Headache carbamazepine

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. 

The most frequently reported side effects are dizziness, nausea, headache, diarrhea, vomiting, upper respiratory tract infections, constipation, dyspepsia, ataxia, and nervousness. It generally has fewer side effects than pheny-toin, valproic add, or carbamazepine. Hyponatremia has been reported in up to 25% ofpatients and is more likely in the elderly. About 25% to 30% of patients who have had a rash with carbamazepine will have a cross-reaction with oxcarbazepine. 

Dose-related side effects include dizziness, sedation, headache, ataxia, fatigue, vertigo, abnormal vision, diplopia, nausea, vomiting, and abdominal pain. It causes more hyponatremia than carbamazepine. 

Interferes w/ DNA synth Dose Adults. Anaerobic Infxns 500 mg IV q6-8h Amebic dysentery 750 mg/d PO for 5-10 d Trichomoniasis 250 mg PO tid for 7 d or 2 g PO X 1 C. difficile 500 mg PO or IV qSh for 7-10 d (PO preferred IV only if pt NPO) Vaginosis 1 applicator-full intravag bid or 500 mg PO bid for 7 d Acne rosacea/skin Apply bid Peds. 30 mg/ kg PO/IV/d q6H, 4 g/d max-s-. Amebic dysentery 35-50 mg/kg/24 h PO in 3 -s- doses for 5-10 d Rx 7-10 d for C. difficile-, in hepatic impair Caution [B, M] Avoid EtOH Contra 1st tri of PRO Disp Tabs, caps, IV, topical lotion, intravag gel, cream SE Disulfiram-like Rxn dizziness, HA, GI upset, anorexia, urine discoloration Interactions t Effects W/ cimetidine T effects OF carbamazepine, fluorouracil, Li, warfarin -1- effects W/ barbiturates, cholestyramine, colestipol, phenytoin EMS t Effects of anticoagulants concurrent EtOH use can cause disulfiram-like Rxn (tach, N/V, sweating, flushing, headache, blurred vision, confusion) may cause a metallic taste and discolored urine OD May cause N/V/D, numbness in hands and feet, Szs, and loss of coordination symptomatic and supportive... 

Like most of the agents that block sodium channels, side effects associated with carbamazepine administration involve the central nervous system (CNS). Drowsiness is the most common side effect, followed by nausea, headache, dizziness, incoordination, vertigo, and diplopia. These effects occur particularly when the drug is first taken, but tolerance often develops over a few weeks. There appears to be little risk of cognitive impairment with carbamazepine. 

Ethosuximide Reduces low threshold Ca2+ currents (T-type) Well absorbed orally, with peak levels in 3-7 h not protein-bound completely metabolized to inactive compounds tjy2 typically 40 h Absence seizures Toxicity Nausea, headache, dizziness, hyperactivity Interactions Valproate, phenobarbital, phenytoin, carbamazepine, rifampicin... 

Patients with bipolar disorders may benefit from risperidone. This has been observed in an open trial of ten patients with rapid cycling bipolar disorder who were refractory to lithium carbonate, carbamazepine, and valproate eight improved after 6 months of treatment. One patient dropped out through non-adherence to therapy and one because of adverse effects (agitation, anxiety, insomnia, and headache) (5). There was a similar beneficial effect in eight adults with moderate to profound mental retardation (6). Risperidone was associated with a significant reduction in aggression and self-injurious behavior, whereas adverse effects were primarily those of sedation and restlessness. 

Adverse effects include nausea, headache, diarrhoea, constipation and rash but are uncommon. Omeprazole inhibits the 2C family of the cytochrome P450 system, decreasing the metabolism of warfarin, diazepam, carbamazepine and phenytoin, and enhancing the action of these drugs (but inhibition is less than with cimetidine). 

A 58-year-old man developed stomatitis and widespread edematous erythema with papules and pustules after taking a combination of carbamazepine and paracetamol for 2 days, a most unusual treatment for headache and fever (62). The stomatitis improved but the eruption persisted for 2 months and was diagnosed as eosinophilic pustular folliculitis, a disorder that is rarely drug-induced. Recovery was achieved with glucocorticoid therapy. 

In 126 patients with carbamazepine-resistant or valproate-resistant epilepsy given lamotrigine, 50% during add-on therapy and 53% during lamotrigine monotherapy had at least 50% reduction in total seizures (15). There were adverse events in 49 patients, including respiratory tract infections n — 11), dizziness (n — 8), headache (n = 7), diplopia (n = 5), tremor (n = 5), somnolence (n — 4), insomnia (n = 4), nausea (n — 4), and weakness (n = 3). Treatment was discontinued in nine patients because of adverse events, in five cases because of rash. 

Of 26 patients with complex partial seizures refractory to phenytoin, carbamazepine, phenobarbital, or primidone, mesuximide produced a 50% or greater reduction in seizure frequency in eight after 8 weeks, and five of those continued to benefit after 3-34 months (1). Drowsiness, gastrointestinal disturbances, hiccups, irritability, and headache were the common adverse effects. 

Two doses of oxcarbazepine have been compared in a double-blind, parallel-group, randomized trial in patients with uncontrolled partial-onset epilepsy who had previously taken carbamazepine monotherapy (10). After two open phases in 143 patients, 96 were randomized to oxcarbazepine 300 or 2400 mg/day for 126 days. The time to meet an exit criterion was significantly in favor of oxcarbazepine 2400 mg/day. In aU, 24 of the 47 non-rando-mized patients withdrew because of an adverse event, most commonly dizziness, ataxia, headache, nansea, vomiting, or fatigne. Three withdrew becanse of laboratory abnormalities, one each with leukopenia, hjrponatre-mia, and hjrperglycemia. Headache, dizziness, and nansea were the only adverse events that occurred in more than 10% in either gronp. Similar adverse events were reported in the randomized patients, but none withdrew. 

Oxcarbazepine. Oxcarbazepine (10,11-dihydro-10-oxo-5i -dibenz [6,/] azepine-5-car-boxamide or 10,ll,dihydro-10-oxo carbamazepine, 12) was designed to avoid the dose-dependent side effects noted in some patients (e.g., nausea, headache, dizziness, ataxia, diplopia) and to minimize enzyme induction and drug-drug interactions displayed by carbamazepine (195,196). As shown previously (Fig. 6.3), the change in structure results in a difference in metabolism. Although both carbamazepine and oxcarbazepine are ultimately converted to the inactive trans diol, oxcarbazepine does not form the active 10,11-epoxide intermediate, but does form the active 10-hydroxy metabolite MHD (197). The mechanism of action of oxcarbazepine is very similar... 

I Adverse Effects. Side effects (see Table 54—6) of carbamazepine may fluctuate daily, paralleling the rise and decline of serum concentrations. The side-effect profile also may follow a circadian rhythm. Neurosensory side effects (e.g., diplopia, blurred vision, nystagmus, ataxia, unsteadiness, dizziness, and headache) are the most common, occurring in 35% to 50% of patients. These side effects are more common during initiation of therapy and may dissipate with continued treatment. Patients have variable threshold concentrations for the occurrence of CNS side effects. If the carbamazepine serum concentration is kept below the individual threshold, the CNS side effects can be minimized. Dosage manipulation, including the use of the controlled- or sustained-release preparations, should be tried before the patient is considered to be intolerant of carbamazepine. Carbamazepine may induce a hyponatremic hyposmolar condition that is similar to the syndrome of inappropriate antidiuretic hormone secretion. The incidence may increase with age. Periodic determinations of serum sodium concentration are recommended, especially in the elderly." ... 

The most frequent CNS adverse reactions of carbamazepine are dizziness, drowsiness, and unsteadiness. In addition, it is known to have caused confusion, headache. 

Carbamazepine has a moderate anticholinergic action that may cause symptoms of dry mouth and constipation. CNS effects include somnolence, ataxia, diplopia, loss of accommodation, dizziness, and headache, which are most prominent with overdosage. Erythroderma, photosensitivity, and skin rashes may also be seen, and, rarely, Stevens-Johnson syndrome or systemic lupus-like syndrome also occur. The drug also has other serious adverse effects, such as suppression of ventricular automaticity, and, rarely, blood dyscrasias (e.g.. agranulocytosis, leukopenia, thrombocytopenia, and aplastic anemia). Due to hepatic metabolism, hepatocellular and cholestatic jaundice may also be seen. 

Gl upset (less frequently than erythromycin), headache. Increases plasma concentration of theophylline and carbamazepine. 

Patients with hypersensitivity reactions to carbamazepine can be expected to show cross-sensitivity (e.g., rash) or related problems to oxcarbazepine. The improved toxicity profile for oxcarbazepine when compared to CBZ may result from absence of the epoxide or CBZ-iminoquinone metabolites (47). The most common side effects are headache, dizziness, nystagmus, blurred vision, somnolence, nausea, ataxia, and fatigue. The Incidence of adverse effects has been related to elevated serum MHD concentrations (52). Adverse effects on cognitive status, hyponatremia, and serious dermatological reactions have been reported, as has hyponatremia (53). 

The observation of toxicity (headache, dizziness, ataxia, nausea, tiredness) in patients taking both carbamazepine and dextropropoxyphene prompted further study. Five carbamazepine-treated patients given dextropropoxyphene 65 mg three times daily had a mean rise in serum carbamazepine levels of 65%, and 3 showed evidence of carbamazepine toxicity. Carbamazepine levels were not taken in a further 2 patients because they withdrew from the study after 2 days of treatment due to adverse effects. In a further study a 66% rise in carbamazepine levels was seen after 6 days of treatment with dextropropoxyphene. ... 

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. 

---