Ampyra

MS Agents

Administer whole. Do not divide, crush, chew, or dissolve the extended-release, film-coated tablets.
May administer with or without food.
Administer tablets every 12 hours; an approximate 12-hour interval is needed between doses. Do not administer more than 10 mg every 12 hours; dalfampridine causes seizures in a dose-dependent fashion.
Missed dose: If a dose is missed, do not administer double or extra doses.

seizures / Delayed / 0-0.3
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known

constipation / Delayed / 3.0-3.0
confusion / Early / 0-1.0

infection / Delayed / 12.0-12.0
insomnia / Early / 9.0-9.0
nausea / Early / 7.0-7.0
headache / Early / 7.0-7.0
dizziness / Early / 7.0-7.0
asthenia / Delayed / 7.0-7.0
back pain / Delayed / 5.0-5.0
pharyngitis / Delayed / 4.0-4.0
paresthesias / Delayed / 4.0-4.0
dyspepsia / Early / 2.0-2.0
vomiting / Early / Incidence not known
vertigo / Early / Incidence not known
urticaria / Rapid / Incidence not known

Ampyra

Rx

Oral potassium channel blocker, also known as 4-aminopyridine
Indicated to improve walking in adult patients with multiple sclerosis (MS); results are independent of immunomodulatory drug therapies
Major dose-limiting side effect is seizures; patients with moderate to severe renal dysfunction cannot receive the drug

10 mg PO every 12 hours. No additional benefit was noted with doses greater than 10 mg twice daily, and adverse effects including seizures were more frequent with higher doses. During clinical trials, a benefit was noted as an increase in walking speed, and a benefit was observed across all 4 major types of multiple sclerosis disease courses. Most patients were also taking immunomodulatory drugs (e.g.,  interferons, glatiramer acetate, or natalizumab). The magnitude of improvement in walking ability was independent of concomitant treatment with an immunomodulatory drug.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

CrCl 51 to 80 mL/minute: No dose adjustment is needed; however, use with caution. Dalfampridine plasma concentrations with a 10 mg PO twice daily dose in these patients may approach those observed at a dose of 15 mg twice daily in patients with normal renal function, which is a dose that may be associated with an increased seizure risk.
CrCl 50 mL/minute or less: Use is contraindicated.

Abacavir; Dolutegravir; Lamivudine: (Moderate) Concurrent treatment with OCT2 inhibitors, such as dolutegravir, may cause increased exposure to dalfampridine. Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking dolutegravir concurrently with dalfampridine should be considered against the risk of seizures.
Amifampridine: (Major) Avoid use of dalfampridine and amifampridine together, due to duplicative effects and an increased risk for serious side effects, such as seizures. Both drugs are aminopyridine class potassium channel blockers. Both drugs increase the seizure risk.
Bupropion: (Moderate) Due to additive risks for seizure, extreme caution when coadministering bupropion with other drugs that lower seizure threshold (e.g., dalfampridine). Use low initial doses and increase the dose gradually. Monitor for seizure activity. Consider benefits against the risk of seizures. Consider alternatives to bupropion. Additionally, bupropion inhibits OCT2 in vitro, but the clinical relevance is not certain. Concurrent treatment with OCT2 inhibitors, such as bupropion, may cause increased exposure to dalfampridine. Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking OCT2 inhibitors concurrently with dalfampridine should be considered against the risk of seizures in these patients.
Bupropion; Naltrexone: (Moderate) Due to additive risks for seizure, extreme caution when coadministering bupropion with other drugs that lower seizure threshold (e.g., dalfampridine). Use low initial doses and increase the dose gradually. Monitor for seizure activity. Consider benefits against the risk of seizures. Consider alternatives to bupropion. Additionally, bupropion inhibits OCT2 in vitro, but the clinical relevance is not certain. Concurrent treatment with OCT2 inhibitors, such as bupropion, may cause increased exposure to dalfampridine. Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking OCT2 inhibitors concurrently with dalfampridine should be considered against the risk of seizures in these patients.
Cimetidine: (Moderate) Concurrent treatment with OCT2 inhibitors, such as cimetidine, may cause increased exposure to dalfampridine. Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking OCT2 inhibitors concurrently with dalfampridine should be considered against the risk of seizures in these patients. Consider alternatives to cimetidine.
Dextromethorphan; Bupropion: (Moderate) Due to additive risks for seizure, extreme caution when coadministering bupropion with other drugs that lower seizure threshold (e.g., dalfampridine). Use low initial doses and increase the dose gradually. Monitor for seizure activity. Consider benefits against the risk of seizures. Consider alternatives to bupropion. Additionally, bupropion inhibits OCT2 in vitro, but the clinical relevance is not certain. Concurrent treatment with OCT2 inhibitors, such as bupropion, may cause increased exposure to dalfampridine. Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking OCT2 inhibitors concurrently with dalfampridine should be considered against the risk of seizures in these patients.
Dolutegravir: (Moderate) Concurrent treatment with OCT2 inhibitors, such as dolutegravir, may cause increased exposure to dalfampridine. Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking dolutegravir concurrently with dalfampridine should be considered against the risk of seizures.
Dolutegravir; Lamivudine: (Moderate) Concurrent treatment with OCT2 inhibitors, such as dolutegravir, may cause increased exposure to dalfampridine. Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking dolutegravir concurrently with dalfampridine should be considered against the risk of seizures.
Dolutegravir; Rilpivirine: (Moderate) Concurrent treatment with OCT2 inhibitors, such as dolutegravir, may cause increased exposure to dalfampridine. Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking dolutegravir concurrently with dalfampridine should be considered against the risk of seizures.
Trilaciclib: (Moderate) Consider the potential benefits of treatment versus the risk of seizures if concomitant use of trilaciclib and dalfampridine is necessary. Trilaciclib is an OCT2 and MATE inhibitor that may increase dalfampridine exposure; elevated dalfampridine exposure may increase the risk of seizures.

Ampyra/Dalfampridine Oral Tab ER: 10mg

20 mg/day PO, administered as 10 mg every 12 hours.

20 mg/day PO, administered as 10 mg every 12 hours.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Dalfampridine is a broad spectrum potassium channel blocker. The mechanism of dalfampridine's therapeutic effect has not been fully elucidated. In animals, inhibition of potassium channels increased action potential conduction in demyelinated axons.

Dalfampridine is administered orally. It is mostly unbound to plasma proteins. The apparent volume of distribution is 2.6 L/kg. The CYP2E1 isoenzyme is the major enzyme responsible for the 3-hydroxylation of dalfampridine. The identity of the CYP enzymes suspected of playing a minor role in the 3-hydroxylation of dalfampridine could not be established unequivocally. Two inactive metabolites are present: 3-hydroxy-4-aminopyridine and 3-hydroxy-4-aminopyridine sulfate, but these are not pharmacologically active. The clearance of dalfampridine is significantly correlated with creatinine clearance. Dalfampridine and metabolite elimination is nearly complete after 24 hours, with 95.9% of the dose recovered in urine and 0.5% recovered in feces. The elimination half-life is 5.2 to 6.5 hours.[43980]
 
Affected Cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2E1, OCT2
CYP2E1 is the major enzyme responsible for the metabolism of dalfampridine. In vitro, dalfampridine is not an inducer or inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4/5. Dalfampridine is not likely to affect the pharmacokinetics of drugs that are substrates of these enzymes. Further, dalfampridine is neither a substrate nor an inhibitor of P-glycoprotein. Dalfampridine appears to be a substrate for organic cation transporter 2 (OCT2); concurrent treatment with OCT2 inhibitors (e.g., cimetidine) may cause increased exposure to dalfampridine and may increase the risk of seizures.[43980]

Absorption of dalfampridine is rapid and complete. The relative bioavailability is 96% as compared with an aqueous oral solution. After administration of a 10 mg tablet to healthy patients in the fasted state, the maximum serum concentration (Cmax) of 17.3 to 21.6 ng/mL occurs in 3 to 4 hours. If dalfampridine is taken with food, a 12% to 17% increase in Cmax and a 4% to 7% decrease in AUC occurs; these changes in exposure are not clinically significant, and dalfampridine can be taken with or without food. Exposure of dalfampridine increases proportionally with dose.

Dalfampridine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate data on the developmental risk associated with use of dalfampridine in pregnant women. Administration of dalfampridine to animals during pregnancy and lactation resulted in decreased offspring viability and growth at clinically relevant doses.[43980]

There are no data on the presence of dalfampridine in human milk, the effects of dalfampridine on the breastfed infant, or the effects on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for dalfampridine and any potential adverse effects on the breastfed infant from dalfampridine or from the underlying maternal condition.