LEVO DENK 500

Indications

• Parkinson's disease
• Dopamine-responsive dystonia

Dosage

Children: Refer to the BNF for Children for recommended doses in paediatric patients.

Adults: Refer to the BNF for specific dosing guidelines based on the individual patient's condition and response.

Mechanism of action

Levodopa crosses the blood-brain barrier and is decarboxylated to form dopamine. This supplemental dopamine compensates for the decreased levels of endogenous dopamine due to neurodegeneration. The activation of dopaminergic receptors in the brain, particularly in the caudate nucleus and substantia nigra, leads to improved motor function. The current understanding suggests that the therapeutic effects of levodopa result from its conversion to dopamine by serotonergic terminals and some intrastriatal cells.

Pharmacodynamics

Levodopa is able to penetrate the blood-brain barrier, unlike dopamine. When combined with a peripheral dopa decarboxylase inhibitor, the conversion of levodopa to dopamine outside the brain is minimized, allowing for a higher concentration of levodopa to reach the central nervous system. Once in the brain, levodopa is converted to dopamine by aromatic L-amino-acid decarboxylase, enhancing dopaminergic neurotransmission.

Pharmacokinetics

Levodopa is absorbed from the gastrointestinal tract, with peak plasma concentrations typically occurring within 1 to 2 hours post-administration. Its bioavailability can be influenced by factors such as the presence of food and the use of dopa decarboxylase inhibitors. Levodopa is distributed widely in body tissues and is metabolized primarily in the liver and kidneys. The elimination half-life of levodopa ranges from 1.5 to 2 hours, and it is excreted predominantly as metabolites in the urine.

Contra-indications

• Hypersensitivity to levodopa or any component of the formulation
• Concurrent use of non-selective monoamine oxidase inhibitors (MAOIs)

Adverse effects

• Nausea
• Vomiting
• Orthostatic hypotension
• Dizziness
• Dyskinesia
• Hallucinations
• Confusion
• Sleep disturbances
• Dry mouth

Interactions

• levodopa+linezolid: Severe (increases risk of elevated blood pressure)
• metoclopramide+levodopa: Severe (decreases effects)
• asenapine+levodopa: Moderate (decreases effects)
• risperidone+levodopa: Moderate (decreases effects)
• entacapone+levodopa: Moderate (increases exposure)
• mao-b inhibitors+levodopa: Moderate (increases effects)
• opicapone+levodopa: Moderate (increases exposure)
• tetrabenazine+levodopa: Moderate (decreases effects)
• tolcapone+levodopa: Moderate (increases exposure)
• amisulpride+levodopa: Unknown (decreases effects)

Precautions

• Use with caution in patients with cardiovascular disease
• Monitor for signs of dyskinesia
• May cause hallucinations or confusion, particularly in elderly patients
• Regular monitoring of blood pressure is recommended

Pregnancy

Levodopa should only be used in pregnancy if the potential benefit justifies the potential risk to the fetus. Consultation with a healthcare provider is essential.

Breast-feeding

Levodopa is excreted in breast milk, and caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Tablets
• Oral solution
• Sustained-release formulations

Mechanism of action

Levodopa by various routes crosses the blood brain barrier, is decarboxylated to form dopamine. This supplemental dopamine performs the role that endogenous dopamine cannot due to a decrease of natural concentrations and stimulates dopaminergic receptors. MOST WIDELY ACCEPTED THEORY IS THAT LEVODOPA INCR LEVEL OF DOPAMINE & THUS ACTIVATION OF DOPAMINE RECEPTORS IN EXTRA-PYRAMIDAL CENTERS IN THE BRAIN (PRIMARILY IN CAUDATE NUCLEUS & SUBSTANTIA NIGRA). The present data indicate that the major effects observed after administration of exogenous levodopa are not due to a direct action of levodopa on dopamine receptors, or to extrastriatal release of dopamine, but to conversion of levodopa to dopamine by serotonergic terminals and probably some intrastriatal cells. EFFECTS OF LEVODOPA ON HUMAN & MURINE MELANOMA CELLS EXAMINED. WHEN EXPONENTIALLY GROWING CELLS WERE EXPOSED TO L-DOPA, CHARACTERISTIC INHIBITION OF THYMIDINE INCORPORATION OBSERVED. IN RATS, DOPAMINERGIC AGONISTS ALL CAUSED DECR IN SERUM PROLACTIN LEVELS.

Pharmacodynamics

Levodopa is able to cross the blood-brain barrier while dopamine is not. The addition of a peripheral dopa decarboxylase inhibitor prevents the conversion of levodopa to dopamine in the periphery so that more levodopa can reach the blood-brain barrier. Once past the blood-brain barrier, levodopa is converted to dopamine by aromatic-L-amino-acid decarboxylase.