Open-label study assessment of safety and adverse effects of subcutaneous apomorphine injections in treating "off" episodes in advanced Parkinson disease.

OBJECTIVE: To assess the safety and adverse effect profile of continued use of intermittent subcutaneous apomorphine to treat "off" episodes in subjects with advanced Parkinson disease. METHODS: The study enrolled subjects with Hoehn and Yahr stage II-V Parkinson disease who were experiencing "off" events despite an optimized oral medication regimen. After baseline assessment and subcutaneous apomorphine dose titration (2-10mg/dose), subjects received > or =12 months of open-label treatment, as needed, for "off" episodes. RESULTS: Of the 546 subjects in the study population, the majority used apomorphine on a daily basis; the average dose was 4.0 mg. A total of 187 subjects discontinued treatment because of adverse events (AEs). Most AEs were mild to moderate and expected with apomorphine. The AEs most commonly classified as definitely, probably, or possibly treatment related were nausea and vomiting, dyskinesia, dizziness, somnolence, hallucination, yawning, and injection site bruising. Serious AEs occurred in 199 subjects, but only 27 were considered to be probably or possibly treatment related. None of the 45 deaths recorded in the study were attributed to apomorphine. CONCLUSIONS: Long-term use of intermittent apomorphine dosing for treatment of "off" episodes was generally associated with mild-to-moderate AEs.

Intermittent subcutaneous apomorphine therapy for 'off' episodes in Parkinson's disease: a 6-month open-label study.

PURPOSE: The outpatient follow-up phase of the apomorphine (APO) 303 study assessed the long-term efficacy and safety of intermittent subcutaneous apomorphine for 'off' episodes in patients with advanced Parkinson's disease. METHODS: We conducted a 6-month open-label outpatient extension of an in-office dose-escalation study. Patients received apomorphine at a dose considered optimal based on safety and efficacy assessments during the dose-titration phase. Outpatient evaluation visits were scheduled at 1 and 2 weeks, and 1, 4 and 6 months. Efficacy parameters included changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor scores; safety assessments included blood pressure (BP) monitoring. RESULTS: Apomorphine significantly (p<0.05) reduced UPDRS motor scores at 20, 40 and 90 minutes post-dose versus pre-dose at all evaluation visits. Significant (p<0.1) reductions from pre-dose in seated and standing systolic BP and diastolic BP were noted at various timepoints post-dose at evaluation visits; however, the changes did not increase over the course of the outpatient phase. The incidence of symptomatic hypotension also did not increase with long-term apomorphine use. CONCLUSIONS: The efficacy and general tolerability of subcutaneous apomorphine throughout this open-label outpatient study suggest that it is suitable for the long-term acute treatment of 'off' episodes in patients with advanced Parkinson's disease.

Continued efficacy and safety of subcutaneous apomorphine in patients with advanced Parkinson's disease.

The study purpose was to assess the efficacy of intermittent subcutaneous apomorphine (APO) as acute therapy for off episodes in advanced Parkinson's disease (PD) patients who had previously received APO for 3 months. Patients (n=62) were randomized to receive double-blind treatment with APO at their typically effective dose (TED; APO), APO at their TED+0.2mL (2.0mg; APO+2), placebo at volume equal to their TED (PL), or placebo at volume equal to their TED+0.2mL (PL+2), for a single off episode. Significantly greater improvement in mean Unified PD rating scale motor scores was seen with pooled APO versus pooled placebo 20min after administration (-24.2 vs. -7.4; p<0.0001); the difference was also significant at 10min (p<0.0001). Overall adverse event incidence did not significantly differ between pooled APO and pooled PL. This study supports the long-term use of intermittent APO as effective acute therapy for off episodes in advanced PD patients.

Unstable angina.

Preview Because unstable angina is often a precursor of myocardial infarction or death, patients with chest pain that persists for more than 20 minutes and is refractory to sublingual nitroglycerin should be hospitalized in an intensive care unit and given appropriate pharmacologic therapy. If symptoms persist despite adequate management with drugs, coronary arteriography should be performed and consideration given to an invasive procedure, such as angioplasty or coronary artery bypass grafting, for high-risk conditions. If necessary, the invasive procedure should be delayed until the patient's condition has stabilized.

Hypertensive heart disease.

Preview Americans often think of coronary artery disease as the most common cardiac disorder, but hypertensive heart disease is estimated to occur in nearly three times more patients, affecting about 20 million Americans. The authors discuss current criteria for diagnosis of hypertensive heart disease, common manifestations, coexisting conditions, comparative sensitivity of diagnostic methods, and treatment goals.

Automated blood pressure monitoring.

Preview Blood pressure measurements obtained through 24-hour automated monitoring are more reliable than office measurements and more strongly correlated with target-organ damage from hypertension. Yet broad use of automated monitoring remains controversial. The authors discuss areas of debate, explain why they favor broader use, and provide practical information for clinicians who want to try this relatively new technology.