Jaclyn Chessher, PharmD

A 27-year-old white woman with a past medical history of intravenous drug abuse and hepatitis C presented to the emergency department with a 4-day history of severe chest pain, shortness of breath, and vomiting. She had been admitted earlier in the month with methicillin-resistant 

 (MRSA) endocarditis and signed herself out against medical advice without completing antibiotic therapy. Blood cultures confirmed MRSA and she was again diagnosed with MRSA endocarditis. Pharmacy staff performed medication reconciliation and all home medications were resumed, including Xarelto (rivaroxaban). Pharmacy staff did not see an indication for Xarelto and investigated further.

Upon investigation, pharmacy staff discovered the patient had a diagnosis of protein S deficiency. Protein S deficiency is a type of inherited thrombophilia associated with increased risk of venous thromboembolism (VTE). Protein S is an endogenous vitamin K—dependent anticoagulant that acts as a nonenzymatic cofactor for activated protein C (aPC).

 The primary effect of aPC is to inactivate coagulation factors Va and VIIIa, which help activate factors II and X, respectively. Inactivating factors II and X halts the clotting cascade; however, a deficiency in protein S would diminish this effect and cause a procoagulant state.

Is Xarelto the best therapeutic option for this patient? Given the patient’s history of noncompliance with her antibiotic and anticoagulation/ antithrombotic therapy, warfarin would not be a good option due the importance of compliance with the medication, the need for bridging anticoagulation, and the required periodic international normalized ratio monitoring.

 Xarelto is a factor Xa inhibitor, and newer agents such as oral direct thrombin and factor Xa inhibitors are gaining in popularity for the treatment of VTE and for VTE prophylaxis in patients without inherited thrombophilia. There are no data that prove the newer agents are any less safe or effective than warfarin treatment in these patients.

Since the patient is of childbearing age and warfarin is pregnancy category X, warfarin would not be a good option. Pradaxa (dabigatran), a direct thrombin inhibitor, would be a safe and effective option; however, it requires twicedaily dosing for VTE prophylaxis, which would present a compliance issue for this patient. Eliquis (apixaban), a factor Xa inhibitor, is a pregnancy category B drug, but it also requires twice-daily dosing and would pose a compliance issue for this patient.

 The pharmacist concluded that Xarelto, which is pregnancy category C, was the best therapeutic option for this patient due to its once-daily dosing for VTE prophylaxis, lack of monitoring requirements, and more desirable pregnancy category.

Jerry Barbee, PharmD, BCPS, is a clinical pharmacist at HCA West Florida Hospital. Jaclyn Chessher, PharmD, is a clinical pharmacist at HCA West Florida Hospital. Ambree Gober is a 2015 PharmD candidate at Auburn University’s Harrison School of Pharmacy. Matt Savoie is a 2015 PharmD candidate at Auburn University’s Harrison School of Pharmacy.

		Witt DM, Nutescu EA, Haines ST. Venous thromboembolism. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. 

Pharmacotherapy: A Pathophysiologic Approach

. 8th ed. New York, NY: McGraw-Hill Medical; 2011:311-352.

		Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schunemann HJ. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. 

. 2012;141(suppl 2):e7S-e47S. doi:10.1378/chest.1412S3.

		Apixaban, dabigatran, rivaroxaban, warfarin. In: Clinical Pharmacology [online database]. Tampa, FL: Elsevier Gold Standard, Inc; 2015. www.clinicalpharmacology-ip.com/default.aspx.

Articles

Protein S deficiency is a type of inherited thrombophilia associated with increased risk of venous thromboembolism.

Protein S Deficiency

Pharmacists can help minimize risk for patients using pain medications.

There are currently more than 100 million Americans suffering from chronic pain, including 65% to 80% of terminal cancer patients, 62% of nursing home residents, and many others who must combat pain on a daily basis.

 Chronic pain afflicts more patients in the United States than diabetes, coronary heart disease, stroke, and cancer combined.

 It reduces a patient’s independence and ability to perform many daily activities and puts a strain on social relationships, mood, and sleep patterns.

This decrease in overall functioning places a burden on the national economy, with total annual costs of health care and lost productivity attributable to pain ranging from $560 billion to $635 billion (2010 dollars) in the United States.

 With the number of patients suffering from pain increasing as the US population ages, the demand for pain management pharmacists will continue to rise.

The most widely accepted definition of pain is “an unpleasant sensory and emotional experience that is associated with actual or potential tissue damage or described in such terms.”

 There are, however, as many different definitions of pain as there are ways that pain can manifest itself in complex patients. Each directly influences the course of therapy for each individual.

Pain is classified by its duration and etiology. Duration of pain is classified in 2 categories: acute pain and chronic pain. Acute pain is a response to injury or tissue damage that generally does not last longer than it takes for normal healing to occur. Typically, this pain lasts less than 6 months, but may become chronic if not adequately treated. Chronic pain, on the other hand, persists longer than the normal course of time associated with injury, typically more than 3 to 6 months. In many cases, the initial injury may not be readily identifiable.

There are several etiologies of pain, including nociceptive pain and neuropathic pain. Nociceptive pain includes somatic pain, which arises from injury to body tissues and tends to be localized but varies in description and experience. Visceral pain is a nociceptive pain arising from the viscera mediated by stretch receptors; it is poorly localized, deep, dull, and cramping.

 Neuropathic pain manifests itself in abnormal neural activity secondary to disease, injury, or dysfunction of the nervous system. This type of pain can arise from the peripheral nervous system or the central nervous system.

Pain varies greatly in duration and etiology and often progresses or regresses as the pathology of the patient’s injury or disease state changes. In many cases, especially in chronic pain patients, complex pain states do not exist as a single well-defined pain, but rather as a mix of several types of pain.

There are many medications used to treat the various etiologies of pain. To maximize efficacy and minimize risk, therapies should be individualized for each patient’s pathology. The goal of proper pain management should always be to improve the patient’s quality of life, decrease the average pain rating, and improve overall functioning. Pharmacists must do their best to minimize patient risk associated with pain management. Proper medication therapy can reduce addiction, short- and long-term adverse effects, and risk of overdose.

For patients suffering from neuropathic pain including, but not limited to, peripheral neuropathic pain (eg, diabetic neuropathy, radiculopathy, postherpetic neuralgia) and central neuropathic pain (eg, post stroke pain, Parkinson’s disease pain, spinal cord injury pain, HIV myelopathy), there are many potential appropriate treatment options. These medications include tricyclic antidepressants, anticonvulsants, gabapentin, pregabalin, selective serotonin reuptake inhibitors, N-methyl-D-aspartate antagonists, topical lidocaine and capsaicin, opioid analgesics, and tramadol. It is the pharmacist’s responsibility to evaluate these medications. Pharmacists play a pivotal role in determining drug efficacy and in monitoring the side effects and interactions of multiple medications to help patients achieve good therapeutic outcomes.

When patients suffer from nociceptive pain, including somatic and visceral pain, certain classes of medications tend to have higher efficacy. These nociceptive pain medications include acetaminophen, nonsteroidal anti-inflammatory drugs, topical lidocaine, capsaicin, corticosteroids, skeletal muscle relaxants, opioid analgesics, and tramadol. Patients taking these medications need to be closely monitored by the pharmacist to ensure both dose and agent are appropriate for the patient’s comorbidities, age, and other possible medication interactions.

It is crucial that the pharmacist always perform a quick equianalgesic calculation to ensure that a patient’s new opioid medication is at a safe and effective dose (Online Table 1). When using the equianalgesic chart, an incomplete cross-tolerance dose reduction of 25% to 50% may be appropriate.

Pharmacist involvement can especially affect outcomes in pain management for patients with multiple disease states taking multiple medications for multiple types of pain. The incidence of adverse medication events is reduced with pharmacist intervention.

Nobody deserves to live with severe pain. Pharmacists can help patients live meaningful and productive lives with adequately managed pain. It is the responsibility of pharmacists to monitor patients’ 4 As: analgesia, activities of daily living, adverse events, and aberrant drug behaviors.

 Proper pain assessment is essential for understanding patients’ pain and providing highly effective treatment while simultaneously minimizing risk.

Assessment and proper planning can also help minimize patient risk. This can start with “The 10 Steps of Universal Precautions in Pain Medicine” (Online Table 2). By applying these recommendations, stigma is reduced and overall outcomes are improved.