Amantadine dosing

The most common side effects related to amantadine and rimantadine are minor dose-related gastrointestinal and central nervous system (CNS) complaints. These include nervousness, lightheadedness, difficulty concentrating, insomnia, and loss of appetite or nausea. CNS side effects occur in approximately 5 to 33% of patients treated with amantadine at doses of 200 mg/day, but are significantly less frequent with rimantadine. Amantadine dose reductions are required in older adults (100 mg/day) because of decreased renal function, but 20 to 40% of infirm elderly patients will experience side effects even at this lower dose. 

Recent evidence points to a local release of catecholamines as the major mode of action of amantadine in parkinsonism. This is the most sensitive effect of amantadine reported to date and occurs at the lowest dose. Althou earlier clues pointed to this action, the results of Grelak et al. clarified this point. They reported that a small transient pressor effect of amantadine alone, intravenously in dogs, was markedly intensified by dopamine-priming. This suggested that amantadine released dopamine and/or other catecholamines from neuronal scores to cause Che peripheral pressor action. The effect was noted at very low amantadine doses. There was no evidence for block of dopamine uptake. Earlier Vernier reported that transient increases in myocardial contractile force occurred following moderate intravenous doses of amantadine. These also suggested local catecholamine release, since they were abolished by reserpinlzatlon and restored by norepinephrine infusion. 

It is not yet clear whether amantadine blocks uptake of dopamine (or ocher catecholamines) in brain to prolong the useful presence of transmitter. While uptake block of dopamine and norepinephrine has been reported at high amantadine doses, it probably does not play a major role and the evidence of several groups is against it O SS. fhe qtiantitative and qualitative relations must be worked out before the role of reuptake block of catecholamines can be assessed. Snyder suggested that catecholamine uptake blockade (mainly block of dopamine uptake by striatum) may contribute to the mode of action of anticholinergics and antihistamines in antiparkinsonian therapy. 

Amantadine (Symmetrel ) NMDA-receptor antagonist that blocks glutamate transmission, promotes DA release, and blocks Ach Start with 1 00 mg daily at breakfast after 1 week, add 1 00 mg daily in the early afternoon decrease dose as creatinine clearance decreases less than... 

Amantadine is often effective for mild symptoms, especially tremor. It may also decrease dyskinesia at relatively high doses (400 mg/day). 

Provide smaller doses of carbidopa/L-dopa add amantadine consider surgeiy... 

Fig. 1.4 Hemagglutination assay results from the active fraction of the red alga Gigartina skottsbergii. a Red blood cells (RBCs) hemagglutinate in the presence of influenza virus top row) and with extract A4 -t- virus or extract A4 alone. The bottom two rows present the back titration of the virus used in this experiment, b In contrast to the other anti-influenza drugs (ribavirin, amantadine, rimantadine, and zanamivir) that do not induce hemagglutination of human as well as chicken RBCs, extract A4 does it in a dose-dependent manner...

Parkinson s disease 100 mg twice/day when used alone. Onset of action is usually within 48 h. Initial dose is 100 mg/day for patients with serious associated medical illnesses or those receiving high doses of other antiparkinson drugs. After one to several weeks at 100 mg once/day, increase to 100 mg twice/day, if necessary. Patients whose responses are not optimal at 200 mg/day may occasionally benefit from an increase up to 400 mg/day in divided doses supervise closely. Patients initially benefiting from amantadine often experience decreased efficacy after a few months. Benefit may be regained by increasing to 300 mg/day, or by temporary discontinuation for several weeks. Other antiparkinson drugs may be necessary. 

Concomitant therapy -Wr en amantadine and levodopa are initiated concurrently, the patient can exhibit rapid therapeutic benefits. Maintain the dose at 100 mg/day or twice/day, while levodopa is gradually increased to optimal benefit. 

Loading dose on first day of 200 mg. Reproduced with permission from Horadam VW, Sharp JG, Smilack JD, et al. Pharmacokinetics of amantadine hydrochloride in subjects with normal and impaired renal function. Ann Intern Med. 1981 94 454-458. 

Neuroleptic malignant syndrome (NMS) Sporadic cases of possible NMS have been reported in association with dose reduction or withdrawal of amantadine therapy. Observe patients carefully when the dosage of amantadine is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. 

K /Na exchange in distal tubule Dose Adults. 5-10 mg PO daily Peds. 0.625 mg/kg/d X in renal impair Caution [B, ] Contra T K, SCr >1.5 mg/dL, BUN >30 mg/dL, diabetic neuropathy Disp Tabs SE T K HA, dizziness, dehydration, impotence Interactions T Risk of hyperkalemia W/ ACEI, K-sparing diuretics, NSAIDs, K salt substitutes T effects OF Li, digoxin, antihypertensives, amantadine T risk of hypokalemia W/ licorice EMS Monitor ECG for signs of hyperkalemia (peaked T waves) T effects of digoxin OD May cause bradycardia, light-headedness, and syncope symptomatic and supportive... 

Hyoscyamine (Anaspaz, Cystospaz, Levsin, Others) [Antispasmodic/Anticholinergic] Uses Spasm w/ GI bladder disorders Action Anticholinergic Dose Adults. 0.125-0.25 mg (1-2 tabs) SL/PO tid-qid, ac hs 1 SR cap ql2h Caution [C, +] T Effects w/ amantadine, antihistamines, antimuscarinics, haloperidol, phenothiazines, TCA, MAOI Contra BOO, GI obst, NAG, MyG, paralytic ileus, ulcerative colitis, MI Disp Caps, tabs SE Dry skin, xerostomia, constipation, anticholinergic SE, heat prostration w/ hot weather Interactions T Effects W/ amantadine, antimuscarinics, haloperidol, phenothiazines,... 

Memantine (Namenda) [Anti Alzheimer Agent/NMDA Receptor Antagonist] Uses Mod/ evere Alzheimer Dz Action N-methyl-D-aspartate recqjtor antagonist Dose Target 20 mg/d, start 5 mg/d, t 5 mg/d to 20 mg/d, wait >1 wk before t dose use doses if >5mg/d Caution [B, /-] Hqjatic/mild-mod renal impair Disp Tabs, sol SE Dizziness Interactions t Effects W amantadine, carbonic anhydrase inhibitors, dextromethorphan, ketamine, Na bicarbonate t effects W/ any drug, herb, food that alkalinizes urine EMS Use NaHCOs w/ caution OD May cause restlessness, hallucinations, drowsiness, and fainting symptomatic and supportive... 

Rimantadine (Flumadine) [Antiviral] Uses Prophylaxis Rx of influenza A viral Infxns but not for HlNl swine flu Action Antiviral Dose Adults Feds >9 y. 100 mg PO bid Feds 2-9 y. 5 mg/kg/d PO, 150 mg/d max daily w/ severe renal/hepatic impair elderly initiate w/in 48 h of Sx onset Caution [C, -] w/ cimetidine avoid w/ PRG, breast-feeding Contra Component amantadine allergy Disp Tabs SE Orthostatic X BP, edema, dizziness, GI upset, X Sz threshold Interactions T Effects W/ cimetidine i effects W/ acetaminophen, ASA EMS Concurrent EtOH usage may result in light-headedness, confusion, syncope, and hypotension OD May cause N/V, tremors, Szs, anticholinergic Sxs, ventricular arrhythmias give IV fluids... 

The storage and release of DA can be modified irreversibly by reserpine (3.1), just as in vesicles containing other catecholamines and serotonin. Dopamine release can be blocked specifically by y-hydroxybutyrate (4.78) or its precursor, butyrolactone, which can cross the blood-brain barrier. High doses of amphetamines do deplete the storage vesicles, but this is not their principal mode of action. Apparently, amantadine (4.79), an antiviral drug that is likewise beneficial in parkinsonism (and also perhaps to relieve fatigue in multiple sclerosis), may also act by releasing DA. 

Peak plasma concentrations of amantadine are reached 1-4 hours after an oral dose. The plasma half-life is between 2 and 4 hours, most of the drug being excreted unchanged in the urine. 

Amantadine has a number of undesirable central nervous system effects, all of which can be reversed by stopping the drug. These include restlessness, depression, irritability, insomnia, agitation, excitement, hallucinations, and confusion. Overdosage may produce an acute toxic psychosis. With doses several times higher than recommended, convulsions have occurred. 

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