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Fifty patients on warfarin therapy for at least six days of duration were enrolled in a warfarin medication use evaluation (MUE), including patients managed by physicians or the pharmacokinetic service (PKS). Patients were distributed equally with regard to "new" and "chronic" warfarin patients.
The MUE criteria evaluated included warfarin dosage adjustment, drug-drug interaction, disease-state interaction, appropriate PT/INR (prothrombin/international normalized ratio) monitoring and vitamin K usage for reversal of anticoagulation effect. Results were evaluated for opportunities for improvement and differences in the performance of physicians and pharmacists with warfarin management. The following areas were considered for improvement: initial geriatric dose of warfarin, "hold orders" not carried out correctly and "hold orders" that fell below the desired INR range while on warfarin therapy, use of vitamin K per standard guidelines, use of interacting medications, over-monitoring, and documentation of warfarin education. Performance of both pharmacists and physicians was compared, and opportunities for potential improvement were identified.
• Disease-related factors.
Fifty-eight percent of warfarin patients had disease-related factors that could affect warfarin response (such as hypothyroidism, diarrhea, and others).
• Drug interactions.
All 50 patients received other drugs that could potentially interact with warfarin in a significant manner. Patients averaged 2.1 potential drug interactions with warfarin. Alternative drugs could have been used to avoid a drug interaction in 25% of cases. Frequently used drugs with a high risk of interaction with warfarin include SMX-TMP, amiodarone, and SSRIs.
• Clear order writing.
Orders can be confusing when holding, starting, or re-starting warfarin. Orders should specify clearly the amount to be given the first day (such as warfarin 5 mg this a.m. and 5 mg q p.m. starting tonight). A few extra seconds to write a legible and easily comprehensible order may prevent a medication error.
"Start lower and go slower." Geriatric patients often are more sensitive to warfarin than younger patients and often require lower doses. Starting doses generally should be 5 mg or less in geriatric patients; maintenance doses often are less than 5 mg daily. This review indicates that when higher doses are used initially, the INR often becomes supratherapeutic and the dose must be held or decreased. This prolongs the time to reach the desired therapeutic range and could prolong hospitalization.
Hold orders often are caused by overshooting the goal INR with higher doses, especially in the elderly. In most physician cases, the INR fell below the therapeutic range when holding the dose; the INR often fell below 1.5 (average time of low INR with hold orders was 2.6 days/patient). The risk of thrombotic events increases significantly with INRs below 1.5. Restarting the warfarin dose sooner, albeit at a lower dose, will help minimize or eliminate the subtherapeutic time.
Cases of over-monitoring were observed in this review; daily monitoring continued after the patient’s dosage had been stabilized. Unnecessary monitoring adds additional work, time, and expense to patient management.
• Vitamin K administration.
Higher doses than recommended by the current literature guidelines were administered in two cases (i.e., 20-25 mg SQ). Subsequently, once the warfarin was resumed, these two patients both exhibited a prolonged period of resistance with subtherapeutic INR values for 8 and 13 days. These high vitamin K doses caused prolonged warfarin resistance and likely contributed to extended hospitalization. National guidelines now recommend lower vitamin K doses if the patient is not bleeding (i.e., 1-5 mg orally in many cases). Overuse of vitamin K will cause warfarin resistance, extended subtherapeutic times, and possibly prolonged hospitalization.
Fewer than 50% of physicians’ new warfarin patients had warfarin education documented in the chart. Education is important for good patient compliance and self-management at home. Warfarin education by a pharmacist in the hospital is not automatic, and a specific physician order for warfarin education is necessary. Remember to include patient teaching well in advance of discharge.
• Adverse reactions.
One warfarin-related adverse drug reaction was observed in the 50 patients. Bleeding occurred in a patient with heparin-induced thrombocytopenia (platelet count dropped to 70,000) who was receiving both danaparoid and warfarin.
• Atrial fibrillation.
A separate survey showed that 35% of atrial fibrillation patients at Huntsville Hospital were receiving warfarin. Many patients had justifiable reasons for not receiving warfarin, such as recent history of GI bleed, poor prognosis, high fall risk, or psychological/situational issues. However, approximately 20% of patients were not receiving warfarin and potentially could have. Studies have demonstrated a significant stroke risk reduction in atrial fibrillation patients, but appropriate patient selection is critical.
Summarizing the results of physician-pharmacist comparative data for "new" warfarin patients, physicians ordered higher initial doses (especially in geriatric patients), achieved the goal INR value more rapidly, had more supratherapeutic INR values and more resulting hold orders, and documented less patient warfarin education. For "chronic" warfarin patients, physicians ordered less INR monitoring, had more subtherapeutic days related to hold orders, had fewer overall percent therapeutic INR days, and documented less patient warfarin education.
In conclusion, here are some "pearls" gathered from the warfarin MUE.
• Disease factors.
Be aware of situations that can affect warfarin response and make adjustments as needed.
• Drug interactions.
Potential interactions are common in warfarin patients. Maintain awareness, avoid interacting drugs when possible, and make adjustments as needed.
• Order writing.
Take a few extra seconds to write clearly understandable orders — it may prevent a medication error.
Geriatric patients generally require lower doses, often 5 mg or less daily. The elderly are at risk for "over-shooting" the goal INR.
• Hold orders.
Hold orders often are due to supratherapeutic INR. Try to avoid falling to a subtherapeutic INR by restarting warfarin at a lower dose as the INR approaches goal range.
Once the INR has been stabilized, daily INR monitoring is not necessary.
• Vitamin K.
New guidelines recommend much lower doses for supratherapeutic INR if the patient is not bleeding.
Pharmacist warfarin education should be specifically ordered well in advance of the planned day of discharge.
• Adverse reactions.
Bleeding is more likely to occur in risk patients (on other antiplatelet/anticoagulation drugs, thrombocytopenia, history of bleed, etc.).
• Atrial fibrillation.
Warfarin demonstrates significant stroke risk reduction in atrial fibrillation patients; patient selection is critical.