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Acetaminophen, Isometheptene, and Dichloralphenazone

Pronunciation

(a seet a MIN oh fen, eye soe me THEP teen, & dye KLOR al FEN a zone)

Index Terms

  • Acetaminophen, Dichloralphenazone, and Isometheptene
  • Dichloralphenazone, Acetaminophen, and Isometheptene
  • Dichloralphenazone, Isometheptene, and Acetaminophen
  • Isomethept/Dichlphn/Acetaminop
  • Isometheptene, Acetaminophen, and Dichloralphenazone
  • Isometheptene, Dichloralphenazone, and Acetaminophen
  • Isometheptene/Apap/Dichlphen
  • Midrin

Dosage Forms

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

Capsule, Oral:

Migragesic IDA: Acetaminophen 325 mg, isometheptene mucate 65 mg, and dichloralphenazone 100 mg [DSC]

Nodolor: Acetaminophen 325 mg, isometheptene mucate 65 mg, and dichloralphenazone 100 mg

Generic: Acetaminophen 325 mg, isometheptene mucate 65 mg, and dichloralphenazone 100 mg

Brand Names: U.S.

  • Migragesic IDA [DSC]
  • Nodolor

Pharmacologic Category

  • Analgesic, Nonopioid
  • Sedative
  • Sympathomimetic

Pharmacology

Acetaminophen: Although not fully elucidated, believed to inhibit the synthesis of prostaglandins in the central nervous system and work peripherally to block pain impulse generation; produces antipyresis from inhibition of hypothalamic health-regulating center

Dichloralphenazone: Prodrug, converted to chloral hydrate (sedative) and antipyrine (analgesic/antipyretic) that reduces patient’s emotional response to painful stimuli

Isometheptene: A sympathomimetic that reduces stimuli leading to vascular headaches via constriction of dilated cranial and cerebral arterioles

Use: Labeled Indications

Headache: Relief of tension headache and vascular headache (potentially effective for relief of migraine headache).

Contraindications

Hypersensitivity to isometheptene, dichloralphenazone, acetaminophen, or any component of the formulation; cardiovascular or cerebrovascular insufficiency (eg, recent MI, stroke); glaucoma; severe renal disease; hypertension; organic heart disease; peripheral vascular disease; hepatic disease; concomitant monoamine oxidase inhibitor (MAOI) therapy

Dosing: Adult

Migraine headache: Oral: Two capsules to start, followed by 1 capsule every hour until relief is obtained (maximum: 5 capsules/12 hours)

Tension headache: Oral: 1 to 2 capsules every 4 hours (maximum: 8 capsules/24 hours)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

Use is contraindicated in patients with severe renal disease.

Dosing: Hepatic Impairment

Use is contraindicated in patients with hepatic disease.

Administration

Administer without regard to food.

Storage

Store at 15°C to 30°C (59°F to 86°F).

Drug Interactions

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

Alpha1-Blockers: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Similarly, Alpha-/Beta-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

Beta-Blockers: May enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Some beta-adrenoceptor mediated effects of Alpha-/Beta-Agonists (Direct-Acting), including anti-anaphylactic effects of epinephrine, may be diminished by Beta-Blockers. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. 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

Cocaine: May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. 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 Alpha-/Beta-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Exceptions: Ergoloid Mesylates; Nicergoline. Avoid combination

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

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

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

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

MAO Inhibitors: May enhance the adverse/toxic effect of Isometheptene. 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

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Consider therapy modification

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

Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other 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 Alpha-/Beta-Agonists (Direct-Acting). Management: Avoid, if possible, the use of direct-acting alpha-/beta-agonists in patients receiving tricyclic antidepressants. If combined, monitor for evidence of increased pressor effects and consider reductions in initial dosages of the alpha-/beta-agonist. Consider therapy modification

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

Test Interactions

Acetaminophen may cause false urine glucose, urine catecholamine, and urinary 5-hydroxyindoleacetic acid test results.

Adverse Reactions

Frequency not defined.

Central nervous system: Dizziness (transient)

Dermatologic: Skin rash

ALERT: U.S. Boxed Warning

Hepatotoxicity:

This product contains acetaminophen. Severe liver damage may occur if a person takes: more than 4,000 mg of acetaminophen in 24 hours; with other drugs containing acetaminophen; with 3 or more alcoholic drinks every day while using this product.

Warnings/Precautions

Concerns related to adverse events:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Hepatotoxicity: [U.S. Boxed Warning]: Acetaminophen may cause severe hepatotoxicity, potentially requiring liver transplant or resulting in death; hepatotoxicity is usually associated with excessive acetaminophen intake (>4 g/day). Risk is increased with alcohol use (eg, ≥3 drinks per day), preexisting liver disease, and intake of more than one source of acetaminophen-containing medications. Chronic daily dosing in adults has also resulted in liver damage in some patients.

• Hypersensitivity: Hypersensitivity and anaphylactic reactions have been reported with acetaminophen use; discontinue immediately if symptoms of allergic or hypersensitivity reactions occur.

• Skin reactions: Rarely, acetaminophen may cause serious and potentially fatal skin reactions such as acute generalized exanthematous pustulosis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Discontinue treatment if severe skin reactions develop.

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.

Disease-related concerns:

• Cardiovascular disease: Use is contraindicated in cardiovascular or cerebrovascular insufficiency (eg, recent MI, stroke), hypertension, organic heart disease, and peripheral vascular disease.

• G6PD deficiency: Use with caution in patients with known G6PD deficiency; rare reports of hemolysis have occurred with acetaminophen use.

• Hepatic impairment: Use is contraindicated in patients with hepatic disease.

• Renal impairment: Use is contraindicated in patients with severe renal disease.

Other warning/precautions:

• Dosage limit: Limit acetaminophen dose from all sources (prescription, OTC) ≤4 g/day (adults).

Monitoring Parameters

Relief of pain

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, fatigue, or nausea. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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