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Thread: Worried about side effects

  1. #1
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    Worried about side effects

    My partner a C7 quad since 25/12/02 and still in re-hab has been suffering really bad nerve pains. A while ago he was transferred from re-hab to A&E with severe abdominal pains. After endless tests, ultra sound, CT scans, X-rays, a laparoscopy, cystoscopy and others the doctors decided it was nerve pain and tried several pain treatments an upped doses of exiting medication. The most recent was an infusion of Lignocaine and Ketamine. The first infusion, over 5 days didnt work so a week later they started again on just Ketamine, again for five days. This apparently works as a sort of nerve blocker and has a permanent effect. The pain has subsided to about a 5/10

    We are really worried as on the last day Luke developed hand shakes and difficulty speaking. When he tries to pick up something his hands flick and shake uncontrollably, similarly when speaking he suddenly loses control of his tongue. Doctors are very dismissive and have been no help...has anyone experienced this before and do they know why? We are really worried it will be permanent and hands that once had fairly good function are rendered useless and speech impaired.
    Any ideas?
    Finally in the last three days eye sight has become really blurred but Dr relates this to increased Tolteridine which is now back to 1g
    Luke's other medication is:-
    Anantidine 100mg x3 daily taken with..
    Oxycontin 40mg x3 daily
    Baclofen 25mg x4 daily
    Gabapentin 1g x3 daily
    Amitriptyline 75mg x1 at night
    Diazepam 2.5mg x3 daily
    Tolteridine 1mg x2daily
    Also
    Temazepam 10-20mg prn
    Oxynorm 5-10mg prn

    Has anyone heard of these side effects before?

  2. #2
    Senior Member dogger's Avatar
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    bloody hell , he must rattle when he moves !

    i'm a C5/6 ,over 11 years post and the only drugs i take now are a couple of beers of a night time . i realise not every one get by without some medication , but this seems like ''try everything from sleeping tablets to anti-spasm pills ''. my opinion is that SCI has some side effects , spasms , pain etc. and if these are not excessive the less drugs used the better . also some of these drugs cause some side effects you are probably not yet aware of . in my case , when i did try anti-spasm drugs they made me weaker , not a great option for me . i probably haven't helped much , each person is different in this , ''one of lifes little challenges '' .
    dogger

  3. #3
    Gosh Will, I understand that your partner needs an effective pain medication but there's no doubt that all those meds are causing the side effects you mentioned. Maybe he can eliminate all but one or two and up those doses of those.

    Good luck, I hope you find a solution soon.

  4. #4
    Senior Member Joe B's Avatar
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    That is a lot of meds to be mixing together. This will screw up the results as far s trying to tell whether one is effective or another. Many of the doses are high but not over the limit. 75 mg of elavil must make him sleep like a rock and feel like a water soaked log in the morning especially combined with an opiate base like Oxycontin. Could be reduced. Valium/diazepam is an enhancer for spasticity and has some effect on nerve pain. 2mg 4xday shouldn't be too much. The baclofen seems about right if he really has problems with spasticity (tightness) or spasms but could be reduced as its combined with the valium/diazepam. Why is he getting the pain meds like oxycontin which is not usually considered effective for nerve pain? Lots to think about and to work with your doc on choosing what is really needed.

    Joe B
    C6-7
    1988

  5. #5

    Too many meds!

    Wow! Meds can have some scary side effects, especially if you're taking a dozen different ones. Shortly after I arrived at the rehab hospital, I had to tell the doctor I had trouble remembering things in the evening, like my name and my husband. Identifying the time of day the problem started helped the doctor pinpoint the med causing the problem. A simple change in meds made me into me again, even in the evening.

    You might want to look up some of the meds yourself. Knowledge is power and helps you deal with the doctors better. Try RxList for information about the drugs.

  6. #6
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    Thanks for your input but it doesnt help much being told that 'wow your on shit loads of drugs....'
    Luke was actually doing prety well an ALL these meds. He has had many extra pains and complications and the Doctors have just benig trying to get these under control so that he can actually do some re-hab. Then they reduce the meds. 8 months without much progress is not good. How do you think it feels to see other patients come and go relatively healthy when you just wish you could be more normal and get on with re-hab instedead of being bed-bound in pain.
    PS Joe - He wishes he could sleep even with the Elavil instead of sleepless in pain. Remember everyone is different. Luke has just had endless problems and not even through re-hab yet!!
    I was actually after something specific, what causes the sudden hand shakes and speach impediment. Has anyone heard of Ketamine treatment doing this as all the other meds have been the same for while without side effects.

    [This message was edited by Will H on Aug 28, 2002 at 08:22 PM.]

  7. #7
    Senior Member Joe B's Avatar
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    Sorry about his having trouble sleeping. I know every injury is different. Dr Young may be able to say something about a ketamine infusion but thats beyond most of our experiences. A search on Medline may give some information but this situation may be unique. I do wish him well.

    Joe B
    C6-7
    1988

  8. #8
    Originally posted by Will H:

    Thanks for your input but it doesnt help much being told that 'wow your on shit loads of drugs....'
    Luke was actually doing prety well an ALL these meds. He has had many extra pains and complications and the Doctors have just benig trying to get these under control so that he can actually do some re-hab. Then they reduce the meds. 8 months without much progress is not good. How do you think it feels to see other patients come and go relatively healthy when you just wish you could be more normal and get on with re-hab instedead of being bed-bound in pain.
    PS Joe - He wishes he could sleep even with the Elavil instead of sleepless in pain. Remember everyone is different. Luke has just had endless problems and not even through re-hab yet!!
    I was actually after something specific, what causes the sudden hand shakes and speach impediment. Has anyone heard of Ketamine treatment doing this as all the other meds have been the same for while without side effects.

    [This message was edited by Will H on Aug 28, 2002 at 08:22 PM.]

    Most of us haven't been on such a long list of meds. Therefore, the side effects from the combinations are difficult to predict. Make sure you know why he is taking every med. Were they all ordered by the same doctor? If not, does each doctor know about all of the other meds, including ones ordered after he/she ordered one? As I said in an earlier post, you can look up each med at

    RxList

    I plugged in the first one to show you the info it provides. See the sections on why to take it, dosage, and side effects.

    ***

    Amantadine Description
    Amantadine hydrochloride is designated chemically as 1-adamantanamine hydrochloride. Its molecular weight is 187.71 with a molecular formula C10H18NCl.

    Amantadine hydrochloride is a stable white or nearly white crystalline powder, freely soluble in water and soluble in alcohol and in chloroform.

    Amantadine has pharmacological actions as both an anti-Parkinson and an antiviral drug.

    Each capsule intended for oral administration contains 100 mg amantadine hydrochloride and the following inactive ingredients: Croscarmellose sodium, Ethylcellulose, FD&C Blue 1, FD&C Red 40, Gelatin, Magnesium stearate, Methylparaben, Microcrystalline cellulose, Pregelatinized starch, Propylparaben, Silicon dioxide, Sodium lauryl sulfate and Titanium dioxide.

    Mechanism of Action

    Parkinson's Disease

    The mechanism of action of amantadine in the treatment of Parkinson's disease and drug-induced extrapyramidal reactions is not known. It has been shown to cause an increase in dopamine release in the animal brain. The drug does not possess anticholinergic activity in dogs at doses of 31.5 mg/kg, equivalent to an approximate human dose of 15.8 mg/kg (based on body surface area conversions).

    Antiviral

    The mechanism by which amantadine exerts its antiviral activity is not clearly understood. It appears to mainly prevent the release of infectious viral nucleic acid into the host cell by interfering with the function of the transmembrane domain of the viral M2 protein. In certain cases amantadine is also known to prevent virus assembly during virus replication. It does not appear to interfere with the immunogenicity of inactivated influenza A virus vaccine.

    Antiviral Activity

    Amantadine inhibits the replication of influenza A virus isolates from each of the subtypes, i.e., H1N1, H2N2 and H3N2. It has very little or no activity against influenza B virus isolates. A quantitative relationship between the in vitro susceptibility of influenza A virus to amantadine and the clinical response to therapy has not been established in man. Sensitivity test results, expressed as the concentration of amantadine required to inhibit by 50% the growth of virus (ED50) in tissue culture vary greatly (from 0.1 mcg/mL to 25.0 mcg/mL) depending upon the assay protocol size of virus inoculum, isolates of influenza A virus strains tested, and the cell type used. Host cells in tissue culture readily tolerated amantadine up to a concentration of 100 mcg/mL

    Drug Resistance

    Influenza A variants with reduced in vitro sensitivity to amantadine have been isolated from epidemic strains in areas where adamantane derivatives are being used. Influenza viruses with reduced in vitro sensitivity have been shown to be transmissible and to cause typical influenza illness. The quantitative relationship between the in vitro sensitivity of influenza A variants to amantadine and the clinical response to therapy has not been established.

    Pharmacokinetics

    Amantadine is well absorbed orally. Maximum plasma concentrations are directly related to dose for doses up to 200 mg/day. Doses above 200 mg/day may result in a greater than proportional increase in maximum plasma concentrations. It is primarily excreted unchanged in the urine by glomerular filtration and tubular secretion. Eight metabolites of amantadine have been identified in human urine. One metabolite, an N-acetylated compound, was quantified in human urine and accounted for 5-15% of the administered dose. Plasma acetylamantadine accounted for up to 80% of the concurrent amantadine plasma concentration in 5 of 12 healthy volunteers following the ingestion of a 200 mg dose of amantadine. Acetylamantadine was not detected in the plasma of the remaining seven volunteers.

    There appears to be a relationship between plasma amantadine concentrations and toxicity. As concentration increases toxicity seems to be more prevalent, however absolute values of amantadine concentrations associated with adverse effects have not been fully defined.

    After the oral administration of a single 100 mg amantadine hydrochloride capsule, several studies showed mean maximum plasma concentrations of 0.2 to 0.4 mcg/mL and mean times to peak concentration of 2.5 to 4 hours. Mean half-lives ranged from 10 to 14 hours. Across other studies, amantadine plasma half-life has averaged 16 ± 6 hours (range 9 to 31 hours) in 19 healthy volunteers.

    Plasma amantadine clearance ranged from 0.2 to 0.3 L/hr/kg after the administration of 5 mg to 25 mg intravenous doses of amantadine to 15 healthy volunteers.

    In six healthy volunteers, the ratio of amantadine renal clearance to apparent oral plasma clearance was 0.79 ± 0.17 (mean ± SD).

    The volume of distribution determined after the intravenous administration of amantadine to 15 healthy subjects was 3 to 8 L/kg, suggesting tissue binding. Amantadine, after single oral 200 mg doses to 6 healthy young subjects and to 6 healthy elderly subjects has been found in nasal mucus at mean ± SD concentrations of 0.15 ± 0.16, 0.28 ± 0.26, and 0.39 ± 0.34 mcg/g at 1.4 and 8 hours after dosing, respectively. These concentrations represented 31 ± 33%, 59 ± 61% and 95 ± 86% of the corresponding plasma amantadine concentrations. Amantadine is approximately 67% bound to plasma proteins over a concentration range of 0.1 to 2.0 mcg/mL. Following the administration of amantadine 100 mg as a single dose, the mean ± SD red blood cell to plasma ratio ranged from 2.7 ± 0.5 in 6 healthy subjects to 1.4 ± 0.2 in 8 patients with renal insufficiency.

    The apparent oral plasma clearance of amantadine is reduced and the plasma half-life and plasma concentrations are increased in healthy elderly individuals age 60 and older. After single dose administration of 25 to 75 mg to 7 healthy, elderly male volunteers, the apparent plasma clearance of amantadine was 0.10 ± 0.04 L/hr/kg (range 0.06 to 0.17 L/hr/kg) and the half-life was 29 ± 7 hours (range 20 to 41 hours). Whether these changes are due to decline in renal function or other age related factors is not known.

    Compared with otherwise healthy adult individuals, the clearance of amantadine is significantly reduced in adult patients with renal insufficiency. The elimination half-life increases two to three fold or greater when creatinine clearance is less than 40 mL/min/1.73 m2 and averages eight days in patients on chronic maintenance hemodialysis. Amantadine is removed in negligible amounts by hemodialysis.

    The pH of the urine has been reported to influence the excretion rate of amantadine. Since the excretion rate of amantadine increases rapidly when the urine is acidic, the administration of urine acidifying drugs may increase the elimination of the drug from the body.

    Indications and Dosage
    Amantadine hydrochloride capsules are indicated for the prophylaxis and treatment of signs and symptoms of infection caused by various strains of influenza A virus. Amantadine hydrochloride capsules are also indicated in the treatment of parkinsonism and drug-induced extrapyramidal reactions.

    Influenza A Prophylaxis

    Amantadine hydrochloride capsules are indicated for chemoprophylaxis against signs and symptoms of influenza A virus infection when early vaccination is not feasible or when the vaccine is contraindicated or not available. In the prophylaxis of influenza, early vaccination on an annual basis as recommended by the Centers for Disease Control's Immunization Practices Advisory Committee is the method of choice. Because amantadine does not completely prevent the host immune response to influenza A infection, individuals who take this drug may still develop immune responses to natural disease or vaccination and may be protected when later exposed to antigenically related viruses. Following vaccination during an influenza A outbreak, amantadine prophylaxis should be considered for the 2 to 4 week time period required to develop an antibody response.

    Influenza A Treatment

    Amantadine hydrochloride capsules are also indicated in the treatment of uncomplicated respiratory tract illness caused by influenza A virus strains especially when administered early in the course of illness. There are no well-controlled clinical studies demonstrating that treatment with amantadine hydrochloride will avoid the development of influenza A virus pneumonitis or other complications in high risk patients.

    There is no clinical evidence indicating that amantadine is effective in the prophylaxis or treatment of viral respiratory tract illnesses other than those caused by influenza A virus strains.

    Parkinson's Disease/Syndrome

    Amantadine is indicated in the treatment of idiopathic Parkinson's disease (Paralysis Agitans), postencephalitic parkinsonism and symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication. It is indicated in those elderly patients believed to develop parkinsonism in association with cerebral arteriosclerosis. In the treatment of Parkinson's disease, amantadine is less effective than levodopa, (-)-3-(3,4-dihydroxyphenyl) L-alanine, and its efficacy in comparison with the anticholinergic antiparkinson drugs has not yet been established.

    Drug-induced Extrapyramidal REACTIONS

    Amantadine hydrochloride is indicated in the treatment of drug-induced extrapyramidal reactions. Although anticholinergic-type side effects have been noted with amantadine when used in patients with drug-induced extrapyramidal reactions, there is a lower incidence of these side effects than that observed with the anticholinergic antiparkinson drugs.

    DOSAGE AND ADMINISTRATION

    The dose of amantadine hydrochloride may need reduction in patients with congestive heart failure, peripheral edema, orthostatic hypotension, or impaired renal function (see Dosage for Impaired Renal Function).

    Dosage for Prophylaxis and Treatment of Uncomplicated Influenza A Virus Illness

    Adult: The adult daily dosage of amantadine hydrochloride is 200 mg, two 100 mg capsules as a single daily dose. The daily dosage may be split into one capsule of 100 mg twice a day. If central nervous system effects develop in once-a-day dosage, a split dosage schedule may reduce such complaints. In persons 65 years of age or older, the daily dosage of amantadine hydrochloride is 100 mg.

    A 100 mg daily dose has also been shown in experimental challenge studies to be effective as prophylaxis in healthy adults who are not at high risk for influenza-related complications. However, it has not been demonstrated that a 100 mg daily dose is as effective as a 200 mg daily dose for prophylaxis nor has the 100 mg daily dose been studied in the treatment of acute influenza illness. In recent clinical trials, the incidence of central nervous system (CNS) side effects associated with the 100 mg daily dose was at or near the level of placebo. The 100 mg dose is recommended for persons who have demonstrated intolerance to 200 mg of amantadine hydrochloride daily because of CNS or other toxicities.

    Children 1 yr.-9 yrs. of age: The total daily dose should be calculated on the basis of 2 to 4 mg/lb/day (4.4 to 8.8 mg/kg/day), but not to exceed 150 mg per day.

    Amantadine hydrochloride syrup should be used for ease and flexibility in administering doses not in 100 mg increments.

    Children 9 yrs.-12 yrs. of age: The total daily dose is 200 mg given as one capsule of 100 mg twice a day. The 100 mg daily dose has not been studied in children. Therefore, there are no data which demonstrate that this dose is as effective as or is safer than the 200 mg daily dose in this patient population.

    Prophylactic dosing should be started in anticipation of an influenza A outbreak and before or after contact with individuals with influenza A virus respiratory tract illness.

    Amantadine should be continued daily for at least 10 days following a known exposure. If amantadine is used chemoprophylactically in conjunction with inactivated influenza A virus vaccine until protective antibody responses develop, then it should be administered for 2 to 4 weeks after the vaccine has been given. When inactivated influenza A virus vaccine is unavailable or contraindicated, amantadine should be administered for the duration of known influenza A in the community because of repeated and unknown exposure.

    Treatment of influenza A virus illness should be started as soon as possible, preferably within 24 to 48 hours after onset of signs and symptoms, and should be continued for 24 to 48 hours after the disappearance of signs and symptoms.

    Dosage for Parkinsonism

    Adult: The usual dose of amantadine hydrochloride is 100 mg twice a day when used alone. Amantadine has an onset of action usually within 48 hours.

    The initial dose of amantadine hydrochloride 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, if necessary.

    Occasionally, patients whose responses are not optimal with amantadine hydrochloride at 200 mg daily may benefit from an increase up to 400 mg daily in divided doses. However, such patients should be supervised closely by their physicians.

    Patients initially deriving benefit from amantadine not uncommonly experience a fall-off of effectiveness after a few months. Benefit may be regained by increasing the dose to 300 mg daily. Alternatively temporary discontinuation of amantadine for several weeks, followed by reinitiation of the drug, may result in regaining benefit in some patients. A decision to use other antiparkinson drugs may be necessary.

    Dosage for Concomitant Therapy

    Some patients who do not respond to anticholinergic antiparkinson drugs may respond to amantadine. When amantadine or anticholinergic antiparkinson drugs are each used with marginal benefit, concomitant use may produce additional benefit.

    When amantadine and levodopa are initiated concurrently, the patient can exhibit rapid therapeutic benefits. Amantadine should be held constant at 100 mg daily or twice daily while the daily dose of levodopa is gradually increased to optimal benefit.

    When amantadine is added to optimal well-tolerated doses of levodopa, additional benefit may result, including smoothing out the fluctuations in improvement which sometimes occur in patients on levodopa alone. Patients who require a reduction in their usual dose of levodopa because of development of side effects may possibly regain lost benefit with the addition of amantadine.

    Dosage for Drug Induced Extrapyramidal


    Adult: The usual dose of amantadine hydrochloride is 100 mg twice a day. Occasionally patients whose responses are not optimal with amantadine hydrochloride at 200 mg daily may benefit from an increase up to 300 mg daily in divided doses.

    Dosage for Impaired Renal Function

    Depending upon creatinine clearance, the following dosage adjustments are recommended:

    CREATININE CLEARANCE AMANTADINE HYDROCHLORIDE DOSAGE
    (mL/min/1.73m2)
    30-50 200 mg 1st day and 100 mg
    each day thereafter
    15-29 200 mg 1st day followed by 100 mg
    on alternate days
    <15 200 mg every 7 days

    The recommended dosage for patients on hemodialysis is 200 mg every 7 days.

    HOW SUPPLIED

    Amantadine Hydrochloride Capsules are available in bottles of 100, and 500 capsules. Each red, gelatin capsule contains 100 mg amantadine hydrochloride and is imprinted with INV and 211.

    Bottles of 100 NDC 62269-211-24
    Bottles of 500 NDC 62269-211-29

    Adverse Reactions
    The adverse reactions reported most frequently at the recommended dose of amantadine (5-10%) are: nausea, dizziness (lightheadedness), and insomnia.

    Less frequently (1-5%) reported adverse reactions are: depression, anxiety and irritability, hallucinations, confusion, anorexia, dry mouth, constipation, ataxia, livedo, raticularis, peripheral edema, orthostatic hypotension, headache, somnolence, nervousness, dream abnormality, agitation, dry nose, diarrhea and fatigue.

    Infrequently (0.1-1%) occurring adverse reactions are: congestive heart failure, psychosis, urinary retention, dyspnea, fatigue, 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.

    Rare (less than 0.1%) occurring adverse reactions are: instance of convulsion, leukopenia, neutropenia, eczematoid dermatitis, oculogyric episodes, suicidal attempt, suicide, and suicidal ideation (see WARNINGS

    Drug Interactions
    Careful observation is required when amantadine is administered concurrently with central nervous system stimulants.

    Coadministration of thioridazine has been reported to worsen the tremor in elderly patients with Parkinson's disease; however, it is not known if other phenothiazines produce a similar response.

    Coadministration of triamterene and hydrochlorothiazide capsules resulted in a higher plasma amantadine concentration in a 61 year old man receiving amantadine (amantadine hydrochloride) 100 mg TID for Parkinson's disease.1 It is not known which of the components of triamterene and hydrochlorothiazide capsules contributed to the observation or if related drugs produce a similar response.

    Warnings and Precautions
    Deaths

    Deaths have been reported from overdose with amantadine. The lowest reported acute lethal dose was 2 grams. Acute toxicity may be attributable to the anticholinergic effects of amantadine. Drug overdose has resulted in cardiac, respiratory, renal or central nervous system toxicity. Cardiac dysfunction includes arrhythmia tachycardia and hypertension

    Suicide Attempts

    Suicide attempts, some of which have been fatal, have been reported in patients treated with amantadine, many of whom received short courses for influenza treatment or prophylaxis. The incidence of suicide attempts is not known and the pathophysiologic mechanism is not understood. Suicide 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.

    CNS Effects

    Patients with a history of epilepsy of other "seizures" should be observed closely for possible increased seizure activity.

    Patients receiving amantadine who note central nervous system effects of blurring of vision should be cautioned against driving or working in situations where alertness and adequate motor coordination are important.

    Other

    Patients with a history of congestive heart failure 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.

    PRECAUTIONS

    Amantadine should not be discontinued abruptly in patients with Parkinson's disease since a few patients have experienced a parkinsonian crisis, i.e. a sudden marked clinical deterioration when this medication was suddenly stopped. The dose of anticholinergic drugs or of amantadine should be reduced if atropine-like effects appear when these drugs are used concurrently.

    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 characterized 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 creatine phosphokinase elevation, leukocytosis and increased serum myoglobin.

    The early diagnosis of this condition is important for the appropriate management of these patients. Considering NMS as a possible diagnosis and ruling out other acute illnesses (e.g. pneumonia, systemic infection, etc.) is essential. This may be especially complex if the clinical presentation includes both serious medical illness 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 central nervous system (CNS) pathology.

    The management of NMS should include: 1) intensive symptomatic treatment and medical monitoring and 2) treatment of any concomitant serious medical problems for which specific treatments are available. Dopamine agonists such as bromocriptine, and muscle relaxants, such as dantrolene are often used in the treatment of NMS; however, their effectiveness has not been demonstrated in controlled studies.

    Other

    Because amantadine is mainly excreted in the urine, it accumulates in the plasma and in the body when renal function declines. Thus, the dose of amantadine should be reduced in patients with renal impairment and in individuals who are 65 years of age or older. The dose of amantadine may need careful adjustment in patients with congestive heart failure, peripheral edema, or orthostatic hypotension.

    Care should 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 enzymes have been reported in patients receiving amantadine, though a specific relationship between the drug and such changes has not been established.

    Drug Interactions

    See DRUG INTERACTIONS section.

    Carcinogenesis, Mutagenesis, Impairment of Fertility

    Long-term in vivo animal studies designed to evaluate the carcinogenic potential of amantadine have not been performed. In several in vitro assays for gene mutation, amantadine did not increase the number of spontaneously observed mutations in four strains of Salmonella typhimurium (Ames Test) or in a mammalian cell line (Chinese Hamster Ovary cells) when incubations were performed either with or without a liver metabolic activation extract. Further, there was no evidence of chromosome damage observed in an in vitro test using freshly derived and stimulated human peripheral blood lymphocytes (with and without metabolic activation) or in an in vivo mouse bone marrow micronucleus test (140-550 mg/kg, estimated human equivalent doses of 11.7-45.8 mg/kg based on body surface area conversion).

    In a three litter reproduction study in rats, amantadine at a dose of 32 mg/kg/day (estimated human equivalent dose of 4.5 mg/kg/day based on body surface area conversions) administered to both males and females slightly impaired fertility. There were no effects on fertility at a dose level of 10 mg/kg/day (estimated human equivalent dose of 1.4 mg/kg/day); intermediate doses were not tested.

    Pregnancy

    Teratogenic Effects

    Pregnancy Category C: Amantadine has been shown to be embryotoxic and teratogenic in rats at 50 mg/kg/day (estimated human equivalent dose of 7.1 mg/kg/day based on body surface area conversion), while a dose of 37 mg/kg/day (estimated human equivalent dose of 5.3 mg/kg/day) was without effect. Embryotoxic and teratogenic effects were not seen in rabbits that received 32 mg/kg/day (estimated human equivalent dose of 9.6 mg/kg/day, based on body surface area conversion). There are no adequate and well-controlled studies in pregnant women. Amantadine should be used during pregnancy only if the potential benefit justifies the potential risk to the embryo or fetus.

    Nursing Mothers

    Amantadine is excreted in human milk. Use is not recommended in nursing mothers.

    Pediatric Use

    The safety and efficacy of amantadine in newborn infants and infants below the age of 1 year have not been established.

    Usage in the Elderly

    Because amantadine is primarily excreted in the urine, it accumulates in the plasma and in the body when renal function declines. Thus, the dose of amantadine should be reduced in patients with renal impairment and in individuals who are 65 years of age or older. The dose of amantadine may need reduction in patients with congestive heart failure, peripheral edema, or orthostatic hypotension (see DOSAGE AND ADMINISTRATION).

    Overdosage
    Deaths have been reported from overdose with amantadine. The lowest reported acute lethal dose was 2 grams. Acute toxicity may be attributable to the anticholinergic effects of amantadine. Drug overdose has resulted in cardiac, respiratory, renal or central nervous system toxicity. Cardiac dysfunction includes arrhythmia, tachycardia and hypertension. Pulmonary edema and respiratory distress (including adult respiratory distress Syndrome - ARDS) have been reported renal dysfunction including increased BUN, decreased creatinine clearance and renal insufficiency can occur. Central nervous system effects that have been reported include insomnia, anxiety, aggressive behavior, hypertonia, hyperkinesia, tremor, confusion, disorientation, depersonalization, fear, delirium, hallucination, psychotic reactions, lethargy, somnolence and coma. Seizures may be exacerbated in patients with prior history of Seizure disorders. Hyperthermia has also been observed in cases where a drug overdose has occurred.

    There is no specific antidote for an overdose of amantadine. However, slowly administered intravenous physostigmine in 1 and 2 mg doses in an adult2 at 1 to 2 hour intervals and 0.5 mg doses in a child3 at 5 to 10 minute intervals up to a maximum of 2 mg/hour have been reported to be effective in the control of central nervous system 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 intravenously. Hemodialysis does not remove significant amounts of amantadine: in patients with renal failure, a four hour hemodialysis removed 7 to 15 mg after a single 300 mg oral dose.4 The pH of the urine has been reported to influence the excretion rate of amantadine. Since the excretion rate of amantadine increases rapidly when the urine is acidic, the administration of urine acidifying drugs 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 hyperactivity and convulsions; if required, sedation, and anticonvulsant therapy should be administered. The patient should be observed for the possible development of arrhythmias and hypotension; if required, appropriate antiarrhythmic and antihypotensive therapy should be given. The blood electrolytes urine pH and urinary output should be monitored. If there is no record of recent voiding, catheterization should be done.

    CONTRAINDICATIONS

    Amantadine hydrochloride is contraindicated in patients with known hypersensitivity to the drug.

  9. #9
    Junior Member
    Join Date
    Dec 2001
    Location
    Sydney
    Posts
    14
    Thanks rtr for the Amantadine info. It seems that was the culprit and the shakes, stutters and blurry vision have stopped now this has ben cancelled.
    Wise, I emailed you but no reply but dont worry we seem to be back on track now. I guess we just get scared when there are adverse effects and no one can offer any advice.
    So pain is now more under control and Luke is pressing on with re-hab slowly as there are stil liver, gut and bladder problems holding us up

  10. #10
    Will,

    I'm glad Luke is doing better. It only takes one experience like this to realize that doctors don't know everything. Keep researching things on your own. Don't ever agree with a doctor unless you understand what he/she is doing, why it is being done, and any potential consequences. Don't hesitate to ask people here for an opinion. From the messages in other forums right now, you can see that we have more than enough opinions to go around.

    Good luck to both of you.

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