Jennifer Chen, PharmD
Entacapone is a reversible and selective inhibitor of catechol-O-methyltransferase (COMT). By disrupting levodopa breakdown, the COMT inhibitors can potentiate the effect of levodopa for managing the motor symptoms of Parkinson’s disease. Therefore, entacapone is used as adjunctive treatments in patients who are experiencing “wearing off” or other motor complications during treatment with carbidopa-levodopa.) It is available alone as Comtan® or in a fixed-dose combination with carbidopa-levodopa as Stalevo®.
In August 2010, FDA alerted patients and health care professionals about the increased risk of cardiovascular events and death with the use of Stalevo. The possible safety issue was observed in a clinical trial called Stalevo Reduction in Dyskinesia Evaluation in Parkinson’s disease (STRIDE-PD) and in meta-analysis involving 15 clinical trials comparing Stalevo with carbidopa-levodopa. Since carbidopa-levodopa has been used extensively and has not been associated with cardiovascular risk, the FDA was concerned that entacapone might have been responsible for the increased risk. It was difficult to draw conclusions from these clinical trials because they were not designed to evaluate entacapone’s cardiovascular safety.
Until recently, two studies were examined to understand the significance of cardiovascular risk with entacapone. One was a retrospective cohort study using data from an electronic commercial insurance database and found the risk for myocardial infarction was not significantly increased in patients 18 to 64 years old with Parkinson’s disease treated with entacapone compared to the control group(1). The other study assessed the risk of myocardial infarction, stroke or death in Medicare patients at least 65 years old with Parkinson’s disease and the result did not support an associate between entacapone use and increased cardiovascular risks(2).
Therefore, on October 26, 2015, the FDA announced that entacapone does not carry an increased risk of cardiovascular events based on recent studies. However, patients and health care professionals are still encouraged to report side effects with Comtan or Stalevo to the FDA.
We want to share some exciting news with you regarding Outcome Resources!
On October 30, Hospice Pharmacy Solutions merged Outcome Resources into its operation. The merger is very beneficial for our clients as we will be able to offer you additional unique and innovative solutions geared specifically to the hospice industry.
The business will be headquartered in Dallas, which is a central location, and operate as Hospice Pharmacy Solutions, LLC. In approximately six months, we will retire the Outcome Resources name.
We want to reassure you that while the name is changing, the exceptional service you have come to expect from Outcome Resources remains the same. This merger gives us the ability to enhance our programs and provide hospices valuable resources to better serve their patients.
You can find more details in this press release, including the new leadership structure.
We’d like to once again thank you for your services to patients and their families at a most vulnerable time in their lives. The work you do is honorable, and we are proud to support your mission.
Stephanie Cheng, PharmD, MPH
Outcome Resources clinical pharmacist Dr. Stephanie Cheng recently had the great opportunity to travel and learn about hospice and palliative care in the United Kingdom, where modern hospice care was founded. She was able to visit Hospice UK, which is a national charity for hospice care that supports over 200 hospices in the UK. Hospice UK provides support through education, advocacy, and raising awareness. She was also able to visit 3 different hospices: St. Joseph’s Hospice, which is the oldest hospice in England, opening in 1905; St. Christopher’s Hospice, which was founded by Dame Cicely Saunders in 1967 and is the oldest modern hospice; and Phyllis Tuckwell Hospice. Through these hospice visits, Dr. Cheng was able meet with different key members of the hospice team such as palliative care physicians, nursing staff, social workers, pharmacists, and coordinators of complementary medicine and community outreach. She was also able to correspond with the Care Quality Commission, which is the independent regulator of health and social care in England.
Dr. Cheng is planning on writing about what she has learned about hospice and palliative care in the UK for the next Outcome Resources newsletter, The Clinician, which will be distributed to all Outcome Resources clients during the first week of January.
|Looking forward to reading about Dr. Cheng's experiences in UK and what she learned about palliative/hospice practices there.
-- Marsha Farrell
Posted 11/4/2015 01:25:27 PM
Stephanie Cheng, PharmD, MPH
The FDA granted accelerated approval of Praxbind (idarucizumab) on October 16, 2015 for use as a specific reversal agent of the anticoagulant effects of Pradaxa (dabigatran etexilate) during emergency surgery/urgent procedures or in episodes of life-threatening or uncontrolled bleeding. This is the first drug to be approved for this indication. Praxbind is currently not available on the market yet; however, the manufacturer stated that it will be available from major U.S. hospital pharmacy distributors as quickly as possible.
Pradaxa (dabigatran) had been given FDA approval in 2010 as the first direct thrombin inhibitor for the indications of (1) to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (2) for the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients who have been treated with a parenteral anticoagulant for 5-10 days and (3) to reduce the risk of recurrence of DVT and PE in patients who have been previously treated. Unlike Coumadin (warfarin), Pradaxa does not require extensive lab monitoring and is given as 75mg BID or 150mg BID. However, there had been no antidotes to its anticoagulant affect until this point.
Praxbind (idarucizumab) is a monoclonal antibody fragment that is to be given IV only at a recommended dose of 5g, provided as two separate 2.5g/50mL vials to be given consecutively. Praxbind specifically binds to Pradaxa and does not interfere with the anticoagulant effects of other anticoagulants or the coagulation cascade.
Under the accelerated approval process, the FDA approves medications for serious conditions that fill an unmet medical need based on an intermediate clinical endpoint in a clinical trial that is reasonably likely to predict a clinical benefit to patients. This allows patients to gain earlier access to promising new medications, but the company is still required to submit additional clinical information after approval to support the clinical benefits of the drug.
Due to the accelerated approval process, Praxbind has only been studied in healthy patients (i.e. patient who do not require an anticoagulant) in 3 clinical trials of a total of 224 subjects. Therefore, the safety and risk profile for patients who do require an anticoagulant has not been assessed. Additionally, because the clinical trials were conducted under widely varying conditions, adverse reaction rates observed cannot be directly compared to other drugs and the rates may not reflect those observed in clinical practice.
Currently, there are no contraindications for Praxbind. However there are warnings and precautions in regards to (1) increased thromboembolic risks to the patient’s underlying disease due to reversal of dabigatran’s anticoagulant effects (2) re-elevation of coagulation markers (i.e. activated partial thromboplastin time (aPTT) or ecarin clotting time (ECT)) (3) Hypersensitivity reaction and (4) risk of serious adverse reactions in patients with hereditary fructose intolerance due to sorbitol excipient.
The role of Praxbind in the hospice setting will be limited, due to the limited use of Pradaxa and expense. Anticoagulant use in generally is not recommended in hospice patients due to the risk of bleeding, especially in the unpredictable declining status of hospice patients. Exception to this is if the patient has a high level of function, relatively longer prognosis for life and a reasonable quality of life, who is deemed to be at high-risk for thrombotic events. However, Praxbind does provide a safety net for life-threatening or uncontrolled bleeding in patients using Pradaxa in an otherwise helpless situation, as no other antidote for Pradaxa had been available up until this point.
Jennifer Chen, PharmD
Belsomra (Suvorexant), which was given FDA approval in August, 2014, became available early this year. Belsomra works as an orexin receptor antagonist. Orexins are chemicals that are involved in regulating the sleep-wake cycle and play a role in keeping people awake. It is the first drug approved with this mechanism of action.
Belsomra is a schedule IV controlled substance, which is the same category as temazepam (Restoril) and zolpidem (Ambien), due to its potential for abuse and dependence. It is available as 5, 10, 15, and 20 mg tablets, and should be taken no more than once per night, within 30 minutes of going to bed. It is recommended that the lowest effective dose be used and the total dose should not exceed 20mg once daily. A Medication Guide addressing safety issues should be handed out with all Belsomra prescriptions.
In clinical trials, patients taking Belsomra fell asleep faster and spent less time awake during the night. However, these studies compared Belsomra to placebo instead of other drugs approved to treat insomnia. Therefore, it is unknown if Belsomra is superior to other hypnotics in terms of effectiveness and safety. The side effects are similar to other sleep medications: somnolence, headache, abnormal dreams, next-day drowsiness, sleep-driving and other complex behaviors while not fully awake. The FDA initially rejected high doses of Belsomra- 30mg and 40mg because they posed a dangerous risk of next-day drowsiness. The clinical trials showed that people who took a 15 mg or 20 mg dose of Belsomra every night for 3 months fell asleep just 6 minutes faster on average than those who got a placebo pill and slept only 16 minutes longer compared to the placebo group. The recommended starting dose of 10 mg was only studied in 62 people for 1 month and it is unclear whether it improves sleep. The 5 mg dose was not studied at all, so its effect is unknown.
Other than a new mechanism of action, Belsomra does not provide any additional benefits in the hospice setting. With a similar efficacy and safety profile, the use of Belsomra is very limited due to its high cost and the availability of other hypnotics.
Cost comparison of Belsomra to other hypnotic alternatives (15-day supply):
Belsomra 10mg QHS --- AWP $158
Zolpidem (Ambien) 10mg QHS --- AWP $70
Temazepam 15mg QHS --- AWP $11
Trazodone 100mg QHS --- AWP $11
Jim Joyner, PharmD, CGP
Rytary is the brand name for a new formulation of “extended-release” carbidopa-levodopa that has recently become available in the U.S. in capsule form. It is indicated for the treatment of mild to moderate to severe Parkinson’s disease. Clinical trials with this new formulation were conducted comparing Rytary with immediate-release carbidopa-levodopa tablets. The study results indicated significant improvements in a patient’s ability to move and perform activities of daily living, as well as experiencing significantly more “on” time and less “off” time without dyskinesia. There are currently no published studies comparing Rytary with the “controlled-release” carbidopa-levodopa tablet (originally Sinemet CR, although generics are now available). The Sinemet CR tablet is formulated as an erodible polymer matrix that slows the release of medication from the tablet. The Rytary capsule contains both immediate-release and extended-release beads. Clinically significant differences in patient response to these two “extended-release” products should be anticipated because of the difference in formulation.
“Controlled or “extended” release carbidopa-levodopa preparations have been formulated in attempts to achieve a steadier climb to peak plasma concentrations that are less extreme and provide greater duration of anti-Parkinson effects. Both Rytary and the older Sinemet CR tablet are formulated to achieve this objective, but use different technology to control dissolution rates. Both dosage forms have been shown to provide more “on” time, less “off” time, and less dyskinesia for Parkinson’s patients than the immediate-release tablets. It remains to be seen how much of an advantage, if any, the new extended-release capsule (Rytary) has over the older extended-release tablet (Sinemet CR).
Rytary is not a generic equivalent to either the immediate release, nor the controlled release carbidopa-levodopa. The manufacturer provides a conversion table for guidance on converting from carbidopa-levodopa immediate release to Rytary.
Available combination strengths of Rytary Extended Release Capsules are as follows: 23.75mg/95mg, 36.25mg/145mg, 48.75mg/195mg, and 61.25mg/245mg.
The starting dose for Rytary in levodopa naïve patients is 23.75mg/95mg three times per day for 3 days. On day 4, the dose may be increased to 36.25mg/145mg three times daily. Further dosage increases may be employed based upon patient response, up to a maximum recommended dose of 97.5mg/390mg three times a day. Capsules should be swallowed whole and should not be chewed or crushed. For patients that cannot swallow capsules whole, Rytary capsules may be opened and the contents can be sprinkled on to a small amount of applesauce for immediate consumption.
Most common adverse effects noted with Rytary were nausea and headache (similar to immediate release carbidopa-levodopa in the comparison trial).
Rytary may offer a significant advantage in Parkinson’s patients who are not able to achieve adequate periods of “on” time during the waking hours, or those who exhibit troublesome dyskinesia with carbidopa-levodopa immediate-release tablets. There is currently no data available to demonstrate any clinical advantage of Rytary over the carbidopa-levodopa CR (controlled release) tablets. From a practical standpoint, Rytary does have an advantage over the “CR tablets” for patients that cannot swallow whole pills, since the carbidopa-levodopa tablets should be swallowed whole and should not be chewed or crushed. As with most new products, Rytary is expensive with a mid-range dosage expected to cost the hospice between $300 - $400 per month.
Jennifer Chen, PharmD
DEA has announced that the 10th annual National Prescription Drug Take-Back will take place on September 26th from 10am to 2pm local time in every state except Pennsylvania and Delaware, where it will take place on September 12th. This is a great opportunity for the public to dispose unwanted and expired medications. These types of medications in the house are a leading cause of accidental poisoning. In addition, inappropriate disposable of medications may also lead to potential safety and health hazards. Check your own medicine cabinets and advise your patients, friends and families. Help get those drugs out of homes and reduce the threat of prescription drug abuse.
What should you do if you miss this event?
Another option for long-term care facilities to dispose of unwanted medications is to transfer those medicines to collectors registered with the DEA. These DEA-authorized collectors safely and securely collect and dispose of pharmaceuticals containing controlled substances and other medicines. In your community, authorized collection sites may be retail pharmacies or hospital pharmacies. These sites may also offer mail-back programs or collection receptacles (or “drop-boxes”) to assist the public in safely disposing of medications. Click here to locate a DEA-authorized collector in your area.
If there is no take-back program or DEA-authorized collectors available in your area, you may also dispose of medicines in household trash or flush certain medicines down the toilet (be sure to know the law in your state before recommending medications to be flushed; for example, flushing medications down the toilet is not recommended in California). The FDA provides an updated list on the drugs recommended for disposal by flushing (last updated in February 2015). For more information on proper drug disposal, please review our previous blog posts on the topic of proper drug disposal.
Esther Liu, PharmD, MSIA, CGP
The U.S. Food and Drug Administration (FDA) approved another anti-clotting drug Savaysa (edoxaban) in January 2015 for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). This medication also has the FDA approved indication to reduce the risk of stroke and blood clots in patients with atrial fibrillation, but it is not recommended for patients with CrCl greater than 95ml/minutes due to its inferior efficacy in comparison to Coumadin (warfarin) at clinical trials.
This is the third oral factor Xa inhibitors approved by FDA as an anticoagulant to treat blood clots and prevent stroke risk in the last four years. The most common side effects for Savaysa observed in clinical trial participants were bleeding and anemia.(1) Just like the other FDA-approved anti-clotting drugs, bleeding, including life-threatening bleeding, is the most serious risk with Savaysa. There is no treatment that has been proven to reverse the anticoagulant effect of Savaysa like the antidote we have for Coumadin.
Factor Xa inhibitors, like Savaysa, are likely to be reserved as a second line therapy due to its lack of antidote to the anticoagulant effect and they are cost-prohibitive compared to Coumadin. When you encounter a patient with one of the new anticoagulants in the hospice setting, it is important to ask the following questions to ensure if the anticoagulation treatment is still suitable for your hospice patients:
1. Is the patient taking the medication for treatment or stroke prevention?
If the patient is taking the medication for stroke prevention in atrial fibrillation, the medication should be considered for discontinuation unless the patient has a high risk for clotting. Outcome Resources provides patient-directed letters to help hospice providers to communicate the rationale of discontinuing the anticoagulant at end of life care.
2. What is the risk vs. benefit of continuing the anticoagulation therapy? What is the likelihood of patient getting another blood clot? Did the patient have a recent clotting event even if the patient is using the medication for clotting prevention?
A study has suggested that anti-coagulants can reduce stroke risk by about 4% per year on average for ambulatory patients with atrial fibrillation.(2) Hospice patients are more likely to suffer from the side effects of bleeding at end of life than having a blood clot event. Therefore, the risks of anticoagulation treatment are greater than the benefits in this population and should be considered for discontinuation.
3. If the hospice patient has a high risk for clotting and has a reasonable functional level (Palliative Performance Scale >40%), why is the patient not able to take Coumadin (warfarin) versus the other anticoagulants?
Coumadin is the most cost-effective medication in the class of anticoagulants even after taking into account for the INR monitoring cost. It is the only oral medication in this class with an antidote for its anticoagulation effects, which makes it a safer option for patients with bleeding risk, especially in the hospice setting. The only drawback to using Coumadin is the requirement of routine INR monitoring on the anticoagulation effect while the newer agents do not. However, recent studies have suggested that routine INR monitoring improves patient adherence to the anticoagulant therapy, which leads to better outcomes from Coumadin in general.(3)
If you have asked these three sets of questions above and the answers still suggested that the patient is a candidate to continue on an anticoagulation therapy, then you can consider some of the newer oral agents, like the factor Xa inhibitors. They are generally more cost-effective than the injectable anti-coagulants like Lovenox.
Here is the clinical pearl of using anticoagulants in hospice setting. 1) Consider discontinuation if possible. 2) If not, Coumadin remains as the gold standard to treat/prevent blood clots before other newer anticoagulants. 3) Reserve the injectable anticoagulants as the last resort as it is both invasive and expensive.
1. FDA approves anti-clotting drug Savaysa: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm429523.htm . Accessed August 27, 2015.
2. Archives of Internal Medicine 1994; 54: 1449-1457.
3. Comparing the New Oral Anticoagulants. Pharmacist’s Letter. June 2014.
4. Anticoagulant Comparison Chart. North American Thrombosis Forum. www.natfonline.org. Accessed August 27, 2015
Jennifer Chen, PharmD
On 8/25/2015, Allergan has issued a voluntary nationwide recall on certain lots of various eye ointments due to contamination of black particle from unscrewing the cap from the aluminum tube. This black particle can potentially be introduced into the product and was found at time of use by a small number of customer. The reported adverse events include foreign body in the eye, superficial eye injury, pain, swelling and blurred vision.
Two of recalled ointments are sold over the counter. The ointments in question are:
This recall only applies to specific lots of the product listed above and does not affect any other Refresh or Allergan product. Specific information on product and lots can be found by clicking here. The lots subject to the recall have expiration dates that range from April 2017 to March 2018. This recall is extended to the patient level, so the pharmacies which have dispensed these products may have already contacted the patients who may have received these products. As an additional precaution, it is advised to check with your patients who are currently using these eye ointments and evaluate if they are affected by this recall.
Stephanie Cheng, PharmD, MPH
On 07/30/2015, Unichem Pharmaceuticals issued a voluntary recall of a specific lot of their Hydrochlorothiazide 25mg tablets as a Plavix (clopidogrel) tablet was found in a bottle of the product. The FDA has notified distributors and pharmacies about the recall. The dispensing pharmacies were expected to identify patients received the specific lot of medication and to bring this to the attention of the consumer level. Unichem has stated that this episode is an isolated event noted at one pharmacy and confined to the recalled lot. They have not received any reports of adverse events related to this recall to date.
The risk of mistakenly taking a Clopidogrel tablet instead of a Hydrochlorothiazide tablet may include an increased risk of side effects associated with Clopidogrel, which include bleeding and/or bruising. Patients with active bleeding or who are allergic to Clopidogrel or any component of the formulation may experience more serious adverse health consequences as a result of unknowingly consuming Clopidogrel. Additionally, missing a dose of Hydrochlorothiazide could result in uncontrolled blood pressure or swelling caused by excess fluid (edema).
The affected Hydrochlorothiazide 25mg lot is GHYL15028 – expiration April 2018. It was packaged in 1000-count bottles and were distributed nationwide directly to wholesalers, retailers and pharmacies from May 21 - 28, 2015. The tablets can be identified as a round light orange/yellow tablet with a beveled edge, with a score mark and U 128 imprint.
There is a “drug identifier tool” under Clinical Resources in the members section of our web-site: www.OutcomeResources.com. You may identify a pill by entering the shape, color, imprint, dosage-form, or scoring on a tablet. This may be very helpful when loose pills are found in the patient’s home or in cases such as this when different tablets are found in the same prescription bottle.
Outcome Resources is including this information on our blog for the hospice clinicians since Hydrochlorothiazide is widely used in hospice for a variety of indications and this news may impact your patients. It is advisable to check with your patients who have current orders for Hydrochlorothiazide 25mg and evaluate if they are affected by this recall. If you suspect that one of your patients has the affected product, call the pharmacy which dispensed the prescription and have the prescription label in hand to provide necessary information to the dispensing pharmacy to verify the lot information for you. In the event you encounter the recalled product, return it to the pharmacy that dispensed it for a replacement.
If you are an Outcome Resources client, the clinical team will reach out to you if we have suspected that one of your patients has received Hydrochlorothiazide from this manufacturer.
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Education Resources and Support for Hospices
Stay up-to-date on the latest hospice pharmacy benefits management information and tools with a variety of education resources and support at no extra charge. We offer presentations live at your facility, over the Internet or viateleconference, online service education programs, customized courses, and courses accredited for nursing continuing education credit.
Our palliative care experts provide clinical consulting on important medication management and care decisions. Our non-dispensing pharmacists provide focused attention and unbiased advice.
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