CRINONE Vaginal gel Ref.[7856] Active ingredients: Progesterone

The pre-treatment physical examination should include special reference to breast and pelvic organs, as well as Papanicolaou smear.

Cautious use in severe hepatic insufficiency.

In cases of breakthrough bleeding, as in all cases of irregular vaginal bleeding, non-functional causes should be considered. In cases of undiagnosed vaginal bleeding, adequate diagnostic measures should be undertaken.

Crinone is not indicated in threatened abortion. Treatment should be discontinued in the event of a missed abortion.

The physician should be alert to the early manifestations of thrombotic disorders (thrombophlebitis, cerebrovascular disorder, pulmonary embolism and retinal thrombosis). Should any of these symptoms occur or be suspected, the drug should be discontinued immediately. Patients who have risk factors for thrombotic disorders should be kept under careful observation.

Although risk of thromboembolism has been associated with estrogens, a link with progestins remains questionable. Therefore, in women with generally recognised risk factors for thrombo-embolic events, such as personal or family history, treatment with Crinone may further increase the risk. In these women, the benefits of Crinone administration need to be weighed against the risks. It should be noted however, that pregnancy itself carries an increased risk of thrombo-embolic events.

Because progestogens may cause some degree of fluid retention, conditions that might be influenced by this factor (e.g, epilepsy, migraine, asthma, cardiac or renal dysfunction) require careful observation.

Patients who have a history of depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree.

A decrease in glucose tolerance has been observed in a small number of patients on oestrogen- progestin combination drugs. The mechanism of this decrease is not known. For this reason, diabetic patients should be carefully observed while receiving progestin therapy.

The excipient sorbic acid may cause local skin reactions (e.g. contact dermatitis) or vaginal irritation.

Crinone is not recommended for use concurrently with other vaginal preparations.

Although there is evidence of interaction between oral progestogens and CYP3A4 inducers, resulting in a decrease of serum progestogen levels, no significant consequences on progesterone levels is expected from concurrent administration of CRINONE vaginal gel with CYP3A inducers.

Pregnancy

In case of corpus luteum deficiency, Crinone can be used during the first month of pregnancy.

Breast-feeding

Do not use during lactation.

Drivers and users of machines are warned that risk of somnolence may occur.

The adverse reactions reported below are classified according to frequency of occurrence as follows:

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)

Crinone is generally well-tolerated. In clinical studies, the following adverse events have been reported during Crinone therapy. Most adverse events observed in clinical studies cannot be distinguished from the symptoms common in early pregnancy.

Common: Headache, somnolence, abdominal pain, breast tenderness, itching or burning.

Post Marketing Reports

In addition, intermenstrual bleeding (spotting), vaginal irritation, hypersensitivity reactions usually manifesting as skin rash, and other mild application site reactions have been reported post-marketing.

Rare events of urticaria and pruritis were noted.

For adverse reactions identified during post-marketing surveillance, quantification of frequency has not been attempted, but it is most likely uncommon to very rare.

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 Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

No incompatibilities were found with the usual contraceptive devices.