Calcium-Channel Blockers (CCBs)


 

Dihydropyridines: Amlodipine, Felodipine, Lacidipine, Lercanidipine, Nicardipine, Nifedipine, Nimodipine

Diltiazem, Verapamil

 

[Intravenous CCBs are outside the scope of this guideline and expert advice should be sought for patients who may be receiving these in the perioperative period]

  Issues for Surgery


For treatment of hypertension – loss of blood pressure (BP) control if omitted.

For treatment of angina – exacerbation of angina if omitted.

For treatment of arrhythmias (verapamil) – exacerbation of arrhythmias if omitted.

Adjunctive treatment in drug-resistant epilepsy – increased risk of seizure if omitted.

Risk of hypotension when continued.


  Advice in the Perioperative period


Elective and Emergency Surgery

Continue1 – monitor BP (and heart rate with diltiazem / verapamil).

Includes combination product: -

  • Tenif® – contains nifedipine + atenolol (also see Beta-adrenoceptor Blocker (Beta-Blockers) (Systemic and Topical) monograph)

EXCEPT:

  • Combination products containing CCB and Angiotensin II Receptor Antagonist / Angiotensin Receptor Blocker (see ACE Inhibitors (ACEi) and Angiotensin II Receptor Antagonists (AIIRA) / Angiotensin Receptor Blockers (ARB) monograph)
  • Combination products containing CCB and hydrochlorothiazide and Angiotensin II Receptor Antagonist / Angiotensin Receptor Blocker (see ACE Inhibitors (ACEi) and Angiotensin II Receptor Antagonists (AIIRA) / Angiotensin Receptor Blockers (ARB) and Diuretics – Thiazides and Related Monographs)

For patients taking modified-release preparations of diltiazem and nifedipine, confirm the specific manufacturer’s brand (see Further Information).

Consideration should be given to prescribing the components of combination products as separate medicines perioperatively.

Post-operative Advice

Restart post-operatively when next dose is due.

Monitor BP (and heart rate with diltiazem / verapamil).


  Interaction(s) with Common Anaesthetic Agents


Inhalational Anaesthetics (see also Hypotension below)

CCBs may reduce the minimum alveolar concentration (MAC) of inhalational anaesthetics by up to 20%2.

Hypotension

CCBs can increase the risk of hypotension when used concomitantly with remifentanil or inhalational / intravenous anaesthetics3, 4, 5, 6.

Concomitant use of verapamil or diltiazem with alfentanil / fentanyl may increase the risk of hypotension4.

Bradycardia

Diltiazem and verapamil can increase the risk of bradycardia when used concomitantly with the following3, 4: -

  • alfentanil, fentanyl or remifentanil (also see Alfentanil, Fentanyl and Remifentanil below)
  • cisatracurium
  • neostigmine

Alfentanil, Fentanyl and Remifentanil (also see Bradycardia and Hypotension above)

Verapamil and diltiazem may increase the effects of alfentanil, fentanyl and remifentanil – monitor for opioid adverse effects (e.g. prolonged sedation, respiratory depression) and adjust dose as necessary3, 4.

Midazolam

Verapamil and diltiazem may increase the plasma concentration and prolong the half-life of midazolam3, 6, 7, 8. Care should be taken when prescribing short-acting benzodiazepines metabolised by the CYP3A4 pathway7. Consider using a lower initial dose (a 50% reduction has been suggested)4, 8.

Neuromuscular Blocking Drugs (NMBDs)

CCBs may prolong neuromuscular blockade when used concomitantly with NMBDs2, 4, 6. The clinical significance is unknown, but bear the potential interaction in mind in case of unexpected response to treatment4.

Dantrolene

Intravenous dantrolene potentially increases the risk of acute hyperkalaemia and cardiovascular collapse when given with verapamil or diltiazem2, 3, 6, 9, this interaction has occurred in animal studies with other CCBs9, 10. It is recommended that co-administration of CCBs, particularly verapamil and diltiazem, with dantrolene should be avoided7, 9. Limited evidence has suggested that amlodipine or nifedipine might not interact with dantrolene in this way4.


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


Hypotension

CCBs can increase the risk of hypotension when used concomitantly with droperidol or prochlorperazine3.

Oxycodone

Verapamil and diltiazem are predicted to increase the exposure to oxycodone – monitor for prolonged sedation and respiratory depression. The dose of oxycodone may need to be reduced3, 4.

Macrolide Antibiotics

Macrolide antibiotics (e.g. clarithromycin, erythromycin), which are inhibitors of CYP3A4, may increase the effects of CCBs leading to hypotension and, for verapamil and diltiazem, bradycardia3, 4, 5, 7, 11, 12, 13, 14, 15, 16, 17. Monitor the patient and consider reducing the dose of the calcium-channel blocker if necessary4.

Whilst single surgical prophylactic doses should not pose a problem, continued post-operative treatment may require close monitoring. Consult current product literature.


  Further Information


CCB Mode of Action 

It should be noted that there is a difference between the dihydropyridine CCBs, which do not act directly on heart rate, and diltiazem or verapamil, which lower heart rate. Introduction of verapamil or diltiazem may be considered in patients who do not tolerate beta-blockers1 – see Beta-adrenoceptor Blockers (Beta-Blockers) (Systemic and Topical) monograph.

Modified-Release (MR) Preparations – Diltiazem & Nifedipine

Different MR preparations of diltiazem (> 60mg dose) and nifedipine may not have the same clinical effect. To avoid confusion between these different formulations, the brand should be specified3.

Nimodipine

The use of nimodipine is confined to prevention and treatment of vascular spasm following aneurysmal subarachnoid haemorrhage3. Additionally, it appears to have some effect in blunting the cardiovascular response to intubation and incision (as does verapamil)2.

 

  References


  1. The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management. European Heart Journal. 2014; 35:2383-2431
  2. Scarth E, Smith S. Drugs in Anaesthesia and Intensive Care, 5th Edition. Oxford University Press; 2016
  3. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 12th April 2019]
  4. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 12th April 2019]
  5. Summary of Product Characteristics – Cardioplen XL® (felodipine) 10 mg Prolonged Release Tablets. Chiesi Limited. Accessed via www.medicines.org.uk 09/10/2019 [date of revision of the text May 2017]
  6. Summary of Product Characteristics – Securon SR® (verapamil). Mylan. Accessed via www.medicines.org.uk 09/10/2019 [date of revision of the text May 2017]
  7. Summary of Product Characteristics – ADIZEM-XL® (diltiazem). Napp Pharmaceuticals Limited. Accessed via www.medicines.org.uk 09/10/2019 [date of revision of the text May 2017]
  8. Diazepam. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 12th April 2019]
  9. Dantrolene Sodium. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 9th October 2019]
  10. Summary of Product Characteristics – Amlodipine 10 mg tablets. Accord Healthcare Limited. Accessed via www.medicines.org.uk 09/10/2019 [date of revision of the text August 2018]
  11. Nifedipine. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 12th April 2019]
  12. Diltiazem Hydrochloride. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 12th April 2019]
  13. Summary of Product Characteristics – Lercanidpine HCl 20 mg film-coated tablets. Recordati Pharmaceuticals Limited. Accessed via www.medicines.org.uk 09/10/2019 [date of revision of the text October 2010]
  14. Summary of Product Characteristics – Cardene® (nicardipine) 30mg. Astellas Pharma Ltd. Accessed via www.medicines.org.uk 09/10/2019 [date of revision of the text April 2017]
  15. Summary of Product Characteristics – Adalat LA® (nifedipine) 60 mg prolonged-release tablets. Bayer plc. Accessed via www.medicines.org.uk 09/10/2019 [date of revision of the text August 2019]
  16. Summary of Product Characteristics – Nimotop® (nimodipine) 30 mg Tablets. Bayer plc. Accessed via www.medicines.org.uk 09/10/2019 [date of revision of the text October 2017]
  17. Verapamil. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 9th October 2019]