Levodopa Other names: L-dopa L-3,4-dihydroxyphenylalanine

The use of selective MAO-B inhibitors (e.g. rasagiline, selegiline, and safinamide) with levodopa may be associated with orthostatic hypotension. Patients who are taking these medicinal products should be monitored closely.

Anticholinergic medicinal products can work synergistically with levodopa, in order to improve tremor. Concurrent use can, however, cause a worsening of involuntary motor disorders. Anticholinergic medicinal products may impair the effect of oral levodopa medicinal products, due to a delayed absorption. A dose adjustment of levodopa may be required.

Inhaled levodopa has not been studied in patients with hepatic impairment. It is recommended to administer this medicinal product cautiously to patients with severe hepatic impairment.

Inhaled levodopa has not been studied in patients with renal impairment. It is recommended to administer this medicinal product cautiously to patients with severe renal disease.

There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and a levodopa/dopa-decarboxylase inhibitor.

Symptomatic postural hypotension has occurred when combinations of levodopa and a dopa-decarboxylase inhibitor are added to the treatment of patients already receiving certain antihypertensives. Dose adjustment of the antihypertensive medicinal products may be required during concomitant use of levodopa.

Dopamine D2 receptor antagonists (e.g. phenothiazines, butyrophenones, risperidone, metoclopramide) and isoniazid may reduce the effectiveness of levodopa. Patients who are taking these medicinal products should be monitored for worsening Parkinson's symptoms.

Concurrent administration of levodopa and amantadine may increase confusion, hallucinations, nightmares, gastro-intestinal disturbances, or other atropine-like side effects. Psychotic reactions have been observed in patients receiving amantadine and levodopa.

The addition of entacapone to a levodopa/dopa-decarboxylase inhibitor has been demonstrated to increase the levodopa bioavailability by 30%. A dose adjustment of levodopa may be required with concomitant use of COMT inhibitors.

Iron salts or multivitamins containing iron salts can form chelates with levodopa and consequently reduce the bioavailability of levodopa.

Levodopa may cause increased intraocular pressure in patients with glaucoma. Patients with chronic glaucoma may be treated cautiously with levodopa provided the intraocular pressure is well-controlled and the patient is monitored carefully for changes in intraocular pressure during therapy.

Levodopa should be administered cautiously to patients with a history of peptic ulcer disease (because of the possibility of upper gastro-intestinal haemorrhage).

Inhaled levodopa should be administered with caution in patients with severe cardiovascular disease. Care should be exercised when levodopa is administered to patients with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias. Cardiac function should be monitored with particular care in such patients during the initiation of treatment with levodopa.

Patients with a major psychotic disorder or a history of psychotic disorder must be treated cautiously with a levodopa/dopa-decarboxylase inhibitor because of the risk of exacerbating psychosis. In addition, certain medicinal products used to treat psychosis may exacerbate the symptoms of Parkinson's disease and may decrease the effectiveness of levodopa. Concomitant use of antipsychotics should be monitored carefully for worsening of Parkinson's motor symptoms especially when D2-receptor antagonists are used.

Because of the risk of bronchospasm, use of levodopa inhalation powder in patients with asthma, chronic obstructive pulmonary disease (COPD), or other chronic underlying lung disease is not recommended. There is limited data regarding chronic effect of inhaled levodopa in respiratory compromised patients.

There are no or limited amount of data from the use of levodopa in pregnant women. Studies in animals have shown reproductive toxicity. Levodopa is not recommended during pregnancy and in women of childbearing potential not using contraception.

Levodopa is excreted in human milk. There is insufficient information on the effects of levodopa in newborns/infants. Breast-feeding should be discontinued during treatment with levodopa.

Fertility

There are no data on the effects of levodopa on human fertility. Animal studies indicated no effect on fertility.

Levodopa may have a major influence on the ability to drive and use machines. Certain side effects such as sleepiness and dizziness, that have been reported with other forms of levodopa medicinal products, may affect some patients' ability to drive or use machines.

Patients being treated with levodopa medicinal products and presenting with somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (e.g. use machines), until such recurrent episodes and somnolence have resolved.

Summary of safety profile

The most frequent adverse reactions reported in the levodopa clinical studies were cough (15.6%), fall (8.7%), upper respiratory tract infection (5.8%), dyskinesia (5.7%) and sputum discoloured (2.8%). Serious adverse reactions of allergic oedema have been reported with levodopa medicinal products but not in clinical studies with levodopa. A symptom complex resembling neuroleptic malignant syndrome and rhabdomyolysis may occur with levodopa/dopa-decarboxylase inhibitor medicinal products, although no cases have been identified in clinical studies with levodopa. Gastrointestinal haemorrhage has been reported with levodopa medicinal products and was observed once in levodopa clinical studies.

Tabulated list of adverse reactions

Adverse reactions are presented by system organ class and frequency in the table below. Frequency categories are defined as follows: very common (≥1/10), common (≥1/100 to <1/10), not known (cannot be estimated from the available data).

Adverse reactions:

^a Cardiac rhythm disorder here is a combined term representing atrial fibrillation, atrial flutter, atrioventricular block, bundle branch block, sick sinus syndrome, bradycardia, and tachycardia.

Description of selected adverse reactions

Sudden sleep onset

Levodopa is associated with somnolence and has been associated very rarely with excessive daytime somnolence and sudden sleep onset episodes.

Impulse control disorders

Pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa.

Coughing

Most cough reported in the clinical studies with levodopa were mild to moderate in intensity, and usually reported within the first 30 days of the treatment. Due to cough, 2% of subjects withdrew from the clinical studies with levodopa.

Sensation of choking

In post-marketing experience, there have been reports of the sensation of choking associated with the drug powder impacting the back of the throat, immediately following administration.