UK MHRA


It is indicated for some locally advanced or metastatic breast cancer. There have been reports of interstitial lung disease and pneumonitis with these medicines, in some cases severe or fatal. Patients taking these medicines are aware of the need to seek advice right away if they develop new or worsening respiratory symptoms.

Acitretin:

Oral forms of the retinoid medicines Acitretin is used in the treatment of severe dermatological diseases that are resistant or unresponsive to standard therapies.

Guidance of UKMHRA:

UKMHRA have recently issued Guidance for specialists to support the safety of patients on oral retinoids. The requirements for monitoring of these safety issues reflect established safety measures for oral retinoid medicines. Prescribing of these medicines is understood to be increasing to more normal levels following reduced use earlier in the pandemic. The Guidance is to remind specialists of the need to implement the Pregnancy Prevention Programme (PPP) and monitor all patients taking oral retinoids and to support them in protecting the safety of patients while remote appointments continue. The guidance also includes advice that can be provided to patients to help them understand the monitoring requirements.

Psychiatric adverse events have been reported in patients taking oral retinoids for skin disorders, and with respect to isotretinoin; these are currently under review. Prescribers are reminded to inform patients of the risk of psychiatric side effects. Patients should also be encouraged to inform friends and family that they are taking an oral retinoid so that they can be alert for any changes in mood.

Remote consultations should occur with at least the same frequency as the usual clinic consultations, to allow adequate monitoring of mental health and other potential adverse events.

Oral forms of the retinoid medicines Alitretinion is used in the treatment of severe dermatological diseases that are resistant or unresponsive to standard therapies. UKMHRA have recently issued Guidance for specialists to support the safety of patients on oral retinoids. The requirements for monitoring of these safety issues reflect established safety measures for oral retinoid medicines. Prescribing of these medicines is understood to be increasing to more normal levels following reduced use earlier in the pandemic. The Guidance is to remind specialists of the need to implement the Pregnancy Prevention Programme (PPP) and monitor all patients taking oral retinoids and to support them in protecting the safety of patients while remote appointments continue. The guidance also includes advice that can be provided to patients to help them understand the monitoring requirements.

Psychiatric adverse events have been reported in patients taking oral retinoids for skin disorders, and with respect to isotretinoin; these are currently under review. Prescribers are reminded to inform patients of the risk of psychiatric side effects. Patients should also be encouraged to inform friends and family that they are taking an oral retinoid so that they can be alert for any changes in mood.

Remote consultations should occur with at least the same frequency as the usual clinic consultations, to allow adequate monitoring of mental health and other potential adverse events.


Aminoglycosides are broad-spectrum bactericidal antibiotics. The group includes gentamicin, amikacin, tobramycin, and neomycin.

Evidence suggests an increased risk of aminoglycoside-associated ototoxicity in patients with mitochondrial mutations, including cases in which the patient’s aminoglycoside serum levels were within the recommended range. These mitochondrial mutations are rare and penetrance is uncertain. Genetic testing should not delay urgently needed aminoglycoside treatment but may be considered, especially before the start of recurrent or long-term treatment.

Antiepileptic drugs:

Antiepileptic drugs are crucial to control seizures and other epilepsy symptoms and untreated epilepsy can cause harm to both the mother and the unborn baby. However, use of these antiepileptic drugs during pregnancy has been associated with a range of harmful effects to the baby.

Clinicians should use this information when discussing treatment options with women with epilepsy at initiation and at routine recommended annual reviews and in women planning to become pregnant.

Summary of key conclusions of review

• Lamotrigine – Studies involving more than 12,000 pregnancies exposed to lamotrigine monotherapy consistently show that lamotrigine at maintenance doses is not associated with an increased risk of major congenital malformations.

• Levetiracetam – Studies involving more than 1,800 pregnancies exposed to levetiracetam do not suggest an increased risk of major congenital malformations.

• For both lamotrigine and levetiracetam, the data on neurodevelopmental outcomes are more limited than those for congenital malformations. The available studies do not suggest an increased risk of neurodevelopmental disorders or delay associated with in-utero exposure to either lamotrigine or levetiracetam; however, the data is inadequate to rule out definitively the possibility of an increased risk.

• For the other key antiepileptic drugs, data show: o an increased risk of major congenital malformations associated with carbamazepine, phenobarbital, phenytoin, and topiramate use during pregnancy o the possibility of adverse effects on neurodevelopment of children exposed in utero to phenobarbital and phenytoin o an increased risk of fetal growth restriction associated with phenobarbital, topiramate, and zonisamide use during pregnancy.

Actions for prescribers

• At initiation and as part of the recommended annual review for patients with epilepsy, specialists should discuss with women the risks associated with antiepileptic drugs and with untreated epilepsy during pregnancy and review their treatment according to their clinical condition and circumstances – we have produced a safety information leaflet to assist with this discussion.

• Urgently refer women who are planning to become pregnant for specialist advice on their antiepileptic treatment.

• All women using antiepileptic drugs who are planning to become pregnant should be offered 5mg per day of folic acid before any possibility of pregnancy.

• For lamotrigine, levetiracetam or any antiepileptic drugs that can be used during pregnancy, it is recommended to

-use monotherapy whenever possible.

-use the lowest effective dose (see later for key dose monitoring advice, including for lamotrigine and levetiracetam)

Reminder of advice to give to women with epilepsy

• Do not stop taking antiepileptic drugs without discussing it with your doctor

• If you are taking an antiepileptic drug and think you may be pregnant, seek urgent medical advice, including urgent referral to your specialist.

Atezolizumab is an immune-stimulatory drug indicated for cancers including those of the bladder, lung, and liver. Cases of severe cutaneous adverse reactions, including Stevens-Johnsons syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in patients treated with immune-stimulatory anti-cancer drugs, including atezolizumab.

Caution:

Advise patients to be vigilant for the signs of severe skin reactions and to seek urgent medical advice if they occur.

Increased risk of non-melanoma skin cancer and progressive multifocal encephalopathy (PML)

Caution:

Periodically perform skin examinations in patients on bendamustine-containing regimens and consider PML in the differential diagnosis for patients on bendamustine with new or worsening neurological, cognitive, or behavioural signs or symptoms.

Restriction of paediatric indication

Caution:

The paediatric indication for chloral hydrate (for children aged 2 years and older) and cloral (previously chloral) betaine (children aged 12 years and older) has been restricted to short-term treatment (maximum 2 weeks) of severe insomnia only when the child or adolescent has a suspected or definite neurodevelopmental disorder and when the insomnia is interfering with normal daily life. Chloral hydrate and cloral betaine should only be used when other therapies (behavioural and pharmacological) have failed.

Chloramphenicol eye drops are an important medicine for treating bacterial eye infections in children and have been used safely for many years. Some eye drops contain borax or boric acid, which are sources of boron – these ingredients are included as buffers to make sure the medicine is not too acidic or alkaline and is comfortable when administered to the eye. Although concerns have been raised about boron and its possible effect on future fertility, these products can be safely given to children younger than 2 years as advised by a doctor or other prescriber. Experts have advised that the amount of liquid that can be absorbed through the eyes of young children and the way these products are prescribed mean that the daily exposure to children would be well below the calculated safety limits.

Restriction of paediatric indication

Caution:

The paediatric indication for chloral hydrate (for children aged 2 years and older) and cloral (previously chloral) betaine (children aged 12 years and older) has been restricted to short-term treatment (maximum 2 weeks) of severe insomnia only when the child or adolescent has a suspected or definite neurodevelopmental disorder and when the insomnia is interfering with normal daily life. Chloral hydrate and cloral betaine should only be used when other therapies (behavioural and pharmacological) have failed.

The authorisation holder for dapagliflozin has withdrawn the indication for type 1 diabetes mellitus. The removal of the type 1 diabetes indication is not due to any new safety concerns and the other indications of dapagliflozin are unchanged. 

Dimethyl fumarate is authorised to treat adults with relapsing-remitting multiple sclerosis.

Updated advice on the risk of progressive multifocal leukoencephalopathy (PML) associated with mild lymphopenia:

The monitoring requirements and discontinuation criteria for dimethyl fumarate have been strengthened following a small number of reports of progressive multifocal leukoencephalopathy (PML) in patients with mild lymphopenia. Continue to monitor lymphocyte counts and advise patients to seek urgent medical attention if they experience any symptoms or signs suggestive of PML.

Fingolimod is authorised to treat patients aged 10 years or older with highly active relapsing-remitting multiple sclerosis that has not responded to at least one disease-modifying therapy or which is severe and rapidly progressive.

Updated advice about the risks of serious liver injury and herpes meningoencephalitis:

-Liver monitoring requirements and criteria for discontinuation of fingolimod have been updated following reports of serious liver injury.

-Fatal cases of encephalitis and meningitis caused by herpes simplex and varicella zoster viruses have also been reported during treatment.

-Advise patients to seek urgent medical attention if they develop any clinical features of liver dysfunction or meningoencephalitis.

-Discontinue fingolimod if significant hepatic injury or herpes meningoencephalitis is confirmed.

Reminder of risks when used in elderly patients for the acute treatment of delirium.


Remind healthcare professionals that elderly patients are at an increased risk of adverse neurological and cardiac effects when being treated with haloperidol for delirium. The lowest possible dose of haloperidol should be used for the shortest possible time, and cardiac and extrapyramidal adverse effects should be closely monitored.

Oral forms of the retinoid medicines isotretinoin is used in the treatment of severe dermatological diseases that are resistant or unresponsive to standard therapies. UKMHRA have recently issued Guidance for specialists to support the safety of patients on oral retinoids. The requirements for monitoring of these safety issues reflect established safety measures for oral retinoid medicines. Prescribing of these medicines is understood to be increasing to more normal levels following reduced use earlier in the pandemic. The Guidance is to remind specialists of the need to implement the Pregnancy Prevention Programme (PPP) and monitor all patients taking oral retinoids and to support them in protecting the safety of patients while remote appointments continue. The guidance also includes advice that can be provided to patients to help them understand the monitoring requirements.

Psychiatric adverse events have been reported in patients taking oral retinoids for skin disorders, and with respect to isotretinoin; these are currently under review. Prescribers are reminded to inform patients of the risk of psychiatric side effects. Patients should also be encouraged to inform friends and family that they are taking an oral retinoid so that they can be alert for any changes in mood.

Remote consultations should occur with at least the same frequency as the usual clinic consultations, to allow adequate monitoring of mental health and other potential adverse events.

Caution:

If a patient reports persistent symptoms when switching between different levothyroxine tablet formulations, consider consistently prescribing a specific product known to be well tolerated by the patient. If symptoms or poor control of thyroid function persist (despite adhering to a specific product), consider prescribing levothyroxine in an oral solution formulation.

In autoimmune conditions and some cancer therapies, methotrexate should be taken only once a week; however, we continue to receive reports of inadvertent overdose due to more frequent dosing (including daily administration). New measures have been implemented to prompt healthcare professionals to record the day of the week for intake and to remind patients of the dosing schedule and the risks of overdose.

It is indicated for some locally advanced or metastatic breast cancer. There have been reports of interstitial lung disease and pneumonitis with these medicines, in some cases severe or fatal. Patients taking these medicines are aware of the need to seek advice right away if they develop new or worsening respiratory symptoms.

It is indicated for some locally advanced or metastatic breast cancer. There have been reports of interstitial lung disease and pneumonitis with these medicines, in some cases severe or fatal. Patients taking these medicines are aware of the need to seek advice right away if they develop new or worsening respiratory symptoms.

SSRIs: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline

SNRIs: desvenlafaxine, milnacipran, venlafaxine, Vortioxetine


Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) are two classes of commonly used antidepressant medicines.

SSRIs and SNRIs are known to increase bleeding risks due to their effect on platelet function. Data from observational studies suggest that the use of SSRI/SNRI antidepressants during the month before delivery may result in a small increased risk of postpartum haemorrhage.

Prescribers should consider this risk in the context of an individual patient’s bleeding and thrombotic risk assessment during the peripartum period and the benefits of antidepressants for the patient’s mental health during this time.

New measures to minimise risk of major adverse cardiovascular events and malignancies.

Caution:

Tofacitinib should not be used in patients older than 65 years of age, people who are current or past smokers, or individuals with other cardiovascular (such as diabetes or coronary artery disease) or malignancy risk factors unless there are no suitable treatment alternatives.

Caution:

Rarely, severe adverse effects can occur on stopping treatment with topical corticosteroids, often after long-term continuous or inappropriate use of moderate to high potency products. To reduce the risks of these events, prescribe the topical corticosteroid of lowest potency needed and ensure patients know how to use it safely and effectively.

Ulipristal acetate 5mg:

The indication of ulipristal acetate 5mg for uterine fibroids has been further restricted due to the risk of serious liver injury and liver failure, with some cases requiring liver transplantation. Although the temporary suspension has been lifted, this medicine should only be used for intermittent treatment of moderate to severe symptoms of uterine fibroids before menopause and when surgical procedures (including uterine fibroid embolisation) are not suitable or have failed.


Ulipristal acetate 30mg:

No concern has been raised about serious liver injury with emergency contraceptive pill containing ulipristal acetate in a single dose of 30mg and so there are no changes to its use.

Fatal cases of tumour lysis syndrome (TLS) have been reported, some occurring in patients with chronic lymphocytic leukaemia receiving the lowest venetoclax dose used in the dose-titration schedule. For all patients, it is important to strictly adhere to the dose-titration schedule and to the measures to minimise the risk of TLS