Pseudobulbar affect

Pseudobulbar affect

Dextromethorphan (DXM) has been re-purposed several times over the past seven decades: first as a cough suppressant, then as a compounded formulation with quinidine for treatment of pseudobulbar affect.  As such, the drug Nuedexta® came on the market.  The off-label indication includes agitation and aggression observed in patients with Alzheimer’s disease.  The level of evidence for this is C – Evidence from observational studies (e.g., retrospective case series/reports providing a significant impact on patient care), unsystematic clinical experience, or from potentially flawed randomized, controlled trials (e.g., when limited options exist for condition). Any estimate of the effect is uncertain.

When considering therapeutic alternatives to the Nuedexta® 20-10mg capsules totaling on or around $800 for a quantity of 30, there are a few considerations.

  1. Fluoxetine 20mg + 30mg dextromethorphan.  This would consist of a 20mg fluoxetine capsule given orally with dextromethorphan polistirex 30mg/5ml.  
  2. Compounded Nuedexta®:  DMQ suspension preparation
    1. An oral liquid preparation containing 11.1 mg quinidine sulfate per 10 mL and 19.7 mg dextromethorphan per 10 mL was prepared as follows:
    2. Procure one 118-mL trade size commercially available over-the-counter dextromethorphan 15 mg/5 mL oral liquid bottle (DM liquid). Crush and refine one 200 mg quinidine sulfate tablet in a glass mortar. Levitate with a minimal amount of the DM liquid. Quantitatively transfer the mortar’s contents to a light-resistant 6-oz. dispensing bottle using the entire remainder of the DM liquid. Add a sufficient amount of Cherry Syrup USP to produce a final volume of 180 mL. Cap the bottle securely and shake well. Label the product for 14 days beyond use date (BUD) with SHAKE WELL and REFRIGERATE auxiliary tags.
    3. THIS IS NOT RECOMMENDED DUE TO LOGISTICS OF PROCUREMENT AND SHORT PRODUCT STABILITY.
  3. Paroxetine 20mg plus dextromethorphan polistirex 30mg/5ml and 
  4. Bupropion SR 100mg plus dextromethorphan polistirex 30mg/5ml

All would start with daily dosing and could increase to twice daily dosing based on response.  Please monitor for an increase in the risk for serotonin syndrome/serotonin toxicity (SS/ST).

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Nausea & Vomiting

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Biosimilars

A biosimilar is a highly similar biological product with no clinically meaningful differences from an existing FDA-approved reference product. “No clinically meaningful differences“ include the safety, efficacy, purity, and potency of the drugs, which has typically been demonstrated by pharmacokinetic (PK) and pharmacodynamic (PD) studies.

Compounding

Compounding is an essential aspect of the pharmacy profession, encompassing sterile and nonsterile preparation of medications. United States Pharmacopeia (USP) Chapters 795 and 797 regulate nonsterile and sterile compounding, respectively.  It allows for personalized dosages to be tailored to individual patients, making it a crucial component of drug delivery. The Food and Drug Administration (FDA) has divided compounded products into two categories: 503A and 503B. Medications prepared for specific patients based on orders from a licensed prescriber fall under 503A, which is considered traditional compounding. Meanwhile, 503B outsourcing facilities are subject to more stringent regulations. These facilities can compound and distribute non-patient-specific preparations, unlike those falling under 503A. Most hospitals and mainstream retail compounding pharmacies operate under 503A.

Cold storage transportation

The stability of drugs being stored can be affected by transportation. Maintaining a temperature between 2 to 8 degrees Celsius is necessary for cold chain products, while frozen products must be kept below minus 10 degrees Celsius. An “ultra-cold chain” may sometimes require holding temperatures below minus 80 degrees Celsius.  Pharmacies commonly handle the packaging and delivery of these drugs, as they are equipped to manage their storage and transportation needs.

Ketamine

Ketamine is FDA-approved as a rapid-acting IV dissociative general anesthetic.  There has been increased interest in its off-label use for pain control, administered via various routes.  This Fast Fact reviews the use of ketamine in palliative care, primarily for analgesia.

As an anesthetic, ketamine is given IV or IM.  For pain, the parenteral solution can be delivered at much lower doses by oral, intranasal, transdermal, rectal, and subcutaneous routes. The onset of analgesia is 15-30 minutes; the duration of action is 15 minutes to 2 hours, possibly longer orally.  A greater portion of ketamine is metabolized to a breakdown product with less affinity for NMDA receptors (norketamine) when taken orally versus IV.  It is not yet clear if this reduces the analgesic properties of oral ketamine in a clinically significant way.