Theophylline seizures with

BUPROPION 1. ANTIBIOTICS - fluoroquinolones 2. ANTICANCER AND IMMUNO-MODULATING DRUGS-corticosteroids, interferons 3. ANTIDEPRESSANTS-TCAs 4. ANTIMALARIALS - chloroquine, mefloquine 5. ANTIPSYCHOTICS 6. BRONCHODILATORS -theophylline 7. CNS STIMULANTS 8. PARASYMPATHOMIMETICS T risk of seizures. This risk is marked in elderly people, in patients with a history of seizures, with addiction to opiates/cocaine/ stimulants, and in diabetics treated with oral hypoglycaemics or insulin Bupropion is associated with a dose-related risk of seizures. These drugs, which lower seizure threshold, are individually epileptogenic. Additive effects occur when combined Extreme caution. The dose of bupropion should not exceed 4S0 mg/day (or 150 mg/day in patients with severe hepatic cirrhosis)... 

Seizures with focal onset have been described during treatment of status asthmaticus in adult patients with no previous history of epilepsy (12). Although, serum theophylline concentrations are an unreliable predictor of seizures, seizures occur most commonly at serum concentrations over 40-50 pg/ml (13). Older patients are more likely to have seizures than younger ones at similar theophylline concentrations (14). Patients with pre-existing central nervous system abnormalities (15) or severe pulmonary disease may also be at increased risk (SEDA-17, 1). Theophylline-induced seizures have been reported in two neonates (SEDA-6, 2) the serum theophylline concentration during seizures was 51 gg/ml. 

Common side effects of theophylline therapy include headache, dyspepsia, and nausea. More serious side effects such as lethal seizures or cardiac arrythmias can occur if blood levels are too high. Many derivatives of theophylline have been prepared in an effort to discover an analogue without these limitations (60,61). However, the most universal solution has resulted from the development of reHable sustained release formulations. This technology limits the peaks and valleys in semm blood levels that occur with frequent dosing of immediate release formulations. ControUed release addresses the problems inherent in a dmg which is rapidly metabolized but which is toxic at levels ( >20 7g/mL) that are only slightly higher than the therapeutically efficacious ones (10—20 p.g/mL). Furthermore, such once-a-day formulations taken just before bedtime have proven especially beneficial in the control of nocturnal asthma (27,50,62). 

Concurrent use of the fluoroquinolones with theophylline causes an increase in serum theophylline levels. When used concurrently with cimetidine, the cimetidine may interfere with the elimination of the fluoroquinolones. Use of the fluoroquinolones with an oral anticoagulant may cause an increase in the effects of the oral coagulant. Administration of the fluoroquinolones with antacids, iron salts, or zinc will decrease absorption of the fluoroquinolones. There is a risk of seizures if fluoroquinolones are given with the NSAIDs. There is a risk of severe cardiac arrhythmias when the fluoroquinolones gatifloxacin and moxifloxacin are administered with drains that increase the QT interval (eg, quini-dine, procainamide, amiodarone, and sotalol). 

Isolated seizures that are not epilepsy can be caused by stroke, central nervous system trauma, central nervous system infections, metabolic disturbances (e.g., hyponatremia and hypoglycemia), and hypoxia. If these underlying causes of seizures are not corrected, they may lead to the development of recurrent seizures I or epilepsy. Medications can also cause seizures. Some drugs that are commonly associated with seizures include tramadol, bupropion, theophylline, some antidepressants, some antipsy-chotics, amphetamines, cocaine, imipenem, lithium, excessive doses of penicillins or cephalosporins, and sympathomimetics or stimulants. 

In summary, the adverse effects associated with the quinolones appear presently to be mild to moderate in severity and reversible upon discontinuation of therapy. Severe systemic adverse reactions are rare [62], It is suggested that the use of these agents should be avoided, as far as possible, in children and pregnant women and that caution be used in their administration to patients with a seizure disorder or those taking theophylline or warfarin [62]. Articles suggesting the appropriate clinical usage for these important antibacterials have appeared [64],... 

Seizures Bupropion is associated with a dose-related risk of seizures. Discontinue bupropion and do not restart in patients who experience a seizure while on treatment. Use extreme caution when bupropion is administered to patients with a history of seizure, cranial trauma, or other predisposition(s) toward seizure, or prescribed with other agents (eg, antipsychotics, other antidepressants, theophylline, systemic steroids) that lower seizure threshold. 

Theophylline should be used with caution in patients with myocardial disease, liver disease, and acute myocardial infarction. The half-life of theophylline is prolonged in patients with congestive heart failure. Because of its narrow margin of safety, extreme caution is warranted when coadministering drugs, such as cime-tidine or zUeuton, that may interfere with the metabolism of theophylline. Indeed, coadministration of zileu-ton with theophylline is contraindicated. It is also prudent to be careful when using theophylline in patients with a history of seizures. 

Side effects are usually associated with the increasing serum concentration of theophylline and includes nausea, vomiting, headache, insomnia, tachypnea, epigastric pain, palpitation, hypotension, irritability. Higher doses can cause persistent vomiting, cardiac arrhythmias, intractable seizures, tachycardia. Other side effects include alopecia, hyperglycemia, inappropriate ADH syndrome, rash. 

Use of caffeine has also been recommended to lower the threshold in patients who do not experience an adequate seizure (104,105 and 106). One report, however, found that caffeine appeared to produce neuronal damage in rats receiving ECS (107). Because adenosine may have neuroprotective effects, one postulated mechanism is the ability of methyixanthines (e.g., caffeine, theophylline) to block adenosine receptors. On a positive note, studies have not found a difference in cognitive disruption between patients receiving ECT with or without caffeine (108). Although the implications of the animal data for humans are not clear, and because shorter seizures may be effective in some patients, a conservative approach would be to augment with caffeine only when seizure duration is less than 20 seconds and response is inadequate ( 38). Alternatively, it may be appropriate to switch to BILAT electrode placement or from methohexital to etomidate when UND electrode stimulation produces inadequate seizure duration (even at maximal stimulus intensity) and response is insufficient ( 97, 98). 

Theophylline should be used only where methods to measure theophylline blood levels are available because it has a narrow therapeutic window, and its therapeutic and toxic effects are related to its blood level. Improvement in pulmonary function is correlated with plasma concentrations in the range of 5-20 mg/L. Anorexia, nausea, vomiting, abdominal discomfort, headache, and anxiety occur at concentrations of 15 mg/L in some patients and become common at concentrations greater than 20 mg/L. Higher levels (more than 40 mg/L) may cause seizures or arrhythmias these may not be preceded by gastrointestinal or neurologic warning symptoms. 

An example of a potentially important drug interaction is that which occurs when fluvoxamine is given along with theophyllin (Figure 6—13). In that case, the theo-phyllin dose must be lowered or else the blood levels of theophyllin will rise and possibly cause side effects, even toxic side effects such as seizures. The same may occur with caffeine. Fluvoxamine also affects the metabolism of atypical anti-psychotics. 

Theophylline [the OFF i lin] is a bronchodilator that relieves airflow obstruction in chronic asthma, and decreases the symptoms of the chronic disease. Previously the main-stay of asthma therapy, theophylline has been largely replaced with (3-agonists and corticosteroids. Theophylline is well absorbed by the gastrointestinal tract, and several sustained-release preparations are available. The drug has a narrow therapeutic window, and an overdose of the drug may cause seizures or potentially fatal arrhythmias. Further, theophylline interacts adversely with many drugs. See pp. 450-451 for a description of newly approved drugs, zileuton, zafirlukast, and montelukast. 

Amfebutamone has been linked to 41 deaths (17). From the reports of suspected adverse events received by the Netherlands Pharmacovigilance Foundation, it appears that more than half concerned patients at risk of smoking-related diseases. In 15 cases there had been simultaneous use of amfebutamone with another antidepressant (10 patients), theophylline (1 patient), or insulin (4 patients). These combinations may lead to an increase in the risk of seizures. Furthermore, two patients reported having taken antiepileptic drugs, despite the fact that amfebutamone is contraindicated in patients with seizure disorders. These results suggest that the guidelines described in the product information are not being adhered to in some cases. 

CIMETIDINE FAMOTIDINE NIZATIDINE, RANITIDINE BRONCHODILATORS -THEOPHYLLINE t efficacy and adverse effects, including seizures. There is conflicting information associated with ranitidine, famotidine and nizatidine Inhibition of metabolism via CYP1A2, cimetidine being the best known inhibitor Use alternative acid suppression, e.g. a proton pump inhibitor (not omeprazole or lansoprazole) or monitor closely considerable patient variation. Check levels on day 3 and then at 1 week. A 30-50% i dose of theophylline may be required. For doses <400 mg/day, the interaction may not be clinically significant... 

Fluvoxamine administered with either caffeine or theophylline can thus cause jitteriness, excessive stimulation, or rarely seizures, so concomitant use should proceed cautiously... 

Overdose with theophylline has assumed greater importance with the advent of sustained-release preparations which prolong toxic effects, with peak plasma concentrations being reached 12-24 h after ingestion. Vomiting may be severe but the chief dangers are cardiac arrhythmia, hypotension, hypokalaemia and seizures. Activated charcoal should be given every 2-4 h until the plasma concentration is below 20 mg/1. Potassium replacement is important to prevent arrhythmias. Diazepam is used to control convulsions. 

Carbapenems (imipenem more than meropenem) are believed to increase central nervons system excitation by inhibition of GABA binding to receptors. Combinations with other GABA inhibiting drngs snch as theophylline or qninolones have been reported to provoke seizures (45,46). 

Fluoroquinolones are potent inhibitors of hepatic cytochrome P450 isozymes (150). They inhibit theophylline metabolism, and accumulation of theophylline has led to seizures (151). Theophylline clearance is reduced by about 10% by norfloxacin, 30% by ciprofloxacin, and 70% by enoxacin (152-162). In a comparison of grepa-floxacin (400 and 600 mg/day) and ciprofloxacin, increased theophylline concentrations associated with clinical symptoms were found with both doses of grepa-floxacin but not in patients taking ciprofloxacin (17). The dosage of theophylline should be reduced when a quino-lone is given. 

Parish RA, Haulman NJ, Burns RM. Interaction of theophylline with erythromycin base in a patient with seizure activity. Pediatrics 1983 72(6) 828-30. 

In an investigation of 510 episodes of raised theophylline concentrations in 214 hospitalized patients, the authors concluded that life-threatening events can occur in critically ill patients or patients with past seizures or dysrhythmias with mildly raised theophyUine concentrations (21-40 pg/ml) (36). 

In healthy volunteers, theophylline reduced circulating pyridoxal phosphate (vitamin B6) concentrations, presumably by noncompetitive inhibition of pyridoxal kinase. Theophylline concentrations of approximately 10 gg/ml produced only partial inhibition, plasma pyridoxal kinase and pyridoxal concentrations being unaffected. The authors speculated that with theophylline overdose and greater inhibition, vitamin B6 deficiency might contribute to seizures (SEDA-14, 2). 

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