UKMi Observatory

Wednesday 31st July 2019

Observatory of recent safe medication

practice research, reports, and publications

Presented by Varinder Rai

Medicines Information Manager - London MI Service

Varinder.rai@nhs.net

All GP practices in England are required to register to receive CAS alerts.

All GP Practices are asked to register directly by 13 Sep 2019. GP Practice to

receive alerts directly from 01 October 2019.

Provisional publication of Never Events reported as occurring between 1

April and 31 May 2019.

Report notes 59 serious incidents including 1 methotrexate overdose

prescribed and administered, 1 wrong strength potassium given, and 1 oral

medication given intravenously.

Recent regulator and statutory body activity

Class 2: FMD Alert. B & S Healthcare livery medicines have been taken

out of the regulated medicines’ supply chain during distribution.

Clexane 8000iu Injection 0.8ml; Neupro 4mg/24 hr patches; and Vimpat

100mg tablets (patient level)

Dovobet Gel, Incruse Inhaler, Provisacor (Crestor) 10mg Tablets, Seebri

Breezhaler, Spiriva Inhalation Powder (pharmacy level)

Class 4: Martindale Phenobarbital Sodium 30mg/ml Injection. The

EAN bar code on some batches scans the batch as Phenobarbital Sodium

Injection 200mg/ml.

Class 4: Emerade 150, 300 and 500 microgram solution for injection

in pre-filled syringe. Risk of Emerade product failing to deliver a dose of

adrenaline due to blockage of the needle.

Recent regulator and statutory body activity

Report Illicit Drug Reactions (RIDR)

https://report-illicit-drug-reaction.phe.gov.uk/

https://report-illicit-drug-reaction.phe.gov.uk/latest-information/

Company led drug alert – Docetaxel Injection 160mg /16ml and

Docetaxel Injection 20mg / 2ml. 24 June.

Pfizer UK Limited is recalling batches as levels of a known impurity, 10-

oxo-docetaxel, may exceed the acceptable level at end of shelf-life.

Recent regulator and statutory body activity

Drug Safety Update

• Technical issues in receiving Drug Safety Updates

• Rivaroxaban (Xarelto▼): reminder that 15 mg and 20 mg tablets

should be taken with food. MHRA has received reports suggesting

lack of efficacy (thromboembolic events) in patients taking 15 or 20 mg

rivaroxaban on an empty stomach.

• Tocilizumab (RoActemra): rare risk of serious liver injury including

cases requiring transplantation. LFTs should be measured before

starting treatment with tocilizumab and monitored every 4–8 weeks for

the first 6 months of treatment followed by every 12 weeks thereafter.

• Febuxostat (Adenuric): increased risk of cardiovascular death and

all-cause mortality in clinical trial in patients with a history of major

cardiovascular disease. Avoid treatment with febuxostat in patients

with pre-existing major cardiovascular unless no other therapy options

are appropriate.

Recent regulator and statutory body activity

Pharmacovigilance Risk Assessment Committee

(PRAC)

Review of cyproterone for risk of meningioma.

PRAC will now examine the available evidence as to whether the MA for

these medicines should be amended.

New measures to avoid dosing errors with methotrexate. PRAC is

recommending new measures include restricting who can prescribe these

medicines, making warnings on the packaging more prominent, providing

educational materials for patients and healthcare professionals and use of

blister packs.

Direct HCP communication

DARZALEX®▼ (daratumumab): Risk of reactivation of hepatitis B virus. All patient

should be screened for HBV before initiation of treatment; and for those already on treatment

and HBV serology is unknown.

Reformulation of Prenoxad to contain 1mg/ml of naloxone hydrochloride. On the

request of the MHRA in response to a historical error where the product had contained

0.91mg/mL rather than 1mg/ml.

Cerliponase alfa (Brineura▼): temporary change in packaging. English language UK

packs unavailable until Aug 19 and German packs will be provided with English patient

leaflets.

Retinoids▼ (Acitretin, Adapalene, Alitretinoin, Bexarotene, Isotretinoin, Tretinoin, and

Tazarotene): risk of teratogenicity and neuropsychiatric disorders. Pregnancy Prevention

Programme materials for oral products updated. Newly diagnosed depression, worsening of

existing depression and anxiety have been reported with oral retinoids.

Febuxostat (Adenuric): increased risk of cardiovascular death and all-cause mortality in

patients treated with febuxostat in the CARES study. Febuxostat should be avoided in with

pre-existing major CV disease.

Manufacturer educational risk minimisation material

ILUVIEN 190 micrograms intravitreal implant in applicator

Various supporting materials are provided to support the administration of Iluvien by

healthcare professionals

RoActemra (tocilizumab). The risk materials include information and guidance on the risk of

drug-induced liver injury, including acute liver failure, hepatitis and jaundice, in some cases

requiring liver transplantation, which have been observed in patients treated with tocilizumab.

Toctino 30mg soft capsules. Risk materials include a pharmacist and prescriber checklist

and patient card to reinforce the risk that retinoids can cause severe birth defects and that

foetal exposure, even for short periods of time, presents a high risk of congenital

malformations and miscarriage.

Alofisel 5 million cells/mL suspension for injection. Supporting risk materials include a

guide for surgeons providing information about conditioning of the fistula, product preparation,

details regarding injection method and important safety considerations and a guide for

pharmacists providing information on receipt and storage.

Summary of Product Characteristics updates

Benlysta (belimumab) powder for concentrate for solution for infusion. Warning included that studies

have shown psychiatric disorders reported in patients receiving belimumab and addition of suicidal

behaviour and suicidal ideation as an uncommon side effect.

Xarelto (rivaroxaban) film-coated tablets. DOACs, including rivaroxaban, are not recommended for

patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome, in particular for

patients that are triple positive.

Yentreve and Cymbalta (duloxetine hydrochloride) hard gastro-resistant capsules. Warning of

symptoms of sexual dysfunction; stating there have been reports of long-lasting sexual dysfunction where

the symptoms have continued despite discontinuation of treatment.

Xeljanz (tofacitinib) film-coated tablets. Contra-indicate use in patients with risk factors for pulmonary

embolism.

Diafer (iron (III) isomaltoside 1000) 50 mg/ml solution for injection. Avoid paravenous leakage when

administrating Diafer as this may lead to irritation of the skin and potentially long lasting brown

discolouration at the site of injection. In case of paravenous leakage, administration must be stopped

immediately.

Biktarvy (bictegravir, emtricitabine, and tenofovir alafenamide) tablets. Angioedema and urticaria have

been added as potential adverse reactions from treatment (frequency = uncommon)

NeisVac-C (meningococcal group c polysaccharide conjugate vaccine adsorbed) injection. Warning

regarding the increased risk of invasive meningococcal disease in patients receiving eculizumab, due to the

inhibition of terminal complement activation

Drug shortages and discontinuations

Supply disruption – Disopyramide 100/150mg cap

100mg capsules manufactured by Sanofi and Mylan will be out of stock

from approximately mid-June 2019 to late-July 2019. Mylan disopyramide

150mg capsules will be out of stock from approximately mid-August 2019

till mid-September 2019

Permanent discontinuation - Myocrisin (Sodium aurothiomalate)

injection (gold injections). Existing stock will last until end of July 2019.

Supply disruption – Nardil (Phenelzine) tablets. Shortage from August to

October 2019. The SPS shortage memo gives further information including

information on unlicensed imports.

CAS alert supply disruption – Marcain Heavy 0.5% (bupivacaine

hydrochloride) injection. Unlicensed stock available to order from

Thursday 11thJuly.

Drug shortages and discontinuations

Shortage of bezafibrate 200mg tablets. Shortage till late July/early

August 2019. The SPS memo advises on the use of alternative fibrate

preparations, and also highlights that this represents an opportunity to

review patients

Shortage of Miochol-E (acetycholine) for intraocular injection.

Shortage till Nov 2019. The SPS memo advises on an alternative product

and highlights differences.

Legislation for DHSC to issue Serious Shortage Protocols (SSPs): 1st

July 2019. PSNC will notify contractors of any SSPs that are issued

National guidance, publications and resources

WHO: Discontinuing guidelines

Ensuring balance in national policies on controlled substances: Guidance for

availability and accessibility of controlled medicines (2011)

WHO guidelines on the pharmacological treatment of persisting pain in children with

medical illnesses (2012)

RPS asks Home Office for guidance on THC levels in cannabidiol oil

Care Quality Commission: The safer management of controlled drugs: Annual

report 2018. Reports on the increase in opioid prescribing across the UK, measures

post Gosport report, concerns on lower schedule controlled drugs and legislation for

cannabis based medicinal products

Who can supply or administer Controlled Drugs under the terms of a Patient

Group Direction and under what circumstances.

This month’s papers - overview

Quality improvement of prescribing safety: a pilot study in primary care using UK

electronic health records. Br J Gen Pract. 2019 Jul 1. doi:

10.3399/bjgp19X704597

Reducing unnecessary sedative-hypnotic use among hospitalised older adults.

BMJ Qual Saf. 2019 Jul 3. doi: 10.1136/bmjqs-2018-009241

Opioids, the pharmacist and the junior doctor: reducing prescribing error. Journal

of Pharmacy Practice and Research. 2019 Jul 9. doi.org/10.1002/jppr.1526

The role of undergraduate teaching, learning and a national prescribing safety

assessment in preparation for practical prescribing: UK medical students'

perspective.

Br J Clin Pharmacol. 2019 Jul 9. doi: 10.1111/bcp.14058.

Effectiveness of ‘do not disturb’ strategies in reducing errors during discharge

prescription writing. Pharmacy Practice and Research. 2019 Jul 10.

doi.org/10.1002/jppr.1543.

This month’s papers - overview

The MOWER (middle of the week everyone gets a re-chart) pilot study: reducing

in-hospital charting error with a multi-intervention. BMC Health Serv Res. 2019

Jun 20;19(1):397.

Diversion of Controlled Drugs in Hospitals: A Scoping Review of Contributors and

Safeguards. J Hosp Med. 2019 Jul;14(7):419-428.

Can nurses' shift work jeopardize the patient safety? A systematic review.

European Review for Medical and Pharmacological Sciences; 2019; vol. 23 (no.

10); p. 4507-4519.

Anticoagulant medication errors in hospitals and primary care: A cross-sectional

study. International Journal for Quality in Health Care; Jun 2019; vol. 31 (no. 5);

p. 346-352.

Medication Related Litigation in Ireland: A Six Year Review. British journal of

clinical pharmacology; Jun 2019.

This month’s papers - details

National audit of antidote stocking in UK emergency departments.

European Journal of Hospital Pharmacy.

• Audit to assess UK hospital compliance (emergency departments) to

the RCEM and NPIS 2017 guidance on antidote availability

• Questionnaires were distributed to Chiefs/procurement with an

emergency department.

• Ensure appropriate and timely availability of antidotes

• Category A (immediately available); category B (available within 1

hour); category C (held supra-regionally; 4-6 hours) antidotes

• Recorded antidote stocked, availability within time frame, and stock

levels kept.

• 233 hospitals were surveyed and 178 replies (76.4%) were received.

This month’s papers - details

National audit of antidote stocking in UK emergency departments.

European Journal of Hospital Pharmacy.

• Category A (41.7%), Category B (19.1%; 24.7% phentolamine excluded); Categories A and B (10.1%);

Category C (1.1%-34.8%)

• Three hospitals reported not stocking any antidote for cyanide poisoning (dicobalt, hydroxycobolamin,

sodium thiosulphate, sodium nitrate).

• Some Trusts kept stock split across the different sites

• Reasons for poor compliance not investigated