Medsafe Logo
Hide menus
Show menus

Safety Information

Revised: 9 September 2014

Early Warning System - Monitoring Communication

Medsafe emphasises that patients should NOT stop using any medicine or medical device subject to a monitoring communication. If you have any concerns with a medicine or medical device you are using, please contact your health professional. A monitoring communication does not mean that the medicine or medical device causes an adverse event.

M² logo Amitriptyline and a possible risk of peripheral coldness (cold hands and/or feet) or Raynaud's phenomenon added to the medicines monitoring scheme

3 February 2014

Lareb, the Dutch Pharmacovigilance Centre, identified a signal of peripheral coldness associated with the use of tricyclic antidepressants. Lareb has received 11 reports of peripheral coldness of the hands and/or feet, with seven of these reports associated with the use of amitriptyline. In New Zealand, there has been one report of localised numbness and one report of aggravated Raynaud's with the use of amitriptyline.

Products Affected

Amitriptyline is a tricyclic antidepressant indicated for the treatment of depression. Tricyclic antidepressants are also used for other unapproved indications.

Product name Sponsor
Amirol AFT Pharmaceuticals
Amitrip Mylan New Zealand
Arrow-Amitriptyline Actavis New Zealand
PAC-Amitriptyline Ipca Pharma (NZ)

Additional Information

Raynaud's phenomenon is described as a reduction in blood flow to the peripheries, which results in discolouration (paleness), pain and sensations of cold and/or numbness in the affected extremities.

The New Zealand data sheets for amitriptyline already list numbness, tingling and paraesthesias of the extremities, as well as peripheral neuropathy and incoordination. Advice on how to take this medicine and other possible side effects can be found in the consumer medicine information (CMI) and data sheets.

The overall benefit-risk balance of amitriptyline remains positive.

Regulator Actions

Medsafe is placing this safety concern on the medicines monitoring (M² logo) scheme to obtain further information. Please report any adverse events with tricyclic antidepressants, in particular suspected peripheral coldness or Raynaud’s phenomenon.

Reporting

Consumers and healthcare professionals are encouraged to send reports of suspected adverse reactions to the Centre for Adverse Reactions Monitoring (CARM).

Medsafe cannot give advice about an individual's medical condition. If you have any concerns about a medicine you are taking Medsafe encourages you to talk to your healthcare professional.

How to report an adverse reaction

Update to Original Communication

During the M² logo period (3 February to 31 July 2014), one case was reported to the Centre for Adverse Reactions Monitoring (CARM). The patient had pre-existing Raynaud’s syndrome; the frequency of symptoms increased when amitriptyline was started and when the dose of amitriptyline was increased. Symptoms included blackened fingers and a loss of sensation up to the elbow. The patient’s symptoms greatly improved when amitriptyline was stopped.

There is published case reports of peripheral coldness/Raynaud’s phenomenon associated with amitriptyline in the literature. A mechanism that may explain this potential adverse reaction is peripheral vasoconstriction due to amitriptyline’s (as a tricyclic antidepressant) action as a serotonin-norepinephrine reuptake inhibitor. An increased level of norepinephrine (amongst other effects) increases stimulation of peripheral alpha-1 and alpha-2 receptors, resulting in vasoconstriction. However, as tricyclic antidepressants also act as direct antagonists of alpha-1 adrenergic function, this mechanism may not fully explain the action.

Peripheral neuropathy, and numbness, tingling and paraesthesias of the extremities are included in the amitriptyline data sheets as possible adverse reactions. Currently, this information is sufficient.

The balance of benefits and risks of harm for amitriptyline remains positive and no further action is required at this time.

0 1 2 4 5 6 7 9 [ /