What Is Roxithromycin?

Roxithromycin, Roxithromycin, English aliases Claramid, Rulid, Western medicine, is a new generation of macrolide antibiotics, mainly acting on Gram-positive bacteria, anaerobic bacteria, chlamydia and mycoplasma. Its in vitro antibacterial effect is similar to that of erythromycin, and its in vivo antibacterial effect is 1 to 4 times stronger than that of erythromycin.

Drug Name: Roxithromycin
Foreign name: Roxithromycin
Whether prescription drugs: prescription

Main indications: Gram-positive bacteria, anaerobic bacteria, chlamydia, and mycoplasma
Dosage: 150mg twice daily or 300mg once daily
Dosage form: capsule
Chemical formula: C41H76N2O15

Introduction of roxithromycin compounds

Roxithromycin Basic Information

Chinese name: roxithromycin

Chinese alias: Beike; Lang Su; Luo Lide; Luo Maixin; Mike Rhodes

English name: (E) -roxithromycin

English alias: roxyithromycin; biaxsig; Brilid; Makrodex; Romycin; Roxithromycinum; Rulid; Rulide; Ru-28965; Surid

CAS number: 80214-83-1

Roxithromycin

Molecular formula: C ₄₁ H ₇₆ N ₂ O ₁₅

Molecular weight: 837.04700

Exact mass: 836.52500

PSA: 216.89000

LogP: 2.20960

Physicochemical properties of roxithromycin

Appearance and properties: white crystalline powder

Density: 1.25g / cm ³

Melting point: 115- 120ºC

Boiling point: 864.7ºC at 760 mmHg

Flash point: 476.7ºC

Refractive index: 1.535

Storage conditions: 2-8ºC

Specific rotation: Take this product, accurately weigh, add absolute ethanol to dissolve and quantitatively dilute to make a solution containing about 20mg per 1ml, and measure it according to law (Appendix VIE of Part Two of the 2010 Pharmacopoeia). To -87 °.

Roxithromycin safety information

Customs Code: 2941500000

Danger category code: R22

Safety instructions: S26

Dangerous goods sign: Xn

Production method of roxithromycin

Using erythromycin as raw material, it reacts with hydroxylamine hydrochloride in triethylamine and methanol to form oxime, and then reacts with methoxyethoxymethyl chloride in acetone to obtain roxithromycin.

Roxithromycin use

This product is a new generation of macrolide antibiotics, mainly used for Gram-positive bacteria, anaerobic bacteria, chlamydia and mycoplasma, etc. ^[1] .

Roxithromycin pharmacopoeia standard

Roxithromycin identification

(1) In the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.

(2) The infrared light absorption spectrum of this product should be consistent with the control spectrum ("Infrared Spectra of Drugs" 786). If inconsistent, take an appropriate amount of this product, add an appropriate amount of acetone, dissolve, evaporate to dryness at room temperature, and measure.

Roxithromycin test

1 alkalinity

Take 0.1g of this product, add 150ml of water, shake to make a suspension containing about 0.7mg per 1ml, and determine it according to law (Appendix VI H of the Pharmacopoeia Part II of 2010 Edition), the pH value should be 8.0 ~ 10.0.

2 related substances

Take this product, add the mobile phase to dissolve and dilute it to make a solution containing about 2.0mg per 1ml, as the test solution; take 1ml precisely, place it in a 100ml measuring bottle, dilute to the mark with the mobile phase, shake well, as Control solution: According to the chromatographic conditions under the content determination item, take 20l of the control solution and inject it into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 20% of the full range; accurately measure the test solution and 20 l of each control solution was injected into the liquid chromatograph, and the chromatogram was recorded to 4 times the peak retention time of the main component. If there is an impurity peak in the chromatogram of the test solution, except for the dimethylformamide peak (measured in the same way as the 0.001% dimethylformamide solution using a mobile phase, and determined by retention time), the area of a single impurity peak must not Greater than the area of the main peak of the control solution (1.0%), the sum of the peak areas of the impurities must not be more than 4 times (4.0%) the area of the main peak of the control solution. Any peaks less than 0.1 times the area of the main peak of the control solution in the chromatogram of the test solution can be ignored. .

3 residual solvents

Methanol and acetone

Take about 0.2g of this product, weigh it accurately, place it in the headspace bottle, add 5ml dimethyl sulfoxide precisely to dissolve, seal, and use it as a test solution: accurately weigh the appropriate amount of methanol and acetone and quantify with dimethylsulfoxide Dilute it to make a mixed solution containing about 0.12 mg of methanol and 0.20 mg of acetone per 1 ml. Precisely measure 5 ml into a headspace bottle, seal it, and use it as a reference solution. According to the residual solvent determination method (the second method of Appendix P of the 2010 Pharmacopoeia, the second method), the capillary column with 6% cyanopropylphenyl-94% dimethylpolysiloxane (or similar polarity) as the fixing solution is Chromatographic column; start temperature of 40 ° C for 5 minutes, increase to 200 ° C at a rate of 30 ° C per minute and maintain for 3 minutes; detector temperature is 250 ° C; inlet temperature is 230 ° C; headspace bottle equilibrium temperature is 105 ° C, equilibration time is 30 minutes. Take the reference solution headspace sample, and the resolution between the peaks of each component should meet the requirements. Take the test solution and the reference solution for headspace injection, record the chromatogram, and calculate the peak area according to the external standard method, which should meet the requirements.

dimethylformamide

Accurately weigh the appropriate amount of this product, add dimethyl sulfoxide to dissolve and quantitatively dilute it to make a solution containing about 50mg per 1ml as a test solution; accurately weigh an appropriate amount of dimethylformamide and use dimethylsulfoxide Quantitative dilution was made into a solution containing about 45 g of dimethylformamide per 1 ml as a reference solution. Capillary column with 6% cyanopropylphenyl-94% dimethylpolysiloxane (or similar polarity) as the fixed solution For a chromatographic column: the initial temperature is 120 ° C, maintained for 4 minutes, raised to 200 ° C at a rate of 30 ° C per minute, and maintained for 5 minutes; the detector temperature is 250 ° C; the inlet temperature is 230 ° C; 1.0 l each of the test solution and the reference solution were injected into the gas chromatograph respectively, and the chromatogram was recorded. The peak area was calculated according to the external standard method, which should meet the requirements.

4 moisture

Take this product and measure it according to the Moisture Determination Method (Appendix M, Method 1 of Part II of the Pharmacopoeia, 2010 Edition). The moisture content must not exceed 3.0%.

5 burning residue

Take 1.0g of this product and check it according to law (Appendix N of Part Two of the 2010 Pharmacopoeia). The residual residue shall not exceed 0.1%.

6 heavy metals

Take the residue left under the burning residue and inspect it according to law (Appendix H of the 2010 edition of the Pharmacopoeia, the second method). The heavy metal must not exceed 10 parts per million.

Determination of roxithromycin

It was determined by high performance liquid chromatography (Appendix VD of Part Two of the Pharmacopoeia, 2010 Edition).

1 Chromatographic conditions and system suitability tests

Use octadecylsilane bonded silica as a filler; use a 0.067mol / L ammonium dihydrogen phosphate solution (adjust the pH to 6.5 with triethylamine)-acetonitrile (65:35) as the mobile phase: the detection wavelength is 210nm. Take appropriate amounts of roxithromycin reference substance and erythromycin standard, add mobile phase to dissolve and dilute to make a mixed solution containing about 1mg per 1ml, and take 20l into the liquid chromatograph. Retention time of roxithromycin peak About 14 minutes, its resolution from the erythromycin peak should not be less than 15.0, and the resolution of the roxithromycin peak from the impurity peak at a relative retention time of about 0.95 should not be less than 1.0, and its relative retention time is about 1.2. The resolution of impurity peaks should not be less than 2.0.

2 Assay

Take an appropriate amount of this product, weigh it accurately, add mobile phase to dissolve and quantitatively dilute to make a solution containing about 1.0mg per 1ml. Precisely measure 20l into the liquid chromatograph and record the chromatogram. Another roxithromycin reference substance was measured in the same way. Calculate the peak area according to the external standard method.

Roxithromycin category

Macrolide antibiotics.

Roxithromycin storage

Sealed and stored in a dry place.

Roxithromycin preparation

(1) roxithromycin dry suspension (2) roxithromycin tablets (3) roxithromycin dispersible tablets (4) roxithromycin capsules (5) roxithromycin granules ^[2]

Roxithromycin drug description

Roxithromycin classification

Antibiotics> Macrolides

Roxithromycin dosage form

1. Tablet: 50mg, 75mg, 150mg;

2. Capsule: 50mg, 75mg, 150mg;

3. Granules: 25mg, 50mg, 75mg.

Roxithromycin pharmacological action

Rhodocomyces roxithromycin is a new generation of macrolide antibiotics. It is a semi-synthetic 14-membered macrolide drug. Its mechanism of action is the same as that of erythromycin, which is mainly combined with the bacterial 50S ribosomal subunit, which inhibits the synthesis of bacterial proteins by blocking transpeptide effect and mRNA translocation, thereby playing an antibacterial effect. It is characterized by its ability to enter macrophages, lung cells, alveoli, and polymorphonuclear leukocytes more quickly. The antibacterial spectrum of roxithromycin is similar to that of erythromycin. Its antibacterial effect in vitro is similar to that of erythromycin, and the antibacterial effect in vivo is 1-4 times stronger than that of erythromycin. Roxithromycin has a slightly worse effect on gram-positive bacteria than erythromycin, and it has a stronger effect on Legionella pneumophila than erythromycin. The antimicrobial effect on Chlamydia pneumoniae, Mycoplasma pneumoniae and Ureaplasma urealyticum is similar or slightly stronger than that of erythromycin. Roxithromycin against Staphylococcus aureus (except MRSA), Streptococcus (including A, B, C type Streptococcus and Streptococcus pneumoniae, but G and Enterococcus), Corynebacterium, Listeria, Catamol Lactobacillus (catarrhalis), Legionella, etc. have strong antibacterial activity; it is effective against oral anaerobic bacteria, bacteroides genus, pneumococcus, peptostreptococcus, propionibacterium acnes, and toxoplasma encephalitis, chlamydia, Mycoplasma, Ureaplasma urealyticum, Treponema pallidum, etc. also have a certain effect; weak effects on Helicobacter, Neisseria gonorrhoeae, meningococcus, pertussis, etc. Roxithromycin can inhibit most gram-positive bacteria, common pathogenic bacteria for respiratory and skin infections, such as Staphylococcus aureus, Staphylococcus epidermidis, pneumococcus, Streptococcus pyogenes, influenza bacilli, mycoplasma pneumoniae and legionella, etc. Its antibacterial activity is similar to that of erythromycin. Effective for genitourinary system infections caused by Chlamydia trachomatis and Mycoplasma urealyticum, and effective for Treponema pallidum.

Roxithromycin pharmacokinetics

Rhodocomyces roxithromycin is resistant to acid and is not damaged by gastric acid, is well absorbed from the gastrointestinal tract, and has a high blood concentration (the peak blood concentration of roxithromycin is the highest of all macrolides). A single oral dose of 150 mg reached a peak after 2 hours, with an average of 6.6 to 7.9 g / ml. Drug absorption is higher in tissues and body fluids than in erythromycin. Drug concentrations in tonsils, sinuses, middle ears, lungs, sputum, prostate and other urogenital tract tissues can reach effective treatment levels. But it is very low in breast milk. The area under the drug concentration-time curve (AUC) and the peak blood drug concentration were directly proportional to the dose. The roxithromycin protein binding rate was 96% at a blood concentration of 2.5 mg / L, and the elimination half-life was 8.4 to 15.5 h, which was much longer than that of erythromycin. The drug is mainly excreted with the stool as the original drug, and some are excreted as desugared metabolites. About 7.4% are excreted through the urine. In patients with renal insufficiency, the half-life is prolonged, and the area under the drug concentration-time curve (AUC) is increased. In patients with severe cirrhosis, the half-life can be doubled. The absorption rate of roxithromycin is not affected by age, and generally has few adverse reactions and low toxicity.

Roxithromycin indication

1. Suitable for the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes.

2. It is suitable for the treatment of sinusitis, otitis media, acute bronchitis and acute bronchitis caused by sensitive bacteria.

3. Suitable for the treatment of pneumonia caused by Mycoplasma pneumoniae or Chlamydia pneumoniae; urethritis and non-specific urethritis (cervicitis) caused by Chlamydia trachomatis.

4. Suitable for the treatment of skin and soft tissue infections caused by sensitive bacteria. Urogenital infections.

Roxithromycin contraindications

Those who are allergic to roxithromycin or other macrolides are contraindicated.

Precautions for roxithromycin

1. Cross-allergies: When patients are allergic to one macrolide, they may also be allergic to other macrolides.

2. Use with caution: (1) those with liver dysfunction; (2) pregnant and lactating women.

3. Liver function should be monitored during long-term medication; theophylline blood concentration should be monitored when roxithromycin is combined with theophylline.

Roxithromycin adverse reactions

The adverse reactions of roxithromycin and roxithromycin were mild and the incidence was low (the total incidence was about 4%).

1. More common gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, but the incidence is significantly lower than erythromycin.

2. Occasionally minor allergic reactions such as rash, urticaria, pruritus, and drug fever.

3. A small number of patients may have abnormal liver function after treatment.

4. Few patients have symptoms such as headache and dizziness after taking the medicine.

Roxithromycin dosage

1. Adults: (1) Treatment of general infections: 150 mg each time, twice daily; or 300 mg each time, once daily. (2) Dose for renal insufficiency: The dose does not need to be adjusted for patients with mild renal insufficiency, and the administration time for patients with severe renal insufficiency is doubled (150 mg each time, once a day). (3) Dose at liver insufficiency: The half-life of patients with severe liver cirrhosis is extended to more than 2 times the normal level. If it is really needed, 150 mg is administered once a day. (4) Dose for the elderly: No need to adjust the dose.

2. Children: 2.5 ~ 5mg / kg each time, twice a day.

Roxithromycin drug interactions

1. Combination of roxithromycin and sulfamethoxazole and isoxazole (1:19), the inhibitory effect on Haemophilus influenzae can be increased by 2 to 4 times, and the incidence of drug resistance can be increased from 47.2% It dropped to 10.0%.

2. The combination of roxithromycin and proton pump inhibitors (such as lansoprazole and omeprazole) will not change the system bioavailability of the two, but can make the local concentration of roxithromycin in the stomach Elevated, this effect may help the combination of roxithromycin and proton pump inhibitors for the eradication of H. pylori.

3. When roxithromycin is used with warfarin, roxithromycin may inhibit the metabolism of warfarin, increase the blood concentration of warfarin, and increase the risk of bleeding.

4. Combination of roxithromycin and benzodiazepines (such as prazolam, diazepam, midazolam, triazolam) can inhibit liver enzymes responsible for benzodiazepine metabolism by reducing Clearance, prolonged half-life, and increased volume of distribution lead to increased blood concentrations of benzodiazepines.

5. The combination of roxithromycin and pimozide may inhibit the metabolism of pimozide, leading to an increase in the plasma concentration of the latter, causing certain cardiovascular adverse reactions such as prolonged QT interval, arrhythmia, and sudden death.

6. The combination of roxithromycin and digoxin can clear the intestinal flora that can inactivate digoxin, leading to a decrease in the degradation of digoxin in the body and an increase in the concentration of digoxin in the blood and a toxic reaction.

7. The combination of roxithromycin and propyriamine may lead to an increase in the plasma concentration of propyriamine.

8. The combination of roxithromycin and astemizole may lead to an increase in plasma levels of astemizole.

9. Use of roxithromycin and cyclosporine, roxithromycin may promote the absorption of cyclosporine and interfere with its metabolism, so that the plasma concentration of cyclosporine is increased.

10. Combination of roxithromycin and ergotamine derivative can cause acute ergot poisoning (such as peripheral vasospasm).

11. Taking roxithromycin with birth control pills has no effect on the effectiveness of oral contraceptives.

12. Roxithromycin has no effect on carbamazepine and ranitidine.

13. The pharmacokinetic effect of roxithromycin on theophylline is similar to erythromycin, but it is lighter and can increase the theophylline half-life by 8% and eliminate 16%. When combined with theophylline, theophylline is not required to be reduced. Dose, but its drug concentration should be monitored.

14. Unlike erythromycin, roxithromycin has no effect on the pharmacokinetic parameters of carbamazepine and can be used simultaneously.

Roxithromycin expert review

Roxithromycin is a new generation of macrolide antibiotics, with antibacterial activity similar to the antibacterial spectrum and erythromycin. It is an inhibitor of bacterial protein synthesis, and has good antibacterial effect on Staphylococcus aureus and Streptococcus, Mycoplasma, Chlamydia, Legionella, Haemophilus influenzae and so on. Foreign reports have reported that oral roxithromycin was administered to 1,313 patients with upper and lower respiratory infections at 200 to 600 mg per day for 3 to 14 consecutive days. The effective rates for treating upper and lower respiratory infections were 88% and 58%, respectively. In another international multicenter clinical study, 3240 patients were treated. The effective rate of upper respiratory tract infection was 96%, the effective rate of acute respiratory attack of chronic bronchitis in lower respiratory tract infection was 94%, and the effective rate of pneumonia was 95. %. Another report reported that oral roxithromycin was administered to 18020 patients with upper respiratory tract infection and 14385 patients with lower respiratory tract infection at 150 mg twice daily for 7 to 14 days. The results showed that acute pharyngitis, tonsillitis, sinusitis, The effective rates of otitis media were 97%, 96%, and 96%, respectively, and the effective rates for bronchitis, acute bronchitis, and pneumonia were 97%, 94%, and 95%, of which the incidence of adverse reactions was 4%. Domestic reports indicate that 50 patients with respiratory system were treated with roxithromycin, 150 to 300 mg each time, twice a day for 7 to 10 consecutive days. Results The number of days for cough, sputum and sore throat to disappear was 4.74 ± 1.71 days. The clinical cure rate was 70%, the clinical effective rate was 90%, the bacteriological clearance rate was 87.36%, and the incidence of adverse reactions was 8%. In a hospital, 68 patients with non-gonococcal urethritis or cervicitis (29 males and 39 females, aged 3 to 56 years) were randomly divided into two groups, 39 patients in the treatment group received roxithromycin orally at 0.15 g each time. Twice a day for 20 consecutive days; 29 patients in the control group received minocycline orally 0.1 g each time, twice a day, with the same course of treatment as before. Results 32 cases and 25 cases were cured in the two groups respectively ^[3] .