Nervous System MHRA alerts

Question 1

Benzodiazepines and opioids

Answer 1

Reminder of risk of potentially fatal resp depression

Question 2

What are some strategies that should be implemented to help reduce the likelihood of dependance to opioids.

If a patient is presenting with increased sensitivity to pain, what could this indicate?

Answer 2

Risk of dependance and addiction with prolonged use (greater than 3months) for non-cancer pain

Warning labels have been added to packets

Before starting treatment, agree a treatment strategy and end of treatment

Taper dose at end of treatment to minimise withdrawal

Explain risk of tolerance and overdose
Provide regular monitoring esp in those with current or past history of substance misuse/mental health disorder

Consider the possibility of hyperalgesia if a patient on long-term opioid therapy presents with increased sensitivity to pain

The MHRA has also issued a safety leaflet for patients

Question 3

How can opioid toxicity occur from fentanyl patches? In which age group is this more prominent?

Answer 3

Life-threatening and fatal opioid toxicity from accidental exposure, particularly in children

Patients and carers should be advised to seek immediate medical attention if overdose is suspected

Question 4

What specific ‘safe usage’ information about fentanyl patches should we warn patients/carers about?

Consider:

• application directions
• lifestyle modifications
• storage and disposal

Answer 4

Inform patients about:

• the importance of:
  not exceeding the prescribed dose
• following the correct frequency of patch application
• avoiding touching the adhesive side of patches, and washing hands after application
• not cutting patches
• avoiding exposure of patches to heat including via hot water
• ensuring that old patches are removed before applying a new one
• following instructions for safe storage and properly disposing of used patches or those which are not needed.

Question 5

Fentanyl patches should NOT be in used in which group of patients? Why?

Answer 5

Do not use patches for non-cancer pain in opioid-naive patients

There is considerable risk of respiratory depression with the use of fentanyl, especially in opioid-naive patients, and significant risk with too rapid an escalation of dose, even in long-term opioid-tolerant patients.

Question 6

SSRIs and SNRIs carry a risk of postpartum haemorrhage how long before delivery?

Answer 6

Small increased risk of postpartum haemorrhage when used in the month before delivery due to increased bleeding risk

Question 7

What have gabapentin and pregabalin been reclassified to?

Which substance interaction with gabapentin/pregabalin be aware of?

Answer 7

Now been reclassified as a Class C controlled substance, Schedule 3 but is exempt from safe custody requirements.

Patients should be informed of potentially fatal risks of interactions between gabapentin/pregabalin and alcohol, and with other medicines that cause CNS depression, particularly opioids.

Question 8

Gabapentin and Pregabalin carry a rare risk of severe blank depression.
Which patients are at a higher risk of experiencing this?

Answer 8

Rare risk of severe respiratory depression even without concomitant opioid medicines.

Patients with compromised respiratory function , respiratory or neurological disease, renal impairment, concomitant use of CNS depressants and elderly people might be at higher risk of experiencing severe respiratory depression and may require dosage adjusments

Patients should be advised to seek medical help if they experience any trouble breathing or shallow breathing; a noticeable change in breathing may be associated with sleepiness.

Question 9

Which formulation of phenytoin carries a risk of death and severe harm?

Answer 9

Risk of death and severe harm from error with injectable phenytoin.

Acquaint safe with appropriate guidance.

Question 10

Valproate/Vaproic Acid is contra-indicated in which patient group?

Answer 10

Contra-indicated in women and girls of childbearing potential unless conditions of pregnancy prevention are met.

Use of valproate in pregnancy is contraindicated for bipolar disorder and must only be considered for epilepsy if there is no suitable alternative treatment

Associated with a significant risk of birth defects and development disorders.

Question 11

Valproate Advice for HealthCare Professionals

Answer 11

Some female patients are not at risk of pregnancy e.g. hysterectomy or not going to be sexually activity at all. However, they should still be supported under the valproate pregnancy prevention programme unless the specialist prescriber agrees that there are compelling reasons that indicate that there’s no risk of pregnancy.

If patient on valproate, should be on highly effective contraception.

Specialists must book in review appointments at least annually with women and girls under the PPP and re-evaluate

Annual Risk Acknowledgement Form

Question 12

Valproate Action for Pharmacists.

• How should valproate be dispensed? what should be included on the carton?
• How often should you discuss the risks with the patient?
• What should always be included in the box?

Answer 12

• valproate medicines are dispensed in whole packs whenever possible
• all packs dispensed to women and girls of childbearing potential should have a warning label either on the carton or via a sticker
• discuss risks in pregnancy with female patients each time you dispense valproate medicines and ensure they have the Patient Guide and have seen their GP or specialist to discuss their treatment and the need for contraception
• Make sure you provide every patient with the statutory patient information leaflet – even if you have to split a pack.

Question 13

Which anti-epileptics are safest in pregnancy?

Answer 13

Lamotrigine (Lamictal) and levetiracetam (Keppra) are the safer of the medicines reviewed during pregnancy.

Question 14

When would high strengths of midazolam be appropriate? What is used to reverse its effects if needed.

Answer 14

High-strength midazolam (5mg/ml in 2ml and 10ml ampoules) should be considered in palliative care and other situations where a higher strength may be more appropriate to administer the prescribed dose, and where the risk of overdosage has been assessed.

It is advised that flumazenil is available when midazolam is used, to reverse the effects if necessary.

Question 15

Clozapine is associated with which fatal GI disturbance?

Answer 15

Risk of potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus.

Question 16

Dopamine agonists e.g. levodopa can be linked to which type of pyschiatric disorder?

Answer 16

Treatment with levodopa is associated with impulse control disorders, including pathological gambling, binge eating and hypersexuality.

If the patient develops an impulse control disorder, levodopa should be withdrawn or the dose reduced until the symptoms resolve

No evidence that ergot- and non-ergot- derived dopamine-receptor agonists will be different so switching to these is not recommended

Question 17

Ergot derived dopamine agonist e.g. bromocriptine, cabergoline and pergolide

Answer 17

Risk of fibrotic reactions

Associated with pulmonary, retroperitoneal and pericardial fibrotic reactions.

• Exclude cardiac valvulopathy with echocardiography before starting treatment (unless in suppression of lactation)
• Renal insufficiency or ureteral or abdominal vascular obstruction might occur, with pain in the loin or flank and leg oedema: abdominal masses or tenderness could suggest retroperitoneal fibrosis

Patients should be monitored for dyspnea, persistent cough, chest pain, cardiac failure and abdominal pain or tenderness.

If long-term treatment is expected then lung-function tests may also be helpful.

Patients taking cabergoline/pergolide should be regularly monitored for cardiac fibrosis by echocardiography (within 3-6 months of initiating treatment and subsequently at 6-12 month intervals)

Stop treatment if echocardiography shows new or worsened valvular regurgitation, valvular restriction, or valve leaflet thickening
exclude pregnancy before administration of cabergoline
advise women who are planning pregnancy that they should stop taking cabergoline 1 month before they try to conceive

Question 18

Domperidone Dose and Licensing (1)

• minimum age/weight
• doses
• max duration

Answer 18

Not licensed in children under 12 or those under 35kg

Should only be used for N and V at lowest dose/shortest duration

The recommended dose in adults and adolescents (12+) and >35kg is 10mg up to TDS.

In children under 12 years of age <35 kg, the recommended maximum dose in 24 hours is 0.75 mg/kg body weight (dose interval: 0.25 mg/kg body weight up to three times a day)

Max duration usually not exceed 7 days

Question 19

Domperidone Serious Side Effects (2)

Answer 19

Small increased risk of serious cardiac side-effects

Contra-indicated:

• conditions where cardiac conduction is, or could be impaired
• underlying cardiac disease,
• when administered concomitantly with drugs that prolong the QT interval - with potent CYP3A4 inhibitors
• severe hepatic impairment

Question 20

Domperidone Formulations (3)

Answer 20

Oral liquid formulations should be given via an appropriate designed, graduated oral syringe to ensure dose accuracy.

Suppositories should only be used in adults and adolescents weighing 35 kg or more, the recommended maximum daily dose in 24 hours is 60 milligrams (dose interval: 30 milligrams twice a day)

Question 21

Ondansetron carries which risk in the first 12 weeks of pregnancy?

Answer 21

Small increased risk of oral clefts following use in the first 12 weeks of pregnancy

Question 22

Metoclopramide (1)

Answer 22

Risk of neurological effects e.g. extrapyramidal disorders and tardive dyskinesia

Particularly in children and young adults

Question 23

Metoclopramide Indications (2)

Answer 23

Adults (18+) should only be used for:

• prevention of postoperative N&V
• radiotherapy-induced N&V
• delayed (but not acute) chemotherapy-induced N&V
• symptomatic treatment of N&V, including that associated with acute migraine (where it may also be sued to improve absorption or oral analgesics)

Children (1-18 years):

• SECOND LINE for treatment of established postoperative nausea and vomiting
• prevention of delayed chemo induced N and V

Question 24

Metoclopramide Doses and length of treatment (3)

Answer 24

Max 5 days use

Usual dose is 10 mg, repeated up to 3 times daily; max. daily dose is 500 micrograms/k

Question 25

Metoclopramide Formulations (4)

Answer 25

• Intravenous doses should be administered as a slow bolus over at least 3 minutes
• Oral liquid formulations should be

Question 26

Codeine (1) should not be used in which patient groups?

Answer 26

• do not use codeine in children under 12 as it is associated with a risk of respiratory side effects.
• not recommended for adolescents (12-18 years old) who have problems with breathing.

Contra-indicated in:

• Children under 12 years old
• Patients of any age known to be CYP2D6 ultra-rapid metabolisers
• Breastfeeding mothers
• <18 who undergo removal of tonsils or adenoids for treatment of sleep apnoea

Question 27

Codeine Doses (2)

• max dose in children aged 12-18 years
• duration of treatment

Answer 27

In children aged 12–18 years, the maximum daily dose of codeine should not exceed 240 mg.

Doses may be taken up to four times a day at intervals of no less than 6 hours.

The lowest effective dose should be used and duration of treatment should be limited to 3 days

Question 28

How should dihydrocodeine be dispensed to minimise the risk of dispensing errors/overdose?

Answer 28

Dihydrocodeine with paracetamol (co-dydramol)

Prescribed and dispense by strength to minimize the risk of dispensing errors and reduce the risk of accidental opioid overdoses.

Question 29

Varenicline

Answer 29

Suicidal behaviour and varenicline

Discontinue treatment and seek prompt medical advice if they develop agitation, depressed mood or suicidal thoughts.

Patients with a history of psychiatric illness should be monitored closely while taking varenicline.