MHRA – Drug Safety Update
Fluoroquinolone antibiotics: new restrictions and precautions for use due to very rare reports of disabling and potentially long-lasting or irreversible side effects
Disabling, long-lasting or potentially irreversible adverse reactions affecting musculoskeletal and nervous systems have been reported very rarely with fluoroquinolone antibiotics. Fluoroquinolone treatment should be discontinued at the first signs of a serious adverse reaction, including tendon pain or inflammation.
Onivyde (irinotecan, liposomal formulations): reports of serious and fatal thromboembolic events
Onivyde has been associated with reports of serious thromboembolic events, such as pulmonary embolism, venous thrombosis, and arterial thromboembolism.
Medicines with teratogenic potential: what is effective contraception and how often is pregnancy testing needed?
New guidance on contraceptive methods and frequency of pregnancy testing to reduce inadvertent exposures during pregnancy in a woman taking a medicine of teratogenic potential.
Letters and drug alerts sent to healthcare professionals in February 2019
Letters were sent about Vyxeos (cytarabine, daunorubicin) and Ozurdex 700 micrograms intravitreal implant (dexamethasone). Alerts were issued about irbesartan, amoxicillin, atropine sulfate, and paracetamol infusion.
Medical Device Alerts issued in February 2019
Alerts issued include important actions for enFlow IV fluid and blood warmers due to a risk of unsafe levels of aluminium leaching from the device. Other alerts were issued on implantable cardiac pacemakers, Accu-Chek Insight insulin pumps, and professional use monitor/defibrillator LIFEPAK 15.
Carbimazole: increased risk of congenital malformations; strengthened advice on contraception
Carbimazole is associated with an increased risk of congenital malformations, especially when administered in the first trimester of pregnancy and at high doses. Women of childbearing potential should use effective contraception during treatment with carbimazole.
Carbimazole: risk of acute pancreatitis
If acute pancreatitis occurs during treatment with carbimazole, immediately and permanently stop treatment.
SGLT2 inhibitors: reports of Fournier’s gangrene (necrotising fasciitis of the genitalia or perineum)
If Fournier’s gangrene is suspected, stop the SGLT2 inhibitor and start treatment urgently (including antibiotics and surgical debridement).
Letters and drug alerts sent to healthcare professionals in January 2019
Letters were sent to healthcare professionals about Lartruvo▼ (olaratumab), quadrivalent influenza vaccine (split virion, inactivated), SGLT2 inhibitors, and carbimazole and thiamazole (synonym: methimazole)-containing products. Class 2 medicines recalls were issued for batches of irbesartan/hydrochlorothiazide and irbesartan tablets.
Tapentadol (Palexia): risk of seizures and reports of serotonin syndrome when co-administered with other medicines
Tapentadol may increase seizure risk in patients taking other medicines that lower seizure threshold, for example, antidepressants and antipsychotics. Serotonin syndrome has also been reported when tapentadol is used in combination with serotoninergic antidepressants.
Ipilimumab (Yervoy): reports of cytomegalovirus (CMV) gastrointestinal infection or reactivation
Patients on ipilimumab who present with diarrhoea or other symptoms of colitis, and those who do not respond to steroid treatment for immune-related colitis, should be investigated to exclude other causes, including infections such as cytomegalovirus (CMV).
Yellow Card App: download the updated App to receive the latest MHRA safety news and report suspected side effects, including in pregnancy
The Yellow Card App has been updated to make it easier to use, to have useful new features, and to support reporting a suspected reaction related to medicine exposure during pregnancy. Download the App today and let us know your thoughts.
Letters and drug alerts sent to healthcare professionals in December 2018
In December 2018, a letter was sent to notify healthcare professionals of the discontinuation of Zovirax (Aciclovir) eye ointment. We also highlight the recent recall of Actavis batches of irbesartan/hydrochlorothiazide tablets from pharmacies as a precautionary measure due to possible contamination with N-nitrosodiethylamine (NDEA).
Medical Device Alerts issued in December 2018
A notice was issued by Allergan about the availability of textured breast implants in the UK.
Article published in advance of December 2018 issue
Oral lidocaine-containing products for infant teething: only to be available under the supervision of a pharmacist
Oral lidocaine-containing products for infant teething are only to be available under the supervision of a pharmacist so that parents and caregivers can receive guidance about managing infant teething symptoms. Non-medicinal options such as a teething ring or massaging the gum should be the first line for relieving infant teething symptoms, and lidocaine-containing products should only be used when simple measures have failed to provide sufficient relief.
Hydrochlorothiazide: risk of non-melanoma skin cancer, particularly in long-term use
Advise patients taking hydrochlorothiazide-containing products of the cumulative, dose-dependent risk of non-melanoma skin cancer, particularly in long-term use, and the need to regularly check for (and report) any suspicious skin lesions or moles. Counsel patients to limit exposure to sunlight and UV rays and to use adequate sun protection.
Systemic and inhaled fluoroquinolones: small increased risk of aortic aneurysm and dissection; advice for prescribing in high-risk patients
In patients at risk for aortic aneurysm and dissection, fluoroquinolones should only be used after careful assessment of the benefits and risks and after consideration of other therapeutic options.
Sildenafil (Revatio and Viagra): reports of persistent pulmonary hypertension of the newborn (PPHN) following in-utero exposure in a clinical trial on intrauterine growth restriction
Sildenafil is not authorised for use in pregnancy for the treatment of intrauterine growth restriction.
Support Yellow Card: improve the safety of medicines in pregnancy and breastfeeding, and in babies and children
Reporting suspected adverse drug reactions to the Yellow Card Scheme helps to support the safe use of medicines in babies, children, and pregnant and breastfeeding women. Show your support for this year’s EU-wide ADR awareness week campaign from 19–23 November 2018, by sharing material on social media and discussing the importance of reporting suspected side effects with colleagues and parents and caregivers.
Letters and drug alerts sent to healthcare professionals in October 2018
Letters were sent to healthcare professionals about Jext adrenaline autoinjectors, rivaroxaban, Ozurdex 700 micrograms intravitreal implant, sildenafil, hydrochlorothiazide, and Epilim Chronosphere (sodium valproate). We also highlight alerts sent about adrenaline autoinjector and Epanutin (phenytoin) supply disruption and a recall notice for Ozurdex 700 micrograms intravitreal implants.
Medical Device Alerts issued in October 2018
An alert was recently issued by MHRA about CoaguChek Test Strips for Point of Care and Home Use due to a risk of false high results. Affected CoaguChek test strips may give false high results for INR values above 4.5 when compared to laboratory results, which may lead to incorrect treatment decisions.
Rivaroxaban (Xarelto▼) after transcatheter aortic valve replacement: increase in all-cause mortality, thromboembolic and bleeding events in a clinical trial
Rivaroxaban treatment in patients who undergo transcatheter aortic valve replacement (TAVR) should be stopped and switched to standard of care.
Ritonavir-containing products: reports of interaction with levothyroxine leading to reduced thyroxine levels
Monitor thyroid-stimulating hormone (TSH) in patients treated with levothyroxine for at least the first month after starting and ending ritonavir treatment.
Ponatinib (Iclusig▼): reports of posterior reversible encephalopathy syndrome
Interrupt treatment if posterior reversible encephalopathy syndrome (PRES) is confirmed and resume treatment only once the event is resolved and the benefit of continued treatment outweighs the risk of PRES.
Transdermal fentanyl patches: life-threatening and fatal opioid toxicity from accidental exposure, particularly in children
Provide clear information to patients and caregivers about how to minimise the risk of accidental exposure and the importance of appropriate disposal of patches. We continue to receive reports of unintentional opioid toxicity and overdose of fentanyl due to accidental exposure to patches.
Letters and drug alerts sent to healthcare professionals in September 2018
A supply disruption alert was issued by the Department of Health & Social Care (DHSC) on EpiPen and EpiPen Junior; see MHRA advice on extension of use beyond the expiry date for certain batches of EpiPen 300 microgram adrenaline autoinjectors. MHRA issued alerts and recalls for batches of Olmetec, Mydriasert, Caspofungin, and Imatinib.
Medical Device Alerts issued in September 2018
Alerts were recently issued by MHRA about flex connectors in Halyard closed suction kits; SureSigns VS & VM patient monitors and viewing stations; and Zimmer Biomet trauma guide wires.
Valproate Pregnancy Prevention Programme: actions required now from GPs, specialists, and dispensers
Valproate medicines must not be used in women of childbearing potential unless the Pregnancy Prevention Programme is in place.
Xofigo▼ (radium-223-dichloride): new restrictions on use due to increased risk of fracture and trend for increased mortality seen in clinical trial
Now only authorised for use in patients with symptomatic bone metastases and no known visceral metastases who have had 2 previous systemic treatments for metastatic castration-resistant prostate cancer or who cannot receive other systemic treatments. Do not use in combination with abiraterone acetate and prednisone/prednisolone.
Daclizumab beta (Zinbryta▼): risk of immune-mediated encephalitis – some cases several months after stopping treatment
Monitoring for encephalitis should continue for 12 months following discontinuation of daclizumab. Inform all patients who have discontinued daclizumab and their caregivers of the common symptoms of encephalitis and the need to contact their doctor immediately if they occur.
Nusinersen (Spinraza▼): reports of communicating hydrocephalus; discuss symptoms with patients and carers and investigate urgently
Advise patients and their caregivers to seek urgent medical attention if any signs or symptoms of communicating hydrocephalus develop during nusinersen therapy for spinal muscular atrophy. Patients with communicating hydrocephalus may require treatment with a cerebrospinal fluid (CSF) shunt.
Letters and drug alerts sent to healthcare professionals in August 2018
Letters were sent about daclizumab beta (Zinbryta▼), alteplase (Actilyse), Esmya (ulipristal acetate), and Xofigo▼ (radium-223-dichloride). MHRA issued alerts and recalls for batches of Nutriflex Omega Special 2500 ml and Nutriflex Lipid Special 2500 ml.
Esmya (ulipristal acetate) and risk of serious liver injury: new restrictions to use and requirements for liver function monitoring before, during, and after treatment
More than one treatment course is authorised only in women who are not eligible for surgery, and liver function monitoring is to be carried out in all women treated with Esmya.
Letters and drug alerts sent to healthcare professionals in July 2018
Letters were sent about valproate medicines, atezolizumab (Tecentriq▼), and nusinersen (Spinraza▼).
Letters sent to healthcare professionals in July 2018
Alerts were recently issued about Novaline haemodialysis bloodlines used with Baxter/Gambro haemodialysis machines and Alaris and Asena enteral syringe pumps.
New pharmacokinetic data show mean exposure of darunavir (brand name Prezista) boosted with cobicistat (available in combination in Rezolsta▼, Symtuza▼) to be lower during the second and third trimesters of pregnancy than during 6–12 weeks postpartum.Darunavir boosted with cobicistat: avoid use in pregnancy due to risk of treatment failure and maternal-to-child transmission of HIV-1
Pressurised metered dose inhalers (pMDI): risk of airway obstruction from aspiration of loose objects
Remind patients to check and remove the mouthpiece cover properly before inhaling a dose and to shake the inhaler to remove loose objects that may have become trapped in the inhaler during storage.
Eltrombopag (Revolade): reports of interference with bilirubin and creatinine test results
If bilirubin and/or creatinine test results are inconsistent with clinical observations, request re-testing using another method to determine the validity of the result.
Parenteral amphotericin B: reminder of risk of potentially fatal adverse reaction if formulations confused
Following receipt of a third case of fatal medication error caused by the administration of Fungizone (a non-lipid-based formulation of amphotericin B) instead of a lipid-based formulation (AmBisome, Abelcet), we remind healthcare professionals that these formulations are not interchangeable.
Medicines taken during pregnancy: please report suspected adverse drug reactions, including in the baby or child, on a Yellow Card
Report to the Yellow Card Scheme suspected adverse reactions associated with medicines taken during pregnancy experienced by women or the baby or child.
Letters sent to healthcare professionals in June 2018
Letters were sent about Cetrotide (cetrorelix acetate), Eperzan▼(albiglutide), darunavir/cobicistat, Keytruda▼ (pembrolizumab), Denzapine (clozapine) 50 mg/mL oral suspension, and Bleo-Kyowa (bleomycin sulphate).
Medical Device Alert issued in June 2018
Alerts were recently issued by MHRA about Smiths Medical medication cassette reservoirs, Alaris Smartsite add-on bag access devices, and Combur10 Test UX and Chemstrip 10 A urinalysis test strips.
Dolutegravir (Tivicay▼, Triumeq▼, Juluca▼): signal of increased risk of neural tube defects; do not prescribe to women seeking to become pregnant; exclude pregnancy before initiation and advise use of effective contraception
New safety recommendations have been issued while an EU review evaluates cases of neural tube defects in babies born to mothers who became pregnant while taking the HIV medicine dolutegravir.
Denosumab (Xgeva▼) for giant cell tumour of bone: risk of clinically significant hypercalcaemia following discontinuation
Monitor patients for signs and symptoms of hypercalcaemia after discontinuation of denosumab treatment for giant cell tumour of bone.
Denosumab (Xgeva▼) for advanced malignancies involving bone: study data show new primary malignancies reported more frequently compared to zoledronate
A pooled analysis has shown an increased rate of new primary malignancies in patients given Xgeva (1-year cumulative incidence 1.1%) compared with those given zoledronic acid (0.6%), when used in the indication of the prevention of skeletal-related events with advanced malignancies involving bone.
Letters sent to healthcare professionals in May 2018
Letters were sent about azithromycin, Lynparza▼(Olaparib), Xgeva▼ (denosumab), Lymphoseek (tilmanocept), ReoPro (abciximab) and dolutegravir; you still have time to complete a quick survey to tell us your views on the way medicines safety issues are communicated.
MHRA – Drug Safety Update
Valproate medicines (Epilim▼, Depakote▼): Pregnancy Prevention Programme materials online
Use materials online now and hardcopies arriving over the coming weeks by post to ensure women and girls of childbearing potential on valproate medicines meet the requirements of the Pregnancy Prevention Programme.
Braltus (tiotropium): risk of inhalation of capsule if placed in the mouthpiece of the inhaler
Train patients to place the Braltus capsule in the correct chamber of the Zonda inhaler.
Letters sent to healthcare professionals in April 2018
Letters were sent about insulin Fiasp and Tresiba and Inhixa (enoxaparin sodium); use survey to feedback your thoughts on Direct Healthcare Professional Communications (DHPCs) and on the way medicines safety issues are communicated.
Medical Device Alerts issued in April 2018; recent alert about Accu-Chek blood glucose test strips
An alert was issued recently about Accu-Chek Aviva, Accu-Chek Performa, and Accu-Chek Inform II test strips – risk of strip error messages and false high and low blood glucose results.
MHRA – Drug Safety Update
Valproate medicines (Epilim▼, Depakote▼): contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met
Valproate medicines must no longer be used in women or girls of childbearing potential unless a Pregnancy Prevention Programme is in place.
Obeticholic acid (Ocaliva▼): risk of serious liver injury in patients with pre-existing moderate or severe hepatic impairment; reminder to adjust dosing according to liver function monitoring
We are aware of reports of serious liver injuries and deaths in patients with primary biliary cholangitis with pre-existing moderate or severe liver impairment who were not adequately dose-adjusted.
Suspect an adverse reaction? Yellow Card it!
Any healthcare professional can submit a Yellow Card, including students.
Letters sent to healthcare professionals in March 2018
Letters were sent to healthcare professionals about Zinbryta▼ (daclizumab beta), Lynparza 50 mg capsules, and radium-223-dichloride (Xofigo▼).
Medical Device Alerts issued in March 2018
An alert was issued about T34 ambulatory syringe pumps.
Misoprostol vaginal delivery system (Mysodelle): reports of excessive uterine contractions (tachysystole) unresponsive to tocolytic treatment
Monitor patients closely and remove the vaginal delivery system immediately in cases of excessive or prolonged uterine contractions, at the onset of labour, or if there is clinical concern for mother or baby.
Mycophenolate mofetil, mycophenolic acid: updated contraception advice for male patients
Mycophenolate mofetil and its active metabolite mycophenolic acid, both used to prevent transplant rejection, are teratogenic and genotoxic.
Gadolinium-containing contrast agents: Omniscan and iv Magnevist no longer authorised, MultiHance and Primovist for use only in liver imaging
Omniscan and intravenous Magnevist are now no longer authorised for use and a product recall of any existing unexpired stock is underway.
Letters sent to healthcare professionals in January 2018
Letters were sent about Buccolam (midazolam), misoprostol vaginal delivery system (Mysodelle), noradrenaline, Relenza (zanamivir), mycophenolate mofetil/mycophenolic acid, Flolan, and Fludara.
Medical Device Alerts issued in January 2018
Alerts were recently issued by MHRA about all Philips HeartStart MRx monitors/defibrillators and Boston Scientific pacemakers and CRT-P.
Daclizumab (Zinbryta▼) and risk of severe liver injury: new restrictions to use and strengthened liver monitoring
The use of daclizumab (daclizumab beta) is now restricted to adults with relapsing multiple sclerosis who have had an inadequate response to at least 2 other disease-modifying therapies (DMTs) and for whom other DMTs are contraindicated or unsuitable.
Recombinant human erythropoietins: very rare risk of severe cutaneous adverse reactions (SCARs)
Recombinant human erythropoietin (r-HuEPO) treatment has been associated with very rare cases of life-threatening severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Drug-name confusion: reminder to be vigilant for potential errors
Take particular care when prescribing or dispensing medicines that could be confused with others (ie, they sound-alike or look-alike).
Co-dydramol: prescribe and dispense by strength to minimise risk of medication error
Previously co-dydramol (dihydrocodeine/paracetamol) was available only in the ratio 1:50 (co-dydramol 10/500 mg).
Herbal medicines: report suspected adverse reactions to the Yellow Card Scheme
If an adverse reaction is suspected, ask patients whether they are taking any herbal medicines and discuss with them the importance of reporting this via the Yellow Card Scheme.
Letters sent to healthcare professionals in December 2017
Letters were sent about cladribine (Litak and Leustat), radium-223-dichloride (Xofigo▼), and ERWINASE.
Medical Device Alerts issued in December 2017
Alerts were recently issued about BD Alaris/Asena syringe pumps and Maxter Catheters nasogastric (NG) feeding tubes.
Gadolinium-containing contrast agents: removal of Omniscan and iv Magnevist, restrictions to the use of other linear agents
A review has found that low levels of gadolinium can be retained in the brain and other tissues after administration of gadolinium-containing contrast agents (GdCAs).
Cladribine (Litak, Leustat) for leukaemia: reports of progressive multifocal encephalopathy (PML); stop treatment if PML suspected
Consider progressive multifocal encephalopathy (PML) in the differential diagnosis for patients with new or worsening neurological signs or symptoms, even several years after treatment with cladribine.
Radium-223 dichloride (Xofigo▼): do not use in combination with abiraterone and prednisone/prednisolone, following clinical trial signal of increased risk of death and fractures
A European review has begun into the safety of radium-223 dichloride following an observed increase in the incidence of deaths and fractures in patients with chemotherapy-naive metastatic castration-resistant prostate cancer receiving radium-223 dichloride in combination with abiraterone acetate (Zytiga) and prednisone/prednisolone as part of a clinical trial.
Eluxadoline (Truberzi▼): risk of pancreatitis; do not use in patients who have undergone cholecystectomy or in those with biliary disorders
Cases of pancreatitis, with or without sphincter of Oddi spasm, have been reported in patients taking eluxadoline.
Fingolimod (Gilenya▼): new contraindications in relation to cardiac risk
Fingolimod can cause persistent bradycardia, which can increase the risk of serious cardiac arrhythmias.
Fingolimod (Gilenya▼): updated advice about risk of cancers and serious infections
Monitor patients closely for skin cancers.
Letters sent to healthcare professionals in November 2017
Letters were sent about eluxadoline (Truberzi), fingolimod (Gilenya), Bleo-Kyowa (bleomycin sulphate), Buccolam (midazolam), and ERWINASE.
Medical Device Alert issued in November 2017
An alert was recently issued about Oxoid ceftazidime antimicrobial susceptibility test discs.
Gentamicin: potential for histamine-related adverse drug reactions with some batches
Some batches of gentamicin sulphate active pharmaceutical ingredient (API) used to manufacture gentamicin may contain higher than expected levels of histamine, which is a residual from the manufacturing process.
Quinine: reminder of dose-dependent QT-prolonging effects; updated medicine interactions
Quinine has dose-dependent QT-interval-prolonging effects and should be used with caution in patients with risk factors for QT prolongation or in those with atrioventricular block.
Oral tacrolimus products: reminder to prescribe and dispense by brand name only
Inadvertent switching between tacrolimus products has been associated with reports of toxicity and graft rejection.
Support our second social media campaign for suspected adverse drug reactions
We are running a second social media campaign to promote the reporting of suspected adverse drug reactions (ADRs) to the Yellow Card Scheme in support of the ADR awareness week taking place 20-24 November 2017.
Antiepileptic drugs: updated advice on switching between different manufacturers’ products
In addition to the 3 risk-based categories of antiepileptic drugs, patient-related factors should be considered when deciding whether it is necessary to maintain continuity of supply for a specific product.
Updates to Public Health England’s Green Book chapter on live attenuated vaccines
Further to our previous advice in 2016, Public Health England have updated their guidance about live vaccination of infants born to a mother who received immunosuppressive biological therapy during pregnancy.
Letters sent to healthcare professionals in October 2017
A letter was sent about injectable methylprednisolone products containing lactose (Solu-Medrone 40 mg); do not use in patients allergic to cow’s milk proteins.
Medical Device Alert issued in October 2017
An alert was issued about Alere HIV Combo professional HIV tests.
Methylprednisolone injectable medicine containing lactose (Solu-Medrone 40 mg): do not use in patients with cows’ milk allergy
Solu-Medrone 40 mg may contain trace amounts of milk proteins.
Gabapentin (Neurontin): risk of severe respiratory depression
Gabapentin has been associated with a rare risk of severe respiratory depression even without concomitant opioid medicines.
Isotretinoin (Roaccutane): rare reports of erectile dysfunction and decreased libido
Cases of sexual dysfunction, predominantly involving erectile dysfunction and decreased libido, have been reported rarely in patients taking oral isotretinoin for severe acne.
Clozapine: reminder of potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus
If constipation occurs during treatment with clozapine (Clozaril, Denzapine, Zaponex), it is vital that it is recognised and actively treated.
Letters sent to healthcare professionals in September 2017
Letters were sent in September about Dacogen (decitabine), Eperzan▼(albiglutide), ERWINASE, ReoPro (abciximab), and recombinant human erythropoietins.
Medical Device Alerts issued in September 2017
Alerts were recently issued about Accu-Chek insulin pumps, Astral lung ventilators, and IntelliVue patient monitors used with 12-lead ECG.
Ibrutinib (Imbruvica▼): reports of ventricular tachyarrhythmia; risk of hepatitis B reactivation and of opportunistic infections
Temporarily discontinue ibrutinib in patients who develop symptoms suggestive of ventricular arrhythmia and assess benefit-risk before restarting therapy.
Corticosteroids: rare risk of central serous chorioretinopathy with local as well as systemic administration
Central serous chorioretinopathy is a retinal disorder that has been linked to the systemic use of corticosteroids. Recently, it has also been reported after local administration of corticosteroids via inhaled and intranasal, epidural, intra-articular, topical dermal, and periocular routes.
Adrenaline auto-injectors: updated advice after European review
It is recommended that 2 adrenaline auto-injectors are prescribed, which patients should carry at all times.
Letters sent to healthcare professionals in July 2017
Letters were sent about ibrutinib, daclizumab, aflibercept, valproate medicines, and arsenic trioxide.
Medical Device Alerts issued in July 2017
An alert was recently issued about Prismaflex haemofiltration machines.
Daclizumab (Zinbryta▼) and risk of severe liver injury: initiation in multiple sclerosis now restricted, promptly review patients already on treatment
While an urgent EU-wide review of new information on liver safety is under way, promptly review patients on treatment.
Bendamustine (Levact): increased mortality observed in recent clinical studies in off-label use; monitor for opportunistic infections, hepatitis B reactivation
Recent clinical trials have shown increased mortality when bendamustine (Levact) was used in combination treatments outside its approved indications.
Nivolumab (Opdivo▼), pembrolizumab (Keytruda▼): reports of organ transplant rejection
There have been reports of rejection of solid organ transplants in patients treated with nivolumab or pembrolizumab.
Letters sent to healthcare professionals in June 2017
Letters were sent about Arsenic Trioxide (Trisenox), Uptravi▼ (selexipag), DepoCyte (cytarabine), Cinryze▼ (C1 esterase inhibitor [human]), and Clexane (enoxaparin sodium).
Medical Device Alerts issued in June 2017
Alerts were recently issued about high concentration oxygen masks, metal-on-metal (MoM) hip replacements, and BVM (Bag-Valve-Mask) manual resuscitation systems.
Denosumab (Prolia, Xgeva▼): reports of osteonecrosis of the external auditory canal
Denosumab is associated with a risk of osteonecrosis of the jaw, osteonecrosis of the external auditory canal has also been reported with denosumab.
Brimonidine gel (Mirvaso): risk of systemic cardiovascular effects; not to be applied to damaged skin
Systemic cardiovascular effects including bradycardia, hypotension, and dizziness have been reported after application.
Pseudoephedrine and ephedrine: regular review of minimising risk of misuse in the UK
Sales restrictions introduced in 2008 continue to be successful in managing the risk of misuse of pseudoephedrine and ephedrine.
e-cigarettes and refill containers (e-liquids): report suspected side effects and safety concerns
Use the Yellow Card Reporting Scheme to support the safety of e-cigarettes and refill containers (e-liquids).
Letters sent to healthcare professionals in May 2017
Letters were sent about Pharmalgen (Bee Venom and Wasp Venom) Initial kits, bendamustine (Levact), and ERWINASE.
Medical Device Alerts issued in May 2017
Alerts were issued about LIFEPAK 1000 automatic external defibrillators, Mitroflow LX (sizes 19mm and 21mm) biological replacement pericardial aortic heart valves, and Accu-Chek Insight insulin pumps.
Finasteride: rare reports of depression and suicidal thoughts
We have received reports of depression and, in rare cases, suicidal thoughts in men taking finasteride 1 mg (Propecia) for male pattern hair loss.
New CPD e-learning module on reporting suspected adverse drug reactions
You can use our free e-learning modules to find out more about how and when to report suspected adverse drug reactions and earn CPD credits at the same time.
Letters sent to healthcare professionals in April 2017, including a reminder of the retigabine (Trobalt) withdrawal
A summary of letters sent to healthcare professionals, including an important reminder about the withdrawal of retigabine (Trobalt) from the market.
Valproate and developmental disorders: new alert asking for patient review and further consideration of risk minimisation measures
Babies born to mothers who take valproate medicines (Epilim▼, Depakote▼) during pregnancy have a 30–40% risk of developmental disability and a 10% risk of birth defects.
Ponatinib (Iclusig▼): risk of vascular occlusive events—updated advice on possible dose reduction
Prescribers should consider reducing the dose of ponatinib to 15 mg a day for patients with chronic phase chronic myeloid leukaemia (CP-CML) who have achieved a major cytogenetic response.
Multiple sclerosis therapies: signal of rebound effect after stopping or switching therapy
Healthcare professionals should report any suspected adverse effects relating to fingolimod (Gilenya▼) or other treatments for multiple sclerosis, including suspected adverse effects occurring after discontinuation, via the Yellow Card Scheme.
Letters sent to healthcare professionals in March 2017
A summary of letters sent to relevant healthcare professionals.
SGLT2 inhibitors: updated advice on increased risk of lower-limb amputation (mainly toes)
Canagliflozin may increase the risk of lower-limb amputation (mainly toes) in patients with type 2 diabetes.
Launch of pilot reporting scheme for harms associated with illicit drugs, particularly new psychoactive substances
We are launching a pilot scheme for healthcare professionals in the UK to report suspected adverse reactions to illicit drugs, particularly new psychoactive substances.
Hyoscine butylbromide (Buscopan) injection: risk of serious adverse effects in patients with underlying cardiac disease
Prescribing information has been updated to help to minimise the risk of serious adverse reactions in patients with cardiac disease.
Yellow Card reporting added to second clinical software system
Healthcare professionals who use Vision can now report suspected adverse reactions to MHRA directly through their clinical software.
Letters sent to healthcare professionals in January 2017
A summary of letters sent to relevant healthcare professionals in January 2017.
Direct-acting antiviral interferon-free regimens to treat chronic hepatitis C: risk of hepatitis B reactivation
All patients should be screened for hepatitis B before starting treatment for chronic hepatitis C with direct-acting antiviral interferon-free regimens.
Direct-acting antivirals to treat chronic hepatitis C: risk of interaction with vitamin K antagonists and changes in INR
INR should be monitored closely during treatment of chronic hepatitis C with direct-acting antivirals in patients also receiving vitamin K antagonists (eg, warfarin), because of possible changes in liver function during treatment.
Apremilast (Otezla ▼): risk of suicidal thoughts and behaviour
There is an increased risk that some patients may experience psychiatric symptoms with apremilast, including depression and suicidal thoughts.
Intravenous N-acetylcysteine (NAC) for paracetamol overdose: reminder of authorised dose regimen; possible need for continued treatment with NAC
The authorised dose regimen for N-acetylcysteine (NAC) in paracetamol overdose is 3 consecutive bags given intravenously over 21 hours.
Letters sent to healthcare professionals in December 2016
A summary of letters sent to relevant healthcare professionals in December 2016.
Cobicistat, ritonavir and coadministration with a steroid: risk of systemic corticosteroid adverse effects
Coadministration of a corticosteroid with an HIV-treatment-boosting agent may increase the risk of adrenal suppression due to a pharmacokinetic interaction.
Spironolactone and renin-angiotensin system drugs in heart failure: risk of potentially fatal hyperkalaemia—clarification, December 2016
In light of feedback, we have clarified our article on concomitant use of these medicines in heart failure.
Letters sent to healthcare professionals in November 2016
A summary of recent letters sent to relevant healthcare professionals, to inform them of updated safety information.
Brimonidine gel (Mirvaso▼): risk of exacerbation of rosacea
Some patients may have exacerbation or rebound symptoms of rosacea.
Show your support for reporting suspected adverse drug reactions
We are running a social media campaign to promote the reporting of suspected adverse drug reactions to the Yellow Card Scheme in support of an awareness week from 7 to 11 November 2016.
Letters sent to healthcare professionals in October 2016
A summary of recent safety letters sent to relevant healthcare professionals
Etoricoxib (Arcoxia): revised dose recommendation for rheumatoid arthritis and ankylosing spondylitis
Prescribing information has been updated to introduce a lower recommended dose of 60 mg daily for patients with rheumatoid arthritis or ankylosing spondylitis.
Letters sent to healthcare professionals in September 2016, including retigabine withdrawal
A summary of letters sent to healthcare professionals in September 2016, including important information for professionals who specialise in epilepsy treatment regarding the withdrawal from the market of retigabine (Trobalt).
Levonorgestrel-containing emergency hormonal contraception: advice on interactions with hepatic enzyme inducers and contraceptive efficacy
Medicines or herbal remedies that induce CYP3A4 enzymes reduce blood levels of levonorgestrel, which may reduce emergency contraceptive efficacy.
Posaconazole (Noxafil): tablets and oral suspension are not directly interchangeable
Switching from posaconazole oral solution to tablets has resulted in cases of dose-related toxicity, whereas switching from tablets to oral solution has resulted in underdosing and lack of efficacy.
Idelalisib (Zydelig▼): updated indications and advice on minimising the risk of infection
Updated advice for healthcare professionals is available, after conclusion of a review of the safety of idelalisib, including the risk of infection.
Letters sent to healthcare professionals in August 2016
A summary of safety letters sent to healthcare professionals in August 2016
Warfarin: reports of calciphylaxis
Calciphylaxis is a very rare but serious condition causing vascular calcification and skin necrosis.
Citalopram: suspected drug interaction with cocaine; prescribers should consider enquiring about illicit drug use
Possible illicit drug use should be considered when prescribing medicines that have the potential to interact adversely.
N-acetylcysteine: risk of false-low biochemistry test results due to interference with Siemens assays
N-acetylcysteine may interfere with assays from Siemens ADVIA Chemistry and Dimension/Dimension Vista instruments, leading to false-low biochemistry test results.
Letters sent to healthcare professionals in June 2016
In June 2016, a letter was sent to healthcare professionals about Thalidomide Celgene.
BCR-ABL tyrosine kinase inhibitors: risk of hepatitis B reactivation
Patients should be tested for hepatitis B virus before starting treatment with BCR-ABL tyrosine kinase inhibitors.
Pomalidomide (Imnovid▼): risk of hepatitis B reactivation
Before starting treatment with pomalidomide, establish hepatitis B virus status in all patients.
Idelalisib (Zydelig▼): interim measures following signal of serious infection and deaths related to infection found in clinical trials
There are new interim treatment recommendations for idelalisib for chronic lymphocytic leukaemia and follicular lymphoma in light of new findings from clinical trials outside its currently authorised drug combinations or indicated populations.
Letters sent to healthcare professionals in April 2016
In April 2016, letters were sent regarding canagliflozin (Invokana▼, Vokanamet▼), BCR-ABL tyrosine kinase inhibitors, pomalidomide (Imnovid▼), and retigabine (Trobalt)
SGLT2 inhibitors: updated advice on the risk of diabetic ketoacidosis
Test for raised ketones in patients with ketoacidosis symptoms, even if plasma glucose levels are near-normal.
Natalizumab (Tysabri▼): progressive multifocal leukoencephalopathy—updated advice to support early detection
Perform a quantitative serum anti-JCV antibody test—including index value—to support risk stratification for progressive multifocal leukoencephalopathy.
Dimethyl fumarate (Tecfidera): updated advice on risk of progressive multifocal leukoencephalopathy
Cases of progressive multifocal leukoencephalopathy have been reported in patients taking dimethyl fumarate for multiple sclerosis, who all had prolonged lymphopenia.
Fingolimod (Gilenya▼): risks of progressive multifocal leukoencephalopathy, basal-cell carcinoma, and opportunistic infections
The immunomodulatory effects of fingolimod increase the risk of progressive multifocal leukoencephalopathy and opportunistic infections.
Apomorphine with domperidone: minimising risk of cardiac side effects
Patients receiving apomorphine and domperidone require an assessment of cardiac risk factors and ECG monitoring to reduce the risk of serious arrhythmia related to QT-prolongation.
Aflibercept (Zaltrap▼): minimising the risk of osteonecrosis of the jaw
Dental examination and appropriate preventive dentistry should be considered before treatment, especially for patients also treated with an intravenous bisphosphonate.
Live attenuated vaccines: avoid use in those who are clinically immunosuppressed
Healthcare professionals working in primary and secondary care should ensure that clinically significant immunosuppression in a patient is identified before administration of a live attenuated vaccine.
Meprobamate: licence to be cancelled
Following an EU wide review of meprobamate, the remaining licence holder in the UK has ceased manufacturing and the licence will be cancelled by the end of 2016.
Paraffin-based skin emollients on dressings or clothing: fire risk
Smoking or a naked flame could cause patients’ dressings or clothing to catch fire when being treated with paraffin-based emollient that is in contact with the dressing or clothing.
Letters sent to healthcare professionals in March 2016
In March 2016, letters were sent regarding SGLT2 inhibitors, insulin lispro, natalizumab, noradrenaline, radium-223 dichloride, aflibercept and idelalisib.