Theophylline dosages

Theophylline is a bronchodilator that is commonly used to treat the symptoms of chronic asthma. The principal enzyme involved in the biotransformation of theophylline is CYPl A2 (126). In a case report, Nebel et al. described an individual who required theophylline dosage adjustment following the initiation and cessation of St. John s wort pharmacotherapy (127). The dose... 

The dose and dosage interval should be rounded to provide clinically accepted values (every 8,12,18, 24, 36, and 48 hours for dosage interval, nearest 5 to 10 mg for conventional dosing or every 24, 36, and 48 hours for dosage interval, nearest 10 to 25 mg for extended interval dosing). This method also has been used to individualize intravenous theophylline dosage regimens. ... 

An oral theophylline dosage regimen should start with a low dose allowing tolerance to develop to the minor caffeine-like side effects frequently associated with the initiation of therapy. This dose should be increased stepwise until slowly... 

When the patient has been stabilized on an effective intravenous regimen, conversion to oral therapy may be performed by dividing the 24-h intravenous theophylline dosage into two or three equal doses of a sustained release formulation. 

Therefore, for the theophylline dosage regimen of 237 mg dose every 8 h,... 

The apparent elearanee of theophylline (given as oral aminophylline, eholine theophyllinate or theophylline) was reduced by 19% in 8 patients with severe, steroid-dependent asthma after 6 weeks of treatment with in-tramuseular methotrexate 15 mg weekly. Three patients complained of nausea and the theophylline dosage was reduced in one of them as the theophylline level was more than 20 mierograms/mL. ... 

It seems probable that aminoglutethimide, a known enzyme inducer, inereases the metabolism of theophylline by the liver, thereby decreasing its levels. The elinieal importanee is uncertain, but it seems likely that the effects of theophylline would be reduced to some extent. Monitor the ef-feets and if neeessary take theophylline levels. Increase the theophylline dosage aeeordingly. 

In contrast, there are 2 case reports of patients who developed theophylline toxicity (theophylline levels raised to 30 mg/L and 41 mg/L), apparently due to the addition of nifedipine. In one case, the toxicity recurred on rechallenge, and resolved when the theophylline dosage was reduced by 60%. During a Swan Ganz catheter study of patient response to nifedipine for pulmonary hypertension, 2 patients developed serious nifedipine adverse effects, which responded to intravenous aminophylline. ... 

Little is known about the effects of smoking cannabis on theophylline levels, but be alert for the need to increase the theophylline dosage in regular users. 

Information appears to be limited to this study but it would seem to be a clinically important interaction. Monitor the serum levels of theophylline and its effects if disulfiram is added, anticipating the need to reduce the theophylline dosage. Note that the extent of this interaction appears to depend upon the dosage of disulfiram used. 

Interactions between theophylline and food have been thoroughly studied but there seems to be no consistent pattern in the way the absorption of different theophylline preparations is affected. Be alert for any evidence of an inadequate response that can be related to food intake. Avoid switching between different preparations, and monitor the effects if this is necessary. Consult the product literature for any specific information on food and encourage patients to take their theophylline consistently in relation to meals where this is considered necessary. Advise patients not make major changes in their diet without consultation. Monitor the effects of both enteral and parenteral nutrition, since theophylline dosage adjustments may he required. 

In 6 healthy subjects oral idrocilamide 600 mg daily for 3 days then 1.2 g for 4 days increased the half-life of a single dose of theophylline 2.5-fold, from 8.5 to 21.6 hours, and reduced the clearance by 67%. This is due to a reduction in the liver metabolism caused by the idrocilamide (see also Caffeine + Idrocilamide , p.ll65). Information is very limited but it indicates that concurrent use should be closely monitored. Anticipate the need to reduce the theophylline dosage with oral idrocilamide. 

The interaction between theophylline and troleandomycin is established and well documented. If troleandomycin is given, monitor the levels of theophylline closely and adjust the dose as necessary. Reductions of 25 to 50% may be needed. The situation with roxithromycin is uncertain since only 1 of 4 studies suggested an interaction, but it would be prudent to be alert for the need to reduce the theophylline dosage. Alternative mac-rolides that usually interact only moderately, or not at all are azithromycin, clarithromycin, dirithromycin, josamycin, midecamycin, rokitamycin and spiramycin. Telithromycin may also he a suitable alternative. However, even with these macrolides it would still be prudent to monitor the outcome because a few patients, especially those with theophylline levels at the high end of the range, may need some small theophylline dosage adjustments. In the case of azithromycin, care should be taken in adjusting the dose based on theophylline levels taken after about 5 days of concurrent use, as they may only he a reflection of a transient drop. In addition, acute infection perse may alter theophylline pharmacokineties. 

The interaetion between theophylline and mexiletine is established and of elinical importanee. Monitor coneurrent use and reduee the theophylline dosage as necessary to prevent the development of theophylline toxieity. It has been suggested that 50% dose reduetions may be neeessary. It seems doubtful if the interaetion between theophylline and toeainide is elinically important but this needs eonfirmation. 

The effect of phenytoin on theophylline is established and of clinical importance. Patients given both drugs should be monitored to confirm that theophylline remains effective. Ideally the serum levels should be measured to confirm that they remain within the therapeutic range. Theophylline dosage increases of up to 50% or more may be required. Conversely, patients should be monitored for signs of toxicity and theophylline levels should be checked in patients who stop phenytoin. The effect of theophylline on phenytoin is not established and the documentation is limited. It may be prudent to monitor phenytoin levels as well. Separating the doses appears to minimise any interaction. Note that theophylline itself can cause seizures, although mostly in overdose, and should be used with caution in patients with epilepsy. 

In a 71-year-old man, propafenone 150 mg daily raised the levels of sustained-release theophylline 300 mg twice daily from a range of 10.2 to 12.8 mg/L to 19 mg/L, and signs of theophylline toxieity developed. The day after propafenone was withdrawn the level fell to 10.8 mg/L. When the propafenone was later restarted the theophylline levels rose again to 17.7 mg/L within one week, but fell when the theophylline dosage was re-dueed by one-third. ... 

The interactions of enoxacin and ciprofloxacin with theophylline are well documented, well established and of clinical importance. The effect of enoxacin is marked and occurs in most patients, whereas the incidence with ciprofloxacin is uncertain and problems do not develop in all patients. The risk seems greatest in the elderly and those with theophylline levels already towards the top end of the therapeutic range. Toxicity may develop rapidly (within 2 to 3 days) unless the theophylline dosage is reduced. 

Koup JR, Toothaker RD, Posvar E, Sedman AJ, Colburn WA. Theophylline dosage adjustment during enoxacin coadm inistration. Antimicrob Agents Chemother (1990) 34, 803-7. 

Theophylline serum levels can be markedly and rapidly increased by fluvoxamine. Toxicity will develop if the theophylline dosage is not suitably reduced. Some preliminary clinical evidence su ests that fluoxetine and citalopram may not interact, and in vitro evidence su ests that paroxetine and sertraline are also unlikely to interact... 

It is established that changes in thyroid status may affect how the body handles theophylline. Monitor the effects and anticipate the possible need to begin to reduce the theophylline dosage if treatment for hyperthyroidism is started (e.g. with radioactive iodine, carbimazole, thiamazole, propylthiouracil, etc.). Similarly, anticipate the possible need to increase the theophylline dosage if treatment is started for hypothyroidism (e.g. with levothyroxine). Stabilisation of the thyroid status may take weeks or even months to achieve so that if monitoring of the theophylline dosage is considered necessary, it will need to extend over the whole of this period. 

An established interaction of clinical importance. Heavy smokers (20 to 40 cigarettes daily) may need much greater theophylline dosage than non-smokers, and increased doses are likely for those who chew tobacco or... 

Information is limited but the interaction appears to be established and of clinical importance. Concurrent use need not be avoided but monitor theophylline levels and reduce the dosage of theophylline as necessary. The report quoted above suggests that a typical asthma patient may initially need the theophylline dosage to be halved, and this dose reduction is recommended by the US manufacturers. Similarly, the dose of theophylline should be reduced if it is given to a patient already taking zileuton, and adjusted according to theophylline levels. This is based on the results of a study in over 1000 patients taking zileuton 600 mg four times daily without apparent problems when this course of action was followed. ... 

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