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Acetaminophen, Caffeine, and Pyrilamine

Pronunciation

(a seet a MIN oh fen, KAF een, & peer IL a meen)

Index Terms

  • Caffeine, Acetaminophen, and Pyrilamine
  • Pyrilamine, Acetaminophen, and Caffeine

Dosage Forms

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

Tablet, Oral, as hydrochloride:

GoodSense Menstrual Relief: Acetaminophen 500 mg, caffeine 60 mg, and pyrilamine maleate 15 mg

Midol Complete: Acetaminophen 500 mg, caffeine 60 mg, and pyrilamine maleate 15 mg [contains edetate disodium, fd&c blue #1 aluminum lake]

Midol Complete: Acetaminophen 500 mg, caffeine 60 mg, and pyrilamine maleate 15 mg [contains fd&c blue #2 aluminum lake]

Brand Names: U.S.

  • GoodSense Menstrual Relief [OTC]
  • Midol Complete [OTC]

Pharmacologic Category

  • Analgesic, Nonopioid
  • Histamine H1 Antagonist
  • Histamine H1 Antagonist, First Generation

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.

Pyrilamine: H1-receptor antagonist.

Use: Labeled Indications

Menstrual period symptom relief: Temporary relief of cramps, headache, bloating, backache, water-weight gain, muscle aches, and/or fatigue associated with menstrual periods.

Contraindications

OTC labeling: When used for self-medication, do not use with other products containing acetaminophen or if you are allergic to acetaminophen, caffeine, pyrilamine, or any component of the formulation.

Dosing: Adult

Menstrual period symptom relief: Oral: Two tablets (acetaminophen 1,000 mg/caffeine 120 mg/pyrilamine 30 mg) every 6 hours as needed; maximum: 6 tablets (acetaminophen 3,000 mg/caffeine 360 mg/pyrilamine 90 mg) per day

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Menstrual period symptom relief: Oral: Children ≥12 years and Adolescents: Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Storage

Store at room temperature.

Drug Interactions

Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). 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

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Monitor therapy

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

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

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

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. 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

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

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 (High risk with Inhibitors). 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 (High risk with Inhibitors). Monitor therapy

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

Pipemidic Acid: May increase the serum concentration of Caffeine and Caffeine Containing Products. 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 is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 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 (High risk with Inhibitors). 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 Acetaminophen and Caffeine monographs.

Warnings/Precautions

Concerns related to adverse effects:

• 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: Acetaminophen has been associated with severe liver damage. Hepatotoxicity is usually associated with excessive intake and often involves more than one product that contains acetaminophen. Limit acetaminophen dose from all sources (prescription and OTC) to ≤4 g/day and avoid or limit ethanol to <3 drinks per day.

• Hypersensitivity reactions: Allergic reactions have been reported with acetaminophen; 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 (FDA 2013).

Disease-related concerns:

• Ethanol use: Use with caution with concomitant alcohol use; consuming ≥3 alcoholic drinks/day may increase the risk of liver damage.

• Hepatic impairment: Use with caution in patients with hepatic impairment.

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:

• Pediatric: May cause excitability, especially in children.

Dosage form specific issues:

• Caffeine: Contains an amount of caffeine similar to 1 cup of coffee; limit the use of other caffeine-containing beverages or foods.

Other warnings/precautions:

• Dosage limit: Limit acetaminophen dose from all sources (prescription, OTC, combination products) and all routes of administration (IV, oral, rectal) to <4 g/day (adults).

• Self-medication (OTC use): When used for self-medication, notify health care provider prior to use if you have glaucoma, liver disease, difficultly in urination due to enlargement of the prostate gland, emphysema, or chronic bronchitis. Discontinue use and contact health care provider if new symptoms occur, redness or swelling is present, for pain that gets worse or lasts >10 days, or for fever that gets worse or lasts >3 days.

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 fatigue or anxiety. 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, 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 health care 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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