Get your own Free Home PageAmantadine has found use primarily as an antiviral agent and in the symptomatic treatment of parkinsonism and subjective alleviation of fatigue in multiple sclerosis. Side effects of amantadine are primarily related to the central nervous system and include hallucinations, confusion, and nightmares.
TREATMENT OF CHRONIC HEPATITIS C WITH AMANTADINE-HYDROCHLORIDE
Jill .P. Smith, M.D., March 1996; Dept. of Medicine, The M. S. Hershey Medical Center, The Pennsylvania State University, Hershey, PA 17033, 1-800-243-1455
Smith's study included 22 patients who were monitored over a four-year period. Only those who failed treatment with interferon were allowed into the study. As a control the same group of patients were monitored during two intervals of no treatment. Patients received 100 milligrams twice a day.
Of the 22 patients, 20 completed the study and two dropped out due to chest pains and shortness of breath. Six of the 20 responded to treatment, 8 had a partial response, and 6 did not respond to amantadine.
"If we used a higher dose, or treated longer, it's possible the partial responders would have responded completely," said Smith. She said the response to treatment might have been greater with a group of patients who had never been treated with interferon, since her study only treated those with interferon-resistant disease.
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Treatment of chronic hepatitis C infection with interferon has been disappointing, with less than one-third achieving a sustained response and most experiencing significant side effects. For these reasons, a prospective open-labeled study was conducted to test the safety and efficacy of the anti-viral drug, amantidine-HCl, in patients with chronic hepatitis C infection who had previously failed therapy with interferon alpha-2b. Twenty-two patients with chronic hepatitis C were treated with amantadine-HCl 100 mg given orally twice daily for six months. Hepatitis C was confirmed by the presence of serum antibodies, detectable hepatitis C RNA by branched chain DNA analysis, and abnormal liver histology by biopsy. The mean age was 43.4 years (17-74 years). Liver histology was consistent with chronic persistent hepatitis (23%), chronic active hepatitis (55%), or cirrhosis (18%). Patients were followed monthly with interim history, physical examination, symptom survey and laboratory tests. Control groups included the same cohort during 2 intervals of no treatment (24 mos. before and 12 mos. after interferon) and during therapy with interferon alpha-2b. Serum alanine aminotransferase (ALT) values decreased from 193 to 75 U/L (P=0.001), and hepatitis C RNA values decreased from 195 to 88 x 10(5) units (P=0.036) with amantidine-HCl therapy. Twenty of the twenty-two patients completed therapy with 6 (30%) did not respond to amantadine-HCl. Responders had lower pretreatment HCV RNA levels than nonresponders. Two patients terminated in mos. 1 due to cardiac-associated side effects. Hepatitis C RNA levels were undetectable in 6 patients at completion of amantadine therapy while RNA levels fell by >50% in eleven patients. ALT values were significantly lower during amantadine-HCl therapy and 6 mos. after termination of therapy than ALT levels during either period without treatment (P=0.0005) or during the period when interferon alpha-2b was given (P=0.001). No deleterious effects on bone marrow were observed. Side effects included difficulty with concentration (2) and constipation (1). Chronic hepatitis C infection may be successfully treated in some patients with a six-month course of amantadine-HCl whereas in others amantadine treatment effectively lowers hepatitis C RNA and hepatic transaminases.
THE EFFECT OF AMANTADINE ON RECURRENT HEPATITIS C FOLLOWING LIVER TRANSPLANTATION
J.A. Goss, MD, C.D. Holt, PharmD, L.I. Goldstein, MD, R. Stribling, MD, A. Pakrasi, RN, G. Kunder, RN, P. Seu, MD, P. Martin, MD and R.W. Busuttil, MD, PhD, The Dumont-UCLA Transplant Center, UCLA School of Medicine, Los Angeles, CA. Presented to American Society of Transplant Surgeons on May 15, 1997
Background: The most common indication for orthotopic liver transplantation (OLT) is chronic active hepatitis C (CAHC). Recurrence occurs in up to 100% of OLT recipients and may result in significant early graft dysfunction. To date, no effective anti-viral therapy has been established for recurrent hepatitis C following OLT. A recent repeat demonstrated that Amantadine (AMD) was effective in the treatment of CAHC in non-transplant patients. Therefore, we administered AMD in non-randomized, prospective fashion in OLT recipients with graft dysfunction due to biopsy proven recurrent hepatitis C (HCV).
Methods: In 31 adult patients undergoing OLT for CAHC, amantadine (200 mg/day) was initiated upon diagnosis of recurrent HCV;
Results: Overall patient and graft survival were 100% and 92%, respectively. Graft loss was independent of recurrent HCV. A significant reduction in serum HCV RNA levels occurred after 3 months of AMD therapy. Furthermore, AMD therapy resulted in a decline in serum transaminases, t. bilirubin, and alkaline phosphatase. After 3 months of AMD therapy, histologic improvement was confirmed by liver biopsy. Overall, AMD was well tolerated, however 6 patients (19.3%) had AMD discontinued secondary to neurotoxicity.
Conclusion: Amantadine is a well-tolerated anti-viral that reduces the serum HCV RNA, t. bilirubin, aminotransferases, and alkaline phosphatase in patients with recurrent HCV after OLT. These early data warrant further randomized controlled trials with extended follow-up and possible combination anti-viral therapy.
Mechanism of Borna Disease Virus Entry into Cells( and prevention by AMANTADINE )
Daniel Gonzalez-Dunia, Beatrice Cubitt, and Juan Carlos de la Torre; Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037; Journal of Virology, Jan. 1998, p. 783-788, Vol. 72, No. 1
We have investigated the entry pathway of Borna disease virus (BDV). Virus entry was assessed by detecting early viral replication and transcription. Lysosomotropic agents (ammonium chloride, chloroquine, and amantadine), as well as energy depletion, prevented BDV infection, indicating that BDV enters host cells by endocytosis and requires an acidic intracellular compartment to allow membrane fusion and initiate infection.
USE OF AMANTADINE FOR CHRONIC FATIGUE SYNDROME
Marjorie A. Bowman, MD, MPA Philadelphia, Pa; Julienne K. Kirk, PharmD; Robert Michielutte, PhD John S. Preisser, PhD; Winston-Salem, NC; Archives of Internal Medicine Editor's Correspondence - June 9, 1997
Fatigue is a chronic and debilitating hallmark of the chronic fatigue syndrome, which is often accompanied by sleep disturbances, myalgias, and depression.[1,2] This condition has been reported worldwide, and case definitions have been developed by the Centers for Disease Control and Prevention.[ 3] Amantadine hydrochloride has been used to treat fatigue associated with conditions such as multiple sclerosis.[ 4-6] We investigated the symptomatic effects of amantadine on 4 patients with chronic fatigue syndrome using a multiple single-subject trial design.[7] Patients who had a diagnosis of chronic fatigue made by their family physicians and who fulfilled the criteria for chronic fatigue syndrome defined by the Centers for Disease Control and Prevention were included.[3] Using a multiperiod, crossover design,[8] with a single subject for each sequence, patients received either placebo (B) or amantadine hydrochloride (A), 100 mg twice daily. Patients were blinded to treatment identification.
Varying the treatment and placebo periods within and between patients allows for the evaluation of assumptions in the analysis and for the determination of whether there is consistency of the treatment effect across patients, and thus any indication of generalizability of the intervention.[7] Fatigue was measured by a numerical rating scale. Patients rated their perceptions of how fatigued they were at noon each day. Daily measurement over 8 weeks provided 56 measurement periods for analysis. The scale was examined both as a metric scale and as a dichotomy. Scores of 5 or less were designated as low fatigue, and scores of 6 or higher represented high fatigue. Potential adverse effects due to amantadine were evaluated using a symptom checklist. Three outcome measures were examined for each patient and tabulated weekly. The number of days of high fatigue, the average fatigue scores, and the number of symptoms were reported. Evaluation of the intervention was based on comparing the mean of the 4 placebo periods with the mean of the 4 treatment periods for each patient. The sign test was applied to the 4 pairs of measurements obtained by reducing the weekly data to single measurements for intervention and placebo for each case.[9,10] Two-sided P values were determined by permutation methods appropriate for small samples using the software package StatXact.[ 11,12] A linear rank test was applied to a table combining all 4 cases for a test of carryover effect.
Four patients completed an 8-week trial, and all participants were white women between the ages of 33 and 46 years. Duration of chronic fatigue ranged from 2 to 9 years. Patient 2 was taking fluoxitine hydrochloride (Prozac), and patient 3 was taking paroxetine (Paxil) for depression. Patient 3 had previously been treated with amantadine and reported success; she was given a 2-week washout period before beginning the trial. Since the mean half-life of amantadine is 15 hours in normal renal function, this washout time frame should be sufficient.
Irrespective of the summary measure used, the intervention was better than the placebo in each of the 4 cases, as shown in the Table, and the sign test gave a 1-sided P value of .06. Although the data were not randomly sampled, we believe that the results of this sign test are valid, because the consistency of the effectiveness of the intervention across the 4 subjects suggests that they may be representative of a population of like patients. The stratified linear rank test for each of the 3 outcomes gave a 2-sided permutation-based P<.001, indicating a strong consistent effect of the intervention across the 4 cases. Tests for carryover effect had P values that were greater than .10, indicating no evidence of a carryover effect; eg, for the numbers of symptoms reported, the median change (A-B) was 4.5 for both sets, A to B and B to A, of treatment transitions. During the treatment weeks, each patient had a higher number of mean days of low fatigue, a lower mean fatigue score, and a lower mean symptom score. Side effects noted were vivid dreams in 1 patient and sleeplessness at some point reported by all patients while receiving active treatment with amantadine. Most patients reported difficulty documenting side effects, as many potential adverse events that may occur with amantadine may also develop in a person with chronic fatigue.
We found that, compared with placebo treatment, amantadine therapy was associated with consistently less fatigue and a decrease in chronic fatigue symptoms in all 4 patients. Although we did not directly test for the magnitude of treatment effects, examination of the decline in fatigue and symptoms during treatment periods suggested a substantial effect from amantadine. The average decline in fatigue score from placebo to treatment weeks was 27.6%, with a range of 11.4% to 60.3% across the 4 patients. The results were even more consistent for the symptom score, with an average decline in reported symptoms from placebo to treatment weeks of 52.6% (range, 42.3% to 61.6%). The effect appeared and disappeared quickly with changes between placebo and treatment of varying treatment lengths. For each outcome, the test for carryover effects when the patients were switched from treatment with amantadine to treatment with placebo was not significant. Alternating periods of treatment and placebo for each patient allowed each to act as her own control.
One limitation of this study included no washout period, partially on the basis of the short half-life of amantadine; therefore, the results are not adequate to indicate if there was a short period of carryover effect of the amantadine, although the limited tests for carryover effects were not significant. There was also no attempt to use varying doses of amantadine. The patient reports are all subjective measures. There were only 4 patients with varying lengths of duration of disease, and the interaction with the antidepressants of patients 2 and 3 is unknown. Although all participants showed clear improvement during amantadine therapy, all continued to have documented fatigue, but to a lesser extent. While there are many limitations to a small trial in which each patient acts as his or her own control, the consistent results of this pilot study suggest that further trials with amantadine for symptomatic relief in chronic fatigue syndrome are indicated.
A MOUSE HEPATOTROPIC VARIANT OF INFLUENZA VIRUS.
Haller O; Arch Virol, 1975, 49:2-3, 99-116
A hepatotropic variant of avian influenza virus A/Turkey/England 63 (Hav 1, Nav 3) was selected by serial passages in mouse liver. Adaptation to this organ was established after 13 in vivo passages and was found to improve during further passages as shown by increasing rates of replication in livers of ICR mice. The mutant virus finally selected was stable and differed from the original virus mainly in lethality upon intraperitoneal injection in mice, in its ability to grow to high titers in livers of susceptible animals and in plaque morphology in chick embryo fibroblasts. No differences were detected in hemagglutination inhibition and neutralization by standard mouse antisera. Pathogenicity for the liver was independent of the route of inoculation, included other laboratory animals sensitive to influenza virus and could be inhibited by amantadine. Fatal hepatitis in 50 per cent of susceptible mice by the intraperitoneal route required from 10 to 20 EID50-. Pathological changes consisted of severe necrosis of liver parenchyma accompanied by release of F antigen into the serum and were apparently due to virus replication in hepatic cells as evidenced by immunofluorescence. The main implications of this animal model for studies on experimental hepatitis and on myxovirus-host interactions in an organ not usually associated with influenza are discussed.
MEXICO - In Mexico Ribavarin is called Ribavarina and is callel by the product names Virazide or Vilona. Amantadine is called Amantadina. Both are readily available at many farmacias and you do not need a prescription to purchase them there. Latest reports of pricing: Ribavirin 96 capsules (400 mg) $300-350 Amantadine 100 tablets (100 mg) $30 - $50 If you do not speak Spanish: Bring a pen and piece of paper and write things down for the farmacia employees. Instead of having to constantly translate things, just write down: "96 capsulas Ribavirina" then, write down, "$350 US," etc. This will save time, and prevent misunderstanding. - TIJUANA - This Farmicia is only a few blocks across the border: Vania Farmacia Juan Valencia Centro Commercial - Viva Tijuana - Local 2202 - Ed. #22 Tel: 83-63-00 Visa and MC accepted - MATAMOROS - If you are going there yourself, the Farmicia is in the "old market" area, a popular place that is known to all Mexican taxi drivers. These folks will allow you to order by phone. If you are taking this route, get an international operator to make the call for you. Only one person speaks English at the Farmacia, so get someone who is bi-lingual to help you make the call. The contact will tell you the total amount to remit and will give you all the instructions. With your order, they require that you send a letter (in English is OK) that states the details of your request (medication name, quantity, capsule dosage...ex. 400 mg. capsules, and total amount enclosed) and your name and mailing address. Payment will be required in advance and a charge (around $20 for U.S. shipments) will be added for packaging and mailing costs: The contact person is Christina de Delgado. Farmacia Regis Centro Tel: 91(88) 13-85-79 or 91(88) 12-04-17 or 91(88) 13-68-54 Fax: 91(88) 16-64-59 10a Abasolo Y Matamoros H. Matamoros, Tam., Mexico Visa & MC are not accepted.
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