Carbamazepine monitoring

Kintz et al. evaluated the potential usefulness of hair analysis in carbamazepine monitoring, i.e., index of dosing history and compliance in 30 epileptic patients under the same medical treatment for at least 6 months. Carbamazepine concentrations in the first proximal 3-cm hair portion ranged from 1.2 to 57.4 ng/mg. The concentration in hair was significantly (p < 0.0001) correlated with the daily dose of the drug (r = 0.793). 

CARBAMAZEPINE CALCIUM CHANNEL BLOCKERS Diltiazem and verapamil T plasma concentrations of carbamazepine (have been cases of toxicity) Diltiazem and verapamil inhibit CYP3A4-mediated metabolism of carbamazepine. They also inhibit intestinal P-gp, which may t bioavailability of carbamazepine Monitor carbamazepine levels when initiating calcium channel blockers, particularly diltiazem/verapamil... 

The effects of buspirone are decreased when the drug is administered with fluoxetine Increased serum levels of buspirone occur if the drug is taken with erythromycin or itraconazole Should any of these combinations be required, the dosage of buspirone is decreased to 2.5 mg BID, and the patient is monitored closely. Venlafaxine blood levels increase with a risk of toxicity when administered witii MAOIs or cimetidine There is an increased risk of toxicity when trazodone is administered with the phenothiazines and decreased effectiveness of trazodone when it is administered with carbamazepine Increased serum digoxin levels have occurred when digoxin is administered with trazodone There is a risk for increased phenytoin levels when phenytoin is administered witii trazodone... 

One chronic adverse effect that is of concern is osteoporosis.32,33 Carbamazepine, phenytoin, phenobarbital, oxcarbazepine, and valproate have all been shown to decrease bone mineral density, even after only 6 months of treatment. Data on the relationship between other AEDs and osteoporosis are not currently available. Multiple studies have shown the risk of osteoporosis due to chronic AED use to be similar to the risk with chronic use of corticosteroids. Patients taking carbamazepine, phenytoin, phenobarbital, or valproate for longer than 6 months should take supplemental calcium and vitamin D. Additionally routine monitoring for osteoporosis should be performed every 2 years, and patients should be instructed on ways to protect themselves from fractures. 

Monitor for acute and chronic adverse effects of AEDs. Acute adverse effects are best detected by a thorough neurologic examination at clinic visits. Instruct patients to report sedation, ataxia, rash, or other problems immediately. Monitor for chronic adverse effects including a loss of bone mineral density, which should be measured every 2 years in patients taking phenytoin, phenobarbital, carbamazepine, and valproate. 

Carbamazepine Manufacturer recommends CBC and platelets (and possibly reticulocyte counts and serum iron) at baseline, and that subsequent monitoring be individualized by the clinician (e.g., CBC, platelet counts, and liver function tests every 2 weeks during the first 2 months of treatment, then every 3 months if normal). Monitor more closely if patient exhibits hematologic or hepatic abnormalities or if the patient is receiving a myelotoxic drug discontinue if platelets are less than 100,000/mm3, if white blood cell (WBC) count is less than 3,000/mm3 or if there is evidence of bone marrow suppression or liver dysfunction. Serum electrolyte levels should be monitored in the elderly or those at risk for hyponatremia. Carbamazepine interferes with some pregnancy tests. 

Oxcarbazepine Hyponatremia (serum sodium concentrations less than 125 mEq/L) has been reported and occurs more frequently during the first 3 months of therapy serum sodium concentrations should be monitored in patients receiving drugs that lower serum sodium concentrations (e.g., diuretics or drugs that cause inappropriate antidiuretic hormone secretion) or in patients with symptoms of hyponatremia (e.g., confusion, headache, lethargy, and malaise). Hypersensitivity reactions have occurred in approximately 25-30% of patients with a history of carbamazepine hypersensitivity and requires immediate discontinuation. 

In a recent study, Walters et al. [141] described the occurrence and loss of several PhC from biosolid-soil mixtures exposed at ambient outdoor conditions for 3 years. Some compounds showed no detectable loss over the monitoring period, including diphenhydramine, fluoxetine, thiabendazole and triclosan, while half-life estimates ranging from 182 to 3,466 days were determined for others such as azithromycin, carbamazepine, ciprofloxacin, doxycycline, tetracycline, 4-epitetracycline, gemfibrozil, norfloxacin and triclosan. These findings highlight the potential use of T. versicolor to reduce the impact of biosolids once released to the environment, which could reduce the concentrations of PhC in much shorter periods of treatment. 

Jerling M, Lindstrom L, Bondesson U, Bertilsson L. Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine evidence from a therapeutic drug monitoring service. 

Isoniazid Carbamazepine, phenytoin Decreased metabolism of other agents (nausea, vomiting, nystagmus, ataxia) Monitor drug SDC... 

Carbamazepine therapy is initiated at 200-400 mg/day in two divided doses, and the typical daily dose is often in the 1000-2000 mg/day range. There are no established plasma levels for carbamazepine specifically established for BEAD, so the levels used in monitoring the drug in the treatment of epilepsy (i.e., 4-12 ig/mL) are typically used. 

Before beginning treatment with carbamazepine, liver function tests, a complete blood count with platelets and reticulocytes, and a pregnancy test should be performed. Long-term monitoring of carbamazepine therapy includes periodic assessment of liver function tests, complete blood count, reticulocyte count, and carbamazepine levels. These should be performed every 2 months during the first 6 months of treatment and every 6-12 months thereafter. 

Carbamazepine is more widely used for treating chronically agitated dementia patients. Its onset of action is delayed by several days to a couple of weeks therefore, other tranquilizing medications such as antipsychotics may need to be used when first starting carbamazepine. Carbamazepine doses have problematic side effects that require blood monitoring, and it also interacts with many medications. 

Unlike carbamazepine, valproic acid has few drug interactions, an added benefit for elderly patients. One interaction worthy of mention, however, is that aspirin can increase levels of valproic acid. For this reason, vascular dementia patients taking an aspirin a day may need a lower dose of valproic acid or at least more careful monitoring of blood levels when starting valproic acid. 

Carbamazepine is believed to be effective in BPD, though the data is far less robust than with valproic acid. It is prescribed at doses up to 1200mg/day. Like valproic acid, it can also canse birth defects and requires laboratory monitoring including serum levels. For more information on the use of carbamazepine, please refer to the discussion of bipolar disorder treatment in Chapter 3. 

H. Qu, J. Kohonen, M. Louhi-Kultanen, S.-P. Reinikainen and J. Kallas, Spectroscopic monitoring of carbamazepine crystallization and phase transformation in ethanol-water solution, Ind. Eng. Chem. Res., 47, 6991-6998 (2008). 

Carbamazepine is an anti-epileptic, which may also be used in the treatment of trigeminal neuralgia. Monitoring of carbamazepine plasma concentrations is required if high doses are administered as carbamazepine tends to be an autoinducer, meaning that the half-life is shortened following repeated administration of the drug. 

Carbamazepine, phenytoin, pheno-barbital, and other anticonvulsants (except for gabapentin) induce hepatic enzymes responsible for drug biotransformation. Combinations between anticonvulsants or with other drugs may result in clinically important interactions (plasma level monitoring ). 

While regular monitoring of plasma phenytoin levels can result in improved seizure control, the benefit derived from measuring other commonly prescribed anticonvulsant drugs is difficult to assess. Phenobarbitone, primidone, and carbamazepine will be discussed briefly. 

Buspirone (BuSpar) [Anxiolytic] WARNING Closely monitor for worsening depression or emergence of suicidality Uses Short-term relief of anxiety Action Antianxiety antagonizes CNS serotonin receptors Dose Initial 7.5 mg PO bid T by 5 mg q2-3d to effect usual 20-30 mg/d max 60 mg/d Contra w/ MAOI Caution [B, /-] Avoid w/ severe hepatic/renal insuff Disp Tabs SE Drowsiness, dizziness, HA, N, EPS, serotonin synd, hostility, depression Notes No abuse potential or physical/psychologic d endence Interactions T Effects W/ erythromycin, clarithromycin, itraconazole, ketoconazole, diltiazem, verapamil, grapefruit juice effects W/ carbamazepine, rifampin, phenytoin, dexamethasone, phenobarbital, fluoxetine EMS T Sedation w/ concurrent EtOH use grapefruit juice may T risk of adverse effects OD May cause dizziness, miosis, N/V symptomatic and supportive... 

Citalopram (Celexa) [Antidepressant/SSRI] WARNING Closely monitor for worsening depression or emergence of suicidality, particularly in pts <24 y Uses Depression Action SSRI Dose Initial 20 mg/d, may t to 40 mg/d X in elderly hqjatic/renal insuff Caution [C, +/-] Hx of mania, Szs pts at risk for suicide Contra MAOI or w/in 14 d of MAOI use Disp Tabs, cap, soln SE Somnolence, insomnia, anxiety, xerostomia, diaphoresis, sexual dysfxn Notes May cause X Na /SIADH Interactions t Effects W/ azole antifungals, cimetidine, Li, macrolides, EtOH t effects OF BBs, carbamazepine, CNS drugs, warfarin X effects W/ carbamaz ine X effects OF phenytoin may cause fatal Rxn W/ MAOIs EMS Use caution w/ CNS depressants, may need a reduced dose concurrent EtOH... 

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