Keeping Up With Clinical Trends — Nuedexta® and Levorphanol

By Michael Nguyen, PharmD
Director of Clinical Pharmacy

Our pharmacists often receive questions about specific medications such as how they are being used to properly treat an injured worker. Two drugs we hear questions about frequently are Nuedexta® and Levorphanol, which are high-cost, specialized medications in neuropathic conditions. Here are some recent questions posed by our clients related to these and why they are being prescribed more in workers’ comp cases:

What is Nuedexta® and why is it being prescribed to our injured workers?

Nuedexta is the brand name of a drug that combines 20 mg of dextromethorphan hydrobromide (an over-the-counter cough suppressant) and 10 mg quinidine sulfate (an antimalarial agent). Nuedexta is FDA-approved for a condition known as Pseudobulbar affect (PBA) which is also sometimes referred to as emotionalism, emotional lability or pathological crying and/or laughing. Pseudobulbar affect is described as a condition that causes sudden and frequent uncontrollable crying and/or laughing, which can be a result of a brain injury or a neurological condition. This condition affects approximately 0.5 to 2 million Americans and impacts nearly half of all stroke patients. Most commonly, in workers’ compensation, we see Nuedexta being prescribed to patients who have suffered traumatic brain injuries (TBIs). 

In 2011, Nuedexta became the first and only medication approved to treat PBA. The maintenance dose is one capsule twice daily. At the average wholesale price (AWP) of $19.08 per capsule, a month’s supply is $1,144.80. Often times to reduce the cost of combination products such as Nuedexta, patients take the drugs separately (e.g., Duexis®[ibuprofen/famotidine]; Vimovo®[naproxen and esomeprazole]), but in the case of Nuedexta this cannot be done. The lowest available commercial dose of quinindine sulfate, one of the ingredients found in Nuedexta is 200 mg which is 20 times the amount found in Nuedexta.

Before Nuedexta became available, doctors treated PBA with drugs prescribed off-label.  These included tricyclic antidepressants (e.g., amitriptyline, desipramine) and selective serotonin reuptake inhibitors (e.g., sertraline; paroxetine), both used to treat central nervous system disorders. Other drugs that have been used off-label for PBA include lamotrigine, carbidopa/levodopa and amantadine. Off-label prescribing is typically reserved for cases where there is no FDA-approved medication for a given condition.For this reason, Nuedexta may be considered an appropriate first-line alternative for PBA since it’s the only drug approved for this condition.

 

What is Levorphanol and why is it so expensive?

Levorphanol is a Schedule II opioid analgesic that has been used in the U.S. since the 1950s. The brand name of levorphanol is Levo-Dromoran® but has long been discontinued. Opioids exert their analgesic effect by targeting the mu-opioid receptor (MOR), but levorphanol is unique in that it is also known to increase norepinephrine and block N-methyl-D-aspartase (NMDA) receptors. These additional mechanisms make levorphanol effective for treating neuropathic pain, along with other medications such as tramadol, methadone and tapentadol.

Levorphanol was previously manufactured by West-Ward Pharmaceuticals, a subsidiary of Hikma Pharmaceuticals, at a cost of $2.14 per tablet (AWP). West-Ward discontinued levorphanol in 2015. A small U.S. specialty pharmaceutical company, Sentynl Therapeutics, Inc. revived levorphanol shortly thereafter and raised the price to $46.90 per tablet in 2015 (a 2,092% increase). As of April 1, 2018, Sentynl is selling levorphanol for $53.40 per tablet (AWP) and is now only available in a 2 mg generic tablet. According to Sentynl, the higher cost of levorphanol is due to the high cost of manufacturing incurred by a smaller size company and historic low demand for the drug. Low volume drugs like levorphanol demand higher cost for sustainability.

Levorphanol has a half-life of about 16 hours and can be considered a long-acting opioid. The manufacturer’s dosing guidelines recommend frequency every 6-8 hours (3-4 times daily). The long half-life of levorphanol can lead to possible drug accumulation which does not make it a first-line option among opioid analgesics for chronic non-cancer pain. Lower cost opioids that may provide comparable efficacy and tolerability include tramadol ER, tapentadol ER, morphine sulfate ER, oxycodone ER or methadone.

 

References:

• Chen JJ. Pharmacotherapeutic Management of Pseudobulbar Affect. Am J Manag Care. 2017;23:-S0
• What Is Pseudobulbar Affect? WebMD website. Available at: https://www.webmd.com/brain/pseudobulbar-affect#1 Accessed: 4/3/18
• Gudin, Jeffrey; Fudin, Jeffrey; Nalamachu, Srinivas (2015). “Levorphanol Use: Past, Present and Future”. Postgraduate Medicine. 128: 46–53.
• Nguyen U, Sparkes S. Unique Levorphanol Dodges Move from Forgotten to Vanished. PainDr website. Available at: http://paindr.com/unique-levorphanol-dodges-move-from-forgotten-to-vanished. Accessed: 4/4/18.