Clinical Overview: Dhivy for Treating Parkinson Disease or its Manifestations Due to Viral, Environmental Toxins

Parkinson disease (PD) compromises patient mobility by exhibiting resting tremors, bradykinesia, muscular rigidity, and postural imbalance.¹ Similar manifestations occur due to viral encephalitis or environmental exposure to manganese or carbon monoxide.

Reduced dopamine levels following loss of dopamine neurons in the basal ganglia cause these manifestations.¹

Dhivy is a levodopa/carbidopa combination formulation approved by the FDA in November 2021 for the treatment of PD or manifestations due to viral or environmental exposures.² Dhivy tablets differ from previously approved combination formulations by containing 3 “functional scores,” which signify they can be split reliably into 4 equal parts.^3,4

This allows Dhivy to be used for easy dose titration/adjustment and potentially decrease patient costs.^3,4

Mechanism of action²

The enzyme dopa decarboxylase, which is present in brain and peripheral tissues, converts levodopa to dopamine. Increased dopamine levels in the brain alleviates the symptoms of PD or viral/environmental toxins, but causes adverse events in the periphery.

Carbidopa does not cross the blood-brain barrier and, therefore, inhibits peripheral dopa decarboxylase only. Use of carbidopa with levodopa increases levodopa concentration in the brain and reduces adverse events (AEs).

Dosage and administration²

Dhivy tablets contain 100 mg levodopa and 25 mg carbidopa. Splitting the tablet at functional scores yields 4 sections, each containing 25 mg levodopa and 6.25 mg carbidopa.

Prescribers should start their patients on 1 Dhivy tablet 3 times a day and increase it slowly to a maximum of 8 tablets a day, if needed. The goal of therapy is to provide symptom relief with minimal AEs. Hence, clinicians should monitor patients for involuntary movements, blepharospasm, dyskinesias, and nausea during dose titration.

Patients should not discontinue Dhivy suddenly because it can precipitate hyperpyrexia and confusion, mimicking neuroleptic malignant syndrome. If discontinuation is necessary, Dhivy should be tapered slowly.

Pharmacists should counsel patients that Dhivy can be taken with or without food, but protein-rich food or iron-containing products can potentially reduce levodopa’s absorption.

AEs²

Commonly experienced AEs include somnolence/sleep attacks; hallucinations and delusions; increased urge for compulsive behaviors, such as gambling, spending money, eating, and sex; choreiform or dystonic dyskinesias; and nausea. Patients may also experience palpitations, orthostatic hypotension, dark saliva and/or urine, and respiratory/urinary tract infections.

Warnings and precautions²

Dhivy is contraindicated in patients taking non-selective monoamine oxidase inhibitors or those who may be hypersensitive to its constituents. Dopamine antagonists and drugs/OTC products containing iron salts reduce Dhivy’s efficacy and worsen PD manifestations. Prescribers should reduce the dose of antihypertensive drugs if Dhivy is administered concomitantly.

Since drowsiness, compulsive behavior urges, depression, and psychotic manifestations such as hallucinations and delusions are often unrecognized by patients, clinicians should assess these specifically during routine visits. Concomitant sedating medications should be avoided, and pharmacists should advise patients not to operate vehicles or machinery that could cause physical harm.

Dose reduction may reduce the incidence of dyskinesias, impulsive behavior, and hallucinations/delusions, but not of sleep attacks. Prescribers should avoid Dhivy if patients experience psychoses or depression with suicidal ideation.

During initial dose adjustment/titration, prescribers should monitor patients with histories of myocardial infarction with residual arrhythmias in an intensive cardiac care facility. They must also monitor those with glaucoma for increased intraocular pressure. Clinicians should recognize that gastrointestinal bleeding can occur in patients with history of peptic ulcer disease.

False negative tests for glucosuria and false positive tests for pheochromocytoma, ketonuria, and hemolytic anemia can occur with Dhivy; hence, health professionals must interpret laboratory tests carefully.

Pregnancy and lactation²

Human pregnancy and lactation data are lacking although levodopa is excreted in milk. Levodopa/carbidopa combination products have shown teratogenic effects in rabbits, but not in mice. Employing Dhivy in pregnancy and lactation should occur only after careful assessment of risks and benefits.

About the Author

Alok Sharma is a Professor of Pharmaceutical Sciences at Massachusetts College of Pharmacy and Health Sciences in Manchester, NH.

References

1. Parkinson’s disease – Symptoms and Causes – Mayo Clinic. Accessed March 11, 2022.https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes

2. DHIVY full prescribing information. September 2021. Accessed March 11, 2022.

https://dhivyhcp.com/assets/pdf/dhivy-full-prescribing-information.pdf

3. Tablet scoring: nomenclature, labeling, and data for evaluation. Food and Drug Administration. Accessed March 11, 2022. https://www.fda.gov/media/81626/download

4. New term will distinguish tablets known to split in half. American Society of Health-System Pharmacists. Accessed March 11, 2022. https://www.ashp.org/news/2012/09/19/new_term_will_distinguish_tablets_known_to_split_in_half