Orphenadrine Citrate

Hospitalized post-operative cardiovascular disease (CVD) patients are often subject to polypharmacy, increasing the risk of potential drug-drug interactions (pDDIs). This observational study assessed 384 post-operative CVD patients for pDDIs using Micromedex Drug-Int® and Lexicomp Interact®. Prevalence, severity, onset and documentation of pDDIs were analyzed using SPSS 23.0, with logistic regression identifying factors associated with at least two major pDDIs or two pDDIs categorized as X, D, or C. Micromedex Drug-Int® revealed a median of 6.23 pDDIs per patient, with 98.7% of patients having ≥1 pDDIs. Of 2,389 pDDIs, 64.1% were major. Lexicomp Interact® data showed a median of 7.15 pDDIs per patient, with 99.2% of patients having ≥1 pDDIs. Class C interactions were the most frequent (62.1%), followed by Classes B, D and X. Additionally, the study identified unique pDDIs from Lexicomp, including Ipratropium-Orphenadrine and Furosemide-Levosulpiride, not listed in Micromedex. The findings highlight the high prevalence of pDDIs in this population, emphasizing the need for regular monitoring. Using pDDI screening tools, clinical pharmacists can be crucial in mitigating these risks, particularly in high-risk patients.

Orphenadrine overdoses can cause antimuscarinic toxicity, respiratory failure, refractory seizures and cardiotoxicity. The dose-toxicity relationship is poorly defined. Orphenadrine is marketed as immediate and sustained release formulations, and it is not known how the formulation impacts on toxicity. We determined the clinical toxicity of orphenadrine in patients referred to a regional poisons centre.

Retrospective case series of patients in New South Wales with orphenadrine deliberate self-poisoning from January 2016 to April 2022 referred to the New South Wales Poisons Information Centre. Demographics, history of exposure, treatment and outcomes were extracted from clinical databases. Receiver-operating characteristic curves were constructed to determine thresholds predicting toxicity.

Forty-eight patients were identified, with information on clinical outcomes in 46 patients and doses in 41 patients. All patients were older than 12 years. The median orphenadrine dose was 770 mg (range 210-10,000 mg), 59 per cent as the immediate release formulation, and 67 per cent reported coingestants. Doses of sustained release formulations were significantly greater than immediate release formulations, median 2,750 mg versus 595 mg. Common clinical features were drowsiness (59 per cent), sinus tachycardia (37 per cent) and confusion (33 per cent). Three patients had mild hypotension, three were intubated for coma, and two had seizures; no patients suffered ventricular dysrhythmias. All patients survived, with 75 per cent being medically cleared within 24 hours of presentation. A dose-toxicity relationship was observed, but conclusions are limited by the small number of cases with moderate or severe toxicity.

All patients survived, and severe cardiac and neurological toxicity were not observed. This contrasts to published case reports noting severe poisoning at similar or lower doses. Formulation may have an impact on outcomes, with lesser toxicity from sustained release products.

Orphenadrine doses up to 10 g were associated with antimuscarinic toxicity and sedation, but not severe cardiotoxicity. More research exploring the effect of dose and formulation on outcomes is required.