Revised: 9 September 2014
Safety Information
Early Warning System - Monitoring Communication
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 ()
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
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.
