Phenazone interaction

Breckenridge A, Orme ML, Thorgeirsson S, Davies DS, Brooks RV. Drug interactions with warfarin studies with dichloralphenazone, chloral hydrate and phenazone (anti-pyrine). Clin Sci 1971 40(4) 351-64. 

Many of the chemical interactions with carbon disulfide appear to be related to loss of microsomal cytochrome P-450. Carbon disulfide suppresses the hepatic cytochrome P-450 microsomal enzyme system. Elimination of phenazone, a drug often used in the study of hepatic microsomal enzyme activity, is significantly and reversibly inhibited in rabbits exposed to 193 ppm carbon disulfide for 5 hours a day, 6 days a week, for 6 months (Orzechowska et al. 1984). It has been proposed that the active sulfur atoms released following carbon disulfide metabolism suppress the cytochrome P-450 enzymes, thus inhibiting detoxification of other drugs or chemicals. 

Lau, A.H. Chang, C.W. Schlesinger, P.K. Evaluation of a potential drug interaction between sucralfate and aspirin. Clin.Pharmacol.Ther, 1986, 39, 151-155 [plasma pharmacokinetics extracted metabolites, salicylic acid, salicyluric acid a-phenylcinnamic acid (IS) gradient column temp 30] Mamolo, M.G. Vio, L. Maurich, V. Higb-pressure liquid chromatographic analysis of paracetamol, caffeine and acetylsalicylic acid in tablets. Salicylic acid quantitation. Farmaco.[Prat]., 1985, 40, 111— 123 [tablets simultaneous ac etcuninophen, caffeine, phenazone, salicylic acid]... 

The probable reason is that the phenobarbital increases the metabolism of these NSAIDs by the liver, thereby hastening their clearance. Phenazone is metabolised by mixed function oxidase enzymes in the liver, for which reason it is extensively used as a model drug for studying whether other drugs induce or inhibit liver enzymes. In one study phenobarbital caused about a 40% reduction thereby demonstrating that the liver enzymes were being stimulated to metabolise the phenazone more rapidly. The clinical importance of these interactions is uncertain (probably small) but be alert for any evidence of reduced NSAID effects if phenobarbital is added. 

An established interaction. The effects of concurrent use should be monitored and the dosage of warfarin increased appropriately. However, note that phenazone is little used clinically, and an alternative NSAID ,... 

In a pharmacokinetic study, 10 elderly women with breast cancer were given anastrozole 1 mg daily for 10 weeks and 5 of them who also had hypertension were additionally given quinapril, after week 4, for 28 days. Quinapril did not affect plasma anastrozole levels and dose modification is not required during concurrent use. A clinical study with cimetidine has shown that it does not affect the pharmacokinetics of anastrozole, which suggests that anastrozole is unlikely to be affeeted by other drugs that inhibit cytochrome P450. Another clinical study showed that anastrozole does not affect the pharmacokinetics of antipyrine (phenazone), so that it is unlikely to interact with those drugs which are known to be affected by enzyme inducers and inhibitors. 

The results of an interaction study between bicalutamide and phenazone suggest that bicalutamide is unlikely to interact with other drugs through enzyme induction. 

Ticlopidine-induced increases in bleeding times are opposed by methylprednisolone and prednisolone but its effects on platelet function are not affected. Ticlopidine decreases the clearance of phenazone (antipyrine), which suggests that it has mild enzyme-inhibiting effects. Beta blockers, calcium-channel blockers and diuretics are reported not to interact with ticlopidine. 

---