INTERACTIONS OCT2 Inhibitors: Concomitant use may cause an increased exposure and potential risk of seizures ( 7.1 )
7.1 OCT2 Inhibitors Concurrent treatment with OCT2 inhibitors, such as cimetidine, may cause increased exposure to dalfampridine <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . Elevated levels of dalfampridine increase the risk of seizures <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 , 5.2 )]</span>. The potential benefits of taking OCT2 inhibitors concurrently with dalfampridine extended-release tablets should be considered against the risk of seizures in these patients.
7.2 Baclofen No interaction was identified between dalfampridine and baclofen <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> .
The use of dalfampridine extended-release tablets are contraindicated in the following conditions: History of seizure [see Warnings and Precautions (5.1) ] Moderate or severe renal impairment (CrCl≤50 mL/min) [see Warnings and Precautions (5.2) ] History of hypersensitivity to dalfampridine extended-release tablets or 4-aminopyridine; reactions have included anaphylaxis [see Warnings and Precautions (5.4) ] History of seizure (4) Moderate or severe renal impairment (CrCl≤50 mL/min) (4) History of hypersensitivity to dalfampridine extended-release tablets or 4-aminopyridine (4)
AND PRECAUTIONS Dalfampridine extended-release tablets can cause seizures; the risk of seizures increases with increasing dalfampridine extended-release tablets doses; discontinue dalfampridine extended-release tablets and do not restart if a seizure occurs (5.1) Avoid concomitant use with other forms of 4-aminopyridine (4-AP, fampridine), since the active ingredient is the same (5.3) Dalfampridine extended-release tablets can cause anaphylaxis. Discontinue and do not restart dalfampridine extended-release tablets if this occurs (5.4)
5.1 Seizures Dalfampridine extended-release tablets can cause seizures. Increased incidence of seizures has been observed at 20 mg twice daily (2 times the maximum recommended dosage) in controlled clinical studies of 9 to 14 weeks duration with dalfampridine in patients with MS. In open-label extension trials in MS patients, the incidence of seizures during treatment with dalfampridine 15 mg twice daily (1.7/100PY) was over 4 times higher than the incidence during treatment with 10 mg twice daily (0.4/100PY). In the post-marketing period seizures have been reported. The majority of seizures occurred at the recommended dose and in patients without a history of seizures, and generally within days to weeks of starting therapy. Dalfampridine extended-release tablets have not been evaluated in patients with a history of seizures or with evidence of epileptiform activity on an EEG, as these patients were excluded from clinical trials. The risk of seizures in patients with epileptiform activity on an EEG is unknown, and could be substantially higher than that observed in dalfampridine extended-release tablets clinical studies. Permanently discontinue dalfampridine extended-release tablets in patients who have a seizure while on treatment. Dalfampridine extended-release tablets are contraindicated in patients with a history of seizures <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> .
5.2 Renal Impairment Dalfampridine extended-release tablets are eliminated through the kidneys primarily as unchanged drug <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span>. Because patients with moderate to severe renal impairment (CrCl ≤50mL/min) would require a dose lower than 10 mg twice daily and no strength smaller than 10 mg is available, dalfampridine extended-release tablets are contraindicated in these patients <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> . In patients with mild renal impairment (CrCl 51 to 80 mL/min), dalfampridine extended-release tablets plasma levels may approach those seen at a dose of 15 mg twice daily, a dose that may be associated with an increased risk of seizures <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1) ]</span> .
5.3 Concurrent Treatment with Other Forms of 4-Aminopyridine Avoid concomitant use with other forms of 4-aminopyridine (4-AP, fampridine) since the active ingredient is the same. Instruct patients to discontinue use of any product containing 4-aminopyridine prior to initiating treatment with dalfampridine extended-release tablets in order to reduce the potential for dose-related adverse reactions.
5.4 Anaphylaxis Dalfampridine extended-release tablets can cause anaphylaxis and severe allergic reactions. Signs and symptoms have included respiratory compromise, urticaria, and angioedema of the throat and or tongue. Dalfampridine extended-release tablets are contraindicated in patients with a history of hypersensitivity to dalfampridine extended-release tablets or 4-aminopyridine. Inform patients of the signs and symptoms of anaphylaxis and instruct them to discontinue dalfampridine extended-release tablets and seek immediate medical care should these signs and symptoms occur.