Migraine in pediatric is a common neurological disease, and its prevalence is varying widely. The medication for the acute attack of pediatric migraine is various. we take advantage of network meta-analysis to address the efficacy and rank of these medications. Database including Pubmed and Cochrane Library were queried using a specific searching strategy. The quality of trials enrolled was assessed according to the Cochrane collaboration'tool for assessing risk of bias. The data analysis was conducted by using the core software for Cochrane reviews (Rev Man 5.3) and the Aggregate Data Drug Information System (Addis v1.16.8). The outcomes were pain-free and pain relief at 2 hours post-dose. Totally, twenty trials with high quality including 6029 migraineurs with 6912 attacks randomly assigned to 14 different drugs. The data of ketorolac and prochlorperazine were missing. We found that sumatriptan nasal spray and zolmitriptan nasal spray were superior to placebo in the two efficacy outcomes, whereas almotriptan, rizatriptan, sumatriptan with naproxen sodium, ibuprofen and ibuprofen suspension were superior to placebo only in one of the efficacy outcomes. And in network meta-analysis, we found the best 3 treatments were ibuprofen, sumatriptan with naproxen sodium and ibuprofen suspension in achieving pain-free. Meanwhile, the best 3 treatments were ibuprofen suspension, ibuprofen, and rizatriptan in achieving pain relief. In conclusion, in acute treatments of pediatric migraine, most triptans and NSAIDS were effective to achieve pain-free or pain-relief. And the most effective treatment to achieve pain-free is sumatriptan with naproxen sodium. Ibuprofen and ibuprofen suspension were the most effective treatments to achieve pain-relief.

Oral Almotriptan maleate (ALM) is used in the treatment of migraine; however, due to its extreme aqueous solubility, shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing. Being flexible and lipophilic in nature, nanostructured lipid carriers (NLCs) represent a promising tool in delivering therapeutic substances to the brain. This investigation is meant to explore the capability of mucoadhesive chitosan-coated NLCs to efficiently deliver ALM to the brain through the nasal route as a non-invasive alternative route for targeting the central nervous system (CNS). D-optimal design was adopted and thirteen different formulae were prepared using hot homogenization and ultrasonication technique; where an accurate amount of the almotriptan was added to the molten lipid mixture followed by the addition of the heated aqueous phase under stirring, then the mixture was subjected to homogenization and ultrasonication. The prepared systems were then assessed for their particle size, PDI (polydispersity index), zeta potential (ZP), and entrapment efficiency (EE). The optimized selected formula; F1; composed of 50/50 Compritol/Labrafil and a co-mixture of 2:1 tween 80: Lauroglycol all coated in chitosan, showed a PS of 255 nm, PDI 0.27, ZP 34.1 mV, and 80% EE. A bi-phasic in-vitro drug release pattern was obtained, enhanced mucoadhesive property and ex-vivo permeability through sheep nasal mucosa were attained. The In-vivo studies performed on albino rabbits showed significantly higher Cmax results in plasma of the optimized ALM-NLC (1.54 μg/mL) compared to those of IN ALM solution (0.25 μg/mL) and ALM oral tablet market product (0.58 μg/mL). Brain Cmax were found to be 3.64 μg/mL, 0.5 μg/mL and 0.48 μg/mL for IN ALM-NLC, oral ALM market product and, IN ALM solution, respectively. Histopathological examination marked the formula as safe.

Triptans are FDA approved and the first-line agents for the treatment of acute migraine episodes with or without aura.[1][2] There are seven triptans available in the United States in a variety of dosage forms: sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, frovatriptan, and eletriptan.[3] Sumatriptan, in the subcutaneous formulation, is also approved for the treatment of cluster headaches.[1] Almotriptan is the only triptan with an FDA indication for use in adolescents to treat migraines lasting at least 4 hours.[4] Zolmitriptan nasal spray is FDA approved for children 12 years or older; the use of other triptans for children is off-label.[5][4] Frovatriptan and naratriptan have an off-label indication for the prevention of menstrual migraine.[6]

Administration of almotriptan as an oral therapy is largely limited because of poor aqueous solubility and rather low bioavailability. The aim of present investigation was to formulate oral mucoadhesive film of almotriptan to improve the drug delivery and desired therapeutic effects. Placebo films (F1-F8) were prepared by varying the concentrations of Proloc 15 (7.5-15% w/v) and Eudragit RL 100/RS 100 (15-30% w/v) polymers. Physicomechanical and pharmaceutical characteristics of drug loaded films (FA1-FA4) were examined. Selected FA4 film was evaluated in vivo by assessing the pharmacokinetic profile and compared with oral therapy in rabbits. FA1-FA4 films exhibited excellent physicomechanical properties and rapid hydration. A biphasic and considerably greater drug release (p < 0.05) was observed in FA3 and FA4 films contain higher amount of hydrophilic polymer. The rate of permeation of almotriptan was found to be significantly higher in FA4 than FA3 film (p < 0.005). Fourier transform infrared spectral scan indicates no incompatibility exists between the drug and polymers used. Differential scanning calorimetry thermogram represents the evidence of almotriptan amorphization and molecular dispersion of it in the film. Scanning electron microscopy images shows that FA4 possess good morphological features and hence suitable for use in the buccal application. In vivo data demonstrated rapid and efficient absorption (p < 0.005) of almotriptan with greater AUC0-12 (>2 folds, p < 0.0001) by FA4 film as compared to oral (control). In general, the data established the potential of FA4 film to improve the therapeutic delivery of almotriptan and offers a promising option in migraine therapy.

Triptans are 5-hydroxytryptamine 1B/1D receptor agonists used in moderate to severe migraine attacks as first line when non-specific, symptomatic, nonsteroidal anti-inflammatory drugs are not effective. To gain insight in the treatment of migraine in the regional context, this retrospective (from January to August of the years 2017 and 2018) study aimed at monitoring the use of triptans approved by the regional health authority in Calabria. The data demonstrate that the overall treatment of migraine with triptans in the different provinces of Calabria falls in the average regional prescription/dispensation. Interestingly, Crotone showed a trend to an increased amount of defined daily dose/1000 inhabitants per day. The present analysis might stand for homogeneity of treatment of migraineurs in Calabria and highlights the need for better understanding the apparent differences in the local pattern of almotriptan use to improve the appropriateness.

The introduction of the second generation triptans in clinical and experimental practice was a major progress in the pharmacotherapy of migraine. Frovatriptan is a second generation triptan with strong 5-HT1B/1D serotonergic agonism and low 5-HT1A/7 receptor affinity, while almotriptan possesses not only the typical 5-HT1B/1D receptor agonist activity, but shows an affinity to the 5-HT1F receptor. The aim of our study was to assess the impact of frovatriptan and almotriptan on hemodynamics in male and female rats. We used a non-invasive "tail-cuff" method to measure the arterial blood pressure. Female and male Wistar rats were treated separately with high and low dosages of frovatriptan and almotriptan. Male and female rats showed reduction in all hemodynamic parameters, but only male rats showed an increase in the heart rate. In general, we could say that both almotriptan and frovatriptan potentiate cardiovascular safety.

Migraine headaches are marked by repeated, paroxysmal attacks of moderate-to-severe throbbing, one-sided headaches which (without treatment) last 4 to 72 hours and are usually associated with symptoms of nausea and vomiting. Migraine headaches are typically exacerbated by motion, bright lights and loud noises. Migraines may be associated with focal neurological symptoms referred to as “aura” which are typically visual, but may be sensory or motor. Migraine headaches are common, affecting at least 18% of women and 6.5% of men in the United States. The pattern of paroxysmal headaches typically arises in adolescence or young adulthood and may be life-long. The headaches often interfere with daily activities and can be incapacitating, result in major time loss from work and precipitate multiple physician and emergency room visits. Patients with migraine may also be at increased risk for other vascular complications such as stroke and eclampsia. The cause of migraine headaches is not fully understood, but appears to be related to arteriolar vasodilation and inflammation of the trigeminal nerve endings, perhaps caused by local release of vasoactive peptides. The most convincing candidate mediator of migraines is the calcitonin gene related protein (CGRP), a neuropeptide found throughout the central and peripheral nervous systems which has potent vasodilator and pain-signaling activities. Circulating levels of CGRP are elevated in pateints with migraines, and the efficacy of migraine therapies such as serotonin receptor agonists and ergot alkaloids is associated with lowering of circulating CGRP levels. Antagonists of CGRP have become a focus of migraine headache prevention and therapy. Therapy of migraine headache usually combines preventive treatments with early intervention for acute attacks. Early treatment approaches to migraine have included a number of different classes of medications including nonsteroidal antiinflammatory agents, opiate and nonopiate analgesics, barbiturates, antiemetics, ergot alkaloids, and serotonin receptor agonists. Medications used specifically to treat migraine headaches and discussed here are the ergot alkaloids and the more recently developed serotonin receptor agonists (triptans). The ergot alkaloids have been in use for many years, and currently available forms include ergotamine (Cafergot: year of approval, 1948) and dihydroergotamine (Migranal: 1946). The triptans include sumatriptan (Imitrex: 1997), zolmitriptan (Zomig: 1997), naratriptan (Amerge: 1998), rizatriptan (Maxalt: 1998), almotriptan (Almogran, Axert: 2001), frovatriptan (Frova: 2001), and eletriptan (Relpax: 2002).

Almotriptan is the first FDA-approved drug used to treat migraine headaches in adults with or without an aura.[1] The drug is also useful in adolescents with a history of a migraine that, when left untreated, lasts 4 hours or longer. Certain triptan medications such as almotriptan and rizatriptan have also shown to be effective and safe for the management of acute migraines and other benign headaches in the pediatric population (less than 18 years of age).[2] 

Introduction: Almotriptan (ALT), a serotonin 5-HT1B/1D agonist has been used in the acute treatment of migraine with or without aura for 20 years, accumulating data on more than 15,000 patients in studies and from an estimated >150 million treated migraine attacks in daily clinical practice. The last major review of ALT was written almost 10 years ago. The current narrative review provides an overview of the experience gained with almotriptan over that time, and highlights data published in the last decade. Areas covered: Randomized clinical trials, observational studies, postmarketing studies and meta-analyses involving ALT for the treatment of acute migraine identified through a systematic literature search. Expert opinion: Triptans are a mainstay of anti-migraine treatment. Findings with ALT over the last 10 years have reinforced the positive efficacy and tolerability results that were reported during the first 10 years following its introduction. In particular, more recent clinical results have confirmed its efficacy in women with menstrual migraine, the usefulness of early intervention, long-term benefit in adults, and also its efficacy and safety in adolescents. Overall, ALT can be considered an optimal choice for managing acute migraine resistant to first-line drugs.

Migraine is increasingly recognized as an extremely burdensome and disabling disorder in both children and adolescents. A proper treatment plan is needed to improve the quality of life of both children and families as well as to minimize the risk of disease progression.

This work aimed at designing efficient safe delivery system for intranasal (IN) brain targeting of the water soluble anti- migraine drug Almotriptan malate (ALM). Solid lipid nanoparticles (SLNs) were prepared by w/o/w double emulsion-solvent evaporation method. Selection of the optimized SLNs formula was based on evaluating particle size (PS), poly dispersity index (PDI) and entrapment efficiency (%EE). Optimized formula exhibited acceptable ranges; PS of 207.9 nm, PDI of 0.41 and %EE of 50.81%. Poloxamer 407 (Plx) at different concentrations (16%, 18%, 20% w/v), with different mucoadhesive polymers (Carbopol-974P, Na alginate, Na-CMC) were evaluated for gelling time and temperature, pH and mucoadhesion. The chosen mucoadhesive in-situ gel formula; 18% Plx 407 based-0.75%w/v Na-CMC, showed acceptable results, so that the optimized SLNs formula was further dispersed in it and evaluated for in vitro release, stability, in vivo and pharmacokinetics studies. Biomarkers' evaluation and histopathological examination were also investigated. Results revealed rapid ALM brain delivery of the optimized formula; Brain/blood ratios at 10 min. for NF (SLNs based IN in-situ gel), ND (Free ALM IN in situ gel) and ALM i.v. (ALM IV solution) were 0.89, 0.19 and 0.31, respectively. Toxicological results confirmed the safety of NF for nasal administration. The achieved out comings are encouraging for further clinical trials of the developed system in humans in future research.

Because there is little published experience with almotriptan during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant.

A practical palladium-mediated cascade Tsuji-Trost reaction/Heck coupling of N-Ts o-bromoanilines with 4-acetoxy-2-butenonic acid derivatives using a Pd(OAc)2/P(o-tol)3/DIPEA system is described for a straightforward synthesis of indole-3-acetic acid derivatives. This methodology was successfully applied to synthesize various substituted indole/azaindole-3-acetic acid derivatives and Almotriptan, which is a drug for the acute treatment of migraines. Moreover, a plausible cyclization mechanism has been proposed.

Almotriptan maleate (ALMT), a highly selective 5-hydroxy tryptamine 1B/1D (5-HT1B/1D) receptor agonist used in the treatment of migraine headache was subjected to various ICH (Q1A (R2)) specified guidelines. The drug underwent significant degradation under hydrolytic (acid, base and neutral), oxidative and photolytic stress conditions, while it was stable under thermal stress condition. A total of seven significant degradation products (DPs) were obtained. A simple, selective and reliable UPLC method has been developed for the separation of ALMT and its DPs using Acquity UPLC HSS Cyano (100 × 2.1 mm, 1.8 μm) column with mobile phase consisting of ammonium acetate (10 mM, pH 4.4) buffer and acetonitrile in gradient elution mode. Chromatographic analysis was performed at a flow rate of 0.3 mL/min using a PDA detector at a wavelength of 230 nm. All the DPs (DP-1 to DP-7) were characterized using UHPLC-ESI-QTOF based on mass fragmentation pattern and accurate m/z values. The developed UPLC method was validated in terms of specificity, linearity, precision and accuracy. The developed stability-indicating method helps in quantification of drug in the presence of DPs.

Migraine is a common neurovascular disorder, affecting millions of people worldwide. Current guidelines recommend triptans as first-line treatment for moderate-to-severe migraine attacks. Frovatriptan is a second-generation triptan with a longer terminal elimination half-life in blood than other triptans (~26 hours). Three double-blind, randomized crossover preference studies have been recently conducted, assessing efficacy and safety of frovatriptan versus rizatriptan, zolmitriptan, and almotriptan, respectively. Frovatriptan showed favorable tolerability and sustained effect, with a significantly lower rate of relapse over 48 hours versus the other triptans. These findings were confirmed in a series of analyses of patient subsets from the three studies, including patients with menstrually related and oral contraceptive-induced migraine, hypertension, obesity, weekend migraine, as well as patients with migraine with aura. In all patient subsets analyzed, lower headache recurrence rates were observed versus the comparator triptans, indicating a more sustained pain-relieving effect on migraine symptoms. A further randomized, double-blind study demonstrated that frovatriptan given in combination with the fast-acting cyclooxygenase inhibitor dexketoprofen provided improved migraine pain-free activity at 2 hours, and gave more sustained pain-free activity at 24 hours, versus frovatriptan alone. These benefits were observed both when the combination was administered early (<1 hour after symptom onset) or late (>1 hour after onset). Different pharmacokinetic, but synergistic, properties between frovatriptan and dexketoprofen may make the combination of these agents particularly effective in migraine treatment, with rapid onset of action and sustained effect over 48 hours. These benefits, together with potential cost-effectiveness advantages versus other triptans could drive selection of the most appropriate treatment for acute migraine attacks.

Introduction Migraine headache is a neurological disorder whose attacks are associated with nausea, vomiting, photophobia and phonophobia. Treatments for migraine aim to either prevent attacks before they have started or relieve attacks (abort) after onset of symptoms and range from complementary therapies to pharmacological interventions. A number of treatment-related adverse events such as somnolence, fatigue, and chest discomfort have previously been reported in association with triptans. The comparative tolerability of available agents for the abortive treatment of migraine attacks has not yet been systematically reviewed and quantified. Methods We performed a systematic literature review and Bayesian network meta-analysis for comparative tolerability of treatments for migraine. The literature search targeted all randomized controlled trials evaluating oral abortive treatments for acute migraine over a range of available doses in adults. The primary outcomes of interest were any adverse event, treatment-related adverse events, and serious adverse events. Secondary outcomes were fatigue, dizziness, chest discomfort, somnolence, nausea, and vomiting. Results Our search yielded 141 trials covering 15 distinct treatments. Of the triptans, sumatriptan, eletriptan, rizatriptan, zolmitriptan, and the combination treatment of sumatriptan and naproxen were associated with a statistically significant increase in odds of any adverse event or a treatment-related adverse event occurring compared with placebo. Of the non-triptans, only acetaminophen was associated with a statistically significant increase in odds of an adverse event occurring when compared with placebo. Overall, triptans were not associated with increased odds of serious adverse events occurring and the same was the case for non-triptans. For the secondary outcomes, with the exception of vomiting, all triptans except for almotriptan and frovatriptan were significantly associated with increased risk for all outcomes. Almotriptan was significantly associated with an increased risk of vomiting, whereas all other triptans yielded non-significant lower odds compared with placebo. Generally, the non-triptans were not associated with decreased tolerability for the secondary outcomes. Discussion In summary, triptans were associated with higher odds of any adverse event or a treatment-related adverse event occurring when compared to placebo and non-triptans. Non-significant results for non-triptans indicate that these treatments are comparable with one another and placebo regarding tolerability outcomes.

Treatment of pediatric migraine remains an unmet medical need. There continues to be a paucity of pediatric randomized controlled trials for the treatment of migraine, both in the acute and preventive settings. Pediatric studies are often complicated by high placebo-response rates and much of our current practice is based on adult trials. This lack of significant pediatric studies results in a wide variation in migraine management both amongst clinicians and between institutions, and evidence-based treatments are not always administered. In this article, we aim to briefly review newly approved abortive and preventive agents for migraine in the pediatric age group. Over-the-counter anti-inflammatory medications, including ibuprofen, naproxen sodium, aspirin, and acetaminophen are reasonable first-line options for abortive therapy. In addition, studies have shown triptans, or migraine-specific agents, to be safe and effective in children and adolescents and several formulations have been approved for the pediatric population, including rizatriptan, almotriptan, zolmitriptan nasal spray, and naproxen sodium/sumatriptan in combination.

Triptans are specific drugs widely used for acute treatment of migraine, being selective 5HT1B/1D receptor agonists. A proper assumption of triptans is very important for an effective treatment; nevertheless patients often underuse, misuse, overuse or use triptans inconsistently, i.e., not following the prescribed therapy. Drug analysis in hair can represent a powerful tool for monitoring the compliance of the patient to the therapy, since it can greatly increase the time-window of detection compared to analyses in biological fluids, such as plasma or urine. In the present study, a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method has been developed and validated for the quantitative analysis in human hair of five triptans commonly prescribed in Italy: almotriptan (AL), eletriptan (EP), rizatriptan (RIZ), sumatriptan (SUM) and zolmitriptan (ZP). Hair samples were decontaminated and incubated overnight in diluted hydrochloric acid; the extracts were purified by mixed-mode SPE cartridges and analyzed by LC-MS/MS under gradient elution in positive multiple reaction monitoring (MRM) mode. The procedure was fully validated in terms of selectivity, linearity, limit of detection (LOD) and lower limit of quantitation (LLOQ), accuracy, precision, carry-over, recovery, matrix effect and dilution integrity. The method was linear in the range 10-1000pg/mg hair, with R(2) values of at least 0.990; the validated LLOQ values were in the range 5-7pg/mg hair. The method offered satisfactory precision (RSD <10%), accuracy (90-110%) and recovery (>85%) values. The validated procedure was applied on 147 authentic hair samples from subjects being treated in the Headache Centre of Modena University Hospital in order to verify the possibility of monitoring the corresponding hair levels for the taken triptans.

The majority of children with recurrent headaches can be effectively treated in the primary health care. Paracetamol and ibuprofen are the recommended first-line pain medications. Limited evidence is available on the effectiveness of triptans in children and adolescents. However, nasal sumatriptan and possibly oral rizatriptan and nasal zolmitriptan can be considered for children and adolescents, as well as oral almotriptan for adolescents. Propranolol is the first-line prophylactic medication for migraine.