ts During RUZURGI
Treatment and With at Least 2% Greater Incidence Than Placebo
Adverse Reaction
RUZURGI
(N=52)
%
Placebo
(N=49)
%
Paresthesia/Dysesthesia*
Abdominal pain**
Dyspepsia
Dizziness
Nausea
Back pain
Hypoesthesia
Muscle spasms
69
25
17
12
10
8
6
6
2
0
2
0
2
2
0
2
* Includes paresthesia, dysesthesia, and oral dysethesia.
** Includes abdominal pain and upper abdominal pain.
Subjects classified as poor metabolizers based on rate of metabolism were more likely toexperience adverse reactions during RUZURGI treatment than intermediate or normalmetabolizers [see Clinical Pharmacology (12.5)].
Expanded Access Experience
In expanded access programs, 162 patients with LEMS (54% female) were treated with RUZURGI. Among patients with available exposure data, the median duration of treatment was1.7 years (range 1 day to 27.6 years) for a total of 766.4 person years. Patient age at the time RUZURGI was initiated ranged from 21 to 84 years (mean 58.7 years). The median of themaximum total daily dosage was 75 mg/day.
In general, the most frequent adverse reactions observed in the expanded access programs weresimilar to those observed in the QT study. Additionally, the following adverse reactions werereported in ≥5% of patients: falls, diarrhea, pneumonia, dyspnea, arthralgia, asthenia, depression,dysphagia, headache, insomnia, vision blurred, anemia, anxiety, constipation, feeling cold,gastroesophageal reflux disease, and pain. Because these reactions were captured retrospectivelyfrom expanded access programs, it is not possible to reliably estimate their frequency or establisha causal relationship to drug exposure.
Pediatric Patients (6 to Less than 17 Years of Age)
Safety of RUZURGI was eva luated in pediatric LEMS and non-LEMS patients 6 to less than 17years of age who were treated in expanded access programs. There were 15 patients ages 6 to lessthan 17 years who received RUZURGI, of whom 9 received RUZURGI for at least 1 year.
Adverse reactions reported in pediatric patients 6 to less than 17 years of age were similar to thoseseen in adult patients.
7 DRUG INTERACTIONS
7.1 Drugs that Lower Seizure Threshold
The concomitant use of RUZURGI and drugs that lower seizure threshold may lead to anincreased risk of seizures [see Warnings and Precautions (5.1)]. The decision to administer RUZURGI concomitantly with drugs that lower the seizure threshold should be carefullyconsidered in light of the severity of the associated risks.
7.2 Drugs with Cholinergic Effects
The concomitant use of RUZURGI and drugs with cholinergic effects (e.g., direct or indirectcholinesterase inhibitors) may increase the cholinergic effects of RUZURGI and of those drugsand increase the risk of adverse reactions [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no data on the developmental risk associated with the use of RUZURGI in pregnantwomen.
Animal studies to assess the potential adverse effects of amifampridine on embryofetaldevelopment have not been conducted.
In the US general population, the estimated background risk of major birth defects andmiscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Thebackground risk of major birth defects and miscarriage for the indicated population is unknown.
8.2 Lactation
Risk Summary
There are no data on the presence of amifampridine o |
