Monitoring unbound or free carbamazepine levels in patients where the total carbamazepine result is within the therapeutic range but the patient is experiencing side effects
Monitoring carbamazepine (free) therapy in uremic patients
Ultrafiltration Followed By Homogeneous Microparticle Agglutination Immunoassay
CARBAMAZEPINE, FREE ORDER FCAR
Free Carbamazepine ORDER FCAR
Serum Red
Container/Tube: Red top
Specimen Volume: 2 mL
Collection Instructions: Tubes should be centrifuged and aliquoted within 2 hours of collection.
If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.
1 mL
Gross hemolysis | Reject |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Serum Red | Refrigerated (preferred) | 7 days | |
Frozen | 28 days | ||
Ambient | 48 hours |
Monitoring unbound or free carbamazepine levels in patients where the total carbamazepine result is within the therapeutic range but the patient is experiencing side effects
Monitoring carbamazepine (free) therapy in uremic patients
Carbamazepine (Tegretol) is an effective treatment for complex partial seizures, with or without generalization to tonic-clonic seizures.(1) It is frequently administered in conjunction with other antiepileptic agents, such as phenytoin and valproic acid.(2) Under normal circumstances, the carbamazepine that circulates in blood is 70% to 80% protein-bound.(3) Only the free drug is able to enter the interstitial space in the brain where the pharmacological effects occur.(4)
Patient management is best guided by monitoring free serum concentrations when protein binding is altered. Altered protein binding occurs in patients with hypoalbuminemia observed during pregnancy, in the malnourished, and liver disease. In patients with renal disease, uremia may develop whose byproducts can displace bound carbamazepine increasing the unbound fraction. Administration of drugs that are able to compete for serum protein binding sites may also increase the unbound fraction of carbamazepine. Since neurologic activity and toxicity of carbamazepine are directly related to the circulating free fraction of drug, adjustment of dosage based on knowledge of the free carbamazepine concentration may be more useful in these patient populations.
Therapeutic concentration: 1.0-3.0 mcg/mL
Critical value: > or =4.0 mcg/mL
In patients with normal renal function, optimal response is often associated with free (unbound) carbamazepine levels above 1.0 mcg/mL, and toxicity may occur when the free carbamazepine is greater than or equal to 4.0 mcg/mL.
Under normal circumstances, the carbamazepine that circulates in blood is 75% protein-bound. Therapies or conditions such as uremia that displace carbamazepine from protein cause a higher free (unbound) fraction of the drug circulating in blood. In uremia, the free carbamazepine level may be a more useful guide for dosage adjustments than the total level. In patients with severe uremia, subtherapeutic total carbamazepine levels in the range of 1.0 to 2.0 mcg/mL may be associated with therapeutic free carbamazepine levels. Toxicity may occur when the free carbamazepine level is greater than or equal to 4.0 mcg/mL (even though the total carbamazepine concentration is <15.0 mcg/mL).
As with the serum levels of other anticonvulsant drugs, total and free carbamazepine levels should be correlated with the patient's clinical condition. Serum levels are best used as a guide in dose adjustment.
Fresh serum with normal protein content is required for optimal analysis.
Specimens subjected to significant heat or other factors that cause protein denaturation may demonstrate an artifactually increased free carbamazepine level.
1. Svinarov DA, Pippenger CE: Relationships between carbamazepine-diol, carbamazepine-epoxide, and carbamazepine total and free steady-state concentrations in epileptic patients: the influence of age, sex, and comedication. Ther Drug Monit 1996;18:660-665
2. Bernus I, Dickinson RG, Hooper WD, Eadie MJ: The mechanism of the carbamazepine-valproate interactions in humans. Br J Clin Phamacol 1997;44:21-27
3. Dasgupta A, Volk A: Displacement of valproic acid and carbamazepine from protein binding in normal and uremic sera by tolmetin, ibuprofen, and naproxen: presence of inhibitor in uremic serum that blocks valproic acid-naproxen interactions. Ther Drug Monit 1996;18:284-287
4 Patsalos PN, Berry DJ, Bourgeois BF, et al: Antiepileptic drugs-best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia 2008;49(7):1239-1276
Free carbamazepine is isolated from serum by ultrafiltration.
The ONLINE TDM Carbamazepine Gen.4 assay is a homogeneous microparticle agglutination immunoassay. It is a 2-reagent system used for the detection of carbamazepine in serum. Kinetic interaction of microparticles (KIMS) will be measured using automated analyzers. In this technology biotinylated drug hapten attached to streptavidin coated latex beads serves as the binding partner to anti-carbamazepine antibody. A competitive reaction to a limited amount of specific anti-carbamazepine antibody takes place between the latex bound hapten and free carbamazepine in the serum sample. A decrease in the apparent signal is proportional to the amount of drug present in the sample.(Package insert: Roche Carbamazepine reagent, Roche Diagnostic Corp, Indianapolis, IN)
Monday through Sunday
This test has been modified from the manufacturer's instructions. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
80157
Test Id | Test Order Name | Order LOINC Value |
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CARF | Carbamazepine, Free, S | 3433-0 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
CARF | Carbamazepine, Free, S | 3433-0 |