Proposed changes to Required Advisory Statements for Medicine Labels (RASML): Triptans

Results updated 17 Nov 2021

Introduction

We asked for comments from interested parties on proposed new advisory statements for labels of over the counter (OTC) medicines containing triptans (sumatriptan, zolmitriptan, rizatriptan, eletriptan), for inclusion in the Required Advisory Statements for Medicine Labels (RASML).

Summary and discussion of responses

The TGA would like to thank those who responded to the consultation. We received 7 submissions. These were supportive overall, but each proposed amendments.

One respondent considered that the warning not to use “without a previous diagnosis of migraine by a doctor” should be replaced with “Do not use without consulting your pharmacist or doctor”. However, the TGA consider that the proposed warning is appropriate to ensure a clear diagnosis of migraine and to exclude other potentially serious neurological conditions.

One respondent considered that warnings against use in specific types of migraine should be included, consistent with the Product Information. The TGA consider that this information can instead be included in the package insert; reasons for this include lack of label space and the large number of other warnings, the relevant forms of migraine are rare and relevant patients are likely to be aware of this information already.

One respondent with concerns about risk of medication overuse headache (MOH), recommended inclusion of a warning not to use more than 10 days per month. While acknowledging the concern, the TGA consider that usage limits would be best assessed individually by medical practitioners and facilitated by pharmacists, as necessary. There is no guidance on maximum frequency of use in approved Product Information.  The proposed warnings should be sufficient to alert patients as to risks of overuse and to speak to a pharmacist or doctor if migraine attacks become more frequent. Reference to ‘migraine attacks’ will be implemented as recommended by the respondent.

Three respondents were concerned that consumers may misunderstand the warning “Do not use if you have taken other migraine medications within 24 hours” to refer to NSAIDS, paracetamol or medicines taken for migraine prophylaxis. Given the warning relates to rarely used and/or unavailable medicines (ergotamine, ergotamine derivatives and methysergide), the respondents considered it preferable to replace/modify the warning for clarity. To address the concern the warning will be replaced, as recommended by one respondent, with the warning “Consult your doctor or pharmacist before use… if you are taking other medicines for migraine”.

Two respondents considered that reference to monoamine oxidase inhibitors should be removed, one due to their infrequent use, another considering the term to be too technical. For these reasons, and to reduce the number of required warnings, the warning “Do not use… if you have taken monoamine oxidase inhibitors (MAOIs; medicines used to treat depression) in the last 2 weeks” will be omitted and the existing warning amended as follows: “Consult your doctor or pharmacist…if you are taking, or have taken in the last two weeks, medicine for depression or anxiety”. As noted by one respondent, MAOIs may be used for anxiety as well as depression. Addition of reference to “anxiety” also covers use of serotonin reuptake inhibitors which may also be used for anxiety, in addition to depression, and are also a potential concern for interactions with triptans.

Two respondents noted additional medicine interactions of concern for eletriptan (ie. CYP3A4 inhibitors such as erythromycin and ketoconazole).  To address this, the medicine interaction warning for eletriptan (which does not interact with MAOIs), will be amended to refer to “any other medicines” as follows: “Consult your doctor or pharmacist before use… if you are taking any other medicines, including for migraine, medication for depression or anxiety”.

Two respondents considered that reference to “peripheral vascular disease (a blood vessel disorder)” was not consumer friendly and could be replaced with “blood vessel disease” or “circulation problems”. However, the TGA prefer to retain reference to “peripheral vascular disease” to maintain accuracy of the warning, with reference to “(a blood vessel disorder)” included to provide further explanation for consumers. The wording of the warning is to be re-ordered slightly as recommended.

One respondent questioned why the heart disease risk factors of “post-menopausal or a male over the age of 40” were specifically included and recommended their removal. The TGA prefer to retain reference to these risk factors for heart disease, which may be less recognised than more obvious risks factors such as obesity and smoking, to ensure consumers are aware of the risks and consult their doctor or pharmacist accordingly.

Two respondents considered that “Do not use…if you have…high blood pressure” should be amended to “uncontrolled high blood pressure” or “…if it is not being treated”, consistent with the product information. While the TGA appreciates the reasoning for this recommendation, it prefers to maintain existing wording as it may be difficult for consumers to determine whether their high blood pressure has been appropriately “controlled” or “treated”. The proposed wording should prompt consumers to ask a pharmacist or doctor if unsure.

Two respondents recommended amendment of the warning “Do not use… if you have liver or kidney problems, unless advised by your doctor”, to simplify the warnings and/or because it is less relevant to rizatriptan specifically. Noting the risks in relation to liver and kidney problems and the large number of existing warnings, it is agreed that the warning can instead be incorporated with existing warnings as follows: “Consult your doctor or pharmacist before use… if you have liver or kidney problems or any other medical conditions.”

One respondent requested consideration of a 24-month transition rather than 18 months, to avoid risk of discarding non-compliant product. The TGA considers that existing implementation timeframes are appropriate and notes that temporary exemptions may be given in extenuating circumstances.

Outcome

Following feedback from the consultation, amendments to the proposed RASML entries are made as shown in the document linked below (see tracked changes). The final entries (see clean version in link below) will be included in the next update of the RASML to occur in late 2021 or early 2022. A transition period of 18 months from commencement of the new RASML will allow for existing medicines that do not comply with new requirements to have their labelling updated.

Final RASML entries for triptans

Published responses

View submitted responses where consent has been given to publish the response.