Instructions Ormax powder for suspension preparation 200 mg/5 ml container 30 ml
Composition
active ingredient: azithromycin;
5 ml of suspension contain 200 mg of azithromycin (in the form of dihydrate);
excipients: sodium benzoate (E 211), sucrose or sucrose with colloidal anhydrous silicon dioxide, sodium phosphate, hydroxypropylcellulose, xanthan gum, colloidal anhydrous silicon dioxide, fruit flavoring "apricot". Does not contain dyes.
Dosage form
Powder for oral suspension.
Main physicochemical properties: white or almost white powder with a characteristic fruity odor.
Pharmacotherapeutic group
Antibacterials for systemic use. Macrolides, lincosamides and streptogramins. Azithromycin. ATC code J01F A10.
Pharmacological properties
Pharmacodynamics.
Azithromycin is a representative of a new generation of macrolide antibiotics, belonging to the azalide subgroup. The antibacterial effect of the drug is due to the blocking of protein biosynthesis of microorganisms sensitive to it by binding to the 50S subunits of ribosomes and inhibiting peptide translocation. The following are sensitive to the drug: Streptococcus pneumoniae (penicillin-sensitive), Streptococcus pyogenes, Staphуlococcus aureus (methicillin-sensitive), H.influenzae, H.parainfluenzae, M.catarrhalis, Pasteurella multocida, Clostridium perfringens, Legionella pneumophila, Fusobacterium spp., Prevotella spp., Porphyromonas spp., Chlamydia trachomatis, Chlamydia pneumoniae, Mycoplasma pneumoniae. Types of microorganisms for which acquired resistance may be problematic: Streptococcus pneumoniae with intermediate sensitivity to penicillin and penicillin-resistant. Complete cross-resistance exists in Streptococcus pneumoniae, group A beta-hemolytic streptococcus, Enterococcus faecalis, Bacteroides fragilis, Staphylococcus MRSA and MRSE (methicillin-resistant Staphylococcus has a very high prevalence of acquired resistance to macrolides, sensitivity to azithromycin in such species is rare).
The prevalence of acquired resistance for selected species may vary with location and time, therefore local information on resistance is required, particularly when treating severe infections. Qualified advice may be sought if the local prevalence of resistance is such that the efficacy of the drug in treating at least some types of infections is questionable.
Pharmacokinetics.
After oral administration, azithromycin is well absorbed and rapidly distributed in the body. The maximum concentration in the blood is detected after approximately 2-3 hours, the bioavailability of azithromycin is approximately 37%. When taken orally, azithromycin is distributed throughout the body. The concentration of azithromycin in the tissues is significantly higher (50 times) than in the blood plasma, which indicates a strong binding of the drug to the tissues. Binding to serum proteins is variable depending on the plasma concentrations and ranges from 12% at 0.5 μg/ml to 52% at 0.05 μg/ml. The terminal plasma half-life fully reflects the half-life from the tissues for 2-4 days. Approximately 12% of an intravenously administered dose of azithromycin is excreted unchanged in the urine over the next 3 days. Particularly high concentrations of unchanged azithromycin are found in human bile. Also in bile are detected 10 metabolites, which are formed by N- and O-demethylation, hydroxylation of the desosamine and aglycone rings and cleavage of the cladinose conjugate. The metabolites of azithromycin are not microbiologically active.
Indication
Infections caused by microorganisms sensitive to azithromycin:
ENT infections (bacterial pharyngitis/tonsillitis, sinusitis, otitis media);
respiratory tract infections (bacterial bronchitis, community-acquired pneumonia);
Skin and soft tissue infections: erythema migrans (initial stage of Lyme disease), erysipelas, impetigo, secondary pyoderma.
Contraindication
Hypersensitivity to azithromycin, erythromycin or any macrolide or ketolide antibiotic, or to any other component of the drug. Due to the theoretical possibility of ergotism, azithromycin should not be administered concomitantly with ergot derivatives.
Interaction with other medicinal products and other types of interactions
Azithromycin should be administered with caution to patients taking other drugs that may prolong the QT interval.
Antacids: In a study of the effect of concomitant administration of antacids on the pharmacokinetics of azithromycin, there was generally no change in bioavailability, although peak plasma concentrations of azithromycin were decreased by 25%. Azithromycin should be taken at least 1 hour before or 2 hours after taking an antacid.
Cetirizine: When azithromycin was coadministered for 5 days with cetirizine 20 mg at steady state, no pharmacokinetic interaction or significant changes in the QT interval were observed.
Digoxin and colchicine. Concomitant use of macrolide antibiotics, including azithromycin, and P-glycoprotein substrates such as digoxin and colchicine has been reported to increase serum levels of the P-glycoprotein substrate. Accordingly, the possibility of increased serum substrate concentrations should be considered when azithromycin is coadministered with a P-glycoprotein substrate such as digoxin or colchicine.
Zidovudine. Single doses of 1000 mg and 1200 mg or multiple doses of 600 mg of azithromycin did not affect the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolites. However, azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of these findings is unknown but may be useful for patients.
Azithromycin does not have a significant interaction with the hepatic cytochrome P450 system. It is believed that the drug does not have the pharmacokinetic drug interactions characteristic of erythromycin and other macrolides. Azithromycin does not induce or inactivate hepatic cytochrome P450 through the cytochrome-metabolite complex.
Ergot: Due to the theoretical possibility of ergotism, the concomitant use of azithromycin with ergot derivatives is not recommended.
There are data on pharmacokinetic studies of the use of the original azithromycin and subsequent drugs, the metabolism of which occurs to a large extent with the participation of cytochrome P450.
Atorvastatin: Coadministration of atorvastatin 10 mg daily and azithromycin 500 mg daily did not alter plasma concentrations of atorvastatin (based on HMG CoA reductase inhibition assay). However, postmarketing cases of rhabdomyolysis have been reported in patients receiving azithromycin with statins.
Carbamazepine: Azithromycin had no significant effect on the plasma levels of carbamazepine or its active metabolites.
Cimetidine: There were no changes in the pharmacokinetics of azithromycin when a single dose of cimetidine was administered 2 hours before azithromycin.
Oral Coumarin Anticoagulants. In a pharmacokinetic interaction study, azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin administered to healthy volunteers. Postmarketing reports of potentiation of the anticoagulant effect have been received following concomitant administration of azithromycin and oral coumarin anticoagulants. Although a causal relationship has not been established, consideration should be given to the frequency of monitoring of prothrombin time and international normalization ratio (INR) when azithromycin is prescribed to patients receiving oral coumarin anticoagulants.
Cyclosporine. A pharmacokinetic study in healthy volunteers receiving oral azithromycin 500 mg/day for 3 days followed by a single oral dose of cyclosporine 10 mg/kg demonstrated a significant increase in Cmax and AUC0-5 of cyclosporine. Some of the related macrolide antibiotics affect the metabolism of cyclosporine. The therapeutic situation should be carefully considered before prescribing these drugs together. If combined use is considered warranted, cyclosporine levels should be closely monitored and the dosage adjusted accordingly.
Efavirenz: Coadministration of a single dose of azithromycin 600 mg and daily administration of efavirenz 400 mg for 7 days did not result in any significant interaction.
Fluconazole. Coadministration of a single dose of azithromycin 1200 mg did not alter the pharmacokinetics of a single dose of fluconazole 800 mg. The total exposure and half-life of azithromycin were not altered by coadministration of fluconazole, but a clinically insignificant decrease in Cmax of azithromycin by 18% was observed.
Indinavir: Coadministration of a single dose of azithromycin 1200 mg had no statistically significant effect on the pharmacokinetics of indinavir administered at a dose of 800 mg three times daily for 5 days.
Methylprednisolone: Azithromycin did not significantly affect the pharmacokinetics of methylprednisolone.
Midazolam: Coadministration of azithromycin 500 mg daily for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of midazolam administered as a single 15 mg dose.
Nelfinavir: Coadministration of azithromycin 1200 mg and nelfinavir at steady-state concentrations (750 mg three times daily) resulted in increased azithromycin concentrations. No clinically significant adverse events were observed, and no dose adjustment is required.
Rifabutin: Concomitant administration of azithromycin and rifabutin did not affect the plasma concentrations of these drugs. Neutropenia has been observed in subjects receiving azithromycin and rifabutin concomitantly. Although neutropenia has been associated with rifabutin, a causal relationship to concomitant azithromycin administration has not been established.
Terfenadine: No interaction has been reported between azithromycin and terfenadine. As with other macrolide antibiotics, azithromycin should be administered with caution in combination with terfenadine.
Theophylline: Azithromycin did not affect the pharmacokinetics of theophylline when azithromycin and theophylline were co-administered.
Triazolam: Coadministration of azithromycin 500 mg on the first day and 250 mg on the second day with 0.125 mg of triazolam had no significant effect on all pharmacokinetic parameters of triazolam.
Trimethoprim/sulfamethoxazole: Coadministration of trimethoprim/sulfamethoxazole 160/800 mg for 7 days and azithromycin 1200 mg on day 7 had no significant effect on the maximum concentrations, total exposure, or urinary excretion of trimethoprim or sulfamethoxazole. Azithromycin concentrations were also unchanged.
Application features
Allergic reactions: As with erythromycin and other macrolide antibiotics, rare serious allergic reactions, including angioedema and anaphylaxis (in isolated cases fatal), and dermatological reactions, including acute generalized exanthematous pustulosis, have been reported. Some of these reactions were recurrent and required longer observation and treatment.
Hepatic impairment. Since the liver is the major route of elimination of azithromycin, caution should be exercised when azithromycin is administered to patients with severe hepatic disease. Cases of fulminant hepatitis, resulting in life-threatening hepatic dysfunction, have been reported with azithromycin. Some patients may have a history of liver disease or may have been taking other hepatotoxic drugs. Liver function tests should be performed if signs and symptoms of hepatic dysfunction develop, such as rapidly progressive asthenia accompanied by jaundice, dark urine, bleeding tendency, or hepatic encephalopathy. Azithromycin should be discontinued if liver dysfunction is detected.
Ergot. In patients taking ergot derivatives, the simultaneous use of some macrolide antibiotics contributes to the rapid development of ergotism. There is no data on the possibility of an interaction between ergot and azithromycin. However, because of the theoretical possibility of ergotism, azithromycin should not be prescribed simultaneously with ergot derivatives.
Superinfections: As with other antibacterial agents, observation for signs of superinfection with nonsusceptible organisms, including fungi, is recommended. Clostridium difficile-associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including azithromycin, and has ranged in severity from mild diarrhea to fatal colitis. Antibacterial therapy alters the normal flora of the colon, resulting in overgrowth of C. difficile. C. difficile produces toxins A and B, which contribute to CDAD. C. difficile strains that overproduce toxins are associated with increased morbidity and mortality, as these infections may be resistant to antimicrobial therapy and may require colectomy. The possibility of CDAD should be considered in all patients with antibiotic-associated diarrhea. Careful medical history is required, as CDAD has been reported to occur within 2 months of taking antibacterial drugs.
Renal impairment: In patients with severe renal dysfunction (glomerular filtration rate < 10 mL/min), a 33% increase in systemic exposure to azithromycin was observed.
Prolongation of cardiac repolarization and QT interval, which increased the risk of cardiac arrhythmias, including torsades de pointes, has been observed with other macrolide antibiotics. A similar effect of azithromycin cannot be completely excluded in patients at increased risk of prolonged cardiac repolarization, therefore, caution should be exercised when prescribing treatment to patients:
with congenital or registered prolongation of the QT interval;
who are currently taking other drugs that prolong the QT interval, such as antiarrhythmic drugs of classes IA (quinidine and procainamide) and III (amiodarone, sotalol, dofetilide), cisapride and terfenadine, neuroleptics such as pimozide, antidepressants such as citalopram, and fluoroquinolones such as moxifloxacin and levofloxacin;
with electrolyte disturbances, especially in the case of hypokalemia and hypomagnesemia;
with clinically relevant bradycardia, cardiac arrhythmia or severe heart failure.
Streptococcal infections.. Penicillin is usually the drug of choice for the treatment of pharyngitis/tonsillitis caused by Streptococcus pyogenes, and is also used for prophylaxis in acute rheumatic fever. Azithromycin is generally effective in the treatment of streptococcal oropharyngeal infections, but there is no evidence to demonstrate the efficacy of azithromycin in the prevention of rheumatic fever. An antimicrobial with antianaerobic activity should be used in combination with azithromycin if anaerobic organisms are suspected to be responsible for the infection.
Other: Safety and effectiveness for the prevention or treatment of Mycobacterium Avium Complex in children have not been established.
Sucrose. 5 ml of suspension contains 2.6 g of sucrose, which may be harmful to teeth and should be taken into account in patients with diabetes mellitus. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Azithromycin powder for oral suspension contains 7.65 mg sodium per dose (1 dose contains 5 ml of suspension). Caution should be exercised when used in patients on a controlled sodium diet.
Use during pregnancy or breastfeeding
Pregnancy. Azithromycin crosses the placenta, but there is no evidence of fetal toxicity in animal studies of the original azithromycin. However, there are no adequate and well-controlled studies in pregnant women. Since animal reproductive studies are not always predictive of human effects, azithromycin should be used during pregnancy only if clearly needed.
Breastfeeding. Azithromycin is excreted in human milk, but there are no adequate and controlled studies of excretion pharmacokinetics. Azithromycin should be used during breastfeeding only in cases where the expected benefit to the mother outweighs the potential risk to the child.
Fertility: Studies in rats have shown a decrease in pregnancy rates following administration of azithromycin. The relevance of these findings to humans is unknown.
Ability to influence reaction speed when driving vehicles or other mechanisms
There is no evidence that azithromycin may impair the ability to drive or operate machinery, but the possibility of developing adverse reactions such as delirium, hallucinations, dizziness, drowsiness, fainting, seizures, and visual disturbances should be considered, which may affect the ability to drive or operate machinery.
Method of administration and doses
To prepare the suspension, the container with the powder should be turned over so that the powder separates from the bottom, then using a dosing syringe, add boiled water at room temperature at the rate of:
| Release form | 200 mg/5 ml, 20 ml | 200 mg/5 ml, 30 ml |
| Amount of water | 14 ml | 20 ml |
After adding water, close the bottle and shake thoroughly until a homogeneous suspension is formed. After that, the date of preparation of the suspension must be written in a special frame on the label. The finished suspension must be stored in the refrigerator. Before each use, the suspension must be shaken well. The suspension should be taken orally once a day, 1 hour before or 2 hours after eating. Immediately after using the suspension, the child should be given a few sips of liquid to wash away and swallow any remaining suspension in the mouth.
If you miss a dose, take it as soon as possible and the next dose should be taken 24 hours later.
Adult use.
For infections of the ENT organs and respiratory tract, skin and soft tissues (except chronic migratory erythema), Ormax is prescribed at a dose of 500 mg (12.5 ml) once a day for 3 days.
For erythema migrans (Lyme disease), Ormax is prescribed once a day for 5 days at a dose of 1000 mg (25 ml) on the 1st day, then 500 mg (12.5 ml) from the 2nd to the 5th day (the total duration of treatment is 5 days).
Application to children.
For infections of the ENT organs and respiratory tract, skin and soft tissues (except chronic migratory erythema), Ormax is prescribed at a dose of 10 mg/kg of body weight once a day for 3 days.
Depending on the child's body weight, the following dosage regimen is recommended:
| Body weight | Daily dose of suspension 200 mg/5 ml |
| 15-24 kg | 5 ml (200 mg) |
| 25-34 kg | 7.5 ml (300 mg) |
| 35-44 kg | 10 ml (400 mg) |
| ³ 45 kg | prescribe doses for adults |
For erythema migrans (Lyme disease), Ormax is prescribed once a day for 5 days at a dose of 20 mg/kg of body weight on the 1st day, then 10 mg/kg of body weight from the 2nd to the 5th day (the total duration of treatment is 5 days).
There is no need to change the dose of the drug for elderly patients. Since elderly patients may be at risk for disturbances in the electrical conduction of the heart, caution is recommended when using azithromycin due to the risk of developing cardiac arrhythmias, including torsades de pointes.
Patients with renal impairment. No dosage adjustment is necessary in patients with mild renal dysfunction (glomerular filtration rate 10-80 mL/min). Azithromycin should be used with caution in patients with severe renal impairment (glomerular filtration rate < 10 mL/min).
Patients with hepatic impairment: Since azithromycin is metabolized in the liver and excreted in the bile, the drug should not be used in patients with severe hepatic impairment. There are no data on the treatment of such patients.
Children. Ormax in the form of a suspension of 200 mg/5 ml should be used in children weighing 15 kg or more. Children weighing less than 15 kg should be used in the form of a suspension of 100 mg/5 ml.
Overdose
Symptoms.
In case of an overdose of azithromycin, severe nausea, vomiting, diarrhea, abdominal pain, and reversible hearing loss are observed.
Treatment.
Administration of activated charcoal and general symptomatic and supportive treatment measures.
Side effects
The following table lists adverse reactions identified in clinical trials and during post-marketing surveillance with all formulations of azithromycin, by system organ class and frequency. Adverse reactions reported during post-marketing surveillance are in italics. The frequency groups are defined using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Adverse reactions possibly or probably related to azithromycin based on data obtained during clinical trials and during post-marketing surveillance
| System and organ class | Adverse reaction | Frequency |
| Infections and infestations | Candidiasis, vaginal infections, pneumonia, fungal infection, bacterial infection, pharyngitis, gastroenteritis, respiratory dysfunction, rhinitis, oral candidiasis | Infrequently |
| Pseudomembranous colitis | Unknown |
| Blood and lymphatic system disorders | Leukopenia, neutropenia, eosinophilia | Infrequently |
| Thrombocytopenia, hemolytic anemia | Unknown |
| On the part of the immune system | Angioedema, hypersensitivity reactions | Infrequently |
| Anaphylactic reaction | Unknown |
| Metabolic | Anorexia | Infrequently |
| From the psyche | Nervousness, insomnia | Infrequently |
| Agitation | Rarely |
| Aggression, anxiety, delirium, hallucinations | Unknown |
| From the nervous system | Headache | Often |
| Dizziness, drowsiness, dysgeusia, paraesthesia | Infrequently |
| Syncope, convulsions, hypoesthesia, psychomotor hyperactivity, anosmia, ageusia, parosmia, myasthenia gravis | Unknown |
| From the organs of vision | Vision impairment | Infrequently |
| From the hearing organs | Hearing disorders, vertigo | Infrequently |
| Hearing impairment, including deafness and/or tinnitus | Unknown |
| From the heart | Palpitation | Infrequently |
| Ventricular flutter/fibrillation (torsade de pointes), arrhythmia including ventricular tachycardia, ECG QT prolongation | Unknown |
| From the vascular side | Tides | Infrequently |
| Arterial hypotension | Unknown |
| From the respiratory system | Dyspnea, epistaxis | Infrequently |
| From the digestive tract | Diarrhea | Very often |
| Vomiting, abdominal pain, nausea | Often |
| Constipation, flatulence, dyspepsia, gastritis, dysphagia, abdominal distension, dry mouth, eructation, mouth ulcers, salivary hypersecretion | Infrequently |
| Pancreatitis, tongue discoloration | Unknown |
| Hepatobiliary system | Liver dysfunction, cholestatic jaundice | Rarely |
| Hepatic failure (rarely fatal), fulminant hepatitis, hepatic necrosis | Unknown |
| Skin and subcutaneous tissue disorders | Rash, pruritus, urticaria, dermatitis, dry skin, hyperhidrosis | Infrequently |
| Photosensitivity, acute generalized exanthematous pustulosis | Rarely |
| Stevens–Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms | Unknown |
| Musculoskeletal system | Osteoarthritis, myalgia, back pain, neck pain | Infrequently |
| Arthralgia | Unknown |
From the urinary system | Dysuria, kidney pain | Infrequently | | Acute renal failure, interstitial nephritis | Unknown |
| Reproductive system and breast disorders | Uterine bleeding, testicular disorders | Infrequently |
| General disorders and local reactions | Oedema, asthenia, malaise, fatigue, facial oedema, chest pain, hyperthermia, pain, peripheral oedema | Infrequently |
| Laboratory indicators | Decreased lymphocyte count, increased eosinophil count, decreased blood bicarbonate, increased basophil count, increased monocyte count, increased neutrophil count | Often |
| Aspartate aminotransferase (AST) increased, alanine aminotransferase (ALT) increased, blood bilirubin increased, blood urea increased, blood creatinine increased, blood potassium changes, alkaline phosphatase increased, chloride increased, glucose increased, platelets increased, haematocrit decreased, bicarbonate increased, sodium abnormal | Infrequently |
| Injury and poisoning | Complications after the procedure | Infrequently |
Information on adverse reactions possibly associated with the prevention and treatment of Mycobacterium Avium Complex is based on data from clinical trials and post-marketing surveillance. These adverse reactions differ in type or frequency from those reported with the immediate-release and long-release formulations.
Adverse Reactions Possibly Associated with the Prevention and Treatment of Mycobacterium Avium Complex
| System and organ class | Adverse reaction | Frequency |
| Metabolic | Anorexia | Often |
| From the nervous system | Dizziness, headache, paresthesia, dysgeusia | Often |
| Hypoesthesia | Infrequently |
| From the organs of vision | Vision impairment | Often |
| From the hearing organs | Deafness | Often |
| Hearing impairment, ringing in the ears | Infrequently |
| From the heart | Palpitation | Infrequently | |
| From the digestive tract | Diarrhea, abdominal pain, nausea, flatulence, gastrointestinal discomfort, frequent loose stools | Very often | |
| Hepatobiliary system | Hepatitis | Infrequently | |
| Skin and subcutaneous tissue disorders | Rash, itching | Often | |
| Stevens–Johnson syndrome, photosensitivity | Infrequently | |
| Musculoskeletal system | Arthralgia | Often |
| General disorders and local reactions | Increased fatigue | Often |
| Asthenia, malaise | Infrequently |
| | | | |
Expiration date
2 years. Shelf life of the finished suspension is no more than 5 days.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
Store at a temperature not exceeding 25 °C. Keep out of the reach of children. Store the prepared suspension for no more than 5 days at a temperature of 2 °C to 8 °C.
Packaging
11.74 g of powder (for 20 ml (800 mg) of suspension) or 17.6 g of powder (for 30 ml (1200 mg) of suspension) in a container sealed with a tamper-evident, child-resistant cap, with a dosing spoon and a dosing syringe in a cardboard box.
Vacation category
According to the recipe.
Producer
Joint Ukrainian-Spanish enterprise "Sperco Ukraine".
