Mycibact Iv 500 mg Tablet

MYCIBACT IV is indicated for the treatment of community acquired pneumonia caused by susceptible organisms, including Legionella pneumophila, in patients who require initial intravenous therapy. The safety and efficacy of MYCIBACT IV for the treatment of infections in children has not been established.

Posology
For more severe infections, the recommended dose of MYCIBACT IV for the treatment of adult patients with community acquired pneumonia requiring hospitalisation due to the indicated organisms is 500 mg as a single daily dose by the intravenous route for at least two days. Intravenous therapy should be followed by azithromycin by the oral route as a single daily dose of 500 mg to complete a 7 to 10 day course of therapy. The timing of the conversion to oral therapy should be done at the discretion of the medical practitioner and in accordance with clinical response.

Special populations
Elderly population
No dosage adjustment is necessary in elderly patients requiring MYCIBACT IV therapy. Elderly patients may be more susceptible to development of Torsade de Pointes dysrhythmia than younger patients (see section 4.4).
Use in children
The safety and effectiveness of MYCIBACT IV for the treatment of infections in children has not been established.

Method of administration
MYCIBACT IV after reconstitution and dilution is for administration by intravenous infusion only. MYCIBACT IV should not be given as a bolus or as an intramuscular injection. The infusate concentration and rate of infusion for azithromycin powder for solution for infusion should be either 1 mg/mL over 3 hours or 2 mg/mL over 1 hour. For instructions for preparation or reconstitution, see section 6.6.

MYCIBACT IV is contraindicated in patients with a known hypersensitivity to azithromycin, erythromycin or any of the macrolide antibiotics, or to any of the excipients of MYCIBACT IV. Because of the theoretical possibility of ergotism, MYCIBACT IV and ergot derivatives should not be co-administered.
Use in hepatic impairment
As the liver is the principal route of excretion of MYCIBACT IV, it should not be prescribed in patients with hepatic disease.

Hypersensitivity
Rare serious allergic reactions including angioedema and anaphylaxis (rarely fatal), dermatologic reactions including acute generalised exanthematous pustulosis (AGEP), Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (rarely fatal) and medicine reaction with eosinophilia and systemic symptoms (DRESS) have been reported. Some of these reactions with azithromycin have resulted in recurrent symptoms and required a longer period of observation and treatment. If an allergic reaction occurs MYCIBACT IV should be discontinued, and appropriate therapy should be instituted. Medical practitioner should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.

Hepatotoxicity
Since the liver is the principal route of elimination for azithromycin, the use of MYCIBACT IV should not be prescribed in patients with hepatic disease (see section 4.3). Cases of fulminant hepatitis potentially leading to life-threatening liver failure have been reported with azithromycin (see section 4.8). Some patients may have had pre-existing hepatic disease or may have been taking other hepatotoxic medicines. In case of signs and symptoms of liver dysfunction, such as rapid developing asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy, liver function tests/ investigations should be performed immediately. MYCIBACT IV administration should be stopped if liver dysfunction has emerged.

Ergot derivatives
In patients receiving ergotamine derivatives, ergotism has been precipitated by co-administration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergot and azithromycin. However, because of the theoretical possibility of ergotism, MYCIBACT IV and ergot derivatives should not be co-administered (see section 4.3).

Prolongation of the QT interval
Prolonged cardiac repolarisation and QT interval, imparting a risk of developing cardiac dysrhythmia and torsades de pointes, have been seen in treatment with other macrolides. A similar effect with azithromycin cannot be completely ruled out in patients at increased risk for prolonged cardiac repolarisation (see Section 4.8); therefore, caution is required when treating patients:
u2022 With congenital or documented QT prolongation
u2022 Currently receiving treatment with other active medicines known to prolong QT interval such as antidysrhythmics of classes Ia and III, cisapride and terfenadine
u2022 With electrolyte disturbance, particularly in case of hypokalaemia and hypomagnesemia
u2022 With clinically relevant bradycardia, cardiac dysrhythmia or severe cardiac insufficiency.

Superinfection
Observation for signs of superinfection with non-susceptible organisms including fungi is recommended.

Clostridium difficile associated diarrhoea
Clostridium difficile associated diarrhoea (Pseudomembranous colitis - CDAD) has been reported with azithromycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibiotics alters the normal flora of the colon allowing an overgrowth of C. difficile. Strains of C. difficile producing hypertoxin A and B contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. Therefore, CDAD must be considered in patients who present with diarrhoea during or subsequent to the administration of any antibiotics. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial. Discontinuation of therapy with azithromycin and the administration of specific treatment for C. difficile should be considered.

Streptococcal infections
Penicillin is usually the first choice for treatment of pharyngitis/tonsillitis due to Streptococcus pyogenes and also for prophylaxis of acute rheumatic fever. Azithromycin is in general effective against streptococcus in the oropharynx, but no data are available that demonstrate the efficacy of azithromycin in preventing acute rheumatic fever.

Renal impairment
In patients with severe renal impairment (GFR < 10 mL /min) a 33 % increase in systemic exposure to azithromycin was observed (see Section 5.2). Acute renal failure and interstitial nephritis have been reported (see section 4.8).

Myasthenia gravis
Exacerbations of the symptoms of myasthenia gravis and new onset of myasthenia syndrome have been reported in patients receiving azithromycin therapy. Safety and efficacy of azithromycin intravenous infusion for treatment of infections in children have not been established.

General
Safety and efficacy for prevention or treatment of MAC in children have not been established. Azithromycin (azithromycin as powder for solution for infusion) should be reconstituted and diluted according to the instructions and should be administered as an intravenous infusion over at least 60 minutes. It should not be administered as an intravenous bolus or an intramuscular injection (see sections 4.2 and 6.6). This medicine contains 114 mg (4,96 mmol) sodium per vial, equivalent to approximately 5,7 % of the WHO recommended maximum daily intake of 2 g sodium for an adult. Paediatric population The efficacy and safety of azithromycin as powder for solution for infusion for the treatment of infections in children and adolescents has not been established.

Cetirizine
In healthy volunteers, co-administration of a 5-day regimen of azithromycin with cetirizine 20 mg at steady state resulted in no pharmacokinetic interaction and no significant changes in the QT interval.
Didanosine (Dideoxyinosine)
Co-administration of 1200 mg/day azithromycin with 400 mg/day didanosine in six HIV positive subjects did not appear to affect the steady-state pharmacokinetics of didanosine as compared to placebo.
Digoxin and colchicine
Concomitant administration of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates such as digoxin and colchicine, has been reported to result in increased serum levels of the P-glycoprotein substrate. Therefore, if azithromycin and P-glycoprotein substrates such as digoxin are administered concomitantly, the possibility of elevated serum digoxin concentrations should be considered. Clinical monitoring, and possibly serum digoxin levels, during treatment with azithromycin and after its discontinuation are necessary.
Ergot derivatives (Ergotamine)
Due to the theoretical possibility of ergotism, the concurrent use of azithromycin with ergot derivatives is not recommended (See Section 4.4).
Zidovudine
Single 1000 mg doses and multiple 1200 mg or 600 mg doses of azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, administration of azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of this finding is unclear, but it may be of benefit to patients.
Azithromycin does not interact significantly with the hepatic cytochrome P450 system. It is not believed to undergo the pharmacokinetic drug interactions as seen with erythromycin and other macrolides. Hepatic cytochrome P450 induction or inactivation via cytochrome-metabolite complex does not occur with azithromycin.
Atorvastatin
Co-administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter the plasma concentrations of atorvastatin (based on a HMG CoA-reductase inhibition assay)
Carbamazepine
In a pharmacokinetic interaction study in healthy volunteers, no significant effect was observed on the 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, on the pharmacokinetics of azithromycin, no alteration of azithromycin pharmacokinetics was seen.
Warfarin
In a pharmacokinetic interaction study, azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin administered to healthy volunteers. There have been reports received in the post-marketing period of potentiated anticoagulation subsequent to co-administration of azithromycin and warfarin. Although a causal relationship has not been established, consideration should be given to the frequency of monitoring prothrombin time when azithromycin is used in patients receiving warfarin.
Ciclosporin
In a pharmacokinetic study with healthy volunteers that were administered a 500 mg/day oral dose of azithromycin for 3 days and were then administered a single 10 mg/kg oral dose of ciclosporin, the resulting ciclosporin C max and AUC were found to be significantly elevated (by 24 % and 21 % respectively), however no significant changes were seen in AUC 0-5. Consequently, caution should be exercised before considering concurrent administration of these medicines. If co-administration of these medicine is necessary, ciclosporin levels should be monitored and the dose adjusted accordingly.
Efavirenz
Co-administration of a single dose of 600 mg azithromycin and 400 mg efavirenz daily for 7 days did not result in any clinically significant pharmacokinetic interactions.
Fluconazole
Co-administration of a single dose of 1200 mg azithromycin did not alter the pharmacokinetics of a single dose of 800 mg fluconazole. Total exposure and half-life of azithromycin were unchanged by the coadministration of fluconazole, however, a clinically insignificant decrease in C max (18 %) of azithromycin was observed.
Indinavir
Co-administration of a single dose of 1200 mg azithromycin had no statistically significant effect on the pharmacokinetics of indinavir administered as 800 mg three times daily for 5 days.
Methylprednisolone
In a pharmacokinetic interaction study in healthy volunteers, azithromycin had no significant effect on the pharmacokinetics of methylprednisolone.
Nelfinavir
Co-administration of azithromycin (1200 mg) and nelfinavir at steady state (750 mg three times daily) resulted in increased azithromycin concentrations. No clinically significant adverse effects were observed, and no dose adjustment was required.
Midazolam
In healthy volunteers, co-administration of azithromycin 500 mg/day for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single 15 mg dose of midazolam.
Rifabutin
Co-administration of azithromycin and rifabutin did not affect the serum concentrations of either medicine. Neutropenia was observed in subjects receiving concomitant treatment of azithromycin and rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship to combination with azithromycin has not been established (see Section 4.8).
Sildenafil
In normal healthy male volunteers, there was no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC and C max, of sildenafil or its major circulating metabolite.
Terfenadine
Pharmacokinetic studies have reported no evidence of an interaction between azithromycin and terfenadine. There have been rare cases reported where the possibility of such an interaction could not be entirely excluded; however, there was no specific evidence that such an interaction had occurred.
Theophylline
There is no evidence of a clinically significant pharmacokinetic interaction when azithromycin and theophylline are co-administered to healthy volunteers.
Triazolam
In 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 had no significant effect on any of the pharmacokinetic variables for triazolam compared to triazolam and placebo.
Trimethoprim/sulfamethoxazole
Co-administration of trimethoprim/sulfamethoxazole DS (160 mg/800 mg) for 7 days with azithromycin 1200 mg on Day 7 had no significant effect on peak concentrations, total exposure or urinary excretion of either trimethoprim or sulfamethoxazole. Azithromycin serum concentrations were similar to those seen in other studies.

Pregnancy
There are no adequate data from the use of azithromycin in pregnant women. In reproduction toxicity studies in animals, azithromycin was shown to pass the placenta, but no teratogenic effects were observed. The safety of azithromycin has not been confirmed with regard to the use of the azithromycin active substance during pregnancy. Therefore, Azithromycin, MYCIBACT IV should only be used during pregnancy if definitely indicated.
Breastfeeding
Azithromycin passes into breast milk. Because it is not known whether azithromycin may have adverse effects on the breast-fed infant, nursing should be discontinued during treatment with MYCIBACT IV. Among other things diarrhoea, fungus infection of the mucous membrane as well as sensitisation is possible in the nursed infant. It is recommended to discard the milk during treatment and up until 2 days after discontinuation of treatment. Nursing may be resumed thereafter.
Fertility
Animal data do not suggest an effect of the treatment of azithromycin on male and female fertility. Human data are lacking.

MYCIBACT IV may cause side effects such as dizziness and visual impairment (see section 4.8), which should be taken into consideration on the ability to drive or operate machinery.

System Organ Class
Frequency
Frequent
Less Frequent
Not known
Infections and infestations
Candidiasis, oral candidiasis, vaginal infection
Pseudomembranous colitis
Blood and lymphatic system disorders
Leukopenia, neutropenia
Thrombocytopenia, haemolytic anaemia
Immune system disorders
Angioedema, hypersensitivity
Anaphylactic reaction (See Section 4.4)
Metabolism and nutrition disorders
Anorexia
Psychiatric disorders
Nervousness, Agitation
Aggression, anxiety
Nervous system disorders
Dizziness, headache, paraesthesia, dysgeusia
Hypoaesthesia, somnolence, insomnia
Syncope, convulsion, psychomotor hyperactivity, anosmia, ageusia, parosmia, myasthenia gravis (See Section 4.4)
Eye disorders
Visual impairment
Abnormal vision
Ear and labyrinth disorders
Deafness
Impaired hearing, tinnitus, vertigo
Cardiac disorders
Palpitations.
Torsades de pointes (See Section 4.4), arrhythmia (See Section 4.4) including ventricular tachycardia
Vascular disorders
Hypotension
Gastrointestinal disorders
Diarrhoea, abdominal pain, nausea, flatulence, Vomiting, dyspepsia
Gastritis, constipation
Pancreatitis, tongue discolouration
Hepatobiliary disorders
Abnormal liver function
Hepatic function abnormal
Hepatic failure (See Section 4.4)**, hepatitis, fulminant, hepatic necrosis, jaundice cholestatic.
Skin and subcutaneous tissue disorders
Pruritis, rash, oedema
Stevens-Johnson syndrome (SJS), photosensitivity reaction, urticaria, Acute Generalised Exanthematous Pustulosis (AGEP), Drug reaction with Toxic epidermal necrolysis (TEN), erythema multiforme eosinophilia and systemic symptoms (DRESS)
Musculoskeletal and connective tissue disorders
Arthralgia
Renal and urinary disorders
Acute renal failure, interstitial nephritis,
General disorders and administration site conditions
Pain and inflammation on the local injection site*
Investigations
Decreased lymphocyte count, increased eosinophil count, decreased blood bicarbonate
Increased Aspartate aminotransferase, increased alanine aminotransferase, increased blood bilirubin, increased blood urea, increased blood creatinine, abnormal blood potassium
Electrocardiogram QT prolonged (See Section 4.4)
* have been reported with the intravenous administration of azithromycin.
** which has rarely resulted in death

Adverse events experienced in higher than recommended doses were similar to those seen at normal doses. The typical symptoms of an overdose with macrolide antibiotics include loss of hearing, severe nausea, vomiting and diarrhoea. In the event of overdose, general symptomatic treatment and supportive measures are indicated as required.