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In a survey conducted in hospitalized patients less than 1% of patients taking propoxyphene hydrochloride at recommended doses experienced side effects. The most frequently reported were dizziness, sedation, nausea and vomiting. Some of these adverse reactions may be alleviated if the patient lies down.

Other adverse reactions include constipation, abdominal pain, skin rashes, lightheadedness, headache, weakness, euphoria, dysphoria hallucinations, and minor visual disturbances.

Propoxyphene therapy has been associated with abnormal liver function tests and more rarely with instances of reversible jaundice (including cholestatic jaundice).

Renal papillary necrosis may result from chronic aspirin use, particularly when the dosage is greater than recommended and when combined with acetaminophen.

Subacute painful myopathy has occurred following chronic propoxyphene overdosage.