Headache


Frovatriptan for the Acute Treatment of Migraine Peer Tfelt-Hansen


Senior Consultant, Department of Neurology and Danish Headache Centre, Glostrup Hospital, University of Copenhagen


Abstract Frovatriptan 2.5 mg has been investigated for the treatment of moderate or severe migraine attacks in six placebo-controlled, randomised controlled trials (RCTs). The mean headache relief (a decrease from moderate or severe to none or mild) was 43 % after frovatriptan and 24 % after placebo. The mean therapeutic gain (active minus placebo) was 19 % (95 % confidence interval 16–22 %). In one large comparative RCT, sumatriptan 100 mg was superior to frovatriptan 2.5 mg for headache relief at two hours (47 versus 37 %). In three cross-over RCTs in which the patients treated migraine attacks as early as possible, frovatriptan 2.5 mg was quite similar to zolmitriptan 2.5 mg, rizatriptan 10 mg and almotriptan 12.5 mg for preference – the primary efficacy measure. It is concluded that frovatriptan is not the triptan of first choice in established moderate to severe migraine attacks (based on systematic reviews and one comparative RCT). However, if the patients can treat their migraine attacks at the start of an attack (and are not triptan-resistant), then frovatriptan is a reasonable treatment choice among the triptans.


Keywords Frovatriptan, sumatriptan, zolmitriptan, rizatriptan, almotriptan, randomised controlled trials, therapeutic gain


Disclosure: The author has no conflicts of interest to declare. Received: 31 March 2011 Accepted: 4 July 2011 Citation: European Neurological Review, 2011;6(4):262–4 Correspondence: Peer Tfelt-Hansen, Department of Neurology, Danish Headache Center, Glostrup Hospital, University of Copenhagen, 2000, Glostrup, Denmark. E: ptha@glo.regionh.dk


Frovatriptan is a 5HT1B/1D receptor agonist1 a triptan with a long terminal half-life (t½).2


and has been developed as Recurrence, the relapse of


migraine headache after an initial successful treatment, is a major problem in migraine treatment.1


recurrence occurs in 30–40 % of treated attacks.1


After treatment with other triptans, The triptans, apart


from frovatriptan, have a relatively short t½ of two to five hours.1,3 Frovatriptan has a t½ of 26 hours and this may reduce the likelihood of early migraine recurrence.2


In this article, I review the use of frovatriptan in acute migraine


treatment. The long t½ of frovatriptan suggests a long duration of action of the drug and frovatriptan has therefore been investigated for prophylaxis of menstrual-associated migraine. For a review of randomised controlled trials (RCTs) with frovatriptan used for the prevention of menstrual-associated migraine – see MacGregor, 2010.4


Pharmacokinetics of Frovatriptan Frovatriptan has an oral bioavailability of 30 %.1–3


t½ is 26 hours.2


Efficacy and Tolerability of Frovatriptan in Acute Migraine Treatment


Frovatriptan has been investigated in both placebo-controlled RCTs and comparative RCTs versus other triptans. There are no trials investigating frovatriptan versus aspirin (with or without metoclopramide) or other non-steroidal anti-inflammatory drugs. The effects of frovatriptan have also been evaluated in a meta-analysis5


and in systematic reviews.1,6 262 The time to


maximum plasma concentration is two to three hours but 60–70 % of the maximum concentration is reached after one hour.2


The terminal


Frovatriptan has been investigated in six placebo-controlled RCTs, mainly in white people;1,6,7 never been fully published.7,8 placebo-controlled RCT.9


the results of one of these trials have In addition, there has been one Korean In the six RCTs the mean therapeutic gain


(active minus placebo) for frovatriptan 2.5 mg was 19 % (95 % confidence interval [CI] 16–22 %) after two hours (based on 2,174 patients treated with frovatriptan [headache relief in 43 %] and 1,299 patients treated with placebo [headache relief in 24 %])1,7 (see Figure 1). Similarly, in the Korean patients the headache relief after two hours was 53 % in patients treated with frovatriptan and 34 % for those receiving placebo (therapeutic gain = 19 %).9 Recurrence rates of 7–25 % (mean 17 %) were reported for frovatriptan 2.5 mg.1


In one comparative parallel group, placebo-controlled RCT, frovatriptan 2.5 mg was inferior to sumatriptan 100 mg but both drugs were superior to placebo.7,8


Sumatriptan was superior to frovatriptan


for headache relief at two hours (47 versus 37 %) and pain free after two hours (18 versus 9 %). The recurrence rates were similar for frovatriptan and sumatriptan (25 versus 31 %) (see Table 1). It should be noted that this was a very large RCT with a total of 1,196 migraine attacks treated.7


In three smaller Italian RCTs, but with the more powerful cross-over design, frovatriptan 2.5 mg was compared with zolmitriptan 2.55 mg,10


rizatriptan 10 mg11 and almotriptan 12.5 mg12 (see Table 2).


In each case, preference rating for the two triptans, the primary efficacy parameter, was the same, as were pain free and pain relief after two hours. In contrast, recurrences were lower for frovatriptan


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