Which children receive vigabatrin? Characteristics of pediatric patients enrolled in the mandatory FDA registry.

Vigabatrin (Sabril®) is an antiepileptic drug (AED) currently indicated in the US as a monotherapy for patients 1month to 2years of age with infantile spasms (IS) and as adjunctive therapy for patients ≥10years of age with refractory complex partial seizures (rCPS) whose seizures have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss. The approval required an FDA mandated registry. This article describes 5years of demographic and treatment exposure data from US pediatric patients (<17years). Participation is mandatory for all US Sabril® prescribers and patients. A benefit-risk assessment must be documented for patient progression to maintenance therapy. This includes demographic diagnosis and reports of ophthalmologic assessments (where available). Patient data were grouped by age as proxies for indication (IS: <3years, rCPS: ≥3 to <17years). As of August 26, 2014, 5546/6823 enrolled patients were pediatric/total; 4472 (81%) were vigabatrin-naïve. Seventy-one percent of patients were <3years of age; 29% were ≥3 to <17years of age. Etiologies of IS were identified as cryptogenic (21%), symptomatic tuberous sclerosis (17%), and symptomatic other (42%). The majority of patients with IS (56%) attempted no prior treatments; 16% received adrenocorticotropic hormone prior to vigabatrin. A third of patients with IS were receiving 1 concomitant treatment with vigabatrin. For patients with rCPS, 39% attempted 1-3 prior treatments; 27% were receiving 2 concomitant treatments at enrollment. A total of 1852 (41%) patients did not undergo baseline ophthalmological assessment; 25% of patients with IS and 42% of patients with rCPS were exempted for neurologic disabilities. Kaplan-Meier estimates predict that 71% and 65% of vigabatrin-naïve patients with IS and rCPS, respectively, would remain in the registry at 6months. Most pediatric vigabatrin patients have IS as an underlying diagnosis, especially those <3years of age. A proportion of those with rCPS remain on long-term vigabatrin despite the risk of adverse events.

Sabril® registry 5-year results: Characteristics of adult patients treated with vigabatrin.

Vigabatrin (Sabril®), approved in the US in 2009, is currently indicated as adjunctive therapy for refractory complex partial seizures (rCPS) in patients ≥ 10 years old who have responded inadequately to several alternative treatments and as monotherapy for infantile spasms (IS) in patients 1 month to 2 years of age. Because of reports of vision loss following vigabatrin exposure, FDA approval required a risk evaluation mitigation strategy (REMS) program. Vigabatrin is only available in the US through Support, Help, And Resources for Epilepsy (SHARE), which includes a mandated registry. This article describes 5 years of demographic and treatment exposure data from adult patients (≥ 17 years old) in the US treated with vigabatrin and monitored in the ongoing Sabril® registry. Registry participation is mandatory for all US Sabril® prescribers and patients. A benefit-risk assessment must be documented by the physician for a patient to progress to maintenance therapy, defined as 1 month of vigabatrin treatment for patients with IS and 3 months for patients with rCPS. Ophthalmologic assessments must be documented during and after completion of therapy. As of August 26, 2014, a total of 6823 patients were enrolled in the registry, of which 1200 were adults at enrollment. Of these patients, 1031 (86%) were naïve to vigabatrin. The majority of adult patients (n=783, 65%) had previously been prescribed ≥ 4 AEDs, and 719 (60%) were receiving ≥ 3 concomitant AEDs at vigabatrin initiation. Prescribers submitted an initial ophthalmological assessment form for 863 patients; an ophthalmologic exam was not completed for 300 (35%) patients and thus, were considered exempted from vision testing. Of these patients, 128 (43%) were exempted for neurologic disabilities. Clinicians discontinued treatment in 8 patients because of visual field deficits (VFD) (5 patients naïve to vigabatrin and 3 patients previously exposed). Based on Kaplan-Meier survival estimates, it is estimated that approximately 71%, 55%, and 40% of adult patients naïve to vigabatrin would remain in the registry at 3, 6, and 12 months, respectively. These demographic data suggest that a proportion of adult patients remain on vigabatrin long-term despite the risks of adverse events and significant underlying AED resistance and neurologic disease.

Vigabatrin for the treatment of infantile spasms: final report of a randomized trial.

A large randomized study was conducted in patients with newly diagnosed infantile spasms to compare 2 doses of vigabatrin in achieving spasm cessation. High (100-148 mg/kg/d) and low (18-36 mg/kg/d) oral doses of vigabatrin were evaluated in a randomized, single-blind study of 14 to 21 days with subsequent open-label treatment up to 3 years. Spasm cessation was defined as 7 consecutive days of spasm freedom beginning within the first 14 days, confirmed by video-electroencephalogram. A total of 221 subjects comprised the modified intent-to-treat cohort. More subjects in the high-dose group achieved spasm cessation compared with the low-dose vigabatrin group (15.9% [17/107] vs 7.0% [8/114]; P = .0375). During follow-up, 39 of 171 (23%) subjects relapsed; 28 of 39 (72%) regained spasm freedom. Adverse events were primarily mild to moderate in severity. Vigabatrin had a dose-dependent effect in spasm reduction. Spasm cessation occurred rapidly and was maintained in the majority of infants.

Valdecoxib for treatment of primary dysmenorrhea. A randomized, double-blind comparison with placebo and naproxen.

OBJECTIVE: To compare the analgesic efficacy of valdecoxib with placebo and naproxen sodium for relieving menstrual cramping and pain due to primary dysmenorrhea. DESIGN: Single-center, double-blind study with a 4-period, 4-sequence crossover design. Patients assessed pain intensity and pain relief at regular intervals up to 12 hours following the initial dose. SETTING: Privately owned outpatient clinic. PATIENTS/PARTICIPANTS: One hundred twenty patients with moderate to severe menstrual cramping were randomized. Eighty-seven patients completed all treatment cycles. INTERVENTIONS: Valdecoxib 20 mg or 40 mg, naproxen sodium 550 mg, or placebo twice a day as required for < or =3 days in a single menstrual cycle. MEASUREMENTS AND MAIN RESULTS: Both doses of valdecoxib (20 and 40 mg) were comparable to naproxen sodium and superior to placebo at all time points assessed for each of the primary end points. Valdecoxib and naproxen sodium had comparable onset and duration of action. Although the study design allowed patients 2 doses per day, only 15% and 20% of patients in the valdecoxib 20 mg and valdecoxib 40 mg groups, respectively, required remedication within the first 12 hours. The incidence of adverse events was similar between active and placebo groups. CONCLUSION: Valdecoxib provided a fast onset of analgesic action, a level of efficacy similar to naproxen sodium, and a high level of patient satisfaction in the relief of menstrual pain due to primary dysmenorrhea. Valdecoxib was effective and well tolerated and thus appears to be a viable treatment for menstrual pain due to primary dysmenorrhea.

Valdecoxib, a cyclooxygenase-2-specific inhibitor, is effective in treating primary dysmenorrhea.

OBJECTIVE: To compare the efficacy of the cyclooxygenase (COX)-2-specific inhibitor valdecoxib with naproxen sodium in treating menstrual pain associated with primary dysmenorrhea. METHOD: This single-center, double-blind, placebo-controlled, randomized, crossover study compared the efficacy and safety of single oral doses of valdecoxib 20 mg and 40 mg with naproxen sodium 550 mg, or placebo, with an option of treatment for up to 3 days, twice daily. Efficacy was assessed by time-weighted sum of total pain relief, sum of pain intensity difference, time-specific pain relief, and pain intensity difference over 12 hours, time to rescue medication or first re-medication, the percentage of patients taking rescue medication, and patient's global evaluation of study medication. RESULTS: Mean time-weighted sum of total pain relief and sum of pain intensity difference were significantly superior to placebo for the first 8 and 12 hours after the initial dose of valdecoxib 20 mg (P <.01) and 40 mg (P <.001). Valdecoxib 20 mg and 40 mg were comparable to naproxen sodium 550 mg for all efficacy measures. Other differences in efficacy measures favoring the higher dose of valdecoxib did not achieve statistical significance, with the exception of sum of pain intensity difference-12. Both doses of valdecoxib were well tolerated. CONCLUSIONS: Both valdecoxib 20- and 40-mg doses were effective and well tolerated for the treatment of primary dysmenorrhea. Valdecoxib 20 mg and 40 mg demonstrate analgesic efficacy, based on onset, magnitude, and duration of analgesia that is similar to naproxen sodium, making it a potential choice for treating women with primary dysmenorrhea.

Intravenous parecoxib sodium foracute pain after orthopedic knee surgery.

Our objective in a randomized, multicenter, double-blind, parallel-group, placebo- and active-controlled study was to evaluate and compare the analgesic effectiveness of single intravenous (IV) doses of parecoxib sodium 20 and 40 mg, morphine 4 mg, and ketorolac 30 mg in the postsurgical orthopedic pain model. After undergoing unilateral total knee replacement surgery, 208 healthy adult patients were randomized to receive placebo or a study drug within 6 hours of discontinuation of patient-controlled analgesia on postoperative day 1. Onset of analgesia was similarly rapid with IV parecoxib sodium 40 mg, morphine, and ketorolac. Level and duration of analgesia were significantly superior with parecoxib sodium than with morphine and were similar for parecoxib sodium and ketorolac. Parecoxib sodium was safe and well tolerated. In conclusion, IV parecoxib sodium 40 mg is as effective as ketorolac 30 mg and is more effective than morphine 4 mg and therefore has potential widespread utility in acute postoperative pain management.