Skip to Content

Acetaminophen, Caffeine, and Isometheptene Mucate

Pronunciation

(a seet a MIN oh fen, KAF een, & eye soe meth EP teen MUE kate)

Index Terms

  • Caffeine, Acetaminophen, and Isometheptene
  • Caffeine, Isometheptene Mucate, and Acetaminophen
  • Isomethepten/Caf/Acetaminophen
  • Isometheptene Mucate, Acetaminophen, and Caffeine
  • Isometheptene/Acetaminoph/Caff

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Prodrin: Acetaminophen 325 mg, caffeine 20 mg, and isometheptene mucate 65 mg

Generic: Acetaminophen 325 mg, caffeine 20 mg, and isometheptene mucate 65 mg

Brand Names: U.S.

  • Prodrin

Pharmacologic Category

  • Antimigraine Agent

Pharmacology

Acetaminophen: Nonopioid analgesic which reduces the perception of pain impulses originating from dilated cerebral vessels.

Caffeine: A cranial vasoconstrictor to enhance the vasoconstrictor effect. It is also used as a central stimulant for relief of headache.

Isometheptene mucate: Sympathomimetic amine which acts by constricting dilated cranial and cerebral arterioles, thus reducing the stimuli that lead to vascular headaches.

Use: Labeled Indications

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

Contraindications

Glaucoma; severe renal disease, hypertension, organic heart disease, and hepatic disease; concurrent monoamine oxidase inhibitor (MAOI) therapy

Dosing: Adult

Headache, migraine: Oral: 1 or 2 caplets to start, followed by 1 caplet every hour until relief is obtained; maximum: 5 caplets within a 12 hour period

Headache, tension: Oral: 1 or 2 caplets every 4 hours; maximum: 8 caplets in 24 hours

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

Use is contraindicated in severe cases of renal disease.

Dosing: Hepatic Impairment

Use is contraindicated in patients with hepatic disease.

Storage

Store at 20°C to 25°C (68°F to 77°F). Avoid exposure to heat.

Drug Interactions

Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy

Acebrophylline: May enhance the stimulatory effect of CNS Stimulants. Avoid combination

Adenosine: Caffeine and Caffeine Containing Products may diminish the therapeutic effect of Adenosine. Management: Monitor for decreased effect of adenosine if patient is receiving caffeine. Discontinue caffeine in advance of scheduled diagnostic use of adenosine whenever possible. Consider therapy modification

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

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

Ciprofloxacin (Systemic): May increase the serum concentration of Caffeine. Monitor therapy

CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Monitor therapy

CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. 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

Deferasirox: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy

Doxofylline: Caffeine and Caffeine Containing Products may enhance the adverse/toxic effect of Doxofylline. Avoid combination

Formoterol: Caffeine and Caffeine Containing Products may enhance the adverse/toxic effect of Formoterol. Caffeine and Caffeine Containing Products may enhance the hypokalemic effect of Formoterol. 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

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

Indacaterol: Caffeine and Caffeine Containing Products may enhance the adverse/toxic effect of Indacaterol. Caffeine and Caffeine Containing Products may enhance the hypokalemic effect of Indacaterol. 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

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

Lithium: Caffeine and Caffeine Containing Products may decrease the serum concentration of Lithium. Monitor therapy

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

Norfloxacin: May increase the serum concentration of Caffeine and Caffeine Containing Products. Monitor therapy

Obeticholic Acid: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy

Olodaterol: Caffeine and Caffeine Containing Products may enhance the adverse/toxic effect of Olodaterol. Caffeine and Caffeine Containing Products may enhance the hypokalemic effect of Olodaterol. Monitor therapy

Peginterferon Alfa-2b: May increase the serum concentration of CYP1A2 Substrates. 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

Regadenoson: Caffeine and Caffeine Containing Products may diminish the vasodilatory effect of Regadenoson. Management: Avoiding using caffeine or other methylxanthine containing products (e.g., theophylline) for at least 12 hours prior to the administration of regadenoson. 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

Stiripentol: May increase the serum concentration of Caffeine and Caffeine Containing Products. Avoid combination

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

Teriflunomide: May decrease the serum concentration of Caffeine and Caffeine Containing Products. Monitor therapy

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

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Vemurafenib: May increase the serum concentration of CYP1A2 Substrates. Management: Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. 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

Adverse Reactions

See individual agents.

ALERT: U.S. Boxed Warning

Hepatotoxicity:

Acetaminophen has been associated with cases of acute liver failure at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 mg/day, and often in combination with other acetaminophen-containing products.

Warnings/Precautions

Concerns related to adverse events:

• Hepatotoxicity: [U.S. Boxed Warning]: Acetaminophen may cause severe hepatic toxicity, potentially requiring liver transplant or resulting in death; hepatotoxicity is usually associated with excessive acetaminophen intake (≥4 g/day) and often in combination with other acetaminophen-containing products. Risk of acute liver failure is increased in patients with active liver disease or concomitant use of alcohol. Have patients avoid ethanol or limit to <3 drinks/day.

• Hypersensitivity/anaphylactic reactions: 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 caution in patients with cardiovascular disease, including hypertension and peripheral vascular disease, or after recent cardiovascular attack. Use is contraindicated in organic heart disease.

Other warnings/precautions:

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

Pregnancy Considerations

Refer to the Acetaminophen and Caffeine monographs for information.

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. 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), urinary retention, change in amount of urine passed, confusion, 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.

Hide