The following serious or otherwise clinically significant adverse reactions are described elsewhere in the labeling: Somnolence [see Warnings and Precautions (5.1) ] Decreased Appetite and Decreased Weight [see Warnings and Precautions (5.2) ] Neutropenia and Thrombocytopenia [see Warnings and Precautions (5.3) ] Withdrawal Symptoms [see Warnings and Precautions (5.4) ] Risks in Patients with Phenylketonuria [see Warnings and Precautions (5.5) ] Suicidal Behavior and Ideation [see Warnings and Precautions (5.6) ] Adverse reactions that occurred in at least 10% of DIACOMIT-treated patients and more frequently than on placebo were somnolence, decreased appetite, agitation, ataxia, weight decreased, hypotonia, nausea, tremor, dysarthria, and insomnia.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact BIOCODEX at 1-866-330-3050 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug, and may not reflect the rates observed in practice. During its development for the treatment of seizures associated with Dravet syndrome, DIACOMIT was administered to 55 healthy male volunteers and 438 patients with Dravet syndrome, including 310 patients treated for 12 months or more.
The conditions and duration of exposure varied greatly, and included single- and multiple-dose clinical pharmacology studies in healthy male volunteers, 2 randomized, double-blind, placebo-controlled, 12-week studies in patients with Dravet syndrome (Sticlo France and Sticlo Italy), and open-label long-term studies. In Sticlo France and Sticlo Italy, 33 patients received DIACOMIT and 31 patients received placebo for a treatment duration of 8 weeks [see Clinical Studies ( 14 )] .
Adverse reactions from these trials are presented below. Approximately 53% of patients were female and the mean age was 9.2 years. All patients were taking clobazam and valproate. There were 2 patients in whom adverse reactions led to discontinuation of DIACOMIT treatment: one patient had an adverse reaction of status epilepticus; the second patient had drowsiness, balance impaired and sialorrhea. The most common adverse reactions, occurring in at least 10% of DIACOMIT-treated patients and more frequently than on placebo, included somnolence (67%), decreased appetite (45%), agitation (27%), ataxia (27%), weight decreased (27%), hypotonia (24%), nausea (15%), tremor (15%), dysarthria (12%), and insomnia (12%).
Table 3 lists the adverse reactions that occurred in 5% or more of DIACOMIT-treated patients and at a rate greater than in patients on placebo in the 2 randomized, double-blind, placebo-controlled, clinical trials in patients with Dravet syndrome (Sticlo France and Sticlo Italy). Table 3. Adverse Reactions in 5% or More of DIACOMIT-Treated Patients and More Frequently than on Placebo in Patients with Dravet Syndrome (Sticlo France and Sticlo Italy) Sticlo France and Sticlo Italy– Pooled Total DIACOMIT (50mg/kg/day) Placebo Adverse Reactions N=33 % N=31 % Gastrointestinal disorders Nausea 15 3 Vomiting 9 0 Salivary hypersecretion 6 0 General disorders and administration site conditions Fatigue 9 3 Pyrexia 6 3 Infections and infestations Bronchitis 6 0 Nasopharyngitis 6 0 Investigations Weight decreased 27 6 Weight increased 6 3 Metabolism and nutrition disorders Decreased appetite 46 10 Nervous system disorders Somnolence 67 23 Ataxia 27 23 Hypotonia 18 13 Tremor 15 10 Dysarthria 12 0 Psychiatric disorders Agitation 27 16 Insomnia 12 7 Aggression 9 0 Adverse Reactions in Pediatric Patients 6 months to Less Than 2 Years of Age In five open-label studies including pediatric patients 6 months to less than 2 years of age with Dravet syndrome, a total of 106 patients received DIACOMIT, with 81 patients exposed for at least 6 months, and 69 patients exposed for at least 1 year.
Adverse reactions in pediatric patients with Dravet syndrome who were 6 months to less than 2 years of age were similar to those seen in patients in Sticlo France and Sticlo Italy.
