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Levodopa Side Effects

Applies to levodopa: compounding powder, oral capsule, oral tablet


Although the optimal timing of the initiation of levodopa therapy is controversial, some investigators have suggested that early treatment of parkinsonism with levodopa delays disease progression and decreases mortality.[Ref]

Nervous system

Nervous system side effects most frequently reported have included involuntary movements and mental status changes (in as many as 50% of treated patients on long-term therapy). The types of involuntary movements due to levodopa have been characterized as choreiform, dystonic and dyskinetic. Fluctuations in motor function occur frequently and often increase as the duration of therapy increases.[Ref]

Choreiform movements due to levodopa therapy may occur in as many as 80% of patients treated for one year and frequently involve facial grimacing, exaggerated chewing, and twisting and protrusion of the tongue.

Several types of motor fluctuations may occur and result in "bradykinetic episodes". Some motor fluctuations are related to the timing of dosage administration. For example, patients may experience "peak of the dose dyskinesia" and a wearing-off effect called "end of the dose akinesia". The "wearing-off effect may result in early morning dystonia. Such motor fluctuations may be managed by increasing the frequency of dosage administration and decreasing the dose administered to achieve a smoother therapeutic effect.

Other motor fluctuations are not related to the timing of dose administration. Such fluctuations are characterized by sudden loss of levodopa effect which may last for minutes to hours and result in akinesia followed by a sudden return of levodopa effect. These "on-off" fluctuations may occur many times per day. "On-off" fluctuations may respond to more frequent dose administration.

Finally, akinesia paridoxica is a sudden episode of akinesia which occurs as patients begin to walk. Akinesia paridoxica frequently results in falls and often responds to levodopa dose reductions.

Other adverse nervous system effects due to levodopa include myoclonus, sleep disturbances (including insomnia, daytime somnolence, altered dreams and episodic nocturnal myoclonus), Meige's syndrome (blepharospasm-oromandibular dystonia) and ocular dyskinesia. In addition, the orofacial movements induced by levodopa have occasionally been reported to cause severe dental erosion.

Some investigators have suggested that levodopa may cause brain dysfunction and may have negative effects on cognitive performance. Levodopa "drug holidays" have been proposed by some investigators as potentially beneficial (perhaps by causing dopamine receptor resensitization). However, the therapeutic value of these drug holidays is controversial.[Ref]


Exacerbation of preexisting ulcer disease with severe upper gastrointestinal bleeding has been reported.[Ref]

Gastrointestinal side effects most commonly reported have included nausea and vomiting. Anorexia and gastrointestinal hemorrhage have been reported rarely.[Ref]


Some authors have suggested that clozapine may be useful in the management of levodopa-induced psychotic symptoms.

Other investigators have suggested that levodopa may induce alterations in the noradrenergic systems of the CNS which may lead to panic attacks.[Ref]

Psychiatric side effects have included hallucinations (particularly visual hallucinations), psychosis, confusion, anxiety, mania, hypomania, depression, rapid mood cycling, nightmares, and hypersexuality.[Ref]


Fever, altered consciousness, autonomic dysfunction and muscle rigidity are the hallmarks of the neuroleptic malignant syndrome. The neuroleptic malignant syndrome (NMS) is associated with a case fatality rate of about 20%. If withdrawal of dopaminergic therapy is suspected as the cause of NMS, dopaminergic therapy should be restarted. If a neuroleptic agent is suspected as the cause, the neuroleptic agent should be immediately discontinued. For patients with NMS suspected to be due to neuroleptic therapy, consideration should be given to dantrolene (or bromocriptine) administration. Intensive monitoring and supportive care are indicated for all patients with NMS.[Ref]

Sudden discontinuation or rapid tapering of levodopa therapy may result in acute worsening of parkinsonism or, less frequently, in a syndrome resembling the neuroleptic malignant syndrome. Cases of psychologic levodopa addiction have also been reported rarely.[Ref]


Some authors have reported marked hemodynamic and clinical improvements in patients with congestive heart failure treated with oral levodopa. However, at least one author has reported marked hemodynamic deterioration following such treatment.[Ref]

Cardiovascular side effects have included hypotension and syncope. Arrhythmias have also been reported rarely.[Ref]


Dermatologic side effects have included a number of cases of malignant melanoma in patients taking levodopa for Parkinson's Disease. Additionally, several cases of maculopapular skin rashes have been reported in patients taking levodopa-containing drugs.[Ref]

Despite reports of melanoma occurring in levodopa-treated patients, some authors have suggested that a causal association is tenuous and other authors have suggested that levodopa may have an antitumor effect on melanoma. Nevertheless, the manufacturers of levodopa-containing drugs report that either the history of melanoma or the presence of suspicious skin lesions is a contraindication for the use of levodopa-containing drugs.[Ref]


Immunologic side effects have included rare reports of a lupus-like syndrome.[Ref]


Hematologic side effects reported rarely have included severe hemolytic and nonhemolytic anemias.[Ref]


Respiratory side effects have included dyskinesias (occasionally of life-threatening severity).[Ref]


Hepatic side effects have included rare cases of asterixis (without abnormalities of liver function tests). The manufacturer of levodopa-containing products reports that abnormal liver function tests may occur.[Ref]


Endocrine side effects have included elevated urinary vanillylmandelic acid levels which have occasionally led to confusion concerning the diagnosis of pheochromocytoma.[Ref]


Renal side effects have included hypokalemia and hyponatremia. Chronic administration of levodopa may also slightly but significantly increase BUN without changes in the glomerular filtration rate.[Ref]


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Some side effects may not be reported. You may report them to the FDA.