Use Of Frovatriptan Research Articles

Computational evaluation on molecular stability, reactivity, and drug potential of frovatriptan from DFT and molecular docking approach

Molecular stability, fundamental chemical reactive sites, global reactivity descriptors in frovatriptan molecule have been investigated by using computational evaluation and molecular docking approach. The density functional theory has been employed with standard functional B3LYP/6–311++G(d,p). The possible minimum energy structure has been predicted by implementing one-dimensional potential energy surface (PES) scan. The charge delocalization for stability of the molecule with natural bond orbital (NBO) analysis and molecular electrostatic potential (MEP) surface analysis to observe the active region for further chemical reaction with surrounding species have been performed. The chemical reactivity and hardness of the molecule in terms of HOMO-LUMO energy gap (ΔEL-H) have been implemented in terms of reactivity parameters. The potential use of frovatriptan as non-linear optical (NLO) material and its thermodynamical studies have also been performed. Moreover, the molecular docking with a predicted target has been performed to check the binding interaction as well as sites of the molecule.

EHMTI-0052. Efficacy of early vs. late use of frovatriptan combined with dexketoprofen vs. frovatriptan alone in the acute treatment of migraine attacks with or without aura

EHMTI-0052. Efficacy of early vs. late use of frovatriptan combined with dexketoprofen vs. frovatriptan alone in the acute treatment of migraine attacks with or without aura

A review of frovatriptan for the treatment of menstrual migraine.

The objective of this review is to provide an overview of menstrual migraine (MM) and of frovatriptan and to assess clinical trial data regarding the efficacy and safety of frovatriptan for the acute and short-term prophylaxis of MM. Randomized controlled trials comparing frovatriptan with placebo or a triptan comparator for the acute or prophylactic treatment of MM were selected for review. MM affects up to 60% of women with migraine. Compared with attacks at other times of the cycle, menstrual attacks are longer, more severe, less responsive to treatment, more likely to relapse, and more disabling than attacks at other times of the cycle. No drugs are licensed for acute treatment of MM; triptans are recommended for treatment of moderate to severe attacks for menstrual and nonmenstrual attacks. Perimenstrual prophylaxis is indicated for patients with predictable MM that does not respond to symptomatic treatment alone. Treatment is unlicensed, but options include triptans, nonsteroidal anti-inflammatory drugs, and hormone manipulation. Frovatriptan is distinctive from other triptans due to its long elimination half-life of 26 hours, which confers a longer duration of action. Post hoc analyses from randomized trials of MM show similar pain relief and pain-free rates for frovatriptan compared with other triptans (2 hours pain-free: relative risk [RR] 1.27, 95% confidence interval [CI] 0.91–1.76) but significantly lower relapse rates (24 hours sustained pain-free: RR 0.34, 95% CI 0.18–0.62). Data from randomized controlled trials show a significant reduction in risk of MM in women using frovatriptan 2.5 mg once daily (RR 1.56, 95% CI 1.31–1.86) or twice daily (RR 1.98, 95% CI 1.68–2.34) for perimenstrual prophylaxis compared with placebo. The twice daily dosing was more effective than once daily (RR 1.27, 95% CI 1.11–1.46). These findings support the use of frovatriptan as a first-line acute treatment for MM and for perimenstrual prophylaxis.

A review of the use of frovatriptan in the treatment of menstrually related migraine

Menstrual migraine (MM) is a highly prevalent condition associated with considerable disability. Migraine attacks occur exclusively around the menstrual period in approximately 10% of women with migraine, that is, pure menstrual migraine, while at least 50% of them also experience migraine at other times of the month, that is, menstrually related migraine (MRM). The therapeutic approach to patients with MRM is based on treatment of the attack, or prophylactic strategies. Triptans are recommended as first-line treatments for moderate to severe migraine attacks, including MM. Frovatriptan is one of the newest triptans. Its high affinity for 5-HT1B/1D receptors and long half-life contribute to its distinctive clinical effect, characterized by a more sustained and prolonged effect than other triptans. Indeed, frovatriptan proved to be effective in treating the acute attack, but was particularly effective in the short-term preventive therapy of MM. In addition, frovatriptan is one of the safest triptans, with the lowest risk of treatment-emergent adverse events. Following extensive evidence from randomized pharmacological trials, frovatriptan has now gained a grade A recommendation from the guidelines for short-term prophylaxis of MM. Recent post-hoc analyses of direct comparative trials also suggest that frovatriptan might have an important role in the acute treatment of MRM. In these studies, frovatriptan showed pain relief and pain-free rates similar to those of zolmitriptan, rizatriptan, and almotriptan, but with significantly lower recurrence rates. More well-designed, randomized, prospective studies, specifically enrolling women with MM, will be needed in the near future to confirm the efficacy of frovatriptan in this migraine subtype.

Two Center, Randomized Pilot Study of Migraine Prophylaxis Comparing Paradigms Using Pre‐Emptive Frovatriptan or Daily Topiramate: Research and Clinical Implications

To compare the efficacy and clinical benefit of 2 paradigms of migraine prevention using pre-emptive frovatriptan and daily topiramate. The study compares the paradigms of pre-emptive use of frovatriptan, a drug approved for acute migraine, and the daily use of topiramate, a Federal Drug Administration-approved and -accepted standard for migraine prophylaxis. Traditionally, preventive treatment of migraine required daily medication. However, recent studies suggest that pre-emptive prophylaxis may be beneficial to those migraineurs who can predict an attack of migraine based on premonitory symptoms and treat during that phase. A total of 76 adult subjects with a diagnosis of migraine were screened for the study. During a 1-month baseline period, subjects demonstrated through a daily diary that they predicted at least 50% of migraine attacks during the premonitory phase and treated with their usual medication. Of these, 55 were randomized to either Group A (daily topiramate) or Group B (frovatriptan during premonitory symptoms); 44 completed the study. The treatment period lasted 2 months. The subjects answered the Migraine-Specific Quality of Life Questionnaire at randomization, and at Weeks 4 and 8. The revised Patient Perception of Migraine Questionnaire was answered 24 hours after taking frovatriptan (Group A, for break-through headaches; Group B, treatment during premonitory symptoms). The number of migraine attacks and headache days per month decreased significantly from baseline for both Groups A and B. Subjects in Group A had considerably more adverse events leading to study withdrawal than in Group B (18% vs 4%). Though this study was not powered to directly compare the efficacy of the 2 drugs, topiramate showed superiority over frovatriptan at Month 2 in reduction of headache days, which was a secondary end point in the study (P = .036). This pilot study demonstrated that statistical benefit for reduction of headache days over baseline for both pre-emptive frovatriptan and daily topiramate. Subjects utilizing pre-emptive frovatriptan experienced fewer adverse events leading to study withdrawal. Subjects utilizing daily topiramate had fewer headache days at Month 2.

Pharmacokinetic evaluation of frovatriptan

Introduction: Migraine is the most common painful neurological disorder, affecting 13% of the general population. Triptans represent a powerful pharmacological tool in acute migraine treatment, however, a significant portion of treated patients cannot have access to this class due to possible adverse affects. Today, a total of seven triptan molecules are available, representing a commonly prescribed migraine treatment. Although there is a need of extensive use of triptans, only 25% of migraine patients are using triptans.Areas covered: This review includes triptans and evidence for the use of frovatriptan. A systematic approach is used to discuss the pharmacodynamic and pharmacokinetic aspects of frovatriptan, considering the emerging data on the clinical efficacy of frovatriptan in the treatment of migraine and cluster headaches. The data were obtained by searching the following key words in MEDLINE: pharmacokinetic, pharmacodynamic, triptans, frovatriptan, migraine, menstrual migraine, relatively to the period 1988 – 2011.Expert opinion: Frovatriptan has been developed in order to improve safety and efficacy of triptans. It shows a favorable tolerability and efficacy profile, limited to 24/48-h headache recurrence, when compared with other triptans. Preclinical data suggest that the pharmacokinetic profile of frovatriptan may differ from other available triptans. In fact, among triptans, frovatriptan showed the highest potency at the 5-HT1B receptor (8.2) and the longer half-life (26 h). These parameters determine the clinical properties of frovatriptan; in particular the lowest rate of headache recurrence in comparison with other triptans.

When to use frovatriptan in migraine? A reply

Dear Sir, We read with interest the comments of Dr. Tfelt-Hansen [1] on the two recently published randomized controlled trials comparing patients’ preference (primary end-point) and efficacy (secondary end-points) of frovatriptan with respect to rizatriptan [2] and almotriptan [3]. In both studies, frovatriptan showed similar preference and short-term efficacy outcomes (pain relief and pain free episodes at 2 h) with respect to the other two triptans. The principal concern of Dr. Tfelt-Hansen was the very early use of frovatriptan in these studies, making their results hardly comparable with those of previous randomized controlled trials [4–6], where patients waited until the headache was moderate or severe. In our studies [2, 3], patients were instructed to take one dose of study medication as early as possible after the onset of migraine and to treat at least 1 out of three attacks, but severity of headache at the time of drug intake was in the majority of patients moderate or severe. As a matter of fact, in the study by Savi et al. [2] 78% of attacks treated with frovatriptan and 74% of those treated with rizatriptan were of moderate or severe intensity. In the study by Bartolini et al. [3] 80% of overall treated attacks were of moderate or severe intensity and 97% of patients had at least one moderate or severe attack. However, these studies had a cross-over design and thus the same patient was treated with both drugs in a randomized sequence. Moreover, early treatment in our studies better reflects reality compared to the artificial design of other studies where patients usually start treatment when the attack intensity becomes moderate or severe. Thus, the results of our studies are much more consistent than those of randomized controlled studies with a parallel group design. In addition, the most significant result of our studies was a more sustained relieving effect on migraine symptoms with frovatriptan, with lower headache recurrence rates over the 48 h; these results are in line with previous reports comparing frovatriptan with placebo [7–9] or sumatriptan [10].

Randomized, placebo-controlled comparison of early use of frovatriptan in a migraine attack versus dosing after the headache has become moderate or severe

SUMMARYObjective: To evaluate whether frovatriptan would provide greater relief if given early during a migraine attack.Research design and methods: Adults with a history of migraine of at least 1 year, and who had 2–8 headaches in the previous month were recruited from 19 US centres for a prospective, placebo-controlled crossover study over 2 migraine attacks. Dose 1 was taken at the onset of mild migraine headache, Dose 2 was taken at least 2 h later if the headache progressed to moderate/severe. Patients were randomized to receive Dose 1 frovatriptan then Dose 2 placebo or Dose 1 placebo followed by Dose 2 frovatriptan. Treatment order was reversed for the second attack. This schedule enabled a comparison of frovatriptan with placebo and a comparison of early and later treatment with frovatriptan.Main outcome measures: Freedom from pain at 2 h for frovatriptan versus placebo as Dose 1; use of Dose 2 and/or rescue medication, pain severity, functional impairment and headache recurrence.Results: In 241 patients who each treated 2 migraine attacks, Dose 1 frovatriptan was more effective than placebo in terms of the proportion of patients who were pain free at 2 h (28% vs 20%, p = 0.04). This benefit was sustained up to 4 h post-dose ( p = 0.003). Early use of frovatriptan significantly reduced re-medication ( p < 0.001). Twenty-four-hour headache recurrence was low in both early (4%) and later use (6%) groups. Sustained pain-free response occurred in 40% of frovatriptan early use patients compared with 31% of later use patients ( p < 0.05). Early use prevented headache progression: 69%–78% had mild/no headache 2–4 h after Dose 1 frovatriptan compared with 54%–63% taking Dose 1 placebo ( p < 0.001). Early use reduced pain burden and functional disability ( p ≤ 0.001). More patients rated early use of frovatriptan as excellent or good (57% vs 46%).Conclusions: Early use of frovatriptan resulted in a higher, earlier and sustained pain-free response, prevented progression to moderate/severe headache and reduced pain burden and functional disability.