Dextromethorphan Hydrobromide And Quinidine Sulfate

Contraindications

4 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 ) 4.1 Quinidine and Related D rugs NUEDEXTA contains quinidine, and should not be used concomitantly with other drugs containing quinidine, quinine, or mefloquine. 4.2 Hypersensitivity 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 ) ] . 4.3 MAOIs 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 ) ] . 4.4 Cardiovascular 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 int

Pregnancy & Breastfeeding

8.1 Pregnancy 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/m 2 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/m 2 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/m 2 basis. When dextromethorphan/quinidine was orally administered (0/0,