Paracetamol Carbamazepine

Stuer et al. [46] evaluated the presence of the 25 most used pharmaceuticals in the primary health sector in Denmark (e.g., paracetamol, acetyl salicylic acid, diazepam, and ibuprofen). They compared PECs with experimental determinations and they conclude that measured concentrations were in general within a factor of 2-5 of PECs. Carballa et al. [45] also determined PECs for pharmaceuticals (17), musk fragrances (2) and hormones (2) in sewage sludge matrix. For that purpose they used three different approaches (1) extrapolation of the per capita use in Europe to the number of Spanish inhabitants for musk fragrances (2) annual prescription items multiplied by the average daily dose for pharmaceuticals and (3) excretion rates of different groups of population for hormones. They indicated that these PECs fitted with the measured values for half of them (carbamazepine, diazepam, ibuprofen, naproxen, diclofenac, sulfamethoxazole, roxithromycin, erythromycin, and 17a-ethiny I e strad iol). 

Cyt 3A3/4 metabolizes clozapine, sertindole, quetiapine common substrates -tricyclic antidepressants, nefazodone, sertraline, carbamazepine, ethosuximide, terfenadine, benzodiazepines, diltiazem, nifedipine, verapamil, erythromycin, cyclosporine, lidocaine, quinidine, cisapride, paracetamol. Common inhibitors -nefazodone, fluvoxamine, fluoxetine, ketoconazole. 

Parikh S, Dillon LC, Scharf SL. Hepatotoxicity possibly due to paracetamol with carbamazepine. Intern Med J 2004 34 441 442. 

Sotalol, metoprolol, propranolol, carvedilol, nifedipine, captopril, cilazapril, milrinone, ticlopidine, acenocoumarol, furosemide, acetylsalicylic acid, salicylic acid, ibuprofen, naproxen, ketoprofen, diclofenac, paracetamol, dipyrone, mildronate, sildenafil, dexa-methasone, carbamazepine, terbinafine/urine UHPLC MS/MS Column Zorbax Rapid Resolution High Definition SB-C18 (50 x 2.1 mm, 1.8 pm) Mobile phase Solvent A 0.1 % HCOOH in water Solvent B MeOH (gradient elution) Detection MS/MS, ionization ESI Protein precipitation LOQ 0.05-0.60 ng/mL [71]... 

It is interesting to note that PVP that contained only one hydrogen bonding carbonyl group per monomer unit was ineffective even at 500 times higher molar concentration than the minimum concentration of HPMC required to completely inhibit the transformation of carbamazepine to its dihydrate from. " In contrast, crystal habit of paracetamol was found to be effectively modified by PVP with higher influence... 

A 58-year-old man developed stomatitis and widespread edematous erythema with papules and pustules after taking a combination of carbamazepine and paracetamol for 2 days, a most unusual treatment for headache and fever (62). The stomatitis improved but the eruption persisted for 2 months and was diagnosed as eosinophilic pustular folliculitis, a disorder that is rarely drug-induced. Recovery was achieved with glucocorticoid therapy. 

Drugs that induce liver microsomal enzymes, such as phenobarbital, phenytoin, carbamazepine, rifampicin, and isoniazid, can make paracetamol poisoning more severe (104,105). In patients taking such drugs the serum paracetamol concentration should be doubled before consulting the usual treatment nomogram. 

Figure 18.13 Optimized chromatogram of a six-component mixture with acids and bases [reproduced with permission from Y. Hu and D.L. Massart, J. Chromatogr., 485, 311 (1989)]. Conditions column, 25cm x 4mm i.d. stationary phase, LiChrosorb RP18 5ixm mobile phase, 1 ml min methanol-phosphate buffer pH 3.0 (1 1) UV diode array detector. Peaks 1 = paracetamol 2 = acetylsalicylic acid 3 — caffeine 4 = benzocaine 5 = carbamazepine 6 = propyphenazone.

The metabolisim of paracetamol is increased in patients taking enzyme-inducing antiepileptics (carbamazepine, phenytoin, pheno-barbital, primidone). Isolated reports describe unexpected hepatotoxicity in patients taking phenobarbital, phenytoin, or carbamazepine after taking paracetamol. Valproate does not appear to affect paracetamol metabolism. 

Paracetamol modestly reduces the AUC of lamotrigine but appears not to affect phen i oin or carbamazepine. 

The serum levels of phenytoin and carbamazepine in 10 epileptics were not significantly affected by paracetamol 1.5 g daily for 3 days. ... 

Not understood. The effect dextropropoxyphene has on the metabolism of the warfarin enantiomers does not appear to have been studied. Dextropropoxyphene does not interact with other cytochrome P450 isoenzyme CYP2C9 substrates such as tolbutamide , (p.486), although it does interact with the CYP3A4 substrate carbamazepine , (p.527). There is also the possibility that the paracetamol component had some part to play (see also Coumarins + Paracetamol (Acetaminophen) , p.438). Alternatively, these eases may just represent idiosyncratic reactions. 

Paracetamol A pharmacokinetic interaction was suspected in a 34-year-old man taking carbamazepine for complex partial seizures, who developed acute liver and renal failure after taking less than 2.5 g a day of paracetamol [102 ]. 

---