What is Zitromax for ?
Zitromax is indicated for the treatment of infections caused by bacteria sensitive to azithromycin ; (nose and pharynx, larynx and trachea), including sinusitis (infection of the sinuses), pharyngitis (inflammation of the pharynx), or tonsillitis (inflammation of the tonsils); skin and soft tissue infections (muscles, tendons, fat); in acute otitis media (middle ear infection) and uncomplicated sexually transmitted diseases in the genitalia of men and women caused by the bacteria Chlamydia trachomatis and Neisseria gonorrhoeae.It is also indicated in the treatment of cancer (skin lesion) due to Haemophilus ducreyi ( bacterial species). Infections that occur along with syphilis (sexually transmitted disease) should be excluded.
How does Zitromax work?
Zitromax is an antibiotic that works by preventing azithromycin-sensitive bacteria from producing proteins, which are the basis of their growth and reproduction. Its peak action is after 2 to 3 hours of oral administration of Zitromax.
Contraindication of Zitromax
Zithromax is contraindicated if you have a history of hypersensitivity (allergic reactions) to azithromycin, erythromycin , any macrolide antibiotic (class of antibiotics which belongs to azithromycin), ketolide (another class of antibiotics), or any component of the formula.
How to use Zitromax
Zitromax can be given with or without food.
Zitromax should be given as a single daily dose.
Use in adults:
For the treatment of sexually transmitted diseases caused by Chlamydia trachomatis , Haemophilus ducreyior Neisseria gonorrhoeae (types of bacteria) sensitive, the dose is 1000mg in a single oral dose.
For all other indications in which the oral formulation is used, a total dose of 1500mg should be administered in daily doses of 500mg for 3 days. As an alternative, the same total dose can be administered for 5 days, in a single dose of 500mg on the 1st day and 250mg, once a day, from the 2nd to the 5th day.
Use in Children:
The maximum total recommended dose for any treatment in children is 1500mg.
In general, the total dose in children is 30mg / kg. In the treatment of pediatric streptococcal pharyngitis (infection of the pharynx caused by Streptococcus ) should be administered under different dosing schedules. The total dose of 30mg / kg should be administered in a single daily dose of 10mg / kg for 3 days, or the same total dose may be administered for 5 days in a single dose of 10mg / kg on the 1st day and 5mg / kg, Once a day, from the 2nd to the 5th day. An alternative for the treatment of children with acute otitis media is a single dose of 30mg / kg.
For the treatment of streptococcal pharyngitis (pharyngeal infection caused by Streptococcus ) in children, the efficacy of Zitromax given as a single daily dose of 10mg / kg or 20mg / kg for 3 days was demonstrated.
Do not exceed the daily dose of 500mg. However, penicillin is generally the drug of choice for the treatment of pharyngitis caused by Streptococcus pyogenes (bacteria type), including prophylaxis of rheumatic fever (heart valve abnormalities).
Zitromax coated tablets should be administered only in children weighing more than 45 kg.
Use in Elderly Patients:
The same dose used in adult patients is used in elderly patients.
Use in Patients with Renal Insufficiency (decreased kidney function):
No dose adjustment is required in patients with mild to moderate renal impairment. In case of severe renal insufficiency, Zitromax should be administered with caution.
Use in Patients with Hepatic Insufficiency (decreased liver function):
The same doses given to patients with normal hepatic function may be used in patients with mild to moderate hepatic impairment. However, patients with severe hepatic impairment should use Zitromax with caution.
Posology for patients initiating treatment with Zitromax IV – Replacement of intravenous (oral) treatment with oral treatment
For treatment of community-acquired pneumonia :
The recommended dose of Zitromax IV, powder for solution for infusion, for the treatment of adult patients with community acquired pneumonia (lung infection acquired outside the hospital setting) caused by susceptible organisms is 500 mg once daily intravenously , for at least 2 days. Intravenous treatment may be followed by oral Zitromax in a single daily dose of 500 mg until completion of a therapeutic cycle (total days of intravenous and oral use of the medication) for 7 to 10 days.
For treatment of pelvic inflammatory disease:
The recommended dose of Zitromax IV, powder for infusion solution, for the treatment of adult patients with pelvic inflammatory disease (internal genital infection) caused by susceptible organisms is 500 mg once daily intravenously for 1 or 2 days. Intravenous treatment may be followed by oral Zitromax in a single daily dose of 250mg until complete a 7-day course of therapy. Replacement of intravenous treatment with oral treatment should be established at the discretion of the physician according to clinical response.
Follow the advice of your doctor, always respecting the times, doses and duration of treatment.
Do not stop the treatment without your doctor’s knowledge.
What should I do if I forget to use Zitromax?
If you forget to take Zitromax at your doctor’s time, take it as soon as you remember.
However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule, usually following the dosing schedule recommended by your doctor.
In this case, do not take the medicine twice as much to make up for forgotten doses. Forgetfulness of the dose may compromise the efficacy of the treatment.
If you have any questions, seek advice from the pharmacist or your doctor, or dental surgeon.
Although rare, with the use of Zitromax you may develop severe allergic reactions such as angioedema(swelling of the deeper parts of the skin or mucosa, usually of allergic origin) and anaphylaxis (severe allergic reaction), rarely fatal, and dermatological reactions including Pustulosis (Severe allergic reaction with formation of vesicles containing pus inside), Stevens Johnson Syndrome (severe allergic reaction with blisters on the skin and mucous membranes), toxic epidermal necrolysis (severe peeling of the upper layer of the skin) rarely fatal and Adverse Drug Reactions with Eosinophilia and Systemic Symptoms (DRESS – Drug Reaction with Eosinophilia and Systemic Symptoms) – (Adverse drug reactions with generalized response).
If any allergic reaction occurs, the use of the drug should be discontinued and appropriate treatment given.
If you have a serious liver problem, tell your doctor, as Zitromax should be used with caution. Hepatic function (liver function), hepatitis (inflammation of the liver), cholestatic jaundice (yellowing of the skin and mucous membranes due to accumulation of biliary pigment due to obstruction), hepatic necrosis (liver cell death), and insufficiency hepatic failure (liver failure), some of which resulted in death. Zitromax should be discontinued immediately if signs and symptoms of hepatitis occur.
Attention: This medicinal product contains Sugar, therefore, should be used with caution in patients with Diabetes .
Adverse Reactions of Zitromax
Zitromax is well tolerated, presenting low incidence of side effects.
Passive episodes of mild reduction in neutrophil counts (blood cells), thrombocytopenia (decreased blood clotting cells: platelets), moniliasis (infection caused by the fungus of the genus Candida), vaginitis (inflammation in the vagina), anaphylaxis ( severe allergic reaction), anorexia (loss of appetite), aggressive reaction, nervousness, agitation, anxiety , dizziness, convulsions, migraine ( headache ), hyperactivity, hypoesthesia (decreased overall sensitivity), paresthesia (abnormal sensation , such as burning, tinglingand itching, perceived on the skin and for no apparent reason), drowsiness, faintingRare cases of taste disorder / smell and / or loss, vertigo, hearing disorders (abnormal functioning of hearing), including hearing loss, deafness and / or tinnitus ( ringing in the ears ), palpitations and arrhythmias (changes in heart rhythm ), including ventricular tachycardia (heart rate), rare reports of QT prolongation and Torsades de Pointes (changes in heart rhythm), hypotension (low blood pressure).
Vomiting / diarrhea (rarely resulting in dehydration), dyspepsia (pain and burning in the stomach and esophagus), constipation (constipation), pseudomembranous colitis (infection of the intestine by C. difficile species), pancreatitis(inflammation in the pancreas), loose stools, abdominal discomfort (pain / colic), flatulence, rare reports of tongue discoloration, liver dysfunction, hepatitis (inflammation of the liver), cholestatic jaundice (yellowing of the skin and mucous membranes due to accumulation of pigments liver failure and liver failure which rarely resulted in death, allergic reactions including pruritus (itching), rash (redness of the skin), photosensitivity (exaggerated skin sensitivity) to light), edema (swelling), urticaria ( allergysevere erythema multiforme (red patches, blisters and ulcerations throughout the body), acute generalized exanthematous pustulosis (PEGA) (severe severe allergic reaction with formation of vesicles containing pus within the body), angioedema, rare cases of severe dermatological reactions including erythema multiforme ), Stevens-Johnson syndrome (severe allergic reaction with blistering of the skin and mucous membranes), toxic epidermal necrolysis (severe peeling of the upper layer of the skin), adverse reactions to drugs with eosinophilia and systemic symptoms (DRESS – Drug Reaction with Eosinophilia and Systemic Symptoms ), arthralgia (joint pain), interstitial nephritis (type of inflammation in the kidneys), acute renal dysfunction, asthenia (weakness), tiredness, malaise.
Tell your doctor, dental surgeon or pharmacist the appearance of undesirable reactions to the use of the medicine.
Also inform the company through its customer service.
Special Population of Zitromax
Do not use Zitromax during breast-feeding without medical advice.
There is no evidence that Zitromax may affect your ability to drive or operate machines.
This medicine should not be used by pregnant women without medical advice or by the dentist.
Composition of Zitromax
Each Zitromax coated tablet contains:
Azithromycin dihydrate equivalent to 500mg azithromycin base.
Excipients: pregelatinized starch, anhydrous dibasic calcium phosphate, croscarmellose sodium, magnesium stearate, sodium lauryl sulfate and white opadry (lactose, hypromellose , titanium dioxide and triacetin).
Overdosage of Zitromax
Seek medical advice in case of overdose with Zitromax, whose symptoms are similar to those observed with the recommended doses.
If large quantities of this medication are used, seek medical help promptly and take the package or package leaflet if possible. Call 0800 722 6001 if you need more guidance.
Zitromax Drug Interaction
In a pharmacokinetic study investigating the effect of simultaneous administration of antacid and azithromycin, no effect on overall bioavailability was observed, although peak plasma concentrations were reduced by about 24%.
In healthy volunteers, coadministration of azithromycin on a 5-day regimen with 20 mg cetirizine at steady state did not result in pharmacokinetic interaction or significant changes in the QT interval.
Coadministration of azithromycin 1200 mg / day with didanosine 400 mg / day in six HIV-positive individuals did not appear to have affected the didanosine steady-state pharmacokinetics when it was compared to placebo.
Concomitant administration of macrolide antibiotics including azithromycin with P-glycoprotein substrates, such as digoxin, have been reported to result in an increase in serum levels of the P-glycoprotein substrate. Therefore, if azithromycin and P-gp substrates, such as digoxin , are given concomitantly, the possibility of elevated serum digoxin concentrations should be considered. Clinical monitoring of serum digoxin levels during and after discontinuation of azithromycin is required.
There is a theoretical possibility of interaction between azithromycin and ergot derivatives.
Single doses of 1000 mg and multiple doses of 1200 mg or 600 mg azithromycin had a small effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite.
However, administration of azithromycin increased concentrations of the clinically active metabolite, phosphorylated zidovudine , in peripheral blood mononuclear cells. The clinical significance of this result has not yet been elucidated; however, may benefit patients.
Azithromycin does not interact significantly with the hepatic cytochrome P450 system. It is believed that azithromycin does not participate in the pharmacokinetic drug interactions as observed with erythromycin and other macrolides. Induction or inactivation of hepatic cytochrome P450 via cytochrome-metabolite complex does not occur with azithromycin.
Pharmacokinetic studies have been conducted between azithromycin and the following drugs known to be significantly involved in cytochrome P450 mediated metabolism.
Co-administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter plasma concentrations of atorvastatin (based on HMG-CoA reductase inhibition tests). However, in postmarketing experience cases of rhabdomyolysis have been reported in patients receiving azithromycin with statins.
In a pharmacokinetic interaction study in healthy volunteers, no significant effects were observed on plasma levels of carbamazepine or its active metabolites in patients receiving azithromycin concomitantly.
A pharmacokinetic study was conducted to evaluate the single dose effects of cimetidine administered two hours prior to azithromycin, in this study no alterations in the pharmacokinetics of azithromycin were observed.
Coumarin-type oral anticoagulants
In a pharmacokinetic interaction study, azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin when administered to healthy volunteers.
In the post-marketing period, reports of potentiation of anticoagulation, following coadministration of azithromycin and coumarin-type oral anticoagulants, were received.
Although a causal relationship has not been established, consideration should be given to the frequency with which prothrombin time monitoring is performed when azithromycin is used in patients receiving coumarin-type oral anticoagulants.
In a pharmacokinetic study in healthy volunteers those given oral doses of 500 mg / day azithromycin for 3 days and then single oral dose of 10 mg / kg cyclosporine, C max resulting from cyclosporine and AUC0-5 were considered significantly high.
Therefore, caution should be exercised before considering the concomitant use of these drugs. If co-administration is required, cyclosporine levels should be monitored and the dose adjusted accordingly.
Coadministration of a single dose of 600 mg of azithromycin and 400 mg daily of efavirenz for 7 days did not result in clinically significant pharmacokinetic interactions.
Coadministration of a single 1200 mg dose of azithromycin did not change the pharmacokinetics of a single 800 mg dose of fluconazole . The total exposure and half-life of azithromycin were not altered by coadministration of fluconazole; however, a clinically insignificant decrease in Cmax (18%) of azithromycin was observed .
Coadministration of a single dose of 1200 mg azithromycin did not produce clinically significant effect on the pharmacokinetics of indinavir when given at 800 mg doses 3 times daily for 5 days.
In a pharmacokinetic interaction study in healthy volunteers, azithromycin did not produce a significant effect on the pharmacokinetics of methylprednisolone .
In healthy volunteers, coadministration of azithromycin 500 mg / day for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single dose of 15 mg midazolam .
Coadministration of azithromycin (1200 mg) and steady state nelfinavir (750 mg, 3 times daily) resulted in increased azithromycin concentration. No clinically significant adverse events have been observed and no dose adjustment is required.
Coadministration of azithromycin with rifabutin did not affect serum drug concentrations. Neutropenia has been observed in subjects treated with azithromycin and rifabutin concomitantly.
Although neutropenia has been related to the use of rifabutin, a causal relationship has not been established for the use of the combination of rifabutin and azithromycin.
In normal and healthy male volunteers, there was no evidence of effect of azithromycin (500 mg daily for 3 days) on AUC and C max of sildenafil or its major circulating metabolite.
Pharmacokinetic studies have shown no evidence of interaction between azithromycin and terfenadine. Rare cases have been reported in which the possibility of this interaction could not be totally excluded; however, there is no consistent evidence that such an interaction has occurred.
There is no evidence of clinically significant pharmacokinetic interaction when azithromycin and theophylline are coadministered in healthy volunteers.
In 14 healthy volunteers co-administration of azithromycin 500 mg on day 1 and 250 mg on day 2 with 0.125 mg triazolam on day 2 did not produce a significant effect on any pharmacokinetic variable of triazolam compared to triazolam and placebo.
Trimethoprim / sulfamethoxazole
Coadministration of trimethoprim and sulfamethoxazole (160 mg / 800 mg) for 7 days with 1200 mg of azithromycin administered on the 7 th day of treatment did not produce a significant effect on peak concentrations, total exposure or urinary excretion of both trimethoprim and sulfamethoxazole . Serum azithromycin concentrations were similar to those observed in other studies.
Action of Zitromax Substance
From the perspective of evaluating pediatric clinical trials, data from Days 11-14 are provided for clinical guidance.
Evaluations of days 24-32 were considered the outcome of the primary cure test.
Acute otitis media
Efficacy using Azithromycin Dihydrate (active substance) for 5 days (10mg / kg on Day 1 followed by 5mg / kg on Days 2-5)
Azithromycin Dihydrate (active substance) (10 mg / kg on Day 1 followed by 5 mg / kg on Days 2-5) was compared in a double-blind, acute otitis media study conducted in the United States. to amoxicillin / potassium clavulanate (4: 1).
Among the 553 patients who were assessed for clinical efficacy, the clinical success rate at Day 11 was 88% for Azithromycin Dihydrate (active substance) and 88% for the control agent. Among the 521 patients evaluated on the Day 30 visit, the success rate was 73% for Azithromycin Dihydrate (active substance) and 71% for the control agent.
In a non-comparative clinical and microbiological study conducted in the United States, where significant rates of beta-lactamase (35%) production were found, 131 patients were evaluated for clinical efficacy. At the 11 day visit, the combined clinical success rate (ie, cure and improvement) was 84% for Azithromycin Dihydrate (active substance). For the 122 patients who were evaluated on day 30 of the visit, the clinical success rate was 70% for Azithromycin Dihydrate (active substance).
Microbiological determinations were made at the pre-treatment visit. Microbiology was not reevaluated at subsequent visits.
The following clinical success rates were obtained from the evaluated group:
|Azithromycin Dihydrate (active substance)||Azithromycin Dihydrate (active substance)|
|S. pneumoniae||61/74 (82%)||40/56 (71%)|
|H. influenzae||43/54 (80%)||30/47 (64%)|
|M. catarrhalis||28/35 (80%)||19/26 (73%)|
|S. pyogenes||11/11 (100%)||7/7 (100%)|
|Total||177/217 (82%)||97/137 (73%)|
In another comparative, controlled, biologic, otitis media clinical study of Azithromycin Dihydrate (active substance) (10 mg / kg on day 1, followed by 5 mg / kg on days 2-5) compared to amoxicillin / potassium clavulanate (4: 1). This study used two of the same researchers as Protocol 02 (above), and these two researchers enrolled 90% of patients in Protocol 03.
Thus, Protocol 3 was not considered an independent study. Significant results of production of beta-lactamase organisms (20%) were found. Ninety-two patients were evaluated for clinical and microbiological efficacy. The combined clinical success rate (ie, cure and improvement) of patients with pathogenic baseline at day 11 visit was 88% for Azithromycin Dihydrate (active substance) versus 100% for control.
At the 30th visit, the clinical success rate was 82% for Azithromycin Dihydrate (active substance) versus 80% for the control group.
Microbiological determinations were made at the pre-treatment visit. Microbiology was not reevaluated at subsequent visits.
On visit days 11 and 30, the following clinical success rates were obtained from the assessed group:
Efficacy using Azithromycin Dihydrate (active substance) for 3 days (10 mg / kg / day)
In a double-blind, controlled, randomized study of acute otitis media in children aged 6 months to 12 years, Azithromycin Dihydrate (active substance) (10 mg / kg per day for 3 days) was compared to amoxicillin / clavulanate potassium (7: 1) every 12 hours for 10 days. Each child received medication and placebo for comparison.
Among the 366 patients evaluated, the clinical efficacy rate (eg healing and improvement) after 12 days of treatment was 83% for Azithromycin Dihydrate (active substance) and 88% for the control agent. Among the 362 patients evaluated after 24-28 days of treatment, the clinical success rate was 74% for Azithromycin Dihydrate (active substance) and 69% for the control agent.
Efficacy using Azithromycin Dihydrate (active substance) 30 mg / kg given as a single dose
In a double-blind, controlled, randomized study, it was performed at nine clinical centers. Pediatric patients 6 months to 12 years of age received 1: 1 Azithromycin Dihydrate (active substance) (fixed at 30 mg / kg as a single dose on Day 1) or amoxicillin / potassium clavulanate (7: 1) divided every 12 hours, for 10 days.
Each child received medication and placebo for comparison.
The clinical response (cure, improvement, failure) was evaluated at the end of therapy (Day 12 – 16) and cure test (Day 28-32).
Safety was assessed throughout the course of the study for all subjects. For the 321 subjects who were assessed at the end of treatment, the clinical success rate (cure and improvement) was 87% for Azithromycin Dihydrate (active substance) and 88% for control. For the 305 subjects who were evaluated in the healing test, the clinical success rate was 75% for both Azithromycin Dihydrate (active substance) and control.
In a non-comparative microbiological clinical study, 248 patients from 6 months of age to 12 months with documented acute otitis media were dosed with a single oral dose of Azithromycin Dihydrate (active substance) (30 mg / kg on day 1 ).
For the 240 patients who were evaluated for intention-to-treat (MITT), the clinical success rate (that is, cure and improvement) at day 10 was 89% and for the 242 patients evaluated between days 24 and 28 , the clinical success rate was 85%.
|Presumed bacteriological eradication|
|10th day||Days 24-28|
|S. pneumoniae||70/76 (92%)||67/76 (88%)|
|H. influenzae||30/42 (71%)||28/44 (64%)|
|M. catarrhalis||10/10 (100%)||10/10 (100%)|
|Total||110/128 (86%)||105/130 (81%)|
Pharyngitis / Tonsilitis
Azithromycin Dihydrate (active substance) (12 mg / kg, once daily for 5 days) was compared to penicillin V (250 mg, 3 times daily) in three controlled double-blind studies conducted in the United States. day for 10 days) in the treatment of Group A-associated pharyngitis beta-hemolytic streptococci (GABHS – group A beta-hemolytic streptococci or S. pyogenes). Azithromycin Dihydrate (active substance) was clinically and clinically superior to penicillin in the clinical and microbiological parameters on Day 14 and Day 30, with the following clinical success (eg cure and improvement) and bacteriological efficacy rates (for combination of patients evaluated documented in the GABHS).
Three American studies on pharyngitis Azithromycin Dihydrate (active substance) vs. penicillin V
|Azithromycin Dihydrate (active substance)||323/340 (95%)||255/330 (77%)|
|Penicillin V||242/332 (73%)||206/325 (63%)|
|Clinical success (healing with improvement)|
|Azithromycin Dihydrate (active substance)||336/343 (98%)||310/330 (94%)|
|Penicillin V||284/338 (84%)||241/325 (74%)|
Approximately 1% of S. pyogenes Azithromycin Dihydrate (active substance) -susceptible isolates were resistant to Azithromycin Dihydrate (active substance) in the following treatment.
Acute Bacterial Exacerbation of Chronic Obstructive Pulmonary Disease (COPD)
In a double-blind, randomized, controlled study of acute bacterial exacerbation of chronic bronchitis, Azithromycin Dihydrate (active substance) (500 mg once daily for 3 days) was compared to clarithromycin(500 mg twice day for 10 days). The main endpoint of this study was the clinical cure rate of Day 21-24. Among the 304 patients analyzed in the Modified Intent to Treat Analysis at Day 21-24 visits, the 3-day clinical cure rate of Azithromycin Dihydrate (active substance) was 85% (125 / 147) compared to 82% (129/157) for 10 days of clarithromycin.
The following data were the clinical cure rates in the visits of Days 21-24 of the patients evaluated bacteriologically by pathogen:
|Pathogen||Azithromycin Dihydrate (active substance) (3 days)||clarithromycin (10 days)|
|S. pneumoniae||29/32 (91%)||21/27 (78%)|
|H. influenzae||12/14 (86%)||14/16 (88%)|
|M. catarrhalis||11/12 (92%)||12/15 (80%)|
Acute bacterial sinusitis
Azithromycin Dihydrate (active substance) (500 mg once daily for 3 days) was compared to amoxicillin + clavulanate (500/125 mg three times daily for 10 days) in a randomized double-blind clinical study of acute bacterial sinusitis. days). Evaluations of clinical responses were performed on days 10 and 28. The first endpoint of this study was prospectively defined in the clinical cure rate on day 28. For the 594 patients analyzed in the modified intent of treatment at day 28 visit, the clinical rate of cure for the 3 days of Azithromycin Dihydrate (active substance) was 71.5% (213/298) compared to 71.5% (206/288) with a confidence of 97.5% of the range of -8, 4 to 8.3, for 10 days of amoxicillin / clavulanate.
In an open-label non-comparative clinical study requiring baseline transantral sinusitis punctures, the following results were the clinical success rates on visits on day 7 and on day 28 for intention to treat patients administering 500 mg Azithromycin Dihydrate (active substance) a once daily for three days for the following pathogens.
Clinical success rate of Azithromycin Dihydrate (active substance) (500 mg per day for 3 days):
|Pathogen||Day 7||Day 28|
|S. pneumoniae||23/26 (88%)||21/25 (84%)|
|H. influenzae||28/32 (87%)||24/32 (75%)|
|M. catarrhalis||14/15 (93%)||13/15 (87%)|
Treatment of Pelvic Inflammatory Disease
The results of an open-label study indicate that three therapeutic regimens (Azithromycin Dihydrate (active substance) versus Azithromycin Dihydrate (active substance) / metronidazole versus doxycycline, metronidazole , cefoxitin and probenecid) were comparable in terms of efficacy and safety for treatment of women with acute pelvic inflammatory disease. Data from this study show an overall clinical success rate (cure + improvement) greater than or equal to 97% in all treatment groups at the end of treatment, with 96% or more of the eradicated pathogens. At follow-up, an equivalent number or greater than 90% of the pathogens were eradicated.
Pharmacotherapeutic group: macrolides, ATC code J01FA
Mode of action
Azithromycin Dihydrate (active substance) is the first antibiotic of the macrolide subclass, known as azalides, and is chemically different from erythromycin. It is obtained by insertion of a nitrogen atom into the lactonic ring of erythromycin A. The chemical name of Azithromycin Dihydrate (active substance) is 9-deoxy-9a-aza-9a-methyl-9a-homoerythromycin A. The molecular weight is 749.0. Azithromycin Dihydrate (active substance) binds to the 23S rRNA of the 50S ribosomal subunit. In this way, it blocks the protein synthesis by inhibiting the transpeptidation / translocation step of the protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit.
QTc prolongation was studied in a randomized, placebo-controlled, parallel trial in 116 healthy subjects who received either chloroquine (1000 mg) alone or in combination with Azithromycin Dihydrate (active substance) (500 mg, 1000 mg and 1500 mg) mg once daily). Coadministration of Azithromycin Dihydrate (active substance) increased the QTc interval in a dose and concentration dependent manner.
Compared to chloroquine alone, the maximal mean (95% upper confidence limit) of the QTcF increase were 5 (10) ms, 7 (12) and 9 (14) ms with coadministration of Azithromycin Dihydrate (active substance) 500 mg, 1000 mg and 1500 mg, respectively.
Mechanism of resistance
The two mechanisms of macrolide resistance most frequently encountered, including Azithromycin Dihydrate (active substance), are target modification (most often by methylation of 23S rRNA) and active efflux. The occurrence of these mechanisms of resistance varies from species to species and within a species the frequency of resistance varies according to geographic location.
The most important ribosomal modification that determines reduced macrolide binding is posttranscriptional (N6) -dimethylation of adenine at nucleotide A2058 (Escherichia coli numbering system) of 23S rRNA by the methylases encoded by erm (erythromycin ribosome methylase) genes. Frequently, ribosomal modifications determine cross-resistance (MLSB phenotype) for other classes of antibiotics, whose ribosomal binding sites overlap with that of macrolides: lincosamides (including clindamycin), and streptogramins B (which include, for example, quinupristin component of quinupristin / dalfopristin). Several erm genes are present in different bacterial species, in particular, streptococci and staphylococci.
Efflux pumps occur in several species, including Gram-negative bacteria, such as Haemophilus influenzae (where they can determine the intrinsically higher minimum inhibitory concentration [MICs]) and staphylococci. In streptococci and enterococci, an efflux pump recognizing 14- and 15-macrolide members (including, respectively, erythromycin and Azithromycin Dihydrate (active substance)) is encoded by mef (A) genes.
Methodology for the determination of in vitro susceptibility of bacteria to Azithromycin Dihydrate (active substance)
Susceptibility testing should be performed using standardized laboratory methods, such as those described by the Clinical and Laboratory Standards Institute (CLSI). These include dilution methods (MIC determination) and disk susceptibility methods. Both the CLSI and the European Committee for Antimicrobial Susceptibility Tests (EUCAST) provide interpretative criteria for these methods.
Based on a number of studies, it is recommended that the in vitro activity of Azithromycin Dihydrate (active substance) be tested in ambient air to ensure a physiological pH of the growth medium. Elevated CO2 stresses, often used for streptococci and anaerobes, and occasionally for other species, result in a reduction in the pH of the medium. This has a greater adverse effect on the apparent potency of Azithromycin Dihydrate (active substance) than on that of other macrolides.
CLSI susceptibility limit values based on broth microdilution or agar dilution tests with incubation in ambient air are given in the table below.
CLSI Interpretive Criteria for Dilution Susceptibility:
a Includes Groups A, B, C, G.
EUCAST = European Committee for Antimicrobial Susceptibility Testing; MIC = minimal inhibitory concentration.
Source: EUCAST website.
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly in the treatment of severe infections. If necessary the specialist should be advised when the local prevalence of resistance is so great that the agent’s usefulness in at least some types of infections is questionable.
Azithromycin Dihydrate (active substance) demonstrates cross-resistance with erythromycin-resistant Gram-positive isolates. As discussed previously, some ribosomal modifications determine cross-resistance with other classes of antibiotics whose ribosomal binding sites overlap with those of macrolides: lincosamides (including clindamycin), and streptogramins B (which include, for example, the quinupristin component of quinupristin / dalfopristine). Macrolide susceptibility decreased over time, particularly for Streptococcus pneumoniae and Staphylococcus aureus , and was also observed in viridans streptococci and Streptococcus agalactiae .
Organisms that are commonly sensitive to Azithromycin Dihydrate (active substance) include:
|Gram-positive aerobic and facultative bacteria (erythromycin-sensitive isolates)||Macrolide-resistant isolates are found relatively frequently among aerobic and facultative Gram-positive bacteria, in particular between methicillin – resistant S. aureus (MRSA) and penicillin-resistant S. pneumoniae (PRSP).|
|Gram-negative aerobic and facultative bacteria||Bordetella pertussis , Campylobacter jejuni , Haemophilus ducreyi *, Haemophilus influenzae *, Haemophilus parainfluenzae *, Legionella pneumophila , Moraxella catarrhalis * and Neisseria gonorrhoeae *. The Pseudomonas spp. and most Enterobacteriaceae are inherently resistant to Azithromycin Dihydrate (active substance), although Azithromycin Dihydrate (active substance) has been used to treat infections with Salmonella enterica|
|Anaerobic||Clostridium perfringens , Peptostreptococcus spp. and Prevotella bivia|
|Other bacterial species||Borrelia burgdorferi , Chlamydia trachomatis, Chlamydophila pneumoniae *, Mycoplasma pneumoniae *, Treponema pallidum and Ureaplasma urealyticum|
|Opportunistic pathogens associated with HIV infection||MAC *, and the eukaryotic microorganisms Pneumocystis jirovecii and Toxoplasma gondii|
* The effectiveness of Azithromycin Dihydrate (active substance) against the indicated species has been demonstrated in clinical studies.
After oral administration to humans, Azithromycin Dihydrate (active substance) is widely distributed throughout the body; the bioavailability is approximately 37%. Azithromycin Dihydrate (active substance) given as capsules after a substantial meal has a bioavailability reduced by at least 50%. The time required to reach peak plasma concentrations is 2 to 3 hours.
In animal studies, high concentrations of Azithromycin Dihydrate (active substance) were observed in phagocytes. In experimental models, higher concentrations of Azithromycin Dihydrate (active substance) are released during active phagocytosis than by non-stimulated phagocytes. In animal models, this results in high concentrations of Azithromycin Dihydrate (active substance) being released to the sites of infection.
Pharmacokinetic studies in humans have demonstrated markedly higher levels of Azithromycin Dihydrate (active substance) in tissues than in plasma (up to 50 times the maximum concentration observed in plasma), indicating that the drug binds strongly to tissues. Concentration in the target tissues as well as the lungs, tonsils and prostate exceeds MIC 90 for most pathogens after a single 500 mg dose.
After oral administration of daily doses of 600 mg Azithromycin Dihydrate (active substance) at C max was 0.33 μg / mL and 0.55 μg / mL on days 1 and 22, respectively. The mean peak concentration observed in leukocytes at the largest dissemination site of Mycobacterium avium-intracellulare was 252 μg / mL (± 49%) and above 146 μg / mL (± 33%) at 24 hours at steady state .
The terminal elimination half-life reflects well the tissue depletion half-life of 2 to 4 days.
Approximately 12% of the intravenously administered dose is excreted in the urine within 3 days as the unchanged drug, most of it within the first 24 hours. Biliary excretion is the main route of elimination of Azithromycin Dihydrate (active substance) as unchanged drug after oral administration. Very high concentrations of unchanged azithromycin dihydrate (active substance) were found in human bile together with 10 metabolites formed by N- and O-demethylation, by hydroxylation of the desosamine and aglycone rings and by cleavage of the cladinose conjugate. Comparison of chromatographic (HPLC) and microbiological analyzes in tissues suggests that metabolites do not participate in the microbiological activity of Azithromycin Dihydrate (active substance).
In elderly volunteers (> 65 years), a slight increase in the values of the area under the curve (AUC) was observed after a 5 day regimen when compared to young volunteers (<40 years), but this increase was not considered clinically significant, in which case dose adjustment is not recommended.
The pharmacokinetics of Azithromycin Dihydrate (active substance) in subjects with mild to moderate renal impairment (glomerular filtration rate 10-80 mL / min) were not affected when given as a single dose of 1 g Azithromycin Dihydrate (active substance ) of immediate release. Statistically significant differences in AUC0-120 (8.8 μg.h / mL vs. 11.7 μg.h / mL), Cmax (1.0 μg / mL vs. 1.6 μg / mL) and renal clearance (2.3 mL / min / kg vs 0.2 mL / min / kg) were observed in the group with severe renal impairment (glomerular filtration rate <10 mL / min) and the group with normal renal function.
In patients with mild to moderate hepatic impairment (class A) (class B), there is no evidence of a marked change in serum pharmacokinetics of azithromycin dihydrate (active substance) when compared to patients with normal hepatic function. In these patients the clearance of Azithromycin Dihydrate (active substance) in urine appears to be increased, possibly to compensate for reduced hepatic clearance .
Preclinical Safety Data
Phospholipidosis (intracellular phospholipid accumulation) was observed in several tissues (eg, eyes, dorsal root ganglia, liver, bladder, kidneys, spleen and / or pancreas) of rats, mice and dogs after multiple doses of Azithromycin Dihydrate ( active substance). Phospholipidosis was observed to a similar degree in the tissues of neonatal rats and puppies. The effect has been demonstrated to be reversible upon discontinuation of Azithromycin Dihydrate (active substance). The significance of the discovery for animals and for humans is not known.
Zitromax Storage Care
Zitromax should be stored at room temperature (15-30 ° C), protected from light and moisture.
Tablets coated white to off-white, grooved, ovals modified.
Batch number and dates of manufacture and validity: see packaging.
Do not use medicine with the expiry date.
Store it in its original packaging.
Before using, note the appearance of the medicine. If it is in the expiration date and you notice any change in the appearance, consult your pharmacist to see if you can use it.
All medicines should be kept out of the reach of children.