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.
Section 4.8: Undesirable effects
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Psychiatric disorders
Emotional lability
Depression Nervousness Sleep disorder Libido decreased
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Reproductive system and breast disorders
Breast pain Breast enlargement Breast tenderness Dysmenorrhea Metrorrhagia
Breast neoplasm Fibrocystic breast Galactorrhea Ovarian cyst Hot flushes Menstrual disorder Amenorrhea Menorrhagia Vaginal candidiasis Vaginitis Genital discharge Vulvovaginal disorder Vaginal dryness Pelvic pain Papanicolaou smear suspicious Libido decreased
The most appropriate MedDRA term is used to describe a certain reaction and its synonyms and related conditions.
The following serious adverse events have been reported in women using COCs, which are discussed in section 4.4 Special warning and precautions for use:
- Venous thromboembolic disorders;
- Arterial thromboembolic disorders;
- Hypertension;
- Liver tumours;
- Occurrence or deterioration of conditions for which association with COC use is not conclusive: Crohn’s disease, ulcerative colitis, epilepsy, migraine, uterine myoma, porphyria, systemic lupus erythematosus, herpes gestationis, Sydenham's chorea, haemolytic uremic syndrome, cholestatic jaundice;
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Section 10: Date of Revision of the text
June 2011 March 2012
Previous text
Updated Text
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 Yasminelle on the day following the usual tablet-free or placebo tablet interval of her previous COC.
The woman should start with Yasminelle 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 Yasminelle preferably on the day of removal, but at the latest when the next application would have been due.
4.4 Special warnings and precautions for use
· Circulatory Disorders
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The use of any combined oral contraceptive carries an increased risk of venous thromboembolism (VTE) compared with no use. The excess risk of VTE is highest during the first year a woman ever uses a combined oral contraceptive.
Epidemiological studies have shown that the incidence of VTE in users of oral contraceptives with low oestrogen content (<50 µg ethinylestradiol) (including Yasminelle) 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.
The use of any combined oral contraceptive carries an increased risk of venous thromboembolism (VTE) compared with no use. The excess risk of VTE is highest during the first year a woman ever uses a combined oral contraceptive. The incidence of VTE associated with pregnancy is estimated as 60 cases per 100,000 pregnancies. VTE is fatal in 1-2% of cases.
Epidemiological studies have shown that the incidence of VTE in users of oral contraceptives women with no known risk factors for VTE who use low dose oestrogen content (<50 µg ethinylestradiol combined oral contraceptives) (including Yasminelle) ranges from about 20 to 40 cases per 100,000 woman-years , but this risk estimate varies according to the progestogen (for levonorgestrel-containing COCs ) to 40 cases per 100,000 women-years (for desogestrel/ gestodene-containing COC). This compares with 5 to 10 cases per 100,000 woman-years for non-users and
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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 ethinylestradiol / drospirenone 0.03 mg / 3 mg 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).
4.5 Interaction with other medicinal products and other forms of interaction
· Influence of other medicinal products on Yasminelle
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.
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.
4.8 Undesirable effects
- 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: 0.31 (upper 97.5 % confidence limit: 0.91)
Pearl Index for method failure: 0.31 0.11 (upper 97.5 % confidence limit: 0.91 0.60).
Overall Pearl Index (method failure + patient failure): 0.31 (upper 97.5 % confidence limit: 0.91).
Main Changes to the SPC
Section 4.2 Posology and method of administration
Updated information provided regarding advice in case of gastro-intestinal disturbances.
Section 4.4 Special warnings and precautions for use
Addition of the following information regarding the risk of circulatory disorders (arterial thrombo-embolic complications or cerebrovascular accident) in COC users:
Risk increases with
· obesity (body mass index over 30 kg/m²).
· a positive family history (arterial thromboembolism ever in a sibling or parent at relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any COC use.
Updated information regarding the possible increased risk of cervical cancer in long-term users of COCs (> 5 years).
Updated information provided regarding monitoring of serum potassium in patients presenting with renal insufficiency during the first treatment cycle.
Section 4.5 Interaction with other medicinal products and other forms of interaction
Updated information provided regarding women on chronic treatment with hepatic enzyme-inducing active substances.
Section 5.2 Pharmacokinetic properties
Updated information regarding the effect of drospirenone on special populations (hepatic impairment).