Diclofenac reduces dose of midazolam needed to produce sedation and hypnosis. Diazepam has a small effect on pharmacokinetics of diclofenac, ibuprofen and naproxen. Diazepam andindometacin appear not to interact adversely,although feelings ofdizziness may be increased. Zaleplon and ibuprofen appear not tointeract.
Clinical evidence,mechanism, importance and management
Diclofenac. In a study in 8 healthy subjects, diazepam increased AUC of diclofenac by 60 % while clearance was reduced by 36 % (See reference number 1). The effects of diazepam on diclofenac appeared to depend on time of administration and may reflect time-dependent effects of diazepam on gastrointestinal function. More study is needed.
Ibuprofen. A study in 8 healthy subjects investigating effects of diazepam on ibuprofen pharmacokinetics found that ibuprofen half-life was increased from 2.39 to 3.59 hrs and clearance was reduced by about one-third when diazepam and ibuprofen were given at 10 pm, but no effect was seen with morning dosing (See reference number 2). The clinical importance of this is uncertain.
Indometacin. Diazepam 10 to 15mg impaired performance of a number of psychomotor tests (digit symbol substitution, letter cancellation, tracking and flicker fusion) in 119 healthy medical students. It also caused subjective drowsiness,mental slowness and clumsiness. When indometacin 50 or 100mg was given effects were little different from diazepam alone, except that feeling of dizziness (common to both drugs) was increased and caused subjective clumsiness (See reference number 3).
Naproxen. A double-blind,crossover study failed to find any clinically important changes in mood or attention in healthy subjects given naproxen and diazepam (See reference number 4). A single-dose study in 10 healthy subjects found that peak serum concentrations of naproxen 500mg were reduced by 23%, time to peak concentration was increased (1.36 to 2 hours) and absorption rate constant was decreased (4.07 to 2.42 h(See reference number –1)) by diazepam 10 mg. Other pharmacokinetic parameters were not affected (See reference number 5). No special precautions appear to be necessary.
A clinical study found that diclofenac 75mg given intravenously to 10 patients reduced dose of intravenous midazolam needed to produce sedation and hypnosis by 35%, when compared with 10 control subjects not given diclofenac (See reference number 6). The clinical importance of this is uncertain.
For interactions of parecoxib with midazolam see NSAIDs; Parecoxib + Miscellaneous interaction
A randomised, single-dose study in 17 healthy subjects found that ibuprofen 600mg had no effect on pharmacokinetics of zaleplon 10mg (See reference number 7).
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