The FDA has approved RiVive (Harm Reduction Therapeutics), a 3-mg naloxone nasal spray, as an over-the-counter (OTC) product for emergency treatment of opioid overdose. Two 4-mg naloxone nasal spray formulations, Narcan and one of its generics, were approved for OTC sale in 2023.

View Comparison Table: Some Drugs for Maintenance Treatment of Opioid Use Disorder

Opioid use disorder is a chronic, relapsing disease with physical and psychiatric components. It is associated with economic hardship, social isolation, incarceration, increased rates of blood-borne infections such as HIV and viral hepatitis, adverse pregnancy outcomes, and increased mortality. According to the NIH, there were 80,411 deaths involving an opioid in the US in 2021, more than in any previous year. Several guidelines on the management of opioid use disorder are available; all recommend maintenance pharmacotherapy as the standard of care.

The FDA has approved a subcutaneously injected, extended-release formulation of the mu-opioid receptor partial agonist and kappa-opioid receptor antagonist buprenorphine (Brixadi – Braeburn) for once-weekly or once-monthly treatment of moderate to severe opioid use disorder. Brixadi is the second subcutaneously injected buprenorphine formulation to be approved in the US; Sublocade, which is administered once monthly, was the first. Buprenorphine is also available for treatment of opioid use disorder in sublingual formulations with and without the opioid antagonist naloxone.

The FDA has approved the over-the-counter (OTC) sale of Narcan (Emergent), a nasal spray that delivers 4 mg of the opioid antagonist naloxone. Narcan nasal spray has been available by prescription since 2015 for emergency treatment of opioid overdose. Generic formulations of Narcan have also been approved; the manufacturers of these products will be required to switch them to OTC status and amend their labeling accordingly. Kloxxado, an 8-mg naloxone nasal spray, remains available only by prescription.

A new CDC guideline for prescribing opioids for pain recently became available. Nonopioid drugs for pain were reviewed in a previous issue.

View Expanded Table: Some Drugs for Management of Opioid Withdrawal Symptoms

The FDA has approved lofexidine (Lucemyra – US WorldMeds/Salix), a centrally acting alpha₂ receptor agonist, to manage withdrawal symptoms in adults abruptly stopping opioid use. Available in the UK since 1992, lofexidine is the first nonopioid to be approved in the US for management of opioid withdrawal symptoms. Clonidine (Catapres, and generics), another central alpha₂ receptor agonist, has been used off-label for this indication for many years.

Use of nonopioid drugs for pain was reviewed in a previous issue. For many types of moderate to severe acute pain, acetaminophen and/or an NSAID may be as effective as an opioid. Immediate-release formulations of full opioid agonists should generally be used for acute pain that is severe enough to require treatment with an opioid. Use of extended-release or long-acting opioid formulations initially and treatment durations >1 week have been associated with an increased risk of unintended long-term use.

The FDA has approved a subcutaneous (SC) extended-release formulation of the mu-opioid receptor partial agonist and kappa-opioid receptor antagonist buprenorphine (Sublocade – Indivior) for once-monthly treatment of moderate to severe opioid use disorder. Sublocade is the first injectable buprenorphine product to be approved in the US. Buprenorphine is also available in sublingual formulations with or without the opioid antagonist naloxone, in a buccal formulation with naloxone, and as a subdermal implant (Probuphine).

Opioid use disorder is a chronic, relapsing disease with both physical and psychiatric components. It is associated with economic hardship, social isolation, incarceration, increased rates of blood-borne infections such as HIV and viral hepatitis, adverse pregnancy outcomes, and increased mortality. According to the CDC, there were 33,091 deaths related to opioid overdose in the US in 2015, more than in any previous year. Several guidelines on the management of opioid use disorder have recently been published.

View Comparison Table: Some Drugs for Maintenance Treatment of Opioid Use Disorder

The FDA has approved subdermal implants of the partial opioid agonist buprenorphine (Probuphine – Titan) for maintenance treatment of opioid dependence in patients stabilized on low to moderate doses of transmucosal buprenorphine. Probuphine was designed to provide continuous low levels of buprenorphine for 6 months and to safeguard against illicit use of the drug.

Belbuca (Endo), a buccal formulation of the partial opioid agonist buprenorphine, has been approved by the FDA for management of pain severe enough to require daily, around-the-clock, long-term opioid treatment. Buprenorphine is also available as a transdermal patch (Butrans) and in a parenteral formulation (Buprenex, and generics) for treatment of pain. A sublingual formulation of buprenorphine and buccal and sublingual formulations containing buprenorphine and the opioid antagonist naloxone are approved for use as alternatives to methadone for treatment of opioid dependence.

The FDA has approved Viekira Pak (Abbvie), a fixed-dose combination of two new direct-acting antiviral agents (ombitasvir, paritaprevir) with the pharmacologic enhancer ritonavir in one tablet, co-packaged with a third new direct-acting antiviral agent (dasabuvir) in a second tablet, for oral treatment of chronic hepatitis C virus (HCV) genotype 1 infection. Genotype 1 is responsible for 70-80% of HCV infections in the US.

The FDA has approved a buccal film formulation of the partial opioid agonist buprenorphine combined with the opioid antagonist naloxone (Bunavail – BioDelivery Sciences) for maintenance treatment of opioid dependence. Sublingual tablet and film formulations of the same combination were approved earlier. The manufacturer of Bunavail claims that the new product is superior to sublingual formulations because of the convenience of buccal administration and better absorption into the blood, permitting use of lower doses.

A new sublingual tablet formulation of the partial opioid agonist buprenorphine combined with the opioid antagonist naloxone (Zubsolv – Orexo) has been approved by the FDA for maintenance treatment of opioid dependence. Zubsolv tablets have relatively greater bioavailability than previously approved sublingual film (Suboxone) and sublingual tablet formulations of buprenorphine/naloxone and, according to an open-label survey, they taste better. The new tablets are smaller and dissolve faster than other tablet formulations, and they are individually sealed in child-resistant packaging.1

Buprenorphine is a Schedule III controlled substance that can be prescribed in an office setting by qualified physicians who register with the Substance Abuse and Mental Health Services Administration.2

Zubsolv is available as triangular tablets containing 1.4 mg of buprenorphine and 0.36 mg of naloxone and round tablets containing 5.7 mg of buprenorphine and 1.4 mg of naloxone, which achieve plasma concentrations of buprenorphine equivalent to those with the 2/0.5-mg and 8/2-mg strengths of other buprenorphine/naloxone tablets. A package of Zubsolv 5.7/1.4-mg tablets costs the same ($211) as a box of Suboxone 8/2-mg films. A bottle of generic buprenorphine/naloxone 8/2-mg tablets costs $250.3

1. A Fischer et al. Pharmaceutical and pharmacokinetic characterization of a novel sublingual buprenorphine/naloxone tablet formulation in healthy volunteers. Drug Dev Ind Pharm 2013 Oct 7 (epub).

2. Buprenorphine: an alternative to methadone. Med Lett Drugs Ther 2003; 45:13.

3. Approximate wholesale acquisition cost (WAC) of 30 tablets or films. Source: $ource® Monthly (Selected from FDB MedKnowledge™) October 5, 2013. Reprinted with permission by FDB, Inc. All rights reserved. ©2013. www.fdbhealth.com/policies/drug-pricing-policy. Actual retail prices may be higher.

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Pain can be acute or chronic. The two major types of chronic pain are nociceptive pain and neuropathic pain. Nociceptive pain can be treated with nonopioid analgesics or opioids. Neuropathic pain is less responsive to opioids and is often treated with adjuvant drugs such as antidepressants and antiepileptics. Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects.

The FDA has approved the partial opioid agonist buprenorphine in a transdermal formulation (Butrans – Purdue) for treatment of moderate to severe chronic pain. Buprenorphine has been available in the US for years in parenteral formulations for pain and in sublingual tablets for opioid dependence.1 Transdermal buprenorphine has been available in Europe for several years.2

Pain can be acute or chronic. Chronic pain has been broadly classified into two types: nociceptive and neuropathic. Nociceptive pain can be treated with nonopioid analgesics or opioids. Neuropathic pain is less responsive to opioids; adjuvant medicines such as antidepressants and anticonvulsants are often used to treat neuropathic pain. Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects.

Pain can be acute or chronic. Chronic pain has been broadly classified into two types: nociceptive and neuropathic. Nociceptive pain is generally treated with nonopioid analgesics and opioids. Antidepressants and anticonvulsants have been used to treat neuropathic pain. Combining two different types of analgesics may nprovide an additive analgesic effect without increasing adverse effects.

Three types of analgesic drugs are available: non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; opioids; and adjuvant drugs that are not usually thought of as analgesics, such as antidepressants, which can act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. Combining two different types of analgesics may provide an additive analgesic effect without necessarily increasing adverse effects.

The FDA has approved the marketing of buprenorphine in sublingual tablets (Reckitt Benckiser) both alone (Subutex) and with naloxone (Suboxone) for treatment of opioid dependence. Previously available only for parenteral use in treatment of pain (Buprenex, and others), it offers an alternative to methadone (Dolophine, and others), which is now often abused (New York Times, February 9, 2003; page 1). As a schedule III narcotic, buprenorphine will be subject to fewer prescribing restrictions than a schedule II drug such as methadone (MJ Kreek and FJ Vocci, J Subst Abuse Treat 2002; 23:93).w1150a

Three types of analgesic drugs are available: first, non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; second, opioids; and third, drugs not usually thought of as analgesics, which act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. Non-opioids can be given concurrently with opioids for an additive analgesic effect.

Three types of analgesic drugs are available: first, non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; second, opioids; and third, some drugs not usually thought of as analgesics, which act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain.

Acute toxic reactions to drugs of abuse continue to be important problems. Since the last Medical Letter article on this subject (volume 32, page 92, 1990), new reactions and new approaches to treating them have been reported.

Three types of analgesic drugs are available in the USA: first, aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; second, opioids; and third, drugs not usually thought of as analgesics, which act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. (American Pain Society, Principles of analgesic Use, 3rd ed, Skokie, illinois: American pain society, 1992).

Dezocine (Dalgan - Astra), a new synthetic opioid agonist/antagonist structurally related to pentazocine (Talwin), was recently approved for parenteral use as an analgesic by the US Food and Drug Administration.