Proposal to make Gina 10 microgram vaginal tablets (Estradiol) available from pharmacies

Question 1

1.  Background on deciding where medicines are available

Accepted Answer

The role of MHRA

MHRA regulates medicines and medical devices in the UK, on behalf of the UK Licensing Authority. This means that MHRA decides whether medicines are available:

on prescription only - ‘prescription only medicine’ (POM)
to buy from pharmacies - ‘pharmacy medicine’ (P)
to buy from other shops - ‘general sales list medicine’ (GSL)

What is re-classification of a medicine?

Making a change on where a medicine is available is called reclassification. This is sometimes referred to as ‘switching’. To decide on this change, MHRA may:

take advice from its committees of external experts
take advice from a group (‘stakeholder group’) of health professionals and representatives of people affected by the classification change
run a public consultation

When a medicine is reclassified, it is usual for reclassification from POM to P to occur in the first instance, and once some experience is gained with the product in the pharmacy (P) setting, further reclassification from P to GSL may occur. In some cases, a medicine may be reclassified directly from POM to GSL, where it meets the necessary requirements and it is safe to do so. To be reclassified directly from POM to GSL, a medicine must meet both the requirements of POM to P and P to GSL reclassifications.

To be reclassified from POM to P a medicine must:

be unlikely to be a direct or indirect danger to human health when used without the supervision of a doctor, even if used correctly
be generally used correctly (i.e. not frequently or to a wide extent used incorrectly)
not contain substances or preparations of substances where the activity of the product or its side effects require further investigation
not normally be prescribed by a doctor for injection (parenteral administration)

To be reclassified from P to GSL, it must be demonstrated that the medicine may be supplied with reasonable safety in outlets other than in pharmacies. ‘Reasonable safety’ is defined as ‘Where the hazard to health, risk of misuse and need for special precautions in handling of the medicine are small, and where the wider sale would be a convenience to the purchaser’.

What evidence is needed?

A company or organisation can ask MHRA for a medicine to be available as a pharmacy medicine or a general sale medicine. To do this, they need to get together evidence to show that the medicine

a) is likely to be used appropriately, and

b) with relatively little danger to the public.

This evidence needs to focus on the risk to the public. This includes evidence on the possible abuse or misuse of the medicine. The evidence may include:

clinical studies
evidence showing acceptable level of side effects
advice of experts
views of relevant health professionals and their professional bodies
views of relevant public associations and individuals with an interest in the medicine under consideration.

Who makes the final decision?

The final decision on whether to approve a change is made by the MHRA, on behalf of the UK Licensing Authority.

Question 2

2.  About Gina

Accepted Answer

Gina is used for the treatment of vaginal atrophy due to oestrogen deficiency in postmenopausal women aged 50 years and above, who have not had a period for at least 1 year. Gina contains estradiol hemihydrate. Low dose vaginal oestrogens have been used for a number of years to treat vaginal atrophy that can arise due to diminished oestrogen production following the menopause.

Vaginal atrophy (VA) is a condition in which the decrease in oestrogen levels causes thinning of the tissues in and around the vagina, decreased flexibility and elasticity of the vagina and a decrease in the mucus production that provides a moist vaginal environment.

The most common symptoms of vaginal atrophy are dryness, soreness, itching, burning and painful intercourse (sexual symptoms of lack of lubrication).

Vaginal atrophy is currently diagnosed based on symptoms alone and without the need, in most women, for any physical examination, making it suitable for a pharmacy setting.

Gina is a local oestrogen therapy that is gradually released directly into the vaginal tissue. This helps to restore the integrity of the vaginal wall, relieving vaginal symptoms of dryness, soreness, itching, burning and painful intercourse.

The Commission on Human Medicines (CHM) has advised that this product can be made available from pharmacies as a Pharmacy (P) medicine. This report outlines the background to this decision. Please tell us your views by using this response form. The deadline for comments is 23 February 2022.

This is the first time an application has been made for a form of hormone replacement product to be available as a Pharmacy (P) medicine.

This report relates specifically to the proposal to reclassify Gina from prescription only to a pharmacy medicine.

Medicines containing low dose vaginal estradiol will still also be available to obtain on prescription from GPs and sexual health clinics.

What is in Gina?

Gina contains 10 micrograms of estradiol hemihydrate in each tablet. Gina is available as film-coated, vaginal tablets supplied in a preloaded applicator. Gina is the same strength as the prescription only medicine Vagifem 10 microgram vaginal tablets. However, the indication for Gina is limited to postmenopausal women aged 50 years and above, who have not had a period for at least 1 year.

What is Gina used for?

Gina is used for the treatment of vaginal atrophy due to oestrogen deficiency in postmenopausal women aged 50 years and above, who have not had a period for at least 1 year. It is a form of local hormone replacement therapy (HRT).

Question 3

3.  Proposal to make Gina available as a Pharmacy (P) medicine

Accepted Answer

Who has made the proposal?

The applicant proposing to make Gina available from pharmacies is Novo Nordisk.

What is the view of the Commission on Human Medicines?

The Commission on Human Medicines has advised that Gina can be available as a Pharmacy medicine. Views on the use of this medicine as a local hormone replacement therapy in the treatment of vaginal atrophy were also sought at a meeting of the Medicines for Women’s Health Expert Advisory Group (MWHEAG). The views of the MWHEAG were summarised and provided for CHM when they considered the reclassification application.

Proposed terms of reclassification

What are the details of this change?

The application proposes to make Gina available from pharmacies as follows:

For vaginal use
Strength: 10 microgram estradiol hemihydrate
For the treatment of vaginal atrophy due to oestrogen deficiency in postmenopausal women aged 50 years and above, who have not had a period for at least 1 year
Dose: (Initial dose): one vaginal tablet daily for two weeks, (Maintenance dose): one vaginal tablet twice a week
Maximum dose: 10 micrograms
Maximum daily dose: 10 micrograms (if using initial dose)

Question 4

4.  How was the proposal assessed for Gina being available as a Pharmacy medicine?

Accepted Answer

A medicine will be non-prescription unless it fulfils the criteria for prescription control (POM criteria) as set out below. Prescription-only medicine status is required if any of the following apply:

A direct or indirect danger exists to human health, even when used correctly, if used without medical supervision
There is frequently incorrect use which could lead to direct or indirect danger to human health
Further investigation of activity and/or side-effects is required
The product is normally prescribed for parenteral administration (by injection)

In the UK, these criteria are laid down in the Human Medicines Regulations 2012, regulation 62(3)^{[footnote 1]}.

The MHRA considered the application against the criteria for prescription control to assess the suitability for pharmacy availability. It was concluded that none of the criteria apply to Gina as all risks can be managed through the product information [SmPC, patient information leaflet (PIL) and labelling] and pharmacist training.

The company has produced pharmacy training materials consisting of a Pharmacy Guide and a Pharmacy Checklist. The checklist can be completed by the woman prior to consultation, or with a pharmacist during the consultation, and acts as an aide memoire for the pharmacist in determining if the medicine is suitable for supply. The patient will have the patient information leaflet and packaging to refer to, which contain the key safety messages.

The assessment of the application against each POM criterion is provided below.

4.1 POM Criterion 1 – The product is likely to present a direct or indirect danger to human health, even when used correctly, if used without medical supervision

The main criterion that must be considered in the reclassification of Gina to pharmacy status is that it does not present a direct or indirect danger to human health if used, even correctly, without the supervision of a doctor. A direct danger may be present if the product causes adverse reactions that are important because of their seriousness, severity, or frequency. A danger may also be present if the reaction is one for which there is no suitable preventative action such as being able to identify the group of patients who are at risk if they use the product without medical supervision so that they can be excluded from using the pharmacy product. Direct danger may arise from drug interactions with commonly used medicines. For the product to be suitable for pharmacy status the drug interactions would need to be preventable.

4.1.1 Direct danger to human health

Side Effects

Low dose locally acting vaginal oestrogens are generally associated with a small range of side effects.

Low dose vaginal estradiol is a well-established product having been widely used for the treatment of vaginal atrophy in the UK since 1991, and its safety profile is well known.

The most common side effects reported from clinical trials are, abdominal pain, vaginal discharge, vaginal discomfort and vaginal bleeding. The product information and pharmacy training materials include a clear message that any vaginal bleeding must warrant a referral to a doctor, to rule out the possible presence of a more serious underlying condition.

Serious side effects to low dose vaginal estradiol are rare.

The product information and the pharmacy training materials provide comprehensive information about all side effects with low dose vaginal estradiol, and on what action to take if they occur. Some amendments to the product information have been made to focus attention on risks more pertinent and proportionate for Gina use following supply from a pharmacy.

Endometrial (womb lining) safety

The MHRA considered the possible risk of not detecting the development of endometrial cancer if a woman was using local oestrogen therapy without medical supervision. It was noted that routine monitoring of changes to the endometrium with local oestrogen therapy is not required in current clinical practice and any medical investigations are likely to be prompted by endometrial symptoms, such as vaginal bleeding.

Therefore, any risk of not detecting endometrial cancer is not expected to increase with the availability of Gina for long term use from a pharmacy. Both the label and leaflet encourage women to check for the presence of any endometrial symptoms which should be referred promptly to a GP for investigation.

The pharmacy training materials include symptoms which would prompt the pharmacist to refer a woman to a doctor rather than supply Gina. Some women carry a higher risk of developing endometrial cancer, such as those who are using systemic HRT^{[footnote 2]} for long periods of time. For these women, the training materials advise pharmacists to supply Gina only after a woman has sought advice from a prescriber.

Risks associated with systemic HRT

Systemic HRT medicines are absorbed into the bloodstream. They include oral tablets and patches (transdermal patches) and gels which are put on the skin. They are known to increase the risk of developing the following conditions, especially when used for a long time:

Breast cancer
Ovarian cancer
Blood clots
Heart disease
Stroke

Unlike systemic HRT medicines, Gina works locally, which means it works directly where it is applied with very little absorption into the bloodstream. Although it is considered that the risk of developing these conditions with Gina is likely to be lower than with systemic HRT, this is not known for certain for most of them. Since Gina is still a form of HRT, these conditions are listed as contraindications in the product information for Gina so that women with a history of these do not use the product without a prescription. Regarding the risk of breast cancer, although it is not known if Gina can be safely used in women who had breast cancer in the past, recent evidence suggests that using Gina does not increase the risk of breast cancer in women who had no breast cancer in the past. This new information is reflected in the product information for Gina.

The risk of oestrogen-dependent malignancies occurring (endometrial and ovarian cancers) is considered to be extremely low and is similar to the number of postmenopausal women reporting these cancers who have not used a low dose vaginal oestrogen. The risk of oestrogen-dependent malignancies occurring is unlikely to change with pharmacy supply of Gina.

General information regarding key safety risks are required to be listed in the Summary of Product Characteristics (SmPC) and patient information of all HRT products. This information is derived from data for systemic HRT. As there is very little absorption of oestrogen into the bloodstream with Gina, these risks are less likely to apply. However, as Gina is a form of HRT information about them is included in the SmPC and PIL, so that these risks can be considered by users, alongside their personal history and risks for these conditions, prior to and during use of Gina.

Interactions between Gina and other medicines

Clinically relevant interaction between Gina and other medicines are unlikely to occur with Gina. Pharmacists will ascertain what other medicines a woman is taking when discussing whether Gina is suitable for her. The pharmacy training materials provide information about medicines which may not be suitable to use in combination with Gina.

4.1.2 Indirect danger to human health

Medicines may present indirect dangers if patients are supplied with a product which is unsuitable for them due to their general health or if pharmacy supply results in care that is inferior to that of patients receiving the medicine on prescription. Also, indirect dangers may occur if a woman’s symptoms mimic the symptoms of other conditions, leading to those conditions being masked, dismissed or worsened by use of the product.

The following potential indirect dangers have been identified for pharmacy supply of Gina:

Ability to diagnose vaginal atrophy
Masking other conditions resulting in delayed diagnosis
Endometrial (lining of the womb) risks
Women with an intact uterus previously treated with unopposed systemic oestrogens (systemic HRT containing only oestrogen)
Women with a history of endometriosis
Other conditions where systemic HRT should not be used
Exacerbation of other conditions
Women with a vaginal infection before using Gina

Ability to diagnose vaginal atrophy

The diagnosis of vaginal atrophy is based on a woman’s vaginal symptoms, such as dryness, soreness, itching, burning and painful intercourse. The pharmacy guide provides adequate information for pharmacists to understand the condition and its presenting symptoms. The guide also includes a list of other symptoms which may indicate a different underlying condition, which would require a referral to a doctor. The pharmacy checklist also includes these symptoms to ensure that pharmacists are able to determine whether the supply of Gina would be suitable.

Masking other conditions resulting in delayed diagnosis

Some symptoms of vaginal atrophy may also be features of other underlying conditions and this introduces an indirect risk that these conditions might be mistakenly diagnosed and treated as vaginal atrophy, with a consequent delay in correct diagnosis and treatment.

The vulval dermatoses^{[footnote 3]} as a group (lichen sclerosus^{[footnote 4]}, lichen planus^{[footnote 5]}) with external itching, fissures^{[footnote 6]} and sometimes pain are the most likely to be confused with vaginal atrophy as the symptoms also include severe itching, soreness, and painful intercourse, similar to vaginal atrophy.

Vulval dermatoses, vulval rash and severe vaginal itching are all included as contraindications to prevent Gina being used inappropriately. However, if these conditions were mistaken for vaginal atrophy and Gina was used for a short time the product would not make these conditions better or worse. The pharmacy checklist includes questions to determine whether there has been an improvement in symptoms. A worsening of symptoms, or a lack of an improvement in symptoms after using Gina for several weeks may indicate an underlying condition, and therefore pharmacists would be encouraged to refer these women to their doctor.

Overall, the risk of masking an underlying condition is considered to be low and can be managed by the information in the leaflet and on the label, and also via interaction with the pharmacist. Information is provided for pharmacists in the pharmacy training materials. A short delay in the diagnosis and correct treatment or use of Gina for any of the listed conditions is unlikely to lead to a worsened outcome.

Endometrial (lining of the womb) risks

The product information includes the following contraindications related to endometrial risks:

Known, past or suspected endometrial cancer
Undiagnosed genital bleeding
Untreated endometrial hyperplasia (excessive thickening of the womb lining)

A previous history of any of these conditions, particularly a history of serious endometrial disease, is likely to be known to the woman and can be established by the pharmacist on direct questioning. The presence of symptoms that might lead to suspicion of an undiagnosed underlying condition can also be identified with appropriate questioning in a pharmacy setting. Therefore, the risk of this indirect danger is manageable via the product information and the pharmacy consultation.

The pharmacy training materials emphasise the importance of encouraging women with undiagnosed symptoms to consult their doctor, e.g. undiagnosed bleeding. The product information has also been updated to include new onset of vaginal bleeding during Gina treatment as a reason for immediate withdrawal of therapy and referral to a doctor.

Women with an intact uterus previously treated with unopposed systemic oestrogens (systemic HRT containing only oestrogen)

Current clinical and regulatory guidance does not recommend use of unopposed systemic oestrogens by women with an intact uterus. However, any use of unopposed systemic oestrogens in this group of women is likely to be under medical supervision, and therefore they are excluded from supply of Gina through pharmacies.

Direct questioning during pharmacy consultations is likely to indicate whether women have previously used oestrogen only HRT. Although the risk of this population using Gina is low, the pharmacy training materials have clearly included the message that this group of women should not be supplied with Gina without prescription. The pharmacy checklist prompts pharmacists to ascertain this information when asking women whether they are currently taking/have previously taken any other medication.

Women with a history of endometriosis^{[footnote 7]}

The product information has been updated so that it is very clear when women with a history of endometriosis can use Gina and when women should be referred to their doctor. As previous history of endometriosis is likely to be known to the woman this information can be obtained by the pharmacist when a request for Gina is made. The pharmacy checklist includes guidance for pharmacists to help determine whether these women could be supplied with Gina; it makes it clear that Gina can safely be supplied from a pharmacy to a woman with a history of endometriosis if:

a) she has previously received a prescription for vaginal oestrogens and her health status is unchanged since her last prescription, and

b) she has no recent symptoms of endometriosis.

The training makes clear that if the above conditions are not met, a woman with a history of endometriosis would need to be referred to a doctor.

Other conditions where systemic HRT should not be used

The following list comprises conditions where systemic HRT cannot be used. This list has also been retained for the supply of Gina:

Known, past or suspected oestrogen-dependent malignant tumours (e.g. breast cancer, ovarian cancer)
Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism)
Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction, ischaemic stroke)
Known thrombophilic disorders
Acute liver disease, or a history of liver disease as long as liver function tests have failed to return to normal
Porphyria

Any of the above conditions, or a history of these conditions, is likely to be known to a woman and can be requested on direct questioning during pharmacy consultations.

The product information and the pharmacy training materials highlight these risks and include possible risk factors and signs to look out for when appropriate. These materials also highlight the difference between local and systemic HRT to explain to women that the risks associated with systemic HRT as outlined above apply less to vaginally administered treatments such as Gina. The pharmacy checklist includes appropriate questions to be used during the pharmacy consultations to help identify whether any of the above conditions are applicable.

Exacerbation of other conditions

The following conditions may be adversely influenced by systemic oestrogen HRT medicines. Whilst these conditions are less likely to be exacerbated by low dose vaginal oestrogens, such as Gina, than with systemic HRT, they may need to be considered by users, alongside their personal history of these conditions, prior to and during use of Gina:

Uterine fibroids (leiomyoma)
Increased risk of developing blood clots (e.g. being unable to walk for a long time because of major surgery/injury/illness, being overweight with a BMI greater than 30 kg/m², having close relatives who have ever had a blood clot in the legs or lungs)
Increased risk of getting womb or ovarian (e.g. having a close relative who has had any of these cancers)
High blood pressure
Liver Disorders (e.g. a benign liver tumour)
Diabetes
Gallstones
Migraines or (severe) headache
Systemic lupus erythematosus (SLE)
Epilepsy
Asthma
A disease affecting the eardrum and hearing (otosclerosis)
A very high level of fat in your blood (triglycerides)
Fluid retention due to cardiac or kidney problems.

Women are advised in the patient information leaflet to tell their doctor if they have or have had any of these conditions and they are using Gina, and to seek their advice if any of these conditions return or get worse whilst using Gina.

Women with a vaginal infection before using Gina

Some women may be more prone to candida infections and candida infections can be worsened by local vaginal oestrogens. Women who have a vaginal infection should not start treatment with Gina until the infection has been treated. Therefore, vaginal infection before starting treatment is included as a contraindication to use of Gina. The product information has also been updated to refer women to a doctor if they have a vaginal infection not adequately treated by a pharmacy treatment.

The pharmacy checklist includes relevant questions to help identify whether women have a vaginal infection before starting treatment with Gina, or if an infection develops whilst using Gina which is not treated satisfactorily by a Pharmacy medicine.

Overall conclusion on POM Criterion 1 (The product is likely to present a direct or indirect danger to human health, even when used correctly, if used without medical supervision)

The first POM criterion is not considered to apply to Gina. Under the proposed terms of the marketing authorisation, including the proposed SmPC, the patient information and the pharmacy training and support materials, lack of medical supervision is not anticipated to result in direct or indirect danger to human health.

4.2 POM Criterion 2 – The product is frequently and to a very wide extent used incorrectly, and as a result is likely to present a direct or indirect danger to human health

Use when contraindicated

Pharmacists must be satisfied with the information provided by a woman before Gina can be supplied. The training and support materials ensure that the appropriate questions are asked to identify any possible contraindications before Gina can be supplied.

Furthermore, the product label has been designed to ensure it is unlikely that Gina will be used inappropriately. If Gina was used incorrectly, it is unlikely that there would be any harmful effects, because the oestrogen levels after using Gina are considered to be within the normal range for postmenopausal women.

Incorrect use

Gina will be available as a single pack size of 24 tablets which includes two separate dosing instructions:

Initial dose: One vaginal tablet daily for two weeks
Maintenance dose: One vaginal tablet twice a week

Each pack will provide up to 3 months treatment: 7 weeks of treatment for women using the product for the first time (i.e. the initial dose followed by the maintenance dose), or 12 weeks of treatment for women being supplied with the product on subsequent occasions (i.e. using only the maintenance dose).

It is unlikely for there to be confusion between the two doses in a pharmacy setting. This is because the product information and the pharmacy training materials clearly state that the initial dose only applies at the start of treatment and not for each pack. Secondly, reminders for women not to use more than the recommended dose and the need to consult a doctor if symptoms are not adequately controlled have been included in the patient information leaflet.

The pharmacy training materials advise pharmacists to review treatment at each purchase. They encourage pharmacists to check whether symptoms have worsened after completion of the first pack. This is to check that their symptoms are caused by vaginal atrophy and not a different underlying condition. Likewise, the materials also encourage pharmacists to check whether there has been some improvement in symptoms after completion of the second pack, as women should expect to experience some improvement in symptoms after this time if their symptoms are due to oestrogen deficiency-related vaginal atrophy. Pharmacy reviews will provide opportunities for pharmacists to reinforce the messages about the correct dose, over and above those on the pack and in the patient information leaflet.

Subsequent pharmacy reviews will provide pharmacists with the opportunity to check for progress in symptoms, contraindications and changes to family history at every visit. These regular pharmacy reviews replace the recommendation in the POM SmPC for treatment to be reviewed every 12 months.

Off-label use

The MHRA has considered the risk of intentionally using more than the recommended dose, for example if women are not experiencing adequate symptom relief. Several measures are included to ensure this risk is likely to be low. To manage this risk in a pharmacy, Gina will only be supplied after a consultation with a pharmacist who will be able to ascertain through questioning whether a woman’s symptoms are being adequately controlled, and what dose is being used to manage the symptoms. Furthermore, to ensure that that there is regular monitoring of a woman’s symptom relief, only one pack of Gina is likely to be supplied per visit to a pharmacy. The information in the leaflet also advises women not to take more than the recommended dose, and further advises women to seek medical advice if symptoms persist.

The pharmacy checklist includes questions which help to determine whether a woman is satisfied with the improvement in vaginal symptoms when she returns to purchase another pack of Gina. Although there are unlikely to be harmful effects if more than the recommended dose is used short-term, if a woman is not satisfied with the improvement in vaginal symptoms, she should be referred to a doctor.

Overall conclusion on POM criterion 2 (The product is frequently and to a very wide extent used incorrectly, and as a result is likely to present a direct or indirect danger to human health.)

The second POM criterion is not considered to apply to Gina, because the risks of direct or indirect danger to human health from incorrect use can be adequately managed through the product information and pharmacy training and support materials.

4.3 POM Criterion 3 – The product contains substances or preparations of substances of which the activity requires, or the side effects require, further investigation

Low dose vaginal estradiol is a well-established product having been widely used for the treatment of vaginal atrophy in the UK since 1991. Its efficacy and safety profile are well known, and there are no issues requiring further investigation.

Overall conclusion on POM criterion 3 (The product contains substances or preparations of substances of which the activity requires, or the side effects require, further investigation)

The third POM criterion is not considered to apply to Gina.

4.4 POM Criterion 4 - The product is normally prescribed by a doctor for parenteral administration (that is, by injection).

Gina is a tablet intended for vaginal administration only.

Overall conclusion on POM criterion 4 (The product is normally prescribed by a doctor for parenteral administration (that is, by injection))

The fourth POM criterion does not apply to Gina.

Question 5

5.  Further details on the application

Accepted Answer

5.1 Risk Management Plan

The application contained a risk management plan (RMP), which documents everything that is known and not known about the safety profile of a product, including any plans for further characterising risks and minimising risks.

The RMP for Gina details the following:

Safety Concerns (Important identified and potential risks)

No important identified risks have been established for low dose vaginal estradiol. This remains true for pharmacy supply.

Potential risks are those that may be associated with low dose vaginal estradiol, but currently available evidence is inconclusive about a link. The following potential risks of low dose vaginal estradiol are considered important:

Oestrogen-dependent malignancies (ovarian cancer)
Endometrial adverse effects (endometrial cancer, endometrial hyperplasia, endometriosis)
Venous thromboembolism (deep vein thrombosis, pulmonary embolism)
Ischaemic stroke
Women with symptoms of contraindicated conditions may receive treatment
Misdiagnosis of post-menopausal vaginal atrophy for P supply

Monitoring of the safety concerns

The safety concerns associated with Gina can be monitored through the routine activities that pharmaceutical companies have to undertake legally to monitor their products, (routine pharmacovigilance). No additional monitoring is considered necessary.

Further characterising the safety concerns (Additional pharmacovigilance)

None of the safety concerns are considered to require further investigation or study, either because current knowledge is considered adequate, or because studies are unlikely to provide useful additional information. Minimising the safety concerns

The risk of all safety concerns and adverse events for Gina are minimised through routine measures including the product information.

The safety concerns for the supply of Gina in the pharmacy will be minimised further through an additional risk minimisation measure of pharmacist training materials and a pharmacy checklist. These will highlight the important potential risks of low dose vaginal estradiol. They will also ensure that pharmacists know how to identify relevant conditions and advise and manage supply to women appropriately.

Measuring the effectiveness of the additional risk minimisation measure of pharmacist training

Following market launch of Gina, the applicant is required to undertake a study, (post-authorisation safety study or PASS), to assess how effective the pharmacist training materials are at ensuring competence and confidence to supply Gina safely and appropriately. It has been agreed that this will take the form of a survey-based study. The pharmacist’s views on the training will be sought, as well as a demonstration of understanding of key messages, and the ability to make correct decisions about whether to supply to a woman or not.

5.2 Pharmacy support materials

As already discussed, additional resources in the form of pharmacy training materials will be provided for pharmacists. Use of these materials is optional and cover the following areas:

Pharmacy Guide

The Pharmacy Guide provides information to pharmacists on the safe use of Gina ensuring it is only supplied when suitable, with appropriate counselling and advice. The guide covers supply to women who have never previously used a local oestrogen therapy, supply to women switching from a prescription locally acting low dose vaginal oestrogen product, including Vagifem and supply to women receiving hormonal therapy, including systemic HRT, whose GPs have confirmed suitability for treatment with Gina. Other symptoms, conditions and concurrent medications which require a GP to confirm suitability for treatment before Gina can be supplied are also listed in the guide. To ensure continuity of care, women are encouraged to inform their doctor and other healthcare professionals that they have obtained Gina from their pharmacy. Women are made aware of how to use Gina, when to expect symptom improvement and when to seek medical advice.

Pharmacy Checklist

The checklist acts as an aide memoire and allows the pharmacist to check the suitability of Gina. The checklist is split into three sections:

Section 1: Women who have never previously used Gina (first visit to the pharmacy)
Section 2: Women who are returning for their second visit (7 weeks) or first 3-monthly visit
Section 3: Women who are returning for their ongoing 3-monthly visits

The pharmacy checklist includes appropriate questions to be used during the pharmacy consultations to help identify whether there has been a change in a woman’s health when they return for a supply of Gina from the pharmacy. It also provides a reminder of symptoms which would require medical advice to be sought, and counselling advice to provide to the woman.

The pharmacy checklist also provides advice for women who are switching from another low dose vaginal oestrogen including Vagifem (without a treatment break), and advice for women who have taken a treatment break whilst using Gina or a low dose vaginal oestrogen.

Download the Pharmacy Checklist.

5.3 Label and leaflet

5.4 Summary of Product Characteristics

Download the Summary of Product Characteristics.

This document is a description of the properties of Gina and the conditions attached to its use. It is intended for use as a reference by healthcare professionals.

Question 6

6.  Consultation with stakeholders

Accepted Answer

As part of the assessment process, MHRA undertook a patient and healthcare professional engagement exercise to inform the CHM decision regarding availability of low dose vaginal estradiol from pharmacies. This included representation from individual patients, patient groups, pharmacists, GPs, professional bodies (FSRH, Royal College of GPs). The exercise explored the access to treatment for vaginal atrophy, whether patients would welcome wider availability, and the professional views of those currently involved in prescribing this medicine on widening access. There was strong support from all stakeholders for making low dose vaginal estradiol available to purchase from pharmacies in addition to being available from GPs on prescription.

MHRA separately discussed widening access of this medicine with health policy officials in the Devolved Administrations and this was also met with strong support.

Question 7

7.  What do you think?

Accepted Answer

Gina 10 microgram vaginal tablets are used for the treatment of vaginal atrophy due to oestrogen deficiency in postmenopausal women aged 50 years and above, who have not had a period for at least 1 year
We propose to make it available in pharmacies
Medicines containing low dose vaginal estradiol will still be available on prescription from GPs
Women will have a choice in where they obtain supply of this medicine from, either on prescription or from pharmacies and may opt to switch between methods of supply
We consider that this product may be available as a pharmacy medicine
The Commission on Human Medicines has advised that this product can be available as a Pharmacy (P) medicine
We want to know what you think about this change.

The Human Medicines Regulations 2012. http://www.legislation.gov.uk/uksi/2012/1916/contents/made ↩
Systemic HRT medicines circulate in the blood and are used to treat hot flushes and other menopausal symptoms ↩
Skin disorders that affect the vulva, causing itching and burning. ↩
Lichen sclerosus is a skin condition that causes itchy white patches on the genitals or other parts of the body. ↩
Lichen planus is a rash that can affect different parts of your body ↩
A tear or open sore (ulcer) ↩
Endometriosis is a condition where tissue similar to the lining of the womb starts to grow in other places, such as the ovaries, fallopian tubes, bladder or bowels ↩

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1. Background on deciding where medicines are available