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SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Azithromycin 500 mg Film-coated tablets

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Each film-coated tablet contains 500 mg of azithromycin (as dihydrate).

For excipients, see 6.1.

3    PHARMACEUTICAL FORM

Film-coated tablets.

White, oblong, biconvex, film coated tablets, scored on one side.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Azithromycin is indicated for the treatment of the following infections when known or likely to be due to one or more susceptible microorganisms (see section5.1):

-    acute exacerbations of chronic bronchitis

-    community-acquired pneumonia

-    bacterial sinusitis

-    pharyngitis/tonsillitis (see 4.4 regarding streptococcal infections)

-    acute otitis media

-    skin and soft tissue infections

-    uncomplicated urethritis and cervicitis due to Chlamydia trachomatis

Consideration should be given to official guidance regarding the appropriate use of antibacterial agents.

4.2 Posology and method of administration

This medicine should be taken in a single daily dose. The tablets should be swallowed whole and may be taken with or without food. The length of treatment for various infectious diseases is set out below.

Posology:

Paediatric population

Children over 45 kg body weight and adults, including elderly patients The total dosage of azithromycin is 1500 mg which should be given over three days (500 mg once daily).

Alternatively, the dosage may be staggered over five days (500 mg as a single dose on the first day, and then 250 mg once daily).

In uncomplicated genital infections due to Chlamydia trachomatis, the dosage is 1000 mg as a single oral dose.

Children and adolescents with a body weight below 45 kg:

Tablets are not indicated for these patients. Other pharmaceutical forms of azithromycin may be used, such as suspensions.

Renal insufficiency:

In patients whose renal function is slightly impaired (creatinine clearance >40 ml/min), dose adjustment is not necessary. No studies have been conducted in patients with a creatinine clearance of <40 ml/min and consequently caution must be exercised in the use of azithromycin for these patients.

Hepatic insufficiency:

Dose adjustment is not required for patients with mild to moderate hepatic dysfunction but the medicinal product should be used with caution in patients with significant hepatic diseases (see section 4.4).

Method of Administration:

Azithromycin 500 mg film-coated tablets should be administered as a single daily dose and may be taken with meals.

4.3 Contraindications

Hypersensitivity to azithromycin, erythromycin or any macrolide or ketolide, or to any of the excipients listed in Section 6.1.

4.4 Special warnings and precautions for use

Superinfections: As with any antibacterial agent, there is a possibility that superinfections could occur (e.g. fungal infections).

Allergic reactions:

As with erythromycin and other macrolides, rare serious allergic reactions, including angioedema and anaphylaxis (rarely fatal), have been reported. Some of these reactions with azithromycin have resulted in recurrent symptoms and required a longer period of observation and treatment.

Renal failure:

No dose adjustment is necessary in patients with mild to moderate renal impairment (GFR 10-80 ml/min). In patients with severe renal impairment (GFR <10 ml/min) a 33% increase in systemic exposure to azithromycin was observed (see Section 5.2 Pharmacokinetic properties).

Hepatic failure:

Since liver is the principal route of elimination for azithromycin, the use of azithromycin should be undertaken with caution in patients with significant hepatic disease. Cases of fulminant hepatitis potentially leading to life-threatening liver failure have been reported with azithromycin (see Section 4.8) . Some patients may have had pre-existing hepatic disease or may have been taking other hepatotoxic medicinal products.

Liver function tests/investigations should be performed in cases where signs and symptoms of liver dysfunction occur such as rapid developing asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy.

When severe liver impairment occurs, the treatment with azithromycin should be ceased.

Ergot alkaloids and Azithromycin:

In patients receiving ergot derivatives, ergotism has been precipitated by coadministration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergot and azithromycin. However, because of the theoretical possibility of ergotism, azithromycin and ergot derivatives should not be coadministered. (see section 4.5).

QT prolongation:

Prolonged cardiac repolarisation and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with other macrolides. A similar effect with azithromycin cannot be completely ruled out in patients at increased risk for prolonged cardiac repolarization (see Section 4.8 Undesirable effects) therefore caution is required when treating patients:

-    With congenital or documented QT prolongation.

-    Currently receiving treatment with other active substances known to prolong QT interval such as antiarrhythmics of classes IA and III, cisapride and terfenadine.

-    With electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesemia.

- With clinically relevant bradycardia, cardiac arrhythmia or severe cardiac insufficiency.

Pneumococcal infections:

As for other macrolides, high resistance rates of Streptococcus pneumoniae (> 30 %) have been reported for azithromycin in some European countries (see section 5.1). This should be taken into account when treating infections caused by Streptococcus pneumoniae.

Neurological or psychiatric diseases:

Azithromycin should be administered with caution to patients suffering from neurological or psychiatric diseases.

Pseudomembranous colitis:

After the use of macrolide antibiotics pseudomembranous colitis has been reported. This diagnosis should therefore be considered for patients who suffer from diarrhoea after start of the treatment with azithromycin. Should pseudomembranous colitis be induced by azithromycin, then anti-peristaltics should be contraindicated.

Clostridium difficile associated diarrhea:

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including azithromycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

Long term use:

There is no experience regarding the safety and efficacy of long term use of azithromycin for the mentioned indications. In case of rapid recurrent infections, treatment with another antibiotic should be considered.

Azithromycin is not indicated for the treatment of infected burn wounds.

In case of sexually transmitted diseases a concomitant infection by T. pallidium should be excluded.

Exacerbations of the symptoms of myasthenia gravis and new onset of myasthenia syndrome have been reported in patients receiving azithromycin therapy (see section 4.8).

4.5 Interaction with other medicinal products and other forms of interaction

Antacids: When studying the effect of simultaneously administered antacids on the pharmacokinetics of azithromycin, no overall change has been observed in the bioavailability, although the peak concentrations of azithromycin measured in the plasma fell by 30 %. Azithromycin should be taken at least 1 hour before or 2 hours after the antacid.

Digoxin: In some patients certain macrolide antibiotics have been reported to impair the metabolism of digoxin in the intestine. Consequently, in patients receiving azithromycin and digoxin, the possibility of a rise in the digoxin concentrations should be borne in mind and digoxin levels monitored.

Methylprednisolone: In a pharmacokinetic interaction study conducted in healthy volunteers, azithromycin had no significant effect on the pharmacokinetics of methylprednisolone.

Zidovudine: 1000 mg single doses and 1200 mg or 600 mg multiple doses of azithromycin had no effect upon the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, administration of azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in mononuclear cells in the peripheral circulation. The clinical significance of these findings is unclear, but may be of benefit to patients.

Didanosine: Co-administration of daily doses of 1200 mg azithromycin with didanosine in six subjects did not appear to affect the pharmacokinetics of didanosine as compared with placebo.

Cetirizine: In healthy volunteers, coadministration of a 5-day regimen of azithromycin with cetirizine 20 mg at steady-state resulted in no pharmacokinetic interaction and no significant changes in the QT interval.

Rifabutin: Co-administration of azithromycin and rifabutin did not affect the serum concentrations of either drug. Neutropenia was observed in subjects receiving concomitant treatment of azithromycin and rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship to combination with azithromycin has not been established (see 4.8).

Ergotamine:

Due to the theoretical possibility of ergotism, the concurrent use of azithromycin with ergot derivatives is not recommended (see Section 4.4 Special warnings and special precautions for use).

Azithromycin does not interact significantly with the hepatic cytochrome P450 system. It is not believed to undergo the pharmacokinetic drug interactions as seen with erythromycin and other macrolides. Hepatic cytochrome P450 induction or inactivation via cytochrome-metabolite complex does not occur with azithromycin.

Pharmacokinetic studies have been conducted between azithromycin and the following drugs known to undergo significant cytochrome P450 mediated metabolism.

Atorvastatin:

Coadministration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter the plasma concentrations of atorvastatin (based on a HMG CoA-reductase inhibition assay).

Carbamazepine:

In a pharmacokinetic interaction study conducted in healthy volunteers, azithromycin had no significant effect on the plasma levels of carbamazepine or its active metabolite.

Cimetidine:

In a pharmacokinetic study investigating the effects of a single dose of cimetidine, given 2 hours before azithromycin, on the pharmacokinetics of azithromycin, no alteration of azithromycin pharmacokinetics was seen.

Coumarin-Type Oral Anticoagulants:

In a pharmacokinetic interaction study, azithromycin did not alter the anticoagulant effect of a single 15-mg dose of warfarin administered to healthy volunteers. There have been reports received in the post-marketing period of potentiated anticoagulation subsequent to coadministration of azithromycin and coumarin-type oral anticoagulants. Although a causal relationship has not been established, consideration should be given to the frequency of monitoring prothrombin time when azithromycin is used in patients receiving coumarin-type oral anticoagulants.

Cyclosporin:

In a pharmacokinetic study with healthy volunteers that were administered a 500 mg/day oral dose of azithromycin for 3 days and were then administered a single 10 mg/kg oral dose of cyclosporin, the resulting cyclosporin C_max and AUC_0-5 were found to be significantly elevated. Consequently, caution should be exercised before considering concurrent administration of these drugs. If coadministration of these drugs is necessary, cyclosporin levels should be monitored and the dose adjusted accordingly.

Efavirenz:

Coadministration of a 600 mg single dose of azithromycin and 400 mg efavirenz daily for 7 days did not result in any clinically significant pharmacokinetic interactions.

Fluconazole:

Coadministration of a single dose of 1200 mg azithromycin did not alter the pharmacokinetics of a single dose of 800 mg fluconazole. Total exposure and half-life of azithromycin were unchanged by the coadministration of fluconazole, however, a clinically insignificant decrease in C_max (18%) of azithromycin was observed.

Indinavir:

Coadministration of a single dose of 1200 mg azithromycin had no statistically significant effect on the pharmacokinetics of indinavir administered as 800 mg three times daily for 5 days.

Methylprednisolone:

In a pharmacokinetic interaction study in healthy volunteers, azithromycin had no significant effect on the pharmacokinetics of methylprednisolone.

Midazolam:

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

Nelfinavir:

Coadministration of azithromycin (1200 mg) and nelfinavir at steady state (750 mg three times daily) resulted in increased azithromycin concentrations. No clinically significant adverse effects were observed and no dose adjustment is required.

Rifabutin:

Coadministration of azithromycin and rifabutin did not affect the serum concentrations of either drug.

Neutropenia was observed in subjects receiving concomitant treatment of azithromycin and rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship to combination with azithromycin has not been established (see Section 4.8 Undesirable effects).

Sildenafil:

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

Terfenadine:

Pharmacokinetic studies have reported no evidence of an interaction between azithromycin and terfenadine. There have been rare cases reported where the possibility of such an interaction could not be entirely excluded; however there was no specific evidence that such an interaction had occurred.

Theophylline:

There is no evidence of a clinically significant pharmacokinetic interaction when azithromycin and theophylline are co-administered to healthy volunteers.

Triazolam:

In 14 healthy volunteers, coadministration of azithromycin 500 mg on Day 1 and 250 mg on Day 2 with 0.125 mg triazolam on Day 2 had no significant effect on any of the pharmacokinetic variables for triazolam compared to triazolam and placebo.

Trimethoprim/sulfamethoxazole:

Coadministration of trimethoprim/sulfamethoxazole DS (160 mg/800 mg) for 7 days with azithromycin 1200 mg on Day 7 had no significant effect on peak concentrations, total exposure or urinary excretion of either trimethoprim or sulfamethoxazole. Azithromycin serum concentrations were similar to those seen in other studies.

CYP3A4 substrates:

Even though azithromycin does not appear to inhibit the enzyme CYP3A4, caution is advised when combining the medicinal product with quinidine, cyclosporine, cisapride, astemizole, terfenadine, ergot alkaloids, pimozide or other medicinal products with a narrow therapeutic index predominantly metabolised by CYP3A4.

Cisapride:

Cisapride is metabolized in the liver by the enzyme CYP 3A4. Because macrolides inhibit this enzyme, concomitant administration of cisapride may cause the increase of QT interval prolongation, ventricular arrhythmias and torsade de pointes.

Astemizol and Alfentanil:

No data are available on interactions with astemizol, and alfentanil. Caution should be exercised with concomitant use of these agents and azithromycin in view of the described potentation of its effect during concomitant use of the macrolide antibiotic erythromycin.

4.6 Pregnancy and lactation

Pregnancy:

Animal reproduction studies have demonstrated that azithromycin crosses the placenta, but have revealed no evidence of teratogenic effects (see further section

5.3). There are no adequate and well controlled studies in pregnant women. Since animal studies are not always predictive of human response, azithromycin should be used during pregnancy only if adequate alternatives are not available.

Breastfeeding:

No data on secretion of azithromycin in breast milk are available, so that azithromycin should only be used in lactating women where adequate alternatives are not available.

Fertility

Animal data do not suggest an effect of the treatment of azithromycin on male and female fertility. Human data are lacking.

4.7 Effects on ability to drive and use machines

Dizziness has been reported, which may affect the ability to drive or operate machinery.

4.8 Undesirable effects

The table below lists the adverse reactions identified through clinical trial experience and post-marketing surveillance by system organ class and frequency. Adverse reactions identified from post-marketing experience are included in italics. The frequency grouping is defined using the following convention: Very common (>1/10); Common (> 1/100 to <1/10); Uncommon (>1/1,000 to <1/100); Rare (> 1/10,000 to <1/1,000); Very Rare (< 1/10,000); and Not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Adverse reactions possibly or probably related to azithromycin based on clinical trial experience and post-marketing surveillance:

very common > 1/10	common > 1/100 to < 1/10	uncommon > 1/1,000 to < 1/100	rare > 1/10,000 to <1/1,000	very rare < 1/10,000	not known frequency cannot be estimated from available data
Infections am	infestations
		Candidiasis Oral candidiasis Vaginal infection			Pseudomembranous colitis (see 4.4)

Blood and lymphatic system disorders
		Leukopenia Neutropenia					Thrombocytopeni a, Haemolytic anaemia
Immune system disorders
		Angioedema Hypersensitivity					Anaphylactic reaction (see section 4.4.)
Metabolism and nutrition disorders
	anorexia
Psychiatric disorders
		Nervousness		Agitation			Aggression Anxiety
Nervous system disorders
	Dizziness Headache Paraesthesia Dysgeusia		Hypoaesthesia Somnolence Insomnia				Syncope, Convulsion, Psychomotor hyperactivity, Anosmia, Ageusia, Parosmia, Exacerbation or aggravation of myasthenia gravis (see 4.4)
Eye disorders
	Visual impairment
Ear and labyrinth disorders
	Deafness	Hearing impaired, tinnitus		Vertigo
Cardiac disorders
		palpitations					Torsades de pointes (see Section 4.4) Arrhythmia including ventricular tachycardia.

Vascular disorders
					Hypotension
Gastrointestinal disorders
Diarrhoea, Abdominal pain, Nausea, Flatulence	Vomiting Dispepsia	Gastritits Constipation			Pancreatitis, Tongue discoloration
Hepatobiliary disorders
		Hepatitis	Hepatic function abnormal		Hepatic failure (see 4.4), which has rarely resulted in death, Hepatitis fulminant, Hepatic necrosis, Jaundice cholestatic
Skin and subcutaneous tissue c		isorders
	Rash, Pruritis	Stevens-Johnson syndrome, Photosensitivity reaction, Urticaria	allergic reactions including angioneurot ic oedema,		Toxic epidermal necrolysis, Erythema multiforme
Musculoskeletal and connective tissue disorders
	Arthralgia
Renal and urinary disorders
					Renal failure acute, Nephritis interstitial
General disorders and administration site conditions
	Fatigue	Chest pain Oedema Malaise Asthenia
Investigations
	Lymphocyte count decreased,	Aspartate aminotransferase increased, alanine			Electrocardiogra m QT prolonged (see section 4.4)

eosinophil count increased, blood bicarbonate decreased

aminotransferase increased, blood bilirubin increased, blood urea increased, blood creatinine increased, blood potassium abnormal

4.9 Overdose

The undesirable effects at doses in excess of those recommended were similar to those after normal doses. The typical symptoms of an overdose with macrolide antibiotics include reversible loss of hearing, severe nausea, vomiting and diarrhoea. In cases of overdose, administration of medicinal charcoal and general symptomatic treatment as well as measures to support vital functions are indicated where necessary.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antibacterials for systemic use ATC classification: J01FA10

Mechanism of action:

Azithromycin is a macrolide antibiotic belonging to the azalide group. The molecule is constructed by adding a nitrogen atom to the lactone ring of erythromycin A.

The mechanism of action of azithromycin is based upon the suppression of bacterial protein synthesis by binding to the ribosomal 50S sub-unit and inhibition of peptide translocation.

PK/PD relationship:

For azithromycin the AUC/MIC is the major PK/PD parameter correlating best with the efficacy of azithromycin

Mechanism of resistance:

Generally, the resistance of different bacterial species to macrolides has been reported to occur by three mechanisms associated with target site alteration, antibiotic modification, or altered antibiotic transport (efflux). The efflux in streptococci is conferred by the mef genes and results in a macrolide-restricted resistance (M phenotype). Target modification is controlled by erm encoded methylases.

A complete cross resistance exists among erythromycin, azithromycin, other macrolides and lincosamides for Streptococcus pneumoniae, beta-haemolytic streptococcus of group A, Enterococcus spp. and Staphylococcus aureus, including methicillin resistant Staphylococcus aureus (MRSA).

Penicillin susceptible Streptococcus pneumoniae are more likely to be susceptible to azithromycin than are penicillin resistant strains of Streptococcus pneumoniae. Methicillin resistant Staphylococcus aureus (MRSA) is less likely to be susceptible to azithromcyin than methicillin susceptible Staphylococcus aureus (MSSA).

Breakpoints

The EUCAST susceptibility breakpoints for typical bacterial pathogens are:

-    Staphylococcus spp ; susceptible < 1 mg/l; resistant > 2 mg/l

-    Haemophilus spp.: susceptible < 0,12 mg/l; resistant >4 mg/l

-    Streptococcus pneumoniae and Streptococcus A, B, C, G: susceptible <0.25 mg/l; resistant> 0.5 mg/l

-    Moraxella catarrhalis: < 0.5 mg/l; resistant > 0.5 mg/l

-    Neisseria gonorrhoeae: < 0.25 mg/l; resistant > 0.5 mg/l

Susceptibility

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Aerobic Gram-positive

Staphylococci MRSA, MRSE Aerobic Gram-negative

Escherichia coli Klebsiella spp.

Pseudomonas aeruginosa Anaerobic

Bacteroides fragilis group

° At the time of publication there are no current data. In primary literature, standard works and treatment guidelines susceptibility is assumed.

5.2 Pharmacokinetic properties

Absorption

Bioavailability after oral administration is approximately 37%. Peak concentrations in the plasma are attained 2-3 hours after taking the medicinal product.

Distribution

Orally administered azithromycin is widely distributed throughout the body.

In pharmacokinetic studies it has been demonstrated that the concentrations of azithromycin measured in tissues are noticeably higher (as much as 50 times) than those measured in plasma, which indicates that the agent strongly binds to tissues.

Binding to serum proteins varies according to concentration and ranges from 12% at 0.5 microgram/ml up to 52% at 0.05 microgram/ml. The mean volume of distribution at steady state (VVss) has been calculated to be 31.1 l/kg.

Elimination

Terminal plasma elimination half-life closely reflects the elimination half-life from tissues of 2-4 days.

Approximately 12% of an intravenously administered dose of azithromycin is excreted unchanged in urine within the following three days. Particularly high concentrations of unchanged azithromycin have been found in human bile. In the same source, 10 metabolites were also detected, which were formed through N- and O-demethylation, hydroxylation of desosamine- and aglycone rings and degradation of cladinose conjugate. Comparison of the results of liquid chromatography and microbiological analyses has shown that the metabolites of azithromycin are not microbiologically active.

Pharmacokinetics in Special populations:

Renal Insufficiency:

Following a single oral dose of azithromycin 1 g, mean C_max and AUC_0-120 increased by 5.1 % and 4.2% respectively, in subjects with mild to moderate renal impairment (glomerular filtration rate of 10-80 ml/min) compared with normal renal function (GFR>80ml/min). In subjects with severe renal impairment, the mean C_max and AUC_0-i₂₀ increased 61% and 35% respectively compared to normal.

Hepatic insufficiency:

In patients with mild to moderate hepatic impairment, there is no evidence of a marked change in serum pharmacokinetics of azithromycin compared to normal hepatic function. In these patients, urinary recovery of azithromycin appears to increase perhaps to compensate for reduced hepatic clearance.

Elderly:

The pharmacokinetics of azithromycin in elderly men was similar to that of young adults; however, in elderly women, although higher peak concentrations (increased by 30-50%) were observed, no significant accumulation occurred.

In elderly volunteers (>65 years), higher (29 %) AUC values were always observed after a 5-day course than in younger volunteers (<45 years). However, these differences are not considered to be clinically relevant; no dose adjustment is therefore recommended.

Infants, toddlers, children and adolescents:

Pharmacokinetics has been studied in children aged 4 months - 15 years taking capsules, granules or suspension. At 10 mg/kg on day 1 followed by 5 mg/kg on days 2-5, the C_max achieved is slightly lower than in adults, with 224 pg/l in children aged 0.6-5 years and after 3 days dosing, and 383 pg/l in those aged 6-15 years. The halflife of 36 h in the older children was within the expected range for adults.

5.3 Preclinical safety data

In animal tests in which the dosages used amounted to 40 times the clinical therapeutic dosages, azithromycin was found to have caused reversible phospholipidosis, but as a rule, no true toxicological consequences were observed which were associated with this.

Electrophysiological investigations have shown that azithromycin prolongs the QT interval.

Carcinogenic potential:

Long-term studies in animals have not been performed to evaluate carcinogenic potential .

Mutagenic potential:

There was no evidence of a potential for genetic and chromosome mutations in in-vivo and in-vitro test models.

Reproductive toxicity:

In animal studies of the embryotoxic effects of the substance, no teratogenic effect was observed in mice and rats. In rats, azithromycin dosages of 100 and 200 mg/kg bodyweight/day led to mild retardation of foetal ossification and maternal weight gain.

In peri- and post-natal studies in rats, mild retardation was observed following treatment with 50 mg/kg/day azithromycin and above.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

-    Pregelatinised starch

-    Crospovidone

-    Calcium hydrogen phosphate, anhydrous

-    Sodium laurilsulfate

-    Magnesium stearate

Coating:

-    hypromellose,

-    titanium dioxide (E171)

-    lactose monohydrate

-    triacetin

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

3 years

6.4    Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5    Nature and contents of container

Blister: PVC/Aluminium

Pack sizes: 3 film-coated tablets.

6.6    Special precautions for disposal

No special requirements <for disposal

7    MARKETING AUTHORISATION HOLDER

Glenmark Pharmaceuticals Europe Limited Laxmi House, 2B Draycott Avenue,

Kenton, Middlesex, HA3 0BU,

United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 25258/0093

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 21/06/2012

10 DATE OF REVISION OF THE TEXT

26/09/2014