Nasal Spray Formulation Research Articles

Pharmacokinetics of ciclesonide and desisobutyryl ciclesonide after administration via aqueous nasal spray or hydrofluoroalkane nasal aerosol compared with orally inhaled ciclesonide: An open-label, single-dose, three-period crossover study in healthy volunteers

Background: Ciclesonide, an intranasal corticosteroid, is administered as a prodrug and is converted to the active metabolite, desisobutyryl ciclesonide, in the upper and lower airways. Previous studies have assessed systemic exposure with the ciclesonide hydrofluoroalkane metered dose inhaler (CIC HFA-MDI) and the ciclesonide aqueous nasal spray (CIC-AQ) formulations. However, systemic exposure with ciclesonide HFA nasal aerosol (CIC-HFA) developed for the treatment of allergic rhinitis has not been investigated. Objective: This study compared the systemic exposure of ciclesonide and desisobutyryl ciclesonide after administration of ciclesonide formulated as an aqueous nasal spray, an HFA nasal aerosol, or as an orally inhaled HFA-MDI. Methods: Healthy adults (aged 18–60 years) were randomly assigned in an open-label, singledose, 3-period crossover design to CIC-AQ 300 µg, CIC-HFA 300 µg, or CIC HFA-MDI 320 µg. Serum samples were collected before study drug administration and at 5, 15, and 30 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 18, 22, and 24 hours after dosing. The primary pharmacokinetic parameters were AUC 0−∞ and C max of desisobutyryl ciclesonide. Adverse events were elicited by direct questioning of participants throughout the study. Results: Thirty volunteers were randomly assigned. Most of the volunteers were male (63% [19/30]) and white (83% [25/30]); the mean age was 36 years and mean weight was 68 kg. Concentrations of desisobutyryl ciclesonide were quantifiable (lower limit of quantitation [LLOQ] = 10 ng/L) in the serum samples of only 5 volunteers (of 30) receiving CIC-AQ, and the highest C max value of desisobutyryl ciclesonide was 26.7 ng/L (mean C max, 15.2 ng/L). The AUC 0−∞ of desisobutyryl ciclesonide for CIC-AQ was below the LLOQ of the bioanalytic assay. Mean C max and AUC 0−∞ of desisobutyryl ciclesonide were 59.1 ng/L and 397.5 ng · h/L, respectively, for CIC-HFA; and 586.2 ng/L and 2685.0 ng · h/L, respectively, for CIC HFA-MDI. Concentrations of the parent compound, ciclesonide, were below the LLOQ in serum samples after administration of CIC-AQ; they were detectable up to 2 hours after administration of CIC-HFA and up to 4 hours after administration of CIC HFA-MDI. Treatment-emergent adverse events occurred with a low frequency in all 3 treatment groups (30% [9/30] overall) and were mild in intensity as determined by the study investigator. Conclusions: In this study, compared with that of CIC HFA-MDI, the systemic exposure of desisobutyryl ciclesonide was 10-fold lower after administration of CIC-HFA and at least 40-fold lower after administration of CIC-AQ. All treatments were well tolerated.

Pharmacokinetic and local tolerability profiles of three potential fentanyl nasal spray formulations developed for breakthrough cancer pain compared with oral transmucosal fentanyl citrate

e20554 Background: The nasal route offers the ability to enhance fentanyl delivery and better match the rapid onset and short duration (30–60 min) of breakthrough cancer pain compared with standard oral delivery. However, conventional nasal fentanyl solutions can be associated with variable, and sometimes supratherapeutic maximum plasma concentrations (Cmax). To optimise rapid absorption and delivery, three novel nasal spray formulations have been developed: fentanyl pectin nasal spray (FPNS), fentanyl chitosan nasal spray (FChNS), and fentanyl in chitosan-poloxamer 188 solute (FChP). Methods: This phase I, open-label, crossover study was conducted in 18 healthy adult volunteers to compare the pharmacokinetic profiles of the three new nasal fentanyl formulations with oral transmucosal fentanyl citrate (OTFC). Subjects were dosed on four occasions, separated by a >3-day washout period, under naltrexone blockade, with the nasal sprays (each containing fentanyl citrate 100μg in 100μL) and OTFC 200μg according to a randomized sequence. Venous plasma fentanyl concentrations were measured before and up to 24 hours post-dose. Local nasal tolerability was assessed by a clinician and a reactogenicity questionnaire. Results: Compared with OTFC, mean AUCs∞ for all three nasal sprays were significantly higher (P<0.05) and bioavailability significantly greater (FPNS 132%; FChNS 154%, FChP 122%). Median tmax (FPNS 19.8min; FChNS 10.2min, FChP 15.6min) were significantly (P<0.001) reduced (OTFC 90min) and mean Cmax significantly increased with all nasal sprays compared with OTFC. Of the three nasal sprays, FPNS had the lowest nasal reactogenicity symptom incidence. Conclusions: Compared with OTFC, all three fentanyl nasal spray formulations demonstrated enhanced pharmacokinetic profiles appropriate for breakthrough cancer pain as evidenced by significantly increased systemic exposure and reduced times to peak plasma values. FPNS exhibited the most favourable tolerability profile. [Table: see text]

PecSys: in situ gelling system for optimised nasal drug delivery

PecSys™ (PS) is a proprietary pectin-based drug delivery system designed to gel when applied to mucosal surfaces and with potential areas of application for drugs used in local and systemic disease therapy. The current area of focus is intranasal drug delivery where PS is being used to optimise absorption of lipophilic drugs into the systemic circulation. Pectin is described as GRAS (generally regarded as safe) with an excellent regulatory position through its long history of pharmaceutical and food usage. Tests to measure the functional gelling properties of pectin raw material and PS have been devised and validated. The PS-based products at the most advanced stages of development are intranasal formulations containing opioid analgesics intended to provide rapid pain relief with simple and convenient dosing and minimal side effects. The profile of such drugs may not be optimal through current routes of delivery and the ability of PS to modulate their pharmacokinetic profiles, such as attenuation of the peak plasma concentration (Cmax), has been demonstrated in clinical testing. The lead product using PS is a fentanyl nasal spray formulation (NasalFent®), which has successfully met the primary objective in a pivotal Phase III clinical study and is scheduled for regulatory filings in the first half of 2009.

Fentanyl pectin nasal spray (FPNS) with PecSys® provides most favorable pharmacokinetic/tolerability profile compared with nasal chitosan-based fentanyl and oral transmucosal fentanyl citrate (OTFC)

The nasal route offers the ability to enhance fentanyl delivery and better match the time course of breakthrough pain compared with oral delivery. However, conventional nasal fentanyl solutions are associated with variable and supratherapeutic maximum plasma concentrations (Cmax). This early Phase I, open-label, crossover study (Archimedes CP037) was conducted in 18 healthy adult volunteers to select an optimal nasal formulation by characterizing and comparing the pharmacokinetic/tolerability profiles of three fentanyl nasal sprays with oral transmucosal fentanyl citrate (OTFC). The three nasal sprays were: fentanyl pectin (FPNS), fentanyl chitosan (FChNS), and fentanyl in chitosan-poloxamer 188 (FChPNS). Volunteers were treated with naltrexone hydrochloride to block centrally mediated opioid effects. Subjects were dosed on four occasions, separated by ≥3-day washout periods, with the three nasal sprays (each containing fentanyl citrate 100mcg in 100mcL) and OTFC 200mcg according to a randomized sequence. Fentanyl venous plasma concentrations were measured before and up to 24 hours post-dose. Tolerability was assessed by clinical nasal assessments and a nasal reactogenicity questionnaire. Mean AUCsinf for all nasal sprays were significantly higher (P < 0.05) than for OTFC; accordingly, Frel compared with OTFC was significantly greater for all nasal sprays (FPNS 132%, FChNS 154%, FChPNS 122%). Median Tmax (FPNS 19.8 min, FChNS 10.2 min, FChPNS 15.6 min) were significantly (P < 0.001) reduced (OTFC 90 min) and mean Cmax significantly increased with all nasal sprays compared with OTFC. FPNS had the lowest nasal reactogenicity symptom incidence. Fentanyl from all nasal spray formulations showed significantly increased absorption and reduced times to peak plasma values compared with OTFC. FPNS exhibited the most favorable tolerability profile. (Sponsored by Archimedes Development Ltd.)

Comparative safety and efficacy of 2 formulations of fluticasone aqueous nasal spray in persistent allergic rhinitis

There are few data on the clinical equivalence of different nasal corticosteroids in persistent allergic rhinitis (AR). Studies measuring plasma concentrations after a single dose may not predict relative systemic bioactivity at steady state. To compare a test formulation of fluticasone propionate with the innovator using a noninferiority design. Twenty-three patients with persistent AR were randomized to completion in a double-blind, placebo-controlled, crossover manner to receive the formulations at 200 microg/d for 4 weeks, with baselines measured after 2-week run-in and washout periods. The primary outcome measure was the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) score. Both formulations produced significant improvements in MiniRQLQ scores as change from baseline (P < .001), with a nonsignificant mean difference (test vs innovator) of -0.06 U (95% confidence interval [CI], -0.41 to 0.52 U) and the lower bound of the 95% CI being above the predefined noninferiority limit of -0.7 U. Both formulations produced significant improvements in peak nasal inspiratory flow rates as change from baseline (P < .01), with a nonsignificant mean difference of 0.5 L x min(-1) (95% CI, 9.8 to 10.8 L x min(-1)). There were also significant reductions in total nasal symptom scores (P < .01), with a nonsignificant mean difference of 0.4 U (95% CI, 0.3 to 1.1 U). No significant suppression of the 10-hour overnight urinary cortisol to creatinine ratio was seen with either formulation. The test formulation was noninferior to the innovator for the primary outcome of MiniRQLQ score. The secondary efficacy and safety end points also support the interchangeability of the 2 formulations.

Pharmacokinetic characteristics and safety and tolerability of a reformulated azelastine hydrochloride nasal spray in patients with chronic rhinitis

Background: Intranasal azelastine hydrochloride (Astelin®, Meda Pharmaceuticals, Somerset, NJ, USA) is a first-line treatment for allergic and non-allergic vasomotor rhinitis with well-established therapeutic efficacy and safety. A new formulation of azelastine nasal spray (Astepro®, Meda Pharmaceuticals, Somerset, NJ, USA), with a sorbitol-based vehicle and sucralose as a taste-masking agent, was developed to reduce the bitter taste of azelastine experienced by some patients. Objective: Two studies were conducted to evaluate the safety, tolerability and pharmacokinetic parameters of this new formulation compared with the original azelastine nasal spray. Methods: In a pharmacokinetic study, 18 healthy volunteers received either a single dose of the new formulation or the original formulation and pharmacokinetic parameters were determined. In a 1-year safety study, patients with chronic rhinitis were randomized to the new formulation (n = 430) or the original formulation (n = 432) to assess tolerability and the potential for adverse effects on the nasal mucosa. Results/conclusions: The new formulation was safe and well tolerated with long-term use and had a comparable pharmacokinetic profile to the original formulation. The overall incidence of treatment-emergent adverse events with the new formulation (48.4%) and the original formulation (49.1%) was similar, with no evidence of increased nasal irritation, nasal septal perforation, severe epistaxis or ulceration with either formulation during the 1-year study.

Clinical pharmacology of the serotonin receptor agonist, zolmitriptan

Migraine is a common, often disabling, neurovascular disease that has been shown to be associated with abnormal serotonergic activity. Drugs that modulate serotonin receptors are commonly used in the acute treatment of a migraine attack. Zolmitriptan, a 5-hydroxytryptophan1B/1D receptor agonist, is once such drug that is used in acute migraine therapy. Zolmitriptan is FDA approved for the treatment of acute migraine attacks and there is recent literature demonstrating its efficacy in the acute treatment of cluster attacks. It is rapidly absorbed and is detectable in the plasma within 2 – 5 min for the nasal spray formulation and within 15 min for the oral formulations. Zolmitriptan reaches peak plasma levels in 2 – 4 h and significant plasma levels are maintained for up to 6 h and lower levels for over 15 h. As zolmitriptan's metabolism is predominantly hepatic, patients with severe hepatic impairment should not receive zolmitriptan. However, only 25% of zolmitriptan is bound to plasma proteins and thus it is unlikely for drug interactions involving the displacement of highly protein-bound drugs. Zolmitriptan is generally very well tolerated and less than half of patients in clinical trials have reported adverse events, most of which are mild and transient, although rare serious cardiovascular events have been reported with all triptans. When patients are appropriately selected, zolmitriptan is both a safe and effective acute care migraine treatment. In this review the biological role of serotonin and its receptors is covered, followed by an in-depth review of the pharmacodynamics, pharmacokinetics and efficacy of zolmitriptan. Finally, the clinical application of zolmitriptan's use in patients is dicussed.

Latest news and product developments

Latest news and product developments

Raman Chemical Imaging for Ingredient-specific Particle Size Characterization of Aqueous Suspension Nasal Spray Formulations: A Progress Report

This study was conducted to evaluate the feasibility of using Raman chemical imaging (i.e., Raman imaging microspectroscopy) to establish chemical identity, particle size and particle size distribution (PSD) for a representative corticosteroid in aqueous nasal spray suspension formulations. The Raman imaging PSD protocol was validated using polystyrene (PS) microsphere size standards (NIST-traceable). A Raman spectral library was developed for the active and inactive compounds in the formulation. Four nasal sprays formulated with beclomethasone dipropionate (BDP) ranging in size from 1.4 to 8.3 microm were imaged by both Raman and brightfield techniques. The Raman images were then processed to calculate the PSD for each formulation. Within each region examined, active pharmaceutical ingredient (API) particles are unambiguously identified and the total number of those particles, particle size and PSD of API free of excipients and PSD of API particles adhered to other excipients are reported. Good statistical agreement is obtained between the reported and measured sizes of the PS microspheres. BDP particles were clearly distinguishable from those of excipients. Raman chemical imaging (RCI) is able to differentiate between and identify the chemical makeup of multiple components in complex BDP sample and placebo mixtures. The Raman chemical imaging method (coupled Raman and optical imaging) shows promise as a method for characterizing particle size and shape of corticosteroid in aqueous nasal spray suspension formulations. However, rigorous validation of RCI for PSD analysis is incomplete and requires additional research effort. Some specific areas of concern are discussed.

Nasal Spray Device And Formulation Attributes May Contribute To Stopping Treatment With Prescription Nasal Sprays

RATIONALE: To assess the most important features of prescription nasal sprays and the key reasons why rhinitis sufferers stop using them. METHODS: Population based cross-sectional survey. A detailed questionnaire assessing allergic rhinitis burden was administered during an allergy season (April - July) to 9,822 individuals. RESULTS: A total of 6932 subjects (70.4% response) were available for analysis. 1574 subjects (22.7%) reported a history of prescription nasal spray use and expressed their opinions on the most important features of a nasal spray. Among these users, the most important features selected from the survey's list were: ease of use (47.4%); few side-effects (45.9%); medication that does not run down throat /out nose (43.2%); and does not irritate nose/throat (43.1%). Medication runs down throat/out nose was the primary reason (62.0%) reported for stopping the nasal spray, followed by bitter taste (43.7%), failure to provide 24-hour relief (34.9%), uncertainty if right amount of medication was received in each spray (31.8%), and unclear when a refill is needed (31.1%). CONCLUSIONS: Device and formulation-related attributes of nasal sprays account for most of the patient defined key barriers to their continued use. Improved formulations and delivery systems that address these key barriers may have the potential to improve adherence and compliance amongst nasal spray users.

DHE in the Pharmacotherapy of Migraine: Potential for a Larger Role

Despite a large array of currently marketed, frequently effective drugs for the acute treatment of migraine headache, comprising various classes and formulations, predictably reliable treatment for most headache types is often lacking. Dihydroergotamine mesylate (DHE) is a comparatively safe and effective therapy for migraine headache that could potentially be used for a broader range of headache types than occurs at present. The features of DHE supporting this assertion include (1) effectiveness in terminating severe, long-lasting headaches, (2) rapid onset of action, (3) very low rates of headache recurrence, (4) minimal risk of medication-overuse headache, and (5) in the nasal spray formulation, suitability for outpatients (especially patients who are very nauseated or vomiting, potentially obviating the need for an office or hospital visit for acute care). Conditions or circumstances for which there are data supporting the expanded use of DHE include menstrual migraine, migraine with central sensitization and cutaneous allodynia, medication-overuse headache, migraine recurrence, and status migrainosus. The introduction of the intranasal formulation of DHE provides both pharmacologic and patient-convenience advantages for use in migraine therapy. This article reviews the rationale for the use of DHE in these common, often difficult-to-treat migraine forms.

Nasal Spray Formulation of Teriparatide Is in the Works

Nasal Spray Formulation of Teriparatide Is in the Works

Post-Marketing Experience with an Opioid Nasal Spray for Migraine: Lessons for the Future

In 1992 a nasal spray formulation of butorphanol, an opioid medication intended for pain relief, was marketed in the USA on an unscheduled basis. Only a few years later, amid widespread reports of abuse and dependence, primarily in migraine patients, its manufacturer voluntarily requested the Food and Drug Administration to reschedule the drug as a Schedule IV narcotic. The events surrounding this episode are reviewed, and four problem areas that might have contributed are identified: (i) inadequate review of previous experience with other formulations of butorphanol; (ii) failure to consider the impact of disease state and drug formulation on the risk of adverse events; (iii) the limited scope of clinical trials prior to approval; and (iv) aggressive marketing efforts. The implications of these lessons for future drug development and post-marketing surveillance in the migraine field are considered.

Preparation of Bupleurum Nasal Spray and Evaluation on Its Safety and Efficacy

Radix Bupleuri is widely used in traditional medicine for the treatment of fever, pain, and inflammation associated with influenza or the common cold. The essential oil extracted from the herb is generally claimed to play the major role in the efficacious treatment of fever. The purpose of the present study was to formulate an intranasal delivery system for the essential oil in an aqueous solution used in the form of nasal spray. From 450 g Radix Bupleuri was extracted the essential oil in the amount of about 0.2 ml, which was slightly water-soluble and viscous with low-fluidity. In order to dissolve the essential oil evenly in the aqueous solution, tween-80 (TW-80, used in 10% (w/v) solution), propylene glycol (PG) and diethylene glycol monoethyl ether (TC) were selected as the favorable solubilizing agents, whose amount was respectively determined by L16(4(5)) orthogonal design. An aqueous solution with clarity and no ciliotoxicity was prepared when TW-80 8% (v/v), PG 14.4% (v/v) and TC 14.4% (v/v) were added. Employed to evaluate the acute toxicity, the rats grew well and were kept active and healthy within 14 d after an intranasal administration of this preparation at the dose of oil from 10 g Bupleuri/kg (50-fold higher than the clinical dose), indicating that there would be no serious toxicity at the normal dose. Intranasal administration of this preparation to 2 kg rabbits with fever induced by subcutaneous injection of turpentine decreased body temperature markedly (0.5, 0.8 and 1.0 degrees C respectively at the dose of oil from 1, 2 and 4 g Bupleuri/body). In addition, the administration significantly reduced fever in 200 g rats induced by intramuscular injection of colicine suspension (0.6 degrees C at the dose of oil from 0.8 g Bupleuri/body). The results suggest that the formulation of nasal spray for the essential oil from Radix Bupleuri can be potentially effective in the treatment of fever.

Simultaneous determination of triamcinolone acetonide and oxymetazoline hydrochloride in nasal spray formulations by HPLC

A high-performance liquid chromatography (HPLC) method with UV detection at 232 nm was developed and validated for the simultaneous determination of triamcinolone acetonide (TAA) and oxymetazoline hydrochloride (OXY) in nasal spray formulations. The chromatographic system consisted of a μBondapak™ CN column (150 mm × 3.9 mm), 5 μm particle size with a mobile phase composition of acetonitrile:ammonium acetate (pH 5.0, 20 mM) (10:90, v/v) at a flow rate of 1.0 mL/min. Calibration curves were linear for both TAA and OXY in the concentration range of 2.5–25.0 μg/mL. The limit of detection and quantitation were 0.29 and 0.88 μg/mL for OXY and 0.24 and 0.73 μg/mL for TAA. The described method was further applied to the analysis and stability studies of two nasal spray formulations I and II prepared from TAA and OXY commercial nasal spray products. The stability of OXY and TAA in the commercial products and the nasal formulations I and II were analyzed after 30 days at room temperature and 30 days at 40 °C/60% relative humidity. The results of the stability study showed that OXY and TAA in the commercial nasal spray products and the nasal formulations I and II were stable at 20–25 °C (room temperature) but TAA was unstable at 40 °C/60% relative humidity. TAA exhibited more than 10% loss at 14 days in both the nasal formulations and in the commercial products. OXY showed increased degradation at 40 °C/60% relative humidity but <10%.

Pharmacotherapy for Nicotine Dependence

Approximately 50% of long-term cigarette smokers die prematurely from the adverse effects of smoking, including on cancer, cardiovascular disease, lung disease, or other illness. This risk can be substantially reduced by smoking cessation, with greater benefits occurring the earlier in the smoking career that cessation occurs. However, cessation provides benefits at any stage, including after the onset of smoking-related disease, by improving the prognosis and quality of life. Clinicians can have a significant impact on reducing tobacco use by their patients by following the US Public Health Service Clinical Practice Guidelines. Proven strategies include structured methods of advising cigarette smokers to quit and guidance to facilitate their efforts, as well as the use of various pharmacotherapies. Pharmacotherapies for tobacco dependence include nicotine replacement medications in the form of gum, transdermal patch, lozenge, sublingual tablet, nasal spray, and vapor inhaler formulations. The only nonnicotine medication that has been approved by the US Food and Drug Administration is bupropion. Combination therapies, long-term medication therapies, and harm reduction strategies may further improve outcome with approved medications. Further, new medications such as varenicline and rimonabant are likely to reach tobacco users who are refractory to current treatments. Increasing the treatment options, increasing availability, and reducing the perceived cost of these medications may have an additional public health impact.

The Effect of Formulation Variables and Breathing Patterns on the Site of Nasal Deposition in an Anatomically Correct Model

This study was conducted to evaluate the effect of formulation variables and breathing patterns on aerosol distribution in the nasal cavity. Placebo nasal spray formulations containing 0.25% w/v Avicel CL611 (viscosity = 4 cP) and 2% w/v methylcellulose (MC; viscosity = 18.2 cP) were radiolabeled with (99m)Technicium. Following spraying into a silicone nose model, through which air was drawn at one of three constant rates (0, 10, and 20 L/min) or one of two breathing profiles (representing fast and slow inhalations), aerosol deposition in the model was quantified by gamma scintigraphy. Regional deposition was expressed as horizontal[inner, middle (h), outer] and vertical distribution [upper, middle (v), lower] in the nose model. Compared to 2% MC, Avicel CL611 significantly increased aerosol deposition in the middle (h) region of the nasal cavity under all breathing conditions, and in the inner region at 0 and 20 L/min and with a slow inhalation. The different breathing rates showed no effect on deposition of 2% MC. However, 10 L/min significantly increased the upper deposition of Avicel compared to 0 and 20 L/min. Nasal sprays with a low viscosity provided greater surface coverage of the nasal mucosa than higher viscosity formulations. Changes in breathing profiles did not affect aerosol deposition in this nose model.

Speed of Onset, Efficacy and Tolerability of Zolmitriptan Nasal Spray in the Acute Treatment of Migraine

Migraine is a common, disabling condition that has a significant impact on patients and relatives, and is a considerable economic burden on society. Migraine patients want fast-acting treatments with high efficacy. Previous studies have demonstrated that orally administered formulations of zolmitriptan are rapidly and highly effective in the acute treatment of migraine. The objective of this study was to assess the efficacy, speed of onset and tolerability of the nasal spray formulation of zolmitriptan in migraine treatment. This multicentre, randomised, double-blind study recruited 2122 patients (aged 18-65 years) who had an established diagnosis of migraine (according to International Headache Society criteria), with or without aura. Patients were randomised to receive zolmitriptan 5mg nasal spray or placebo to treat up to two migraine attacks within 15 minutes of headache pain becoming moderate or severe. The primary endpoint was headache response (reduction in migraine pain from severe/moderate to mild/none) at 2 hours, 1 hour, 30 minutes and 15 minutes post-dose (analysed using a step-down approach). Secondary endpoints included headache response at 4 hours, pain-free rates at 30 minutes and 1, 2 and 4 hours, and sustained headache response and pain-free status at 24 hours post-dose. The headache response rate at 2 hours post-dose was 66.2% for the zolmitriptan group, compared with 35.0% for the placebo group (p < 0.001). Zolmitriptan nasal spray also produced significantly higher headache response rates than placebo at all earlier timepoints assessed, starting as early as 15 minutes post-dose (p < 0.001). Similar results were obtained for the analysis of the first attack. Significantly higher pain-free rates were obtained with zolmitriptan nasal spray, compared with placebo, from 15 minutes post-dose onward (p < 0.005). Zolmitriptan nasal spray was also significantly superior to placebo for headache response at 4 hours, sustained headache response at 24 hours and sustained pain-free rate at 24 hours. Zolmitriptan nasal spray was well tolerated, with most adverse events being of short duration and mild or moderate intensity. Zolmitriptan nasal spray is highly effective in the acute treatment of migraine and has a very fast onset of action, producing significant headache response and pain-free rates as early as 15 minutes post-dose (the earliest assessment in this study). In addition to the very fast onset of action, zolmitriptan nasal spray produced significantly higher sustained headache response and pain-free rates at 24 hours post-dose compared with placebo. These desirable efficacy outcomes were combined with good tolerability.

Pharmacological treatment of attacks in juvenile migraine

Although migraine is a common complaint in childhood and adolescence, there is a lack of controlled clinical studies regarding treatment. In the young patient, the pharmacological approach should be preceded by setting up non-pharmacological measures which include behavioural intervention. The sole use of symptomatic therapies should be limited to patients who complain of up to four partially or totally disabling attacks, or those who suffer from headache for more than 4 days per month. The therapeutic armamentarium includes non-specific symptomatic drugs, such as analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), as well as anti-emetics and specific drugs, such as the triptans. Analgesics and NSAIDs are the most frequently used drugs in childhood and adolescence for the symptomatic treatment of migraine attacks of slight or moderate intensity. The first-choice drug for those under 12 years of age is acetaminophen. Among NSAIDs, two double-blind, randomized, placebo-controlled studies were conducted for ibuprofen, supporting its efficacy. In the past, ergot derivatives played an important role in the treatment of spontaneous migraine attacks, particularly in adults, but after the triptan revolution their role was strongly confined to a small number of patients. Although they are considered first-choice drugs for moderate and severe migraine attacks in adults, triptans are still under study in migraine patients under 18 years of age. The Health Ministry rules do not approve their use in patients under 18 years. They can only be given legally if the therapeutic plan for their use is previously approved by the Ethics Committee and after informed consent from the patient/parents. Promising results have been obtained, particularly for sumatriptan in nasal spray formulation as well as for zolmitriptan and rizatriptan, showing a high tolerability and safety profile.

Parental satisfaction with sumatriptan nasal spray in childhood migraine.

Migraine headaches are a frequently encountered neurologic problem in children. The utility of the triptans has not been as clearly documented in this population, although it is well delineated in acute migraine attacks in adults. We conducted a retrospective chart review of our experience with using sumatriptan nasal spray in children aged 5 to 12 years from our headache clinic population with migraine headaches. The nasal spray formulation is used frequently in our clinic population with patients who have failed over-the-counter therapy with ibuprofen or acetaminophen. None of the triptans are approved by the US Food and Drug Administration for use in children or adolescents (12 years and older). One hundred of these patients were identified, and their parents or guardians completed a standardized questionnaire regarding their child's response to sumatriptan nasal spray in acute migraine. Fifty-seven of 100 families completed the questionnaire, and 44 of 57 families (77%) reported good to excellent relief of their child's migraine attacks with sumatriptan nasal spray. In our cohort of pediatric patients, sumatriptan nasal spray was effective and well tolerated when used for abortive therapy of acute migraine attacks.