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Dextropropoxyphene
General information
The most frequent adverse reactions to dextropropoxyphene are dizziness, sedation, and nausea and vomiting. Other reported reactions include constipation, abdominal pain, skin rashes, light-headedness, headache, weakness, euphoria, dysphoria, minor reversible visual disturbances, and liver dysfunction [ ].
A systematic review of single-dose dextropropoxyphene for postoperative pain identified 130 published articles [ ]. Of these, 11 placebo-controlled studies met the inclusion criteria for the review, 6 of dextropropoxyphene (65 mg) and five of the same dose of dextropropoxyphene plus paracetamol (650 mg) (co-proxamol). Pooled data from the studies showed that the incidence of nausea, drowsiness, and headache with dextropropoxyphene alone was not significantly different from placebo. Previous reports have suggested that dextropropoxyphene is significantly associated with dizziness, sedation, and nausea and vomiting. However, co-proxamol caused significantly increased dizziness (relative risk 2.2, 95% CI = 1.1, 4.3) and drowsiness (2.1, 1.5, 2.9). The relative risk of headache was reduced to 0.5 (0.3, 0.9). Analgesic effect was greater with co-proxamol than with dextropropoxyphene alone.
Organs and systems
Cardiovascular
Dextropropoxyphene-induced cardiogenic shock has been described [ ].
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A 32-year-old man became deeply comatose, with intraventricular conduction disturbances, after taking dextropropoxyphene 4.6 g. Treatment-resistant seizures lasted for hours. He was treated with an intra-aortic balloon pump and a continuous infusion of milrinone for 7 days and recovered fully.
The mechanism of cardiotoxicity of dextropropoxyphene is unknown, but the membrane-stabilizing effect of its major metabolite, norpropoxyphene, seems to play a central part. The cardiac effects are not reversed by naloxone [ ], but dopamine may be effective.
Respiratory
Hypersensitivity pneumonitis has been associated with co-proxamol (paracetamol plus dextropropoxyphene) [ ].
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A 61-year-old man, who was taking prednisolone 20 mg and co-proxamol as required for cranial arteritis, presented with a 2-month history of increasing breathlessness. His chest X-ray showed vague shadowing in both lower zones, consistent with an interstitial abnormality, and a lung biopsy confirmed focal interstitial hypersensitivity pneumonitis. After a diffuse rash appeared, the co-proxamol was withdrawn and then reintroduced. The rash recurred and the breathlessness deteriorated. A subsequent challenge with paracetamol did not produce the same symptoms. The dosage of prednisolone was not altered.
Sensory systems
Nerve deafness in a 44-year-old woman, dependent on co-proxamol (dextropropoxyphene plus paracetamol), has been reported [ ].
Metabolism
Severe hypoglycemia has been reported in the elderly [ ].
Hematologic
Hemolytic anemia has been attributed to dextropropoxyphene [ ].
Gastrointestinal
Four cases each of necrotizing anorectitis and proctitis have been reported after long-term (2–24 months) use of suppositories containing dextropropoxyphene and paracetamol [ ]. Perineal ulceration can also occur [ ].
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