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AZALIA 75 MICROGRAM FILM-COATED TABLETS

Active substance(s): DESOGESTREL / DESOGESTREL

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Azalia 75 microgram film-coated tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

One film-coated tablet contains 75 microgram desogestrel.
Excipient with known effect: 52.34 mg lactose (as lactose monohydrate).
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Film-coated tablet.
White or almost white, round, biconvex film-coated tablets of about 5,5 mm in diameter,
with a sign “D” on one side and “75” on the other side.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Contraception

4.2

Posology and method of administration

Posology
Tablets must be taken every day at about the same time so that the interval between two
tablets always is 24 hours. The first tablet should be taken on the first day of menstrual
bleeding. Thereafter one tablet each day is to be taken continuously, without taking any notice
on possible bleeding. A new blister is started directly the day after the previous one.
How to start Azalia
No preceding hormonal contraceptive use [in the past month]
Tablet-taking has to start on day 1 of the woman's natural cycle (day 1 is the first day of her
menstrual bleeding). Starting on days 2-5 is allowed, but during the first cycle a barrier
method is recommended for the first 7 days of tablet-taking.

Following first-trimester abortion
After first-trimester abortion it is recommended to start immediately. In that case there is no
need to use an additional method of contraception.
Following delivery or second-trimester abortion
Contraceptive treatment with Azalia after delivery can be initiated before the menstruations
have returned. If more than 21 days have elapsed pregnancy ought to be ruled out and an
additional method of contraception should be used for the first week.
For additional information for breastfeeding women see Section 4.6.
How to start Azalia when changing from other contraceptive methods
Changing from a combined hormonal contraceptive (combined oral contraceptive (COC),
vaginal ring, or transdermal patch)
The woman should start Azalia preferably on the day after the last active tablet (the last tablet
containing the active substances) of her previous COC or on the day of removal of her vaginal
ring or transdermal patch. In these cases, the use of an additional contraceptive is not
necessary. Not all contraceptive methods may be available in all EU countries.
The woman may also start at the latest on the day following the usual tablet-free, patch-free,
ring-free, or placebo tablet interval of her previous combined hormonal contraceptive, but
during the first 7 days of tablet-taking an additional barrier method is recommended.
Changing from a progestogen-only-method (minipill, injection, implant) or from a
progestogen-releasing intrauterine system (IUS)
The woman may switch any day from the minipill (from an implant or the IUS on the day of
its removal, from an injectable when the next injection would be due).
Management of missed tablet
Contraceptive protection may be reduced if more than 36 hours have elapsed between two
tablets. If the user is less than 12 hours late in taking any tablet, the missed tablet should be
taken as soon as it is remembered and the next tablet should be taken at the usual time. If she
is more than 12 hours late, she should use an additional method of contraception for the next 7
days. If tablets were missed in the first week and intercourse took place in the week before the
tablets were missed, the possibility of a pregnancy should be considered.
Advice in case of gastrointestinal disturbances

In case of severe gastro-intestinal disturbance, absorption may not be complete and
additional contraceptive measures should be taken. If vomiting occurs within 3-4
hours after tablet-taking, absorption may not be complete. In such an event, the advice
concerning missed tablets, as given in subsection “Management of missed tablet” is
applicable.
Treatment surveillance
Before prescription, a thorough case history should be taken and a thorough gynaecological
examination is recommended to exclude pregnancy. Bleeding disturbances, such as
oligomenorrhoea and amenorrhoea should be investigated before prescription. The interval
between check-ups depends on the circumstances in each individual case. If the prescribed
product may conceivably influence latent or manifest disease (see section 4.4), the control
examinations should be timed accordingly.
Despite the fact that Azalia is taken regularly, bleeding disturbances may occur. If bleeding is
very frequent and irregular, another contraceptive method should be considered. If the
symptoms persist, an organic cause should be ruled out.

Management of amenorrhoea during treatment depends on whether or not the tablets have
been taken in accordance with the instructions and may include a pregnancy test.
The treatment should be stopped if a pregnancy occurs.
Women should be advised that Azalia does not protect against HIV (AIDS) and other sexually
transmitted diseases.
Paediatric population
The safety and efficacy of desogestrel in adolescents below 18 years has not yet been
established. No data are available.
Method of administration
For oral administration.

4.3




Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
Active venous thromboembolic disorder.
Presence or history of severe hepatic disease as long as liver function values have not
returned to normal.
Known or suspected sex-steroid sensitive malignancies.
Undiagnosed vaginal bleeding.




4.4

Special warnings and precautions for use

If any of the conditions/risk factors mentioned below is present, the benefits of progesterone
use should be weighed against the possible risks for each individual woman and discussed
with the woman before she decides to start with {(Invented) name}. In the event of
aggravation, exacerbation, or first appearance of any of these conditions, the woman should
contact her physician. The physician should then decide on whether the use of {(Invented)
name} should be discontinued.
The risk for breast cancer increases in general with increasing age. During the use of
combined oral contraceptives (COCs) the risk of having breast cancer diagnosed is slightly
increased. This increased risk disappears gradually within 10 years after discontinuation of
COC use and is not related to the duration of use, but to the age of the woman when using the
COC. The expected number of cases diagnosed per 10 000 women who use COCs (up to 10
years after stopping) relative to never users over the same period have been calculated for the
respective age groups and is presented in the table below.
Age category

Expected cases COC-users

16-19 years
20-24 years
25-29 years
30-34 years
35-39 years
40-44 years

4.5
17.5
48.7
110
180
260

Expected cases nonusers
4
16
44
100
160
230

The risk in progestogen-only contraceptives (POCs), such as {(Invented) name} is possibly of
similar magnitude as that associated with COCs. However, for POCs the evidence is less
conclusive. Compared to the risk of getting breast cancer ever in life, the increased risk
associated with COCs is low. The cases of breast cancer diagnosed in COC users tend to be
less advanced than in those who have not used COCs. The increased risk in COC users may
be due to an earlier diagnosis, biological effects of the pill or a combination of both.
Since a biological effect cannot be excluded, an individual benefit/risk assessment should be
made in women with pre-existing breast cancer and in women in whom breast cancer is
diagnosed while using desogestrel-only pill.
Since a biological effect of progestogens on liver cancer cannot be excluded an individual
benefit/risk assessment should be made in women with liver cancer.
When acute or chronic disturbances of liver function occur the woman should be referred to a
specialist for examination and advice.
Epidemiological investigations have associated the use of COCs with an increased incidence
of venous thromboembolism (VTE, deep venous thrombosis and pulmonary embolism).
Although the clinical relevance of this finding for desogestrel used as a contraceptive in the
absence of an oestrogenic component is unknown, {(Invented) name} should be discontinued
in the event of a thrombosis. Discontinuation of {(Invented) name} should also be considered
in case of long-term immobilisation due to surgery or illness. Women with a history of
thromboembolic disorders should be aware of the possibility of a recurrence.
Although progestogens may have an effect on peripheral insulin resistance and glucose
tolerance, there is no evidence for a need to alter the therapeutic regimen in diabetics using
progestogen-only pills. However, diabetic patients should be carefully observed during the
first months of use.
If a sustained hypertension develops during the use of {(Invented) name}, or if a significant
increase in blood pressure does not adequately respond to antihypertensive therapy,
discontinuation with the use of {(Invented) name} should be considered.
Treatment with {(Invented) name} leads to decreased estradiol serum levels, to a level
corresponding with the early follicular phase. It is as yet unknown whether the decrease has
any clinically relevant effect on bone mineral density.
The protection with traditional progestogen-only pills against ectopic pregnancies is not as
good as with combined oral contraceptives, which has been associated with the frequent
occurrence of ovulations during the use of progestogen-only pills. Despite the fact that
{(Invented) name} consistently inhibits ovulation, ectopic pregnancy should be taken into
account in the differential diagnosis if the woman gets amenorrhoea or abdominal pain.
Chloasma may occasionally occur, especially in women with a history of chloasma
gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or
ultraviolet radiation whilst taking {(Invented) name}.
The following conditions have been reported both during pregnancy and during sex steroid
use, but an association with the use of progestogens has not been established: jaundice and/or
pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus;
haemolytic uraemic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis-related
hearing loss; (hereditary) angioedema.
Medical examination/consultation

Prior to the initiation or reinstitution of {(Invented) name} a complete medical history
(including family history) should be taken and pregnancy must be ruled out. Blood pressure
should be measured and a physical examination should be performed, guided by the contraindications (see section 4.3) and warnings (see section 4.4). The woman should also be
instructed to carefully read the user leaflet and to adhere to the advice given. The frequency
and nature of examinations should be based on established practice guidelines and be adapted
to the individual woman.
Women should be advised that {(Invented) name} does not protect against HIV infections
(AIDS) and other sexually transmitted diseases.
Reduced efficacy
The efficacy of {(Invented) name}” may be reduced in the event of e.g. missed hormonecontaining tablets (see section 4.2), gastro-intestinal disturbances during hormone-containing
tablet taking (see section 4.2) or concomitant medication (see section 4.5).
Changes in vaginal bleeding pattern
During the use of a progestogen-only contraceptive, vaginal bleeding may become more
frequent or of longer duration in some women, whereas in others bleeding may become
incidental or be totally absent. These changes are often a reason for the woman to reject the
method or to be non-compliant. Acceptance of bleeding pattern can be improved by offering
women who have chosen to use {(Invented) name} careful counselling on this point.
Evaluation of vaginal bleeding should be done on an ad hoc basis and may include
examination to exclude malignancy or pregnancy.
{(Invented) name} film-coated tablets contain 52.34 mg lactose (as lactose monohydrate).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or
glucose-galactose malabsorption should not take this medicine.

4.5

Interaction with other medicinal products and other forms of interaction

Interactions between hormonal contraceptives and other medicinal products may lead to
breakthrough bleeding and/or contraceptive failure. The following interactions have been
reported in the literature (mainly with combined contraceptives but occasionally also with
progestogen-only contraceptives).
Hepatic metabolism: Interactions can occur with medicinal products that induce microsomal
enzymes, which can result in increased clearance of sex hormones (such as hydantoins (e.g.
phenytoin), barbiturates (e.g. phenobarbital), primidone, carbamazepine, rifampicin, and
possibly also for oxcarbazepine, topiramate, rifabutin, felbamate, ritonavir, nelfinavir,
griseofulvin and products containing St. John’s wort (Hypericum perforatum)).
Maximal enzyme induction is not seen for 2-3 weeks, but may then be sustained for at least 4
weeks after the cessation of drug therapy. Women on treatment with any of these medicinal
products should temporarily use a barrier method in addition to Azalia.
With microsomal enzyme-inducing drugs, the barrier method should be used during the time
of concomitant drug administration and for 28 days after their discontinuation. For women on
long-term therapy with hepatic enzyme inducers a non-hormonal method of contraception
should be considered.

During treatment with medical charcoal, the absorption of the steroid in the tablet may be
reduced and thereby the contraceptive efficacy. Under these circumstances, the advice as
given for missed tablets in section 4.2. is applicable.
Hormonal contraceptives may interfere with the metabolism of other drugs. Accordingly,
plasma and tissue concentrations may either increase (e.g. cyclosporine) or decrease.
Note: The prescribing information of concomitant medications should be consulted to identify
potential interactions.
Laboratory tests
Data obtained with COCs have shown that contraceptive steroids may influence the results of
certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal
function, serum levels of (carrier) proteins, e.g. corticosteroid binding globulin and
lipid/lipoprotein fractions, parameters of carbohydrate metabolism and parameters of
coagulation and fibrinolysis. The changes generally remain within the normal range. To what
extent this also applies to progestogen-only contraceptives is not known.

4.6

Fertility, pregnancy and lactation

Pregnancy
Azalia is not indicated during pregnancy. If pregnancy occurs during treatment with Azalia,
further intake should be stopped.
Animal studies have shown that very high doses of progestogenic substances may cause
masculinisation of female foetuses.
Extensive epidemiological studies have revealed neither an increased risk of birth defects in
children born to women who used COCs prior to pregnancy, nor a teratogenic effect when
OCs were taken inadvertently during early pregnancy. Pharmacovigilance data collected with
various desogestrel-containing COCs also do not indicate an increased risk.
Breast-feeding
Desogestrel does not influence the production or the quality (protein, lactose, or fat
concentrations) of breast milk. However, small amounts of etonogestrel, (the metabolite of
desogestrel) are excreted in the breast milk. As a result, 0.01-0.05 microgram etonogestrel per
kg body weight per day may be ingested by the child (based on an estimated milk ingestion of
150 ml/kg/day).
Limited long-term follow-up data are available on children, whose mothers started using
Azalia during the 4th to 8th week post-partum. They were breast-fed for 7 months and followed
up to 1.5 years (n=32) or to 2.5 years (n=14) of age. Evaluation of growth and physical and
psychomotor development did not indicate any differences in comparison to nursing infants,
whose mother used a copper-IUD.
Based on the available data, Azalia may be used during lactation. The development and
growth of a nursing infant, whose mother uses Azalia, should, however, be carefully
observed.

4.7

Effects on ability to drive and use machines
Desogestrel has no or neglible influence on the ability to drive and use machines.

4.8

Undesirable effects

The most commonly reported undesirable effect in the clinical trials is bleeding irregularity.
Some kind of bleeding irregularity has been reported in up to 50% of women using
desogestrel. Since desogestrel causes ovulation inhibition close to 100%, in contrast to other
progestogen-only pills, irregular bleeding is more common than with other progestogen-only
pills. In 20-30% of the women, bleeding may become more frequent, whereas in another 20%
bleeding may become less frequent or totally absent. Vaginal bleeding may also be of longer
duration.
After a couple of months of treatment, bleedings tend to become less frequent. Information,
counselling and a bleeding diary can improve the woman's acceptance of the bleeding pattern.
The most commonly reported other undesirable effects in the clinical trials with desogestrel
>2.5%) were acne, mood changes, breast pain, nausea and weight increase. The undesirable
effects are mentioned in the table below.
All undesirable effects are listed by system organ class and frequency; common (≥1/100 to
<1/10), uncommon (≥1/1,000 to <1/100) and rare (≥1/10,000 to <1/1,000).
System Organ
Class
(MedDRA)*

Frequency of adverse reactions
Uncommon
Rare
Common
≥ 1/100 to <1/10
≥ 1/1,000 to <
≥1/10,000 to
1/100
<1/1,000

Infections and
infestations
Psychiatric
disorders

Vaginal infection

Nervous system
disorders
Eye disorders
Gastrointestinal
disorders
Skin and
subcutaneous tissue
disorders
Reproductive
system and breast
disorders

Mood altered,
Libido decreased,
Depressed mood
Headache

Nausea

Contact lens
intolerance
Vomiting

Acne

Alopecia

Breast pain,
Menstruation
irregular,
Amenorrhoea

Dysmenorrhoea,
Ovarian cyst

General disorders
and administration
site condition
Investigations
Weight increased
*MedDRA version 16.1

Fatigue

Rash,
Urticaria,
Erythema nodosum

Breast discharge may occur during use of Azalia. On rare occasions, ectopic pregnancies have
been reported (see section 4.4). In addition, (aggravation of) angioedema and/or aggravation
of hereditary angioedema may occur (see section 4.4).
In women using (combined) oral contraceptives a number of (serious) undesirable effects
have been reported. These include venous thromboembolic disorders, arterial thromboembolic
disorders, hormone-dependent tumours (e.g. liver tumours, breast cancer), and chloasma,
some of which are discussed in more detail in section 4.4.
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
"www.mhra.gov.uk/yellowcard".

4.9

Overdose
There have been no reports of serious deleterious effects from overdose. Symptoms
that may occur in this case are nausea, vomiting and, in young girls, slight vaginal
bleeding. There are no antidotes and further treatment should be symptomatic.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Hormonal contraceptives for systemic use, Progestogens, ATC
code: G03AC09
Azalia film-coated tablet is a progestogen-only pill, which contains the progestogen
desogestrel.
Mechanism of action
Like other progestogen-only pills, Azalia is best suited for use during breast feeding and for
women who may not or do not want to use oestrogens. In contrast to traditional progestogenonly pills, the contraceptive effect of Azalia is achieved primarily by inhibition of ovulation.
Other effects include increased viscosity of the cervical mucus.
When studied for 2 cycles, using a definition of ovulation as a progesterone level greater than
16 nmol/L for 5 consecutive days, the ovulation incidence was found to be 1% (1/103) with a
95% confidence interval of 0.02%-5.29% in the intention-to-treat group (user and method
failures). Ovulation inhibition was achieved from the first cycle of use. In this study, when
desogestrel was discontinued after 2 cycles (56 continuous days), ovulation occurred on
average after 17 days (range 7-30 days).
In a comparative efficacy trial (which allowed a maximum time of 3 hours for missed pills)
the overall intention-to-treat Pearl-Index found for desogestrel was 0.4 (95% confidence
interval 0.09-1.20), compared to 1.6 (95% confidence interval 0.42-3.96) for 30 μg
levonorgestrel.

The Pearl-Index for desogestrel is comparable to the one historically found for combined OCs
in the general OC-using population.
Treatment with desogestrel leads to decreased estradiol levels, to a level corresponding to the
early follicular phase. No clinically relevant effects on carbohydrate metabolism, lipid
metabolism and haemostasis have been observed.
Paediatric population
No clinical data on efficacy and safety are available in adolescents below 18 years.

5.2

Pharmacokinetic properties

Absorption
After oral dosing of desogestrel is rapidly absorbed and converted into etonogestrel. Under
steady-state conditions, peak serum levels are reached 1.8 hours after tablet-intake and the
absolute bioavailability of etonogestrel is approximately 70%.
Distribution
Etonogestrel is 95.5-99% bound to serum proteins, predominantly to albumin and to a lesser
extent to sex hormone binding globuline (SHGB).
Biotransformation
Desogestrel is metabolised via hydroxylation and dehydrogenation to the active metabolite
etonogestrel. Etonogestrel is metabolised via sulphate and glucuronide conjugation.
Elimination
Etonogestrel is eliminated with a mean half-life of approximately 30 hours, with no difference
between single and multiple dosing. Steady-state levels in plasma are reached after 4-5 days.
The serum clearance after i.v. administration of etonogestrel is approximately 10 l per hour.
Excretion of etonogestrel and its metabolites either as free steroid or as conjugates, is with
urine and faeces (ratio 1.5:1). In lactating women, etonogestrel is excreted in breast milk with
a milk/serum ratio of 0.37-0.55. Based on these data and an estimated milk intake of
150 ml/kg/day, 0.01-0.05 microgram etonogestrel maybe ingested by the infant.

5.3

Preclinical safety data
Toxicological studies did not reveal any effects other than those, which can be
explained from the hormonal properties of desogestrel.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Tablet core:
Lactose monohydrate,
Potato starch,
Povidone K-30,
Silica, colloidal anhydrous,
Stearic acid,
all-rac-α-Tocopherol
Tablet coat:
Poly[vinyl alcohol];
Titanium dioxide, E171;
Macrogol 3000;
Talc

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
Two years.

6.4

Special precautions for storage

Store in the original package in order to protect from light and moisture.
This medicinal product does not require any special temperature storage conditions.
6.5

Nature and contents of container

Azalia film-coated tablets are packaged in a blister made of transparent, hard PVC/PVDCAluminium foil. Each blister is placed in a laminated aluminium sachet. The blisters in
the sachets are packed into a folded carton box with a patient leaflet and etui storing bag.
Pack sizes: 1x28, 3x28, 6x28, 13x28 film-coated tablets.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with
local requirements

7

MARKETING AUTHORISATION HOLDER
Gedeon Richter Plc.

Gyömrői út 19-21
1103, Budapest Hungary

8

MARKETING AUTHORISATION NUMBER(S)
PL 04854/0089

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION

Date of first authorisation: 18/06/2010

10

DATE OF REVISION OF THE TEXT
15/02/2015

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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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