Trip Answers

Question answered:24/06/08

Interpretation: Is there any evidence taking amlodipine (5mg) and propranolol (40mg) could result in heart block and heart failure?

 

The BNF notes in Appendix 1 (interactions):

 

"Calcium-channel Blockers has the following interaction information:
Dihydropyridine calcium-channel blockers include amlodipine, felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine, and nisoldipine

 

Beta blockers: enhanced hypotensive effect when calcium-channel blockers given with beta-blockers

 

Since systemic absorption may follow topical application of beta-blockers to the eye the possibility of interactions, in particular, with drugs such as verapamil should be borne in mind." [1]

 

The SPC for Amlostin (Amlodipine) 5mg notes:

 

"Effects of amlodipine on other medicinal products
Amlodipine may potentiate the effect of other antihypertensives as beta-adrenoceptor blocking agents, ACE-inhibitors, alpha-1-blockers and diuretics. In patients with an increased risk (for example after myocardial infarction) the combination of a calcium channel blocker with a beta-adrenoceptor blocking agent may lead to heart failure, to hypotension and to a (new) myocardial infarction." [2]

 

There are a number of patient information leaflets for amlodipine tablets. We consulted the PIL for Amlodipine tablets 5mg and 10mg manufactured by Actavis UK. This recommends:

 

"Check with your doctor or pharmacist if you are taking any of the following:

 

Diltiazem (for angina), ketoconazole (antifungal), itraconazole (antifungal) or ritonavir (antiviral). These medicines may increase amlodipine levels in your blood.
Any other medicine to treat high blood pressure including ACE inhibitors (e.g. captopril, enalapril, lisinopril, ramipril), beta-blockers (e.g. atenolol, metoprolol, propranolol), other calcium antagonists (e.g. nifedipine, verapamil) and diuretics (e.g. bendroflumethiazide, furosemide). The combination of these with amlodipine may cause you to become dizzy or faint due to low blood pressure." [3]

 

In addition, we consulted the PIL for Propranolol 10mg, 40mg, 80mg and 160mg tablets and this advises:

 

"BEFORE TAKING YOUR MEDICINE
Make sure you have told your doctor if you:
are taking other medicines such as adrenaline (epinephrine); anaesthetics (eg lidociane); clonidine; anti-arrhythmic agents (eg amiodarone, disopyramide, quinidine); calcium channel blockers (eg diltiazem, verapamil); digitalis glycosides (eg digoxin); chlorpromazine, cimetidine; ergotamine, dihydroergotamine; hydralazine; indometacin; insulin, and including any that you can buy without prescription." [4]

 

We consulted the CKS guideline on hypertension for further information on potential interactions between calcium channel blockers and beta-blockers. In the section on beta-blockers, CKS warns:

 

"Beta-blockers
What drug interactions can occur with beta-blockers?
 - Never prescribe a beta-blocker with verapamil, as severe bradycardia, asystole, severe hypotension and/or heart failure can occur.
 - Caution is needed if a beta-blocker is taken with diltiazem ¡X monitor carefully (pulse, blood pressure) as bradycardia and atrioventricular block can occur with diltiazem. Asystole/sudden death has also been reported.
 - Bradycardia can be caused by beta-blockers in combination with anti-arryhythmics, diltiazem, and digoxin. Monitor the blood pressure and pulse, and adjust treatment as necessary." [5]

 

In the section of the CKS guideline on hypertension on drug interactions can occur with rate-limiting calcium-channel blockers, CKS states again:

 

"Verapamil should not be used with a beta-blocker because of the risk of reduced cardiac output and heart failure."[6]

 

Finally, we ran a search in the Medline database for studies reporting an adverse interaction between amlodipine and propranolol but found no studies.

 

For further information on this issue, we would recommend contacting the Medicines Information service who have access to additional pharmacology databases than ourselves. Should you wish us to refer this query on your behalf, please let us know via the 'Contact Us' link at: http://www.clinicalanswers.nhs.uk/index.cfm?action=contact

 

References
1. BNF No. 55 March 2008. (http://www.bnf.org.uk/bnf/bnf/current/41001i466.htm)
2. SPC for Amlostin 5 mg tablets. September 2004.
(http://emc.medicines.org.uk/emc/industry/default.asp?page=displaydoc.asp&documentid=15139)
3. PIL. Amlodipine. Tablets 5mg, 10mg (Actavis UK Ltd). February 2008
(http://emc.medicines.org.uk/emc/industry/default.asp?page=displaydoc.asp&documentid=18031)
4. SPC for Propranolol Tablets 10mg, 40mg, 80mg, 160mg (Actavis UK Ltd). January 2007. (http://emc.medicines.org.uk/emc/industry/default.asp?page=displaydoc.asp&documentid=18141)
5. CKS. Hypertension. January 2007. (http://www.cks.library.nhs.uk/hypertension#-246401)
6. CKS. Hypertension. January 2007. (http://www.cks.library.nhs.uk/hypertension#-246387)

---

DISCLAIMER: TRIPanswers is a collection of clinical questions and answers.  Each provider will have their own methodology in answering questions and these are likely not to be as rigorous as systematic review.  If you have any doubt as to the implications of this contact the Q&A Service Provider for further information. This document is presented for information purposes only. This document cannot and should not be used as a basis of diagnosis or choice of treatment, and is in no way intended to replace professional medical care or attention by a qualified practitioner. TRIPanswers and TRIP Database Ltd are not responsible or liable for, directly or indirectly, ANY form of damage whatsoever resulting from the use/misuse of information contained in or implied by this document.  Also, ensure you have read the terms and conditions for using the site.