Ruzurgi

Myasthenic Agents, Other

May take without regard to food.
If a dose is missed, do not take double or extra doses.[63790] [64128]

A 1 mg/mL suspension can be prepared when patients require a dosage in less than 5 mg increments, have difficulty swallowing tablets, or require feeding tubes.
Firdapse 1 mg/mL suspension
Place the required number of tablets in a 50 to 100 mL container. Crushing the tablets prior to making the suspension is not necessary.
Add 10 mL of Sterile Water per tablet.
Wait 5 minutes.
Shake well for 30 seconds.
Shake well before drawing up each dose.
Storage: Store under refrigeration for up to 24 hours.
Ruzurgi 1 mg/mL suspension
Place three 10-mg tablets in a 30 mL container. Crushing the tablets prior to making the suspension is not necessary.
Add 30 mL of Sterile Water.
Shake well for 30 seconds.
Shake well before drawing up each dose.
Storage: Store under refrigeration for up to 24 hours.

seizures / Delayed / 2.0-2.0

elevated hepatic enzymes / Delayed / 14.0-14.0
hypertension / Early / 12.0-12.0
myasthenia / Delayed / 10.0-10.0
cataracts / Delayed / 10.0-10.0
constipation / Delayed / 7.0-7.0
lymphadenopathy / Delayed / 7.0-7.0
depression / Delayed / 5.0
cystitis / Delayed / 5.0
dysphagia / Delayed / 5.0
blurred vision / Early / 5.0
peripheral edema / Delayed / 5.0
dyspnea / Early / 5.0
hypercholesterolemia / Delayed / 5.0
anemia / Delayed / 5.0
erythema / Early / 5.0

dysesthesia / Delayed / 69.0-69.0
paresthesias / Delayed / 62.0-69.0
abdominal pain / Early / 14.0-25.0
dyspepsia / Early / 17.0-17.0
headache / Early / 14.0-14.0
nausea / Early / 10.0-14.0
diarrhea / Early / 14.0-14.0
back pain / Delayed / 8.0-14.0
dizziness / Early / 10.0-12.0
muscle cramps / Delayed / 6.0-12.0
asthenia / Delayed / 10.0-10.0
hypoesthesia / Delayed / 6.0-6.0
insomnia / Early / 5.0
anxiety / Delayed / 5.0
influenza / Delayed / 5.0
infection / Delayed / 5.0
gastroesophageal reflux / Delayed / 5.0
arthralgia / Delayed / 5.0
fever / Early / 5.0
weight loss / Delayed / Incidence not known
weakness / Early / Incidence not known

FIRDAPSE, Ruzurgi

Rx

Oral aminopyridine potassium channel blocker
Used for the treatment of Lambert-Eaton myasthenic syndrome (LEMS)
May cause seizures; contraindicated in patients with a history of seizures

15 to 30 mg/day PO initially, given in 3 to 4 divided doses. In patients who are poor metabolizers of N-acetyltransferase 2 (NAT2), initiate treatment at 15 mg/day. Increase dose by 5 mg/day every 3 or 4 days, based on clinical response and tolerability. Max: 80 mg/day; do not exceed 20 mg/dose.

15 to 30 mg/day PO initially, given in 3 to 4 divided doses. In patients who are poor metabolizers of N-acetyltransferase 2 (NAT2), initiate treatment at 15 mg/day. Increase dose by 5 mg/day every 3 or 4 days, based on clinical response and tolerability. Max: 80 mg/day; do not exceed 20 mg/dose.

5 to 15 mg/day PO initially, given in 3 to 4 divided doses. In patients who are poor metabolizers of N-acetyltransferase 2 (NAT2), initiate treatment at 5 mg/day. Increase dose by 2.5 mg/day every 3 or 4 days, based on clinical response and tolerability. Max: 40 mg/day; do not exceed 10 mg/dose.

15 to 30 mg/day PO initially, given in 2 to 3 divided doses. In patients who are poor metabolizers of N-acetyltransferase 2 (NAT2), initiate treatment at 15 mg/day. Increase the dose by 5 to 10 mg/day, divided in up to 5 doses per day, based on clinical response and tolerability. Max: 100 mg/day; do not exceed 30 mg/dose.

7.5 to 15 mg/day PO initially, given in 2 to 3 divided doses. In patients who are poor metabolizers of N-acetyltransferase 2 (NAT2), initiate treatment at 7.5 mg/day. Increase the dose by 2.5 to 5 mg/day, divided in up to 5 doses per day, based on clinical response and tolerability. Max: 50 mg/day; do not exceed 15 mg/dose.

Start at the lowest initial total daily dosage, regardless of the degree of hepatic impairment; monitor closely for adverse reactions. Consider further dosage modification or discontinuation in these patients based on clinical efficacy and tolerabilty.
Adults: Initially, 15 mg/day PO, given in divided doses.
 
Children and Adolescents:
-weighing less than 45 kg: Initially, 5 mg/day (Firdapse) or 7.5 mg/day (Ruzurigi) PO, given in divided doses.
-weighing 45 kg or more: Initially, 15 mg/day (Firdapse or Ruzurgi) PO, given in divided doses.

Adults
CrCl 15 to 90 mL/minute: 15 mg/day PO initially.
CrCl less than 15 mL/minute: No dosage recommendations available.
 
Children and Adolescents
CrCl 15 to 90 mL/minute: 5 mg/day PO (Firdapse) or 7.5 mg/day PO (Rizurgi) initially in patients weighing less than 45 kg and 15 mg/day PO (Firdapse or Rizurgi) initially in patients weighing 45 kg or more.
CrCl less than 15 mL/minute: No dosage recommendations available.

Albuterol; Budesonide: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Amitriptyline: (Major) Carefully consider the need for concomitant treatment with tricyclic antidepressants and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Tricyclic antidepressants may increase the risk of seizures.
Amphetamine: (Major) Carefully consider the need for concomitant treatment with amphetamines and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Amphetamines may increase the risk of seizures.
Amphetamine; Dextroamphetamine Salts: (Major) Carefully consider the need for concomitant treatment with amphetamines and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Amphetamines may increase the risk of seizures.
Amphetamine; Dextroamphetamine: (Major) Carefully consider the need for concomitant treatment with amphetamines and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Amphetamines may increase the risk of seizures.
Aripiprazole: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Asenapine: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
atypical antipsychotic: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Azelastine; Fluticasone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Beclomethasone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Benzphetamine: (Major) Carefully consider the need for concomitant treatment with benzphetamine and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Benzphetamine may increase the risk of seizures.
Betamethasone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Brexpiprazole: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Budesonide: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Budesonide; Formoterol: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Bupropion: (Major) Carefully consider the need for concomitant treatment with bupropion and amifampridine, as coadministration may increase the risk of seizures. Consider alternatives to bupropion. If use together is medically necessary, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Bupropion is known to have a dose-dependent risk for seizures.
Bupropion; Naltrexone: (Major) Carefully consider the need for concomitant treatment with bupropion and amifampridine, as coadministration may increase the risk of seizures. Consider alternatives to bupropion. If use together is medically necessary, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Bupropion is known to have a dose-dependent risk for seizures.
Cariprazine: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Celecoxib; Tramadol: (Major) Carefully consider concomitant use of amifampridine with tramadol due to increased seizure risk. The concomitant use of amifampridine and other drugs that lower the seizure threshold, such as tramadol, may lead to an increased risk of seizures.
Chlordiazepoxide; Amitriptyline: (Major) Carefully consider the need for concomitant treatment with tricyclic antidepressants and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Tricyclic antidepressants may increase the risk of seizures.
Chlorpromazine: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold.
Ciclesonide: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Clomipramine: (Major) Carefully consider the need for concomitant treatment with tricyclic antidepressants and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Tricyclic antidepressants may increase the risk of seizures.
Clozapine: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Codeine; Phenylephrine; Promethazine: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold.
Codeine; Promethazine: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold.
Corticosteroids: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Cortisone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Cyclobenzaprine: (Major) Carefully consider the need for concomitant treatment with cyclobenzaprine and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Cyclobenzaprine may increase the risk of seizures.
Dalfampridine: (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.
Deflazacort: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Desipramine: (Major) Carefully consider the need for concomitant treatment with tricyclic antidepressants and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Tricyclic antidepressants may increase the risk of seizures.
Dexamethasone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Dextroamphetamine: (Major) Carefully consider the need for concomitant treatment with amphetamines and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Amphetamines may increase the risk of seizures.
Dextromethorphan; Bupropion: (Major) Carefully consider the need for concomitant treatment with bupropion and amifampridine, as coadministration may increase the risk of seizures. Consider alternatives to bupropion. If use together is medically necessary, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Bupropion is known to have a dose-dependent risk for seizures.
Diethylpropion: (Major) Carefully consider the need for concomitant treatment with diethylpropion and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Diethylpropion may increase the risk of seizures.
Donepezil: (Moderate) Coaministration of amifampridine and donepezil may increase the risk for adverse reactions due to additive cholinergic effects. Monitor patients closely for new or worsening side effects such as headache, visual disturbances, watery eyes, excessive sweating, shortness of breath, nausea, vomiting, diarrhea, bradycardia, loss of bladder control, confusion, or tremors.
Donepezil; Memantine: (Moderate) Coaministration of amifampridine and donepezil may increase the risk for adverse reactions due to additive cholinergic effects. Monitor patients closely for new or worsening side effects such as headache, visual disturbances, watery eyes, excessive sweating, shortness of breath, nausea, vomiting, diarrhea, bradycardia, loss of bladder control, confusion, or tremors.
Doxepin: (Major) Carefully consider the need for concomitant treatment with tricyclic antidepressants and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Tricyclic antidepressants may increase the risk of seizures.
Fludrocortisone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Flunisolide: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Fluphenazine: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold.
Fluticasone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Fluticasone; Salmeterol: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Fluticasone; Vilanterol: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Formoterol; Mometasone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Galantamine: (Moderate) Coaministration of amifampridine and galantamine may increase the risk for adverse reactions due to additive cholinergic effects. Monitor patients closely for new or worsening side effects such as headache, visual disturbances, watery eyes, excessive sweating, shortness of breath, nausea, vomiting, diarrhea, bradycardia, loss of bladder control, confusion, or tremors.
Haloperidol: (Major) Carefully consider the need for concomitant treatment with haloperidol and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Haloperidol may increase the risk of seizures.
Hydrocortisone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Iloperidone: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Imipramine: (Major) Carefully consider the need for concomitant treatment with tricyclic antidepressants and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Tricyclic antidepressants may increase the risk of seizures.
Isocarboxazid: (Major) The concomitant use of amifampridine and drugs that lower seizure threshold may lead to an increased risk of seizures; carefully consider the risks versus benefits of combined use. Monoamine oxidase inhibitors (MAOIs) are associated with a risk for seizures in susceptible patients. Because the effect of MAOIs on the convulsive threshold may be variable, adequate precautions should be taken.
Lisdexamfetamine: (Major) Carefully consider the need for concomitant treatment with lisdexamfetamine and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Lisdexamfetamine may increase the risk of seizures.
Loxapine: (Major) Carefully consider the need for concomitant treatment with loxapine and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Loxapine may increase the risk of seizures.
Lumateperone: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Lurasidone: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Methamphetamine: (Major) Carefully consider the need for concomitant treatment with methamphetamine and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Methamphetamine may increase the risk of seizures.
Methylphenidate Derivatives: (Major) Carefully consider the need for concomitant treatment with methylphenidate derivatives and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Methylphenidate derivatives may increase the risk of seizures.
Methylprednisolone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Molindone: (Major) Carefully consider the need for concomitant treatment with molindone and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Molindone may increase the risk of seizures.
Mometasone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Monoamine oxidase inhibitors: (Major) The concomitant use of amifampridine and drugs that lower seizure threshold may lead to an increased risk of seizures; carefully consider the risks versus benefits of combined use. Monoamine oxidase inhibitors (MAOIs) are associated with a risk for seizures in susceptible patients. Because the effect of MAOIs on the convulsive threshold may be variable, adequate precautions should be taken.
Neostigmine: (Moderate) Coaministration of amifampridine and neostigmine may increase the risk for adverse reactions due to additive cholinergic effects. Monitor patients closely for new or worsening side effects such as headache, visual disturbances, watery eyes, excessive sweating, shortness of breath, nausea, vomiting, diarrhea, bradycardia, loss of bladder control, confusion, or tremors.
Neostigmine; Glycopyrrolate: (Moderate) Coaministration of amifampridine and neostigmine may increase the risk for adverse reactions due to additive cholinergic effects. Monitor patients closely for new or worsening side effects such as headache, visual disturbances, watery eyes, excessive sweating, shortness of breath, nausea, vomiting, diarrhea, bradycardia, loss of bladder control, confusion, or tremors.
Nortriptyline: (Major) Carefully consider the need for concomitant treatment with tricyclic antidepressants and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Tricyclic antidepressants may increase the risk of seizures.
Olanzapine: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Olanzapine; Fluoxetine: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Olanzapine; Samidorphan: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Olopatadine; Mometasone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Paliperidone: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Perphenazine: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold.
Perphenazine; Amitriptyline: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold. (Major) Carefully consider the need for concomitant treatment with tricyclic antidepressants and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Tricyclic antidepressants may increase the risk of seizures.
Phendimetrazine: (Major) Carefully consider the need for concomitant treatment with phendimetrazine and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phendimetrazine may increase the risk of seizures.
Phenelzine: (Major) The concomitant use of amifampridine and drugs that lower seizure threshold may lead to an increased risk of seizures; carefully consider the risks versus benefits of combined use. Monoamine oxidase inhibitors (MAOIs) are associated with a risk for seizures in susceptible patients. Because the effect of MAOIs on the convulsive threshold may be variable, adequate precautions should be taken.
Phenothiazines: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold.
Phentermine: (Major) Carefully consider the need for concomitant treatment with phentermine and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phentermine may increase the risk of seizures.
Phentermine; Topiramate: (Major) Carefully consider the need for concomitant treatment with phentermine and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phentermine may increase the risk of seizures.
Physostigmine: (Moderate) Coaministration of amifampridine and physostigmine may increase the risk for adverse reactions due to additive cholinergic effects. Monitor patients closely for new or worsening side effects such as headache, visual disturbances, watery eyes, excessive sweating, shortness of breath, nausea, vomiting, diarrhea, bradycardia, loss of bladder control, confusion, or tremors.
Prednisolone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Prednisone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Prochlorperazine: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold.
Promethazine: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold.
Promethazine; Dextromethorphan: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold.
Promethazine; Phenylephrine: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold.
Protriptyline: (Major) Carefully consider the need for concomitant treatment with tricyclic antidepressants and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Tricyclic antidepressants may increase the risk of seizures.
Pyridostigmine: (Moderate) Coaministration of amifampridine and pyridostigmine may increase the risk for adverse reactions due to additive cholinergic effects. Monitor patients closely for new or worsening side effects such as headache, visual disturbances, watery eyes, excessive sweating, shortness of breath, nausea, vomiting, diarrhea, bradycardia, loss of bladder control, confusion, or tremors.
Quetiapine: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Risperidone: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Rivastigmine: (Moderate) Coaministration of amifampridine and rivastigmine may increase the risk for adverse reactions due to additive cholinergic effects. Monitor patients closely for new or worsening side effects such as headache, visual disturbances, watery eyes, excessive sweating, shortness of breath, nausea, vomiting, diarrhea, bradycardia, loss of bladder control, confusion, or tremors.
Theophylline, Aminophylline: (Major) Carefully consider the need for aminophylline, as use with amifampridine may increase the risk of seizures. Consider alternatives to aminophylline. If use together is medically necessary, closely monitor patients for seizure activity and closely monitor theophylline concentrations. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Aminophylline is converted to theophylline and is known to have a dose-dependent risk for seizures. (Major) Carefully consider the need for theophylline, as use with amifampridine may increase the risk of seizures. Consider alternatives to theophylline. If use together is medically necessary, closely monitor patients for seizure activity and closely monitor theophylline concentrations. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Theophylline is known to have a dose-dependent risk for seizures.
Thioridazine: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold.
Thiothixene: (Major) Carefully consider the need for concomitant treatment with thiothixene and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Thiothixene may increase the risk of seizures.
Tramadol: (Major) Carefully consider concomitant use of amifampridine with tramadol due to increased seizure risk. The concomitant use of amifampridine and other drugs that lower the seizure threshold, such as tramadol, may lead to an increased risk of seizures.
Tramadol; Acetaminophen: (Major) Carefully consider concomitant use of amifampridine with tramadol due to increased seizure risk. The concomitant use of amifampridine and other drugs that lower the seizure threshold, such as tramadol, may lead to an increased risk of seizures.
Tranylcypromine: (Major) The concomitant use of amifampridine and drugs that lower seizure threshold may lead to an increased risk of seizures; carefully consider the risks versus benefits of combined use. Monoamine oxidase inhibitors (MAOIs) are associated with a risk for seizures in susceptible patients. Because the effect of MAOIs on the convulsive threshold may be variable, adequate precautions should be taken.
Triamcinolone: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
Tricyclic antidepressants: (Major) Carefully consider the need for concomitant treatment with tricyclic antidepressants and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Tricyclic antidepressants may increase the risk of seizures.
Trifluoperazine: (Major) Carefully consider the need for concomitant treatment with phenothiazines and amifampridine, as coadministration may increase the risk of seizures. Consider an alternative to the phenothiazine. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phenothiazines may lower seizure threshold and should be used with caution with concomitant medications which may also affect seizure threshold.
Trimipramine: (Major) Carefully consider the need for concomitant treatment with tricyclic antidepressants and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Tricyclic antidepressants may increase the risk of seizures.
Ziprasidone: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.

FIRDAPSE/Ruzurgi Oral Tab: 10mg

20 mg/dose and 80 mg/day PO.

20 mg/dose and 80 mg/day PO.

Weighing 45 kg or more: 20 mg/dose and 80 mg/day PO for Firdapse; 30 mg/dose and 100 mg/day PO for Rizurgi.
Weighing less than 45 kg: 10 mg/dose and 40 mg/day PO for Firdapse; 15 mg/dose and 50 mg/day PO for Rizurgi.

6 to 12 years weighing 45 kg or more: 20 mg/dose and 80 mg/day PO for Firdapse; 30 mg/dose and 100 mg/day PO for Rizurgi.
6 to 12 years weighing less than 45 kg: 10 mg/dose and 40 mg/day PO for Firdapse; 15 mg/dose and 50 mg/day PO for Rizurgi.
1 to 5 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Amifampridine is a broad spectrum potassium channel blocker that prolongs cell membrane depolarization allowing for more calcium to be transferred to the nerve ending. As a result, the vesicular release of acetylcholine and impulse transmission at central, autonomic, and neuromuscular synapses is increased.[63790] [63803]

Amifampridine is administered orally. Amifampridine has a moderate to high volume of distribution. In vitro human plasma protein binding is approximately 25%.[64128] The drug is rapidly and extensively metabolized (acetylated) by N-acetyltransferase 2 (NAT2) to 3-N-acetyl-amifampridine, which is an inactive metabolite.[63790] [64128] Metabolism of amifampridine by N-acetyltransferase 1 (NAT1) may also occur but at a much slower rate.[64128] Approximately 93% to 100% of an administered dose is eliminated in the urine as amifampridine or 3-N-acetyl-amifampridine within 24 hours.[63790] Oral clearance is 149 to 214 L/hour.[64128] The terminal half-life ranges from 1.8 to 2.5 hours in healthy adult subjects.[63790] Average elimination half-life is 3.6 to 4.2 hours.[64128]
 
Affected cytochrome P450 isoenzymes and drug transporters: none

Amifampridine is absorbed in a dose-proportional manner with a Tmax ranging from 20 minutes to 1 hour. Steady-state is reached within 1 day of dosing. After single and multiple oral dose administration, AUC, Cmax, and Cmin are highly variable among individuals. Exposure increases proportionally with doses ranging from 20 to 80 mg. Food does not have a clinically significant effect on exposure. Compared to administration in the fasting state, administration of 20 and 30 mg/day doses with a standard high fat meal decreased Cmax 41% and 52%, respectively, with an increase in median Tmax to 1 hour. AUC was only significantly reduced for the 30 mg/day dose (23%).

There are no data on the developmental risk associated with amifampridine use during human pregnancy.[63790] Administration of amifampridine phosphate (7.5, 22.5, or 75 mg/kg/day) to rats during pregnancy and lactation resulted in an increase in stillbirths and pup death, reduced pup weight, and delayed sexual development. The no-effect dose for adverse developmental effects (7.5 mg/kg/day) is less than amifampridine exposure (AUC) in humans at the maximum recommended human dose. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to amifampridine; information about the registry can be obtained at www.firdapsepregnancystudy.com or by calling 1-855-212-5856.[63790]

There are no data on the presence of amifampridine in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for amifampridine and any potential adverse effects on the breast-fed infant from amifampridine (e.g., seizures) or the underlying maternal condition. In the lactating rat, amifampridine was excreted in milk and reached concentrations similar to those in maternal plasma; however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug concentrations in human milk.