The Hospice Clinician Blog

New Hospice Medication Update: Butrans

The FDA has recently approved Butrans, a new transdermal opioid patch. The opioid in Butrans, buprenorphine, has been available in the U.S . for several years in the form of Suboxone and Subutex sublingual tablets. The buprenorphine patch has been used for the management of chronic pain in Europe for years under the brand name of Norspan, but it is new to the U.S. market.

The transdermal patch is available in three strengths, 5mcg/hr, 10mcghr, and 20mcg/hr and provides continuous release of the medication for seven days. It is classified as a DEA schedule III controlled substance, similar to moderate-strength opioids such as Vicodin or Norco. Butrans is indicated for chronic severe non-malignant pain when lower doses of strong opioids are indicated. The highest strength Butrans patch (20mcg/hr) is approximately equivalent to 50mg of oral morphine per day. Doses greater than 20mcg/hr are not recommended due to the potential for adverse cardiac effects (QTc prolongation).

Buprenorphine is a partial mu opioid agonist. This means that, even though buprenorphine is an opioid that can produce typical opioid agonist effects (analgesia) and side effects (euphoria and respiratory depression) in hospice patients, its maximal effects are less than those of full agonists such as morphine and methadone. The agonist effects of buprenorphine increase linearly with increasing doses of the drug until at moderate doses they reach a plateau and no longer continue to increase with further increases in dose—the “ceiling effect.” For this reason, buprenorphine is believed to have a lower risk of abuse, addiction, and side effects compared to full opioid agonists. In high doses, buprenorphine may actually trigger some opioid withdrawal symptoms in persons who have been receiving other opioids and have developed some physical dependence, however, this effect may not be clinically significant at the lower doses employed with the transdermal patch.

The Butrans patch is not indicated for management of short-term post-operative pain, but may be beneficial for management of chronic severe pain in hospice patients who are vomiting or have swallowing difficulties. The eventual role of the Butrans patch in chronic pain management is still being established. Cost for the new drug was not available at the time of this post, however, as with all new branded medications, we can expect a hefty price-tag.

http://www.purduepharma.com/PI/prescription/ButransPI.pdf 

Series on Pediatric Hospice & Palliative Care Patients

The July issue of The Clinician, our quarterly clinical newsletter, will feature the final article in our three-part series on pediatric palliative care. In the upcoming article, Julia Harder, PharmD, will discuss the management of some of the most common non-pain symptoms encountered in pediatric palliative care. Specific symptom complexes that will be addressed include: anxiety & depression, agitation, insomnia, anorexia-cachexia, nausea-vomiting, constipation, and dyspnea. Specific medication strategies will be presented for managing each of these troubling symptoms in pediatric hospice patients. All clients of Outcome Resources receive complimentary copies of The Clinician each quarter. Previous issues of The Clinician can be obtained by contacting Jim Joyner, PharmD, at jjoyner@outcomeresources.com Be sure to check the Blog for the upcoming Part 3 in the series.

Dowload Part 1 of Pediatric Palliative Care Series: Current Concepts in Drug Therapy

Dowload Part 2 of Pediatric Palliative Care Series: Pain Management

Pain Management in Hospice Patients: Buprenorphine (Subutex, Suboxone)

Buprenorphine (Subutex, Suboxone) tablets are now being used to treat severe pain, not just opioid addiction. Since 2002 Buprenorphine has been widely used to treat opioid addiction by preventing the symptoms of opioid withdrawal.

More recently it is being used to treat severe pain, although the tablets only have an FDA approved indication for addiction treatment at this time. Subutex contains buprenorphine alone, and Suboxone contains buprenorphine and naloxone. The naloxone is there to prevent opioid effects if patients try to inject it.

Buprenorphine is a strong opioid with analgesic properties similar to morphine, methadone, oxycodone, hydromorphone, and fentanyl. It has an advantage over these traditional full agonist opioids in that there is less risk for psychological or physical dependence and it results in fewer withdrawal symptoms when it is stopped. There is also less risk for psychotomimetic effects (delusions, hallucinations). The FDA has recognized the lower risk factor for abuse with Buprenorphine and has assigned it a Schedule III controlled drug classification as opposed to the more stringent Schedule II classification seen with other strong opioids.

Some subtle differences in Buprenorphine pharmacology may account for the decreased risks seen when comparing to more traditional strong opioids. Drugs such as Morphine, Methadone, Fentanyl and others are full-agonists at the mu opioid receptor which means they bind tightly to the drug receptor sites in the body. Withdrawal of therapy for drugs with complete and tight binding at their receptor sites is associated with significant withdrawal symptoms. Buprenorphine is a partial-agonist the mu opioid receptor and is actually an antagonist at the kappa opioid receptor. It essentially is loosely bound to the mu receptor. This partial agonist property and the mixed agonist-antagonist activity may result in a decreased potential for abuse, withdrawal, and psychotomimetic effects in patients using Buprenorphine.

Subutex and Suboxone are available in tablets for sublingual administration. They are not effective by the oral route. Strengths are 2mg and 8mg tablets. The dosage range is 2 to 16mg three to four times a day for pain (instead of once a day for addiction treatment). Unlike traditional full-agonist strong opioids (morphine, methadone, fentanyl, oxycodone, and hydromorphone), Buprenorphine seems to have a "ceiling dose" after which increased doses produce no increase in opioid agonist effects.

This was demonstrated in clinical trials at doses of 16 to 32mg. The onset of action of the tablets is about 15 minutes, with peak activity at 60 minutes and a duration of analgesic activity of 6 to 8 hours. There is also an injectable solution available for intramuscular or intravenous administration. This injectable solution carries an FDA approved indication for the treatment of severe pain. The IM/IV dosage is 0.3mg at six hour intervals as necessary. IV doses should be administered slowly over 2 minutes.

The cost of a 15 day supply of a mid-range dose of Subutex (4mg three times per day) is in the range of $360.00. This makes Subutex one of the highest, if not the highest cost opioid drug on the market. The role of Buprenorphine in the management of chronic pain is still being defined. It has some significant advantages including: a lower potential for psychotomimetic side effects, lower abuse potential, reduced potential for severe withdrawal reactions, and no requirement for a schedule II triplicate prescription. Due to the fact that its duration of action is only 6 to 8 hours, Burprenorphine does not have the characteristics of a desirable long acting opioid that one would use for maintenance therapy of severe chronic pain. The greatest negative is the extremely high cost which makes it an unrealistic option for most hospice organizations at this time. The evolving role for Buprenorphine in the management of pain may be one that is targeted at acute severe pain in the hospital and clinic setting.

Revised Labeling & Warnings for Hospice Medications

Revised Proton Pump Inhibitors Labeling

The FDA has revised labeling for prescription and OTC proton pump inhibitors (PPIs), to include new safety information about a possible increased risk of hip, wrist, and spine fracture associated with the use of these medications. The new safety information is based on the FDA's review of 7 epidemiological studies that found those at greatest risk for these fractures received high doses of PPIs or had used them for 1 year or more. The majority of the studies evaluated individuals 50 years of age and older, with increased fracture risk primarily observed in this age group. However, randomized clinical trials of PPIs have not found an increased risk of fracture of the hip, wrist, or spine.

Revised Warning Sections for Ultram and Ultracet

Ortho-McNeil-Janssen and the FDA are notifying health care professionals of changes to the Warnings section of the prescribing information for Ultram (tramadol) and Ultracet (tramadol/acetaminophen). The revised information highlights the risk of suicide for patients who are addiction prone or taking tranquilizers or antidepressant drugs, as well as the risk of overdosage. Tramadol-related deaths have occurred in patients with previous histories of emotional disturbance or suicidal ideation or attempts, as well as in those who have previously misused tranquilizers, alcohol, and other CNS-active drugs.

Generic Memantine for Alzheimer's Approved by the FDA

Generic Memantine Approved

The FDA has approved Sun Pharmaceuticals' Abbreviated New Drug Application for memantine hydrochloride 5 and 10 mg tablets, indicated for the treatment of moderate to severe Alzheimer's disease. The medication is the generic equivalent of Namenda by Forest Laboratories.

Briefing Document on Memantine from the FDA

Opioid Medication Shortages in Hospice Care

Best Practices for Dealing with Opioid Shortages in Hospice

Occasionally hospice and palliative care programs have to deal with shortages of medications that are essential to providing quality end-of-life care. We are reminded to remain aware of this issue as it has been a year since the major shortage of opioids affected hospices nationwide. Whether a regional or national shortage, there are some things you can do to help alleviate the problem until resolved.  

• Check with your pharmacies regularly to determine which opioids are available at which pharmacies. Availability may change frequently. This seems to vary not just from one region of the country to another but from one pharmacy to another within the same town. If your hospice has a relationship with a Pharmacy Benefit Manager, utilize their assistance and possible Mail Order options (if shortage is regional.)
• Communicate and share this current supply information among nurses and physicians to reduce problems and delays related to ordering products that are not available.
• Physicians and nurses should be prepared to convert patients from one opioid to another in the event of specific product shortages. Once again, if your hospice has a relationship with a Pharmacy Benefit Manager, utilize their pharmacist consultation services to assist.
• Have equianalgesic conversion references available to help nurses and physicians with opioid conversions.

We have included an abbreviated opioid conversion chart to help. For more information about conversion to methadone, refer to our previous blog article Methadone for Hospice Patients.

DRUG	ORAL DOSE	PARENTERAL DOSE
Morphine	30 mg	10 mg
Oxymorphone	10 mg	-
Hydromorphone	7.5 mg	1.5 mg
Oxycodone	20 mg	-
Methadone	Varied: Pharmacist Consultation Recommended	1/2 Oral Dose
Hydrocodone	30 mg	-
Codeine	200 mg	-
Propoxyphene	180 mg	-
Meperidine	300 mg	75 mg
Fentanyl Patch	25mcg patch is approximately equivalent to 50mg oral Morphine/day	-

Morphine: MS-Contin, MS IR, Roxanol

Oxymorphone: Opana ER, Opana

Hydromorphone: Dilaudid

Oxycodone: Oxycontin, Oxyfast, Oxy IR, Percocet, Percodan

Methadone: Methadose

Hydrocodone: Lortab, Norco, Vicodin

Codeine: Tylenol w/ Codeine

Propoxyphene: Darvocet, Darvon

Meperidine: Demerol

Fentanyl patch: Duragesic

 

New OxyContin Formulation and Generic Alprazolam Approved

New OxyContin Formulation Approved

The FDA has approved a new formulation of OxyContin (Purdue Pharma) designed to discourage medication misuse and abuse. The reformulated OxyContin is intended to prevent the product from being cut, broken, chewed, crushed or dissolved to release more medication. This formulation may result in less risk of overdose due to tampering, likely resulting in less abuse by snorting or injection.

However, according to Dr. Bob Rappaport, director of the FDA's Division of Anesthesia and Analgesia Products, the new formulation provides only an "incremental advantage" over the current version of the drug. "Prescribers and patients need to know that its tamper-resistant properties are limited and need to carefully weigh the benefits and risks of using this medication to treat pain."

Many addiction experts are skeptical about how tamper-resistant the new formulation will prove to be. According to the FDA, Purdue Pharma will be required to conduct post-marketing analysis on how - or if - the new formula reduces abuse of the drug.

FDA News Release on New OxyContin Formulation 

Generic Alprazolam Orally Disintegrating Tablets Approved

The FDA has granted market approval to Actavis Group for alprazolam 0.25, 0.5, 1, and 2 mg orally disintegrating tablets, indicated for the management of anxiety disorder and the short-term relief of anxiety symptoms. The medication is generically equivalent to Niravam (Schwarz Pharma). The company will begin distributing the product immediately.

Find out more about Pharmacy Services for your Hospice at the NHPCO MLC!

Next week is NHPCO's Annual Management & Leadership Conference in Washington DC and the Outcome Resources team looks forward to seeing you there! If you have the chance to attend this year, stop by Booth #202 in the Exhibit Hall. We will have a special treat for the first 100 attendees that come by at the Opening Reception on April 22nd from 5:15pm - 7:00pm. Also, be sure to enter to win our contests and pick up information to share with your team. If you are not attending, request your Free Information Kit or a Free Consultation to learn more.

Outcome Resources is a Pharmacy Benefit Manager for hospices. Take a look at some of the benefits available to your hospice by partnering with OR:

 

• With one contract, your hospice receives one low discounted rate on ALL medications.
• Your patients have their choice of pharmacies (including mail order options) while your hospice receives one clear and concise invoice.
• Easier management of hospice patients in skilled facilities since all closed-door pharmacies are included on your invoice.
• With custom-tailored plan design and formulary control, you are in control of the medications that are dispensed and paid for by hospice.
• Your pharmacies are paid electronically every 15 days and processing claims through our program means fast and easy dispensing along with reduced chance for error.
• Unlimited Access to a team of experienced PharmDs for patient consults, drug information, and education programs.
• Online access to reports and patient medication information means you always have management tools at your fingertips.
• Dedicated lines of communication with your Account Claims Manager and Pharmacists to eliminate time-wasting transfers and phone trees.
• Partnership with a company dedicated solely to hospices - we understand your specific complex requirements.
• You can keep your hospice's medication dollars in the local economy, supporting the community that in turn supports your hospice.

 

Pediatric Palliative Care: Current Concepts in Drug Therapy

While the elderly constitute the vast majority of patients requiring hospice and palliative care, approximately 50,000 infants, children and adolescents die annually in the United States. Of these, epidemiologic studies estimate that 15,000 might benefit from palliative care. In addition, the National Hospice and Palliative Care Organization has estimated that palliative care would be an appropriate model of care for approximately 1.5 to 2 million children in the United States living with serious medical conditions. As the medical community has become more aware of this need, pediatric palliative care has received increasing attention as an emerging sub-specialty of palliative care focusing on achieving the best possible quality of life for children with life-threatening conditions and their families.

This article is the first in a series of three articles focusing on pediatric palliative care, and will introduce the topic by comparing palliative care of children to that of adults, reviewing pediatric pharmacokinetics, and giving general guidelines for pediatric medication administration. Subsequent articles will focus in more detail on pain management and the management of other symptoms commonly experienced by children at the end of life.

Click Here to Download the full article Pediatric Palliative Care: Current Concepts in Drug Therapy

Photo Credit http://www.flickr.com/photos/spigoo/ / CC BY 2.0

Baclofen: Effective for Cancer Pain in Hospice Patients

A group of investigators from a Japanese palliative care unit published an article describing the benefits of Baclofen (Lioresal) for managing cancer pain. ⁽¹⁾ This is significant since Baclofen, an effective muscle relaxant, has not previously been studied for its effect as an adjuvant medication specifically for managing cancer pain. Baclofen has potent antispasmodic activity making it a logical choice for numerous conditions associated with muscle spasm and pain related to muscle spasm. There are also reports in the medical literature that describe the effectiveness of Baclofen for certain neuropathic pain syndromes such as trigeminal neuralgia as well as post herpetic neuralgia. ⁽²⁾ Baclofen's mechanism for pain relief is thought to be mediated via the GABA receptors in the central nervous system, a mechanism distinctly separate from that of the opioids which are the primary category of drugs used to manage cancer pain in hospice patients. ⁽³⁾ Adding Baclofen to opioid therapy may make sense from the perspective of attacking the pain from two separate mechanisms of action.

 

This study was limited to 25 cancer patients who had pain resulting from the following conditions: spinal metastasis, pelvic plexus invasion, thoracic wall invasion, neck invasion, bone metastasis, brachial plexus invasion, celiac plexus invasion, and thalamic pain. The maintenance dosage range was 10mg-40mg per day in 2 to 4 divided doses. Pain was rated by the patient on a numerical rating scale (NRS) of 0 to 10. A 50% or greater reduction in pain according to the NRS was reported by 21 of the 25 patients after the addition of Baclofen. Side effects of sleepiness and GI symptoms were minimized by initiating therapy at a low initial dose of 10mg/day and titrating up to 40mg/day with gradual increases every 2 days depending upon response. Weakness is also a common side effect related to the muscle relaxant properties of Baclofen, however, in this study weakness was only noted in 1 patient. Baclofen was continued for a median duration of 114 days in the 21 patients who reported positive effectiveness.

The effectiveness of Baclofen in a few of the cancerous conditions is not too surprising since these conditions were likely to have a significant neuropathic pain component (ex; pelvic plexus invasion or spinal mets). The interesting finding is that it was also effective for other pain types such as bone metastases. This study suggests that Baclofen can be an effective adjuvant analgesic for managing cancer pain in combination with opioid therapy.

References: (1.) Yomiya, Matsuo, Tomiyasu, et al. Amer.J.Hosp&PalliatCare Med. 2009;Vol26, No2, 112-118. (2.) Fromm, et al. Arch Neurol. 1980;37:768-771 (3.) Chen, Pan . Neuroscience. 2006;142:595-606