Increased risk in esophageal obstruction with slow-release medications.
Although medication-induced (pill) esophagitis has been recognized for a long time, little data are available on the risk of recently introduced slow-release medications. These formulations may have an obstructive capability (undissolved medication blocking an obstructed lumen) or may cause tissue irritation (continuous leakage from a slowly disintegrating pill). We observed a patient with esophageal carcinoma who developed complete obstruction when three Procardia XL (nifedipine) extended-release tablets blocked the narrowed lumen. An intact Procardia XL tablet and a washed shell as a control were implanted subcutaneously in a rat. The intact pill produced a large inflammatory mass: in contrast, no inflammatory response was noted at the control site implanted with a washed shell. In vitro testing of seven different slow-release medications revealed a wide difference in their solubility at a neutral pH and in gastric juice of pH 1.8 (simulation of esophageal or gastric environment). Theolair-SR (anhydrous theophylline, sustained-release) tablets had the highest obstructive, but no irritating potential. Cardizem SR (diltiazem hydrochloride) sustained-release capsules dissolved promptly without obstructive potential. Adalat CC (nifedipine) extended-release tablets also dissolved early at both pH values. Cardizem CD (diltiazem hydrochloride) extended-release capsules and Calan SR (verapamil hydrochloride) sustained-release oral caplets disintegrated into granules that had a low obstructive potential, but their prolonged presence increased the risk of tissue irritation. Ecotrin (enteric-coated aspirin) tablets had a high obstructive and no irritating potential in the first 24 hours, after which they disintegrated and directly contacted the tissue. Procardia XL extended-release tablets had an insoluble shell that continued to leak a tissue-irritating content even after 48 hours, generating a prolonged obstructive and irritating condition. In conclusion, slow-release medications greatly increase the risk of esophageal injury. Their obstructive and tissue-irritating potentials differ widely. Slow-release formulations should be contraindicated in patients who have obstructive esophageal and gastric disorders.
Simko
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Section of Gastroenterology, Brooklyn Veterans Administration Medical Center, NY 11209, USA.
Joseph
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Michael
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D000368:Aged; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D003692:Delayed-Action Preparations / Q000009:adverse effects; D004195:Disease Models, Animal; D004355:Drug Stability; D004938:Esophageal Neoplasms / Q000188:drug therapy; D004940:Esophageal Stenosis / Q000139:chemically induced* / Q000175:diagnosis; D004947:Esophagus; D017809:Fatal Outcome; D005547:Foreign Bodies / Q000209:etiology*; D005750:Gastric Juice / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage* / Q000009:adverse effects*; D051381:Rats; D012867:Skin / Q000473:pathology
D003692:Delayed-Action Preparations; D009543:Nifedipine