AVENTURA, FLA. – Clinicians interested in providing naloxone for their patients at risk for an opioid overdose should consider the pros and cons of the different formulations, addiction medicine specialists say.

In addition, clinicians should become familiar with legislation affecting how naloxone can be prescribed to lay persons in their state, according to the specialists, who spoke at the annual meeting of the American Academy of Addiction Psychiatry.

During a workshop on expanding access to the opioid antagonist to patients at risk and their families to help prevent opioid overdoses, Dr. Eric D. Collins, physician-in-chief at Silver Hill Hospital, New Canaan, Conn., described naloxone as “an effective and generally safe intervention that requires minimal training” and can be administered by a layperson. “Any prescriber can provide naloxone to persons at risk of opioid overdose” and in some states, can provide naloxone to anyone at risk of witnessing an opioid overdose, he added.

Dr. Seddon R. Savage, director of the Dartmouth Center on Addiction Recovery and Education, Hanover, N.H., said that although providing naloxone is a late intervention, it saves lives. “So clearly, it is critical that we embrace that strategy,” she said.

Providing naloxone is among the current strategies used to address the misuse of prescription opioids and to reduce mortality and morbidity related to opioids. These strategies include the development of tamper-resistant products, public campaigns increasing awareness about the importance of locking up pain medications and disposing of them safely, drug take back programs, and pharmacy-based interventions.

Overdose death rates fall

To date, “good solid evidence for efficacy in reducing mortality and opioid overdoses only exists” for maintenance therapy of opioid dependence and naloxone distribution, said Dr. Savage, who also is medical director of the chronic pain and addiction program at Silver Hill Hospital. She cited a 2013 study that found a significant reduction in opioid overdose deaths rate after a program that provided education about overdoses and nasal naloxone kits to potential bystanders (users, families, and friends) was implemented in 19 communities in Massachusetts with high overdose rates. Training included 10-60 minutes of training in recognizing and intervening in an overdose (BMJ 2013; 346:f174).

For pain medicine specialists, Dr. Savage said, “it is reasonable to consider” providing naloxone to patients at risk for overuse tied to unmet pain needs, accidental overuse, or self-treatment of other symptoms; as well as those with history of recreational drug use or addiction. Primary care clinicians can target their patients being treated with opioids for pain and those with known or a suspected addiction to opioids. Addiction medicine specialists can consider prescribing naloxone to their patients with opioid addiction on or off opioid agonist therapy (OAT), such as buprenorphine.

However, challenges prevail in prescribing naloxone, which include wide variations in naloxone legislation and Good Samaritan laws in states, resources needed to train lay people to administer naloxone, and recent increases in the cost of intranasal naloxone. The latter is the most widely used form of the drug to treat overdoses, said Dr. Savage, who also is affiliated with Dartmouth Medical School in Hanover.

Familiarity with laws advised

Dr. Savage advised clinicians to become familiar with the policies regarding naloxone prescribing and Good Samaritan laws in their jurisdictions. Legislation that exists in some states but not others include protection from possession of controlled substance and paraphernalia (in 22 states and the District of Columbia [D.C.] as of August 2014), protection from criminal liability for lay administration of naloxone (23 states and D.C.), protection from civil liability for lay administration (20 states and D.C.) and protection of prescribers from criminal liability (13 states). In 24 states, third party prescribing is allowed.

Naloxone – which binds to opioid receptors and in patients on opioids, thereby reversing the effects of opioids, including respiratory depression – can precipitate opioid withdrawal symptoms in some patients, said Dr. Collins, who also is affiliated with Columbia University in New York. He referred to a 2004 study that found that the most common adverse events after naloxone was used to treated a suspected opioid overdose outside of the hospital were confusion ( 32%) and headache (22%), nausea and vomiting (9%), and aggressiveness (8%), but serious complications were rare (Eur. J. Emerg. Med. 2004;11:19-23). Seizures were reported in 4% and tachycardia was reported in 6%. Dr. Collins said he has never seen a case of allergy to naloxone, the only contraindication to the drug.

Since aggressiveness might be associated with withdrawal, Dr. Savage said training for naloxone providers often includes how to manage a combative person. The risk of tachycardia has been raised as a concern, particularly in situations where law enforcement personnel who are not medically trained are delivering naloxone, but those patients are transported to medical facilities, she pointed out.

Intranasal (IN) naloxone, which is not approved by the Food and Drug Administration, is the most widely used method of administering naloxone by police and other first responders. They use a standard dose of 0.4 contained in a syringe with an atomizer, delivering one 0.2 mg dose per nostril. Another option is the autoinjector that provides an injection of naloxone with a speaker that provides instructions guiding the user. This option was approved by the FDA in 2014.

Evidence that the intranasal form is effective dates back to 2005, with a study that found a dose of 2 mg/2 cc in a prefilled syringe delivered with an atomizer by Denver paramedics was effective in 43 of 52 (83%) people. IV naloxone was needed in nine individuals who did not respond to the IN dose, including five who had nasal pathology (J. Emerg. Med. 2005; 29:265-71). In a more recent study that randomized 100 patients admitted to an emergency department with an opioid overdose to a lower IN dose (0.4 mg) or IV naloxone, the IN route proved as effective as the IV route in reversing respiratory depression and central nervous system effects (Arch. Med. Sci. 2014;10:309-14).

Dr. Eric Collins (right) watches an EMT during a training session in New Canaan, Ct., that included instruction on naloxone administration.

Broad effectiveness found

Dr. Collins said the various options have advantages and drawbacks, and if only one option is available for whatever reason, “they all work.” IM and IV formulations have the fastest onset of action, are the least expensive, and are FDA-approved but carry the risk of a needlestick injury. IN naloxone is not FDA-approved, and might have a slightly slower and less predictable effect but has no risk of a needlestick injury. In addition, IN naloxone is inexpensive and easy to use. The recently FDA-approved Evzio autoinjector pre-filled with naloxone solution, administered IM or subcutaneously, has a faster onset with a predictable effect and no risk of a needle stick. It also includes audio instructions that walks the user through its use. But it costs about $400 per kit, which is a drawback, he said.

Dr. Savage pointed out that administering naloxone is only part of intervening in an opioid overdose and that training is needed when naloxone is dispensed or prescribed to patients or their families. Included in such training would be when to call for help, how to identify signs of an overdose, how to position patients for rescue, understanding rescue breathing, and knowing when the admininstration of naloxone is indicated. Since naloxone wears off in about half an hour, depending on the route and other variables, people should be told that they need to call for emergency support and transport for ongoing care because many opioids end up lasting longer than the effects of naloxone.

The FDA is considering making naloxone available over the counter, but such a move will take several years. It can be provided by pharmacies in states that have a collaborative practice agreement in place that supports distribution to people addicted to opioids, their families, and friends, she said. For example, in Rhode Island, a collaborative practice agreement exists allowing Walgreens pharmacies to dispense naloxone without a prescription.

Based on an informal poll taken during the workshop, none of those in attendance had started to prescribe naloxone for their patients, although they were interested in doing so or were figuring out how to make it available. During the discussion period, barriers they cited included the time and resources needed to train people to administer naloxone, the cost, and the lack of awareness among pharmacies about their ability to obtain intranasal kits. Suggestions among participants include having nurses or pain medicine fellows provide training and education, and using videos for training. A physician at the Atlanta Veterans Affairs Medical Center pointed out that naloxone is provided at no charge to all VA hospitals, although patients might have a co-pay.

Among the resources provided by Dr. Savage and Dr. Collins for clinicians interested in providing naloxone to patients at risk of an opioid overdose and to family members of others who might witness an overdose was an American Medical Association webinar on naloxone safety, information on how to start prescribing and dispensing naloxone rescue kits, and patient information videos. More information on how to start a program is available at http://www.naloxoneinfo.org.

Dr. Savage and Dr. Collins said they had no direct commercial interests related to the topic of the workshop.

emechcatie@frontlinemedcom.com

Making naloxone available to patients at risk for opioid overdoses