Active ingredients: Azithromycin
ZITROMAX 200 mg / 5 ml powder for oral suspension
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").
Zithromax 200mg / 5ml powder for oral suspension contains sucrose (5ml suspension contains 3.87g of sucrose).
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Furthermore, due to the sucrose content, caution is required in the treatment of diabetic patients.
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 upper and lower respiratory tract infections, skin and soft tissue infections and odontostomatological infections: 500 mg per day, in a single administration, for 3 consecutive days.
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").
Pediatric population
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.
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 administration (see also below the "Instructions for preparation and administration of the suspension" ).
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.
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 use").
The same dosage as in patients with normal hepatic function can be used in patients with mild to moderate hepatic impairment (see "Precautions for use").
The drug should always be administered in a single daily dose.
ZITROMAX (azithromycin) powder for 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.
INSTRUCTIONS FOR THE PREPARATION AND ADMINISTRATION OF THE SUSPENSION
- Shake the bottle containing the powder before adding water.
- Use the special dispenser positioned on the closure cap of the package and fill it with water up to the line (corresponding to 9 ml), for one time only.
- Pour the water from the dispenser into the bottle.
- Shake well so that all the powder passes into suspension.
One milliliter of suspension thus reconstituted contains 40 mg of azithromycin (equal to 200 mg for a 5 ml dose).
Always shake the suspension before use.
The reconstituted suspension must be administered using one of the two graduated dispensers attached to the package:
- "double spoon" graduated dispenser: to be used for children weighing between 15 kg and 45 kg. The dispenser consists of a small teaspoon (capacity 5 ml) on one side, and a large teaspoon (capacity 10 ml) on the other side
- graduated "syringe" dispenser: to be used for children weighing less than 15 kg
1) INSTRUCTIONS FOR USING THE "DOUBLE SPOON" GRADUATED DOSER
2) INSTRUCTIONS FOR USING THE "SYRINGE" GRADUATED DOSER
- The syringe is calibrated in mg and ml of drug and kg of the child's weight
- Unscrew the plastic cap and insert the syringe, with the adapter, into the bottle
- Aspirate the prescribed amount of suspension
- Detach the syringe from the adapter
- Administer the suspension with the syringe directly into the child's mouth
Close the bottle with the special cap. Rinse the graduated dispenser used well.
ATTENTION
For the treatment of acute otitis media in children, the dosage of 30 mg / kg can also be performed in a single administration, filling the graduated dispenser "syringe" as many times as necessary until the prescribed dose is reached.
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.
* 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:
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. 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 or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Other information
COMPOSITION
ZITROMAX 200 mg / 5 ml 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 ingredient: Azithromycin dihydrate 5.01 g equal to Azithromycin base 4.78 g
- Excipients: Tribasic sodium phosphate anhydrous, hydroxypropylcellulose, xanthan gum, cherry flavor, vanilla cream, banana flavor, sucrose.
PHARMACEUTICAL FORM AND CONTENT
Powder for oral suspension - bottle containing 600 mg of azithromycin.
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.
