Carbamazepine adverse effects

Evidence for these interactions is limited and in some cases the effects are only modest. Nevertheless, it would seem prudent to monitor the outcome of adding azole antifungals to established carbamazepine treatment, being alert for any evidence of increased carbamazepine adverse effects. 

The interaction between carbamazepine and cimetidine is established but of minimal importance. Patients receiving long-term treatment with carbamazepine should be warned that for the first few days after starting to take cimetidine they may possibly experience some increase in carbamazepine adverse effects (nausea, headache, dizziness, fatigue, drowsiness, ataxia, an inability to concentrate, a bitter taste). However, because the serum levels are only transiently increased, these effects should subside and disappear by the end of a week. Ranitidine appears to be a noninteracting alternative to cimetidine. 

FIGURE 27-3. Serum concentrations of carbamazepine in the presence and absence of appropriate dose titration. Carbamazepine induces its own metabolism, so maintenance dose requirements are much greater than starting doses. To avoid excessive adverse effects, starting doses should be 25% to 30% of the target maintenance doses and increased gradually to the target maintenance dose, usually over 3 to 4 weeks. 

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. 

Oxcarbazepine Modulate sodium channels Loading dose Not recommended due to excessive adverse effects Maintenance dose 600-1200 mg/day. Start at 300 mg twice daily and titrate upward as indicated by response Half-life Not established Parent drug 2 hours 1 0-monohydroxy metabolite 9 hours Apparent volume of distribution 0.5-0.7 L/kg Protein binding 40% Primary elimination route Hepatic Diplopia, dizziness, somnolence Hyponatremia, 25-30% cross sensitivity in patients with hypersensitivity to carbamazepine... 

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. 

Topiramate Topamax Suspension 300 mg/5 mL Tablet 25, 100, 200 mg Doses should be slowly adjusted up and down according to response and adverse effects (e.g., 150-300 mg twice daily and increase by 300-600 mg/day at weekly intervals) 50-200 mg/day in divided doses drug-drug interactions than carbamazepine, but causes more gastrointestinal side effects and hyponatremia Evidence is limited regarding efficacy Not recommended for the... 

Adverse Effects Adverse effects due to oxcarbazepine include drowsiness, dizziness, gastrointestinal upset, and hyponatremia, the latter two of which may be more likely than with carbamazepine. It is less likely than carbamazepine to cause hematologic abnormalities.34... 

Carbamazepine and valproic acid had equal retention rates for tonic-clonic seizures, but carbamazepine was superior for partial seizures, and valproic acid caused more adverse effects. 

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... 

Carbamazepine stimulates antidiuretic hormone activity and has been used for the treatment of neurohypophyseal diabetes insipidus. Carbamazepine induces microsomal enzymes and its metabolism is subject to auto-induction. Frequently occurring adverse effects are sedation, dry mouth, dizziness and gastrointestinal disturbances. Photosensitivity reactions, urticaria and Stevens-Johnson syndrome have been described. The elderly are more prone to mental confusion, cardiac abnormalities and problems due to inappropriate ADH secretion. 

Oxcarbazepine is a derivative of carbamazepine and although its precise mechanism of action is unknown it has similar properties as carbamazepine and is also used for the treatment of primary generalized tonic-clonic seizures and partial seizures. Also the adverse effects are similar to those of carbamazepine. However the drug interaction profile is different as oxcarbazepine has hardly any enzyme-inducing capacity. 

Elderly no data specifically concerning the elderly is available for second generation AEDs adverse effects with first generation AEDs result from kinetic alterations carbamazepine is often poorly tolerated. 

Oxcarbazepine is chemically and pharmacologically closely related to carbamazepine, but it has much less capacity to induce drug-metabolizing enzymes. This property decreases the problems associated with drug interactions when oxcarbazepine is used in combination with other drugs. The clinical uses and adverse effect profile of oxcarbazepine appear to be similar to those of carbamazepine. 

Stemebring B., A. Linden, K. Anderson, and A. Melander (1992). Carbamazepine kinetics and adverse effects during and after ethanol exposure in alcoholics and healthy volunteers. European Journal of Clinical Pharmacology 43 393-397. 

Carbamazepine has been shown to be better tolerated as long-term monotherapy than DVP in children with epilepsy or febrile convulsions (Herranz et ah, 1988). Nevertheless, a comparison of the adverse effect profile in the Kowatch sample (Kowatch et ah, 2000) shows that nausea (46%), rash (8%), and dizziness (8%) were more prevalent in youngsters taking CBZ, compared to children on DVP, who experienced overall less nausea (20%), rash (0%), and dizziness (0%). 

Assessment of physical, as well as psychiatric status, is also critically important. The presence of intercurrent medical disorders, as well as any medication used to manage them, increases the likelihood of an adverse outcome with an otherwise appropriate medication. With a recent history of myocardial infarction, certain tricyclic antidepressants (TCAs) or low-potency antipsychotics might be contraindicated due to potential adverse effects on cardiac function. Another example is the avoidance of carbamazepine in a bipolar patient with a persistently low white blood cell count. Finally, b-blockers are typically contraindicated in a patient with asthma. 

In this context, the first role of the laboratory is to detect specific adverse effects to target organs (see Role of the Laboratory later in this chapter). Monitoring will generally be tailored to the specific therapy used because of its known potential for causing certain problems. Examples include periodic blood counts with carbamazepine or clozapine and thyroid and renal function studies with long-term maintenance lithium. 

The most common dose-related adverse effects of carbamazepine are diplopia and ataxia. The diplopia often occurs first and may last less than an hour during a particular time of day. Rearrangement of the divided daily dose can often remedy this complaint. Other dose-related complaints include mild gastrointestinal upsets, unsteadiness, and, at much higher doses, drowsiness. Hyponatremia and water intoxication have occasionally occurred and may be dose-related. 

Oxcarbazepine is less potent than carbamazepine, both in animal models of epilepsy and in epileptic patients clinical doses of oxcarbazepine may need to be 50% higher than those of carbamazepine to obtain equivalent seizure control. Some studies report fewer hypersensitivity reactions to oxcarbazepine, and cross-reactivity with carbamazepine does not always occur. Furthermore, the drug appears to induce hepatic enzymes to a lesser extent than carbamazepine, minimizing drug interactions. Although hyponatremia may occur more commonly with oxcarbazepine than with carbamazepine, most adverse effects that occur with oxcarbazepine are similar in character to reactions reported with carbamazepine. 

If these measures fail, clonidine, fluphenazine, clonazepam, or carbamazepine should be tried. The pharmacologic properties of these drugs are discussed elsewhere in this book. Clonidine reduces motor or vocal tics in about 50% of children so treated. It may act by reducing activity in noradrenergic neurons in the locus coeruleus. It is introduced at a dose of 2-3 mcg/kg/d, increasing after 2 weeks to 4 mcg/kg/d and then, if required, to 5 mcg/kg/d. It may cause an initial transient fall in blood pressure. The most common adverse effect is sedation other adverse effects include reduced or excessive salivation and diarrhea. Phenothiazines such as fluphenazine sometimes help the tics, as do dopamine... 

Carbamazepine has been considered to be a reasonable alternative to lithium when the latter is less than optimally efficacious. The mode of action of carbamazepine is unclear, and oxcarbazepine is not effective. Carbamazepine may be used to treat acute mania and also for prophylactic therapy. Adverse effects (discussed in Chapter 24) are generally no greater and sometimes less than those associated with lithium. Carbamazepine may be used alone or, in refractory patients, in combination with lithium or, rarely, valproate. 

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