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Amantadine / Symmetrel / Monograph
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Drug monograph
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Pharmacology
Antiparkinson
While the mechanism of action of amantadine in the treatment of Parkinson's=
syndrome and drug-induced extrapyramidal reactions is not known, it is=
believed to release brain dopamine from nerve endings making it more=
available to activate dopaminergic receptors. The drug does not possess=
anticholinergic activity in animal tests at doses similar to those used=
clinically.
The antiviral activity of amantadine for the prophylaxis of Asian (A(2))=
influenza in humans appears not to be related to the possible mode of=
action of this drug in Parkinson's syndrome.
In man, amantadine is readily absorbed, passes the blood-brain barrier and=
appears in the saliva and nasal secretions. The drug can be detected in the=
blood and cerebrospinal fluid at relatively low, but dose-related, levels.=
No evidence of metabolites has been found and 90% or more of the dose can=
be recovered in the urine unchanged.
After oral administration of a single dose of 100 mg, maximum blood levels=
are reached in approximately 4 hours, based on mean time of the peak=
urinary excretion rate; the peak excretion rate is approximately 5 mg/hour;=
the mean half-life of the excretion rate approximates 15 hours.
Compared with otherwise healthy adult individuals, the clearance of=
amantadine is significantly reduced in adult patients with renal=
insufficiency. The elimination half-life increases 2 to 3 fold when=
creatinine clearance is less than 40 mL/min./1.73m(2) and averages 8 days=
in patients on chronic maintenance hemodialysis.
The renal clearance of amantadine is reduced and plasma levels are increased=
in otherwise healthy elderly patients age 65 years and older. The drug=
plasma levels in elderly patients receiving 100 mg daily have been reported=
to approximate those determined in younger adults taking 200 mg daily.=
Whether these changes are due to the normal decline in renal function or=
other age factors is not known.
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=20
Indications
Amandatine is useful in the treatment of Parkinson's syndrome and in the=
short-term management of drug-induced extrapyramidal symptoms.
In Parkinson's syndrome, amantadine has been used alone and in combination=
with anticholinergic antiparkinson drugs and with levodopa. The final=
therapeutic benefit seen with amantadine is significantly less than that=
seen with levodopa. The maximal therapeutic benefit to be obtained with=
amantadine is usually seen within 1 week. However, initial benefits may=
diminish with continued dosing.
Amantadine is useful as an adjunct in patients who do not tolerate optimal=
doses of levodopa alone or in combined therapy with a decarboxylase=
inhibitor. In these patients, the addition of amantadine may result in=
better control of Parkinson's syndrome and may help to smooth out=
fluctuations in performance.
The comparative efficacy of amantadine and anticholinergic antiparkinson=
drugs has not yet been established. When amantadine or anticholinergic=
antiparkinson drugs are each used with marginal benefit, concomitant use=
may permit the same degree of control, often with a lower dose of the=
anticholinergic medication.
Amantadine is effective in reducing severity or abolishing drug-induced=
extrapyramidal reactions including parkinsonism syndrome, dystonia and=
akathisia. It is not effective in the management of tardive dyskinesia.
Although anticholinergic-type side effects have been noted when used in=
patients with drug-induced extrapyramidal reactions, there appears to be a=
lower incidence of these side effects than that observed with=
anticholinergic antiparkinson drugs.
Antiparkinsonian agents should not usually be used prophylactically during=
neuroleptic administration. However, they may be given when needed to=
suppress extrapyramidal symptoms. Therefore, amantadine may be used in the=
management of extrapyramidal symptoms which cannot be controlled by=
reduction of neuroleptic dosage, but should be discontinued as soon as it=
is no longer required. Amantadine should be withdrawn after a period of=
time to determine whether there is recrudescence of extrapyramidal=
symptoms.
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Contraindications
Known hypersensitivity to amantadine.
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Warnings
A small number of suicidal attempts, some of which have been fatal, have=
been reported in patients treated with amantadine. The incidence of=
suicidal attempts is not known and the pathophysiologic mechanism is not=
understood. Suicidal attempts and suicidal ideation have been reported in=
patients with and without prior history of psychiatric illness. Amantadine=
can exacerbate mental problems in patients with a history of psychiatric=
disorders or substance abuse.
Patients who attempt suicide may exhibit abnormal mental states which=
include disorientation, confusion, depression, personality changes,=
agitation, aggressive behavior, hallucinations, paranoia, other psychotic=
reactions, and somnolence or insomnia. Because of the possibility of=
serious adverse effects, caution should be observed when prescribing=
amantadine to patients being treated with drugs having CNS effects, or for=
whom the potential risks outweigh the benefit of treatment. Because some=
patients have attempted suicide by overdosing with amantadine,=
prescriptions should be written for the smallest quantity consistent with=
good patient management.
Patients with a history of epilepsy or other seizures should be observed=
closely for possible increased seizure activity.
Patients with a history of CHF or peripheral edema should be followed=
closely as there are patients who developed congestive heart failure while=
receiving amantadine.
Patients with Parkinson's disease improving on amantadine should resume=
normal activities gradually and cautiously, consistent with other medical=
considerations, such as the presence of osteoporosis or phlebothrombosis.
Occupational Hazards: Patients receiving amantadine who note CNS effects or=
blurring of vision should be cautioned against driving or working in=
situations where alertness and adequate motor coordination are important.
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Precautions
General: Amantadine should not be discontinued abruptly since a few patients=
with Parkinson's syndrome experienced a parkinsonian crisis, i.e., sudden=
marked clinical deterioration, when this medication was suddenly stopped.
Neuroleptic Malignant Syndrome (NMS): Sporadic cases of possible Neuroleptic=
Malignant Syndrome (NMS) have been reported in association with dose=
reduction or withdrawal of amantadine therapy. NMS is an uncommon but=
life-threatening syndrome characterised by fever or hyperthermia;=
neurologic findings including muscle rigidity, involuntary movements,=
altered consciousness; other disturbances such as autonomic dysfunction,=
tachycardia, tachypnea, hyper- or hypotension; laboratory findings such as=
creatinine phosphokinase elevation, leukocytosis, and increased serum=
myoglobin.
The diagnostic evaluation of patients with this syndrome is complicated. In=
arriving at a diagnosis, it is important to identify cases where the=
clinical presentation includes both serious medical illness (e.g.,=
pneumonia, systemic infection, etc.) and untreated or inadequately treated=
extrapyramidal signs and symptoms (EPS). Other important considerations in=
the differential diagnosis include central anticholinergic toxicity, heat=
stroke, drug fever, and primary CNS pathology.
The management of NMS should include: Intensive symptomatic treatment and=
medical monitoring; and treatment of any concomitant serious medical=
problems for which specific treatments are available. There is no general=
agreement about specific pharmacological treatment regimens for=
uncomplicated NMS.
Patients with Special Diseases and Conditions: Because amantadine is not=
metabolized and is mainly excreted in the urine, it may accumulate in the=
plasma and in the body when renal function declines. The dose of amantadine=
should be reduced in patients with renal impairment and in patients who are=
65 years of age or older (see Dosage). The dose of amantadine may need=
careful adjustment in patients with congestive heart failure, peripheral=
edema, or orthostatic hypotension.
Care shoud be exercised when administering amantadine to patients with liver=
disease, a history of recurrent eczematoid rash, or to patients with=
psychosis or severe psychoneurosis not controlled by chemotherapeutic=
agents. Rare instances of reversible elevation of liver enzyme levels have=
been reported in patients receiving amantadine, though a specific=
relationship between the drug and such changes has not been established.
Pregnancy: Amantadine has been shown to be embryotoxic and teratogenic in=
rats at 50 mg/kg/day, approximately 12 times the recommended human dose,=
but not at 37 mg/kg/day. Embryotoxic and teratogenic drug effects were not=
seen in rabbits that received up to 25 times the recommended human dose.
There are not adequate and well controlled studies in pregnant women.=
Therefore, amantadine should not be used in women with childbearing=
potential, unless in the opinion of the physician, the expected benefit to=
the patient outweighs the possible risk to the fetus.
Lactation: Since amantadine is secreted in human milk, its use is not=
recommended in nursing mothers.
Children: The safety and efficacy of use of amantadine in neonates and=
infants less than 1 year old have not been established.
Drug interactions: The dose of anticholinergic drugs or of amantadine should=
be reduced if atropine-like effects appear when these drugs are used=
concurrently.
Careful observation is required when amantadine is administered concurrently=
with CNS stimulants.
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Adverse Effects
Adverse reactions reported below have occurred in patients while receiving=
amantadine alone or in combination with anticholinergic antiparkinsonian=
drugs and/or levodopa.
The adverse reactions reported most frequently (5 to 10%) are: nausea,=
dizziness (lightheadedness) and insomnia.
Less frequently reported (1 to 5%) are: depression, anxiety and=
irritability, hallucinations, confusion, anorexia, dry mouth, constipation,=
ataxia, livedo reticularis, peripheral edema, orthostatic hypotension,=
headache, somnolence, nervousness, dream abnormality, agitation, dry nose,=
diarrhea and fatigue.
Infrequently occurring adverse reaction (0.1 to 1%) are: CHF, psychosis,=
urinary retention, dyspnea, skin rash, vomiting, weakness, slurred speech,=
euphoria, confusion, thinking abnormality, amnesia, hyperkinesia,=
hypertension, decreased libido, and visual disturbance, including punctuate=
subepithelial or other corneal opacity, corneal edema, decreased visual=
acuity, sensitivity to light, and optic nerve palsy.
Rarely occurring adverse reactions (less than 0.1%) are: instances of=
convulsion, leukopenia, neutropenia, ezcematoid dermatitis and oculogyric=
episodes. Other rare occurring adverse reactions are: suicidal attempt,=
suicide, and suicidal ideation (see Warnings).
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Overdose
Symptoms: Deaths have been reported from overdose with amantadine. The=
lowest reported acute lethal dose was 2 g. An elderly patient with=
Parkinson's syndrome who took an overdose of 2.8 g of amantadine in a=
suicidal attempt, developed acute toxic psychosis, urinary retention, and a=
mixed acid-base disturbance. The toxic psychosis was manifested by=
disorientation, confusion, visual hallucinations and aggressive behavior.=
Convulsions did not occur, possibly because the patient had been receiving=
phenytoin prior to the acute ingestion of amantadine.
Treatment: There is no specific antidote. Slowly administered i.v.=
physostigmine in 1 and 2 mg doses at 1 to 2 hour intervals in an adult, and=
0.5 mg doses at 5 to 10 minute intervals in a child up to a maximum of 2=
mg/hour, have been reported to be effective in the control of CNS toxicity=
caused by amantadine hydrochloride. For acute overdosing, general=
supportive measures should be employed, along with immediate gastric lavage=
or induction of emesis. Fluids should be forced, and if necessary, given=
i.v.
Hemodialysis does not remove significant amounts of amantadine hydrochloride=
in patients with renal failure; a 4 hour hemodialysis removed 7 to 15 mg=
after a single 300 mg oral dose.
The pH of the urine has been reported to influence the excretion rate of=
amantadine. Since the excretion rate of the drug increases rapidly when the=
urine is acidic, the administration of urine-acidifying fluids may increase=
the elimination of the drug from the body. The blood pressure, pulse,=
respiration and temperature should be monitored. The patient should be=
observed for the possible development of arrhythmias, hypotension,=
hyperactivity, and convulsions; if required, appropriate therapy should be=
administered. The blood electrolytes, urine pH and urinary output should be=
monitored. If there is no record of recent voiding, catheterization should=
be done. The possibility of multiple drug ingestion by the patient should=
be considered.
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Dosage
Parkinson's Syndrome: The initial dose of amantadine is 100 mg daily for=
patients with serious associated medical illnesses or who are receiving=
high doses of other antiparkinson drugs. After one to several weeks at 100=
mg once daily, the dose may be increased to 100 mg twice daily. When=
amantadine and levodopa are initiated concurrently, amantadine should be=
held constant at 100 mg daily or twice daily while the daily dose of=
levodopa is gradually increased to optimal dose. When used alone, the usual=
dose of amantadine is 100 mg twice a day.
Patients whose responses are not optimal with amantadine at 200 mg daily may=
benefit from an increase to 300 mg daily in divided doses. Patients who=
experience a fall-off of effectiveness may regain benefit by increasing the=
dose to 300 mg daily; such patients should be supervised closely by their=
physicians.
Drug-Induced Extrapyramidal Symptoms: The usual dose of amantadine is 100 mg=
twice a day. Occasionally, patients whose responses are not optimal with=
amantadine at 200 mg daily may benefit from an increase up to 300 mg daily=
in divided doses.
In the Presence of Impaired Renal Function: Table I outlines the recommended=
dosage adjustments dependent upon creatinine clearance, based upon the=
current National Advisory Committee on Immunization (NACI) Canada=
Communicable Disease Report, May 29, 1992.
----------------------------------------------------------------=20
Table I=20
----------------------------------------------------------------=20
Creatinine Clearance (mL/min/1.73m(2)) Dosage=
----------------------------------------------------------------
>=3D80 100 mg twice daily=20
60-79 Alternating daily doses of 200 and 100 mg=20
40-59 100 mg once daily=20
30-39 200 mg twice weekly=20
20-29 100 mg thrice weekly=20
10-19 Alternating weekly doses of 200 and 100 mg=
----------------------------------------------------------------
The recommended dosage for patients on hemodialysis is 20 mg every 7 days.
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Supplied
Capsules: Each red, soft gelatin capsule contains: Amantadine HCl 100 mg.=
Also contains parabens. Alcohol-free, lactose-free, sodium-free,=
sulfite-free and tartrazine-free. Bottles of 100. Store at room temperature=
(15 to 30=B0C).
Syrup: Each 5 mL of clear colorless syrup contains: Amantadine HCl 50 mg.=
Also contains parabens. Alcohol-free, lactose-free, sodium-free,=
sulfite-free and tartrazine-free. Bottles of 500 mL. Store at room=
temperature (15 to 30=B0C).
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Research
The research information is available separately on Internet Mental Health.
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Note: This information is from a Canadian monograph. There can be=
differences in indications, dosage forms and warnings for this drug in=
other countries.
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Internet Mental Health (<http://www.mentalhealth.com>)=20
copyright =A9 1995-1998 by Phillip W. Long, M.D.
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janet paterson - 51 now /41 dx /37 onset - almonte/ontario/canada
http://www.newcountry.nu/pd/members/janet/index.htm
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2006, Week 4 December 2006, Week 3 December 2006, Week 2 December 2006, Week 1 November 2006, Week 5 November 2006, Week 4 November 2006, Week 3 November 2006, Week 2 November 2006, Week 1 October 2006, Week 5 October 2006, Week 4 October 2006, Week 3 October 2006, Week 2 October 2006, Week 1 September 2006, Week 5 September 2006, Week 4 September 2006, Week 3 September 2006, Week 2 September 2006, Week 1 August 2006, Week 5 August 2006, Week 4 August 2006, Week 3 August 2006, Week 2 August 2006, Week 1 July 2006, Week 5 July 2006, Week 4 July 2006, Week 3 July 2006, Week 2 July 2006, Week 1 June 2006, Week 5 June 2006, Week 4 June 2006, Week 3 June 2006, Week 2 June 2006, Week 1 May 2006, Week 5 May 2006, Week 4 May 2006, Week 3 May 2006, Week 2 May 2006, Week 1 April 2006, Week 5 April 2006, Week 4 April 2006, Week 3 April 2006, Week 2 April 2006, Week 1 March 2006, Week 5 March 2006, Week 4 March 2006, Week 3 March 2006, Week 2 March 2006, Week 1 February 2006, Week 4 February 2006, Week 3 February 2006, Week 2 February 2006, Week 1 January 2006, Week 5 January 2006, Week 4 January 2006, Week 3 January 2006, Week 2 January 2006, Week 1 December 2005, Week 5 December 2005, Week 4 December 2005, Week 3 December 2005, Week 2 December 2005, Week 1 November 2005, Week 5 November 2005, Week 4 November 2005, Week 3 November 2005, Week 2 November 2005, Week 1 October 2005, Week 5 October 2005, Week 4 October 2005, Week 3 October 2005, Week 2 October 2005, Week 1 September 2005, Week 5 September 2005, Week 4 September 2005, Week 3 September 2005, Week 2 September 2005, Week 1 August 2005, Week 5 August 2005, Week 4 August 2005, Week 3 August 2005, Week 2 August 2005, Week 1 July 2005, Week 5 July 2005, Week 4 July 2005, Week 3 July 2005, Week 2 July 2005, Week 1 June 2005, Week 5 June 2005, Week 4 June 2005, Week 3 June 2005, Week 2 June 2005, Week 1 May 2005, Week 5 May 2005, Week 4 May 2005, Week 3 May 2005, Week 2 May 2005, Week 1 April 2005, Week 5 April 2005, Week 4 April 2005, Week 3 April 2005, Week 2 April 2005, Week 1 March 2005, Week 5 March 2005, Week 4 March 2005, Week 3 March 2005, Week 2 March 2005, Week 1 February 2005, Week 4 February 2005, Week 3 February 2005, Week 2 February 2005, Week 1 January 2005, Week 5 January 2005, Week 4 January 2005, Week 3 January 2005, Week 2 January 2005, Week 1 December 2004, Week 5 December 2004, Week 4 December 2004, Week 3 December 2004, Week 2 December 2004, Week 1 November 2004, Week 5 November 2004, Week 4 November 2004, Week 3 November 2004, Week 2 November 2004, Week 1 October 2004, Week 5 October 2004, Week 4 October 2004, Week 3 October 2004, Week 2 October 2004, Week 1 September 2004, Week 5 September 2004, Week 4 September 2004, Week 3 September 2004, Week 2 September 2004, Week 1 August 2004, Week 5 August 2004, Week 4 August 2004, Week 3 August 2004, Week 2 August 2004, Week 1 July 2004, Week 5 July 2004, Week 4 July 2004, Week 3 July 2004, Week 2 July 2004, Week 1 June 2004, Week 5 June 2004, Week 4 June 2004, Week 3 June 2004, Week 2 June 2004, Week 1 May 2004, Week 5 May 2004, Week 4 May 2004, Week 3 May 2004, Week 2 May 2004, Week 1 April 2004, Week 5 April 2004, Week 4 April 2004, Week 3 April 2004, Week 2 April 2004, Week 1 March 2004, Week 5 March 2004, Week 4 March 2004, Week 3 March 2004, Week 2 March 2004, Week 1 February 2004, Week 5 February 2004, Week 4 February 2004, Week 3 February 2004, Week 2 February 2004, Week 1 January 2004, Week 5 January 2004, Week 4 January 2004, Week 3 January 2004, Week 2 January 2004, Week 1 December 2003, Week 5 December 2003, Week 4 December 2003, Week 3 December 2003, Week 2 December 2003, Week 1 November 2003, Week 5 November 2003, Week 4 November 2003, Week 3 November 2003, Week 2 November 2003, Week 1 October 2003, Week 5 October 2003, Week 4 October 2003, Week 3 October 2003, Week 2 October 2003, Week 1 September 2003, Week 5 September 2003, Week 4 September 2003, Week 3 September 2003, Week 2 September 2003, Week 1 August 2003, Week 5 August 2003, Week 4 August 2003, Week 3 August 2003, Week 2 August 2003, Week 1 July 2003, Week 5 July 2003, Week 4 July 2003, Week 3 July 2003, Week 2 July 2003, Week 1 June 2003, Week 5 June 2003, Week 4 June 2003, Week 3 June 2003, Week 2 June 2003, Week 1 May 2003, Week 5 May 2003, Week 4 May 2003, Week 3 May 2003, Week 2 May 2003, Week 1 April 2003, Week 5 April 2003, Week 4 April 2003, Week 3 April 2003, Week 2 April 2003, Week 1 March 2003, Week 5 March 2003, Week 4 March 2003, Week 3 March 2003, Week 2 March 2003, Week 1 February 2003, Week 4 February 2003, Week 3 February 2003, Week 2 February 2003, Week 1 January 2003, Week 5 January 2003, Week 4 January 2003, Week 3 January 2003, Week 2 January 2003, Week 1 December 2002, Week 5 December 2002, Week 4 December 2002, Week 3 December 2002, Week 2 December 2002, Week 1 November 2002, Week 5 November 2002, Week 4 November 2002, Week 3 November 2002, Week 2 November 2002, Week 1 October 2002, Week 5 October 2002, Week 4 October 2002, Week 3 October 2002, Week 2 October 2002, Week 1 September 2002, Week 5 September 2002, Week 4 September 2002, Week 3 September 2002, Week 2 September 2002, Week 1 August 2002, Week 5 August 2002, Week 4 August 2002, Week 3 August 2002, Week 2 August 2002, Week 1 July 2002, Week 5 July 2002, Week 4 July 2002, Week 3 July 2002, Week 2 July 2002, Week 1 June 2002, Week 5 June 2002, Week 4 June 2002, Week 3 June 2002, Week 2 June 2002, Week 1 May 2002, Week 5 May 2002, Week 4 May 2002, Week 3 May 2002, Week 2 May 2002, Week 1 April 2002, Week 5 April 2002, Week 4 April 2002, Week 3 April 2002, Week 2 April 2002, Week 1 March 2002, Week 5 March 2002, Week 4 March 2002, Week 3 March 2002, Week 2 March 2002, Week 1 February 2002, Week 4 February 2002, Week 3 February 2002, Week 2 February 2002, Week 1 January 2002, Week 5 January 2002, Week 4 January 2002, Week 3 January 2002, Week 2 January 2002, Week 1 December 2001, Week 5 December 2001, Week 4 December 2001, Week 3 December 2001, Week 2 December 2001, Week 1 November 2001, Week 5 November 2001, Week 4 November 2001, Week 3 November 2001, Week 2 November 2001, Week 1 October 2001, Week 5 October 2001, Week 4 October 2001, Week 3 October 2001, Week 2 October 2001, Week 1 September 2001, Week 5 September 2001, Week 4 September 2001, Week 3 September 2001, Week 2 September 2001, Week 1 August 2001, Week 5 August 2001, Week 4 August 2001, Week 3 August 2001, Week 2 August 2001, Week 1 July 2001, Week 5 July 2001, Week 4 July 2001, Week 3 July 2001, Week 2 July 2001, Week 1 June 2001, Week 5 June 2001, Week 4 June 2001, Week 3 June 2001, Week 2 June 2001, Week 1 May 2001, Week 5 May 2001, Week 4 May 2001, Week 3 May 2001, Week 2 May 2001, Week 1 April 2001, Week 5 April 2001, Week 4 April 2001, Week 3 April 2001, Week 2 April 2001, Week 1 March 2001, Week 5 March 2001, Week 4 March 2001, Week 3 March 2001, Week 2 March 2001, Week 1 February 2001, Week 4 February 2001, Week 3 February 2001, Week 2 February 2001, Week 1 January 2001, Week 5 January 2001, Week 4 January 2001, Week 3 January 2001, Week 2 January 2001, Week 1 December 2000, Week 5 December 2000, Week 4 December 2000, Week 3 December 2000, Week 2 December 2000, Week 1 November 2000, Week 5 November 2000, Week 4 November 2000, Week 3 November 2000, Week 2 November 2000, Week 1 October 2000, Week 5 October 2000, Week 4 October 2000, Week 3 October 2000, Week 2 October 2000, Week 1 September 2000, Week 5 September 2000, Week 4 September 2000, Week 3 September 2000, Week 2 September 2000, Week 1 August 2000, Week 5 August 2000, Week 4 August 2000, Week 3 August 2000, Week 2 August 2000, Week 1 July 2000, Week 5 July 2000, Week 4 July 2000, Week 3 July 2000, Week 2 July 2000, Week 1 June 2000, Week 5 June 2000, Week 4 June 2000, Week 3 June 2000, Week 2 June 2000, Week 1 May 2000, Week 5 May 2000, Week 4 May 2000, Week 3 May 2000, Week 2 May 2000, Week 1 April 2000, Week 5 April 2000, Week 4 April 2000, Week 3 April 2000, Week 2 April 2000, Week 1 March 2000, Week 5 March 2000, Week 4 March 2000, Week 3 March 2000, Week 2 March 2000, Week 1 February 2000, Week 5 February 2000, Week 4 February 2000, Week 3 February 2000, Week 2 February 2000, Week 1 January 2000, Week 5 January 2000, Week 4 January 2000, Week 3 January 2000, Week 2 January 2000, Week 1 December 1999, Week 5 December 1999, Week 4 December 1999, Week 3 December 1999, Week 2 December 1999, Week 1 November 1999, Week 5 November 1999, Week 4 November 1999, Week 3 November 1999, Week 2 November 1999, Week 1 October 1999, Week 5 October 1999, Week 4 October 1999, Week 3 October 1999, Week 2 October 1999, Week 1 September 1999, Week 5 September 1999, Week 4 September 1999, Week 3 September 1999, Week 2 September 1999, Week 1 August 1999, Week 5 August 1999, Week 4 August 1999, Week 3 August 1999, Week 2 August 1999, Week 1 July 1999, Week 5 July 1999, Week 4 July 1999, Week 3 July 1999, Week 2 July 1999, Week 1 June 1999, Week 5 June 1999, Week 4 June 1999, Week 3 June 1999, Week 2 June 1999, Week 1 May 1999, Week 5 May 1999, Week 4 May 1999, Week 3 May 1999, Week 2 May 1999, Week 1 April 1999, Week 5 April 1999, Week 4 April 1999, Week 3 April 1999, Week 2 April 1999, Week 1 March 1999, Week 5 March 1999, Week 4 March 1999, Week 3 March 1999, Week 2 March 1999, Week 1 February 1999, Week 4 February 1999, Week 3 February 1999, Week 2 February 1999, Week 1 January 1999, Week 5 January 1999, Week 4 January 1999, Week 3 January 1999, Week 2 January 1999, Week 1 December 1998, Week 5 December 1998, Week 4 December 1998, Week 3 December 1998, Week 2 December 1998, Week 1 November 1998, Week 5 November 1998, Week 4 November 1998, Week 3 November 1998, Week 2 November 1998, Week 1 October 1998, Week 5 October 1998, Week 4 October 1998, Week 3 October 1998, Week 2 October 1998, Week 1 September 1998, Week 5 September 1998, Week 4 September 1998, Week 3 September 1998, Week 2 September 1998, Week 1 August 1998, Week 5 August 1998, Week 4 August 1998, Week 3 August 1998, Week 2 August 1998, Week 1 July 1998, Week 5 July 1998, Week 4 July 1998, Week 3 July 1998, Week 2 July 1998, Week 1 June 1998, Week 5 June 1998, Week 4 June 1998, Week 3 June 1998, Week 2 June 1998, Week 1 May 1998, Week 5 May 1998, Week 4 May 1998, Week 3 May 1998, Week 2 May 1998, Week 1 April 1998, Week 5 April 1998, Week 4 April 1998, Week 3 April 1998, Week 2 April 1998, Week 1 March 1998, Week 5 March 1998, Week 4 March 1998, Week 3 March 1998, Week 2 March 1998, Week 1 February 1998, Week 5 February 1998, Week 4 February 1998, Week 3 February 1998, Week 2 February 1998, Week 1 January 1998, Week 5 January 1998, Week 4 January 1998, Week 3 January 1998, Week 2 January 1998, Week 1 December 1997, Week 5 December 1997, Week 4 December 1997, Week 3 December 1997, Week 2 December 1997, Week 1 November 1997, Week 5 November 1997, Week 4 November 1997, Week 3 November 1997, Week 2 November 1997, Week 1 October 1997, Week 5 October 1997, Week 4 October 1997, Week 3 October 1997, Week 2 October 1997, Week 1 September 1997, Week 5 September 1997, Week 4 September 1997, Week 3 September 1997, Week 2 September 1997, Week 1 August 1997, Week 5 August 1997, Week 4 August 1997, Week 3 August 1997, Week 2 August 1997, Week 1 July 1997, Week 5 July 1997, Week 4 July 1997, Week 3 July 1997, Week 2 July 1997, Week 1 June 1997, Week 5 June 1997, Week 4 June 1997, Week 3 June 1997, Week 2 June 1997, Week 1 May 1997, Week 5 May 1997, Week 4 May 1997, Week 3 May 1997, Week 2 May 1997, Week 1 April 1997, Week 5 April 1997, Week 4 April 1997, Week 3 April 1997, Week 2 April 1997, Week 1 March 1997, Week 5 March 1997, Week 4 March 1997, Week 3 March 1997, Week 2 March 1997, Week 1 February 1997, Week 5 February 1997, Week 4 February 1997, Week 3 February 1997, Week 2 February 1997, Week 1 January 1997, Week 5 January 1997, Week 4 January 1997, Week 3 January 1997, Week 2 January 1997, Week 1 December 1996, Week 5 December 1996, Week 4 December 1996, Week 3 December 1996, Week 2 December 1996, Week 1 November 1996, Week 5 November 1996, Week 4 November 1996, Week 3 November 1996, Week 2 November 1996, Week 1 October 1996, Week 5 October 1996, Week 4 October 1996, Week 3 October 1996, Week 2 October 1996, Week 1 September 1996, Week 5 September 1996, Week 4 September 1996, Week 3 September 1996, Week 2 September 1996, Week 1 August 1996, Week 5 August 1996, Week 4 August 1996, Week 3 August 1996, Week 2 August 1996, Week 1 July 1996, Week 5 July 1996, Week 4 July 1996, Week 3 July 1996, Week 2 July 1996, Week 1 June 1996, Week 5 June 1996, Week 4 June 1996, Week 3 June 1996, Week 2 June 1996, Week 1 May 1996, Week 5 May 1996, Week 4 May 1996, Week 3 May 1996, Week 2 May 1996, Week 1 April 1996, Week 5 April 1996, Week 4 April 1996, Week 3 April 1996, Week 2 April 1996, Week 1 March 1996, Week 5 March 1996, Week 4 March 1996, Week 3 March 1996, Week 2 March 1996, Week 1 February 1996, Week 5 February 1996, Week 4 February 1996, Week 3 February 1996, Week 2 February 1996, Week 1 January 1996, Week 5 January 1996, Week 4 January 1996, Week 3 January 1996, Week 2 January 1996, Week 1 December 1995, Week 5 December 1995, Week 4 December 1995, Week 3 December 1995, Week 2 December 1995, Week 1 November 1995, Week 5 November 1995, Week 4 November 1995, Week 3 November 1995, Week 2 November 1995, Week 1 October 1995, Week 5 October 1995, Week 4 October 1995, Week 3 October 1995, Week 2 October 1995, Week 1 September 1995, Week 5 September 1995, Week 4 September 1995, Week 3 September 1995, Week 2 September 1995, Week 1 August 1995, Week 5 August 1995, Week 4 August 1995, Week 3 August 1995, Week 2 August 1995, Week 1 July 1995, Week 5 July 1995, Week 4 July 1995, Week 3 July 1995, Week 2 July 1995, Week 1 June 1995, Week 5 June 1995, Week 4 June 1995, Week 3 June 1995, Week 2 June 1995, Week 1 May 1995, Week 5 May 1995, Week 4 May 1995, Week 3 May 1995, Week 2 May 1995, Week 1 April 1995, Week 5 April 1995, Week 4 April 1995, Week 3 April 1995, Week 2 April 1995, Week 1 March 1995, Week 5 March 1995, Week 4 March 1995, Week 3 March 1995, Week 2 March 1995, Week 1 February 1995, Week 4 February 1995, Week 3 February 1995, Week 2 February 1995, Week 1 January 1995, Week 5 January 1995, Week 4 January 1995, Week 3 January 1995, Week 2 January 1995, Week 1 December 1994, Week 5 December 1994, Week 4 December 1994, Week 3 December 1994, Week 2 December 1994, Week 1 November 1994, Week 5 November 1994, Week 4 November 1994, Week 3 November 1994, Week 2 November 1994, Week 1 October 1994, Week 5 October 1994, Week 4 October 1994, Week 3 October 1994, Week 2 October 1994, Week 1 September 1994, Week 5 September 1994, Week 4 September 1994, Week 3 September 1994, Week 2 September 1994, Week 1 August 1994, Week 5 August 1994, Week 4 August 1994, Week 3 August 1994, Week 2 August 1994, Week 1 July 1994, Week 5 July 1994, Week 4 July 1994, Week 3 July 1994, Week 2 July 1994, Week 1 June 1994, Week 5 June 1994, Week 4 June 1994, Week 3 June 1994, Week 2 June 1994, Week 1 May 1994, Week 5 May 1994, Week 4 May 1994, Week 3 May 1994, Week 2 May 1994, Week 1 April 1994, Week 5 April 1994, Week 4 April 1994, Week 3 April 1994, Week 2 April 1994, Week 1 March 1994, Week 5 March 1994, Week 4 March 1994, Week 3 March 1994, Week 2 March 1994, Week 1 February 1994, Week 4 February 1994, Week 3 February 1994, Week 2 February 1994, Week 1 February 1994 January 1994 December 1993 November 1993
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