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

Chemical formula: C₉H₁₁NO₄  Molecular mass: 197.188 g/mol  PubChem compound: 6047

Interactions

Levodopa interacts in the following cases:

Selective MAO-B inhibitors

The use of selective MAO-B inhibitors with levodopa may be associated with orthostatic hypotension. Monitor patients who are taking these drugs concurrently.

Dopamine D₂ receptor antagonists, isoniazid

Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone, metoclopramide) and isoniazid may reduce the effectiveness of levodopa. Monitor patients for worsening Parkinson’s symptoms.

Iron salts

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

Dyskinesia

Levodopa may cause or exacerbate dyskinesias. If troublesome dyskinesias occur, prescribers may need to consider stopping treatment with levodopa and/or adjusting the patient’s daily medications for the treatment of Parkinson’s disease. In one study, 4% of patients treated with levodopa 84 mg reported dyskinesia, compared with 1% for patients on placebo.

Glaucoma

Levodopa may cause increased intraocular pressure in patients with glaucoma. Monitor patients for increased intraocular pressure during therapy with levodopa.

Falling asleep, somnolence

Patients treated with levodopa, the active ingredient in levodopa, have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes resulted in accidents. Although many of these patients reported somnolence, some reported no warning signs (sleep attack) and believed that they were alert immediately prior to the event. Some of these events have been reported more than 1 year after the initiation of treatment.

Prescribers should reassess patients for drowsiness or sleepiness. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities.

Before initiating treatment with levodopa, advise patients about the potential to develop drowsiness and ask about factors that may increase the risk for somnolence with levodopa such as the concomitant use of sedating medications and the presence of sleep disorders. Consider discontinuing levodopa in patients who report significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.).

If treatment with levodopa continues, patients should be advised not to drive and to avoid other activities that might result in harm if the patients become somnolent. There is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.

Impulse control, compulsive behaviors

Patients treated with levodopa can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone. In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued.

Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with levodopa. Consider stopping the medication if a patient develops such urges while taking levodopa.

Hallucinations, psychosis

In placebo-controlled trials, hallucinations were reported in less than 2% of patients treated with levodopa. Hallucinations may be responsive to reducing levodopa therapy. Hallucinations may be accompanied by confusion, insomnia, and excessive dreaming. Abnormal thinking and behavior may present with one or more symptoms, including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.

Because of the risk of exacerbating psychosis, patients with a major psychotic disorder should ordinarily not be treated with levodopa. In addition, medications that antagonize the effects of dopamine used to treat psychosis may exacerbate the symptoms of Parkinson’s disease and may decrease the effectiveness of levodopa.

Bronchospasm, asthma, COPD, chronic lung disease

Because of the risk of bronchospasm, use of levodopa in patients with asthma, COPD, or other chronic underlying lung disease is not recommended.

In a double-blind, placebo-controlled, crossover clinical study, 25 otherwise healthy subjects with mild or moderate asthma on a stable regimen of asthma medication received placebo or levodopa 84 mg every 4 hours for a total of three doses. Cough was the most frequent adverse reaction, reported by 60% of subjects following administration of levodopa and 0% following administration of placebo. Following administration of levodopa, 10 subjects (40%) had temporary reductions from baseline (between 15% and 59%) for FEV1; 4 of these subjects also had a reduction in FEV1 following administration of placebo. Subjects with a reduction in FEV1 remained asymptomatic and did not require rescue treatment.

Pregnancy

Risk Summary

There are no adequate data on the developmental risk associated with the use of levodopa in pregnant women. In animal studies, carbidopa/levodopa has been shown to be developmentally toxic (including teratogenic effects) [see Data]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Data

Animal Data

When administered to pregnant rabbits throughout organogenesis, carbidopa/levodopa caused both visceral and skeletal malformations in rabbits. No teratogenic effects were observed when carbidopa/levodopa was administered to pregnant mice throughout organogenesis.

There was a decrease in the number of live pups delivered by rats receiving carbidopa/levodopa during organogenesis.

Nursing mothers

Risk Summary

The prolactin-lowering action of dopamine suggests that levodopa may interfere with lactation, although there are limited data on the effects of levodopa on milk production in lactating women.

Levodopa has been detected in human milk. There are no adequate data on the effects of levodopa on the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for levodopa and any potential adverse effects on the breastfed infant from levodopa or from the underlying maternal condition.

Carcinogenesis, mutagenesis and fertility

Carcinogenesis

In rats, oral administration of carbidopa/levodopa for two years resulted in no evidence of carcinogenicity.

Mutagenesis

Studies to assess the potential mutagenic or clastogenic effects of levodopa have not been conducted.

Impairment of Fertility

In reproduction studies in rats, oral administration of carbidopa/levodopa resulted in no effects on fertility.

Adverse reactions


  • Falling Asleep During Activities of Daily Living and Somnolence
  • Withdrawal-Emergent Hyperpyrexia and Confusion
  • Hallucinations/Psychosis
  • Impulse Control/Compulsive Behaviors
  • Dyskinesia
  • Bronchospasm in Patients with Lung Disease
  • Glaucoma

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adverse Reactions in Study 1

Table 1 lists the adverse reactions that occurred in at least 2% of patients with Parkinson’s disease who were treated with levodopa 84 mg and higher than placebo for OFF periods in Study 1. Study 1 was a double-blind, placebo-controlled study, in which 114 patients received levodopa 84 mg (two 42 mg capsules) for an average of 2 doses per day, to a maximum of 5 times a day, and 112 patients received placebo. levodopa-treated patients were 45-82 years of age (mean 63.5 years of age) and were predominantly male (72%) and white (94%). All patients were also treated with oral carbidopa/levodopa. The most common adverse reactions (≥5% and higher than placebo) in Study 1 were cough, nausea, upper respiratory tract infection, and sputum discolored.

Table 1. Adverse Reactions at an Incidence ≥2% and More Frequent with Levodopa than with Placebo in Study 1:

Adverse Reactions Levodopa 84 mg

N=114

%
Placebo

N=112

%
Respiratory, thoracic and mediastinal disorders
Cough 15 2
Sputum discolored 5 0
Nasal discharge discoloration 2 0
Oropharyngeal pain 2 0
Gastrointestinal disorders
Nausea 5 3
Vomiting 3 0
Infections and infestations
Upper respiratory tract infection 6 3
Nasopharyngitis 3 2
Bronchitis/pneumonia 2 0
Nervous system disorders
Dyskinesia 4 1
Headache 2 0
Injury, poisoning and procedural complications
Fall 3 2
Laceration 2 0
Skin abrasion 2 0
General disorders and administration site conditions
Chest discomfort 2 0
Investigations <>
Blood bilirubin increased 2 0
Red blood cell count decreased 2 0
Musculoskeletal and connective tissue disorders
Pain in extremity 2 1
Psychiatric disorders
Insomnia 2 1
Vascular disorders
Orthostatic hypotension/blood pressure decreased 2 0

Adverse Reactions Leading to Discontinuation in Study 1

In Study 1, 6 of 114 patients (5%) in the levodopa 84 mg group and 3 of 112 patients (3%) in the placebo group discontinued because of adverse reactions. The most common of these adverse reactions was cough, which lead to discontinuation in 2% of patients in the levodopa 84 mg group and none in the placebo group.

Postmarketing Experience

The following adverse reaction has been identified during post approval use of levodopa. Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: sensation of choking immediately following administration.

Cross-check medications

Review your medication to ensure that there are no potentially harmful drug interactions or contraindications.

Ask the Reasoner

Related medicines

© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.