Trozocina - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf Life and Storage

Active ingredients: Azithromycin

Trozocin 200 mg / 5 ml powder for oral suspension

Why is Trozocin used? What is it for?

PHARMACOTHERAPEUTIC CATEGORY

Antibacterials for systemic use; macrolides.

THERAPEUTIC INDICATIONS

Treatment of infections caused by azithromycin-sensitive germs.

  • upper respiratory tract infections (including otitis media, sinusitis, tonsillitis and pharyngitis);
  • lower respiratory tract infections (including bronchitis and pneumonia);
  • odontostomatological infections;
  • skin and soft tissue infections.

Contraindications When Trozocin should not be used

Hypersensitivity to the active substance or to any of the excipients (see "Composition").

Hypersensitivity to erythromycin or to any of the macrolide or ketolide antibiotics

Severe hepatic insufficiency.

Azithromycin is generally contraindicated in pregnancy, lactation and very early childhood (see "Special warnings").

Precautions for use What you need to know before taking Trozocin

In patients with severe renal impairment (GFR <10 ml / min.), A 33% increase in systemic exposure to azithromycin was observed.

No dosage adjustment is required in patients with mild to moderate renal impairment (GFR 10 - 80 mL / min) while caution should be exercised in those with severe impairment (GFR <10 mL / min).

Since the liver is the major route of elimination, caution should be exercised under medical supervision in the use of azithromycin in patients with hepatic disease or hepatic insufficiency.

The same dosage as in patients with normal hepatic function can be used in patients with mild to moderate hepatic impairment.

Cases of fulminant hepatitis leading to life-threatening conditions of liver failure have been reported with azithromycin (see "Side Effects"). Some patients may have suffered from pre-existing liver disease or may have been treated with other hepatotoxic therapies. In case of signs and symptoms of hepatic dysfunction such as rapid development of asthenia with jaundice, dark urine, bleeding tendency or hepatic encephalopathy, liver function tests should be performed immediately. Should hepatic dysfunction occur, azithromycin administration should be discontinued.

In patients treated with ergotamine derivatives, co-administration of macrolide antibiotics has precipitated ergotism crises. There is currently no data available on the theoretical possibility of an ergotism crisis; therefore, azithromycin and ergotamine should not be administered simultaneously.

As for any other antibiotic preparation, special observation is recommended for the possible occurrence of superinfections with non-sensitive microorganisms including fungi.

Interactions Which drugs or foods can modify the effect of Trozocin

Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.

Antacids

In a pharmacokinetic study of the effects of concomitant administration of antacids and azithromycin, no effect on the bioavailability of azithromycin was observed, although an approximately 25% reduction in maximum serum concentrations was observed. Therefore, patients in therapy with azithromycin and antacids should not take the two drugs at the same time.

Cetirizine

In healthy volunteers, co-administration of a 5-day regimen of azithromycin and 20 mg cetirizine at steady state revealed no pharmacokinetic interactions or significant alterations in the QT interval.

Didanosine (Dideoxinosine)

Co-administration of daily doses of azithromycin 1200 mg / day and didanosine 400 mg / day in 6 HIV positive patients was observed to have no effect on the steady state pharmacokinetics of didanosine compared to placebo.

Digoxin (P-gp substrates)

Concomitant administration of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates such as digoxin has been reported to increase serum levels of the P-glycoprotein substrate. Thus, if azithromycin and P-gp substrates such as digoxin are administered simultaneously, the possibility of elevated serum substrate concentrations should be considered.

Ergotamine

Due to the possible onset of ergotism, the concomitant use of azithromycin and ergotamine derivatives is not recommended (see "Precautions for use").

Zidovudine

Administration of single 1000 mg doses and multiple 1200 mg or 600 mg doses of azithromycin did not substantially change the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. concentrations of phosphorylated zidovudine, its clinically active metabolite, in peripheral mononuclear cells. The clinical significance of this finding is unclear, but may nevertheless be of benefit to the patient.

Azithromycin does not interact significantly with the hepatic cytochrome P450 system. It is not expected to be involved in pharmacokinetic interactions as found with erythromycin and other macrolides. In fact, with azithromycin, there is no induction or inactivation of hepatic cytochrome P450 through the complex of its metabolites. Pharmacokinetic studies have been conducted between azithromycin and the following drugs, for which significant cytochrome-mediated metabolic activity is known P450.

Atorvastatin

Concomitant administration of atorvastatin (10 mg / day) and azithromycin (500 mg / day) did not cause alterations in HMG CoA reductase activity. However, from post-marketing experience cases of rhabdomyolysis have been reported in patients treated with azithromycin and statins.

Carbamazepine

In an interaction study in healthy volunteers, no significant effect on plasma levels of carbamazepine or its active metabolite was observed in patients taking concomitant azithromycin.

Cimetidine

In a pharmacokinetic study conducted to evaluate the effects of a single dose of cimetidine administered 2 hours after azithromycin, there was no evidence of alterations in the pharmacokinetics of azithromycin.

Cyclosporine

Significant increases in Cmax and AUC0-5 of cyclosporine. Therefore, the possible simultaneous administration of the two drugs requires caution. If the co-administration of the two drugs is strictly necessary, the levels of cyclosporine should be carefully monitored and the dosage of the latter should be modified accordingly.

Efavirenz

Co-administration of a single daily dose of azithromycin (600 mg) and efavirenz (400 mg) for 7 days produced no clinically significant pharmacokinetic interactions. No dosage adjustment is required when azithromycin is administered in combination with efavirenz.

Fluconazole

Coadministration of a single dose of azithromycin (1200 mg) did not alter the pharmacokinetics of a single dose of fluconazole (800 mg). Total exposure time and half-life of azithromycin were not affected by co-administration with fluconazole, while a clinically insignificant decrease in Cmax (18%) was observed. No dosage adjustment is required when azithromycin is administered in combination with fluconazole

Indinavir

Coadministration of a single dose of azithromycin (1200 mg) did not show a statistically significant effect on the pharmacokinetics of indinavir administered three times daily for 5 days in doses of 800 mg. No dosage adjustment is required when azithromycin it is given in combination with indinavir.

Methylprednisolone

A pharmacokinetic study conducted in healthy volunteers showed that azithromycin does not significantly affect the pharmacokinetics of methylprednisolone.

Midazolam

In healthy volunteers, concomitant administration of azithromycin 500 mg / day for 3 days did not result in clinically significant changes in the pharmacokinetics and pharmacodynamics of a single 15 mg midazolam dose.

Nelfinavir

Concomitant administration of azithromycin (1200 mg) and nelfinavir at steady state (750 mg three times daily) resulted in increased azithromycin concentrations. Although no clinically significant adverse reactions were observed and no dosage adjustment is required, Careful monitoring of azithromycin side effects is advised.

Rifabutin

Concomitant administration of azithromycin and rifabutin does not change the serum concentrations of the two drugs.

Cases of neutropenia have been observed in some patients taking the two drugs at the same time; although rifabutin is known to cause neutropenia, it has not been possible to establish a causal relationship between the above episodes of neutropenia and the combination rifabutinazithromycin (see "Undesirable effects").

Sildenafil

In healthy male volunteers, there was no evidence of any effect of azithromycin (500 mg daily for 3 days) on the AUC and Cmax of sildenafil or its major circulating metabolites.

Theophylline

Co-administration of azithromycin and theophylline to healthy volunteers did not show a clinically significant interaction between the two drugs.

Terfenadine

Pharmacokinetic studies revealed no interactions between azithromycin and terfenadine. In patients who took the two drugs at the same time there have been rare cases of interaction for which it has not been possible to establish or exclude a certain correlation. Triazolam In 14 healthy volunteers, co-administration of azithromycin 500 mg on Day 1 and 250 mg on Day 2 and triazolam 0.125 mg on Day 2 had no significant effect on the pharmacokinetic variables of triazolam compared to triazolam and placebo.

Trimethoprim / Sulfamethoxazole

After concomitant administration of trimethoprim / sulfamethoxazole (160 mg / 800 mg) and azithromycin (1200 mg) for 7 days, there was no significant effect on peak concentrations, exposure time or urinary excretion on day 7. of both trimethoprim and sulfamethoxazole. Serum concentrations of azithromycin are similar to those seen in other studies. No dosage adjustment is required when azithromycin is co-administered with trimethoprim / sulfamethoxazole.

Coumarin-type oral anticoagulants

In a pharmacokinetic study in healthy volunteers, azithromycin was found not to alter the anticoagulant effect of a single 15 mg dose of warfarin. In the post-marketing phase, cases of potentiation of anticoagulant action have been reported following the concomitant administration of azithromycin and coumarin-type oral anticoagulants. Although a causal relationship has not been established, it is advisable to re-evaluate the frequency with which to monitor the time to prothrombin when administering azithromycin to patients receiving coumarin-type anticoagulants.

As for the concomitant use of azithromycin and other drugs that act on coagulation, since specific interaction studies have not been conducted, careful monitoring of those patients taking the above drugs in combination is recommended.

Warnings It is important to know that:

As with erythromycin and other macrolides, severe allergic reactions, including angioedema and anaphylaxis (rarely fatal), have been observed rarely, and may recur, even in the absence of new drug intake, after symptomatic treatment has been discontinued.

These reactions require drug discontinuation and symptomatic treatment followed by a prolonged observation period.

Cases of Clostridium difficile associated diarrhea (CDAD) have been reported with the use of nearly all antibiotics, including azithromycin, ranging in severity from mild diarrhea to fatal colitis. Treatment with antibiotics alters the normal flora of the colon and leads to an overgrowth of C. difficult .

The C. difficult produces toxins A and B which contribute to the development of diarrhea. The strains of C. difficult that produce excess toxins cause increased morbidity and mortality rates, as these infections are typically refractory to antibacterial therapy and often require a colectomy. The possibility of associated diarrhea should be considered C. difficult in all patients who present with diarrhea following antibiotic treatment. A careful medical history is also required as cases of C. difficile associated diarrhea have been reported even more than two months after antibiotic administration.

Prolongation of cardiac repolarization and QT interval has been found in treatment with other macrolides, with the risk of developing cardiac arrhythmia and torsades de pointes. In patients with a higher risk of prolongation of cardiac repolarization, this cannot be completely ruled out. a similar effect with azithromycin (see "Undesirable effects"). Therefore, since the situations listed below may carry an increased risk of ventricular arrhythmias (including torsades de pointes) which can cause cardiac arrest, azithromycin should be used with caution in patients with pro-arrhythmic conditions (in particularly women and elderly patients) such as:

  • congenital or documented QT prolongation.
  • Concomitant treatment with other substances known to induce QT prolongation, such as class IA (quinidine and procainamide) and class III (dofetilide, amiodarone and sotalol) antiarrhythmics, cisapride and terfenadine; antipsychotic agents such as pimozide; antidepressants such as citalopram; and fluoroquinolones such as moxifloxacin and levofloxacin.
  • Electrolyte disturbances, particularly in cases of hypokalaemia and hypomagnesaemia.
  • Clinically significant bradycardia, arrhythmia or severe heart failure.

There have been reports of exacerbation of the symptoms of myasthenia gravis and "new" onset of myasthenic syndrome in patients treated with azithromycin (see "Undesirable effects").

Pregnancy and breastfeeding

There are no adequate data on the use of azithromycin in pregnancy. Reproductive toxicology studies in animals showed that azithromycin crosses the placenta but no teratogenic effects were observed. The safety of use of azithromycin in pregnancy has not been confirmed; therefore, azithromycin should only be used in pregnancy if the benefits outweigh the risks.

Secretion of azithromycin into breast milk has been reported, but there are no adequate and well-controlled clinical studies which have characterized the pharmacokinetics of excretion of azithromycin into breast milk in lactating women. Since many drugs are excreted in breast milk, TROZOCINA (azithromycin) should therefore be used in women during lactation and in very early childhood only when the potential benefits clearly outweigh the risks and under medical supervision.

Fertility

In fertility studies in rats, a reduced pregnancy rate was observed following administration of azithromycin. The relevance of this data in man is not known.

The suspension contains 3.9 g of sucrose for every 5 ml: this should be taken into account if the powder for oral suspension is administered to patients with genetic or acquired dysfunctions of carbohydrate metabolism. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase isomaltase insufficiency should not take this medicine.

Effects on ability to drive and use machines

No effect of azithromycin on the ability to drive and use machines has been reported.

Dosage and method of use How to use Trozocin: Dosage

10 mg / kg / day for 3 consecutive days.

For children weighing 45 kg or more, the same dosage as for adults (500 mg / day for three consecutive days) can be used.

The same dosage schedule indicated for adults can be applied to the elderly patient. Since elderly patients may have pro-arrhythmic conditions, particular caution is recommended due to the risk of developing cardiac arrhythmia and torsades de pointes (see "Special Warnings").

For the treatment of acute otitis media in children, the recommended dosage is 10 mg / kg / day for 3 consecutive days or 30 mg / kg in a single administration.

For the treatment of streptococcal pharyngitis in children, both the dose of 10 mg / kg and that of 20 mg / kg, both in a single administration and for three consecutive days, have been shown to be effective; however, the daily dose of 500 mg. In clinical trials with the two dosages, overlapping efficacy was observed, but greater bacterial eradication was seen at 20 mg / kg / day. However, in the treatment of Streptococcus pyogenes pharyngitis and in the prophylaxis of rheumatic fever, penicillin is the drug of choice.

The maximum total recommended dose for any pediatric therapy is 1500 mg.

The drug should always be administered in a single daily dose.

Trozocin (azithromycin) powder for oral suspension can be taken either on an empty stomach or after meals. Food intake before administering the product can mitigate any undesirable gastrointestinal effects caused by azithromycin.

PREPARATION OF THE SUSPENSION

Shake the bottle containing the powder before adding water. Add water to the bottle using the special dispenser attached to the package. Shake well. Always shake the suspension before use.

ATTENTION:

  • For the treatment of acute otitis media in children, the dosage of 30 mg / kg can also be carried out in a single administration, filling the graduated dispenser as many times as necessary until the prescribed dose is reached.
  • For the treatment of streptococcal pharyngitis in children, the dosage below can be doubled, taking care not to exceed 500 mg per day.
  1. The graduated dispenser is calibrated in mg and mL of drug and kg of the child's weight.
  2. Unscrew the plastic cap and insert the graduated dispenser with the adapter into the bottle.
  3. Aspirate the prescribed amount of suspension.
  4. Detach the graduated dispenser from the adapter.
  5. Administer TROZOCIN with the graduated dispenser directly into the child's mouth.

Close the bottle with the special cap, rinse the dispenser well


Weight kg) Dosage schedule <15 10 mg / kg / day for 3 days 15-25 200 mg (5 ml) / day for 3 days 26-35 300 mg (7.5 mL) / day for 3 days 36-45 400 mg (10 ml) / day for 3 days >45 500 mg / day for 3 days (same dosage as adult)

Overdose What to do if you have taken too much Trozocin

Adverse events occurring with higher than recommended doses were similar to those seen with normal doses.

In case of accidental ingestion / intake of an excessive dose of Trozocin, notify your doctor immediately or go to the nearest hospital.

If you have any questions about the use of Trozocin, ask your doctor or pharmacist.

Side Effects What are the side effects of Trozocin

Like all medicines, Trozocin can cause side effects, although not everybody gets them.

Adverse reactions reported in clinical trials and / or postmarketing use are listed in the tables below. The frequency of adverse reactions is defined as follows:

Very common (≥1 / 10), Common (≥1 / 100,

Adverse reactions probably or possibly related to azithromycin derived from clinical studies or from post-marketing surveillance

Adverse reactions possibly or possibly related to azithromycin derived from clinical studies or post-marketing surveillance:


Very common (≥1 / 10) Common (≥1 / 100, Uncommon (≥1 / 1,000 to Rare (≥1 / 10,000, Frequency not known Infections and infestations Candidiasis, Vaginal infections, Pneumonia, Fungal infections, Bacterial infections, Pharyngitis, Gastroenteritis, Respiratory disorders, Rhinitis, Oral candidiasis Pseudo-membranous colitis (see section 4.4) Disorders of the blood and lymphatic system Leukopenia, Neutropenia, Eosinophilia Thrombocytopenia, Hemolytic anemia Disorders of the immune system Angioedema, Hypersensitivity Anaphylactic reaction (see section 4.4) Metabolism and nutrition disorders Anorexia Psychiatric disorders Nervousness, Insomnia Agitation Agitation, Aggression, Anxiety, Delirium, Hallucinations Nervous system disorders Headache Dizziness, Somnolence, Dysgeusia, Paresthesia Syncope, Convulsions, Hypoesthesia, Hyperactivity, Psychomotor Anosmia, Ageusia, Parosmia, Myasthenia gravis (see section 4.4) Eye disorders Visual impairment Ear and labyrinth disorders Ear disorders, Vertigo Hearing impairment including deafness and / or tinnitus Cardiac pathologies Palpitations Torsades de pointes (see section 4.4) Arrhythmia (see section 4.4) including ventricular tachycardia, QT prolongation (see section 4.4) Vascular pathologies Hot flashes Hypotension Respiratory, thoracic and mediastinal disorders Dyspnea, Epistaxis Gastrointestinal disorders Diarrhea Vomiting, Abdominal pain, Nausea Constipation, Flatulence, Dyspepsia, Gastritis, Dysphagia, Abdominal distension, Dry mouth, Burping, Mouth ulceration, Salivary hypersecretion Pancreatitis, tongue discoloration Hepatobiliary disorders Impaired liver function Cholestatic jaundice Hepatic failure (rarely leading to death) (see section 4.4), Fulminant hepatitis, Hepatic necrosis Skin and subcutaneous tissue disorders Rash, Itching, Urticaria, Dermatitis, Dry skin, Hyperhidrosis Reactions of photosensitivity Stevens-Johnson syndrome, Toxic epidermal necrolysis, Erythema multiforme Musculoskeletal and connective tissue disorders Osteoarthritis, Myalgia, Back pain, Neck pain Arthralgia Renal and urinary disorders Dysuria, Kidney pain Acute renal failure, Interstitial nephritis Reproductive system and breast disorders Metrorrhagia, Testicular disorders General disorders and administration site conditions Pain at the injection site, * Inflammation at the injection site Edema, Asthenia, Malaise, Fatigue, Face edema, Chest pain, Pyrexia, Pain, Peripheral edema Diagnostic tests Lymphocyte count decreased, Eosinophil count increased, Blood bicarbonate decreased, Basophil increased, Monocyte increased, Neutrophil increased Aspartate amino transferase increased, Alanine amino transferase increased, Blood bilirubin increased Blood urea increased, Blood creatinine increased Abnormal blood potassium, Blood alkaline phosphatase increased, Chlorine increased, Glucose increased, Platelet increased "hematocrit, Increased bicarbonate, Sodium abnormality Injury and poisoning Post procedural complications

* only with powder for solution for infusion

Adverse reactions possibly or probably related to use in the prophylaxis and treatment of Mycobacterium Avium Complex infections, derived from clinical studies and post-marketing surveillance. These adverse reactions differ both in type and frequency from those reported with the formulations a immediate or prolonged release:



Very common (≥1 / 10) Common (≥1 / 100, Uncommon (≥1 / 1,000 to Metabolism and nutrition disorders Anorexia Nervous system disorders Dizziness, Headache, Paresthesia, Dysgeusia Hypoesthesia Eye disorders Visual impairment Ear and labyrinth disorders Deafness Hearing impairment, Tinnitus Cardiac pathologies Palpitations Gastrointestinal disorders Diarrhea, Abdominal pain, Nausea, Flatulence, Abdominal discomfort, Loss of stool Hepatobiliary disorders Hepatitis Skin and subcutaneous tissue disorders Rash, Itching Stevens-Johnson syndrome, Photosensitivity reactions Musculoskeletal and connective tissue disorders Arthralgia General disorders and administration site conditions Fatigue Asthenia, Malaise

Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.

Expiry and Retention

Expiry: see the expiry date indicated on the package. The expiry date refers to the last day of the month.

Attention do not use the medicine after the expiry date indicated on the package.

The expiry date indicated refers to the product in intact and correctly stored packaging

After reconstitution, the oral suspension is stable for 10 days at room temperature.

DO NOT USE IN CASE OF EVIDENT SIGNS OF DETERIORATION. USE THE SPECIAL CONTAINERS FOR THE SEPARATE COLLECTION OF DRUGS FOR DISPOSAL.

KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

COMPOSITION

Trozocin powder for oral suspension - 1 bottle of 600 mg

The reconstituted suspension contains 40 mg of azithromycin per ml (200 mg for a dose of 5 ml).

The composition per 100 grams of powder is as follows:

Active principle

Azithromycin dihydrate 5.01 g

equal to Azithromycin base 4.78 g

Excipients

Anhydrous tribasic sodium phosphate, hydroxypropylcellulose, xanthan gum, cherry flavor, vanilla cream, banana flavor, sucrose.

PHARMACEUTICAL FORM AND CONTENT

Powder for oral suspension - 1 bottle of 600 mg Once reconstituted the suspension will contain 200 mg / 5ml.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

Further information on Trozocin can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical safety data06.0 INFORMATION PHARMACEUTICALS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER08 .0 MARKETING AUTHORIZATION NUMBER 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, ADDITIONAL DETAILED INSTRUCTIONS ON ESTEMPORANEA PREPARATION AND CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

TROZOCIN

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Trozocin 500 mg film-coated tablets

Each film-coated tablet contains:

Active principle:

Azithromycin dihydrate 524.110 mg

equal to Azithromycin base 500 mg

Trozocin 200 mg / 5 ml powder for oral suspension - 1 bottle of 1500 mg

The reconstituted suspension contains 40 mg of azithromycin per ml (200 mg for a dose of 5 ml).

The composition per 100 grams of powder is as follows:

Active principle:

Azithromycin dihydrate 5.01 g

equal to Azithromycin base 4.78 g

Excipients: the tablets contain lactose; the suspension contains sucrose.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Divisible film-coated tablets.

Powder for oral suspension.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Treatment of infections caused by azithromycin-sensitive germs.

- upper respiratory tract infections (including otitis media, sinusitis, tonsillitis and pharyngitis);

- lower respiratory tract infections (including bronchitis and pneumonia);

- odontostomatological infections;

- skin and soft tissue infections;

- non-gonococcal urethritis (from Chlamydia trachomatis);

- soft ulcer (from Haemophilus ducreyi).

04.2 Posology and method of administration

Adults

For the treatment of infections of the upper and lower respiratory tract, skin and soft tissues and odontostomatological infections: 500 mg per day in a single administration, for three consecutive days.

For the treatment of sexually transmitted diseases caused by sensitive strains of Chlamydia trachomatis you hate Haemophilus ducreyi: 1000 mg, taken once, in a single oral administration.

Senior citizens

The same dosage schedule indicated for adults can be applied to the elderly patient.

Since elderly patients may present with pro-arrhythmic conditions, particular caution is recommended due to the risk of developing cardiac arrhythmia and torsades de pointes (see section 4.4 Special warnings and precautions for use).

Children

10 mg / kg / day for 3 consecutive days.

For children weighing 45 kg or more, the same dosage as for adults (500 mg / day for three consecutive days) can be used.


Weight kg) Dosage schedule 10 mg / kg / day for 3 days 15-25 200 mg (5 ml) / day for 3 days 26-35 300 mg (7.5 mL) / day for 3 days 36-45 400 mg (10 ml) / day for 3 days >45 500 mg / day for 3 days (same dosage as adult)

For the treatment of acute otitis media in children, the expected dosage is 10 mg / kg / day for 3 consecutive days or 30 mg / kg in a single dose.

For the treatment of streptococcal pharyngitis in children, both the 10 mg / kg and 20 mg / kg doses, both in a single administration and for three consecutive days, have been shown to be effective; however, the daily dose of 500 mg should not be exceeded. In clinical studies with the two dosages, a comparable efficacy was observed, but with the dosage of 20 mg / kg / day there was a greater bacterial eradication. However, in the treatment of pharyngitis from Streptococcus pyogenes and in rheumatic fever prophylaxis, penicillin is the drug of choice.

The maximum total recommended dose for any pediatric therapy is 1500 mg.

The drug should always be administered in a single daily dose.

Trozocin (azithromycin) tablets and oral suspension can be taken either on an empty stomach or after meals. Food intake before administering the product may attenuate any gastrointestinal side effects caused by azithromycin.

The tablets should be swallowed whole.

Shake the bottle containing the powder before use. Add water to the bottle using the special dispenser attached to the package. Shake well. Always shake the suspension before use.

Altered kidney function

No dosage adjustment is required in patients with mild to moderate renal impairment (GFR 10 - 80 ml / min.) While caution should be exercised in those with severe impairment (GFR

Altered liver function

The same dosage as in patients with normal hepatic function can be used in patients with mild to moderate hepatic impairment (see 4.4 and 5.2).

04.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 (list of excipients).

Hypersensitivity to erythromycin or to any of the macrolide or ketolide antibiotics.

Severe hepatic insufficiency.

Azithromycin is generally contraindicated in pregnancy, lactation and very early childhood (see 4.6).

04.4 Special warnings and appropriate precautions for use

As with erythromycin and other macrolides, severe allergic reactions, including angioedema and anaphylaxis (rarely fatal), have been reported rarely, and may recur, even in the absence of re-administration, after symptomatic treatment has been discontinued.

These reactions require drug discontinuation and symptomatic treatment followed by a prolonged observation period.

In patients with severe renal impairment (GFR Pharmacokinetic properties).

In patients with mild to moderate hepatic impairment, no evidence of significant changes in serum azithromycin pharmacokinetics has been demonstrated compared to people with normal hepatic function. In these patients, the elimination of azithromycin via urine appears to increase, possibly as compensation for reduced hepatic clearance. However, since the liver is the major route of elimination, caution should be exercised under medical supervision in the use of azithromycin in patients with hepatic disease or hepatic insufficiency. Cases of fulminant hepatitis have been reported with azithromycin which may lead to life-threatening conditions of liver failure (see section 4.8 Undesirable effects). Some patients may have suffered from pre-existing liver disease or may have been treated with other hepatotoxic therapies. If they have signs and symptoms of liver dysfunction such as rapid development of asthenia with jaundice, dark urine, bleeding tendency or hepatic encephalopathy, liver function tests should be performed immediately If liver dysfunction occurs, azithromycin administration should be discontinued.

In patients treated with ergotamine derivatives, co-administration of macrolide antibiotics has precipitated ergotism crises. There is currently no data available on the theoretical possibility of an ergotism crisis; therefore, azithromycin and ergotamine should not be administered simultaneously.

As with any other antibiotic preparation, particular observation is recommended for the possible occurrence of superinfections with non-sensitive microorganisms including fungi.

Cases of diarrhea associated with Clostridium difficile (CDAD), the severity of which can range from mild diarrhea to fatal colitis. Treatment with antibiotics alters the normal flora of the colon and leads to an overgrowth of C. difficult.

The C. difficult produces toxins A and B which contribute to the development of diarrhea. The strains of C. difficult that produce excess toxins cause increased morbidity and mortality rates, as these infections are typically refractory to antibacterial therapy and often require a colectomy. The possibility of associated diarrhea should be considered C. difficult in all patients who present with diarrhea following antibiotic treatment. A careful medical history is also required since cases of diarrhea associated with C. difficult they have also been reported over two months after antibiotic administration.

In case of sexually transmitted infections it is necessary to exclude a concomitant infection with Treponema pallidum.

Prolongation of cardiac repolarization and QT interval has been found in treatment with other macrolides, with the risk of developing cardiac arrhythmia and torsades de pointes. In patients with a higher risk of prolongation of cardiac repolarization, it cannot be completely ruled out. a similar effect with azithromycin (see Section 4.8 Undesirable effects). Therefore, since the situations listed below may carry an increased risk of ventricular arrhythmias (including torsades de pointes) which can cause cardiac arrest, azithromycin should be used with caution in patients with pro-arrhythmic conditions (in particularly women and elderly patients) such as:

- Congenital or documented QT prolongation.

- concomitant treatment with other substances known to induce QT prolongation, such as class IA (quinidine and procainamide) and class III (dofetilide, amiodarone and sotalol) antiarrhythmics, cisapride and terfenadine; antipsychotic agents such as pimozide; antidepressants such as citalopram; and fluoroquinolones such as moxifloxacin and levofloxacin.

- electrolyte disturbances, in particular in case of hypokalaemia and hypomagnesemia.

- clinically significant bradycardia, arrhythmia or severe heart failure.

There have been reports of exacerbation of symptoms of myasthenia gravis and "new" onset of myasthenic syndrome in patients treated with azithromycin (see section 4.8).

The safety and efficacy of intravenous azithromycin in the treatment of infections in children have not been established.

The safety and efficacy in the prevention or treatment of Mycobacterium Avium Complex in children they have not been determined.

The suspension contains 3.9 g of sucrose for every 5 ml: this should be taken into account if the powder for oral suspension is administered to patients with genetic or acquired dysfunctions of carbohydrate metabolism. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase isomaltase insufficiency should not take this medicine.

The tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

04.5 Interactions with other medicinal products and other forms of interaction

Antacids

In a pharmacokinetic study of the effects of concomitant administration of antacids and azithromycin, no effect on the bioavailability of azithromycin was observed, although an approximately 25% reduction in maximum serum concentrations was observed. Therefore, patients in therapy with azithromycin and antacids should not take the two drugs at the same time.

Cetirizine

In healthy volunteers, co-administration of a 5-day regimen of azithromycin and cetirizine 20 mg at steady state showed no pharmacokinetic interactions or significant alterations in the QT interval.

Didanosine (Dideoxinosine)

Co-administration of daily doses of azithromycin 1200 mg / day and didanosine 400 mg / day in 6 HIV-positive patients was observed to have no effect on overall pharmacokinetics. steady state didanosine compared to placebo.

Digoxin (P-gp substrates)

Concomitant administration of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates such as digoxin has been reported to increase serum levels of the P-glycoprotein substrate. Thus, if azithromycin and P-gp substrates such as digoxin are administered simultaneously, the possibility of elevated serum substrate concentrations should be considered.

Ergotamine

Due to the possible onset of ergotism, the concomitant use of azithromycin and ergotamine derivatives is not recommended (see 4.4 Special warnings and precautions for use).

Zidovudine

Administration of single 1000 mg doses and multiple 1200 mg or 600 mg doses of azithromycin did not substantially change the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. concentrations of phosphorylated zidovudine, its clinically active metabolite, in peripheral mononuclear cells. The clinical significance of this finding is unclear, but may nevertheless be of benefit to the patient.

Azithromycin does not significantly interact with the hepatic cytochrome P450 system. It is not believed to be involved in pharmacokinetic interactions as found with erythromycin and other macrolides. In fact, with azithromycin, there is no induction or inactivation of hepatic cytochrome P450 via the complex of its metabolites.

Pharmacokinetic studies have been conducted between azithromycin and the following drugs, for which significant cytochrome P450 mediated metabolic activity is known.

Atorvastatin

Concomitant administration of atorvastatin (10 mg / day) and azithromycin (500 mg / day) did not cause alterations in HMG CoA reductase activity. However, from post-marketing experience cases of rhabdomyolysis have been reported in patients treated with azithromycin and statins.

Carbamazepine

In an interaction study in healthy volunteers, no significant effect on plasma levels of carbamazepine or its active metabolite was observed in patients taking concomitant azithromycin.

Cimetidine

In a pharmacokinetic study conducted to evaluate the effects of a single dose of cimetidine administered 2 hours after azithromycin, there was no evidence of alterations in the pharmacokinetics of azithromycin.

Cyclosporine

Significant increases in Cmax and AUC0-5 of cyclosporine. Therefore, the possible simultaneous administration of the two drugs requires caution. If the co-administration of the two drugs is strictly necessary, the levels of cyclosporine should be carefully monitored and the dosage of the latter should be modified accordingly.

Efavirenz

Co-administration of a single daily dose of azithromycin (600 mg) and efavirenz (400 mg) for 7 days produced no clinically significant pharmacokinetic interactions.

No dosage adjustment is required when azithromycin is administered in combination with efavirenz.

Fluconazole

Coadministration of a single dose of azithromycin (1200 mg) did not alter the pharmacokinetics of a single dose of fluconazole (800 mg). Total exposure time and half-life of azithromycin were not affected by co-administration with fluconazole, while a clinically insignificant decrease in Cmax (18%) was observed. No dosage adjustment is required when azithromycin is administered in combination with fluconazole

Indinavir

Coadministration of a single dose of azithromycin (1200 mg) did not show a statistically significant effect on the pharmacokinetics of indinavir administered three times daily for 5 days in doses of 800 mg. No dosage adjustment is required when azithromycin it is given in combination with indinavir.

Methylprednisolone

A pharmacokinetic study conducted in healthy volunteers showed that azithromycin does not significantly affect the pharmacokinetics of methylprednisolone.

Midazolam

In healthy volunteers, concomitant administration of azithromycin 500 mg / day for 3 days did not result in clinically significant changes in the pharmacokinetics and pharmacodynamics of a single 15 mg midazolam dose.

Nelfinavir

Concomitant administration of azithromycin (1200 mg) and nelfinavir allo steady state (750 mg three times daily) resulted in increased azithromycin concentrations. Although no clinically significant adverse reactions were observed and no dosage adjustment required, careful monitoring for azithromycin side effects is advised.

Rifabutin

Concomitant administration of azithromycin and rifabutin does not change the serum concentrations of the two drugs.

Cases of neutropenia have been observed in some patients taking the two drugs at the same time; although rifabutin is known to cause neutropenia, it has not been possible to establish a causal relationship between the above episodes of neutropenia and the rifabutin-azithromycin combination (see 4.8 Undesirable Effects).

Sildenafil

In healthy male volunteers, there was no evidence of any effect of azithromycin (500 mg daily for 3 days) on the AUC and Cmax of sildenafil or its major circulating metabolites.

Theophylline

Co-administration of azithromycin and theophylline to healthy volunteers did not show a clinically significant interaction between the two drugs.

Terfenadine

Pharmacokinetic studies revealed no interactions between azithromycin and terfenadine. In patients who took the two drugs at the same time there have been rare cases of interaction for which it has not been possible to establish or exclude a certain correlation.

Triazolam

In 14 healthy volunteers, co-administration of azithromycin 500 mg on day 1 and 250 mg on day 2 and triazolam 0.125 mg on day 2 had no significant effect on the pharmacokinetic variables of triazolam compared to triazolam and placebo.

Trimethoprim / Sulfamethoxazole

After concomitant administration of trimethoprim / sulfamethoxazole (160 mg / 800 mg) and azithromycin (1200 mg) for 7 days, there was no significant effect on peak concentrations, exposure time or urinary excretion on day 7. of both trimethoprim and sulfamethoxazole. Serum concentrations of azithromycin are similar to those seen in other studies. No dosage adjustment is required when azithromycin is co-administered with trimethoprim / sulfamethoxazole.

Coumarin-type oral anticoagulants

In a pharmacokinetic study in healthy volunteers, azithromycin was found not to alter the anticoagulant effect of a single 15 mg dose of warfarin.

In the post-marketing phase, cases of potentiation of anticoagulant action have been reported following the concomitant administration of azithromycin and coumarin-type oral anticoagulants. Although a causal relationship has not been established, it is advisable to re-evaluate the frequency with which to monitor the time to prothrombin when administering azithromycin to patients receiving coumarin-type anticoagulants.

With regard to the concomitant use of azithromycin and other drugs that act on coagulation, since specific interaction studies have not been conducted, careful monitoring of those patients taking the above drugs in combination is recommended.

04.6 Pregnancy and breastfeeding

There are no adequate data on the use of azithromycin in pregnancy. Reproductive toxicology studies in animals showed that azithromycin crosses the placenta but no teratogenic effects were observed. The safety of use of azithromycin in pregnancy has not been confirmed; therefore, azithromycin should only be used in pregnancy if the benefits outweigh the risks.

Secretion of azithromycin into breast milk has been reported, but there are no adequate and well-controlled clinical studies which have characterized the pharmacokinetics of excretion of azithromycin into breast milk in lactating women. Since many drugs are excreted in breast milk, trozocin (azithromycin) should therefore be used in lactating and very early infancy women only when the potential benefits clearly outweigh the risks and under medical supervision.

Fertility

In fertility studies in rats, a reduced pregnancy rate was observed following administration of azithromycin. The relevance of this data in man is not known.

04.7 Effects on ability to drive and use machines

No effect of trozocin (azithromycin) on the ability to drive and use machines has been reported.

04.8 Undesirable effects

The tables below list adverse reactions reported in clinical trials and / or post-marketing use, classified by system, organ and frequency. Adverse reactions identified in post-marketing use are shown in italics. The frequency of adverse reactions is defined as follows:

Very common (≥1 / 10), Common (≥1 / 100,

Within the frequency classes, adverse reactions are reported in order of decreasing severity.

Adverse reactions possibly or possibly related to azithromycin derived from clinical studies or post-marketing surveillance:


Very common (≥1 / 10) Common (≥1 / 100, Uncommon (≥1 / 1,000 to Rare (≥1 / 10,000, Frequency not known Infections and infestations Candidiasis, Vaginal infections, Pneumonia, Fungal infections, Bacterial infections, Pharyngitis, Gastroenteritis, Respiratory disorders, Rhinitis, Oral candidiasis Pseudo-membranous colitis (see section 4.4) Disorders of the blood and lymphatic system Leukopenia, Neutropenia, Eosinophilia Thrombocytopenia, Hemolytic anemia Disorders of the immune system Angioedema, Hypersensitivity Anaphylactic reaction (see section 4.4) Metabolism and nutrition disorders Anorexia Psychiatric disorders Nervousness, Insomnia Agitation Agitation, Aggression, Anxiety, Delirium, Hallucinations Nervous system disorders Headache Dizziness, Somnolence, Dysgeusia, Paresthesia Syncope, Convulsions, Hypoesthesia, Hyperactivity, Psychomotor Anosmia, Ageusia, Parosmia, Myasthenia gravis (see section 4.4) Eye disorders Visual impairment Ear and labyrinth disorders Ear disorders, Vertigo Hearing impairment including deafness and / or tinnitus Cardiac pathologies Palpitations Torsades de pointes (see section 4.4) Arrhythmia (see section 4.4) including ventricular tachycardia, QT prolongation (see section 4.4) Vascular pathologies Hot flashes Hypotension Respiratory, thoracic and mediastinal disorders Dyspnea, Epistaxis Gastrointestinal disorders Diarrhea Vomiting, Abdominal pain, Nausea Constipation, Flatulence, Dyspepsia, Gastritis, Dysphagia, Abdominal distension, Dry mouth, Burping, Mouth ulceration, Salivary hypersecretion Pancreatitis, tongue discoloration Hepatobiliary disorders Impaired liver function Cholestatic jaundice Hepatic failure (rarely leading to death) (see section 4.4), Fulminant hepatitis, Hepatic necrosis Skin and subcutaneous tissue disorders Rash, Itching, Urticaria, Dermatitis, Dry skin, Hyperhidrosis Reactions of photosensitivity Stevens-Johnson syndrome, Toxic epidermal necrolysis, Erythema multiforme Musculoskeletal and connective tissue disorders Osteoarthritis, Myalgia, Back pain, Neck pain Arthralgia Renal and urinary disorders Dysuria, Kidney pain Acute renal failure, Interstitial nephritis Reproductive system and breast disorders Metrorrhagia, Testicular disorders General disorders and administration site conditions Pain at the injection site, * Inflammation at the injection site Edema, Asthenia, Malaise, Fatigue, Face edema, Chest pain, Pyrexia, Pain, Peripheral edema Diagnostic tests Lymphocyte count decreased, Eosinophil count increased, Blood bicarbonate decreased, Basophil increased, Monocyte increased, Neutrophil increased Aspartate amino transferase increased, Alanine amino transferase increased, Blood bilirubin increased Blood urea increased, Blood creatinine increased Abnormal blood potassium, Blood alkaline phosphatase increased, Chlorine increased, Glucose increased, Platelet increased "hematocrit, Increased bicarbonate, Sodium abnormality Injury and poisoning Post procedural complications

* Only with powder for solution for infusion.

115% "> Adverse reactions possibly or probably related to" use in the prophylaxis and treatment of infectionsMycobacterium Avium Complex, derived from clinical trials and post-marketing surveillance. These adverse reactions differ in both type and frequency from those reported with the immediate or prolonged release formulations:


Very common (≥1 / 10) Common (≥1 / 100, Uncommon (≥1 / 1,000 to Metabolism and nutrition disorders Anorexia Nervous system disorders Dizziness, Headache, Paresthesia, Dysgeusia Hypoesthesia Eye disorders Visual impairment Ear and labyrinth disorders Deafness Hearing impairment, Tinnitus Cardiac pathologies Palpitations Gastrointestinal disorders Diarrhea, Abdominal pain, Nausea, Flatulence, Abdominal discomfort, Loss of stool Hepatobiliary disorders Hepatitis Skin and subcutaneous tissue disorders Rash, Itching Stevens-Johnson syndrome, Photosensitivity reactions Musculoskeletal and connective tissue disorders Arthralgia General disorders and administration site conditions Fatigue Asthenia, Malaise

04.9 Overdose

Adverse events occurring with higher than recommended doses were similar to those seen with normal doses. In the event of an overdose, appropriate general symptomatic and supportive measures are indicated.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antibacterials for systemic use - Macrolides. ATC code: J01FA10.

Azithromycin is the first of a sub-class of macrolide antibiotics, called azalides, and is chemically different from erythromycin. Chemically it is derived from the insertion of a nitrogen atom in the lactone ring of erythromycin A.

Its chemical name is: 9-deoxy-a-aza-9a-methyl-9a-homoerythromycin A. The molecular weight is 749.0.

Azithromycin exerts its activity by inhibiting bacterial protein synthesis by binding to the 50s ribosomal subunits and thus preventing peptide translocation, but without affecting nucleic acid synthesis. The azithromycin proves in vitro activity against a "wide range of bacteria which includes:

Gram-positive aerobes: Staphylococcus aureus, Streptococcus pyogenes (Streptococcus beta-hemolytic group A), Streptococcus pneumoniae, Alpha haemolytic streptococci (viridant group), other streptococci e Corynebacterium diphteriae. Erythromycin-resistant gram-positive bacteria such asStreptococcus faecalis (enterococcus) and many strains of methicillin-resistant Staphilococci show cross-resistance even against azithromycin;

Gram-negative aerobes: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Acinetobacter spp., Yersinia spp., Legionella pneumophila, Bordetella pertussis, Bordetella parapertussis, Shigella spp., Pasteurella spp., Vibrio cholerae and parahaemolyticus, Pleisiomonas shigelloides.

Azithromycin demonstrates variable activity against Escherichia coli, Salmonella enteritidis, Salmonella typhi, Enterobacter spp., Aeromonas hydrophila And Klebsiella spp.

In case of infections with such bacterial species in vitro susceptibility tests should be performed. Proteus spp., Serratia spp., Morganellaspp. and Pseudomonas aeruginosa they are usually hardy.

Anaerobic bacteria: Bacteroides fragilis, Bacteroides spp., Clostridium perfringens, Peptococcus spp., Peptostreptococcus spp., Fusobacterium necrophorum And Propionibacterium acnes.

Microorganisms that cause venereal diseases: Chlamydia trachomatis, Treponema pallidum, Neisseria gonorrhoeae and Haemophilus ducreyi.

Other microorganisms: Borrelia burgdorferi (Lyme disease agent), Chlamydia pneumoniae, Toxoplasma gondii, Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma urealyticum, Pneumocystis carinii, Mycobacterium avium, Campylobacter spp., And Listeria monocytogenes.

05.2 Pharmacokinetic properties

Absorption

Azithromycin is more stable at gastric pH compared to erythromycin.

In humans, after oral administration, azithromycin is rapidly and widely distributed throughout the body; the time required to obtain peak plasma levels is 2-3 hours.

Distribution

In animal studies, high concentrations of azithromycin have been observed within phagocytic cells. In experimental models, moreover, high concentrations of azithromycin are released by activated phagocytes compared to non-activated phagocytes. This phenomenon determines, in the animal model, high concentrations of azithromycin at the site of infection.

Pharmacokinetic studies in humans have shown tissue levels of azithromycin higher than those in plasma (up to 50 times the maximum concentrations observed in plasma), thus indicating that the drug is highly bound to tissues. Concentrations in target organs such as the lung , tonsils and prostate, exceed the MIC90 values ​​for the most common pathogens, after a single oral administration of 500 mg.

Elimination

The terminal plasma half-life closely reflects the tissue depletion half-life (2 to 4 days). Approximately 12% of an IV dose is excreted in the urine as unchanged drug over 3 days, most of it in the first 24 hours. Biliary elimination is the major route of elimination of unchanged drug after oral administration. Very high concentrations of unchanged drug were found in human bile together with 10 metabolites, the latter formed by N- and O-demethylation processes, by hydroxylation of desosamine and the aglyconic ring and by cleavage of cladinose-conjugates. HPLC and a microbiological method to evaluate the tissue concentrations of these metabolites have shown that they play no role in the antimicrobial activity of azithromycin.

Pharmacokinetics in special categories of patients

Senior citizens

A study conducted on healthy volunteers showed that after a 5-day regimen the AUC values ​​are slightly higher in elderly subjects (> 65 years) than in younger subjects (

Altered kidney function

Following once oral administration of 1 gram azithromycin, no pharmacokinetic effects have been observed in patients with mild to moderate renal dysfunction (GFR 10 - 80 ml / min.). Statistically significant differences were found in AUC0-120 (8.8 mg-hr / mL vs. 11.7 mg-hr / mL), Cmax (1.0 mg / mL vs. 1.6 mg / mL) and CLr (2.3 mL / min) values. ./kg vs. 0.2ml / min.kg) among the severe renal dysfunction group (GFR

Altered liver function

In patients with mild (Class A) to moderate (Class B) hepatic impairment, there was no evidence of significant changes in serum azithromycin pharmacokinetics compared to subjects with normal hepatic function. In these patients, elimination of azithromycin through urine it appears to increase, probably as a compensation for decreased hepatic clearance.

05.3 Preclinical safety data

In animal studies conducted with high doses that exceeded 40 times the maximum dose used in clinical practice, azithromycin was found to cause reversible phospholipidosis, generally without obvious toxicological consequences. The effect was shown to be reversible on discontinuation of the drug. treatment with azithromycin The significance of these findings for both animals and humans is unknown.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Trozocin 500 mg film-coated tablets

Pregelatinised starch, anhydrous acid calcium phosphate, carmellose sodium, magnesium stearate, sodium lauryl sulfate, deionized water.

The lining contains: titanium dioxide, lactose, hypromellose, triacetin, deionized water.

Trozocin 200 mg / 5 ml powder for oral suspension - 1 bottle of 1500 mg

Anhydrous tribasic sodium phosphate, hydroxypropylcellulose, xanthan gum, cherry flavor, vanilla cream, banana flavor, sucrose.

06.2 Incompatibility

Not relevant.

06.3 Period of validity

Trozocin 500 mg film-coated tablets: 2 years.

Trozocin 200 mg / 5 ml powder for oral suspension: 2 years in intact packaging.

Once reconstituted, the powder for oral suspension will keep for 10 days at room temperature.

06.4 Special precautions for storage

This medicine does not require any special storage conditions.

06.5 Nature of the immediate packaging and contents of the package

Trozocin 500 mg film-coated tablets

PVC blister containing 3 film-coated scored tablets of 500 mg.

Trozocin 200 mg / 5 ml powder for oral suspension

High density polyethylene bottle containing 1500 mg of active ingredient with child resistant closure and suitable dispenser.

Once reconstituted the suspension will contain 200 mg / 5 ml.

06.6 Instructions for use and handling

Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.

07.0 MARKETING AUTHORIZATION HOLDER

SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A.

Viale Shakespeare, 47

00144 Rome

08.0 MARKETING AUTHORIZATION NUMBER

"TROZOCIN 500 mg film-coated tablets" 3 tablets - A.I.C. n. 027948064

"TROZOCIN 200 mg / 5 ml powder for oral suspension" 1 bottle of 1500 mg - A.I.C. n. 027948052

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

May 1992 / May 2007

10.0 DATE OF REVISION OF THE TEXT

November 2013

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL

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