Merck Sharp & Dohme Limited

4.2 Posology and method of administration

Ovestin cCream is an estrogen-only product for intravaginal use.

One applicator-dose (applicator filled to the red mark) is 0.5g Ovestin Ccream containing 0.5 mg estriol.

Adults and Elderly

• Treatment of atrophic vaginitis

For initiation and continuation of treatment of postmenopausal symptoms, the lowest effective dose for the shortest

duration (see also section 4.4) should be used.

The usual dose for atrophic vaginitis associated with the menopause is one applicator-dose per day for 2 to 3

weeks.

As maintenance dosage, one applicator-dose twice a week is recommended.

Medication should be discontinued every 2 to 3 months for a period of 4 weeks to assess the necessity for further

treatment.

• Pre-surgery therapy

One applicator-dose per day should begin 2 weeks before the operation.

• Post-surgery therapy

Following surgery a period of at least 2 weeks should be allowed before resuming therapy using one applicator dose

twice a week.

In women not taking HRT or women who switch from another continuous combined HRT product, treatment with

Ovestin Ccream may be started on any day. Women who switch from cyclic HRT regimen should start Ovestin

Ccream treatment one week after completion of the cycle.

Route of Administration

Ovestin cCream is administered intravaginally by means of a calibrated applicator.

The following 'Instructions for Use' should be given to the patient and are included in the Patient Information Leaflet:

How to Apply the Cream

Use the applicator to apply the cream in the vagina. It is a good ideaA good time to do this is before going to bed.

The applicator has a ring marked on the body. Fill the applicator up to the ring mark with Ovestin cream to get the

correct dose.

1. Remove the cap from the tube, invert it, and turn it upside down. Then use the sharp point to open the tube.

2. Screw the end of the applicator onto the tube.

3. Squeeze the tube to fill the applicator with the cream up to the red ring mark until (the plunger will stops (at the

ring mark).

4. Unscrew applicator from the tube and replace put the cap back on the tube.

5. To apply the cream, lie down, insert put the end of the applicator deep into the vagina and slowly push plunger all

the way in.

Cleaning the applicator

After use, pull the plunger out of the barrel. Wash the plunger and barrel in hand hot, soapy water. Do not use

detergents. Rinse well with clean water afterwards.

DO NOT PUT THE APPLICATOR IN BOILING WATER.

A missed dose should be administered as soon as remembered, unless it is more than 12 hours overdue. In the latter

case the missed dose should be skipped and the next dose should be administered at the normal time. Two doses

should never be administered on the same day.

Cyclic administration of a progestagen to prevent endometrial stimulation is not necessary provided the daily dose

does not exceed 1 applicator-dose (0.5mg estriol) and this maximum dose is not used for more than several weeks (see

section 4.4 Endometrial hyperplasia).

Children

There are no clinical trials to support the use in children.

The text in blue below has been added to the SPC as part of a core safety profile update.

1.   NAME OF THE MEDICINAL PRODUCT
Ovestin 1 mg cream
[and consequentially, the word ‘cream has been removed after the word ‘Ovestin’ throughout the SPC]

2.  QUALITATIVE AND  QUANTITATIVE COMPOSITION
1mg estriol in 1g cream
For a full list of excipients, see section 6.1.

3.  PHARMACEUTICAL FORM
Vaginal cream
Homogeneous, smooth, white to nearly white mass of creamy consistency.

4.5  Interactions with other medicinal products and other forms of interaction
No examples of interactions between Ovestin and other medicines have been reported in clinical practice. Although data are limited, interactions between Ovestin and other medicinal products may occur. The following interactions have been described with use of combined oral contraceptives which may also be relevant for Ovestin. The metabolism of estrogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes, such as anticonvulsants (e.g. hydantoins, barbituates, carbamezapin), anti-infectives (e.g.griseofulvin, rifamycins, the antiretroviral agents nevirapine and efavirenz). and herbal preparations containing St John’s wort (Hypericum Perforatum). Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Clinically, an increased metabolism of estrogens may lead to decreased effectiveness of Ovestin and changes in uterine bleeding profile.

Estriol may possibly increase the pharmacological effects of corticosteroids, succinylcholine, theophyllines and troleandomycin.

4.6 Pregnancy and lactation
The word ‘cream’ has been removed

4.7  Effects on ability to drive and use machines
As far as is known Ovestin has no effect on alertness and concentration.
None stated
The SPC and API will be circulated shortly.

Text in bold and underlined has been added.

Text with strikethrough has been removed.

6.1     LIST OF EXCIPIENTS

            2 octyldodecanol (eutanol G); cetyl palmitate; glycerin; cetyl alcohol;             stearyl alcohol; Polysorbate 60; sorbitan monostearate;    chlorhexidine dihydrochloride; lactic acid; sodium hydroxide to pH             4,         purified water.

10.       DATE OF (PARTIAL) REVISION OF THE TEXT

November 2005 August 2004