Samitrogen 500mg 9 Caps, Azithromycin
THERAPEUTIC INDICATIONS:SAMITROGEN containing azithromycin, which is an azalide antibiotic, a new group of antibiotics originating from the eritromcina. Azithromycin is indicated in infections caused by susceptible organisms, in the lower respiratory tract infections, including bronchitis and pneumonia, and infections of skin and soft tissue infections, otitis media and upper respiratory tract infections, including sinusitis, and pharyngitis. (Penicillin is usually the drug of choice in the treatment of Streptococcus pyogenes pharyngitis and in the prophylaxis of rheumatic fever.
Azithromycin is generally effective in the eradication of streptococci from the oropharynx, but currently there are no data establishing the efficacy of azithromycin in subsequent prevention of rheumatic fever).
Sexually transmitted infections, azithromycin is indicated in men as in women in the treatment of uncomplicated genital infections due to Chlamydia trachomatis. Is also indicated for the treatment of chancroid due to Haemophilus ducreyi.
Is also indicated in the treatment of genital infections caused uncomplicated Neisseria gonorrhoeae than MDR. Concomitant infection should be excluded by Treponema pallidum.
Azithromycin has been shown in vitro activity against a broad spectrum of bacteria including:
Gram-positive aerobic bacteria: Staphylococcus aureus, Streptococcus pyogenes (group A beta hemolytic streptococcus), Streptococcus pneumoniae, alpha hemolytic streptococci (viridans group), other streptococci and Corynebacterium diphtheriae.
Azithromycin has demonstrated cross-resistance to erythromycin resistant Gram-positive strains that, including: Streptococcus faecalis (Enterococcus) and most of methicillin-resistant strains of staphylococci.
Gram-negative aerobic bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Acinetobacter species, Yersinia species, Legionella pneumophilia, Bordetella pertussis, Bordetella parapertussis, Shigella species, Pasteurella species, Vibrio cholerae and parahaemolyticus, Plesiomonas shigelloides. The activity against Escherichia coli, Salmonella enteritidis, Salmonella typhi, Enterobacter species, Aeromonas hydrophila and Klebsiella species is variable and should be tested for susceptibility.
Usually strains resistant Proteus species, Serratia species, Morganella species and Pseudomonas aeruginosa.
Anaerobic bacteria: Bacteroides fragilis Bacteroides species, Clostridium perfringens, and Peptococcus species Peptoestreptococcus, Fusobacterium necrophorum and Propionibacterium acnes.
Pathogens transmitted diseases sexual ZERTALIN is active against Chlamydia trachomatis and also shows good activity against Treponema pallidum, Neisseria gonorrhoeae and Haemophilus ducreyi.
Other agencies: Borrelia burgdorferi (causative agent of Lyme disease), Chlamydia pneumoniae, Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma urealyticum, Campylobacter and Listeria monocytogenes.
Opportunistic pathogens associated with HIV infections: Mycobacterium avium-intracellulare complex, Pneumocystis carinii and Toxoplasma gondii.
CLINICAL PHARMACOLOGY IN HUMANS: Azithromycin is the first member of a class of antibiotics designated chemically as azalides. Chemically is caused by the insertion of a nitrogen atom in the lactone ring of erythromycin A.
The mechanism of action of azithromycin is by inhibiting protein synthesis by the bacteria, through binding to the 50S ribosomal subunit, preventing the translocation of peptides.
After oral administration in humans, azithromycin is widely distributed throughout the body. Its bioavailability is about 37%. The administration of azithromycin capsules after a meal rich decreases bioavailability by at least 50%. The time required to reach peak plasma levels are two to three hours. The terminal half-life of plasma elimination half-life closely reflects the tissue depletion of two to four days.
In elderly volunteers (aged 65), after a five-day regimen were observed values â€‹â€‹of the area under the curve (AUC) slightly higher than those observed in young volunteers (under 40) but these do not were considered clinically significant, and therefore not recommended a dose adjustment.
In patients with moderate renal impairment (creatinine clearance below 40 ml / min), no evidence of significant changes in the pharmacokinetics of azithromycin in serum, compared with patients with normal renal function. There are no results of pharmacokinetic studies concerning the use of azithromycin in patients with more severe renal insufficiency.
In patients with mild (class A) to moderate (Class B) there is no evidence of significant changes in the pharmacokinetics of azithromycin in serum, compared with patients with normal liver function. It seems that in these patients increases the urinary recovery of azithromycin, probably to compensate for the decrease in hepatic clearance.
Pharmacokinetic studies have demonstrated levels much higher azithromycin in tissues than in plasma (up to 50 times the maximum concentration observed in the plasma), indicating that the drug binds strongly to tissue. After a 500 mg dose, concentrations in target tissues such as lung, tonsil and prostate exceed the MIC90 for likely pathogens in the tissues.
After intravenous administration of antibiotics, about 12% is excreted in the urine in three days as unchanged drug, most within 24 hours. Have been found very high concentrations of unchanged drug in human bile, along with ten metabolites formed by N and O demethylation, by hydroxylation of the aglycone ring desoxamina and breaking of the conjugate and cladinose.
Comparison of the levels in tissues by microbiological methods and high pressure liquid chromatography, suggests that metabolites play no role in the microbiological activity of azithromycin.
In animal studies, there have been high concentrations of azithromycin in phagocytes. In experimental models, it has been observed that there is increased release of azithromycin for the active phagocytosis when compared with unstimulated phagocytes. In animal models, this results in the release of high concentrations of azithromycin at the site of infection.
CONTRAINDICATIONS: The use of ZERTALIN is contraindicated in patients with a history of allergic reactions to azithromycin or any macrolide antibiotic.
PRECAUTIONS: As with erythromycin and other macrolides have been reported rarely cases of severe allergic reactions, including angioedema and anaphylaxis (rarely fatal).
Some of these reactions with azithromycin have resulted in recurrent symptoms, requiring longer periods of observation and treatment. No information is available concerning the use of azithromycin in patients with creatinine clearance below 40 ml / min, for the above, caution should be exercised before prescribing azithromycin in these patients.
Because the liver is the major route of elimination of azithromycin should be used with caution in patients with significant liver disease. In patients who are given ergot derivatives, ergotism has been precipitated when administered simultaneously with some macrolide antibiotics. No information is available concerning the possibility of interactions between azithromycin and ergot. However, due to the theoretical possibility of ergotism, should not be administered simultaneously azithromycin and ergot derivatives. As with any antibiotic should be monitored for signs of superinfection with nonsusceptible organisms including fungi.
Effects on ability to drive motor vehicles or use machines: No evidence that azithromycin may affect ability to drive motor vehicles and operate machinery.
RESTRICTIONS ON USE PRECAUTIONS DURING PREGNANCY OR BREASTFEEDING: Animal reproduction studies have shown that azithromycin crosses the placenta, but revealed no evidence of harm to the fetus. There are no data on secretion in breast milk. No security has been set for use during pregnancy and lactation.
Azithromycin should only be administered to pregnant or breast-feeding when there are no suitable alternatives available.
ZERTALIN is usually well tolerated with a low frequency of side effects, which include:
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea (rarely resulting in dehydration) and loose stools, dyspepsia, abdominal discomfort (pain, cramps), constipation and flatulence, pseudomembranous colitis and rarely discoloration of the tongue.
Special Senses: It is reported hearing impairment with macrolide antibiotics.
There have been reports of hearing impairment, including hearing loss, deafness and / or tinnitus in many patients receiving azithromycin. Many of these have been associated with prolonged use of high doses in research studies.
In these cases, when the tracking information was available, most events were reversible. There have been rare reports of altered sense of taste.
Genitourinary: interstitial nephritis have been reported and acute renal failure.
Liver, bile duct: Abnormalities in liver function including hepatitis and cholestatic jaundice and rare cases of necrosis and liver failure, which have rarely resulted in death. However, not been established a causal relationship.
Psychiatric: aggressive reactions, nervousness, agitation and anxiety.
Central and Peripheral Nervous System: Dizziness, vertigo, seizures (seen with other macrolides), headache, somnolence, paresthesia, and hyperactivity.
Leukocytes: In clinical studies there have been occasional transient episodes of mild neutropenia, although no causal relationship has been established with azithromycin.
Skin and appendages: We have had allergic reactions including itching, rash, photosensitivity, edema, urticaria and angioedema. Have occurred rarely serious skin reactions including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.
Cardiovascular: palpitations and arrhythmias have been reported, including ventricular tachycardia (as with other macrolides), but their causal relationship with azithromycin has not been established.
General: asthenia have been reported, although no causal relationship has been established; also been reported moniliasis and anaphylaxis (rarely fatal), but has not shown a causal relationship.
DRUG INTERACTIONS AND OTHER GENDER:
Antacids: In a pharmacokinetic study investigating the effects of simultaneous administration of antacids with azithromycin, there was no effect on the bioavailability as such, although the peak serum concentration was reduced by up to 30%. Patients receiving both azithromycin and antacids should not take these drugs simultaneously.
Carbamazepine: In a pharmacokinetic interaction study in healthy volunteers, there was no significant effect on plasma levels of carbamazepine or its active metabolite in patients receiving concomitant azithromycin.
Cimetidine: In a pharmacokinetic study investigating the effects of a single dose of cimetidine, given 2 hours before azithromycin, there was no alteration in the pharmacokinetics of the latter.
Cyclosporine: In the absence of conclusive data from clinical or pharmacokinetic studies on the potential interaction between azithromycin and cyclosporin, caution should be exercised before the administration of these drugs. If coadministration is necessary, should be monitored cyclosporine levels and adjust the dose according to need.
Digoxin has been reported that some macrolide antibiotics alter the microbial metabolism of digoxin in the gut of certain patients. It should be borne in mind the possibility that digoxin reach high concentrations in patients receiving azithromycin (an azalide antibiotic related macrolides), and digoxin.
Ergot: Due to the theoretical possibility of ergotism, no concomitant use of azithromycin with ergot derivatives.
Methylprednisolone: â€‹â€‹In a pharmacokinetic study conducted in healthy volunteers, azithromycin had no significant effect on the pharmacokinetics of methylprednisolone.
Theophylline: No evidence of pharmacokinetic interaction when administered together azithromycin and theophylline in healthy volunteers.
Terfenadine: Pharmacokinetic studies have reported no evidence of interaction between azithromycin and terfenadine. There have been rare cases reported where the possibility of such interaction may not be totally excluded, but no specific evidence that this interaction has occurred.
Oral anticoagulants of the coumarin type: In a pharmacokinetic interaction study, azithromycin did not alter the anticoagulant effect of a single dose of 15 mg of warfarin when administered to healthy volunteers. In post-marketing studies has been reports of potentiation of anticoagulation as a result of concomitant administration of azithromycin and oral anticoagulants. Although not shown a causal relationship must be taken into consideration the frequency of monitoring of prothrombin time.
Zidovudine: The administration of single doses of 1.000 mg and repeated doses of 1.200 or 600 mg of azithromycin did not affect plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, administration of azithromycin increased the concentration of phosphorylated zidovudine, clinically active metabolite in peripheral blood mononuclear cells.
It is unclear clinical significance of this finding, but may be beneficial for patients.
Didanosine: Co-administration of daily doses of 1,200 mg of azithromycin with didanosine in six patients did not appear to affect the pharmacokinetics of didanosine, compared with placebo.
Rifabutin: Concomitant administration of azithromycin and rifabutin does not alter serum concentrations of either drug. Although neutropenia has been observed with the use of rifabutin has not established a causal relationship to combination with azithromycin.
Laboratory Test Alterations: To date there are no known interferences in laboratory tests induced by azithromycin.
PRECAUTIONS AND RELATION TO EFFECTS OF Carcinogenesis, Mutagenesis, Impairment of Fertility: No studies have been done long term studies in animals to evaluate the potential carcinogenicity.
Azithromycin has shown no mutagenic potential in standard laboratory tests, as evidence of lymphoma in mice, human lymphocyte clastogenic test and test clastogenic in mouse bone marrow.
DOSAGE AND ADMINISTRATION: Oral.
ZERTALIN should be administered as single daily dose. The dosing period relative to the infection is mentioned below. ZERTALIN can be taken with food.
Adults: For treatment of sexually transmitted disease caused by Chlamydia trachomatis, Haemophilus ducreyi or susceptible strains of Neisseria gonorrhoeae, ZERTALIN dose is 1,000 mg as single dose. For all other indications, the total dose of 1.500 mg ZERTALIN is administered at 500 mg daily for three days.
Elderly: It uses the same dose as in adults.
Patients with renal impairment: In patients with mild renal impairment (creatinine clearance below 40 ml / min) can be used the same dose in patients with normal renal function. No information is available regarding the use of ZERTALIN in patients with more severe renal impairment.
Patients with hepatic impairment may be given the same dosage to patients with mild to moderate hepatic impairment than patients with normal hepatic function.
Children: Except for the treatment of strep throat, the total dose of azithromycin in children is 30 mg / kg in three days, administered as single daily dose of 10 mg / kg / day for three days.
ZERTALIN tablets should only be administered to children weighing over 45 kg.
For strep throat, has been shown to be effective in ZERTALIN single dose of 10 mg / kg or 20 mg / kg for three days, but is not recommended to administer higher doses of 500 mg daily. In clinical studies in which we compared two dose schedules, similar clinical efficacy was observed, but was evident with a more bacteriological eradication dose of 20 mg / kg. However, penicillin is the drug of choice for the treatment of pharyngitis caused by Streptococcus pyogenes, including prophylaxis of rheumatic fever.
Overdosage: MANIFESTATIONS AND MANAGEMENT (antidotes): Adverse events reported with administration of higher than recommended doses were similar to those seen at normal doses. In case of overdose, according to the needs, symptomatic treatment is recommended and general supportive measures.