Influenza vaccines Theophylline

Theophylline Cimetidine, erythromycin, influenza vaccine, oral contraceptives Potentiation. 

Grabowski N, May JJ, Pratt DS, Richtsmeier WJ, Bertino JS Jr. The effect of spht virus influenza vaccination on theophylline pharmacokinetics. Am Rev Respir Dis 1985 131(6) 934-8. 

Patriarca PA, Kendal AP, Stricof RL, Weber JA, Meissner MK, Dateno B. Influenza vaccination and warfarin or theophylline toxicity in nursing-home residents. NEngl J A/erf(1983) 308, 1601-2. 

Gomolin IH, Chapron DJ, Luhan PA. Lack of effect of influenza vaccine on theophylline levels and warfarin anticoagulation in the elderly. J Am Geriatr Soc (1985) 33, 269-72. 

Normally none of the influenza vaccines (whole-virion, split-virion and surface antigen) interact with theophylline, but there are three reports describing rises in serum theophylline levels in a few patients (some to toxic levels), which was attributed to the use of an influenza vaccine. 

Three patients who had been taking oral choline theophyllinate (oxtriphylline) 200 mg (equivalent to 128 mg of theophylline) every 6 hours for at least 7 days had a rise in their serum theophylline levels of 219%, 89%, and 85%, respectively, within 12 to 24 hours of receiving 0.5 mL oftriva-lent split-virion influenza vaccine Fluogen, Parke Davis). In some cases effects persisted for up to 72 hours, and two patients showed signs of theophylline toxicity. A subsequent study in 4 healthy subjects found that the same dose of vaccine more than doubled the half-life of theophylline, from 3.3 to 7.3 hours, and halved its clearance. ... 

The clearance of theophylline (given as choline theophyllinate) was reduced by 25% one day after influenza vaccination (trivalent influenza vaccine, F/wogen, Parke Davis) in 8 healthy subjects, but this was of borderline significance. Theophylline metabolism had returned to pre-vaccination levels after 7 days."... 

A patient with COPD treated with sustained-release theophylline 300 mg twice daily (theophylline levels between 7 and 12 mg/L) developed nausea and palpitations the day after he received a trivalent influenza vaccination Fluogen). His theophylline level was increased to 26 [mg/L]. His dose was reduced to 200 mg twice daily and the adverse effects resolved. However, a few days later his COPD had become symptomatic and the theophylline level was found to be subtherapeutic, so the dose was raised to 300 mg twice daily, as before. ... 

A very thoroughly investigated interaction, the weight of evidence being that no adverse interaction normally occurs with any type of influenza vaccine in children, adults or the elderly. Even so, bearing in mind the occasional and unexplained reports of an interaction it would seem pmdent to monitor the effects of concurrent use (for nausea headaches, palpitations), although problems are very unlikely to arise now that purer vaccines are available (see Mechanism ). Note that any rise in theophylline levels is likely to be transient. 

Britton L, Ruben FL. Serum theophylline levels after influenza vaccine. CanMedAssocJ (1982) 126,1375. 

Feldman CH, Rabinowitz A, Levison M, Klein R, Feldman BR, Davis WJ. Effects of influenza vaccine on theophylline metabolism in children with asthma. AmRevRespirDis (1985) 131 (4 Suppl), A9. 

Agents that may increase theophylline levels include allopurinol, beta blockers (nonselective), calcium channel blockers, cimetidine, oral contraceptives, corticosteroids, disulfiram, ephedrine, influenza virus vaccine, interferon, macrolides, mexiletine, quinolones, thiabendazole, thyroid hormones, carbamazepine, isoniazid, and loop diuretics. 

After influenza immunization there was a reduction in blood theophylline concentrations in patients and healthy volunteers (58). The authors concluded that flu vaccine may influence the pharmacokinetics of several drugs, and a second group found that theophylline oxidation was significantly reduced at 1 day, but not at 7 days, after immunization (57). However, others did not confirm these effects (55,59). The lack of a clinical interaction with theophylline has also been confirmed by a report of the US Immunization Practices Advisory Committee (9). 

Uncertain. If an interaction occurs, it has been suggested it is probably due to inhibition of the liver enzymes concerned with the metabolism of theophylline, possibly secondary to interferon production, resulting in theophylline accumulation in the body. - One suggestion is that vaeeine contaminants, which are potent interferon-inducing agents, may be responsible (rather than the vaccine itself), so that an interaction would seem to be less likely with modem highly-purified subunit vaccines. In one study where an interaction occurred, an increase in seram interferon levels was detected, whereas, in two of the studies showing no interaction, no interferon production was detected. " Influenza infection per se can result in decreased theophylline clearance and theophylline toxicity. "... 

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