amantadine (Endantadine, Symmetrel)

Dosing and uses of Endantadine, Symmetrel (amantadine)

• Adult
• Pediatric
• Geriatric

 

Adult dosage forms and strengths

capsule/tablet

• 100mg

syrup

• 50mg/5mL

 

Parkinson Disease

Serious illness or high dose of other antiparkinson agents: 100 mg/day PO initially; may be increased to 100 mg q12hr after at least 1 week

Up to 400 mg/day, but only in special circumstances

 

Drug-Induced Extrapyramidal Symptoms

100 mg PO q12hr; not to exceed 300 mg/day

 

Levodopa-induced Dyskinesia (Orphan)

Orphan designation for treatment of levodopa-induced dyskinesia

Sponsor

• Osmotica Pharmaceutical Corporation; Regulatory, Clinical Operations & Legal; Lumina Station #2, Suite 209-A; Wilmington, NC 28403

 

Dosage modifications

Renal impairment

• CrCl 30-50 mL/min: 200 mg PO on 1st day, then 100 mg/day PO
• CrCl 15-29 mL/min: 200 mg PO on 1st day, then 100 mg PO every other day
• CrCl <15 mL/min; hemodialysis: 200 mg PO weekly

 

Administration

Administer in 2 divided doses to decrease adverse CNS effects; administer 2nd dose several hours before bedtime to minimize insomnia

 

Pediatric dosage forms and strengths

capsule/tablet

• 100mg

syrup

• 50mg/5mL

 

Influenza A Treatment

NOTE: Because of resistance, amantadine is no longer recommended for prophylaxis or treatment of influenza A; refer to current ACIP recommendations

1-9 years or <40 kg (any age): 5 mg/kg/day PO in single dose or divided q12 hr; not to exceed 150 mg/day

≥10 years and <40 kg: 5 mg/kg/day PO divided q12hr

≥10 years and ≥40 kg: 100 mg PO q12hr

 

Geriatric dosage forms and strengths

 

Parkinson Disease

>65 years: Therapy should be based on renal function

 

Endantadine, Symmetrel (amantadine) adverse (side) effects

1-10%

Agitation

Anorexia

Anxiety

Ataxia

Confusion

Constipation

Depression

Diarrhea

Dizziness

Dream abnormality

Dry nose

Fatigue

Hallucinations

Headache

Insomnia

Irritability

Livedo reticularis

Nausea

Nervousness

Orthostatic hypotension

Peripheral edema

Somnolence

Xerostomia

 

<1%

Amnesia

CHF

Decreased libido

Dyspnea

Eczematoid dermatitis

Euphoria

Hyperkinesis

Hypertension

Instances of convulsions

Leukopenia

Neutropenia

Oculogyric episodes

Psychosis

Rash

Slurred speech

Urinary retention

Visual disturbances

Vomiting

Weakness

 

Warnings

Contraindications

Hypersensitivity to amantadine, rimantadine

Untreated narrow-angle glaucoma

Breastfeeding

 

Cautions

Since 2008-09 influenza season, Centers for Disease Control and Prevention (CDC) advises against use for treatment or prophylaxis of influenza in Us

CHF, peripheral edema, orthostatic hypotension

Renal impairment, liver disease

Advanced age

History of seizures, eczematoid rash, severe psychosis or psychoneurosis

Dosages >200 mg/day

Consider reducing anticholinergic dosages before initiating amantadine therapy

Avoid abrupt withdrawaL

Risk of neuroleptic malignant syndrome (NMS) with dosage reduction or withdrawaL

May impair ability to perform hazardous tasks

Possibility of reduced effectiveness after several months; may regain efficacy if dosage is increased

Parkinson patients

• Risk of uncontrollable sexual, gambling, or other urges
• May be linked to higher melanoma risk

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Drug enters breast milk; not recommended

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Endantadine, Symmetrel (amantadine)

Mechanism of action

Prevents release of infectious viral nucleic acid

May promote dopamine release from presynaptic fibers or block reuptake of dopamine into presynaptic neurons

 

Absorption

Bioavailability: 86-90%

Onset: Within 48 hr (antidyskinetic)

Peak plasma time: 2-4 hr

Peak plasma concentration (100-mg single dose): 0.24 mcg/mL

 

Distribution

Protein bound: 67%

Vd: 1.5-6.1 L/kg (normal renal function)

 

Metabolism

Not appreciably metabolized; small amounts of acetyl metabolite identified

 

Elimination

Half-life: 16 hr (average with normal renal function)

Total body clearance: 0.2-0.3 L/hr/kg

Excretion: Urine (80-90% unchanged) by glomerular filtration and tubular secretion