Amantadine Side Effects

Not all side effects for amantadine may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to amantadine: oral capsule, oral capsule liquid filled, oral solution, oral syrup, oral tablet

In addition to its needed effects, some unwanted effects may be caused by amantadine. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking amantadine:

Less common
  • Blurred vision
  • confusion
  • difficult urination
  • dizziness or lightheadedness
  • fainting
  • seeing, hearing, or feeling things that are not there
  • swelling of the hands, feet, or lower legs
Rare
  • Convulsions (seizures)
  • decreased vision or any change in vision
  • difficulty in coordination
  • fever, chills, or sore throat
  • increased blood pressure
  • increase in body movements
  • irritation and swelling of the eye
  • loss of memory
  • mental depression
  • severe mood or mental changes
  • skin rash
  • slurred speech
  • thoughts of suicide or attempts at suicide
  • unexplained shortness of breath

Some of the side effects that can occur with amantadine may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Agitation, anxiety, or nervousness
  • difficulty concentrating
  • headache
  • irritability
  • loss of appetite
  • nausea
  • purplish red, net-like, or blotchy spots on the skin
  • trouble in sleeping or nightmares
Less common or rare
  • Constipation
  • decrease in sexual desire
  • diarrhea
  • drowsiness
  • dryness of the mouth, nose, and throat
  • false sense of well-being
  • vomiting
  • unusual tiredness or weakness

For Healthcare Professionals

Applies to amantadine: compounding powder, oral capsule, oral syrup, oral tablet

General

The adverse effects of amantadine are generally mild and, when they occur, may diminish or cease after a week or more on the medication. The most commonly reported side effects have included nausea, dizziness/lightheadedness, and insomnia in 5% to 10% of patients. All side effects, particularly those involving the central nervous system, may be more likely and more severe in patients with renal dysfunction and/or advanced age. Close monitoring for undue adverse effects is highly recommended.[Ref]

Nervous system

Nervous system side effects have included dizziness/lightheadedness and insomnia in 5% to 10% of patients. Hallucinations, confusion, ataxia, headache, somnolence, agitation, and fatigue have been reported in 1% to 5% of patients. Weakness, slurred speech, and hyperkinesia have been reported in 0.1% to 1% of patients and instances of convulsion have been reported in less than 0.1% of patients. At least one case of dropped head syndrome (associated with unbalanced contraction of the neck muscles) has been reported. Neuroleptic malignant syndrome, involuntary muscle contractions, coma, stupor, hypokinesia, hypertonia, gait abnormalities, paresthesia, EEG changes, and tremor have been reported during postmarketing experience. Agitation, hallucinations, stupor, and slurred speech have also occurred after abrupt discontinuation.[Ref]

Most cases of CNS toxicity have occurred in patients with renal insufficiency, seizure disorders, or psychiatric illnesses, and in elderly patients receiving 200 mg/day for influenza prophylaxis.[Ref]

Psychiatric

A case report describes a psychotic episode consisting of abnormal behavior in a young woman following a week of concomitant therapy with Naldecon. The patient had no personal or family history of psychiatric illness and no history of recreational substance use. It is not clear whether the episode was due to the amantadine, the phenylpropanolamine in the Naldecon, or an interaction between the two.

An exacerbation of panic occurred in one patient approximately 2 weeks after the initiation of amantadine therapy for Parkinson's disease. The causal relationship is unclear.

Severe CNS adverse effects have most often been associated with dosages greater than approximately 2 mg/kg/day and/or amantadine blood levels exceeding 1 mcg/mL. Most cases of CNS toxicity have occurred in patients with renal insufficiency, seizure disorders, or psychiatric illnesses, and in elderly patients receiving 200 mg/day for influenza prophylaxis.[Ref]

Psychiatric side effects have included depression, anxiety, irritability, nervousness, and dream abnormality in 1% to 5% of patients. Psychosis, euphoria, thinking abnormality, amnesia, and decreased libido have been reported in 0.1% to 1% of patients and suicidal attempt, suicidal ideation, and suicide have been reported in less than 0.1% of patients. Aggressive behavior, delirium, delusions, manic reaction, paranoid reaction, delusions of parasitosis, pathological gambling, increased libido (including hypersexuality), and impulse control symptoms have been reported during postmarketing experience. Delirium, delusions, paranoid reaction, anxiety, and depression have also occurred after abrupt discontinuation.[Ref]

Gastrointestinal

Gastrointestinal side effects have included nausea in 5% to 10% of patients; diarrhea, constipation, anorexia, and dry mouth in 1% to 5% of patients; and vomiting in 0.1% to 1% of patients. Dysphasia has been reported during postmarketing experience.[Ref]

Cardiovascular

Cardiovascular side effects have included orthostatic hypotension in 1% to 5% of patients, and congestive heart failure and hypertension in 0.1% to 1% of patients. Cardiac arrest, arrhythmias (including malignant arrhythmias), hypotension, and tachycardia have been reported during postmarketing experience.[Ref]

Congestive heart failure with severe lower limb edema was diagnosed in one patient receiving amantadine, but resolved following drug discontinuation. A positive correlation with amantadine therapy could not be established, although no other cause for this patient's heart failure was found.[Ref]

Ocular

At least two cases of decreased visual acuity have been reported following approximately three weeks of amantadine therapy. Both resolved after drug discontinuation. In one case, the visual disturbance was related to a corneal edema similar to that seen with amiodarone.[Ref]

Ocular side effects have included visual disturbance, including punctuate subepithelial or other corneal opacity, corneal edema, decreased visual acuity, sensitivity to light, and optic nerve palsy in 0.1% to 1% of patients and oculogyric episodes in less than 0.1% of patients. Keratitis and mydriasis have been reported during postmarketing experience.[Ref]

Other

Other side effects have included peripheral edema (1% to 5%). Edema and fever have been reported during postmarketing experience.[Ref]

Respiratory

Respiratory side effects have included dry nose (1% to 5%) and dyspnea (0.1% to 1%). Acute respiratory failure, pulmonary edema, and tachypnea have been reported during postmarketing experience.[Ref]

Hematologic

Hematologic side effects have included leukopenia and neutropenia in less than 0.1% of patients. Leukocytosis and agranulocytosis have been reported during postmarketing experience.[Ref]

Dermatologic

Livedo reticularis occurs mainly on the legs. It is generally reversible over weeks to months following drug discontinuation.[Ref]

Dermatologic side effects have included livedo reticularis (1% to 5%), skin rash (0.1% to 1%), and eczematoid dermatitis (less than 0.1%). Pruritus and diaphoresis have been reported during postmarketing experience.[Ref]

Hypersensitivity

Hypersensitivity side effects have included allergic reactions including anaphylactic reactions during postmarketing experience.[Ref]

Genitourinary

Genitourinary side effects have included urinary retention (0.1% to 1%).[Ref]

Renal

Renal side effects have included elevations in BUN and serum creatinine during postmarketing experience.[Ref]

Hepatic

Hepatic side effects have included elevations in bilirubin, GGT, SGOT, and SGPT during postmarketing experience.[Ref]

Metabolic

Metabolic side effects have included elevated alkaline phosphatase and lactate dehydrogenase during postmarketing experience.

Musculoskeletal

Musculoskeletal side effects have included elevated creatine kinase during postmarketing experience.[Ref]

Endocrine

A 66-year-old female patient with Parkinson disease developed syndrome of inappropriate antidiuretic hormone secretion nine days after starting amantadine and entacapone. The patient did not recover following discontinuation of entacapone. Five days after entacapone was stopped, amantadine was discontinued. The patient gradually improved following amantadine discontinuation.[Ref]

Endocrine side effects have included at least one case of syndrome of inappropriate antidiuretic hormone secretion.[Ref]

References

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2. Centers for Disease Control and Prevention "Prevention and control of influenza: recommendations of the advisory committee on immunization practices (ACIP)." MMWR Morb Mortal Wkly Rep 47(RR-6) (1998): 1-26

3. "Antiviral drugs for prophylaxis and treatment of influenza." Med Lett Drugs Ther 47 (2005): 93-5

4. "Product Information. Symmetrel (amantadine)." DuPont Pharmaceuticals, Wilmington, DE.

5. Keyser LA, Karl M, Nafziger AN, Bertino JS "Comparison of central nervous system adverse effects of amantadine and rimantadine used as sequential prophylaxis of influenza A in elderly nursing home patients." Arch Intern Med 160 (2000): 1485-8

6. Bryson YJ, Monahan C, Pollack M, Shields WD "A prospective double-blind study of side effects associated with the admininstration of amantadine for influenza A virus prophylaxis." J Infect Dis 141 (1980): 543-7

7. Millet VM, Dreisbach M, Bryson YJ "Double-blind controlled study of central nervous system side effects of amantadine, rimantadine, and chlorpheniramine." Antimicrob Agents Chemother 21 (1982): 1-4

8. Hayden FG, Hoffman HE, Spyker DA "Differences in side effects of amantadine hydrochloride and rimantadine hydrochloride relate to differences in pharmacokinetics." Antimicrob Agents Chemother 23 (1983): 458-64

9. Millet VM, Dreisbach M, Bryson YJ "Double-blind controlled study of central nervous system side effects of amantadine, rimantadine, and chlorpheniramine." Antimicrob Agents Chemother 21 (1982): 1-4

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

11. Somani SK, Degelau J, Cooper SL, Guay DR, Ehresman D, Zaske D "Comparison of pharmacokinetic and safety profiles of amantadine 50- and 100-mg daily doses in elderly nursing home residents." Pharmacotherapy 11 (1991): 460-6

12. Smith EJ "Amantadine-induced psychosis in a young healthy patient." Am J Psychiatry 165 (2008): 1613

13. Dolin R, Reichman RC, Madore HP, et al "A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A infection." N Engl J Med 307 (1982): 580-4

14. Armbruster KF, Rahn AC, Ing TS, Halper IS, Oyama JH, Klawans HL "Amantadine toxicity in a patient with renal insufficiency." Nephron 13 (1974): 183-6

15. Swick BL, Walling HW "Drug-induced delusions of parasitosis during treatment of Parkinson's disease." J Am Acad Dermatol 53 (2005): 1086-7

16. Noveske FG "Breakthrough panic after amantadine treatment in a parkinson's disease patient." J Clin Psychiatry 57 (1996): 374

17. Degelau J, Somani S, Cooper SL, Irvine PW "Occurrence of adverse effects and high amantadine concentrations with influenza prophylaxis in the nursing home." J Am Geriatr Soc 38 (1990): 428-32

18. Mawdsley C, Williams IR, Pullar IA, Davidson DL, Kinloch NE "Treatment of parkinsonism by amantadine and levodopa." Clin Pharmacol Ther 13 (1972): 575-83

19. Borison RL "Amantadine-induced psychosis in a geriatric patient with renal disease." Am J Psychiatry 136 (1979): 111-2

20. "Antiviral drugs for influenza." Med Lett Drugs Ther 51 (2009): 89-92

21. Stroe AE, Hall J, Amin F "Psychotic episode related to phenylpropanolamine and amantadine in a healthy female." Gen Hosp Psychiatry 17 (1995): 457-8

22. Rizzo M, Biandrate P, Tognoni, Morselli PL "Amantadine in depression: relationship between behavioural effects and plasma levels." Eur J Clin Pharmacol 5 (1973): 226-8

23. Strange KC, Little DW, Blatnik B "Adverse reactions to amantadine prophylaxis of influenza in a retirement home." J Am Geriatr Soc 33 (1991): 700-5

24. Ing TS, Daugirdas JT, Soung LS, et al "Toxic effects of amantadine in patients with renal failure." Can Med Assoc J 120 (1979): 695-8

25. Nestelbaum Z, Siris SG, Rifkin A, Klar H, Reardon GT "Exacerbation of schizophrenia associated with amantadine." Am J Psychiatry 143 (1986): 1170-1

26. Jefferson T, Demicheli V, Rivetti D, Jones M, Di Pietrantonj C, Rivetti A "Antivirals for influenza in healthy adults: systematic review." Lancet 367 (2006): 303-13

27. Kataoka H, Ueno S "Dropped head associated with amantadine in Parkinson disease." Clin Neuropharmacol 34 (2011): 48-9

28. Postma JU, van Tilburg W "Visual hallucinations and delirium during treatment with amantadine (Symmetrel)." J Am Geriatr Soc 23 (1975): 212-5

29. McEvoy JP, McCue M, Spring B, et al "Effects of amantadine and trihexyphenidyl on memory in elderly normal volunteers." Am J Psychiatry 144 (1987): 573-7

30. Silver H, Geraisy N "Effects of biperiden and amantadine on memory in medicated chronic schizophrenic patients - a double-blind cross-over study." Br J Psychiatry 166 (1995): 241-3

31. Beal E "Parkinson disease: Amantadine administration is associated with impulse control disorders in PD." Nat Rev Neurol 7 (2011): 62

32. Salgado JC, Gutknecht DR "A reticular rash." Am J Med 119 (2006): 577-8

33. Vale JA, Maclfan KS "Amantadine-induced heart-failure." Lancet 1 (1977): 548

34. Blanchard DL "Amantadine caused corneal edema." Cornea 9 (1990): 181

35. Pearlman JT, Kadish AH, Ramseyer JC "Vision loss associated with amantadine hydrochloride use." JAMA 237 (1977): 1200

36. Alonso Navarro H, Sanz-Aiz A, Izquierdo L, Jimenez Jimenez FJ "Syndrome of Inappropriate Antidiuretic Hormone Secretion Possibly Associated With Amantadine Therapy in Parkinson Disease." Clin Neuropharmacol 32 (2009): 167-168

37. Simpson DM, Davis GC "Case report of neuroleptic malignant syndrome associated with withdrawal from amantadine." Am J Psychiatry 141 (1984): 796-7

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