AMPYRA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for AMPYRA (AMPYRA).

How it works

Dalfampridine is a potassium channel blocker that improves conduction in demyelinated axons by prolonging action potential duration and increasing neurotransmitter release at synaptic junctions.

What the body does with it

Metabolism	Primarily metabolized via conjugation with sulfate; minimal involvement of CYP450 enzymes; approximately 90% excreted unchanged in urine
Excretion	Primarily renal elimination via glomerular filtration and active tubular secretion. ~90% of administered dose excreted unchanged in urine. Fecal/biliary excretion negligible (<1%).
Half-life	Terminal elimination half-life approximately 5-7 hours. No clinically significant accumulation with twice-daily dosing.
Protein binding	97-99% bound to plasma proteins, primarily alpha-1-acid glycoprotein. Binding is saturable.
Volume of Distribution	Approximately 2.6 L/kg. Indicates extensive distribution into total body water and tissues.
Bioavailability	Oral bioavailability is ~95%, with minimal first-pass metabolism.
Onset of Action	Oral administration: improvement in walking speed observed within 2-4 weeks. Subtherapeutic effects may begin earlier.
Duration of Action	Duration of effect: approximately 12 hours with twice-daily dosing. Effects on walking speed last throughout the dosing interval.

Classification & Brands

Dosing & administration

10 mg orally twice daily (every 12 hours). Maximum 10 mg per dose.

Dosage form	TABLET, EXTENDED RELEASE
Renal impairment	Contraindicated if CrCl ≤50 mL/min. No dose adjustment for CrCl >50 mL/min.
Liver impairment	No formal studies; use caution in severe hepatic impairment (Child-Pugh C). No adjustment for mild or moderate impairment.
Pediatric use	Not approved in pediatric patients. Safety and efficacy not established.
Geriatric use	No specific dose adjustment; consider renal function (CrCl). Contraindicated if CrCl ≤50 mL/min.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for AMPYRA (AMPYRA).

Breastfeeding	Unknown if dalfampridine is excreted in human milk. The M/P ratio is not available. Because of potential serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Teratogenic Risk	Pregnancy Category C. In animal studies, dalfampridine (4-aminopyridine) caused fetal harm including reduced fetal weights and skeletal abnormalities at maternal toxic doses. No adequate and well-controlled studies in pregnant women. Potential fetal risk exists, especially during the first trimester due to neuronal development. Use only if benefit justifies potential risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of seizure disorder","Moderate to severe renal impairment (CrCl ≤50 mL/min)","Concurrent use with other 4-aminopyridine-containing products"]

Clinical Precautions

Precautions	["Risk of seizures, especially with history of seizure disorder, renal impairment (CrCl ≤50 mL/min contraindicated), or high doses","Monitor renal function before and during therapy","Do not use with other forms of 4-aminopyridine","Hematologic effects including anemia and leukopenia rarely reported"]
Food/Dietary	No significant food interactions. However, consumption of high-fat meals may slightly delay absorption but does not reduce overall exposure. Avoid alcohol due to increased seizure risk and potential additive CNS effects.

Clinical Tips & Counseling

Drug interactions

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AMPYRA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for AMPYRA (AMPYRA).

How it works

Dalfampridine is a potassium channel blocker that improves conduction in demyelinated axons by prolonging action potential duration and increasing neurotransmitter release at synaptic junctions.

What the body does with it

Metabolism	Primarily metabolized via conjugation with sulfate; minimal involvement of CYP450 enzymes; approximately 90% excreted unchanged in urine
Excretion	Primarily renal elimination via glomerular filtration and active tubular secretion. ~90% of administered dose excreted unchanged in urine. Fecal/biliary excretion negligible (<1%).
Half-life	Terminal elimination half-life approximately 5-7 hours. No clinically significant accumulation with twice-daily dosing.
Protein binding	97-99% bound to plasma proteins, primarily alpha-1-acid glycoprotein. Binding is saturable.
Volume of Distribution	Approximately 2.6 L/kg. Indicates extensive distribution into total body water and tissues.
Bioavailability	Oral bioavailability is ~95%, with minimal first-pass metabolism.
Onset of Action	Oral administration: improvement in walking speed observed within 2-4 weeks. Subtherapeutic effects may begin earlier.
Duration of Action	Duration of effect: approximately 12 hours with twice-daily dosing. Effects on walking speed last throughout the dosing interval.

Classification & Brands

Dosing & administration

10 mg orally twice daily (every 12 hours). Maximum 10 mg per dose.

Dosage form	TABLET, EXTENDED RELEASE
Renal impairment	Contraindicated if CrCl ≤50 mL/min. No dose adjustment for CrCl >50 mL/min.
Liver impairment	No formal studies; use caution in severe hepatic impairment (Child-Pugh C). No adjustment for mild or moderate impairment.
Pediatric use	Not approved in pediatric patients. Safety and efficacy not established.
Geriatric use	No specific dose adjustment; consider renal function (CrCl). Contraindicated if CrCl ≤50 mL/min.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for AMPYRA (AMPYRA).

Breastfeeding	Unknown if dalfampridine is excreted in human milk. The M/P ratio is not available. Because of potential serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Teratogenic Risk	Pregnancy Category C. In animal studies, dalfampridine (4-aminopyridine) caused fetal harm including reduced fetal weights and skeletal abnormalities at maternal toxic doses. No adequate and well-controlled studies in pregnant women. Potential fetal risk exists, especially during the first trimester due to neuronal development. Use only if benefit justifies potential risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of seizure disorder","Moderate to severe renal impairment (CrCl ≤50 mL/min)","Concurrent use with other 4-aminopyridine-containing products"]

Clinical Precautions

Precautions	["Risk of seizures, especially with history of seizure disorder, renal impairment (CrCl ≤50 mL/min contraindicated), or high doses","Monitor renal function before and during therapy","Do not use with other forms of 4-aminopyridine","Hematologic effects including anemia and leukopenia rarely reported"]
Food/Dietary	No significant food interactions. However, consumption of high-fat meals may slightly delay absorption but does not reduce overall exposure. Avoid alcohol due to increased seizure risk and potential additive CNS effects.

Clinical Tips & Counseling

Drug interactions

Loading safety data…