Carbamazepine


  Issues for Surgery


For treatment of epilepsy – precipitation of rebound seizures or status epilepticus if omitted.

For prophylaxis of bipolar disease (mood stabilisation) – risk of rebound bipolar symptoms if omitted.

For treatment of trigeminal neuralgia or diabetic neuropathy (unlicensed use) – loss of pain control if omitted.


  Advice in the Perioperative period


Elective and Emergency Surgery

Continue – check sodium levels pre-operatively (see Further Information).

Patients should be advised to take their regular medications on the day of surgery1, 2, 3.

Abrupt withdrawal of any anticonvulsant drug should be avoided1.

Ensure that the patient is maintained on a specific manufacturer’s product (see Further Information).

Post-operative Advice

Regular dosing of the patient’s usual oral medication should be re-established as early as possible post-operatively2, 3.

If patients are unable to take their regular oral medication post-operatively, consider alternative routes/forms or alternative medication, particularly when taken for epilepsy / bipolar disease. Care should be taken since there may be different doses / frequencies required when changing between formulations of the same medicine. Consult current product literature.

NB: carbamazepine is NOT available as an intravenous formulation. If an intravenous formulation is required, discuss with a Neurologist to determine the most appropriate preparation, dose, route and frequency to be used.

Monitor renal function and electrolytes, particularly sodium (see Further Information).


  Interaction(s) with Common Anaesthetic Agents


For general information regarding the use of anaesthetic agents in patients with epilepsy – see Antiepileptics – A General Overview.

Neuromuscular Blocking Drugs (NMBDs)

For patients who have been taking carbamazepine for longer than one week: the activity of competitive NMBDs (e.g atracurium, pancuronium) is reduced by carbamazepine – a rapid recovery from neuromuscular blockade is possible. Patients must be monitored closely – anticipate the need to use a larger dose of NMBD and expect an accelerated recovery1, 4, 5.

NB: if carbamazepine is given acutely (e.g. during surgery) the effects of NMBDs may be increased4.

Corticosteroids

The clearance of dexamethasone / hydrocortisone is increased (decreased exposure and efficacy) in patients taking carbamazepine due to enzyme induction – monitor and adjust the corticosteroid dose as necessary1, 4, 6, 7.

Alfentanil / Fentanyl

Carbamazepine is predicted to decrease the exposure to alfentanil / fentanyl – manufacturer advises caution1, 4, 6. Patients may require increased doses – monitor and adjust opioid dose accordingly.

Benzodiazepines

Carbamazepine is an inducer of hepatic drug-metabolising enzymes; therefore, metabolism of benzodiazepines may be enhanced8. This has been noted with diazepam in particular4. Monitor concurrent use for benzodiazepine efficacy – an increase in the dose of the benzodiazepine might be needed4.


  Interaction(s) with other Common Medicines used in the Perioperative Period


Antimicrobials

Macrolide antibiotics can increase the concentration of carbamazepine plasma levels (see below)2, 6, 9. Where concurrent use is unavoidable, patients should be monitored for any symptoms of toxicity (dizziness, diplopia, ataxia, mental confusion)4.

  • clarithromycin – greatly and rapidly increases carbamazepine concentrations despite dose reductions of up to 40%. Several cases of toxicity have been seen. Monitor patient and adjust the dose accordingly (a dose reduction of 30 – 50% has been suggested).
  • erythromycin – greatly and rapidly increases carbamazepine concentrations, which has resulted in toxicity in several cases. Symptoms commonly begin within 24 hours of starting erythromycin. Avoid concurrent use unless carbamazepine concentrations can be closely monitored.

Carbamazepine may reduce the serum levels of doxycycline, potentially to below the accepted therapeutic minimum – monitor for treatment failure and consider increasing doxycycline dose1, 4, 9.

Ciprofloxacin might increase the exposure to carbamazepine – bear this in mind in case of an increase in carbamazepine adverse effects4. However, please note that ciprofloxacin can lower the seizure threshold and trigger seizures; hence it is generally avoided in patients with a history of seizures.

There is increased risk of hepatotoxicity with concurrent use of carbamazepine with the following antimicrobials1: -

  • clavulanic acid (found in co-amoxiclav)
  • doxycycline
  • flucloxacillin

Whilst single surgical prophylactic doses should not pose a problem for most antimicrobials (except ciprofloxacin and macrolides), continued post-operative treatment may require close monitoring. Consult current product literature.

Non-Steroidal Anti-inflammatory Drugs (NSAIDs)

Carbamazepine and NSAIDs can increase the risk of hyponatraemia(see Further Information).

NSAIDs might increase plasma levels of carbamazepine6 – monitor the patient for symptoms of carbamazepine toxicity if used concomitantly.

Gastrointestinal Drugs

Omeprazole may increase carbamazepine levels4, 6. Although single-dose studies suggest that omeprazole raises carbamazepine levels, multiple-dose studies have found no interaction4. Monitor the patient for symptoms of carbamazepine toxicity if using omeprazole and carbamazepine concomitantly.

Analgesia (for NSAIDs see above under Non-Steroidal Anti-inflammatory Drugs (NSAIDs))

Carbamazepine may decrease activity of paracetamol, leading to reduction in paracetamol efficacy4, 6. In addition, long-term administration of carbamazepine and paracetamol may be associated with hepatotoxicity6 – ensure that post-operative use of paracetamol is for short-term use only.

Carbamazepine appears to halve the concentrations of tramadol, which is expected to reduce its analgesic effects – consider an alternative4. NB: Tramadol should be avoided in patients with a history of epilepsy due to an increase in seizure risk1, 4.

Antiemetics (For metoclopramide see also Neurological Side Effects below)

Limited evidence suggests that carbamazepine may reduce phenothiazine (e.g. prochlorperazine) concentrations. If a diminished response to phenothiazine antiemetics occurs, increase the dose4; but see Antiepileptics – A General Overview for advice on the use of phenothiazines in patients with history of seizures.

Carbamazepine may decrease the exposure to oral ondansetron and slightly decrease the exposure to intravenous ondansetron. Be aware that ondansetron might be less effective and monitor the patient4.

Neurological Side-Effects

Concurrent use of carbamazepine and the following drugs may increase the occurrence of neurological side effects6, 9: -

  • sedatives
  • analgesics
  • sedative antihistamines
  • metoclopramide (also see ‘Antiepileptics – A General Overview’ for advice on the use of metoclopramide in patients with a history of seizures)

  Further Information

 

MHRA/CHM Advice: Antiepileptic Drugs: updated advice on switching between different manufacturer’s products (November 2017)1

Epilepsy
Carbamazepine is a category 1 antiepileptic and patients should be maintained on a specific manufacturer’s product1. (For more information see ‘Antiepileptics – A General Overview).

Other Indications
There is no specific advice available for maintaining patients on a specific manufacturer’s product for indications other than epilepsy.

Hyponatraemia

Hyponatraemia can occur with carbamazepine (due to syndrome of inappropriate antidiuretic hormone [SIADH] secretion)1, 6, 10, particularly in patients with pre-existing disorders associated with low serum sodium concentration, or in patients who are being concomitantly treatment with medicines that lower serum sodium concentration e.g. diuretics, NSAIDs6. Monitor sodium levels in the perioperative period.

Blood, Hepatic or Skin Disorders

Patients should be monitored for signs of blood, liver or skin disorders (e.g. fever, rash, mouth ulcers, bruising or bleeding). Carbamazepine should be withdrawn in cases of aggravated liver dysfunction or acute liver disease. Leucopenia that is severe, progressive, or associated with clinical symptoms requires withdrawal1, 6. A Neurologist should be consulted to ensure an appropriate management plan is in place.


  References


  1. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press http://www.medicinescomplete.com [Accessed on 29th July 2019]
  2. Perks A, Cheema S, Mohanraj R. Anaesthesia and epilepsy. BJA: British Journal of Anaesthesia. 2012; 108(4):562-571
  3. Carter EL, Adapa RM. Adult epilepsy and anaesthesia. BJA Education. 2015; 15(3):111-117
  4. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 29th July 2019]
  5. Atracurium Besilate. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 29th June 2019]
  6. Summary of Product Characteristics – Carbagen® (carbamazepine) 400mg Prolonged-Release Tablets. Mylan. Accessed via www.medicines.org.uk 30/06/2019 [date of revision of the text July 2017]
  7. Antiepileptics (Corticosteroids – Interactions of Corticosteroids). In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 29th June 2019]
  8. Diazepam. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 29th June 2019]
  9. Carbamazepine. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 29th June 2019]
  10. Hirst C, Allahabadia A, Cosgrove J. The adult patient with hyponatraemia. BJA Education. 2015; 15(5):248-252