Zithromax - Package Leaflet

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

Active ingredients: Azithromycin

ZITROMAX 250 mg hard capsules

Zithromax package inserts are available for pack sizes:
  • ZITROMAX 250 mg hard capsules
  • ZITROMAX 100 mg powder for oral suspension, ZITROMAX 150 mg powder for oral suspension, ZITROMAX 200 mg powder for oral suspension, ZITROMAX 300 mg powder for oral suspension, ZITROMAX 400 mg powder for oral suspension
  • ZITROMAX 200 mg / 5 ml powder for oral suspension
  • ZITROMAX 2 g granules for prolonged-release oral suspension
  • ZITROMAX 500 mg film-coated tablets, ZITROMAX 200 mg / 5 ml powder for oral suspension

Why is Zithromax 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,
  • non-gonococcal urethritis (from Chlamydia trachomatis),
  • soft ulcer (from Haemophilus ducreyi).

Contraindications When Zithromax should not be used

Hypersensitivity to the active substance azithromycin, to erythromycin, to any of the macrolide or ketolide antibiotics, or to any of the excipients.

Precautions for use What you need to know before taking Zithromax

Altered kidney function

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).

Hepatotoxicity

Since the liver is the major route of elimination of azithromycin, its use in patients with major liver disease should be undertaken with caution. Cases of liver impairment, hepatitis, cholestatic jaundice, hepatic necrosis and fulminant hepatitis have been reported with azithromycin. potentially due to liver failure, some of which have been fatal (see "Side Effects"). Some patients may have had previous liver disease or may have taken other hepatotoxic medicinal products. In cases where signs and symptoms of liver dysfunction develop, such as rapid onset asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy, liver function tests / tests should be performed immediately.

Immediately discontinue azithromycin treatment if signs of liver dysfunction occur.

Derivatives of ergotamine

In patients treated with ergotamine derivatives the co-administration of macrolide antibiotics has precipitated ergotism crises. Currently there are no data available on the possibility of an interaction between ergotamine and azithromycin. However, due to the theoretical possibility of ergotism, azithromycin and ergotamine should not be administered simultaneously.

Superinfections

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 change the effect of Zithromax

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. Co-administration of azithromycin granules for prolonged-release oral suspension with a single dose of 20 ml of co-magaldrox (aluminum hydroxide and magnesium hydroxide) did not affect the rate and extent of absorption of azithromycin.

Cetirizine

In healthy volunteers, co-administration of a 5-day regimen of azithromycin and 20 mg cetirizine at steady state did not reveal any pharmacokinetic interactions or significant alterations in the QT interval.

Didanosine

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

Digoxin (P-glycoprotein substrates)

The intake of macrolide antibiotics, including azithromycin with P-glycoprotein substrates such as digoxin, has been reported to cause increased serum levels of P-glycoprotein substrates. Therefore, the possibility of an increase in serum digoxin levels should be considered if azithromycin and P-glycoprotein substrates such as digoxin are taken concomitantly. Clinical monitoring and monitoring for possible elevated digoxin levels are required during and after discontinuation of azithromycin treatment.

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. With azithromycin, in fact, there is no induction or inactivation of hepatic cytochrome P450 through the complex of its metabolites.

Ergotamine

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

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

HMG-CoA reductase inhibitors (Statins)

Concomitant administration of atorvastatin (10 mg / day) and azithromycin (500 mg / day) did not alter plasma concentrations of atorvastatin (based on an HMG CoA reductase inhibition assay) and therefore did not cause changes in activity. of HMG CoA reductase. However, there have been post-marketing reports of rhabdomyolysis in patients receiving 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.

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.

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.

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. No clinically significant adverse reactions were observed and no dosage adjustment was required.

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 effect of azithromycin (500 mg / day for 3 days) on the AUC and Cmax of sildenafil or its major circulating metabolite.

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. Some rare cases have been reported in which the possibility of such an interaction could not be completely excluded; however, there is no scientific evidence that the interaction occurred.

Triazolam

In 14 healthy volunteers, concomitant 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. both trimethoprim and sulfamethoxazole Serum concentrations of azithromycin are similar to those found in other studies.

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 recommended to re-evaluate the frequency with which to monitor the time to prothrombin when administering azithromycin to patients receiving coumarin-type anticoagulants.

Warnings It is important to know that:

Hypersensitivity and anaphylactic reactions

As with erythromycin and other macrolides, severe allergic reactions, including angioedema and anaphylaxis (rarely fatal), dermatological reactions including Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (rarely fatal) have been observed. and drug eruption with eosinophilia and systemic symptoms (DRESS). Some of these reactions associated with azithromycin administration have resulted in relapses and therefore require a prolonged period of observation and treatment.

In the event of an allergic reaction, the drug should be discontinued and appropriate therapy instituted. Physicians should be aware that allergic symptoms may return once symptomatic therapy is discontinued.

Clostridium difficile associated diarrhea

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. difficile.

C. difficile produces toxins A and B which contribute to the development of diarrhea. Strains of C. difficile that produce excess toxins cause increased morbidity and mortality rates, as these infections are typically refractory to antibacterial therapy and often require colectomy. The possibility of C. difficile-associated diarrhea should be considered 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 the QT interval

In treatment with macrolides, including azithromycin, prolongation of cardiac repolarization and QT interval was found on ECG, leading to the risk of developing cardiac arrhythmia and torsades de pointes (see "Undesirable Effects"). Therefore, since the following situations may lead to an increased risk of ventricular arrhythmias (including torsades de pointes), which can lead to cardiac arrest, azithromycin should be administered with caution in patients with concomitant proarrhythmic conditions (especially in women and elderly patients).

Prescribers should consider the risk of QT interval prolongation, which can be fatal, when evaluating the benefit-risk of azithromycin in patient groups at risk, such as:

  • Patients with congenital or documented prolongation of the QT interval;
  • Patients treated with other active substances that prolong the QT interval, such as Class IA antiarrhythmics (quinidine and procainamide) and Class III (dofetilide, amiodarone and sotalol), cisapride and terfenadine, antipsychotic drugs such as pimozide, antidepressants such as citalopram, fluoroquinolones such as moxifloxacin, levofloxacin and chloroquine.
  • Patients with electrolyte disturbances, especially in cases of hypokalaemia and hypomagnesaemia;
  • Patients with clinically relevant bradycardia, cardiac arrhythmia or severe heart failure;
  • Women and the elderly who may be more sensitive to the (drug-related) effects of QT interval alteration.

Myasthenia Gravis

Exacerbation of symptoms of myasthenia gravis and initial onset of myasthenic syndrome have been reported in patients receiving azithromycin (see "Undesirable effects").

The medicine contains lactose: If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Fertility, pregnancy and breastfeeding

Ask your doctor or pharmacist for advice before taking any medicine.

There are no adequate data on the use of azithromycin in women during pregnancy. The safety of azithromycin during pregnancy has not been established. Therefore azithromycin should only be used in pregnancy if the benefit outweighs the risk.

Fertility

In fertility studies conducted in rats, a reduction in the fertility rate was noted following administration of azithromycin. The relevance of these findings to humans is unknown.

Pregnancy

Animal reproduction studies have been conducted using scaled doses up to reaching moderately toxic maternal concentrations. From these studies there was no evidence of any hazard to the fetus due to azithromycin. In reproductive toxicology studies in animals azithromycin has shown to pass the placenta, but no teratogenic effects were observed.

Feeding time

Azithromycin has been reported to be secreted into breast milk. Therefore, azithromycin should only be used in breastfeeding women in cases where, in the opinion of the physician, the potential benefit justifies the potential risk to the baby.

Effects on ability to drive and use machines

There are no data showing that azithromycin can affect patients' ability to drive or operate machinery.

Dosage and method of use How to use Zithromax: Dosage

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 3 consecutive days. For the treatment of sexually transmitted diseases caused by strains of Chlamydia trachomatis or Haemophilus ducreyi: 1000 mg, taken once, in a single oral administration.

Senior citizens

The same dosage schedule can be applied to the elderly patient. Since elderly patients are more prone to cardiac arrhythmias, particular caution is recommended due to the risk of developing cardiac arrhythmias and torsades de pointes (see "Special Warnings").

Patients with liver or kidney problems:

Patients with liver or kidney problems should inform their doctor, as this may need to change the normal dosage. No dosage adjustment is required in patients with mild to moderate renal impairment (GFR 10 - 80 mL / min) and caution should be exercised in those with severe renal impairment (GFR <10 mL / min) (see "Precautions for The "use") The same dosage as in patients with normal hepatic function may be used in patients with mild to moderate hepatic impairment (see "Precautions for use").

Administration after a substantial meal reduces the bioavailability of ZITROMAX (azithromycin) capsules by 50%. For this reason each dose should be administered at least 1 hour before or 2 hours after meals.

The capsules must be swallowed whole.

Overdose What to do if you have taken too much Zithromax

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 ZITROMAX, notify your doctor immediately or go to the nearest hospital.

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

Side Effects What are the side effects of Zithromax

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

The table below lists the adverse reactions identified during the conduct of clinical studies and during post-marketing surveillance, divided by system organ class and frequency. Adverse reactions identified during postmarketing surveillance are shown in italics. Frequency is defined using the following parameters: Very common (≥1 / 10); Common (≥ 1/100,

Adverse reactions with possible or probable correlation to azithromycin based on the results of clinical studies and post-marketing surveillance.

Systemic organic classification Adverse reaction Frequency Infections and infestations Candidiasis, vaginal infection, pneumonia, fungal infection, bacterial infection, pharyngitis, gastroenteritis, respiratory disorder, rhinitis, oral candidiasis Uncommon Pseudomembranous colitis (see "Special Warnings") Not known Disorders of the blood and lymphatic system Leukopenia, neutropenia, eosinophilia Uncommon Thrombocytopenia, haemolytic anemia Not known Disorders of the immune system Angioedema, hypersensitivity Uncommon Anaphylactic reaction (see section "Special warnings") Not known Metabolism and nutrition disorders Anorexia Uncommon Psychiatric disorders Nervousness, insomnia Uncommon Agitation Rare Aggression, anxiety, delirium, hallucinations Not known Disorders of the nervous system Headache common Dizziness, somnolence, dysgeusia, paraesthesia Uncommon Syncope, convulsions, hypoesthesia, psychomotor hyperactivity, anosmia, ageusia, parosmia, Myasthenia gravis (see section "Special warnings") Not known Eye disorders Visual impairment Uncommon Ear and labyrinth disorders Ear disorders, dizziness Uncommon Hearing impairment including deafness and / or tinnitus Not known Cardiac pathologies Palpitations Uncommon Torsades de pointes (see section "Special warnings"), arrhythmia (see section "Special warnings") including ventricular tachycardia, prolongation of the "QT interval at" electrocardiogram (see section "Special warnings") Not known Vascular pathologies Hot flashes Uncommon Hypotension Not known Respiratory, thoracic and mediastinal disorders Dyspnea, epistaxis Uncommon Gastrointestinal disorders Diarrhea Very common Vomiting, abdominal pain, nausea common Constipation, flatulence, dyspepsia, gastritis, dysphagia, abdominal distension, dry mouth, belching, mouth ulceration, salivary hypersecretion Uncommon Pancreatitis, discolouration of the tongue Not known Hepatobiliary disorders Abnormal liver function, cholestatic jaundice Rare Hepatic failure (rarely fatal) (see section "Special warnings"), fulminant hepatitis, hepatic necrosis Not known Skin and subcutaneous tissue disorders Rash, itching, hives, dermatitis, dry skin, hyperhidrosis Uncommon Photosensitivity reaction, drug eruption with eosinophilia and systemic symptoms (DRESS) Rare Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme Not known Musculoskeletal and connective tissue disorders Osteoarthritis, myalgia, back pain, neck pain Uncommon Arthralgia Not known Renal and urinary disorders Dysuria, kidney pain Uncommon Acute renal failure, interstitial nephritis Not known Diseases of the reproductive system and breast Metrorrhagia, testicular disorders Uncommon General disorders and administration site conditions Edema, asthenia, malaise, fatigue, face edema, chest pain, pyrexia, pain, peripheral edema Injection site pain *, injection site inflammation * common Diagnostic tests Lymphocyte count decreased, eosinophil count increased, blood bicarbonate decreased, basophils increased, monocytes increased, neutrophils increased common Increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), increased blood bilirubin, increased blood urea, increased blood creatinine, altered blood potassium, increased blood alkaline phosphatase, increased chloride levels, increased blood glucose, platelet increase, hematocrit decrease, blood bicarbonate increase, sodium level changes Uncommon Trauma and poisoning Post procedural complications Uncommon

* for the powder for solution for infusion only

Adverse reactions possibly or probably related to prophylaxis and treatment of Mycobacterium avium Complex based on experience from clinical trials and post-marketing surveillance. These adverse reactions differ from those reported with immediate-release or prolonged-release formulations, in type or in frequency:

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

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

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Undesirable effects can also be reported directly through the national reporting system at the "address www.agenziafarmaco.it/it/responsabili". By reporting side effects you can help provide more information on the safety of this medicine.

Expiry and Retention

Keep this medicine out of the sight and reach of children.

Expiry: see the expiry date indicated on the package. The expiry date indicated refers to the product in intact and correctly stored packaging.

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

For the tablets there are no special precautions for the storage of the product.

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

DO NOT USE IN CASE OF EVIDENT SIGNS OF DETERIORATION.

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

Other information

COMPOSITION

Each 250 mg hard capsule contains:

  • Active ingredient: Azithromycin dihydrate 262.05 mg equal to Azithromycin base 250 mg
  • Excipients: Anhydrous lactose, corn starch, magnesium stearate, sodium lauryl sulfate. The caps contain: gelatin, titanium dioxide.

PHARMACEUTICAL FORM AND CONTENT

Hard capsules. Blister pack containing 6 capsules of 250 mg.

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.

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