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  • CLASSES

    Non-Opioid Antitussive and Expectorant Combinations

    DEA CLASS

    OTC, Rx

    DESCRIPTION

    Oral non-opioid antitussive (dextromethorphan) and expectorant (guaifenesin) combination
    Used to quiet cough and induce expectoration
    Products mostly marketed for cough due to common cold

    COMMON BRAND NAMES

    Alka-Seltzer Plus Max Cough, Mucus & Congestion, Alka-Seltzer Plus Mucus and Congestion, AllFen DM, Altarussin DM, Amibid DM, Aquabid DM, Aquatab DM, Bidex-DMI, Cheracol D, Chest Congestion Relief DM, Congesta DM, Coricidin HBP Chest Congetion and Cough, Delsym Children's Cough + Chest Congestion DM, Delsym Cough + Chest Congestion DM, Delsym DM Children's Cough + Chest Congestion, Diabetic Tussin DM, Duraganidin DM, Fenesin DM, G-Bid DM TR, Gani-Tuss DM NR, Genatuss DM, Geri_Tussin DM, GFN 600/DM 30, Giltuss Children's Cough & Chest, Giltuss Diabetic Cough & Cold, Giltuss HBP Cough & Chest Congestion, Guai-Dex, Guaiasorb DM, Guaidrine DM, Guaifenex DM, Guiatuss DM, Humibid CS, Humibid DM, Iobid DM, Iophen DM-NR, Maxi-Tuss G, Maxi-Tuss GMX, Mucinex Children's Cough, Mucinex Children's Cough Mini-Melts, Mucinex Children's FreeFrom Daytime Cough & Mucus, Mucinex DM, Mucinex Fast-Max DM Max, Mucus Children's Cough, Mucus Relief, Mucus Relief DM, MucusRelief DM, Naldecon, Nalspan Senior DX, Orgadin-Tuss DM, PediaCare Cough & Congestion, Pulexn DM, Q-Tussin DM, Robafen DM, Robafen DM Clear, Robafen DM Max, Robitussin Adult Cough + Chest Congestion DM, Robitussin Adult Peak Cold, Robitussin Children's Honey Cough & Congestion DM, Robitussin Cough + Congestion DM Maximum, Robitussin Cough and Congestion, Robitussin DM, Robitussin Honey Cough + Chest Congestion DM, Scot-Tussin Senior, Siltussin DM DAS, Siltussin-DM, Siltussin-DM Diabetic DAS-Na, Siltussin-DM Diabetic DAS-Na Maximum Strength, Triaminic Cough & Congestion, TRISPEC DMX, Tussi-Bid, Tussi-Organidin DM NR, Tussidin DM NR, Vicks DayQuil Mucus Control DM, Z-Cof LAX, Zotex DMX

    HOW SUPPLIED

    AllFen DM/Bidex-DMI/Congesta DM/Dextromethorphan Hydrobromide, Guaifenesin/Dextromethorphan, Guaifenesin/Humibid CS/Mucus Relief/Mucus Relief DM/MucusRelief DM/Zotex DMX Oral Tab: 20-400mg, 57.5-775mg
    Altarussin DM/Aquatab DM/Cheracol D/Chest Congestion Relief DM/Delsym DM Children's Cough + Chest Congestion/Dextromethorphan Hydrobromide, Guaifenesin/Dextromethorphan, Guaifenesin/Diabetic Tussin DM/Duraganidin DM/Gani-Tuss DM NR/Genatuss DM/Geri_Tussin DM/Giltuss Children's Cough & Chest/Guaiasorb DM/Guai-Dex/Guiatuss DM/Iophen DM-NR/Maxi-Tuss G/Maxi-Tuss GMX/Mucinex Children's Cough/Mucinex Children's FreeFrom Daytime Cough & Mucus/Naldecon/Nalspan Senior DX/Orgadin-Tuss DM/Pulexn DM/Q-Tussin DM/Robafen DM/Robafen DM Clear/Robafen DM Max/Robitussin Cough and Congestion/Robitussin DM/Siltussin DM DAS/Siltussin-DM/Siltussin-DM Diabetic DAS-Na/Siltussin-DM Diabetic DAS-Na Maximum Strength/Tussidin DM NR/Tussi-Organidin DM NR Oral Liq: 5mL, 10-100mg, 10-200mg, 5-100mg
    Altarussin DM/Cheracol D/Chest Congestion Relief DM/Delsym Children's Cough + Chest Congestion DM/Delsym Cough + Chest Congestion DM/Delsym DM Children's Cough + Chest Congestion/Dextromethorphan Hydrobromide, Guaifenesin/Dextromethorphan, Guaifenesin/Diabetic Tussin DM/Duraganidin DM/Gani-Tuss DM NR/Genatuss DM/Geri_Tussin DM/Giltuss Children's Cough & Chest/Giltuss Diabetic Cough & Cold/Giltuss HBP Cough & Chest Congestion/Guaiasorb DM/Guai-Dex/Guiatuss DM/Iophen DM-NR/Maxi-Tuss G/Maxi-Tuss GMX/Mucinex Children's Cough/Mucinex Children's FreeFrom Daytime Cough & Mucus/Mucinex Fast-Max DM Max/Mucus Children's Cough/Orgadin-Tuss DM/PediaCare Cough & Congestion/Pulexn DM/Q-Tussin DM/Robafen DM/Robafen DM Clear/Robitussin Adult Cough + Chest Congestion DM/Robitussin Adult Peak Cold/Robitussin Children's Honey Cough & Congestion DM/Robitussin Cough and Congestion/Robitussin DM/Robitussin Honey Cough + Chest Congestion DM/Scot-Tussin Senior/Siltussin DM DAS/Siltussin-DM/Siltussin-DM Diabetic DAS-Na/Triaminic Cough & Congestion/TRISPEC DMX/Tussidin DM NR/Tussi-Organidin DM NR/Vicks DayQuil Mucus Control DM Oral Sol: 5mL, 10mL, 15mL, 20mL, 10-100mg, 10-187mg, 10-200mg, 15-200mg, 20-200mg, 20-400mg, 5-100mg
    Aquatab DM/Dextromethorphan Hydrobromide, Guaifenesin/Dextromethorphan, Guaifenesin/G-Bid DM TR/Mucinex DM/Mucus Relief DM/Tussi-Bid/Z-Cof LAX Oral Tab ER: 30-600mg, 30-835mg, 60-1200mg
    Cheracol D/Dextromethorphan Hydrobromide, Guaifenesin/Dextromethorphan, Guaifenesin/Genatuss DM/Guiatuss DM/Pulexn DM/Q-Tussin DM/Robafen DM/Robafen DM Clear/Robitussin DM/Siltussin-DM Oral Syrup: 5mL, 10-100mg
    Coricidin HBP Chest Congetion and Cough/Robitussin Cough + Congestion DM Maximum Oral Cap: 10-200mg
    Mucinex Children's Cough Mini-Melts Oral Gran: 5-100mg

    DOSAGE & INDICATIONS

    For the temporary relief of cough, especially non-productive cough, due to minor throat and bronchial irritation such as may occur with the common cold.
    Oral dosage (immediate-release oral tablets, granules, solutions, syrups, suspensions)
    Adults, Adolescents, and Children 12 years and older

    Usual dose range based on dextromethorphan component: 20 mg PO every 4 hours as needed or 30 mg PO every 6 to 8 hours as needed. Maximum: 120 mg/day of dextromethorphan.

    Children 6 to 11 years

    10 mg of the dextromethorphan component PO every 4 hours as needed. Some products are not intended for use in children under 12 years of age.

    Children 2 to 5 years

    5 mg of the dextromethorphan component PO every 4 hours as needed. Some products are not intended for use in children under 12 years of age.

    Oral dosage (extended-release and biphasic-release 12-hour tablets)
    Adults, Adolescents, and Children 12 years and older

    Usual dose range: 30 to 60 mg of the dextromethorphan component PO every 12 hours as needed. Do not exceed 2 doses per 24 hours.

    MAXIMUM DOSAGE

    Do not exceed recommended dosage limits for the specific product prescribed. In general, maximum dosing is established based on the dextromethorphan component of the product selected. The following are general guidelines.

    Adults

    Dextromethorphan 120 mg/day PO; guaifenesin 2.4 grams/day PO.

    Geriatric

    Dextromethorphan 120 mg/day PO; guaifenesin 2.4 grams/day PO.

    Adolescents

    Dextromethorphan 120 mg/day PO; guaifenesin 2.4 grams/day PO.

    Children

    12 years: Dextromethorphan 120 mg/day PO; guaifenesin 2.4 grams/day PO.
    6 to 11 years: Dextromethorphan 60 mg/day PO. Do not use extended-release dosage forms.
    2 to 5 years: Dextromethorphan 30 mg/day PO. Do not use extended-release dosage forms.
    Less than 2 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; however, lower doses may be warranted to avoid adverse reactions due to decreased metabolism of dextromethorphan.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Oral Administration

    May give without regard to food or meals. May administer with food or milk to minimize GI irritation.
    Have patient drink plenty of fluids to facilitate expectoration.

    Oral Solid Formulations

    Extended-release preparations (e.g., biphasic or extended-release tablets):
    Administer tablets whole; do not crush, break, or chew.
    Administer with a full glass of water.
     
    Immediate-release tablets or capsules:
    Administer with a full glass of water.
    For liquid-filled capsules, swallow whole.
     
    Oral granules:
    Open packet, sprinkle entire contents onto tongue, and swallow.
    For best taste, do not chew.

    Oral Liquid Formulations

    Oral Solutions or Syrups:
    Administer using a calibrated oral measuring device (calibrated oral syringe, dose cup or spoon) to give an accurate dosage.

    STORAGE

    Generic:
    - Do not refrigerate
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Alka-Seltzer Plus Max Cough, Mucus & Congestion:
    - Avoid excessive heat (above 104 degrees F)
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Alka-Seltzer Plus Mucus and Congestion:
    - Avoid excessive heat (above 104 degrees F)
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    AllFen DM:
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    Altarussin DM:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Ambi:
    - Store at room temperature (between 59 to 86 degrees F)
    Amibid DM :
    - Store between 68 to 77 degrees F
    Aquabid DM :
    - Store between 68 to 77 degrees F
    Aquatab DM:
    - Store between 68 to 77 degrees F
    Bidex-A:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Bidex-DM:
    - Store at room temperature (between 59 to 86 degrees F)
    Bidex-DMI:
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    Cheracol D:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Chest Congestion Relief DM:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Cofex-DM :
    - Store at room temperature (between 59 to 86 degrees F)
    Congesta DM :
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    Coricidin HBP Chest Congetion and Cough:
    - Avoid excessive heat (above 104 degrees F)
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Delsym Children's Cough + Chest Congestion DM:
    - Do not refrigerate
    - Store at room temperature (between 59 to 86 degrees F)
    Delsym Cough + Chest Congestion DM:
    - Do not refrigerate
    - Store at room temperature (between 59 to 86 degrees F)
    Delsym DM Children's Cough + Chest Congestion:
    - Do not refrigerate
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Dex-Tuss DM:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Diabetic Tussin DM:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    DM/GUAI:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Duradex:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Duradex Forte:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Duraganidin DM :
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Duratuss DM:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Duratuss DM 12 Tannate:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    ExeFen-DM:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Extuss LA :
    - Protect from light
    - Store at room temperature (between 59 to 86 degrees F)
    Fenesin DM:
    - Store between 68 to 77 degrees F
    Gani-Tuss DM NR :
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    G-Bid DM TR:
    - Store between 68 to 77 degrees F
    Genatuss DM:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Geri_Tussin DM:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    GFN 600/DM 30 :
    - Store between 68 to 77 degrees F
    Giltuss Children's Cough & Chest:
    - Do not refrigerate
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Giltuss Diabetic Cough & Cold:
    - Store at room temperature (between 59 to 86 degrees F)
    Giltuss HBP Cough & Chest Congestion:
    - Store at room temperature (between 59 to 86 degrees F)
    Guaiasorb DM:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Guai-Dex :
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Guaidrine DM:
    - Store between 68 to 77 degrees F
    Guaifenex DM:
    - Store between 68 to 77 degrees F
    Guia-D :
    - Store at room temperature (between 59 to 86 degrees F)
    Guiadrine DX :
    - Protect from freezing
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Guiatuss DM:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    H-T Tussin:
    - Store at room temperature (between 59 to 86 degrees F)
    Humibid CS:
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    Humibid DM:
    - Store between 68 to 77 degrees F
    Hydro-Tussin DM:
    - Store at room temperature (between 59 to 86 degrees F)
    Iobid DM :
    - Store between 68 to 77 degrees F
    Iophen DM-NR :
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Maxi-Tuss G:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Maxi-Tuss GMX:
    - Store at room temperature (between 59 to 86 degrees F)
    Mindal DM :
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Mucinex Children's Cough:
    - Do not refrigerate
    - Store at room temperature (between 59 to 86 degrees F)
    Mucinex Children's Cough Mini-Melts:
    - Store between 68 to 77 degrees F
    Mucinex Children's FreeFrom Daytime Cough & Mucus:
    - Do not refrigerate
    - Store at room temperature (between 59 to 86 degrees F)
    Mucinex DM:
    - Store between 68 to 77 degrees F
    Mucinex Fast-Max DM Max:
    - Do not refrigerate
    - Store at room temperature (between 59 to 86 degrees F)
    Muco-Fen DM:
    - Store at room temperature (between 59 to 86 degrees F)
    Mucus Children's Cough:
    - Do not refrigerate
    - Store at room temperature (between 59 to 86 degrees F)
    Mucus Relief:
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    Mucus Relief DM:
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    MucusRelief DM:
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    Naldecon:
    - Do not refrigerate
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Nalspan Senior DX:
    - Do not refrigerate
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Orgadin-Tuss DM:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    PediaCare Cough & Congestion:
    - Do not refrigerate
    - Store at room temperature (between 59 to 86 degrees F)
    Phlemex:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Pulexn DM:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Q-Tussin DM:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Relacon LAX:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Respa-DM:
    - Store at room temperature (between 59 to 86 degrees F)
    Robafen DM:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Robafen DM Clear:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Robafen DM Max:
    - Do not refrigerate
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Robitussin Adult Cough + Chest Congestion DM:
    - Do not refrigerate
    - Store between 68 to 77 degrees F
    Robitussin Adult Peak Cold:
    - Store at room temperature (between 59 to 86 degrees F)
    Robitussin Children's Honey Cough & Congestion DM:
    - Do not refrigerate
    - Store between 68 to 77 degrees F
    Robitussin Cough + Congestion DM Maximum:
    - Avoid excessive heat (above 104 degrees F)
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Robitussin Cough and Congestion:
    - Do not refrigerate
    - Store at room temperature (between 59 to 86 degrees F)
    Robitussin DM:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Robitussin Honey Cough + Chest Congestion DM:
    - Do not refrigerate
    - Store at room temperature (between 59 to 86 degrees F)
    Robitussin Pediatric Infant DM:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Ru-Tuss-DM:
    - Store at room temperature (between 59 to 86 degrees F)
    Scot-Tussin Senior:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Siltussin DM DAS :
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Siltussin-DM :
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Siltussin-DM Diabetic DAS-Na :
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Siltussin-DM Diabetic DAS-Na Maximum Strength:
    - Do not refrigerate
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Simuc-DM:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Sudal DM:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Touro DM:
    - Store at room temperature (between 59 to 86 degrees F)
    Triaminic Cough & Congestion:
    - Do not refrigerate
    - Store at room temperature (between 59 to 86 degrees F)
    TRISPEC DMX:
    - Store at room temperature (between 59 to 86 degrees F)
    Tussi-Bid:
    - Store between 68 to 77 degrees F
    Tussiden DM :
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Tussidin DM NR:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Tussi-Organidin DM NR:
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 15 to 30 degrees C (59 - 86 degrees F)
    - Store in a cool, well ventilated, dry place
    Vicks DayQuil Mucus Control DM:
    - Store at room temperature (between 59 to 86 degrees F)
    Vicks DayQuil Nature Fusion:
    - Store at room temperature (between 59 to 86 degrees F)
    Vicks Formula 44:
    - Store at room temperature (between 59 to 86 degrees F)
    Vicks Formula 44E:
    - Store at room temperature (between 59 to 86 degrees F)
    Vicks Nature Fusion Cough & Chest Congestion:
    - Store at room temperature (between 59 to 86 degrees F)
    Z-Cof LA:
    - Protect from light
    - Store at room temperature (between 59 to 86 degrees F)
    Z-Cof LAX:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Zotex DMX:
    - Store at room temperature (between 59 to 86 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Asthma, bronchitis, emphysema, fever, headache, tobacco smoking, vomiting

    Dextromethorphan; guaifenesin combinations should not be used for persistent or chronic cough such as occurs with tobacco smoking, asthma, emphysema, or chronic bronchitis or any other condition where cough is associated with excessive secretions, unless under the supervision of a health care professional. A recurrent or persistent cough (lasting for more than one week), or a cough accompanied by fever, nausea/vomiting, rash, or persistent headache may be signs of a more serious condition and should be evaluated by a physician.

    Hepatic disease

    Since dextromethorphan is extensively metabolized in the liver, the combination of dextromethorphan and guaifenesin should be given with caution in patients with hepatic disease. An increased risk of toxicity is possible in these patients.

    Driving or operating machinery

    Because dextromethorphan; guaifenesin combinations may cause dizziness or confusion, patients should be cautioned regarding driving or operating machinery until they know how this product will affect them.

    Children, infants

    In January 2007, the CDC warned caregivers and healthcare providers of the risk for serious injury or fatal overdose from the administration of cough and cold products to children and infants less than 2 years of age. This warning followed an investigation of the deaths of three (3) infants less than 6 months of age that were attributed to the inadvertent inappropriate use of these products. The symptoms preceding these deaths have not been clearly defined, and there is a lack of conclusive data describing the exact cause of death. The report estimated that 1519 children less than 2 years of age were treated in emergency departments during 2004—2005 for adverse events related to cough and cold medications. In October 2007, the FDA Nonprescription Drug Advisory Committee and the Pediatric Advisory Committee recommended that nonprescription cough and cold products containing pseudoephedrine, dextromethorphan, chlorpheniramine, diphenhydramine, brompheniramine, phenylephrine, clemastine, or guaifenesin not be used in children less than 6 years of age. In January 2008, the FDA issued a Public Health Advisory recommending that OTC cough and cold products not be used in infants and children less than 2 years. An official ruling regarding the use of these products in children greater than 2 years has not yet been announced. The FDA recommends that if parents and caregivers use cough and cold products in children greater than 2 years, labels should be read carefully, caution should be used when administering multiple products, and only measuring devices specifically designed for use with medications should be used. While some combination cough/cold products containing these ingredients are available by prescription only and are not necessarily under scrutiny by the FDA, clinicians should thoroughly assess each patient's use of similar products, both prescription and nonprescription, to avoid duplication of therapy and the potential for inadvertent overdose.

    Pregnancy

    Safe use of cough/cold products in pregnancy has not been established, particularly for combination cough products, so dextromethorphan; guaifenesin should be given during pregnancy only if clearly needed. The expectorant guaifenesinhas been weakly associated with neural tube defects and inguinal hernias. However, the evidence is not sufficient and it is prudent to avoid this medication in the first trimester unless the potential benefits outweigh the risks. Because dextromethorphan acts as a low-affinity antagonist to the glutamate receptor subtype N-methyl-D-aspartate (NMDA) in the CNS, there has been some concern about the safe use of dextromethorphan during pregnancy. Human surveillance data and retrospective studies have shown dextromethorphan to be relatively safe during the first trimester. In one controlled study, there were no cases of neural tube defects, and no differences in number of live births, spontaneous or elective abortions, stillbirths, or major or minor malformations among infants exposed to dextromethorphan during the first trimester and those who were not.[26485] The results suggested that use during pregnancy does not pose a risk to the fetus; however, due to the small sample size, an increased risk of rare malformations could not be ruled out.[26485] The majority of animal studies have not found teratogenic effects. A study in avian embryos determined that dextromethorphan may have adverse developmental effects; however, the avian data have limited applicability to human gestation.[24591] Increased fluids to ease expectoration are usually recommended for first-line treatment in the pregnant patient. When administered to pregnant females, product formulations that also contain alcohol or other drugs should not be used.

    Breast-feeding

    Use dextromethorphan; guaifenesin with caution during lactation; consider if guaifenesin alone would be adequate. Guaifenesin is considered compatible with breast-feeding at usual prescribed and non-prescription doses. Limited data are available regarding the use of dextromethorphan by breast-feeding women. Despite the lack of published data, dextromethorphan is often considered to be compatible with breast-feeding when usual antitussive doses are taken by the mother, due to the lack of expected harm in the breast-fed infant. Some dextromethorphan cough products contain alcohol, and these products should be avoided while breast-feeding. Some dextromethorphan; guaifenesin products contain alcohol, and alcohol-containing products should be avoided while breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.[39683]

    MAOI therapy

    Dextromethorphan should be used cautiously, if at all, in patients receiving MAOI therapy; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine).

    Geriatric

    There are no particular precautions for the use of dextromethorphan; guaifenesin products in the ambulatory, non-debilitated geriatric patient compared to use in younger adults. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities. According to the OBRA guidelines, cough, cold, and allergy medications should be used only for a limited duration (less than 14 days) unless there is documented evidence of enduring symptoms that cannot otherwise be alleviated and for which a cause cannot be identified and corrected.

    ADVERSE REACTIONS

    Severe

    seizures / Delayed / Incidence not known
    serotonin syndrome / Delayed / Incidence not known

    Moderate

    respiratory depression / Rapid / Incidence not known
    dysarthria / Delayed / Incidence not known
    confusion / Early / Incidence not known
    hallucinations / Early / Incidence not known
    nephrolithiasis / Delayed / Incidence not known

    Mild

    nausea / Early / 1.0-10.0
    rash / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    drowsiness / Early / Incidence not known
    dizziness / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    vomiting / Early / Incidence not known
    headache / Early / Incidence not known
    irritability / Delayed / Incidence not known
    restlessness / Early / Incidence not known

    DRUG INTERACTIONS

    Abiraterone: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
    Acetaminophen; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Alfentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Amiodarone: (Moderate) Use of dextromethorphan with amiodarone may result in increased and prolonged dextromethorphan exposure. Amiodarone inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amlodipine; Celecoxib: (Moderate) Use of dextromethorphan with celecoxib may result in increased dextromethorphan exposure. Celecoxib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Artemether; Lumefantrine: (Moderate) Use of dextromethorphan with lumefantrine may result in increased dextromethorphan exposure. Lumefantrine inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Atazanavir; Cobicistat: (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Because of the potential risk and severity of serotonin syndrome, coadministration of dextromethorphan and IV methylene blue should be avoided if possible. Methylene blue has been demonstrated to be a potent monoamine oxidase inhibitor (MAOI) and may cause potentially fatal serotonin toxicity (serotonin syndrome) when combined with serotonin reuptake inhibitors (SRIs). Dextromethorphan increases central serotonin effects. If methylene blue is judged to be indicated, all SRIs, including dextromethorphan, must be ceased prior to treatment/procedure/surgery. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Because of the potential risk and severity of serotonin syndrome, coadministration of dextromethorphan and IV methylene blue should be avoided if possible. Methylene blue has been demonstrated to be a potent monoamine oxidase inhibitor (MAOI) and may cause potentially fatal serotonin toxicity (serotonin syndrome) when combined with serotonin reuptake inhibitors (SRIs). Dextromethorphan increases central serotonin effects. If methylene blue is judged to be indicated, all SRIs, including dextromethorphan, must be ceased prior to treatment/procedure/surgery. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Buprenorphine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering buprenorphine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Buprenorphine; Naloxone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering buprenorphine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Celecoxib: (Moderate) Use of dextromethorphan with celecoxib may result in increased dextromethorphan exposure. Celecoxib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Celecoxib; Tramadol: (Moderate) Use of dextromethorphan with celecoxib may result in increased dextromethorphan exposure. Celecoxib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Chlorpheniramine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Cinacalcet: (Moderate) Use of dextromethorphan with cinacalcet may result in increased dextromethorphan exposure. Cinacalcet inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Citalopram: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Clobazam: (Moderate) Use of dextromethorphan with clobazam may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Clobazam inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. A dosage reduction of dextromethorphan may be necessary for some patients. During one in vivo study, co-administration of dextromethorphan and clobazam resulted in increased AUC and Cmax of dextromethorphan by 90% and 59%, respectively.
    Cobicistat: (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Codeine; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Codeine; Phenylephrine; Promethazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Codeine; Promethazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dacomitinib: (Moderate) Use of dextromethorphan with dacomitinib results in increased dextromethorphan exposure. Dacomitinib is a potent inhibitor of CYP2D6 and dextromethorphan is a sensitive CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. The Cmax and AUC of dextromethorphan were increased by approximately 10-fold when coadminstered with a single dose of dacomitinib.
    Darifenacin: (Minor) Use of dextromethorphan with darifenacin may result in increased dextromethorphan exposure. Darifenacin is a moderate inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Darunavir; Cobicistat: (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Delavirdine: (Moderate) Use of dextromethorphan with delavirdine may result in increased dextromethorphan exposure. Delavirdine inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Desvenlafaxine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with desvenlafaxine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. In addition, the manufacturer of desvenlafaxine recommends that the dose of CYP2D6 substrates, such as dextromethorphan, be reduced by up to 50% if used with desvenlafaxine 400 mg/day, a CYP2D6 inhibitor.
    Donepezil; Memantine: (Moderate) Dextromethorphan is a NMDA antagonist and may lead to additive adverse effects if combined with memantine, also an NMDA antagonist. It may be prudent to avoid coadministration of dextromethorphan with memantine. If coadministration cannot be avoided, monitor for increased adverse effects such as agitation, dizziness and other CNS events.
    Dronedarone: (Moderate) Use of dextromethorphan with dronedarone may result in increased dextromethorphan exposure. Dronedarone inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Duloxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with duloxetine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Eliglustat: (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Escitalopram: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Fedratinib: (Moderate) Use of dextromethorphan with fedratinib may result in increased dextromethorphan exposure. Fedratinib is a moderate inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Fenfluramine: (Moderate) Use fenfluramine and dextromethorphan with caution due to an increased risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Fentanyl: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering fentanyl with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Fluoxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with fluoxetine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. In addition, fluoxetine inhibits CYP2D6 and may increase systemic dextromethorphan exposure. Increased dextromethorphan concentrations may result in adverse effects consistent with the serotonin syndrome.
    Fluvoxamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with fluvoxamine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Givosiran: (Moderate) If possible, avoid concomitant use of dextromethorphan with givosiran due to the risk of increased dextromethorphan-related adverse reactions. If use is necessary, consider decreasing the dextromethorphan dose. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Dextromethorphan is a sensitive CYP2D6 substrate. Givosiran may moderately reduce hepatic CYP2D6 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway.
    Grapefruit juice: (Minor) Intake of grapefruit juice or seville orange juice increased dextromethorphan bioavailability in one study. Patients with increased concentrations of dextromethorphan may experience drowsiness or serotonergic side effects (dizziness, nervousness or restlessness, nausea, vomiting, stomach upset) not usually noted with prescribed or nonprescription product doses. Grapefruit juice and seville orange juice contain compounds that can inhibit P-glycoprotein in the intestinal wall, and dextromethorphan absorption may be affected by P-glycoprotein activity. Dextromethorphan is largely metabolized by CYP2D6, so this particular interaction with grapefruit juice may be more relevant in patients who are poor CYP2D6 metabolizers.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Because of the potential risk and severity of serotonin syndrome, coadministration of dextromethorphan and IV methylene blue should be avoided if possible. Methylene blue has been demonstrated to be a potent monoamine oxidase inhibitor (MAOI) and may cause potentially fatal serotonin toxicity (serotonin syndrome) when combined with serotonin reuptake inhibitors (SRIs). Dextromethorphan increases central serotonin effects. If methylene blue is judged to be indicated, all SRIs, including dextromethorphan, must be ceased prior to treatment/procedure/surgery. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Imatinib: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Isocarboxazid: (Contraindicated) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotonergic agent and its active metabolites.
    Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Levomilnacipran: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with levomilnacipran. Dextromethorphan has serotonergic activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Linezolid: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Lorcaserin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with lorcaserin. Both medications have serotonergic activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan, increasing dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased dextromethorphan exposure may result in adverse effects consistent with the serotonin syndrome.
    Memantine: (Moderate) Dextromethorphan is a NMDA antagonist and may lead to additive adverse effects if combined with memantine, also an NMDA antagonist. It may be prudent to avoid coadministration of dextromethorphan with memantine. If coadministration cannot be avoided, monitor for increased adverse effects such as agitation, dizziness and other CNS events.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Because of the potential risk and severity of serotonin syndrome, coadministration of dextromethorphan and IV methylene blue should be avoided if possible. Methylene blue has been demonstrated to be a potent monoamine oxidase inhibitor (MAOI) and may cause potentially fatal serotonin toxicity (serotonin syndrome) when combined with serotonin reuptake inhibitors (SRIs). Dextromethorphan increases central serotonin effects. If methylene blue is judged to be indicated, all SRIs, including dextromethorphan, must be ceased prior to treatment/procedure/surgery. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Methylene Blue: (Major) Because of the potential risk and severity of serotonin syndrome, coadministration of dextromethorphan and IV methylene blue should be avoided if possible. Methylene blue has been demonstrated to be a potent monoamine oxidase inhibitor (MAOI) and may cause potentially fatal serotonin toxicity (serotonin syndrome) when combined with serotonin reuptake inhibitors (SRIs). Dextromethorphan increases central serotonin effects. If methylene blue is judged to be indicated, all SRIs, including dextromethorphan, must be ceased prior to treatment/procedure/surgery. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Milnacipran: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with milnacipran. Dextromethorphan has serotonergic activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Mirabegron: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Mirtazapine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with mirtazapine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Monoamine oxidase inhibitors: (Contraindicated) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotonergic agent and its active metabolites.
    Nefazodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with nefazodone. Both drugs have serotonergic activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Olanzapine; Fluoxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with fluoxetine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. In addition, fluoxetine inhibits CYP2D6 and may increase systemic dextromethorphan exposure. Increased dextromethorphan concentrations may result in adverse effects consistent with the serotonin syndrome.
    Oliceridine: (Moderate) If concomitant use of oliceridine and dextromethorphan is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Oritavancin: (Moderate) Administration of oritavancin, a weak inducer of CYP2D6 and CYP3A4, with dextromethorphan resulted in a 31% reduction in the ratio of dextromethorphan to dextrorphan concentrations in the urine. The efficacy of dextromethorphan may be reduced if these drugs are administered concurrently.
    Ozanimod: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome.
    Panobinostat: (Major) Avoid coadministrating panobinostatwith sensitive CYP2D6 substrates such as dextromethorphan due to increased dextromethorphan exposure. Consider alternatives to dextromethorphan if possible. If concomitant use cannot be avoided, closely monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Panobinostat inhibits CYP2D6. When a single 60-mg dose of dextromethorphan (DM) was administered after 3 doses of panobinostat (20 mg on days 3, 5, and 8), the DM Cmax increased by 20% to 200% and DM exposure (AUC) increased by 20% to 130% (interquartile ranges) vs. when DM was given alone; however, the change in exposure was highly variable among the patients studied.
    Paroxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with paroxetine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. In addition, paroxetine inhibits CYP2D6 and may increase systemic dextromethorphan exposure. Increased dextromethorphan concentrations may result in adverse effects consistent with the serotonin syndrome.
    Pazopanib: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
    Peginterferon Alfa-2b: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
    Phenelzine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotonergic agent and its active metabolites.
    Procarbazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with procarbazine, an antineoplastic agent with monoamine oxidase inhibitor (MAOI) activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Propafenone: (Minor) Use of dextromethorphan with propafenone might increase dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. In vitro studies suggest that propafenone inhibits CYP2D6, but clinically relevant interactions have not been reported due to this potential action. Dextromethorphan is a CYP2D6 substrate.
    Quinine: (Moderate) Although clinical drug interaction studies have not been performed, antimalarial doses of quinine (greater than or equal to 600 mg/day in adults) may inhibit the metabolism of CYP2D6 substrates such as dextromethorphan and may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Rasagiline: (Contraindicated) Dextromethorphan prescription products are 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 dextromethorphan before starting an MAOI, including rasagiline. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Rolapitant: (Moderate) Rolapitant increases exposure to dextromethorphan. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Rolapitant is a moderate CYP2D6 inhibitor with a prolonged effect; the inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. During drug interaction studies, exposure (AUC) to dextromethorphan following a single dose of rolapitant increased close to 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in dextromethorphan exposure (AUC), the last time point measured.
    Safinamide: (Contraindicated) Dextromethorphan prescription products are 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 dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Selegiline: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan.
    Serotonin-Receptor Agonists: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with serotonin-receptor agonists ("triptans"). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Sertraline: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with sertraline. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. In addition, sertraline inhibits CYP2D6 and may increase systemic dextromethorphan exposure. Increased dextromethorphan concentrations may result in adverse effects consistent with the serotonin syndrome.
    Sibutramine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with sibutramine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    St. John's Wort, Hypericum perforatum: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with St. John's Wort. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Tedizolid: (Minor) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tedizolid. Tedizolid is an antibiotic that is also a weak, reversible, non-selective MAO inhibitor in vitro. In theory, tedizolid has potential to interact with serotonergic agents, but interactions are thought to be unlikely. In clinical interaction studies with a related antibiotic (linezolid), interactions with dextromethorphan were studied, but serotonin syndrome or adverse effects were not reported. No drug-drug interaction precautions with dextromethorphan are specifically mentioned in the tedizolid label. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Terbinafine: (Moderate) Use of dextromethorphan with systemic terbinafine may result in increased dextromethorphan exposure. Terbinafine inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
    Tocilizumab: (Minor) Concomitant use of tocilizumab and dextromethorphan may lead to a decrease in the efficacy of dextromethorphan; clinical significance of this interaction is not known or established. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. A 5% decrease in dextromethorphan exposure and a 29% decrease in its metabolite, dextrorphan was noted 1 week after a single tocilizumab infusion. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Dextromethorphan is a CYP2D6 substrate.
    Tranylcypromine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotonergic agent and its active metabolites.
    Tricyclic antidepressants: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tricyclic antidepressants. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Vemurafenib: (Minor) Use of dextromethorphan with vemurafenib increases dextromethorphan exposure. Vemurafenib is a weak CYP2D6 inhibitor and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Coadministration of vemurafenib and dextromethorphan increased the AUC of dextromethorphan by 47% and the dextromethorphan Cmax by 36%.
    Venlafaxine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with venlafaxine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
    Vilazodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with vilazodone. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Viloxazine: (Moderate) Monitor for an increase in dextromethorphan-related adverse effects if concomitant use of viloxazine is necessary. Concomitant use may increase dextromethorphan exposure; viloxazine is a weak CYP2D6 inhibitor and dextromethorphan is a CYP2D6 substrate.
    Vortioxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with vortioxetine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.

    PREGNANCY AND LACTATION

    Pregnancy

    Safe use of cough/cold products in pregnancy has not been established, particularly for combination cough products, so dextromethorphan; guaifenesin should be given during pregnancy only if clearly needed. The expectorant guaifenesinhas been weakly associated with neural tube defects and inguinal hernias. However, the evidence is not sufficient and it is prudent to avoid this medication in the first trimester unless the potential benefits outweigh the risks. Because dextromethorphan acts as a low-affinity antagonist to the glutamate receptor subtype N-methyl-D-aspartate (NMDA) in the CNS, there has been some concern about the safe use of dextromethorphan during pregnancy. Human surveillance data and retrospective studies have shown dextromethorphan to be relatively safe during the first trimester. In one controlled study, there were no cases of neural tube defects, and no differences in number of live births, spontaneous or elective abortions, stillbirths, or major or minor malformations among infants exposed to dextromethorphan during the first trimester and those who were not.[26485] The results suggested that use during pregnancy does not pose a risk to the fetus; however, due to the small sample size, an increased risk of rare malformations could not be ruled out.[26485] The majority of animal studies have not found teratogenic effects. A study in avian embryos determined that dextromethorphan may have adverse developmental effects; however, the avian data have limited applicability to human gestation.[24591] Increased fluids to ease expectoration are usually recommended for first-line treatment in the pregnant patient. When administered to pregnant females, product formulations that also contain alcohol or other drugs should not be used.

    Use dextromethorphan; guaifenesin with caution during lactation; consider if guaifenesin alone would be adequate. Guaifenesin is considered compatible with breast-feeding at usual prescribed and non-prescription doses. Limited data are available regarding the use of dextromethorphan by breast-feeding women. Despite the lack of published data, dextromethorphan is often considered to be compatible with breast-feeding when usual antitussive doses are taken by the mother, due to the lack of expected harm in the breast-fed infant. Some dextromethorphan cough products contain alcohol, and these products should be avoided while breast-feeding. Some dextromethorphan; guaifenesin products contain alcohol, and alcohol-containing products should be avoided while breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.[39683]

    MECHANISM OF ACTION

    Dextromethorphan and guaifenesin act synergistically to suppress and treat the symptoms of cough.
    Dextromethorphan: Dextromethorphan is a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors in the brain and spinal cord. It is the d-isomer of levorphanol but has none of the analgesic, respiratory depressive, or sedative effects associated with opiate agonists. The antitussive effects of dextromethorphan are similar to codeine. Dextromethorphan acts on the cough center in the medulla to raise the threshold for coughing by decreasing the excitability of the cough center. Naloxone, an opiate-antagonist, does not block the antitussive effects of dextromethorphan.
    Guaifenesin: Guaifenesin loosens and thins phlegm and bronchial secretions to ease expectoration. By reducing the viscosity and adhesiveness of secretions, guaifenesin increases the efficacy of the mucociliary mechanism in removing accumulated secretions from the upper and lower airway. The increased flow of less viscous secretions promotes ciliary action and changes a dry, unproductive cough to one that is more productive and less frequent. Despite its long history of use since the 1950's, the efficacy of guaifenesin has only recently been substantiated. Guaifenesin is used for dry, nonproductive cough when there is the presence of tenacious mucus and/or mucus plugs. The results of a few studies have favored active treatment with guaifenesin over placebo in treating productive cough due to upper respiratory illness (URI).

    PHARMACOKINETICS

    Dextromethorphan; guaifenesin combination products are administered orally.
    Dextromethorphan: Dextromethorphan is approximately 60% to 70% protein bound. Dextromethorphan is metabolized primarily by liver enzymes undergoing O-demethylation, N-demethylation, and partial conjugation with glucuronic acid and sulfate. In humans, (+)-3-hydroxy-Nmethyl-morphinan, (+)-3-hydroxymorphinan, and traces of unmetabolized drug were found in urine after oral administration. Dextromethorphan is primarily metabolized by the CYP2D6 isoenzyme. In normal metabolizers (extensive metabolizers), the elimination half-life of dextromethorphan is approximately 13 hours.
    Guaifenesin: It is rapidly hydrolyzed (60% within 7 hours) and then excreted in the urine, with beta-(2-methoxyphenoxy)-lactic acid as its major urinary metabolite. Excessive use of guaifenesin may result in urolithiasis; renal stones have been documented to contain beta-(2-methoxyphenoxy)-lactic acid and other guaifenesin metabolites. Additional pharmacokinetic information is not known.
     
    Affected Cytochrome P450 isoenzymes and drug transporters: CYP2D6
    Dextromethorphan is metabolized via CYP2D6; potent inhibitors of this enzyme can increase dextromethorphan exposure.

    Oral Route

    Dextromethorphan: Dextromethorphan is rapidly absorbed from the GI tract, with antitussive activity appearing within 15 to 30 minutes. Food does not affect absorption. Antitussive activity can last for 3 to 6 hours.
    Guaifenesin: Guaifenesin is rapidly absorbed from the GI tract. No unchanged drug is detected in the urine following administration of oral guaifenesin.