Ibuprofen with lithium

Ragheb M, Ban TA, Buchanan D, et al. Interaction of indomethacin and ibuprofen with lithium in manic patients under a steady-state lithium level. J Clin Psychiatry 1980 41 397-398. 

Lithium toxicity can occur as a result of intentional overdose therefore, care must be taken when administering lithium to potentially suicidal patients with BPAD. Inadvertent lithium toxicity may also occur. For example, diuretics and nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil, Motrin) slow the excretion of lithium and can lead to accidental toxicity. Consequently, the patient should be advised not to take such commonly available medications while treated with lithium. In addition, dehydration resulting from varied causes such as diarrhea, vomiting, and profuse sweating can lead to accidental lithium toxicity. One should advise the patient who takes lithium to be careful to remain well hydrated at all times and to contact his/her physician if any medical condition arises that may cause rapid fluid losses (e.g., stomach virus, high fevers). 

Case Example A 48-year-old bipolar woman, stabilized on lithium 1,200 mg/day for the past 6 months, had a plasma level that varied between 0.8 and 1.0 mEq/L. She developed a recurrence of her rheumatoid arthritis, for which her internist prescribed ibuprofen (800 mg t.i.d.). A week later, she was brought to the emergency room in a confused, disoriented, and lethargic state. She was also ataxic and had periodic generalized myoclonic jerks. TDM revealed a lithium level of 4.0 mEq/L, and despite a rapid fall to under 0.5 mEq/L with plasma dialysis, her neurological status continued to deteriorate. After 5 days, she died. 

Notes Drugs associated with the exacerbation of psoriasis include lithium, beta-adrenergic receptor blocking agents and antimalarials. Withdrawal of corticosteroid therapy may activate pustular psoriasis. NSAIDs, such as ibuprofen... 

Non-steroidal anti-inflammatory agents, including ibuprofen and selective Cox-2 inhibitors (cyclo-oxygenase 2), can increase plasma lithium concentrations add with caution to patients stabilized on lithium... 

Clinically important, potentially hazardous interactions with acitretin, aldesleukin, aminoglycosides, amiodarone, amoxicillin, ampicillin, aspirin, bacampicillin, bismuth, carbenicillin, chloroquine, cisplatin, cloxacillin, co-trimoxazole, dapsone, demeclocycline, dexamethasone, diclofenac, dicloxacillin, etodolac, etoricoxib, etretinate, fenoprofen, flurbiprofen, folic acid antagonists, haloperidol, hydrocortisone, ibuprofen, indomethacin, influenza vaccines, ketoprofen, ketorolac, lithium, magnesium trisalicylate, meclofenamate, mefenamic acid, methicillin, mezlocillin, minocycline, nabumetone, nafcillin, naproxen, NSAIDs, omeprazole, oxacillin, oxaprozin, oxytetracycline, paromomycin, penicillin G, penicillin V, penicillins, phenylbutazone, piperacillin, piroxicam, polypeptide antibiotics, prednisolone, prednisone, probenecid, procarbazine, rofecoxib, salicylates, salsalate, sapropterin, sulfadiazine, sulfamethoxazole, sulfapyridine, sulfasalazine, sulfisoxazole, sulindac, tazobactum, tenoxicam, tetracycline, ticarcillin, tolmetin, trimethoprim, vaccines... 

Most of the renal tubular reabsorption ofU occurs in the proximal tubule. Nevertheless, Id retention can be increased by any diuretic that leads to depletion of Na, particularly the thiazides (see Chapter 28). Renal excretion can be increased by administration of osmotic diuretics, aceta-zolamide or aminophylline, and triamterene. Spironolactone does not increase the excretion of LiL Some nonsteroidal anti-inflammatory agents can facilitate renal proximal tubular resorption of Id and thereby increase concentrations in plasma to toxic levels. This interaction appears to be particularly prominent with indomethacin, but also may occur with ibuprofen, naproxen, and COX-2 inhibitors, and possibly less so with sulindac and aspirin. A potential drug interaction can occur with angiotensin-converting enzyme inhibitors, causing lithium retention (see Chapter 29). 

A 58-year-old woman, with a stable serum-lithium level of between 0.5 and 0.9 mmol/L, developed renal impairment associated with severe lithium toxicity, within 5 days of starting to take celecoxib 400 mg twice daily. Her lithium level was 4 mmol/L. Of note, and a possible contributory factor, was the presence of ibuprofen, which she had taken with her lithium for several years without incident. ... 

Three patients stabilised on lithium, with plasma levels of 0.7 to 0.9 mmol/L, were given ibuprofen 1.2 or 2.4 g daily for 7 days. The serum-lithium levels of one patient rose from 0.8 to 1 mmol/L and he experienced nausea and drowsiness. The 2 other patients, including the one on the 1.2-g ibuprofen dose, did not show this interaction. ... 

Three other case reports describe patients with symptoms of lithium toxicity that occurred within 1 to 7 days of them starting to take ibuprofen 1.2 g daily.In another case, episodes of unsteadiness and tremor associated with raised lithium levels were attributed to varying use of prescribed ibuprofen 400 mg three times daily. ... 

In their continuing studies Heathcock and his co-workers have reported that preformed lithium enolates of hindered aryl esters condense with aldehydes to give predominantly tf rco-/3-hydroxy-acids after hydrolysis. Optically active hydroxy-acids have been prepared from optically active propargyl alcohols, which are readily available in high optical purity by reduction of propargyl ketones with /3-3-pinanyl-9-borabicyclo[3.3.1]nonane. ° A 1,6-eliminative epoxide cleavage provides an effective synthesis of a naturally occurring aromatic hydroxy-acid, which is a metabolite of ibuprofen. ... 

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