Lithium serum-level monitoring

Parameters to monitor Perform the following laboratory tests prior to and periodically during lithium therapy Serum creatinine complete blood count urinalysis sodium and potassium fasting glucose electrocardiogram and thyroid function tests. Check lithium serum levels twice weekly until dosage is stabilized. Once steady state has been reached, monitor the level weekly. Once the patient is on maintenance therapy, the level may be checked every 2 to 3 months. 

The reasons for this interaction are not understood, although trimethoprim may affect the renal excretion of lithium. The general importance of this interaction is uncertain. If concurrent use is undertaken it would clearly be prudent to monitor the clinical response, as it would appear that in this situation serum level monitoring might not always be a reliable guide to toxicity. Consider also Lithium + Antibacterials , p.lll3. 

LITHIUM The dosage of lithium is individualized according to serum levels and clinical response to the drug. The desirable serum lithium levels are 0.6 to 1.2 mEq/L Blood samples are drawn immediately before die next dose of lithium (8-12 hours after the last dose) when lithium levels are relatively stable During die acute phase die nurse monitors serum lithium levels twice weekly or until die patient s manic phase is under control. During maintenance therapy, the serum lidiium levels are monitored every 2 to 4 months. 

Lithium clearance increases by 50% to 100% during pregnancy. Serum levels should be monitored monthly during pregnancy and weekly the week before delivery. At delivery, a dose reduction to prepregnancy doses and adequate hydration are recommended. 

Lithium ions. Lithium salts (e.g., acetate, carbonate) are effective in controlling the manic phase. The effect becomes evident approx. 10 d after the start of therapy. The small therapeutic index necessitates frequent monitoring of Li+ serum levels. Therapeutic levels should be kept between 0.8-1.0 mM in fasting morning blood samples. At higher values there is a risk of adverse effects. 

III.a.4.3. Changes in renal blood flow. Blood flow through the kidney is partially controlled by the production of renal vasodilatory prostaglandins. If the synthesis of these prostaglandins is inhibited (e.g. by indomethacin), the renal excretion of lithium is reduced with a subsequent rise in serum levels. The mechanism underlying this interaction is not entirely clear, as serum lithium levels are unaffected by some potent prostaglandin synthetase inhibitors (e.g. aspirin). If an NSAID is prescribed for a patient taking lithium the serum levels should be closely monitored. 

Oxcarbazepine is a keto derivative of carbamazepine but offers several advantages over carbamazepine. Oxcarbazepine does not require blood cell count, hepatic, or serum drug level monitoring. It causes less cytochrome P450 enzyme induction than does carbamazepine (but may decrease effectiveness of oral contraceptives containing ethinyl estradiol and levonorgestrel). As opposed to carbamazepine, oxcarbazepine does not induce its own metabolism. These properties, combined with its similarity to carbamazepine, led many clinicians to use this medication for the treatment of bipolar disorder. Randomized controlled trials suggested efficacy in the treatment of acute mania compared with lithium and haloperidol, but these trials were quite small and did not include a placebo control (Emrich 1990). 

As noted earlier, lithium is contraindicated in patients with unstable congestive heart failure or the sick sinus node syndrome ( 307, 328). In older patients or those with prior cardiac histories, a pretreatment ECG should be obtained. Except for the potential adverse interactions with diuretics, the concomitant use of other cardiac drugs is generally safe. Because verapamil may lower serum levels of lithium, however, more careful monitoring may be required to assure continued therapeutic effects (329). Some data also indicate that verapamil may predispose to lithium neurotoxicity. Conversely, increased lithium levels leading to toxicity has occurred with methyidopa and enalapril. When antihypertensive therapy is necessary, b-blockers are a reasonable choice when lithium is coadministered. 

Because no antidote is available, treatment is supportive. A patient s condition should be monitored closely, including fluid intake and output, mental status, and serum levels of lithium, creatinine, and electrolytes. Patients with normal renal function should be able to clear lithium unassisted. If necessary, attempts should be made to remove excess lithium from the body by gastric lavage and emesis. 

Increases in serum lithium concentration have been reported in patients receiving antibacterials (e.g., metronidazole, spectinomycin, tetracyclines, and tlcarcillinJ Regular monitoring of lithium plasma levels is advised when it is combined with cisplatin in cancer patientsJ ... 

Lithium has a narrow therapeutic serum level. The level is monitored every 3-5 days initially and every 2-3 months thereafter. 

The documentation of these interactions is variable and limited, and although only some NSAIDs have been shown to interact, it seems likely that they will all interact to a greater or lesser extent. What is known indicates that most NSAIDs should be avoided, especially if other risk factors are present, unless serum-lithium levels can be very well monitored (initially every few days) and the dosage reduced appropriately. The effeets of sulindac appear to be unpredictable (serum levels raised, lowered or unchanged) so that good monitoring is still necessary. 

Several recent reviews have documented the current status of lithium therapy and its hazards including a task force of the American Psychiatric Association and observations on extensive series of patients followed by individual clinicians (47, 48 ). Another summarizes the issues relating to monitoring of serum levels during treatment (49 ). These reports give perspective to previous information rather than adding new facts. 

A carefully monitored single case (51 ) has documented the relationship of maternal to foetal lithium levels in a woman treated with lithium for the second and third trimester of pregnancy. The close similarities in maternal, umbilical and neonatal lithium levels confirm the absence of a placental barrier. Minor vomiting occurred in the infant until 1 week after delivery when the serum levels of lithium had fallen to below 0.2 mEq/1. 

Toxicity is closely related to serum lithium levels and can occur at therapeutic doses. Facilities for serum lithium determinations are required to monitor therapy. 

Indications and Dosages Alert During acute phase, a therapeutic serum lithium concentration of 1-1.4 mEq/L is required. For long-term control, the desired level is 0.5-1.3 mEq/L. Monitor serum drug concentration and clinical response to determine proper dosage. 

It has narrow therapeutic index and treatment requires facility for therapeutic monitoring of serum lithium levels. 

After resolution of the acute phase, maintenance levels of at least 0.8 mEq/L are necessary for optimal efficacy and should be checked once every 6 to 12 months, or more often if clinically indicated. Other follow-up tests include periodic thyroid function tests, blood urea nitrogen, serum creatinine, serum calcium (because lithium may cause hypoparathyroidism), and an EGG. Thyroid function tests and renal function should be monitored approximately every 6 to 12 months (see the section Maintenance/Prophylaxis Treatment in Chapter 10). 

During pregnancy, serum lithium levels need to be carefully monitored. The 50% to 100% increase in glomerular filtration rate (GFR) that normally occurs in the third trimester will proportionally lower lithium levels due to its increased clearance. Thus, dosage may need to be increased to maintain a therapeutic range ( 341). Because the GFR and lithium clearance quickly return to normal after delivery, it may be wise to stop the drug shortly before delivery and restart a few days after delivery at a lower dose. In summary ... 

Lang, E., Davis, S. (2002). Lithium neurotoxicity The development of irreversible neurological impairment despite standard monitoring of serum lithium levels. Journal of Clinical Neuroscience, 9, 308-309. 

Lithium is administered orally, usually as lithium carbonate in tablet form at a total dose of up to 30 mmol (2 g) per day. Treatment is monitored using regular estimations of blood lithium, taken 12 hr after the previous dose (40, 41). These serum lithium concentrations should lie in the range 0.4-0.8 mM, and higher levels may be associated with toxic side effects, which can include tremor, dizziness, drowsiness, and diarrhea (42, 43). 

Lithium carbonate tablets are also readily analyzed by flame emission spectroscopy after first dissolving them in mineral acids (2,42). Both lithium and sodium levels must be carefully controlled in these tablets. Clinically, lithium levels in serum should be maintained between 3.5 and 7 ppm and may be monitored easily and rapidly by either emission or absorption spectroscopy (43, 44). 

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