NUEDEXTA- dextromethorphan hydrobromide and quinidine sulfate capsule, gelatin coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

DEXTROMETHORPHAN HYDROBROMIDE (UNII: 9D2RTI9KYH) (DEXTROMETHORPHAN - UNII:7355X3ROTS), QUINIDINE SULFATE (UNII: J13S2394HE) (QUINIDINE - UNII:ITX08688JL)

Available from:

Avanir Pharmaceuticals, Inc.

INN (International Name):

DEXTROMETHORPHAN HYDROBROMIDE

Composition:

DEXTROMETHORPHAN HYDROBROMIDE 20 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

NUEDEXTA is indicated for the treatment of pseudobulbar affect (PBA). PBA occurs secondary to a variety of otherwise unrelated neurologic conditions, and is characterized by involuntary, sudden, and frequent episodes of laughing and/or crying. PBA episodes typically occur out of proportion or incongruent to the underlying emotional state. PBA is a specific condition, distinct from other types of emotional lability that may occur in patients with neurological disease or injury. NUEDEXTA contains quinidine, and should not be used concomitantly with other drugs containing quinidine, quinine, or mefloquine. NUEDEXTA is contraindicated in patients with a history of NUEDEXTA, quinine, mefloquine or quinidine-induced thrombocytopenia, hepatitis, bone marrow depression or lupus-like syndrome. NUEDEXTA is also contraindicated in patients with a known hypersensitivity to dextromethorphan (e.g. rash, hives) [ see Warnings and Precautions ( 5.1 ) ] . NUEDEXTA is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping NUEDEXTA before starting an MAOI [ see Drug Interactions ( 7.1 ) ] . NUEDEXTA is contraindicated in patients with a prolonged QT interval, congenital long QT syndrome or a history suggestive of torsades de pointes,  and  in patients with heart failure [ see Warnings and Precautions ( 5.3 ) ] . NUEDEXTA is contraindicated in patients receiving drugs that both prolong QT interval and are metabolized by CYP2D6 (e.g., thioridazine and pimozide), as effects on QT interval may be increased [ see Drug Interactions ( 7.2 ) ] .  NUEDEXTA is contraindicated in patients with complete atrioventricular (AV) block without implanted pacemakers, or in patients who are at high risk of complete AV block. Risk Summary There are no adequate data on the developmental risk associated with the use of NUEDEXTA in pregnant women. In oral studies conducted in rats and rabbits, a combination of dextromethorphan/quinidine demonstrated developmental toxicity, including teratogenicity (rabbits) and embryolethality, when given to pregnant animals (see Data) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.  Data Animal Data When dextromethorphan/quinidine was administered orally (0/0, 5/100, 15/100, and 50/100 mg/kg/day) to pregnant rats during the period of organogenesis, embryo-fetal deaths were observed at the highest dose tested and reduced skeletal ossification was observed at all doses. The lowest dose tested (5/100 mg/kg/day) is approximately 1/50 times the recommended human dose (RHD) of 40/20 mg/day on a mg/m2 basis. Oral administration to pregnant rabbits during organogenesis in two separate studies (0/0, 5/60, 15/60, and 30/60 mg/kg/day; 0/0, 5/100, 15/100, and 50/100 mg/kg/day) resulted in an increased incidence of fetal malformations at all but the lowest dose tested. The no-effect dose (5/100 mg/kg/day) is approximately 2/100 times the RHD on a mg/m2 basis. When dextromethorphan/quinidine was orally administered to female rats during pregnancy and lactation in two separate studies (0/0, 5/100, 15/100, and 30/100 mg/kg/day; 0/0, 5/100, 15/100, and 50/100 mg/kg/day), pup survival and pup weight were decreased at all doses, and developmental delay was observed in offspring at the mid and high doses. A no-effect dose for adverse developmental effects was not identified. The lowest dose tested (5/100 mg/kg/day) is approximately 1/50 times the RHD on a mg/m2 basis. When dextromethorphan/quinidine was orally administered (0/0, 5/50, 15/50, 25/50 mg/kg) to male and female rats on postnatal day (PND) 7, the highest dose resulted in neuronal death in brain (thalamus and medulla oblongata). PND 7 in rat corresponds to the third trimester of the gestation through the first several months of life but may extend to approximately three years of age in humans. Risk Summary       Quinidine is excreted in human milk. It is not known whether dextromethorphan is excreted in human milk. There are no data on the effects of quinidine or dextromethorphan on the breastfed infant or the effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for NUEDEXTA and any potential adverse effects on the breastfed infant from NUEDEXTA or from the underlying material condition. The safety and effectiveness in pediatric patients below the age of 18 have not been established. Of the total number of patients with PBA in clinical studies of NUEDEXTA, 14 percent were 65 years old and over, while 2 percent were 75 and over. Clinical studies of NUEDEXTA did not include sufficient number of patients aged 65 and over to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Dose adjustment of NUEDEXTA is not required in patients with mild to moderate renal impairment [ see   Clinical Pharmacology ( 12.3 )] . The pharmacokinetics of NUEDEXTA have not been evaluated in patients with severe renal impairment; however, increases in dextromethorphan and/or quinidine levels are likely to be observed. Dose adjustment of NUEDEXTA is not required in patients with mild to moderate hepatic impairment. The pharmacokinetics of NUEDEXTA have not been evaluated in patients with severe hepatic impairment; however, increases in dextromethorphan and/or quinidine levels are likely to be observed. NUEDEXTA is a low-affinity uncompetitive NMDA antagonist and sigma-1 receptor agonist that has not been systematically studied in animals or humans for its potential for abuse, tolerance, or physical dependence. However, NUEDEXTA is a combination product containing dextromethorphan and quinidine, and cases of dextromethorphan abuse have been reported, predominantly in adolescents. While clinical trials did not reveal drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this experience the extent to which NUEDEXTA will be misused, diverted, and/or abused once marketed. Therefore, patients with a history of drug abuse should be observed closely for signs of NUEDEXTA misuse or abuse (e.g. development of tolerance, increases in dose, drug-seeking behavior). 

Product summary:

NUEDEXTA is supplied as brick red gelatin capsules imprinted with “DMQ 20-10”. NUEDEXTA is supplied in the following package configuration: Storage Store NUEDEXTA capsules at controlled room temperature, 25°C (77°F); excursions permitted to 15° - 30°C (59° - 86°F) [See USP Controlled Room Temperature].

Authorization status:

New Drug Application

Summary of Product characteristics

NUEDEXTA- DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE CAPSULE,
GELATIN COATED
AVANIR PHARMACEUTICALS, INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
NUEDEXTA SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR NUEDEXTA.
NUEDEXTA (DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE)
CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 2010
INDICATIONS AND USAGE
NUEDEXTA is a combination product containing dextromethorphan
hydrobromide (an uncompetitive
NMDA receptor antagonist and sigma-1 agonist) and quinidine sulfate (a
CYP450 2D6 inhibitor) indicated
for the treatment of pseudobulbar affect (PBA). (1)
DOSAGE AND ADMINISTRATION
Starting dose: one capsule daily by mouth for 7 days. (2.1)
Maintenance dose: After 7 days, 1 capsule every 12 hours. (2.1)
DOSAGE FORMS AND STRENGTHS
Capsules: Dextromethorphan hydrobromide 20 mg/quinidine sulfate 10 mg.
(3)
CONTRAINDICATIONS
Concomitant use with quinidine, quinine, or mefloquine. (4.1)
Patients with a history of quinidine, quinine or mefloquine-induced
thrombocytopenia, hepatitis, or other
hypersensitivity reactions. (4.2)
Patients with known hypersensitivity to dextromethorphan. (4.2)
Use with an MAOI or within 14 days of stopping an MAOI. Allow 14 days
after stopping NUEDEXTA before
starting an MAOI. (4.3)
Prolonged QT interval, congenital long QT syndrome, history suggestive
of torsades de pointes, or heart
failure. (4.4)
Complete atrioventricular (AV) block without implanted pacemaker, or
patients at high risk of complete
AV block. (4.4)
Concomitant use with drugs that both prolong QT interval and are
metabolized by CYP2D6 (e.g.,
thioridazine or pimozide). (4.4)
WARNINGS AND PRECAUTIONS
Thrombocytopenia or other hypersensitivity reactions: Discontinue if
occurs. (5.1)
Hepatitis: Discontinue if occurs. (5.2)
QT Prolongation: Monitor ECG if concomitant use of drugs that prolong
QT interval cannot be avoided or
if concomitant CYP3A4 inhibitors used. (5.3)
Left ventricular hypertrophy (LV