Medicine Safety Update: New advice for men taking valproate

3rd October 2024

In a new Drug Safety Update Published on the 5th September 2024, the Medicines and Healthcare products Regulatory Agency (MHRA) advise men taking valproate and their partners to use effective contraception as a precaution.

The new update is as a result of a retrospective observational study which indicated a potential small increased risk of neurodevelopmental disorders to children associated with paternal exposure to valproate at conception. The study suggested that compared to children whose fathers took other antiseizure medications - lamotrigine or levetiracetam, children whose fathers took valproate during the 3 month period before they were conceived had a small increased risk of neurodevelopmental disorders.  This potential risk is much lower than the risk of neurodevelopmental disorder in children born to mothers taking valproate during pregnancy.

The new Drug Safety Update includes information and advice for healthcare professionals and patients. It also contains information about the study findings and information on reporting suspected adverse drug reactions to the Yellow Card Scheme. Healthcare professionals, patients, and caregivers are asked to provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset timing, treatment dates, and product brand name when reporting.

Advice of the Commission on Human Medicines:

• There should be a clear recommendation for the male patient and their female partner to use effective contraceptive birth control during treatment and for 3 months after stopping.
• Male patients should be advised to avoid sperm donation during treatment for 3 months after stopping valproate treatment.
• Male patients should have their treatment reviewed regularly and those planning to conceive should discuss alternative treatments with their prescriber.
• Healthcare professionals should inform male patients of reproductive potential of the possible risk at initiation of valproate or at their next medication review.

Advice for healthcare professionals:

• Inform male patients (of any age) who may father children of the possible risk at initiation of valproate or at their next regular treatment review – this counselling should be given irrespective of the indication for valproate and also after intravenous use of valproate.
• As a precaution, recommend that male patients use effective contraception (condoms, plus contraception used by the female sexual partner) throughout the valproate treatment period and for 3 months after stopping valproate, to allow for one completed sperm cycle not exposed to valproate.
• At the next regular treatment review, discuss with men on oral valproate treatment whether they are planning a family in the next year and if they are, refer to a specialist to discuss alternative treatment options.
• If a female patient reports they are pregnant or planning a pregnancy with a man on valproate (including those undergoing IVF), refer for prenatal counselling.
• Advise men not to donate sperm during valproate treatment and for 3 months after stopping valproate.
• Report any suspected adverse drug reactions associated with valproate on a Yellow Card.

Advice for healthcare professionals to provide to male patients:

• It is recommended that you and your female sexual partner should both use effective birth control (condoms and another form of female contraception) as a precaution while you are taking valproate and for at least 3 months after stopping valproate.
• Allow at least 3 months to pass after stopping valproate before trying to father a child.
• You should not donate sperm whilst taking valproate and for 3 months after stopping.
• Do not stop taking valproate unless you are advised to do so by a healthcare professional.
• If your partner is pregnant or you are undergoing IVF treatment, talk to a healthcare professional who can counsel you further if you have any concerns.
• At your next regular treatment review, you will be offered a discussion on the risks and other treatments available, if you have concerns or are planning a family you will get an appointment sooner.
• If you father a child while you are taking valproate or in the 3 months after stopping valproate, there is a potential small increased risk of the child being diagnosed with a mental or movement related developmental disorder (neurodevelopmental disorder)
• Advice will be added to the valproate patient guide; in the meantime see MHRA’s Advice for male patients on valproate to use contraception and Visual risk communication diagram
• Report any suspected adverse drug reactions associated with valproate on a Yellow Card

Useful resources

MHRA Drug Safety Update volume 18, issue 2: September 2024 https://www.gov.uk/drug-safety-update/valproate-use-in-men-as-a-precaution-men-and-their-partners-should-use-effective-contraception

Emc (medicines.org.uk): Epilim 200 mg Gastro-resistant tablets - Risk Management Materials https://www.medicines.org.uk/emc/product/519/rmms#about-medicine

MHRA Collection Valproate safety measures https://www.gov.uk/government/collections/valproate-safety-measures

FutureNHS: Valproate (Background) https://future.nhs.uk/MedicinesSafetyImprovement/view?objectId=47573808

FutureNHS: Valproate Q&A January 2024 v0.1 https://future.nhs.uk/MedicinesSafetyImprovement/view?objectId=195803557

Specialist Pharmacy Service: MSATS – Safe use of valproate event February 2024. https://www.sps.nhs.uk/articles/msats-safe-use-of-valproate/#:~:text=valproate

Dermatology Prescribing in Primary Care

5th September 2024 

Emollients have a key role in treating a multitude of dry skin conditions, including eczema and psoriasis, and can be bought over the counter as well as being prescribed. Despite this, emollients are often underutilised in the treatment of these conditions, as it can be considered time consuming to apply them and they are often needed long-term for maximum effect. Continuous use is necessary to receive full clinical benefit, which means persisting with the treatment regimen even when the eczema or psoriasis is in remission.

How can we improve adherence?

Informed, shared decision making, based on a range of emollients is thought to be key in encouraging adherence and optimising emollient treatment for conditions such as eczema.

Information (including written information) about treatment should be provided to the patient and they should be signposted to other useful resources as appropriate. The rationale for continued emollient treatment should be explained to the patient, and the importance of regular application preventing further flares should be stressed.

Patients should be given easy access to self-care advice and application information (such as technique, quantity to apply and frequency). A range of information sources for the public can be found at the end of the article.

How much emollient should be prescribed?

For patients who have long term chronic skin conditions, prescribing an appropriate quantity of suitable emollient can prevent A&E attendance and admission, which has benefits for the whole system, as it is cost efficient, as well as increasing health and wellbeing and reducing stress for patients and their families. It is important to provide patients with enough emollient to enable them to use it regularly and adhere to their regimen, therefore preventing flare-ups in their condition.

Prescribing may involve trialling different emollients (in small quantities) until a suitable preparation that is acceptable to the individual is found. The Lincolnshire emollient guidance contains all the preparations which can be used in Lincolnshire. These have been agreed by dermatology specialists, and it should not be necessary to prescribe outside of this.

Interpreting the NHSE over-the-counter guidance

Emollients are products which can be bought over the counter, and if the patient has a minor self-limiting condition rather than a chronic long-term diagnosis, such as mild irritant dermatitis or mild dry skin, then it may be appropriate to recommend that the patient buy the product and self-treat.

There are some chronic long-term conditions such as any of the following, which should not have to be treated solely by the patient purchasing over the counter products. These conditions are:

- Eczema, dermatitis or psoriasis

- Ichthyosis

- Or those who need emollients to compliment another treatment, such as phototherapy.

If the patient has one of the above conditions, then it is likely that they will need regular access to these medications, and it is appropriate to issue them on prescription. As with any medication, it is important to ask about usage at medication reviews, and to adjust quantities as dictated by patient need, to reduce wastage and increase efficacy. It is also important to ensure that there are appropriate indications recorded for emollients, and the indication is a documented dermatological condition. Prescribing of emollients for non-clinical, cosmetic purposes is not recommended and should be reviewed.

Bath and shower emollients and soap substitutes

The use of bath and shower emollients is controversial and, until recently, evidence to inform practice was lacking. It is generally accepted that soap is drying and potentially irritating to skin and is best avoided by those with dry skin conditions. There is therefore clinical consensus that soap substitutes are necessary for people with dry skin conditions to wash with, and a guide on how to use these emollients as soap substitutes is available here: Bathing, showering and washing clothes | ECO (eczemacareonline.org.uk)

The recently published BATHE study aimed to address some of the uncertainty regarding emollient bath additives (i.e. those that are poured into bath water). This pragmatic randomised controlled trial (n=483) in children with eczema (aged one to eleven years) found no evidence of a clinically meaningful benefit from emollient bath additives, when used in addition to standard eczema management. This study indicated that efforts and resources should be targeted at effective use of leave-on emollients and soap substitutes in children with eczema, rather than the use of bath emollients. A full summary of the clinical evidence is available here.

Proprietary wash products (such as soap substitute shower gels) can be expensive, and evidence to justify their use over lower-cost alternatives is lacking. People with eczema should therefore be advised to wash with a regular leave-on emollient that is suitable for use as a soap substitute. Bath and Shower emollients are available to purchase over the counter if the patient wishes to use them.

Bath and shower emollients are therefore included in the NHS England » Items which should not be routinely prescribed in primary care. Lincolnshire is prescribing less of these items than other ICBs – well done and keep it up!

Bandaging for dermatological conditions

Bandaging can sometimes be a useful adjuvant to eczema treatments. Covering the eczema with bandages can help with the itch–scratch cycle and flare ups. It prevents damage to the skin from scratching, aids healing and enhances the absorption of topical therapies (emollients, and topical corticosteroids used with caution). There are two types commonly used:

- Impregnated paste bandages can be useful for treating eczema of the limbs, especially chronic and/or lichenified eczema. Examples are zipzoc and icthopaste.

- Wet wraps are ideal for treating extensive eczema that is not controlled by conventional treatments. These should be initiated by healthcare professionals with experience in wet-wrapping eczema, and support may be required in primary care (to supply replacements on average 3 monthly). In Lincolnshire we commonly use the skinnies viscose brand. We don’t use silk versions in atopic eczema.

Silk Garments

Silk garments are also included in the NHS England » Items which should not be routinely prescribed in primary care guidance. Lincolnshire does still have some prescribing of these items; the items listed below are the ones identified by EPACT2 as falling into the category, as should not be being prescribed.

Silk garments have primarily been used in the past for patients with atopic eczema although they have also been used for a variety of other conditions including vulvar conditions, epidermolysis bullosa and burns. A range of garments are available including eye masks, socks, gloves, vests, pyjamas, and body suits.

Silk garments are classified as medical devices. Currently, manufacturers need to ensure that their devices are safe and fit for their intended purpose to gain the CE mark; there is no requirement for clinical trials of efficacy. NHS England has designated silk garments as having low clinical effectiveness, and a lack of robust evidence of clinical efficacy. A summary of the available evidence is available here, but the small sample sizes in the available trials limit any conclusions which can be drawn.

Due in part to the limited evidence available, the NIHR HTA programme commissioned the CLOTHES trial to look at whether silk garments had a role in reducing eczema severity. This concluded that silk garments are unlikely to be cost effective to the NHS.

It is important when reviewing silk garment prescribing not to confuse all Skinnies brand prescribing with silk garments. Very, very rarely a tertiary referral centre may recommend a silk garment for one of the rarer dermatological diseases and potentially burn injuries. These recommendations should come from very specialist clinics, and the GP should expect to see evidence of MDT consultation and seek advice on duration of treatment, so that they are aware of how best to approach prescribing.

Resources for patients

Eczema NHS Choices – Atopic eczema https://www.nhs.uk/conditions/atopic-eczema/

The National Eczema Society produces several factsheets, including one on emollients. Access via Information & Advice | National Eczema Society

The Nottingham Support Group for Carers of Children with Eczema produces information leaflets. Subjects include ‘Skin moisturisers in atopic eczema’ and ‘Bathing and showering’. Access via http://www.nottinghameczema.org.uk/information/index.aspx#Treatments

The British Association of Dermatologists has a Patient Information Leaflet about Atopic eczema and psoriasis. Access via http://www.bad.org.uk/for-the-public/patient-information-leaflets

Psoriasis NHS Choices – Psoriasis https://www.nhs.uk/conditions/psoriasis/

The Psoriasis and Psoriatic Arthritis Alliance have a number of resources, including one about ‘Emollients and psoriasis’. Access via Psoriasis and Psoriatic Arthritis Alliance (PAPAA)

General NHS Choices – Emollients https://www.nhs.uk/conditions/Emollients

Eczema Care Online has lots of useful resources: Intro | ECO (eczemacareonline.org.uk)

References

Lincolnshire Emollient Guidance accaessed via PACEF :: Lincolnshire Prescribing and Clinical Effectiveness (lincolnshire-pacef.nhs.uk) on 14/8/2024

Atopic eczema in primary care: evidence update and implications for practice (bjgp.org) accessed online on 14/8/2024

PrescQIPP Bulletin 239: Emollients; June 2020 accessed online on 14/8/2024 at 239. Emollients 2.0 (prescqipp.info)

NICE Guideline CG57; June 2023 accessed online on 14/8/2023 available at CG57 Atopic eczema in under 12s: diagnosis and management (update): Evidence review A 07/06/2023 (nice.org.uk)

EPACT2 accessed online at Oracle Analytics Interactive Dashboards - Items not for Routine Prescribing (nhsbsa.nhs.uk) on 23/8/2024

NHS England » Items which should not routinely be prescribed in primary care: policy guidance accessed online on 23/8/2024

NHS England » Guidance on conditions for which over the counter items should not routinely be prescribed in primary care accessed online on 23/8/2024

Emollient bath additives for the treatment of childhood eczema (BATHE): multicentre pragmatic parallel group randomised controlled trial of clinical and cost effectiveness accessed online on 23/8/2024 at BMJ 2018;361:k1332

Specialist Pharmacy Service “Clinical evidence for emollient bath and shower preparations” accessed online on 23/8/2024

Specialist Pharmacy Service “Clinical evidence for silk garments” accessed online on 23/8/2024

The Drug Tariff accessed online on 2/9/2024 Drug Tariff Part IX | NHSBSA

Lincolnshire Position Statement on the ongoing supply of Pancreatic Enzyme Replacement Therapy (PERT)

22nd August 2024 (Updated 28/8/24)

The ongoing supply issues surrounding pancreatic enzyme replacement therapy (PERT) has progressed. These intermittent supply issues mean some people are running out of PERT or experiencing difficulties or delays in accessing PERT. Therefore, there is a need for clinical and symptom management advice that is different to normal clinical practice. For the full statement please see here.

Please also see below wording and statement intended for patients.

Patient letter: Supply issues associated with Pancreatic Enzyme Replacement Therapy (PERT)

The ICB is working with United Lincolnshire Hospital Trust (ULHT) and community pharmacies to put in place a process to manage the current very severe shortage of pancreatic enzyme replacement therapy (PERT)

Advice has already been sent out to all clinicians on the management of patients affected by the supply problems. The ICB and ULHT have also jointly produced this letter, which is intended to provide further information and advice to patients. Please read this here.

Updated Lincolnshire Emollient Formulary Guidance

8th August 2024

The Lincolnshire Emollient Formulary Guidance has been updated in line with the recent Epimax Ointment and Epimax Paraffin-Free Ointment drug safety update. The drug safety update was issued following reports of ocular surface toxicity and ocular chemical injury.

The following changes have been made:

• ‘Do NOT use on the face, to avoid contact with the eyes’ added to Epimax Ointment and Epimax Paraffin-Free Ointment.
• Links to the drug safety update added to guidance for reference.

Please find the guidance here.

Please find the drug safety update here.