Subcutaneous Injection Of Sumatriptan Research Articles

447 Modulation of Patient Reported Outcomes and Opioid Consumption Following Open Craniotomy: The Efficacy and Safety of Subcutaneous Sumatriptan

INTRODUCTION: Traditional pain management regimens following open craniotomy commonly employ opioid medications. As a medication class, opioids present a considerable adverse effect profile and the potential for medication abuse. Alternative medication regimens to better address post-craniotomy pain while mitigating opioid-related adverse effects are insufficiently studied. However, as a dural-based 5-HT1D receptor agonist that regulates vasoconstriction and inflammatory peptide signaling, sumatriptan shows promise to improve pain scores and reduce opioid requirements. METHODS: This is a single academic center, retrospective cohort study of 130 consecutive adult patients undergoing open craniotomy between 7/2015 and 8/2021. Patients were divided between a Control and Sumatriptan cohort contingent upon administration of a single 6mg subcutaneous injection of sumatriptan within 1-hour of surgery completion and prior to opioid administration. Opioid consumption at 6, 12 and 24-hours postoperative and admission total, inpatient length of stay (LOS) and 30-day global representation/readmission were evaluated. RESULTS: 130 patients were equally divided between the Sumatriptan and Control cohorts for analysis. No difference in baseline demographics was noted. A significant reduction of mean pain score at 6, 12 and 24-hours following surgery substantially favored the Sumatriptan cohort (p < 0.05). Further, a nonsignificant reduction in opioid requirements was observed at all timepoints favoring the sumatriptan cohort (p > 0.05). 30-day global ED evaluation and readmission rates between cohorts were similar (p > 0.05). Overall LOS in the Sumatriptan and Control cohorts were 5.3 ± 3.6 vs 6.5 ± 5.6 days (p > 0.05). No difference in the rate of incisional or intracerebral hemorrhage was noted between cohorts (p > 0.05). CONCLUSIONS: In the present study, patients in the Sumatriptan cohort demonstrated enhanced pain control and reduced opioid requirements suggesting sumatriptan represents a safe and efficacious agent for the modulation of pain following open craniotomy.

Subcutaneous sumatriptan for the treatment of postcraniotomy pain (SUPS trial): protocol for a randomised double-blinded placebo controlled trial

IntroductionPostcraniotomy pain protocols use opioids, which are considered suboptimal analgesia following this procedure. Multimodal analgesia components are sparse. Our null hypothesis states that sumatriptan is not different to placebo in...

Pharmacokinetic Characterization and Dose Selection of a Novel Sumatriptan Nasal Spray Formulation, DFN-02.

This 3-way, single-dose, randomized crossover study evaluated the pharmacokinetics (PK) and dose proportionality of 5-, 10-, and 15-mg doses of intranasal sumatriptan (DFN-02) coformulated with a permeation enhancer (DDM) in 18 healthy adults. The objective was to determine which DFN-02 dose approximates the PK of a 6-mg dose of sumatriptan delivered via subcutaneous injection in the deltoid muscle of the arm. Sumatriptan plasma concentrations peaked with DFN-02 between 10 and 15 minutes postdose, declining thereafter, with a t1/2 of about 2.5 hours; mean Cmax and AUC0-∞ values increased linearly across doses. After DFN-02 doses of 5, 10, and 15mg, mean Cmax was 40.7 ± 14.2, 71.2 ± 22.1, and 101.0 ± 49.5ng/mL, and mean AUC0-∞ was 49.9 ± 20.6, 87.1 ± 31.2, and 120.5 ± 53.3ng·h/mL, respectively. The increase in sumatriptan bioavailability was less than dose-proportional among the DFN-02 doses studied. Based on the established PK of a 6-mg subcutaneous sumatriptan injection (mean Tmax , 12 minutes; mean Cmax , 74 ± 15ng/mL in the deltoid area of the arm) and the peak and time to peak sumatriptan concentrations of the DFN-02 doses tested, a 10-mg dose of DFN-02 was found to be the closest match. Overall, DFN-02 was well tolerated at doses of 5to 15mg, and no new safety concerns were identified.

The effect of sumatriptan on cephalic arteries: A 3T MR-angiography study in healthy volunteers

To explore a possible differential effect of sumatriptan on extracerebral versus cerebral arteries, we examined the superficial temporal (STA), middle meningeal (MMA), extracranial internal carotid (ICAextra), intracranial internal carotid (ICAintra), middle cerebral (MCA) and basilar arteries (BA). The arterial circumferences were recorded blindly using high-resolution magnetic resonance angiography before and after subcutaneous sumatriptan injection (6 mg) in 18 healthy volunteers. We found significant constrictions of MMA (16.5%), STA (16.4%) and ICAextra (15.2%) ( P ≤ 0.001). Smaller, but statistically significant, constrictions were seen in MCA (5.5%) and BA (2.1%) ( P ≤ 0.012). ICAintra change 1.8% was not significant ( P = 0.179). The constriction of cerebral arteries was significantly smaller than the constriction of extracerebral arteries ( P < 0.000001). Sumatriptan constricts extracerebral arteries more than cerebral arteries. We suggest that sumatriptan may exert its anti-migraine action outside of the blood-brain barrier.

Satisfaction With and Confidence in Needle-Free Subcutaneous Sumatriptan in Patients Currently Treated with Triptans

To evaluate patient satisfaction with and confidence in Sumavel® DosePro® (needle-free subcutaneous sumatriptan) among current triptan users administering Sumavel DosePro for up to 4 migraine attacks. Sumavel DosePro is a needle-free, single-use device that facilitates subcutaneous injection of sumatriptan 6 mg and confers relief as early as 10 minutes after dosing. In this open-label, multicenter study, Sumavel DosePro was self-administered for ≤4 migraine attacks (over a ≤60-day period) involving moderate or severe baseline pain by adult migraineurs who currently were using triptans (any form, any dosage) and reported being less than very satisfied with their current therapy (i.e., baseline satisfaction ranging from satisfied to very dissatisfied). Treatment satisfaction was measured via the Patient Perception of Migraine Questionnaire, revised (PPMQ-R). Among the 212 patients using Sumavel DosePro to treat ≥1 migraine attack, PPMQ-R Overall Satisfaction (primary endpoint) increased significantly from baseline to the end of treatment (mean ± SD 65.7 ± 19.8 vs. 73.7 ± 29.1, P = .0007), an improvement that met the criterion for clinical significance. From baseline to the end of treatment, PPMQ-R scores also improved significantly for Efficacy (62.2 ± 17.6 vs. 76.2 ± 23.7, P < .0001), Functionality (59.0 ± 22.3 vs. 73.8 ± 25.3, P < .0001), and Tolerability (83.9 ± 13.1 vs. 86.4 ± 15.0, P = .02), but declined for Ease of Use (82.6 ± 15.3 vs 67.8 ± 27.6, P < .0001). For all global satisfaction domains, the percentage of patients satisfied or very satisfied increased from baseline to the end of treatment (Overall Satisfaction 36.3% vs. 64.0%, Satisfaction with Medication Effectiveness 40.1% vs. 68.2%, Satisfaction with Side Effects 48.6% vs. 67.3%). The percentage of patients who were confident or very confident in treating repeated migraine attacks also increased (baseline: 41.0%, 90% confidence interval [CI] 35.4, 46.9 vs. end of treatment: 66.5%, 90% CI 58.9, 70.1). The efficacy results (pain relief, pain-free response, sustained 24-hour pain relief and pain-free response) were consistent with those previously observed with needle-based sumatriptan. Patients currently treated with triptans and less than very satisfied with their acute migraine therapy experienced a statistically significant and clinically relevant increase in satisfaction with therapy and enhanced confidence in treatment after use of Sumavel DosePro for up to 4 migraine attacks.

Sumatriptan as a treatment for cyclic vomiting syndrome: A clinical trial

Cyclic vomiting syndrome (CVS) is associated with migraine. This study aimed to evaluate the efficacy of sumatriptan in treating CVS. Twelve patients were enrolled in this trial. Sumatriptan was administered either subcutaneously [(age x 4 + 20)/100 x 3 mg] or by nasal spray (NS; 20 mg). Response to the treatment was classified as complete, effective, or noneffective. Eleven patients, who presented with 35 attacks, were treated by subcutaneous injection of sumatriptan. The treatment was responsive in 19 attacks. The efficacy of sumatriptan was high in attacks that occurred in cases with a family history of migraine compared to those without (p = .0482). Five patients were treated with sumatriptan NS for six attacks. The treatment was completely responsive in two of six attacks. We observed no adverse effects associated with sumatriptan treatment in this trial. We conclude that sumatriptan has potential efficacy in treating of patients with CVS.

Treatment of Subcutaneous Injection of Sumatriptan for Patients with Intractable Migraine and SUNCT Syndrome

Treatment of Subcutaneous Injection of Sumatriptan for Patients with Intractable Migraine and SUNCT Syndrome

Interindividual variability of oral sumatriptan pharmacokinetics and of clinical response in migraine patients

The marketing of sumatriptan, a selective serotonin (5-HT) 1B/1D agonist, first of the class of triptans, has increased the therapeutic options for the treatment of migraine attacks. However, almost one third of patients in clinical trials fail to have headache relief after oral administration of sumatriptan. To evaluate whether the interindividual differences in the clinical response following oral administration of sumatriptan are due to differences in its pharmacokinetics. We compared the pharmacokinetics of sumatriptan after oral (100 mg) and subcutaneous (6 mg) administration in two age- and gender-matched groups: ten subjects (group A) with satisfactory response and ten (group B) with unsatisfactory response to oral sumatriptan. Patients were studied during headache-free intervals. Blood samples were taken serially from baseline to 360 min after oral administration and from baseline to 180 min after subcutaneous injection. Sumatriptan plasma concentrations were determined by high-performance liquid chromatography (HPLC) with an electrochemical detector. Following oral dosing, patients of group A absorbed sumatriptan significantly faster and achieved early plasma levels significantly higher than patients of group B. The systemic exposure to sumatriptan during the first 2 h, which are the most important for rapid onset of action and for antimigraine efficacy, was significantly greater in group A than in group B (P < 0.001, Student's t test for independent data). On the other hand, after subcutaneous injection of sumatriptan, the profile of the curves was similar in all patients, and there were no differences in pharmacokinetics between group A and group B. The slow rate and low extent of absorption of the drug during the first 2 h after dosing observed in patients of group B could explain their unsatisfactory response to oral sumatriptan.

Acute myocardial infarction after sumatriptan administration for cluster headache

The pain of cluster headache attacks is severe, excruciating and selectively responsive to subcutaneous sumatriptan. Serious cardiovascular events attributed to sumatriptan are extremely rare and have most often been reported in patients at significant cardiovascular risk, or in overt cardiovascular disease. They also have occurred, however, in patients without evidence of cardiovascular disease. We describe a 42-year-old man with episodic cluster headache without history of coronary artery disease who was admitted to our coronary care unit for acute myocardial infarction after 3 h of subcutaneous injection of sumatriptan. During hospitalisation cluster headache attacks were successfully treated with e.v. indomethacin.

Inter-digestive and post-prandial antro-pyloro-duodenal motor activity in humans: effect of 5-hydroxytryptamine 1 receptor agonism.

Little is known about the effect of 5-hydroxytryptamine 1 (5-HT(1)) receptor agonism on the co-ordinated motor activity of the gastric antrum, pylorus and duodenum under fasting and fed conditions. To evaluate the effect of sumatriptan, a 5-HT(1) agonist, on fasting and fed antro-pyloro-duodenal motility. In study 1, antro-pyloro-duodenal motility was recorded for two phase IIIs of the migrating motor complex and then, following either a subcutaneous injection of sumatriptan 6 mg or saline control, for at least one additional phase III in 11 healthy volunteers (21-36 years). In study 2, the post-prandial motility was recorded for 3 h after either a subcutaneous injection of sumatriptan 6 mg or saline control in 10 healthy volunteers (18-36 years). Sumatriptan prolonged the migrating motor complex cycle (P = 0.009) by increasing the duration of phase II (P = 0.02) but not phases I and III. Post-prandially, sumatriptan reduced the activity index (P = 0.017) by reducing the frequency of co-ordinated motor activity involving the antrum and/or the duodenum (P < 0.05). 5-HT(1) receptor agonism increases the periodicity of the migrating motor complex and reduces the occurrence of post-prandial co-ordinated motor activity involving the gastric antrum, pylorus and duodenum.

Sumatriptan ameliorates headache induced by hypobaric hypoxia

AbstractHypobaric hypoxia induces headache in approximately 50% of individuals who visit high-altitude lands without an acclimatization period. We describe two cases of severe headache, on which acetazolamide had no apparent effect. Subcutaneous injection of sumatriptan (a 5-HT1B/1D agonist) ameliorated headache and increased blood pressure almost simultaneously. It is suggested that some kinds of high altitude headache can be effectively treated by sumatriptan.

Evidence against strong correlation between chest symptoms and ischemic coronary changes after subcutaneous sumatriptan injection.

To evaluate the adverse events possibly caused by sumatriptan injection and explore the relationship between chest symptoms along with sumatriptan injection and coronary ischemia among Japanese patients with migraine. A cumulative total of 112 subcutaneous injections in 62 patients were evaluated. ECG was continuously monitored before and until 5 minutes after injection on 92 occasions. Sixteen men and 46 women aged from 16 to 60 (mean 39+/-12) years. Their clinical diagnoses were migraine with aura, migraine without aura, cluster headache, and others. Chest symptoms occurred following 17% of all injections and in 15% of all patients. None of these chest symptoms was accompanied by ECG changes. Although the risk of coronary ischemia with sumatriptan treatment is commonly stated, our data suggest that chest symptoms following sumatriptan injection are not strongly associated with coronary ischemia in the Japanese population. The mechanism of chest symptoms following sumatriptan administration should be further elucidated.

Blink Reflex in Migraine and Tension‐Type Headache

The blink reflex was studied in 19 patients with migraine, 10 patients with tension-type headache, and 30 healthy controls. Significantly lower values of R2 and R2' amplitude and size were found in the migraine group, compared with the healthy control group. The differences were independent of the stimulation side (headache or nonheadache) and highly significant (P<0.001). The abnormalities of R2 and R2' amplitude and size were found only during the headache phase of migraine, being normal between migraine attacks. R1 latency and amplitude were normal in all patients. The blink reflex was normal in all the patients with tension-type headache. Subcutaneous injection of sumatriptan in 10 of the 19 migraineurs, during the headache phase, restored R2 and R2' amplitude and size values to normal. Our findings indicate that the brain stem interneuron part of the blink reflex arc may be diffusely suppressed in migraine, only during the headache phase. Furthermore, blink reflex may be an objective laboratory method to monitor the effectiveness of specific drugs proposed for the treatment of migraine.

Sumatriptan nasal spray (20 mg/dose) in the acute treatment of cluster headache.

Subcutaneous injection of sumatriptan is an effective treatment for attacks of cluster headache with a short onset of action. This open, randomized study evaluates whether sumatriptan nasal spray at its highest commercially available dose (20 mg/dose) is equally effective. In 26 patients, four consecutive attacks were treated alternately with nasal spray and subcutaneous injection. Treatment was given within 5 min of onset of pain, and the time interval for the start and completeness of pain relief, provided these occurred within 15 min of administration, were recorded by the patient. After completion of the study, the patients were also asked to indicate which treatment they preferred, based on efficacy, side effects, and handling of the preparation. Forty-nine of the 52 treatments with injection resulted in complete relief of pain within 15 min, with a mean of 9.6 min. The remaining three attacks were reduced by a mean of 86.7% at 15 min. Only 7 of the 52 treatments with nasal spray in the nostril ipsilateral to pain resulted in complete relief within this time period, with a mean of 13.0 min. In 18 of these treatments pain was reduced by a mean of 42.2% at 15 min, whereas no effect on pain was obtained at this time in the remaining 27 treatments. The effect was almost identical when the nasal spray was administered in the nostril on the non-painful side. As an overall judgement, only 2 of the 26 patients preferred nasal spray to injection. We conclude that sumatriptan nasal spray 20 mg/dose is less effective than subcutaneous injection in relieving pain in the great majority of cluster headache sufferers.

Effect of subcutaneous sumatriptan, a selective 5HT1 agonist, on the systemic, pulmonary, and coronary circulation.

Sumatriptan (GR43175) is a selective 5-hydroxytryptamine (5HT1) receptor agonist effective in the acute treatment of migraine. Recent in vitro experiments suggest that it has vasoactive properties in vascular beds distinct from the cerebral circulation. The object of this study was to assess the vasoactive effects of the standard 6-mg subcutaneous dose of sumatriptan used in migraine on the systemic and pulmonary circulations and the coronary artery vasculature. Ten patients undergoing diagnostic coronary arteriography were studied with digital subtraction angiography and invasive hemodynamic monitoring. After subcutaneous injection of sumatriptan, there was no significant change in heart rate or ECG morphology. There was a significant rise in the systemic (20%, p < 0.05 by ANOVA) and pulmonary artery (40%, p < 0.05 by ANOVA) pressures. There was no change in cardiac output, but there was a significant increase in total systemic (27%, p < 0.05) and total pulmonary vascular resistance (40%, p < 0.05). Sumatriptan caused a significant reduction (p < 0.001 by ANOVA) in mean absolute coronary artery diameter, from 4.36 +/- 1.60 mm at baseline to 3.67 +/- 1.49 mm (16%) at 10 minutes and to 3.63 +/- 1.49 mm (17%) at 30 minutes after injection. There were no clinical sequelae. Sumatriptan, a 5HT1 receptor agonist administered by the subcutaneous route, causes a vasopressor response in the systemic and pulmonary arterial circulations and coronary artery vasoconstriction.

Subcutaneous Sumatriptan in Acute Migraine-Reply

In Reply. —Dr Korenfeld raises the question of whether visual disturbances associated with subcutaneous sumatriptan could have resulted from relative ischemia secondary to posterior ciliary artery or central renal artery vasoconstriction. When we reviewed the patients who were experiencing visual difficulties, we noted that seven of the 734 sumatriptan-treated patients had true visual disturbances. These complaints generally began minutes after the subcutaneous injection of sumatriptan and resolved within several minutes to 1 hour. In only a single patient who received a second dose of sumatriptan was the visual disturbance duplicated by the second injection. No long-term visual complaints were noted except in a single patient who had blurred vision in one eye, which began several hours after the sumatriptan injection, and a subsequent ophthalmologic evaluation concluded that this problem was secondary to her severe myopia and not to sumatriptan. Whether the posterior ciliary artery or the central retinal artery has