Ketorolac toxicity

Apart from the salicylates NSAIDs include several classes of weak acids like propionic acid derivatives such as ibuprofen, carprofen, fenbufen, fenoprofen, flurbiprofen, ketorolac, loxoprofen, naproxen, oxaprozin, tiaprofenic acid and suprofen. Phenylbutazone is the most important representative of the pyrazolon derivatives which have a bad reputation for their risk of potentially fatal bone-marrow toxicity. To the acetic acid derivatives belong in-domethacin, diclofenac and sulindac. Sulindac is a pro-drug with less toxicity than indomethacin. The enolic acids include piroxicam, droxicam and tenoxicam. Meloxicam is an analog of piroxicam and has a high selectivity for COX-2. 

No signiflcanf advanfage over ofher oral NSAlDs cosf and clinical sifuafion should govern use no reason fo confinue parenferal course of therapy wifh oral ketorolac (more expensive, more toxic)... 

Thus, NSAIDs tend to be differentiated on the basis of toxicity and cost-effectiveness. For example, the gastrointestinal and renal side effects of ketorolac limit its use. Some surveys suggest that indomethacin or tolmetin are the NSAIDs associated with the greatest toxicity, while salsalate, aspirin, and ibuprofen are least toxic. The selective COX-2 inhibitors were not included in these analyses. 

Iyer V. Ketorolac (Toradol) induced lithium toxicity. Headache 1994 34(7) 442 1. 

NS AIDs ANTIGOUT DRUGS-PROBENECID T levels of indometacin, ketorolac and possibly dexketoprolien, ketoprofen, naproxen, tenoxicam and tiaprofenic acid Probenecid competitively inhibits renal metabolism of these NSAIDs Watch for signs of toxicity of these NSAIDs. Consider using an alternative NSAID. The manufacturers of ketorolac advise avoiding co-adminis-tration of ketorolac and probenecid... 

The most frequent adverse event reported with ketorolac use is transient stinging and burning after instillation of the ophthalmic solution. Rarely, allergic reactions and superficial keratitis have occurred. Although inconsistent cases of corneal toxicity have been reported with NSAIDs, prolonged use of NSAIDs in a select group of patients showed the potential for corneal melt. Because other treatment options exist for allergic eye disease, NSAIDs do not need to be used in patients with compromised corneas or those at risk for potentially serious adverse corneal reactions. 

If topical anesthetic abuse is suspected, discontinuation is critical. A broad-spectrum topical antibiotic such as 0.5% moxifloxacin three times daily is used to protect the disrupted corneal epithelium from secondary infection as the tissue heals. Topical NSAIDs, such as 0.1% diclofenac sodium solution or 0.5% ketorolac solution, and a therapeutic soft contact lens help to reduce pain. Cycloplegic and topical steroids are indicated if an anterior chamber reaction is present.Toxic keratitis can heal without permanent vision loss within days after discontinuing the use of the anesthetic but may result in permanent scarring, vascularization, and visual loss. Surgical treatment, such as a penetrating keratoplasty, may be necessary. 

The gastrointestinal toxicity of the NSAIDs is well documented, and it appears that combined use increases this risk. The CSM in the UK state that not more than one NSAID should be used concurrently. " The marked rise in plasma levels of indometacin with diflunisal gives an additional reason why this combination in particular should not be used. Some NSAIDs cause more gastrointestinal toxicity than others, a suggested broad rank order of seven NSAIDs is as follows. Highest risk (azapro-pazone) intermediate risk (diclofenac, indometacin, ketoprofen and naproxen, with piroxicam more risky) lowest risk (ibuprofen), which has been home out in another analysis. The ranking was based on epidemiological studies and the yellow card database. Ketorolac may also be... 

Probenecid reduces the clearance of dexketoprofen, diflunisal, in-dometacin (toxicity seen), ketoprofen, ketorolac, naproxen, sodium meclofenamate, tenoxicam and tiaprofenic acid and raises their levels. Ketorolac and probenecid are specifically contraindicated. The uricosuric effects of probenecid are not affected by in-dometacin but may be slightly reduced by sulindac. 

The interaction between indometacin and probenecid is established and adequately documented. Concurrent use should be well monitored because, while clinical improvement can undoubtedly occur, some patients may develop indometacin toxicity (headache, dizziness, light-headedness, nausea, etc.). This is particularly likely in those with some renal impairment. Reduce the indometacin dosage as necessary. Information about other NSAIDs is limited, but these interactions also appear to be established. The clinical importance of most of them is uncertain, but probably small. Reports of adverse effects seem to be lacking, but it would still be prudent to be alert for any evidence of increased adverse effects. Reduce the NSAID dosage if necessary. The exception is ketorolac, which its manufacturers contraindicate with probenecid because of the marked increases seen in its plasma levels. 

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