Self-medication with triptans

Market shares of the various triptans in 2009

Since both Naramig® and Almogran® have been available in Germany for many years, these over-the-counter triptans are by no means outstanding innovations.

However, the fact that the two triptans were able to be released from prescription requirements by the Federal Institute for Drugs and Medical Devices (BfArM) means a fundamentally new assessment of the safety of these substances and ultimately of the entire class of triptans.

This is all the more astonishing when one recalls the history of the market launch of triptans. The parent substance of the class, sumatriptan (original trade name Imigran®), was unjustly criticized at its market launch due to alleged serious safety concerns. Its undeniably good efficacy, which eclipsed all previously available treatment options for acute migraine attacks, was countered by concerns about potentially serious side effects, particularly possible circulatory disorders (heart attacks or strokes). The tightness in the chest and throat area, described by many patients as the most unpleasant side effect, seemed to confirm these fears in some cases. The fact that the market launch of Imigran® in 1993 also coincided with the introduction of drug budgeting for German physicians in private practice made the acceptance of this substance even more difficult. By 1997 at the latest, with the introduction of the "second-generation triptans"—zolmitriptan (AscoTop®), naratriptan (Naramig®), and rizatriptan (Maxalt®)—the recognition of triptans as an effective, well-tolerated, and safe class of drugs was unstoppable. Currently, seven different triptans are available in Germany, in addition to eletriptan (Relpax®), almotriptan (Almogran®), and frovatriptan (Allegro®).

Market shares of OTC triptans versus prescription triptans in 2009

All other triptans can also trigger the tightness in the chest and throat described for sumatriptan. However, in practice, only a minority of patients are affected. Even with sumatriptan, this side effect occurs in only a very small proportion of patients and usually disappears largely with prolonged use. Furthermore, this side effect occurs particularly with subcutaneous injection, and less frequently with the more commonly used tablets, nasal sprays, or suppositories. If this tightness were actually a consequence of coronary artery constriction (as initially postulated), one would have expected an increased incidence of heart attacks during treatment. However, in the more than 20 years since sumatriptan (and subsequently the other triptans) was introduced to the market, no substantiated evidence for this has been found. Coronary angiographies have shown that the diameter of the coronary arteries does not change significantly after triptan use, neither in healthy individuals nor in patients with confirmed coronary artery disease. In fact, it is now assumed that the feeling of tightness in the chest and throat area is a result of a spasm of smooth muscles in the esophagus and is therefore, although unpleasant, harmless!

Nevertheless, the dosage guidelines from the early years of sumatriptan's introduction still apply to all triptans: It must not be used in cases of known or suspected circulatory disorders of the head, heart, or other organs, nor in cases of untreated or inadequately treated hypertension. Regarding the use of sumatriptan during pregnancy, a liberalization of guidelines has begun due to increasing experience. Strict indications for its use during pregnancy remain in place. Sufficient experience with its use in pregnant women is lacking. Animal studies have not shown any evidence of embryotoxic/teratogenic effects.

Recommendations regarding the use of triptans in cases of migraine aura are imprecise. Available studies show neither a shortening of the aura by taking a triptan (sumatriptan or eletriptan) nor an increased incidence of complications. However, since triptans, unlike their effect on the coronary arteries, can presumably constrict blood vessels in the head, their use is generally discouraged in more complex auras (e.g., familial hemiplegic migraine, brainstem auras, formerly called basilar migraine) or, in the case of typical auras, only during the headache phase of the migraine, i.e., after any aura has completely subsided.

After treating millions of migraine attacks with triptans over the past 10 years, and with the worldwide understanding that triptans are not only effective but also largely safe compared to other migraine medications, the question arises as to why all triptans are not available without a prescription, or why the pack sizes of Formigran® and Dolotriptan® have been limited to 2 tablets. The main reason is:

• Like ergotamine preparations in the past and painkillers and especially caffeine-containing painkiller combination preparations today, triptans are also capable of triggering drug-induced headaches.

In practice, this manifests as a continuous increase in the frequency of migraine attacks once a threshold of 10 days per month for triptan use has been exceeded. The rule also applies to triptans that they should not be used more than 10 days per month. The limited package size of both over-the-counter triptans takes this into account. Of course, it cannot be prevented that a patient overusing medication might buy several boxes of over-the-counter triptans online or in pharmacies. However, the small package size (at a relatively high price) should easily be interpreted by the patient as an indication that triptans should not be taken in large quantities. The package size thus serves as a warning from the Federal Institute for Drugs and Medical Devices (BfArM) behind over-the-counter triptans – similar to the limitation of over-the-counter paracetamol to a maximum of 10 g per package.

The reason not all triptans are available without a prescription is that not all manufacturers have applied for their substance to be released from prescription-only status, or their applications have been rejected (for example, sumatriptan: in England it is available without a prescription in pharmacies, but in Germany, its release from prescription-only status was not approved). The properties of the individual triptans and their evaluations certainly play a role here. Triptans differ, sometimes significantly, in terms of their potency, speed of action, and duration of effect. However, tolerability is of paramount importance when considering whether a prescription is necessary. Naratriptan (Formigran®) and almotriptan (Dolortriptan®) in particular are considered to have very few side effects, which understandably makes them ideal candidates for over-the-counter availability.

Comparing Formigran® and Dolortriptan®, both can be rated as equally well-tolerated. According to study data, Dolortriptan® appears to be slightly superior to Formigran® in terms of potency, whereas Formigran® exhibits a longer duration of action. Both share the characteristic of being effective even when other painkillers have proven ineffective.

• Almogran® and Naramig® remain prescription-only. They can also be prescribed to those with statutory health insurance in packs of 6 tablets or more.
• Formigran® and Dolortriptan® are only available from pharmacies and are sold in packs of two without a prescription. These medications are not covered by statutory health insurance.

Both over-the-counter triptans represent a significant improvement in the options for self-medicating migraine attacks. If the aforementioned dosage restrictions are observed, they are generally very well tolerated. However, if triptan use approaches the threshold of 10-20 days per month (at least 6 or more days), a doctor should be consulted to prevent or treat triptan overuse headache.

An application for exemption from prescription requirements was also submitted for 10 mg rizatriptan. This application was rejected on July 5, 2011.

Authors: Dr. Axel Heinze, Prof. Dr. Hartmut Göbel