Ini ada sedikit pengetahuan dasar mengenai DDI. Setelah saya baca.. lumayan bagus dan gampang dimengerti.. makanya saya share di sini.
Dalam hal ini dijelaskan interaksi obat yang melibatkan interaksi farmakokinetika dan farmakodinamika.
Untuk calon arahat dan nobby_ta ketika meresepkan obat.. bisa juga memperhatikan hal2 di bawah ini..
Untuk yang lain, ingat2 jika ada dapat obat yang tertulis di bawah ini.. Semoga bermanfaat. Background and Introduction
Finding the most appropriate medication regimen for our patients is a difficult task. Patients often require multiple medications placing them at risk for drug-drug interactions (DDIs), a situation that occurs when 1 of a combination of drugs alters the effect of another drug. Drug-drug interactions may result in decreased therapeutic benefit, adverse effects, or patient harm. The frequency of potential DDIs was estimated to be from 6.2% to 6.7% per year using prescription drug claims data from 2 large health plans. Another study estimated 374,000 plan participants were exposed to clinically important potential DDIs utilizing pharmacy drug claims data for nearly 46 million participants in a pharmacy benefit management organization over a 25-month period. A review of 4 drugs -- warfarin, digoxin, cyclosporine, and simvastatin/ lovastatin -- found that an estimated 1.3-2.7 million insured adults were prescribed a potentially interacting combination. Non-prescription medications, herbal preparations, and complementary medications also contribute to patient polypharmacy and the potential for DDIs.
This activity will provide the clinician with a basic understanding of the most common types of DDIs. In addition, the activity will provide a general overview of DDI mechanisms and strategies to help the clinician identify, prevent, and manage DDIs.
DDIs contribute to patient morbidity and may cause emergency department visits, hospitalizations, and re-admissions.[6,7] Examples of patient morbidity caused by DDIs include gastrointestinal (GI) bleeding, renal dysfunction, electrolyte imbalance, hypertension, hypotension, bradycardia, arrhythmia, drug toxicity, and decreased drug effect.[6-8] Juurlink and colleagues performed 3 population-based, nested case-control studies to evaluate whether elderly patients taking glyburide, digoxin, or an angiotensin-converting enzyme inhibitor (ACEI) who were admitted with drug toxicity had been prescribed an interacting agent within the previous week. They found that patients on glyburide admitted for hypoglycemia were 6 times more likely to have been treated with sulfamethoxazole/ trimethoprim (SMX/TMP). Patients admitted for digoxin toxicity were 12 times more likely to have been started on clarithromycin in the previous week. Patients on ACEIs were 20 times more likely to have been started on a potassium-sparing diuretic in the previous week.
Certain medications have been removed from the market due to patient morbidity and mortality caused as result of DDIs. Development of the dangerous arrhythmia, torsades de pointes (TdP), resulted in death in several instances. Examples from the literature of mortality associated with DDIs include ciprofloxacin in fatal seizures, moclobemide-clomipramine overdose in fatal serotonin syndrome, and fatal outcome from a warfarin and nonsteroidal anti-inflammatory drug (NSAID) interaction. Other examples are fatal interactions between tranylcypromine and imipramine, and also between methotrexate and trimethoprim. Terfenadine, astemizole, and grepafloxacin are examples of drugs taken off the market due to the risk of TdP arrhythmias caused by DDIs. Removal of drugs from the market will eliminate the risk of DDIs in certain situations. Unfortunately, the elimination of all risk is impossible due to, in part, the lack of suitable drug alternatives. Many clinicians have witnessed patient harm caused by DDIs, and many interactions that have caused hospital admission for toxicity could have been avoided. However, in many cases knowledge of DDIs is lacking.[15,16]
DDI Risk Factors to Identify in Practice
Our most complex patients are at highest risk for DDIs. Polypharmacy, narrow therapeutic range of the medication, decreased hepatic and/or renal function of the patient each may increase the risk for DDIs. Each may be identified prior to coadministration. One should consider the potential for DDIs at all steps of the drug-delivery process. In a retrospective review of patients admitted to the emergency department, patients taking 3 or more medications or patients who were 50 years or older taking 2 or more medications had a considerable risk for DDIs. Furthermore, an increasing number of medications administered further increased the risk for adverse effects. Patients taking 2 medications had a 13% risk while patients taking 5 medications had a 38% risk for DDIs. Patients taking 7 or more medications had an 82% risk of developing adverse drug interactions.
Advanced age is an additional risk factor for DDIs. Aparasu and colleagues found that the risk for DDIs increases significantly after 44 years of age and is greatest for patients over 74 years of age. The need for multiple medications often arises with advancing age that may further the risk for DDIs. Almost 25% of the elderly outpatients referred to a diagnostic clinic in The Netherlands for decreased cognition, functional dependence, or both who were taking more than 1 medication were found to have potential adverse effects or decreased drug effect possibly due to a DDI. In general, when multiple medications are prescribed in the elderly population, the risk for DDIs increases exponentially.
Other patient-related risks for DDIs noted below, include very young age, female sex, genetics, decreased organ function, use of a medication having a narrow therapeutic range (eg, warfarin, digoxin, and cyclosporine), major organ impairment, metabolic or endocrine risk conditions (eg, hypothyroidism, hypoproteinemia), and acute medical issues (eg, dehydration).[4,6,17-19]
Patient-Related Risks for Drug-Drug Interactions
* Acute medical condition (eg, dehydration, infection);
* Age extremes (ie, the very young and the elderly);
* Decreased renal/ hepatic function;
* Female sex;
* Metabolic or endocrine condition (eg, obesity, hypothyroidism);
* Multiple medication use;
* Narrow therapeutic range of medication; and
Non-patient factors may also affect the risk for DDIs. For example, an increasing number of clinicians or pharmacists involved with the dispensing of medication may increase the risk for DDI. Risk may also increase when computer alerts are too frequent or too infrequent. Pharmacy work flow, and work load also may influence risk of DDIs.
DDIs should be considered at each step of the drug-delivery process. All members of the healthcare team should consider the risk for DDIs when a new medication is prescribed, dispensed, or administered to a patient.Drug Class Effects and Drug-Drug Interaction Capabilities
Many clinicians have been confronted with the assumption that "all azoles" or "all statins" should be avoided in certain situations. All members of a drug class, however, should not be assumed to have the same DDI capabilities. Such assumptions may ultimately result in providing the patient with a potentially less suitable agent or increasing unnecessary monitoring. For example, erythromycin and clarithromycin may interfere with carbamazepine metabolism and cause increased carbamazepine concentrations. In contrast, azithromycin does not interfere with carbamazepine metabolism.
Alerts in computer software are intended to notify clinicians of potential DDIs, yet such alerts can contribute to the class effect assumption of DDIs. False-positive results may contribute to clinician desensitization of computer alerts, making them prone to over-riding alerts and missing clinically important interactions.[16,21] Clinicians should use alternative DDI resources when confronted with an alert possibly based on a class effect to make clinical decisions on use of the regimen or therapeutic alternatives.
Interpatient Variability Contributes to Drug-Drug Interactions
Patient- and situation-specific factors, such as with patient-specific medication timing, can contribute to DDIs. For example, initiation, discontinuation, or dosage adjustment of thyroid replacement in the patient stabilized on warfarin requires increased INR monitoring due to the potential for altered warfarin effect. When thyroid replacement therapy is added to patients stabilized on warfarin, the warfarin effect may be increased, potentially resulting in overanticoagulation. Conversely, when thyroid medication is discontinued from a patient receiving stable warfarin therapy, the warfarin dosage may need to be gradually adjusted upward to account for a decrease in the anticoagulant effects. Warfarin anticoagulation may be challenging in patients with complex medical states. Patient situations that may influence the anticoagulant effect of warfarin include decreased hepatic function, decreased oral intake, or active infection. Other factors include patient pharmacogenetics, diet, and the narrow therapeutic range of warfarin. DDIs may be particularly difficult to identify in patients with complex medical states and regimens requiring therapeutic adjustment. However, if warfarin is added to the patient already stabilized on thyroid replacement, it is likely that only usual warfarin management will be required.
Patient-specific drug dosing requirements may contribute to DDIs. For example, the ability of fluconazole to inhibit metabolism of certain medications increases with increasing dose. Therefore, the patient requiring single-dose fluconazole is less likely to encounter significant DDIs than the patient requiring daily-dose fluconazole.
Finally, clinicians should consider the possibility that a DDI may occur -- even if statistically rare. As Horn and Hansten explain , a 1 in 1000 incidence of a DDI-induced adverse event requires the observation of 3000 patients on the same regimen to have a 95% likelihood of observing the adverse event.Gastrointestinal Absorption and Drug-Drug Interactions
When considering potential DDIs caused by interference with gastrointestinal (GI) absorption, in general quinolones should not be coadministered with cations at the same time (eg. iron, calcium, magnesium, aluminum), due to possible chelation in the GI tract. Instead, the drugs should be administered separately by at least 2 hours. Coadministration of proton pump inhibitors should be avoided with ketoconazole because ketoconazole requires an acidic media for absorption. Increased GI motility caused by metoclopramide may decrease absorption of cefprozil by decreasing the cefprozil GI transit time. The interaction between fluoxetine and metoprolol is not due to interference with GI absorption. Fluoxetine may increase the concentration of metoprolol due to decreased metoprolol metabolism.
A DDI such as those described due to interference with the absorption, distribution, metabolism, and elimination resulting in change of drug concentration is termed a pharmacokinetic interaction. In addition to GI absorption interactions as described above, DDIs may also occur due to distribution interactions (eg, alterations in plasma protein binding) elimination interactions (eg, altered renal excretion), and metabolism interactions. Metabolism, particularly via the cytochrome P450 system (CYP) found predominantly in the liver, is the cornerstone of drug biotransformation. Table 1 describes types of pharmacokinetic drug interactions and provides examples of each.