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HelpTest ID: CARF Carbamazepine, Free, Serum
Useful For
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 patients who are uremic
Method Name
Ultrafiltration followed by Homogeneous Microparticle Agglutination Immunoassay
Reporting Name
Carbamazepine, Free, SSpecimen Type
Serum RedSpecimen Required
Collection Container/Tube: Red top (serum gel/SST are not acceptable)
Submission Container/Tube: Plastic vial
Specimen Volume: 2 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial within 2 hours of collection.
Specimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum Red | Refrigerated (preferred) | 7 days | |
| Frozen | 28 days | ||
| Ambient | 48 hours |
Clinical Information
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 kidney disease, uremia may develop whose byproducts can displace bound carbamazepine increasing the unbound fraction. Administration of drugs that can 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.
Reference Values
Therapeutic concentration: 1.0-3.0 mcg/mL
Critical value: ≥4.0 mcg/mL
Interpretation
In patients with normal kidney 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, 75% of the carbamazepine that circulates in blood is 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.
Clinical Reference
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(6):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(1):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(3):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
5. Kanner A.M, Ashman E, Gloss D, et al. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2018;91(2):74-81
Day(s) Performed
Monday through Sunday
Report Available
Same day/1 dayTest Classification
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.CPT Code Information
80157
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| CARF | Carbamazepine, Free, S | 3433-0 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| CARF | Carbamazepine, Free, S | 3433-0 |
Forms
If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.
| mml-anticonvulsants |