APOKYN
Clinical safety rating
cautionComprehensive clinical and safety monograph for APOKYN (APOKYN).
Apomorphine is a non-ergoline dopamine agonist that stimulates dopamine D2 and D1 receptors. It also activates D3, D4, and D5 receptors and has some serotonergic and adrenergic activity.
| Metabolism | Primarily hepatic via N-demethylation to norapomorphine; also undergoes sulfation and glucuronidation. CYP enzymes involved include CYP2B6, CYP2C19, and CYP3A4. |
| Excretion | Renal (approx. 90% as metabolites and unchanged drug; <5% unchanged in urine); biliary/fecal (minor, <10%) |
| Half-life | Terminal elimination half-life approximately 30–60 minutes (range 0.5–1 hour); clinically, rapid clearance necessitates continuous or frequent dosing for sustained effect |
| Protein binding | Approximately 99% bound to plasma proteins (primarily albumin) |
| Volume of Distribution | Approximately 1.5–2 L/kg (wide distribution, extensive tissue binding) |
| Bioavailability | Subcutaneous injection: approximately 100% (complete absorption); oral: negligible (<2%) due to extensive first-pass metabolism; intravenous: 100% |
| Onset of Action | Subcutaneous injection: 5–15 minutes (mean 10 minutes); intravenous: immediate (1–2 minutes) |
| Duration of Action | Subcutaneous injection: 45–60 minutes (dose-dependent, up to 90 minutes with higher doses); clinical effect correlates with plasma concentrations; used for rescue in OFF episodes |
| Molecular Weight | 267.33 |
Subcutaneous injection: 0.2 mL (2 mg) as a test dose, then 0.1-0.6 mL (1-6 mg) as needed for episodes of hypomobility; maximum single dose: 0.6 mL (6 mg); maximum daily dose: 2.0 mL (20 mg).
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended; use with caution in renal impairment. Data for GFR-based modifications are insufficient. |
| Liver impairment | No specific dose adjustment recommended; use with caution in moderate to severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Not established; safety and efficacy in pediatric patients have not been studied. |
| Geriatric use | No specific dose adjustment; elderly patients may be more sensitive to adverse effects; initiate at low end of dosing range. |
| 1st trimester | Apomorphine is not recommended in first trimester due to lack of data and potential for emesis and hypotension. |
| 2nd trimester | Limited data; use only if benefit outweighs risk. May cause maternal hypotension and nausea. |
| 3rd trimester | Avoid use near term due to potential for adverse effects on newborn (hypotension, respiratory depression). |
Clinical note
Comprehensive clinical and safety monograph for APOKYN (APOKYN).
| Placental transfer | Apomorphine crosses the placenta in animal studies; limited human data suggest transfer occurs with potential fetal exposure. |
| Breastfeeding | Apomorphine is excreted into breast milk in small amounts; however, due to potential for adverse effects (hypotension, nausea) in the infant, caution is advised. Monitor infant for signs of sedation, poor feeding, or respiratory issues. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Apomorphine is classified as Pregnancy Category C. In animal studies, maternal toxicity and fetal effects (reduced fetal weight, delayed ossification) were observed at doses ≥3 mg/kg/day (approximately 0.3 times the maximum recommended human dose). No adequate and well-controlled studies exist in pregnant women. For first trimester: potential risk based on animal data; second and third trimesters: unknown risk. Use only if potential benefit justifies potential risk to fetus. |
| Fetal Monitoring | Monitor for severe nausea and vomiting (antiemetic pretreatment recommended), hypotension, syncope, QTc prolongation (ECG), and injection site reactions. No specific fetal monitoring required beyond routine obstetric care. Assess for signs of dopamine agonist effects (e.g., dyskinesia, hallucinations). |
| Fertility Effects | Apomorphine may impair fertility in males and females based on animal studies (decreased implantation and pregnancy rates). In humans, no formal fertility studies; however, dopamine agonists can alter prolactin levels, potentially affecting ovulation and spermatogenesis. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to apomorphine or any component of the formulationConcurrent use of 5-HT3 antagonists (e.g., ondansetron)Severe hypotension or cardiovascular instabilityHistory of malignant melanoma (due to potential for dopaminergic stimulation)
| Precautions | Cardiovascular effects: severe hypotension, syncope, bradycardia, and QT prolongation; monitor blood pressure and ECG, Nausea and vomiting: almost universal; pre-treatment with antiemetic (e.g., trimethobenzamide) required, Falling asleep during activities of daily living: risk of sudden sleep onset, Psychiatric effects: hallucinations, confusion, psychosis; may exacerbate existing disorders, Dyskinesias: may be precipitated or worsened, Impulse control disorders: compulsive behaviors reported, Hemolytic anemia: rare but severe risk; monitor blood counts, Skin reactions: injection site reactions, panniculitis, and pain |
| Food/Dietary | Avoid high-protein meals as they may delay absorption; take on an empty stomach for consistent response. No specific food contraindications. |
| Clinical Pearls | Administer with an antiemetic (e.g., trimethobenzamide) to prevent severe nausea/vomiting. Use extreme caution in patients with prolonged QT interval. Injection sites must be rotated; do not inject into areas with bruising, redness, or hard lumps. Onset of effect is within 10 minutes but duration is short (about 1 hour). Monitor for orthostatic hypotension and dyskinesias. |
| Patient Advice | Take exactly as prescribed; do not use more often than directed. · Administer only into the abdomen, thigh, or upper arm; rotate injection sites. · Do not inject into areas with broken, bruised, or red skin. · Avoid driving or operating machinery until you know how the drug affects you. · Rise slowly from sitting or lying to reduce dizziness. · Report severe nausea, vomiting, hallucinations, or compulsive behaviors immediately. |
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