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CLAMELLE 500MG TABLETS

Active substance(s): AZITHROMYCIN DIHYDRATE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Clamelle ® 500mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 500 mg azithromycin as dihydrate.
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Film-coated tablet
Pale blue, oblong, biconvex film-coated tablets, with imprint PLIVA on one side and
500 on the other side.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Treatment of confirmed asymptomatic Chlamydia trachomatis genital
infection in individuals aged 16 years and over and the epidemiological
treatment of their sexual partners.
Consideration should be given to official guidance on the appropriate use of
antibacterial agents.

4.2

Posology and method of administration
Posology
A single 1g (2 x 500mg tablets) dose.
Elderly
It is not necessary to alter the dose in elderly.

4.3

Contraindications
Hypersensitivity to the active substance or any macrolide antibiotic, or any of
the excipients listed in section 6.1.
Relative for Azithromycin sold as a Pharmacy Medicine.
Symptomatic infection.
Symptoms suggestive of other STIs e.g. any unusual genital or anal swellings
or lesions.
Children aged under 16 years.
Renal or hepatic impairment.
History of cardiac disease.
Individuals receiving ciclosporin, digoxin, ergotamine, terfenadine,
theophylline, disopyramide, rifabutin and coumarin anticoagulant therapy,
such as warfarin.
Individuals receiving azithromycin for treatment of other infections.
Pregnancy and breast feeding.

4.4

Special warnings and precautions for use
As with erythromycin and other macrolides, rare serious allergic reactions
including angioneurotic oedema and anaphylaxis (rarely fatal), and Drug
Reaction with Eosinophilia and Systemic Symptoms (DRESS) have been
reported with azithromycin (see section 4.8).
Vomiting: To reduce the risk of vomiting, advise the individual to take the
dose before bed and at least 2hrs after food or drink. If vomiting occurs after
taking the dose pharmacist advice should be sought.
Oral contraception: if vomiting or diarrhoea occurs whilst taking Clamelle
500mg tablets refer to the oral contraceptive’s instructions for measures to
minimise the risk of contraception failure.
Diarrhoea/pseudomembranous colitis caused by Clostridium difficile has
occurred. Due to this, patients with diarrhoea should be carefully monitored.
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:
In individuals receiving azithromycin and antacids, azithromycin should be
taken at least 1 hour before or 2 hours after the antacid.
Nelfinavir:
Co-administration of 1200 mg azithromycin and steady state nelfinavir (750
mg 3 times daily) resulted in a mean decrease of AUC of 16% for nelfinavir,
an increase of AUC of azithromycin of 113%, and an increase of Cmax of

136%. Dose adjustment is not necessary, but the increased potential for known
side-effects of azithromycin should be considered.
CYP3A4:
Although azithromycin does not seem to inhibit the enzyme CYP3A4,
possible inhibition of this enzyme cannot be excluded. Consequently, caution
is advised when given in combination with pimozide and other drugs with a
narrow therapeutic window and a metabolism catalysed by CYP3A4.
Due to interaction, Clamelle 500mg tablets are contraindicated if individual is
concomitantly taking any of the following medications (see also section 4.3):
Ciclosporin:
Some of the related macrolide antibiotics interfere with the metabolism of
ciclosporin. In the absence of conclusive pharmacokinetic studies or data
investigating the potential for an interaction between azithromycin and
ciclosporin, Clamelle 500mg tablets are contraindicated.
Coumarin-Type Oral Anticoagulants:
In a pharmacodynamic interaction study, azithromycin did not alter the
anticoagulant effect of a single 15mg dose of warfarin administered to healthy
volunteers. There have been reports received in the post-marketing period of
potentiated anticoagulation subsequent to co-administration of azithromycin
and coumarin-type oral anticoagulants. Although a causal relationship has not
been established, Clamelle 500mg tablets are contraindicated.
Digoxin:
Some of the macrolide antibiotics have been reported to impair the metabolism
of digoxin (in the gut) in some individuals. Since there is the possibility of
raised digoxin levels, Clamelle 500mg tablets are contraindicated.
Disopyramide:
Some of the related macrolide antibiotics have been reported to increase serum
disopyramide levels, which can result in ventricular fibrillation.
Ergot derivatives:
Because of the theoretical possibility of ergotism, azithromycin and ergot
derivatives should not be co-administered.
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.
Terfenadine:
There is a theoretical risk of serious dysrhythmias due to prolongation of QTc
interval.
Theophylline:

Theophylline levels may be increased in patients taking azithromycin.
4.6

Pregnancy and lactation
Clamelle 500mg tablets are contraindicated during pregnancy and lactation.

4.7

Effects on ability to drive and use machines
Azithromycin has the potential to cause dizziness and somnolence. If affected,
the individual should not drive or operate machinery.

4.8

Undesirable effects
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:

System Organ
Class
Blood and
lymphatic
system
disorders

Infections and
infestations

Immune system
disorders

Very
Common

Common

Uncommon

Rare

> 1/10

≥ 1/100 to <
1/10

≥ 1/1,000 to
< 1/100

≥ 1/10,000
to
< 1/1,000

Leukopenia,
neutropenia,
eosinophilia
Candidiasis, oral
candidiasis,
vaginal
infection,
pneumonia,
fungal infection,
bacterial
infection,
pharyngitis,
gastroenteritis,
respiratory
disorder,
rhinitis.
Angioedema,
hypersensitivity

Unknown

Thrombocytopenia,
haemolytic anaemia

Pseudomembranous
colitis (see section
4.4)

Anaphylactic
reaction (see

System Organ
Class

Very
Common

Common

Uncommon

Rare

> 1/10

≥ 1/100 to <
1/10

≥ 1/1,000 to
< 1/100

≥ 1/10,000
to
< 1/1,000

Unknown

section 4.4)
Metabolism
and nutrition
disorder

Anorexia
Nervousness,
insomnia

Psychiatric
disorders

Nervous system
disorders

Dizziness,
Headache,
Hypoaesthesia,
Paraesthesia, somnolence,
dysgeusia

Eye disorders

Visual
impairment

Ear and
labyrinth
disorders

Deafness

Cardiac
disorders

Vascular
disorders
Respiratory,
thoracic and
mediastinal
disorders
Diarrhoea,
abdominal
Vomiting,
Gastrointestinal pain,
nausea,
dyspepsia,
disorders
flatulence,

Aggression,
Agitation,
anxiety, delirium,
restlessness
hallucination
Syncope,
convulsion,
psychomotor
hyperactivity,
anosmia, ageusia,
parosmia
Myasthenia gravis
(see Section 4.4)

Hearing
impairment
including
tinnitus,
Ear disorder,
Vertigo

Palpitations

Torsades de pointes
(see section 4.4),
arrhythmia (see
section 4.4)
including
ventricular
tachycardia.
Electrocardiogram
QT prolonged (see
section 4.4

Hot flush

Hypotension

Dyspnoea,
Epistaxis
Constipation,
gastritis
dysphagia,
abdominal
distension, dry
mouth,

Pancreatitis, tongue
discolouration

System Organ
Class

Very
Common

Common

Uncommon

Rare

> 1/10

≥ 1/100 to <
1/10

≥ 1/1,000 to
< 1/100

≥ 1/10,000
to
< 1/1,000

Unknown

eructation,
mouth
ulceration.
salivary
hypersecretion.

Hepatobiliary
disorders

Skin and
subcutaneous
tissue disorders

Musculoskeletal
and connective
tissue disorders
Renal and
urinary
disorders
Reproductive
system and
breast
disorders
General
disorders and
administration
site conditions
Investigations

Hepatitis

Rash,
pruritus,

Arthralgia

Stevens-Johnson
syndrome,
Photosensitivity
reaction,
urticaria,
dermatitis, dry
skin,
hyperhidrosis
Osteoarthritis,
myalgia, back
pain, neck pain
Dysuria, renal
pain
Metrorrhagia,
testicular
disorder

Fatigue

Lymphocyte
count
decreased,
eosinophil
count
increased,
blood
bicarbonate
decreased,
basophils

face edema,
chest pain,
pyrexia,
peripheral pain,
oedema,
malaise, asthenia
Aspartate
aminotransferase
increased,
alanine
aminotransferase
increased, blood
bilirubin
increased, blood
urea increased,
blood creatinine

Hepatic
function
abnormal,
jaundice
cholestatic

Hepatic failure
(which has rarely
resulted in death)
(see section 4.4),
hepatitis fulminant,
hepatic necrosis,
toxic epidermal
necrolysis,
erythema
multiforme, Drug
reaction with
eosinophilia and
systemic symptoms
(DRESS)

Renal failure acute,
nephritis interstitial

System Organ
Class

Very
Common

Common

Uncommon

Rare

> 1/10

≥ 1/100 to <
1/10

≥ 1/1,000 to
< 1/100

≥ 1/10,000
to
< 1/1,000

increased,
monocytes
increased,
neutrophils
increased

increased, blood
potassium
abnormal, blood
alkaline
phosphatase
increased,
chloride
increased,
glucose
increased,
platelets
increased,
hematocrit
decreased,
bicarbonate
increased,
abnormal
sodium
Post procedural
complications

Injury and
poisoning

Unknown

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal
product is important. It allows continued monitoring of the benefit/risk balance
of the medicinal product. Healthcare professionals are asked to report any
suspected adverse reactions via the Yellow Card Scheme; website:
www.mhra.gov.uk/yellowcard
4.9

Overdose
Adverse events experienced in higher than recommended doses were similar
to those seen at normal doses. In the event of overdosage, general
symptomatic and supportive measures are indicated as required.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
ATC code: J01FA10
Mechanism of Action:

Azithromycin is an azalide, a subclass of the macrolide antibiotics. The mode
of action of azithromycin is based upon suppression of bacterial RNAdependent protein synthesis, by reversibly binding to the 23S ribosomal RNA
in the 50S subunit of the ribosomes.
Mechanism of resistance:
Stable resistance to azithromycin has not been described for Chlamydia
trachomatis.
In vitro evidence to date indicates that whilst certain point mutations in the
23S rRNA gene may lead to decreased sensitivity to macrolides, including
azithromycin, such strains seem to carry a prohibitive physiological cost which
may make their maintenance in the wild (i.e. dissemination in clinical cases)
presently unlikely.
Breakpoints:
Chlamydiae are obligate intra-cellular pathogens. Determination of sensitivity/
resistance to antibiotics in vitro requires a cell culture technique which is
inappropriate for routine monitoring of resistance. The complexity of the
chlamydial life cycle is such that a universally agreed method for determining
minimal inhibitory concentrations and breakpoints of antibiotics is not
available. Comparative activity of antibiotics on chlamydia can be compared
within a laboratory using the same method. Qualitative results can be
compared between laboratories, but caution is required when applying
numerical values to comparative data in this setting.
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.
Stable resistance to azithromycin has not been described for Chlamydia
trachomatis.

5.2

Pharmacokinetic properties
Absorption
Azithromycin is well absorbed following oral administration and rapidly
passes from serum to tissues and various organs. After a single 500 mg oral
dose of azithromycin, 37% of the drug is absorbed, and a peak plasma
concentration (0.41µg/ml) is achieved in 2-3 hours.
Distribution
Azithromycin is widely distributed throughout the body, achieving high tissue
concentration (up to 50 times higher than observed concentration in plasma).
Volume of distribution is approximately 31 l/kg.
Azithromycin is rapidly distributed to a wide range of tissues and achieves
high tissue concentrations ranging between 1 and 9µg/ml, depending on the
tissue. Therapeutic concentrations of azithromycin are maintained in tissues
for five to seven days after the ingestion of last oral dose.

Azithromycin achieves very high concentrations in phagocytic cells, which
migrate to infected sites.
Elimination
Plasma terminal elimination half-life closely reflects the tissue depletion halflife of 2-4 days. Biliary excretion of azithromycin is a major route of
elimination. Approximately 50% biliary excretion is in the form of unchanged
compound. The other half are 10 metabolites formed by N- and Odemethylation, by hydroxylation of desosamine and aglycone rings, and by
cleavage of the cladinose conjugate. Comparison of HPLC and
microbiological assay suggests that metabolites play no part in the
microbiological activity of azithromycin. Approximately 6% of administered
dose is excreted in urine.
Elderly
In elderly volunteers (> 65 years), slightly higher (30%) AUC values were
seen than in younger volunteers (< 45 years), but this is not considered
clinically significant and hence no dose adjustment is recommended.
5.3

Preclinical safety data
In higher-dose animal studies azithromycin has been noted to cause reversible
phospholipidosis, generally without discernible toxicological consequences.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Core:
Calcium hydrogen phosphate, anhydrous
Hypromellose
Maize starch
Pregelatinised starch
Microcrystalline cellulose
Sodium laurylsulfate
Magnesium stearate
Film-coating:
Hypromellose
Colour Indigotin (E132)
Titanium dioxide (E171)
Polysorbate 80
Talc

6.2

Incompatibilities
Not applicable

6.3

Shelf life
36 months

6.4

Special precautions for storage
Store below 25 °C in a dry place, in original packaging.

6.5

Nature and contents of container
Blisters (PVC/Al foil) packed in a carton box containing 2 tablets.

6.6

Special precautions for disposal
There are no special instructions for disposal.

7

MARKETING AUTHORISATION HOLDER
Actavis Group PTC ehf
Reykjavíkurvegi 76-78
220 Hafnarfjordur
Iceland.

8

MARKETING AUTHORISATION NUMBER(S)
PL 30306/0296

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
17 May 2004

10

DATE OF REVISION OF THE TEXT
16/08/2016

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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