The Supreme Court on Wednesday issued its decision in the much-watched case of Wyeth v. Levineâ€”which many in pharma hoped would firmly establish FDA decisions as a bulwark against common-law liability suits in state courts. The decision, as you’ve no doubt heard already, went against Wyeth. Pharm Exec‘s coverage is here. The opinion is here. The estimable Drug and Device Law Blog has provided links to today’s coverage here as well as a quick-and-dirty analysis of the opinion
The case as heard by the Supreme Court deals in a great deal of legal complexity, but the underlying lawsuit that inspired it is based on a fairly simple idea: Diana Levine was severely injured when she was given Wyeth’s Phenergan by a physician’s assistant who was attempting to inject the drug directly into the vein but instead either got it into the artery or injected it in such a way that it leaked out of the vein (“perivascular extravasation”) and mixed with arterial blood. The labeling for the drug warns what can happen, but Levine and her lawyers argued that Wyeth should have acted independently of FDA and contraindicated injection directly into the vein (or “IV push).
Well there are warnings, and there are warnings, so we took a look at the Phenergan PI to see what it had to say. It’ll no doubt make you feel even more sympathy for Diana Levine, but if you’re like me, it will make you wonder whether it makes sense to prevent problems with warnings when a warning like this didn’t suffice:
From the “Contraindications” section of the label:
Under no circumstances should PHENERGAN Injection be given by intra-arterial injection due to the likelihood of severe arteriospasm and the possibility of resultant gangrene (see WARNINGSâ€”Injection Site Reactions).</b>
PHENERGAN Injection should not be given by the subcutaneous route; evidence of chemical irritation has been noted, and necrotic lesions have resulted following subcutaneous injection. The preferred parenteral route of administration is by deep intramuscular injection.
Under “Injection Site Reactions”:
PHENERGAN Injection can cause severe chemical irritation and damage to tissues, regardless of the route of administration. Irritation and damage can also result from perivascular extravasation, unintended intra-arterial injection, and intraneuronal or perineuronal infiltration.
Signs, Symptoms, and manifestations of severe tissue irritation include burning, pain, erythema, swelling, severe spasm of distal vessels, thrombophlebitis, venous thrombosis, phlebitis, abscesses, tissue necrosis, and gangrene. Administration of PHENERGAN Injection has resulted in nerve damage ranging from temporary sensory loss to palsies and paralysis. Injection into or near a nerve may result in permanent tissue damage. In some cases, surgical intervention (including fasciotomy, skin graft, and/or amputation) may be required (see ADVERSE REACTIONS).
Inadvertent Intra-Arterial Injection
Due to the close proximity of arteries and veins in the areas most commonly used for intravenous injection, extreme care should be exercised to avoid perivascular extravasation or unintentional intra-arterial injection. Reports compatible with unintentional intra-arterial injection of PHENERGAN Injection, usually in conjunction with other drugs intended for intravenous use suggest that pain, severe chemical irritation, severe spasm of distal vessels, and resultant gangrene requiring amputation are likely under such circumstances. Intravenous injection was intended in all the cases reported but perivascular extravasation or arterial placement of the needle is now suspect. There is no proven successful management of unintentional intra-arterial injection or perivascular extravasation after it occurs. Sympathetic block and heparanization have been employed during the acute management of unintentional intra-arterial injection, because of the results of animal experiments with other known arteriolar irritants. Aspiration of dark blood does not preclude intra-arterial needle placement, because blood is discolored upon contact with PHENERGAN Injection. Use of syringes with rigid plungers or of small-bore needles might obscure typical arterial backflow if this is relied upon alone.
When used intravenously, PHENERGAN Injection should be given in a concentration of no greater than 25 mg per mL, and at a rate not to exceed 25 mg per minute. When administering any irritant drug intravenously, it is usually preferable to inject it through the tubing of an intravenous infusion set that is known to be functioning satisfactorily. In the event that a patient complains of pain during intended intravenous injection of PHENERGAN Injection, the injection should be stopped immediately to provide for evaluation of possible arterial placement or perivascular extravasation.
Under “Adverse Reactions”:
INTRA-ARTERIAL INJECTION MAY RESULT IN GANGRENE OF THE AFFECTED EXTREMITY.
Under “Dosage and Administration”:
The preferred parenteral route of administration for PHENERGAN Injection is by deep intramuscular injection. The proper intravenous administration of this product is well tolerated, but use of this route is not without some hazard. Not for subcutaneous administration.
UNINTENTIONAL INTRA-ARTERIAL INJECTION CAN RESULT IN GANGRENE OF THE AFFECTED EXTREMITY (see CONTRAINDICATIONS, WARNINGSâ€”Injection Site Reactions). SUBCUTANEOUS INJECTION IS CONTRAINDICATED, AS IT MAY RESULT IN TISSUE NECROSIS (see CONTRAINDICATIONS, WARNINGSâ€”Injection Site Reactions, and ADVERSE REACTIONS).