Influence of allopurinol on drug metabolism in man

Rawlins, M. D.; Smith, Stephen

doi:10.1111/j.1476-5381.1973.tb08258.x

Cited by 19 publications

(7 citation statements)

References 14 publications

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“…Some drugs potentiate the anticoagulant effect, resulting in an increased prothrombin time and risk of bleeding. These drugs include phenylbutazone,l42-44] cimetidine,l45-47] metronidazole, [48] allopurinol, [49] aspirin, [50][51][52] retoprofen)53] meclofenamic acid (meclofenamate))54] phenytoin,l55] dextroproproxyphene,[56J" quinidine, [57] sulindac, [58,59], erythromycin,l60-63] norfloxacin [64] and thyroxine.l 65 ,66] Other drugs, such as barbiturates [67][68][69] and rifampicin (rifampin), [70][71][72] increase hepatic metabolism, which decreases the anticoagulant effect, thereby increasing the dosage requirements. Discontinuation of these drugs Aspirin and other nonsteroidal anti-inflammatory drugs inhibit platelet cyclo-oxygenase which may impair platelet aggregation, [73][74][75][76][77] and they may cause gastric mucosallesions,178-84] These 2 factors probably account for the increased risk of bleeding in patients taking these drugs during anticoagulant therapy.…”

Section: Reasons Why Older Patients May Be At Increased Risk For Antimentioning

confidence: 99%

Anticoagulants in Older Patients

Beyth

Landefeld

1995

Drugs & Aging

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Although anticoagulants are beneficial in the prevention and management of many thromboembolic disorders, they can cause serious bleeding. However, the risk of anticoagulant-related bleeding is not clearly defined for older patients, who are likely to benefit the most from anticoagulant therapy. Older patients may be at increased risk for anticoagulant-related bleeding because of their increased incidence of adverse drug reactions, increased prevalence of comorbidity and polypharmacy and increased vascular and endothelial fragility. Furthermore, the anticoagulant effect of warfarin is increased in older patients. Therefore, it is important to determine whether or not heparin-related and warfarin-related bleeding are more common in older patients. Most studies that have examined age as a risk factor for heparin-related bleeding have found bleeding to be more frequent in older patients: patients 60 years and older were approximately 3 times as likely to develop bleeding during heparin therapy than were younger patients. Studies that have examined age as a risk factor for warfarin-related bleeding have found conflicting results. Seven studies, enrolling a total of 14,388 patients, found that older patients were approximately twice as likely to bleed during warfarin therapy. In contrast, 7 studies, enrolling a total of 2940 patients, found no increase in the frequency of warfarin-related bleeding in older patients. These findings provide a basis for weighing the risks of anticoagulant therapy and for making decisions about the use of anticoagulants in older patients. These findings also indicate the potential value of methods to decrease the frequency of anticoagulant-related bleeding in older patients. Such methods include maintaining the anticoagulant effect within the therapeutic range and recognising other modifiable factors, such as medication use, that may promote bleeding.

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Section: Reasons Why Older Patients May Be At Increased Risk For Antimentioning

confidence: 99%

Anticoagulants in Older Patients

Beyth

Landefeld

1995

Drugs & Aging

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“…These combinations also might result in an increased risk of bleeding 12,30, 31, 32, 33. 34, 35, 36 The literature describing warfarin and simvastatin interactions is limited to a few case reports. Simvastatin is a substrate for CYP3A4 and may potentially interact with warfarin metabolism through competitive inhibition of the enzyme 37,38.…”

Section: Discussionmentioning

confidence: 99%

Analysis of potential interactions between warfarin and prescriptions in Estonian outpatients aged 50 years or more

Gavronski

Hartikainen

Zharkovsky

2012

Pharmacy Practice (Internet)

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In Estonia, warfarin is widely prescribed by general practitioners to prevent and treat thromboembolic diseases. To date, there has been no systematic analysis of the potential risk of warfarin interactions with other drugs in the outpatient population.ObjectiveThe aim of the study was to analyze the incidence of potential interactions in prescription schemes in Estonia in a cohort of outpatients receiving warfarin treatment.MethodsThe retrospective study population included 203,646 outpatients aged 50 years or older of whom 7,175 received warfarin therapy. Patients who had used at least one prescription drug for a minimum period of 7 days concomitantly with warfarin were analyzed. Potential drug interactions were analyzed using Epocrates online, Stockley's Drug Interactions and domestic drug interaction databases. ResultsThe average number of drugs used concomitantly with warfarin was 4.8 (SD=1.9) (males: 4.7 SD=2.0, females: 4.9 SD=2.0). No potential interactions in treatment regimens were found in 38% of patients, one potential interaction was observed in 29% and two or more potential interactions were observed in 33% of patients. The mean number of all potential interactions was 1.2 per patient and about the same in men and women. Potential interactions were associated with the number of drugs. Warfarin-related interactions were detected in 57% of patients, and the number of interactions related to warfarin per patient varied from 1 to 5. Most frequent were use of warfarin with NSAIDs (14%), followed by simvastatin (9%) and amiodarone (7%). ConclusionsThis study shows that 57% of outpatients in Estonia receiving warfarin have drugs potentially interacting with warfarin in their treatment schemes. Most interactions (14%) with warfarin are associated with the prescription of NSAIDs.

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“…While Pond et al (1975) and Rawlins and Smith (1973) observed no effect of allopurinol on oxidative metabolism, it has been shown that allopurinol can prolong the half-lives of non-xanthine drugs that are metabolised in the liver by microsomal enzymes (Vesell et aI., 1970). In vivo and in vitro studies in rats have indicated that allopurinol inhibits the formation of I-methyluric acid from theophylline.…”

Section: Allopurinolmentioning

confidence: 96%

Pharmacokinetic Drug Interactions with Theophylline

Jonkman

Upton

1984

Clinical Pharmacokinetics

117

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Since up to 90% of a theophylline dose is biotransformed, drugs influencing microsomal enzyme systems in the liver may affect the elimination of theophylline. Other integrated mechanisms (e.g. hepatic uptake) may also be altered by concurrent administration of other drugs. Whatever the mechanism, the interaction may be sufficient to necessitate adjustment of the theophylline dosage, preferably guided by plasma theophylline determinations. Comedication with phenobarbitone may require an increase of the theophylline dose by about 30% due to increased clearance resulting from enzyme induction. Similarly, with phenytoin and carbamazepine a dose increase of about 40 to 50% may be required. In the case of rifampicin, isoniazid or sulphinpyrazone comedication, an increase of the theophylline dose by about 20 to 25% may be needed. On the other hand, other drugs decrease theophylline clearance, making a reduction in the dose of concurrent theophylline advisable: with usual doses of erythromycin, propranolol and isoprenaline (isoproterenol), a reduction of about 25% is needed; with cimetidine and oral contraceptives by about 30% or more; and with triacetyloleandomycin (troleandomycin) by about 50%. In high doses, the xanthine oxidase inhibitor allopurinol can also retard theophylline elimination, and a reduction of the theophylline dose by about 20% may be advisable. Conflicting results have been reported on the influence of frusemide (furosemide) and influenza vaccines, while data regarding the effect of corticosteroids, benzodiazepines and verapamil on theophylline kinetics are not yet conclusive. Many drugs, however, appear not to significantly affect theophylline clearance. Some are from the same therapeutic group as the drugs mentioned above and offer clinical alternatives for coadministration with theophylline. Examples of drugs not found to have a significant effect on theophylline pharmacokinetics are ranitidine, josamycin, midecamycin, amoxycillin, tetracycline, cephalexin, cefaclor, orciprenaline, metoprolol, antacids, medroxyprogesterone acetate, metoclopramide and metronidazole. Most of the drugs discussed in this review appear not to affect the volume of distribution of theophylline significantly.

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Influence of allopurinol on drug metabolism in man

Cited by 19 publications

References 14 publications

Anticoagulants in Older Patients

Anticoagulants in Older Patients

Analysis of potential interactions between warfarin and prescriptions in Estonian outpatients aged 50 years or more

Pharmacokinetic Drug Interactions with Theophylline

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