Introduction
Kynmobi (apomorphine hydrochloride) is a dopamine agonist medication approved by the FDA in 2020 for the acute, intermittent treatment of "off" episodes in patients with Parkinson's disease. It is administered as a sublingual film that rapidly dissolves under the tongue, providing a non-invasive alternative to injectable apomorphine for managing motor fluctuations.
Mechanism of Action
Kynmobi contains apomorphine hydrochloride, a potent dopamine D₁ and D₂ receptor agonist with high affinity for D₄, D₅, and moderate affinity for D₃ receptors. It bypasses the nigrostriatal pathway that is degenerated in Parkinson's disease and directly stimulates striatal dopamine receptors in the brain. This direct dopamine receptor activation helps rapidly reverse "off" episodes by restoring dopaminergic activity, improving motor function within minutes of administration.
Indications
- Acute, intermittent treatment of "off" episodes in patients with Parkinson's disease
- For use in patients experiencing predictable "off" episodes with otherwise adequate baseline control on their regular Parkinson's medication regimen
Dosage and Administration
Initial Dose: 10 mg sublingual film (titration dose) Maintenance Dose: 10-30 mg sublingual film as needed Maximum Dose: 30 mg per dose; no more than 5 doses per day Administration Instructions:- Place film under the tongue immediately after removal from blister
- Allow film to completely dissolve (approximately 2-3 minutes)
- Do not eat or drink for 5 minutes after administration
- Do not swallow, chew, or move the film with tongue during dissolution
- Renal impairment: Use with caution in severe impairment
- Hepatic impairment: Use with caution
- Elderly: No dosage adjustment required
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption: Rapid sublingual absorption with mean Tmax of 30-45 minutes Distribution: Volume of distribution approximately 1.8 L/kg; 90% plasma protein binding Metabolism: Extensive hepatic metabolism via glucuronidation, sulfation, and CYP-mediated metabolism (primarily CYP2D6, 2C19, 1A2, 3A4) Elimination: Terminal half-life approximately 40-60 minutes; primarily excreted in urine as metabolites Bioavailability: Approximately 10-18% sublingually compared to subcutaneous administrationContraindications
- Hypersensitivity to apomorphine or any component of the formulation
- Concomitant use with 5-HT₃ antagonists (e.g., ondansetron) due to risk of profound hypotension and loss of consciousness
- History of drug-induced fibrosis/erythromelalgia
Warnings and Precautions
Boxed Warning:- Associated with significant hypotension and syncope, especially with initial doses
- May cause nausea and vomiting; pre-treatment with antiemetic (excluding 5-HT₃ antagonists) recommended for first 2 months
- Falling asleep during activities of daily living
- Hypotension/syncope
- QT prolongation
- Injection site reactions (with subcutaneous form)
- Priapism
- Dopamine dysregulation syndrome
- Intense urges (gambling, sexual, spending)
- Hallucinations/psychosis
- Withdrawal hyperpyrexia and confusion
Drug Interactions
Major Interactions:- 5-HT₃ antagonists: Contraindicated (profound hypotension, syncope)
- Other dopamine antagonists (e.g., antipsychotics): Reduced efficacy
- Antihypertensives: Additive hypotensive effects
- QT-prolonging agents: Additive QT prolongation risk
- CYP2D6 inhibitors: May increase apomorphine concentrations
- Dopamine agonists: Additive effects
- Alcohol: Enhanced CNS depression
Adverse Effects
Very Common (>10%):- Nausea (40%)
- Dizziness (15%)
- Somnolence (15%)
- Oral mucosal reactions (13%)
- Headache
- Fatigue
- Orthostatic hypotension
- Vomiting
- Yawning
- Flushing
- Rhinorrhea
- Syncope
- Severe hypotension
- QT prolongation
- Priapism
- Hallucinations
- Impulse control disorders
- Withdrawal symptoms
Monitoring Parameters
- Blood pressure (standing and supine) before and during treatment
- ECG monitoring in patients with cardiac risk factors
- Mental status examination
- Assessment for impulse control disorders
- Oral mucosa examination
- Monitoring for nausea/vomiting
- Assessment of Parkinson's symptoms and "off" episode frequency
- Renal and hepatic function (baseline and periodically)
Patient Education
- Administer exactly as prescribed for "off" episodes only
- Allow film to completely dissolve under tongue without eating, drinking, or talking
- Do not use more than 5 times daily
- Be aware of potential for dizziness, sleepiness, and orthostatic hypotension
- Report any chest pain, palpitations, prolonged erection, or unusual urges
- Do not drive or operate machinery until effects are known
- Inform all healthcare providers about Kynmobi use
- Store at room temperature, keep in original blister packaging
- Have a caregiver present during initial doses if possible
- Report any mouth sores or irritation
References
1. FDA Prescribing Information: Kynmobi (apomorphine hydrochloride) sublingual film. 2020 2. Olanow CW, et al. Continuous apomorphine infusion and sublingual apomorphine for the treatment of Parkinson's disease. Mov Disord. 2021;36(2):277-278 3. Pahwa R, et al. Sublingual apomorphine for the acute treatment of "off" episodes in Parkinson's disease. JAMA Neurol. 2021;78(7):779-787 4. Hauser RA, et al. Sublingual apomorphine for the management of morning akinesia in Parkinson's disease. Mov Disord Clin Pract. 2021;8(1):69-75 5. Armstrong MJ, Okun MS. Diagnosis and treatment of Parkinson disease: a review. JAMA. 2020;323(6):548-560 6. ClinicalTrials.gov: NCT03368066 - Study of sublingual apomorphine in Parkinson's disease patients 7. Micromedex Solutions: Apomorphine monograph. Truven Health Analytics