The University of Arizona, aware of the relevance of the issue, provides up-to-date lists of drugs that can prolong the QT interval, 13 classifying those drugs as follows:. RISK OF TORSADES: drugs generally accepted to carry a risk of torsades de pointes : amiodarone, 7,8 amitriptyline, 7 clarithromycin, 7,8 chlorpromazine, 7,8 disopyramide, 7 erythromicin, 7,8 haloperidol, 7,8 imipramine, 7,8 nortriptyline, 7 pentamidine, 7,8 pimozide, 7,8 quinidine, 7,8 sotalol, 7,8 thioridazine.
Chloroquine is accepted by the QTdrugs. Other drug interactions of chloroquine are shown in Chart 2. The drug interactions related to the use of the biological agents adalimumab, etanercept, and infliximab should be considered, because there is an increase in the risk of severe infections when those agents are administered in association with abatacept, 7,12 anakinra 7,12 or rilonacept. In addition, the concomitant use of etanercept and cyclophosphamide has been reported to be associated with an increase in the risk of developing non-cutaneous solid tumors, contraindicating the simultaneous use of those drugs.
Although the clinical significance of the interaction has not yet been well assessed, an increase in the risk of neutropenia as an adverse effect of etanercept used simultaneously with sulfasalazine has been reported. Safety reports on the simultaneous administration of drugs are scarce. Most of them are pharmacokinetic studies with a small number of patients, and assess the existence of an alteration in the safety profile of each drug when concomitantly used.
The sources consulted suggest the concomitant use of the following drugs as safe:. It is almost impossible to remember all known drug interactions, even when referring to the drugs used within a specialty, such as rheumatology.
According to the WHO's Guide to Good Prescribing: a practical manual 14 , a treatment to be applied should be chosen based on efficacy, safety, applicability, and cost. That manual teaches how to choose and not what to choose. This study approaches not the efficacy of the drugs, but the second criterion for choosing the drugs, safety. In reality, this study assesses the safety of drug combination. Not all damage caused by drugs or drug combination can be avoided, but, since most harm results from the inadequate selection of the combinations, it can be prevented.
For several inadequate associations, high risk groups can be identified. Usually, those are exactly the groups of patients who should be carefully considered: elderly, children, pregnant women, and individuals with kidney or liver disease. Such patients can have alterations in both the pharmacodynamics and pharmacokinetics of the drugs administered.
According to the Guide to Good Prescribing, step 5, information, instructions, and warnings should be provided to patients. This study highlights the need for providing the patient with information about the signs and symptoms of possible drug interactions, considering that drug interaction is unpredictable. A practical solution would be to choose an alternative with no interaction, but, if none is available or possible, sometimes drugs that interact with each other can be prescribed when adequate precautions are taken.
If the effects of the interactions are well monitored, they can often be allowed, usually with dose adjustment. Many interactions are dose-related, as can be observed with the drugs approached in this study: the use of the same drug for oncological purpose and its use at reduced doses for antirheumatic purposes differ.
For example, dipyrone can increase the toxicity of high doses of methotrexate, but does not seem to have a similar effect on the methotrexate doses used for rheumatic diseases. Low doses of methotrexate do not seem to interact with carbamazepine, while high doses seem to do so. Some drug interactions can be prevented by using another member of the same group of drugs, such as chloroquine and hydroxychloroquine. The potential of the former to prolong the QT interval on ECG, causing consequent life-threatening arrhythmias, does not recommend its use in association with other drugs with the same potential antiarrhythmic drugs, anti-infectious agents, azole antifungals, quinolones, aminoglycosides, tricyclic antidepressants and SSRI, antipsychotics.
It is worth emphasizing the following: immunosuppressants are drugs with a low therapeutic index; several frequently used drugs are enzyme inducers or inhibitors, and, thus, can alter the serum concentration of other substances or metabolites active-toxic ; and, finally, elderly patients, those with cardiac, liver or kidney dysfunction, and those submitted to polypharmacy are more susceptible to drug interactions.
Thus, a large number of drugs with potential for interaction can be safely administered when precautions are taken. That is step 6 of the Guide to Good Prescribing: monitor the treatment. The next step is: keep up-to-date about drugs! For preventing adverse reactions consequent to drug interactions, the following is proposed:.
Would it not be useful if each patient were educated to carry along a prescription card that would be presented and whose filling should be required to every professional involved with the patient's care? One limitation of our study is the number of sources researched. The study was not aimed at fully covering the issue, but at providing a contribution to rheumatology professionals involved with the responsible health care of patients with chronic diseases that require complex therapies.
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Hoefler R. A pharmacoepidemiologic study of drug interactions in a Brazilian teaching hospital. Clinics ; 61 6 Brown CH.
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Overview of drug interactions. US Pharm. Polypharmacy among people with rheumatoid arthritis: the role of age, disease duration and comorbidity. Musculoskeletal Care ; 5 4 Effect of drug interactions on outcomes of patients receiving warfarin or theophylline. Am J Hosp Pharm ; 51 5 Updated periodically. Baxter K, ed. Stockley's Drug Interactions: a source book of interactions, their mechanisms, clinical importance and management. London: Pharmaceutical Press; Tatroo DS, ed.
Drug interaction facts TM St Louis: Wolters Kluwer Health; Clinically important drug interactions with Disease Modifying Antirheumatic Drugs. Drugs Aging ;13 4 Lacaille D. Rheumatology: 8. Advanced Therapy. Can Med Assoc J ; 6 UpToDate, Inc. Stockley's Herbal Medicines Interactions.
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