When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
"According to two epidemiological studies published in 2009, one retrospective cohort study (Lidegaard et al.) and one case control study (van Hylckama Vlieg et al.), the risk of venous thromboembolism occurring in Yasmin users was between those for levonorgestrel-containing COCs (so-called second generation COCs) and desogestrel/gestodene-containing COCs (so called third generation COCs).
One prospective cohort study (EURAS) showed the risk of venous thromboembolism in Yasmin users to be comparable to that of so-called second generation preparations. A further prospective cohort study (Ingenix) showed a comparable risk of thrombosis in Yasmin users and other COC users, including levonorgestrel." and the following text has been added: "Epidemiological studies have shown that the risk of VTE for drospirenone-containing OCs is higher than for levonorgestrel-containing OCs (so-called second generation preparations) and may be similar to the risk for desogestrel/gestodene-containing OCs (so-called third generation preparations)." In section 10, "June 2011" has been inserted as date of revision of text.
Changes to SPC as a result of renewal application approval.
4.4 Special warnings and precautions for use
Under subheading “Warnings”
Deletion of :
“Data from a large, prospective 3-armed cohort study has shown that the incidence of VTE in women with or without other risk factors for VTE who used Yasmin is in the same range as that for users of other low dose oestrogen combined oral contraceptives, including levonorgestrel-containing OCs (so-called ‘second’ generation OCs).”
Insertion of:
“According to two epidemiological studies published in 2009, one retrospective cohort study (Lidegaard et al.) and one case control study (van Hylckama Vlieg et al.), the risk of venous thromboembolism occurring in Yasmin users was between those for levonorgestrel-containing COCs (so-called second generation COCs) and desogestrel/gestodene-containing COCs (so called third generation COCs).
One prospective cohort study (EURAS) showed the risk of venous thromboembolism in Yasmin users to be comparable to that of so-called second generation preparations. A further prospective cohort study (Ingenix) showed a comparable risk of thrombosis in Yasmin users and other COC users, including levonorgestrel.”
4.8 Undesirable effects
Addition of rare adverse event “hypersensitivity”, “erythema nodosum” and “erythema multiforme”
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
“7 March 2010” inserted as date of last renewal
10. DATE OF REVISION OF THE TEXT
“September 2010” inserted as date
Previous Text
UpdatedText
4.2 Posology and method of administration
· Changing from another combined oral contraceptive (COC)
· Changing from another combined hormonal contraceptive (combined oral contraceptive (COC), vaginal ring, or transdermal patch
The woman should start with Yasmin on the day following the usual tablet-free or placebo tablet interval of her previous COC.
The woman should start with Yasmin preferably on the day following the usual tablet-free or placebo tablet interval after the last active tablet (the last tablet containing the active substances) of her previous COC, but at the latest on the day following the usual tablet-free or placebo tablet interval of her previous COC. In case a vaginal ring or transdermal patch has been used, the woman should start using Yasmin preferably on the day of removal, but at the latest when the next application would have been due.
4.5 Interaction with other medicinal products and other forms of interaction
· Influence of other medicinal products on Yasmin
Interactions between oral contraceptives and other medicinal products may lead to breakthrough bleeding and/or contraceptive failure. The following interactions have been reported in the literature.
This has been established with hydantoins, barbiturates, primidone, carbamazepine and rifampicin; oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and the herbal remedy St. John's Wort (hypericum perforatum) are also suspected.
This has been established with Hepatic metabolism: Interactions can occur with drugs that induce microsomal enzymes which can result in increased clearance of sex hormones (e.g. phenytoin,hydantoins, barbiturates, primidone, carbamazepine and rifampicin; and possibly also oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and products containing the herbal remedy St. John's Wort (hypericum perforatum)) are also suspected.
The mechanism of this interaction appears to be based on the hepatic enzyme-inducing properties of these active substances. Maximal enzyme induction is generally not seen for 2-3 weeks but may then be sustained for at least 4 weeks after the cessation of drug therapy.
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Also HIV protease (e.g. ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine), and combinations of them, have been reported to potentially affect hepatic metabolism.
Interference with Enterohepatic Circulation: Some clinical reports suggest that enterohepatic circulation of estrogens may decrease when certain antibiotic agents are given, which may reduce ethinylestradiol concentrations (e.g. penicillins, tetracyclines).
Contraceptive failures have also been reported with antibiotics, such as ampicillin and tetracyclines. The mechanism of this effect has not been elucidated.
- Occurrence or deterioration of conditions for which association with COC use is not conclusive: Crohn’s disease, ulcerative colitis, epilepsy, migraine, endometriosis, uterine myoma, porphyria, systemic lupus erythematosus, herpes gestationis, Sydenham's chorea, haemolytic uremic syndrome, cholestatic jaundice;
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Combined oral contraceptives, when taken correctly, have a failure rate of approximately 1% per year. The failure rate may increase when pills are missed or taken incorrectly.
Pearl Index for method failure: 0.09 Overall Pearl Index (method failure + patient failure): 0.57 (upper two-sided 95 % confidence limit: 0.90).
"Epidemiological studies have shown that the incidence of VTE in users of oral contraceptives with low oestrogen content (<50 µg ethinylestradiol) (including Yasmin) ranges from about 20 to 40 cases per 100,000 woman-years, but this risk estimate varies according to the progestogen. This compares with 5 to 10 cases per 100,000 woman-years for non-users.
Epidemiological studies have shown that the incidence of VTE in women with no known risk factors for VTE who use low dose oestrogen (<50 mcg ethinylestradiol) combined oral contraceptives ranges from about 20 cases per 100,000 women-years (for levonorgestrel-containing COCs) to 40 cases per 100,000 women-years (for desogestrel/gestodene-containing COCs). This compares with 5 to 10 cases per 100,000 woman-years for non-users and 60 cases per 100,000 pregnancies. VTE is fatal in 1-2% of cases.
Data from a large, prospective 3-armed cohort study has shown that the incidence of VTE in women with or without other risk factors for VTE who used Yasmin is in the same range as that for users of other low dose oestrogen combined oral contraceptives, including levonorgestrel-containing OCs (so-called ‘second generation OCs)."
Section 7. Marketing Authorisation Holder
The Marketing Authorisation Holder was changed from "HE Clissmann, Dublin." to "Bayer Limited, The Atrium, Blackthorn Road, Dublin 18.".
Section 8. Marketing Authorisation Number(s)
The PA number was changed from "PA 12/91/1" to "PA 1410/23/1".
Section 10. Date of Revision of the Text
The date was changed from "September 2006" to "October 2007".
SECTION 4.2 POSOLOGY AND METHOD OF ADMINISTRATION
Updated data regarding the start of treatment with Yasmin following use of a progestogen-only contraceptive method.
SECTION 4.3 CONTRAINDICATIONS
Addition of a contraindication: ‘Pancreatitis or a history thereof if associated with severe hypertriglyceridemia’.
SECTION 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE
Changes to the following sections:
Circulatory disorders
- migraine
- obesity
- positive family history (arterial thromboembolism ever in a sibling or parent at a relatively early age)
· addition of sickle cell disease to the list of other medical conditions associated with adverse vascular events
Other conditions
· new information regarding the effect of Yasmin on serum potassium levels
· addition of the following warning: ‘In women with hereditary angioedema exogenous estrogens may induce or exacerbate the symptoms of angioedema’.
SECTION 4.5 INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION
Influence of other medicinal products on Yasmin
· new advice regarding women on chronic treatment with hepatic enzyme inducing drugs: reliable, non-hormonal contraceptive method of contraception is recommended
Influence of Yasmin on other medicinal products
· new information regarding the effect of oral contraceptives on the metabolism of other active substances. This may influence the plasma and tissue concentrations of certain drugs e.g. cyclosporin, lamotrigine
SECTION 4.8 UNDESIRABLE EFFECTS
Addition of the following adverse effect: ‘In women with hereditary angioedema exogenous estrogens may induce or exacerbate the symptoms of angioedema’.
SECTION 5.1 PHARMACODYNAMIC PROPERTIES
Updated ATC code.
SECTION 5.2 PHARMACOKINETIC PROPERTIES
Changes to the following section:
Drospirenone
· new information regarding the maximum serum levels of drospirenone after single ingestion
· new information regarding the terminal half life of serum drospirenone
· new information regarding the metabolism of drospirenone by cytochrome P450 3A4 and the demonstration of the ability of drospirenone to inhibit this enzyme and cytochrome P450 1A1, cytochrome P450 2C9 and cytochrome P450 2C19 in vitro.
· new information regarding the maximum steady state concentration of drospirenone in serum
· new information regarding the properties of drospirenone in special populations (renal impairment, hepatic impairment, ethnic groups)