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Acetaminophen, Guaifenesin, and Phenylephrine


General


Pronunciation

(a seet a MIN oh fen, gwye FEN e sin, & fen il EF rin)


Brand Names: U.S.

  • Mucinex Fast-Max Cold & Sinus [OTC]
  • Mucinex Sinus-Max Congestion [OTC]
  • Sudafed PE Pressure+Pain+Mucus [OTC]
  • Tylenol Sinus Congestion/Pain [OTC] [DSC]
  • Tylenol Sinus Severe [OTC]

Indications


Use: Labeled Indications

Allergies/common cold/hay fever: Temporary relief of symptoms (eg, headache, minor aches/pains, nasal congestion, sinus congestion/pressure) associated with hay fever, other respiratory allergies, or the common cold; temporarily reduces fever; helps loosen phlegm and thin bronchial secretions.


Contraindications


OTC labeling: When used for self-medication, do not use with any other drug containing acetaminophen; in combination with or within 14 days of stopping a monoamine oxidase inhibitor (MAOI); if you are hypersensitive to acetaminophen, guaifenesin, phenylephrine, or any component of the formulation.


Dosing and Administration


Dosing: Adult

Note: When calculating the maximum daily dose, consider all sources of acetaminophen (prescription and OTC) and all routes of administration. Do not exceed the maximum recommended daily dose.

Allergies/common cold/hay fever: Oral: Acetaminophen 325 mg/guaifenesin 200 mg/phenylephrine 5 mg: Two tablets every 4 hours (maximum: 10 tablets [acetaminophen 3,250 mg/guaifenesin 2,000 mg/phenylephrine 50 mg]/24 hours).


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Allergies/common cold/hay fever: Oral: Children ≥12 years and Adolescents: Refer to adult dosing


Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturers labeling.


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturers labeling; use caution in patients with hepatic impairment or active liver disease.


Administration

Swallow whole; do not crush, chew, or dissolve.


Storage

Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Liquid, Oral:

Mucinex Fast-Max Cold & Sinus: Acetaminophen 650 mg, guaifenesin 400 mg, and phenylephrine hydrochloride 10 mg per 20 mL (177 mL) [contains brilliant blue fcf (fd&c blue #1), edetate disodium, fd&c red #40, propylene glycol, sodium benzoate]

Tablet, Oral:

Mucinex Sinus-Max Congestion: Acetaminophen 325 mg, guaifenesin 200 mg, and phenylephrine hydrochloride 5 mg [contains fd&c red #40 aluminum lake, fd&c yellow #6 aluminum lake]

Sudafed PE Pressure+Pain+Mucus: Acetaminophen 325 mg, guaifenesin 200 mg, and phenylephrine hydrochloride 5 mg

Tylenol Sinus Congestion/Pain: Acetaminophen 325 mg, guaifenesin 200 mg, and phenylephrine hydrochloride 5 mg [DSC]

Tylenol Sinus Severe: Acetaminophen 325 mg, guaifenesin 200 mg, and phenylephrine hydrochloride 5 mg


Drug Interactions

Acetaminophen: May increase the serum concentration of Phenylephrine (Systemic). Monitor therapy

Alcohol (Ethyl): May enhance the hepatotoxic effect of Acetaminophen. Monitor therapy

Alpha1-Blockers: May diminish the vasoconstricting effect of Alpha1-Agonists. Similarly, Alpha1-Agonists may antagonize Alpha1-Blocker vasodilation. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Exceptions: Amobarbital; Butabarbital; Butalbital; Methohexital; PENTobarbital; Secobarbital; Thiopental. Monitor therapy

Benzylpenicilloyl Polylysine: Alpha1-Agonists may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Consider use of a histamine skin test as a positive control to assess a patients ability to mount a wheal and flare response. Consider therapy modification

Busulfan: Acetaminophen may increase the serum concentration of Busulfan. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Monitor therapy

Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Consider therapy modification

Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Monitor therapy

Dasatinib: Acetaminophen may enhance the hepatotoxic effect of Dasatinib. Dasatinib may increase the serum concentration of Acetaminophen. Consider therapy modification

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Ergot Derivatives: May enhance the hypertensive effect of Alpha1-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha1-Agonists. Exceptions: Ergoloid Mesylates; Nicergoline. Avoid combination

FentaNYL: Alpha1-Agonists may decrease the serum concentration of FentaNYL. Specifically, fentanyl nasal spray serum concentrations may decrease and onset of effect may be delayed. Monitor therapy

Fosphenytoin-Phenytoin: May decrease the serum concentration of Acetaminophen. Specifically, serum concentrations of acetaminophen may be decreased (leading to decreased efficacy), but the formation of the toxic N-acetyl-p-benzoquinone imine (NAPQI) metabolite may be increased (leading to increased hepatotoxicity). Monitor therapy

Hyaluronidase: May enhance the vasoconstricting effect of Phenylephrine (Systemic). Management: Avoid the use of hyaluronidase to enhance dispersion or absorption of phenylephrine. Use of hyaluronidase for other purposes in patients receiving phenylephrine may be considered as clinically indicated. Avoid combination

Imatinib: Acetaminophen may enhance the hepatotoxic effect of Imatinib. Monitor therapy

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Ioflupane I 123: Phenylephrine (Systemic) may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy

Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Monitor therapy

LamoTRIgine: Acetaminophen may decrease the serum concentration of LamoTRIgine. Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

MAO Inhibitors: May enhance the hypertensive effect of Alpha1-Agonists. While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Exceptions: Linezolid; Tedizolid. Avoid combination

MetyraPONE: May increase the serum concentration of Acetaminophen. More importantly, by inhibiting the conjugative metabolism of acetaminophen, metyrapone may shift the metabolism towards the oxidative route that produces a hepatotoxic metabolite. Monitor therapy

Mipomersen: Acetaminophen may enhance the hepatotoxic effect of Mipomersen. Monitor therapy

Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when nitric oxide is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine. Monitor therapy

Phenylephrine (Systemic): Acetaminophen may increase the serum concentration of Phenylephrine (Systemic). Monitor therapy

Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Monitor therapy

Probenecid: May increase the serum concentration of Acetaminophen. Probenecid may also limit the formation of at least one major non-toxic metabolite, possibly increasing the potential for formation of the toxic NAPQI metabolite. Consider therapy modification

Propacetamol: May increase the serum concentration of Phenylephrine (Systemic). Management: Monitor patients closely for increased side effects of phenylephrine if propacetamol is used concomitantly. Patients with underlying blood pressure issues or arrhythmias may need closer monitoring and may warrant consideration of alternative therapies. Monitor therapy

Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Monitor therapy

SORAfenib: Acetaminophen may enhance the hepatotoxic effect of SORAfenib. SORAfenib may increase the serum concentration of Acetaminophen. Consider therapy modification

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Tetracaine (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Monitor therapy

Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha1-Agonists. Tricyclic Antidepressants may diminish the vasopressor effect of Alpha1-Agonists. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. This appears most likely with daily acetaminophen doses exceeding 1.3 or 2 g/day for multiple consecutive days. Monitor therapy


Warnings/Precautions


Concerns related to adverse effects:

- Hepatotoxicity: Acetaminophen has been associated with acute liver failure, at times resulting in liver transplant and death. Hepatotoxicity is usually associated with excessive acetaminophen intake and often involves more than one product that contains acetaminophen. Do not exceed the maximum recommended daily dose (>4 g daily). In addition, chronic daily dosing may also result in liver damage in some patients.

- Hypersensitivity/anaphylactic reactions: Hypersensitivity and anaphylactic reactions have been reported; discontinue immediately if symptoms of allergic or hypersensitivity reactions occur.

- Skin reactions: Serious and potentially fatal skin reactions, including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have occurred rarely with acetaminophen use. Discontinue therapy at the first appearance of skin rash, skin reddening, or blisters.

Disease-related concerns:

- Cardiovascular disease: Use with caution in patients with cardiovascular disease (including hypertension and ischemic heart disease).

- Diabetes: Use with caution in patients with diabetes mellitus.

- Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥3 alcoholic drinks/day may increase the risk of liver damage. Avoid ethanol or limit to <3 alcoholic drinks/day.

- Hepatic impairment: Use with caution in patients with hepatic impairment or active liver disease.

- Increased intraocular pressure/glaucoma: Use with caution in patients with increased intraocular pressure or glaucoma.

- Prostatic hyperplasia/urinary obstruction: Use with caution in patients with prostatic hyperplasia and/or GU obstruction.

- Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

- Elderly: Use with caution in the elderly; more likely to experience adverse reactions to sympathomimetics.

Dosage form specific issues:

- Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol ( ≥99 mg/kg/day) have been associated with a potentially fatal toxicity (gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer 's labeling.

- Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Other warnings/precautions:

- Dosage limit: Limit acetaminophen dose to <4 g/day.

- Self-medication (OTC use): When used for self-medication (OTC), patients with persistent or chronic cough (associated with COPD, asthma or smoking) and/or productive cough (eg, copious amounts of phlegm) should be evaluated by a healthcare provider prior to use. Discontinue use and notify healthcare provider if pain, cough, or nasal congestion gets worse or lasts >7 days; fever gets worse or lasts >3 days; cough comes back or occurs with rash or headache that lasts; if any new symptoms or nervousness, dizziness, or sleeplessness occur; or if redness or swelling is present.


Pregnancy Considerations

Refer to individual agents


Actions


Pharmacology

Acetaminophen: Inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation.

Guaifenesin: Acts as an expectorant by increasing the effective hydration of the respiratory tract, maintains the sol layer needed for ciliary clearance and reduces the viscosity of respiratory mucus.

Phenylephrine: Causes vasoconstriction of the arterioles of the nasal mucosa.

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