Cilomilast (Ariflo®) Does Not Potentiate the Cardiovascular Effects of Inhaled Salbutamol

Lack of Pharmacokinetic Interactions Between Cilomilast and Theophylline or Smoking in Healthy Volunteers

“…Indeed, the studies re-ported here present no evidence of a clinically significant interaction between cilomilast and theophylline when the two agents were coadministered in healthy volunteers. The absence of any adverse drug-drug interaction between cilomilast and theophylline supports earlier findings demonstrating a lack of drug-drug interaction potential of cilomilast when coadministered with other commonly prescribed drugs in COPD, such as salbutamol, 14 digoxin, 15 and warfarin. 16 The coadministration studies also served to highlight the ability to switch patients from theophylline to cilomilast-containing regimens in a single dosing regimen, without a need for a washout period, as the pharmacokinetic profile of cilomilast was unaffected by theophylline coadministration.…”

“…Indeed, the studies reported here present no evidence of a clinically significant interaction between cilomilast and theophylline when the two agents were coadministered in healthy volunteers. The absence of any adverse drug‐drug interaction between cilomilast and theophylline supports earlier findings demonstrating a lack of drug‐drug interaction potential of cilomilast when coadministered with other commonly prescribed drugs in COPD, such as salbutamol, 14 digoxin, 15 and warfarin 16 …”

“…Moreover, therapeutic levels of theophylline have been shown to induce marked pharmacodynamic alterations, such as an increase in heart rate and arrhythmias, whereas cilomilast has no significant effect on the cardiovascular system. 14 Although such prescribing would be highly unlikely in a clinical setting, the hypothetical risk for increased gastrointestinal adverse events following coadministration of theophylline and cilomilast was not observed.…”

“…This highlights the benefit for those individuals who appear intolerant to the effects of theophylline to be switched to cilomilast, which has a more favorable prescribing profile. Moreover, therapeutic levels of theophylline have been shown to induce marked pharmacodynamic alterations, such as an increase in heart rate and arrhythmias, whereas cilomilast has no significant effect on the cardiovascular system 14 …”

An update and appraisal of the cilomilast Phase III clinical development programme for chronic obstructive pulmonary disease

“…This review summarizes data obtained since 2001 pertaining primarily to the cilomilast Phase III clinical development programme, highlights some of the potential concerns both specific to cilomilast and to PDE4 inhibitors in general, in particular their low therapeutic ratio, and assesses the likelihood that cilomilast will reach the market. Readers interested in the preclinical pharmacology of cilomilast, Phase I and Phase II clinical trials including details on absorption, distribution, metabolism and pharmacokinetics, safety and tolerability should consult previously published material [9, 12, 21–26]. For completeness and for reference, the most salient facts from the Phase II trials are described below, and a summary of key data relating to cilomilast is provided in Table 1.…”