What are the side effects of Nuedexta (dextromethorphan and quinidine)?

From the Guidelines

Nuedexta can cause several side effects, primarily due to its quinidine component, including QT-interval prolongation, nausea, diarrhea, fever, hepatic dysfunction, thrombocytopenia, and hemolytic anemia, as reported in the most recent guidelines 1. The side effects of Nuedexta, a combination of dextromethorphan and quinidine, can be significant and impact patient morbidity, mortality, and quality of life.

• Common side effects include dizziness, diarrhea, and nausea, which can be managed with supportive care.
• More serious side effects, such as QT-interval prolongation and torsades de pointes, can be life-threatening and require immediate medical attention.
• The quinidine component of Nuedexta can also cause hypotension, acceleration of the ventricular response to atrial fibrillation, and other cardiac complications, particularly in patients with pre-existing heart conditions 1.
• Additionally, Nuedexta may interact with other medications, especially those affecting serotonin levels, potentially causing serotonin syndrome.
• Patients taking Nuedexta should be closely monitored for any signs of adverse effects and report them to their healthcare provider promptly.
• It is essential to weigh the benefits and risks of Nuedexta therapy, considering the potential for serious side effects, and to use the medication only as prescribed 1.

From the FDA Drug Label

ADVERSE REACTIONS Quinidine preparations have been used for many years, but there are only sparse data from which to estimate the incidence of various adverse reactions. The adverse reactions most frequently reported have consistently been gastrointestinal, including diarrhea, nausea, vomiting, and heartburn/esophagitis In one study of 245 adult outpatients who received quinidine to suppress premature ventricular contractions, the incidences of reported adverse experiences were as shown in the table below. The most serious quinidine-associated adverse reactions are described above under WARNINGS Adverse Experiences in a 245-Patient PVC Trial Incidence (%) Incidence (%) diarrhea 85 (35) “upper gastrointestinal distress” 55 (22) lightheadedness 37 (15) headache 18 (7) fatigue 17 (7) palpitations 16 (7) angina-like pain 14 (6) weakness 13 (5) rash 11 (5) visual problems 8 (3) change in sleep habits 7 (3) tremor 6 (2) nervousness 5 (2) discoordination 3 (1) Vomiting and diarrhea can occur as isolated reactions to therapeutic levels of quinidine, but they may also be the first signs of cinchonism, a syndrome that may also include tinnitus, reversible high-frequency hearing loss, deafness, vertigo, blurred vision, diplopia, photophobia, headache, confusion, and delirium Cinchonism is most often a sign of chronic quinidine toxicity, but it may appear in sensitive patients after a single moderate dose. A few cases of hepatotoxicity, including granulomatous hepatitis, have been reported in patients receiving quinidine. All of these have appeared during the first few weeks of therapy, and most (not all) have remitted once quinidine was withdrawn Autoimmune and inflammatory syndromes associated with quinidine therapy have included fever, urticaria, flushing, exfoliative rash, bronchospasm, psoriaform rash, pruritus and lymphadenopathy, hemolytic anemia, vasculitis, pneumonitis, thrombocytopenic purpura, uveitis, angioedema, agranulocytosis, the sicca syndrome, arthralgia, myalgia, elevation in serum levels of skeletal-muscle enzymes, and a disorder resembling systemic lupus erythematosus. Convulsions, apprehension, and ataxia have been reported, but it is not clear that these were not simply the results of hypotension and consequent cerebral hypoperfusion. There are many reports of syncope. Acute psychotic reactions have been reported to follow the first dose of quinidine, but these reactions appear to be extremely rare Other adverse reactions occasionally reported include depression, mydriasis, disturbed color perception, night blindness, scotomata, optic neuritis, visual field loss, photosensitivity, and abnormalities of pigmentation.

The side effects of quinidine include:

• Gastrointestinal reactions: diarrhea, nausea, vomiting, heartburn/esophagitis, and upper gastrointestinal distress
• Cardiovascular reactions: lightheadedness, palpitations, angina-like pain, and syncope
• Neurological reactions: headache, fatigue, weakness, tremor, nervousness, discoordination, and convulsions
• Dermatological reactions: rash, and exfoliative rash
• Hepatic reactions: hepatotoxicity, including granulomatous hepatitis
• Hematological reactions: hemolytic anemia, thrombocytopenic purpura, and agranulocytosis
• Psychiatric reactions: depression, apprehension, and acute psychotic reactions
• Ophthalmological reactions: visual problems, blurred vision, diplopia, photophobia, and optic neuritis
• Other reactions: fever, urticaria, flushing, bronchospasm, pruritus, lymphadenopathy, vasculitis, pneumonitis, uveitis, angioedema, arthralgia, myalgia, and elevation in serum levels of skeletal-muscle enzymes 2

From the Research

Side Effects of Nuedexta

The side effects of Nuedexta (dextromethorphan and quinidine) are not extensively detailed in the provided studies, but some information can be gathered:

• Dextromethorphan/quinidine has been shown to cause dosage-dependent corrected QT interval (QTc) prolongation 3
• The quinidine component of DM/Q may have an impact on safety, particularly with regards to drug interaction and QT prolongation potential 4
• Concentrations of dextrorphan (which is responsible for many of the parent drug's side effects) and quinidine are lower than those observed in clinical practice with these drugs administered alone, which may reduce the risk of some side effects 4
• Patients with pseudobulbar affect may not tolerate DM/Q adverse effects, or may be at risk for drug interactions, due to their underlying medical conditions and concurrent medications 4
• Caution is warranted when initiating DM/Q treatment, particularly in patients with underlying risk factors for torsade de pointes and in those receiving medications that may interact with DM/Q 4
• In clinical trials, dextromethorphan/quinidine was generally well tolerated, with no particular safety or tolerability concerns 3, 5
• One case report noted that a patient experienced no deleterious side effects while taking fixed-dose 20 mg/10 mg dextromethorphan/quinidine 6