APOMORPHINE HYDROCHLORIDE
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Non-ergoline dopamine agonist with high affinity for D2 and D3 receptors, moderate affinity for D4, D5, and adrenergic receptors; activates striatal dopamine receptors to improve motor function.
| Metabolism | Hepatic via CYP3A4, CYP2C9, and CYP2C19; main metabolite is apomorphine-8-O-sulfate; first-pass effect with rapid clearance. |
| Excretion | Approximately 90% of an intravenous dose is excreted in urine within 24 hours, primarily as unchanged drug and sulfate conjugates. Biliary/fecal excretion is minimal (<5%). |
| Half-life | Terminal elimination half-life is 40–60 minutes in adults with normal renal function; prolonged to 3–6 hours in end-stage renal disease. |
| Protein binding | Approximately 90–99% bound, primarily to albumin. |
| Volume of Distribution | 1.8–2.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Subcutaneous: 100% (absolute); sublingual: 16–18%; oral: <1% due to extensive first-pass metabolism. |
| Onset of Action | Subcutaneous: 5–15 minutes; intravenous: immediate (1–5 minutes); sublingual: 10–30 minutes. |
| Duration of Action | Subcutaneous: 60–120 minutes; intravenous: 30–60 minutes; sublingual: 45–90 minutes. Duration is dose-dependent and varies with disease state. |
Subcutaneous injection: 0.2 mL (2 mg) test dose, then 0.2-0.6 mL (2-6 mg) as needed for acute hypomobility episodes; maximum single dose 0.6 mL (6 mg). Sublingual: 2-10 mg sublingually as needed, not more than every 2 hours, maximum 30 mg/day. Continuous subcutaneous infusion: 0.5-2.0 mg/hour via infusion pump.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment for mild to moderate impairment. Severe impairment (GFR <15 mL/min): avoid use as apomorphine is renally eliminated and accumulation may occur; use with caution and reduce dose if necessary at GFR 15-29 mL/min. |
| Liver impairment | Child-Pugh A and B: no dose adjustment necessary. Child-Pugh C: pharmacokinetics not studied; use with caution and monitor closely. |
| Pediatric use | Safety and efficacy not established; no pediatric dosing recommendations. |
| Geriatric use | Elderly patients may be more sensitive to neuropsychiatric effects; initiate at low end of dosing range (e.g., 1-2 mg subcutaneously) and titrate slowly; monitor for hypotension and falls. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Breastfeeding | No data on apomorphine excretion in human milk. M/P ratio unknown. Due to potential for serious adverse reactions in breastfeeding infants (e.g., somnolence, hypotension, dyskinesia), breastfeeding is not recommended during therapy. |
| Teratogenic Risk | Apomorphine hydrochloride is a dopamine agonist indicated for Parkinson's disease. Limited human pregnancy data; animal studies show fetotoxicity and teratogenicity at doses near maternal toxic doses. FDA Pregnancy Category C. First trimester: Avoid use unless benefit outweighs risk. Second/third trimester: No established safety; potential fetal effects include altered dopamine receptor development. Postnatal: Risk of neonatal withdrawal if used near term. |
■ FDA Black Box Warning
None.
| Common Effects | Constipation |
| Serious Effects |
["Concurrent use with serotonin 5-HT3 antagonists (e.g., ondansetron)","Hypersensitivity to apomorphine or sulfite-containing products","Severe asthma or sulfite allergy"]
| Precautions | ["Risk of hypotension, syncope, and orthostatic hypotension","Severe nausea and vomiting (pretreat with antiemetic)","Potential for hallucination, dyskinesia, and impulse control disorders","Do not mix with serotonin 5-HT3 antagonists (e.g., ondansetron) due to severe hypotension","Use caution in patients with cardiovascular disease, hypotension, or renal impairment"] |
| Food/Dietary | Avoid alcohol: may increase drowsiness and hypotension. Grapefruit juice: may increase risk of QT prolongation. No specific food interactions; maintain normal diet but monitor for changes in blood pressure. |
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| Fetal Monitoring | Monitor maternal vital signs (BP, HR) frequently due to risk of orthostatic hypotension. Monitor fetal growth and well-being via ultrasound if used in pregnancy. Assess for signs of neonatal withdrawal (e.g., irritability, feeding difficulties) after delivery. Periodic complete blood counts and liver function tests recommended due to potential neutropenia and hepatotoxicity. |
| Fertility Effects | In animal studies, apomorphine impaired fertility at high doses (reduced sperm motility, decreased implantation). In humans, no controlled studies; however, hyperprolactinemia secondary to treatment may affect ovulation. Use with caution in patients attempting conception. |
| Clinical Pearls | Administer subcutaneously; avoid intravenous use due to risk of hemolytic anemia and hypotension. Onset is rapid (5-15 minutes) with short duration (1 hour). Use an antiemetic (e.g., domperidone or trimethobenzamide) for 3 days before starting to prevent nausea. Do not use with 5-HT3 antagonists (e.g., ondansetron) due to profound hypotension. Monitor for dyskinesia, orthostatic hypotension, and QT prolongation. Avoid in patients with dementia, psychosis, or severe respiratory depression; caution in hepatic/renal impairment. Test dose (0.2-0.5 mL) is required before first prescription. |
| Patient Advice | Take this medication exactly as prescribed; it is for on-demand treatment of 'off' episodes. · Inject under the skin (subcutaneous) as directed; do not inject into a vein or muscle. · You may feel dizzy or lightheaded when standing up; rise slowly from sitting or lying down. · Nausea is common; your doctor may prescribe an anti-nausea medicine to take before each dose. · Report any chest pain, fainting, or severe dizziness immediately. · Avoid alcohol and grapefruit juice while using this medication. · Do not change your dose or frequency without consulting your doctor. · Keep this medication away from children and pets. |