures, and 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: some macrolide antibiotics, including azithromycin, have been linked to hearing impairment in patients. A few individuals have experienced hearing loss, tinnitus, or deafness after taking azithromycin. Epidemiological studies suggest that these auditory effects may be associated with prolonged, high-dose use of the drug; however, follow-up of these patients indicates that most recover their hearing over time. Rarely, azithromycin has also been reported to cause taste disturbances.
4. Abnormal laboratory findings: Elevated serum levels of ALT, AST, creatinine, LDH, bilirubin, and alkaline phosphatase, along with decreased white blood cell, neutrophil, and platelet counts.

Do not use in individuals allergic to azithromycin, erythromycin, or any other macrolide medication.

1. Eating can affect the absorption of azithromycin, so it should be taken orally either 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 dysfunction, so caution should be exercised when administering azithromycin to these patients.
3. Since the hepatic and biliary systems are the primary routes of azithromycin excretion, use with caution in patients with hepatic impairment; it should not be administered to patients with severe liver disease. Regular monitoring of liver function is recommended during treatment.
4. If an allergic reaction occurs during medication (such as angioedema, skin reactions, Stevens-Johnson syndrome, or toxic epidermal necrolysis), discontinue the drug immediately and take appropriate measures.
5. During treatment, if patients develop diarrhea symptoms, the possibility of pseudomembranous colitis should be considered. If diagnosed, appropriate treatment measures should be implemented, including maintaining fluid and electrolyte balance, as well as supplementing protein levels.
6. If any adverse events and/or side effects occur while using this product, please consult your doctor.
7. Please inform your doctor if you are taking other medications concurrently.
8. Please keep out of reach of children.

Animal studies have shown no adverse effects of this product on fetuses; 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. Additionally, no data are available yet on whether this product is excreted into breast milk, so cautious consideration is advised for nursing mothers.

Regardless of the type of infection, the recommended total dose of azithromycin for children should not exceed 1500 mg. Azithromycin dry suspension is intended for children weighing more than 45 kg; dosing and administration are the same as for adults. However, the efficacy and safety of azithromycin in treating otitis media in infants younger than 6 months, community-acquired pneumonia in this age group, and pharyngitis or tonsillitis in children under 2 years old have not yet been established.

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

According to research data on drug interactions conducted abroad, the following information about this product has been obtained:
Antacids: In a pharmacokinetic study examining the simultaneous administration of an antacid with azithromycin, the peak concentration of azithromycin was reduced by approximately 25%, though no significant impact on overall bioavailability was observed. Patients who need to take both azithromycin and an antacid should avoid taking these medications at the same time. Cetirizine: Healthy volunteers who orally administered azithromycin and cetirizine (20 mg) concurrently for 5 days showed no pharmacokinetic interactions between the two drugs at steady-state concentrations, and no notable changes in the QT interval were observed. Didanosine (dideoxynucleoside): Compared to placebo, six HIV-positive patients who took 1200 mg of azithromycin daily alongside 400 mg of didanosine did not experience any alterations in the steady-state pharmacokinetics of didanosine. Digoxin: There have been reports suggesting that certain macrolide antibiotics may influence digoxin’s intestinal metabolism in some patients. Therefore, patients receiving both azithromycin and digoxin should be monitored closely, as there is a potential for increased digoxin blood levels. Zidovudine: A single dose of 1000 mg or multiple doses of 1200 mg or 600 mg of azithromycin had minimal effects on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolites in HIV-positive individuals. However, oral administration of azithromycin significantly boosted the intracellular concentration of phosphorylated zidovudine—a clinically active metabolite—in peripheral blood mononuclear cells. While the clinical implications of this finding remain unclear, it may potentially offer therapeutic benefits to patients. Azithromycin does not significantly affect the hepatic cytochrome P450 system. Unlike erythromycin and other macrolide antibiotics, azithromycin does not alter the pharmacokinetics of other drugs, nor does it induce hepatic cytochrome P450 enzymes or lose activity by forming cytochrome-mediated metabolic complexes. Ergot: Due to theoretical concerns about ergotism, the concurrent use of azithromycin with ergot derivatives is generally discouraged. Pharmacokinetic studies have been conducted to evaluate the interactions between azithromycin and several key drugs primarily metabolized via the hepatic cytochrome P450 system: Atorvastatin: Co-administration of 10 mg of atorvastatin daily with 500 mg of azithromycin had no significant effect on atorvastatin plasma concentrations (as measured by HMG-CoA reductase inhibition assay). Carbamazepine: Pharmacokinetic studies in healthy volunteers demonstrated that co-administration of carbamazepine with azithromycin did not significantly alter the plasma concentrations of either carbamazepine or its active metabolite. Cimetidine: A single-dose pharmacokinetic study of cimetidine revealed no meaningful changes in azithromycin pharmacokinetics when cimetidine was administered two hours prior to azithromycin. Oral Anticoagulants (Coumarins): Pharmacokinetic studies in healthy volunteers indicated that azithromycin did not affect the anticoagulant activity of a single 15-mg dose of warfarin. However, post-marketing reports have suggested that concurrent use of azithromycin with coumarin-based oral anticoagulants may enhance anticoagulation. Although a causal relationship has not yet been established, patients on such combinations should undergo frequent monitoring of their prothrombin time. Cyclosporine: In healthy volunteers, a pharmacokinetic study involving three consecutive days of 500 mg of azithromycin followed by a single dose of cyclosporine (10 mg/kg) revealed a significant increase in cyclosporine’s peak concentration and area under the curve over 5 hours. Therefore, caution is advised when these drugs are used together, and cyclosporine levels should be closely monitored to allow for appropriate dose adjustments if necessary. Efavirenz: Co-administration of a single dose of 600 mg of azithromycin with efavirenz (400 mg daily for 7 days) did not result in any clinically significant pharmacokinetic changes. Fluconazole: When a single dose of 800 mg fluconazole was administered concurrently with a single dose of 1200 mg azithromycin, no notable alterations were observed in fluconazole’s pharmacokinetics. Similarly, total exposure and half-life of azithromycin remained unchanged, although the peak plasma concentration decreased by 18%, a change deemed clinically insignificant. Indinavir: Co-administration of a single dose of 1200 mg azithromycin had no significant impact 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 did not significantly affect the pharmacokinetic parameters of methylprednisolone. Midazolam: Concurrent administration of azithromycin (500 mg daily for 3 days) and midazolam (a single 15-mg dose) resulted in no significant changes to midazolam’s pharmacokinetics or pharmacodynamics in healthy volunteers. Nelfinavir: Co-administration of 1200 mg azithromycin with nelfinavir (750 mg three times daily until steady-state plasma concentrations were achieved) did not lead to any clinically meaningful drug interactions, eliminating the need for dosage adjustments. Rifabutin: Co-administration of rifabutin with this product did not affect the serum concentrations of either drug. However, combining azithromycin with rifabutin can lead to neutropenia. While neutropenia is associated with rifabutin use, whether it is also linked to concomitant use with azithromycin remains inconclusive. Terfenadine: Pharmacokinetic studies have shown no evidence of drug interactions between azithromycin and terfenadine.Although cases of interaction between these two drugs have been rarely reported, and the possibility of such an interaction cannot be entirely ruled out, there is currently no specific evidence to confirm that it has occurred. Theophylline: In healthy volunteers, azithromycin showed no significant interaction with theophylline. Triazolam: Compared to placebo, 14 healthy volunteers who received azithromycin (500 mg on Day 1, 250 mg on Day 2) concurrently with triazolam (0.125 mg on Day 2) exhibited no notable impact on triazolam’s pharmacokinetics. TMP/SMZ: When healthy volunteers took TMP/SMZ 160 mg/800 mg daily for 7 consecutive days and then simultaneously administered a single dose of azithromycin 1200 mg on Day 7, no significant changes were observed in TMP/SMZ plasma concentrations, total exposure, or urinary clearance rates. Azithromycin levels in the blood also remained consistent with findings from previous studies.

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

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 research 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*. Notably, azithromycin exhibits cross-resistance with erythromycin-resistant Gram-positive bacteria. Most species of *Enterococcus* (enterococci), as well as methicillin-resistant *Staphylococcus aureus*, are resistant to this drug. Gram-negative aerobic microorganisms: *Haemophilus influenzae* and *Moraxella catarrhalis*. Other microorganisms: *Chlamydia trachomatis*. In vitro and clinical studies suggest that azithromycin may help prevent diseases caused by the Mycobacterium avium complex (comprising *Mycobacterium avium* and *Mycobacterium intracellulare*). Importantly, β-lactamase-producing bacteria do not exhibit resistance to azithromycin, as the drug remains unaffected by these enzymes. While in vitro studies have been conducted against certain additional microorganisms—such as streptococci of groups C, F, and G, viridans streptococci, *Bordetella pertussis*, *Haemophilus ducreyi*, *Legionella pneumophila*, various species of *Bacteroides* and *Peptostreptococcus*, *Borrelia burgdorferi*, *Mycoplasma pneumoniae*, *Treponema pallidum*, and *Ureaplasma urealyticum*—their clinical significance remains unclear at present. **Toxicological Effects:** - **Genotoxicity:** Results from human lymphocyte assays, mouse bone marrow micronucleus tests, and an in vitro mouse lymphoma cell assay showed no evidence of mutagenic activity for azithromycin. - **Reproductive Toxicity:** Reproductive toxicity studies in rats and mice revealed no teratogenic effects when azithromycin was administered orally at doses that induced moderate maternal toxicity (200 mg/kg/day)—a dose level roughly 2 to 4 times higher than the recommended human therapeutic dose of 500 mg/kg/day based on body surface area calculations. No adverse effects on fertility or fetal development were observed. However, adequate and rigorously controlled clinical trials in pregnant women have not yet been conducted. Given that animal reproductive studies do not always reliably predict outcomes in humans, azithromycin should only be used during pregnancy if absolutely necessary. Additionally, it is currently unknown whether azithromycin is excreted in human breast milk; however, since many drugs are known to pass into breast milk, caution should be exercised when prescribing this medication to breastfeeding women. **Carcinogenicity:** To date, there are no available data from long-term carcinogenicity studies involving azithromycin in animals.

After oral administration, the drug is rapidly absorbed, with a bioavailability of 37%. Following a single dose of 0.5 g orally, peak plasma concentration (Cmax) is achieved within 2.5 to 2.6 hours, reaching levels of 0.4 to 0.45 mg/L. The drug exhibits extensive distribution throughout the body, with tissue concentrations often 10 to 100 times higher than plasma levels at any given time. Notably, it accumulates particularly in macrophages and fibroblasts, where it can be actively transported by macrophages to sites of inflammation. The elimination half-life (t1/2β) after a single dose is approximately 35 to 48 hours, and more than 50% of the administered dose is excreted unchanged via the biliary route. Within 72 hours post-administration, about 4.5% of the drug is eliminated unchanged through urine. It’s worth noting that the serum protein binding of this drug decreases as plasma concentrations rise: at a plasma level of 0.02 μg/mL, protein binding is around 15%, while at 2 μg/mL, it drops to just 7%. According to data from international studies, patients with mild to moderate renal impairment (glomerular filtration rate of 10–80 mL/min) show no significant changes in pharmacokinetic parameters. However, in patients with severe renal dysfunction (glomerular filtration rate <10 mL/min), there are notable differences compared to individuals with normal kidney function, with systemic exposure increasing by approximately 33%.

Seal tightly and store in a dry place.

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

24 months.

Chinese Pharmacopoeia, 2005 Edition, Volume II. ^[1]