KYNMOBI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KYNMOBI (KYNMOBI).
Apomorphine is a non-ergoline dopamine receptor agonist with high affinity for D4 and moderate affinity for D2, D3, D5, and D1 receptors. It also has affinity for serotonergic (5-HT1A, 5-HT2A, 5-HT2B) and adrenergic (α1, α2) receptors. It improves motor function in Parkinson disease by stimulating striatal dopamine receptors.
| Metabolism | Extensively metabolized in the liver by glucuronidation via UGT1A1 and UGT2B7; also undergoes sulfation. N-demethylation via CYP1A2 and CYP3A4 may occur. No active metabolites identified. |
| Excretion | Apomorphine is predominantly metabolized in the liver. Renal excretion accounts for approximately 80% of the dose, with 10% excreted as unchanged drug and 70% as metabolites. Biliary/fecal excretion accounts for the remaining 20%. |
| Half-life | The terminal elimination half-life of apomorphine is approximately 40 minutes. This short half-life necessitates continuous administration via subcutaneous infusion for sustained clinical effect. |
| Protein binding | Apomorphine is approximately 90% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | The volume of distribution is approximately 200 L (about 2.9 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Bioavailability of apomorphine is low and variable after oral administration (<5%). Subcutaneous administration provides 100% bioavailability. Sublingual film (KYNMOBI) has a bioavailability of approximately 18% relative to subcutaneous injection. |
| Onset of Action | Onset of action after subcutaneous injection is approximately 10-20 minutes. For sublingual film (KYNMOBI), onset occurs within 15-30 minutes. |
| Duration of Action | Duration of action after a single subcutaneous dose is approximately 60-90 minutes. Continuous infusion provides sustained effect, typically allowing reduction in off-time without dyskinesias. The sublingual film provides a similar duration of 60-90 minutes. |
Sublingual film: 10 mg, 15 mg, 20 mg, 25 mg, or 30 mg as a single dose for acute off episodes; may repeat once within 4 hours if inadequate response; maximum 30 mg per dose and 3 doses per day.
| Dosage form | FILM |
| Renal impairment | No specific dose adjustment provided; use caution in severe renal impairment (CrCl <30 mL/min) as data limited. |
| Liver impairment | No specific dose adjustment provided; use caution in Child-Pugh Class C as data limited. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. |
| Geriatric use | No specific geriatric dose adjustment; pharmacokinetics similar to younger adults; monitor for hypotension and hallucinations. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KYNMOBI (KYNMOBI).
| Breastfeeding | It is not known whether apomorphine is excreted in human milk. No data on M/P ratio. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | Apomorphine has not been studied in pregnant women. In animal studies, apomorphine was not teratogenic in rats or rabbits at doses up to 10 mg/kg/day (approximately 6 and 12 times the maximum human dose, respectively, on a mg/m² basis). No fetal malformations were observed. However, embryolethality and decreased fetal body weight occurred at maternally toxic doses in rabbits. Use during pregnancy only if potential benefit justifies potential risk to the fetus; first trimester risks are unknown. |
■ FDA Black Box Warning
KYNMOBI can cause serious adverse reactions, including severe nausea and vomiting, symptomatic orthostatic hypotension (particularly with concomitant antihypertensives), syncope, QT prolongation, and hallucinations/psychosis. It should not be used with serotonergic drugs due to risk of serotonin syndrome.
| Serious Effects |
Concomitant use with serotonergic drugs (e.g., SSRIs, SNRIs, MAOIs, triptans) due to risk of serotonin syndrome; severe hepatic impairment; history of QT prolongation or concomitant QT-prolonging drugs; hypersensitivity to apomorphine or its components; use of 5-HT3 antagonists (e.g., ondansetron) for antiemesis (risk of profound hypotension).
| Precautions | Orthostatic hypotension/syncope; nausea/vomiting (pretreat with antiemetic); hallucinations/psychosis; impulse control disorders; dyskinesias; coronary and cerebral ischemia; QT prolongation; priapism; somnolence/sudden sleep onset; falls; cardiac valvulopathy (due to ergot-like activity); potential for abuse (dopaminergic dysregulation syndrome). |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure and heart rate, particularly for hypotension and QT prolongation. Assess for nausea, vomiting, dyskinesia, and neuropsychiatric symptoms. Fetal monitoring is not specifically required but standard obstetric monitoring is recommended if used during pregnancy. |
| Fertility Effects | Apomorphine has been associated with increased prolactin levels in humans, which may transiently reduce fertility due to suppression of gonadotropin-releasing hormone. In animal studies, no adverse effects on fertility were observed in rats at doses up to 10 mg/kg/day. |