Amantadine toxicity

Yang CC, Deng JF Anticholirtergic syndrome with severe rhabdomyolysis—an unusual feature of amantadine toxicity. Intensive Care Med 1997 23(3) 355-356. [PMiD 9083247] (Case report.)... 

An interaction between amantadine and co-trimoxazole is Clinical evidence, mechanism, importance and management thought to have caused acute confusion in an elderly man and amantadine toxicity in a patient with end-stage renal disease. 

Michalski LS, Hantsch CE, Hou SH. Amantadine toxicity in a renal transplant patient. Abstracts of the 2003 North American Congress of Clinical Toxicolc Annual Meeting, 93. 

A patient has been described who developed amantadine toxicity when given hydrochlorothiazide-triamterene. 

Amantadine toxicity (ataxia, agitation, hallucinations) developed in a patient within a week of starting to take two tablets of Dyazide (hydrochlorothiazide with triamterene) daily. The symptoms rapidly disappeared when all the drugs were withdrawn. In a later study this patient showed about a 50% rise in amantadine plasma levels (from 156 to 243 nanograms/mL) after taking the diuretic for 7 days. ... 

Nevertheless, be aware that amantadine toxicity (e.g. headache, nausea, or dizziness) could possibly result from the concurrent use of quinine or qui-nidine. 

Chang KC, Kim MK, Wee WR, Lee JH. Comeal endothelial dysfunction associated with amantadine toxicity. Cornea 2008 27 1182-5. 

Michalski LS, Hantsch Bardsley C, Holt DR, Milner JE, Hou SH. Altered mental status in a transplant patient. Amantadine toxicity. Kidney Int 2009 75 (2) 243-4. 

Albumin. Albumin is available in highly pure and uniform form, and exhibits low toxicity and good biological stability. It has been used as a carrier for methotrexate and a variety of antiviral drugs [amantadine, fioxuridine (5-fluorodeoxyuridine), and cytar-abine (cytosine arabinoside)] to treat macrophage tumors and infections caused by DNA viruses growing in macrophages. Heavily modified albumins are known... 

Rimantadine, amantadine Central nervous system toxicity... 

Several drug interactions involving amantadine and rimantadine are clinically significant. Anticholinergic drugs can potentiate the toxicity of amantadine. Thiazide-triamterene, trimethoprim-sulfamethoxazole, quinine, and quinidine increase plasma amantadine levels. Cimetidine decreases rimantadine clearance, and aspirin and acetaminophen decrease rimantadine plasma levels. 

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. 

Phosphonoformate is a pyrophosphate analog and inhibits both DNA polymerases and reverse transcriptase. However, toxicity may prevent longterm treatment of AIDS patients. Amantadine has a narrow antiviral specificity. It specifically inhibits initiation of the replication of influenza virus RNA of type A (but not of type B). Active only against retroviruses, 3 -azidothymidine is a reverse transcriptase inhibitor, which acts by a chain termination mechanism. It was synthesized in the early 1960s but only recently has been used in treatment of AIDS victims. More recently a series of 2, 3 -dideoxynucleosides, such as dideoxyinosine, have also been used.d Acyclic phosphonates, such as phosphonylmethoxypropyladenine, avoid the need for metabolic phosphorylation of the drug.6... 

FOOD TOXICANTS, NATURALLY OCCURRING] (Vol 11) Amantadine hydrochloride [665-66-7]... 

Pharmacokinetics Both drugs are well absorbed orally. Amantadine distributes throughout the body and readily penetrates into the central nervous system (CNS), whereas rimantadine does not cross the blood-brain barrier to the same extent. Amantadine is not extensively metabolized. It is excreted into the urine and may accumulate to toxic levels in patients with renal failure. On the other hand, rimantadine is extensively metabolized by the liver. Metabolites and parent drug are eliminated by the kidney. 

Three Japanese women aged 78-87 years who had taken amantadine 100-200 mg/day for 1 month to 5 years, in two cases together with co-careldopa, developed multifocal myoclonus and two were confused (13). Amantadine concentrations were high in the two patients in whom they were measured, at over 3000 ng/ml a concentration over 1000 ng/ml is regarded as toxic. Amantadine was withdrawn and the myoclonus disappeared within 1-2 weeks and did not recur. Cortical myoclonus has also been described with levo-dopa and bromocriptine, but the mechanism is not known. 

Ing TS, Daugirdas JT, Soung LS, Klawans HL, Mahurkar SD, Hayashi JA, Geis WP, Hano JE. Toxic effects of amantadine in patients with renal failure. Can Med Assoc J 1979 120(6) 695-8. 

How do amantadine and rimantadine differ with regard to renal elimination and potential for CNS toxicity ... 

D The most appropriate therapy would be a neuraminidase inhibitor such as oseltamivir since amantadine and rimantadine do not cover influenza B. Treatment of influenza must be initiated within 48 hours of symptoms for maximum efficacy. Influenza vaccination is only effective for the prevention of influenza and not for symptomatic therapy. If this were influenza A and amantadine was chosen to treat this patient, dose adjustments would be necessary due to her renal insufficiency. She would also be at increased risk of CNS toxicity due to her age and possible accumulation of the drug due to her renal insufficiency. 

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