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    Drugs & Diseases

    isometheptene/dichloralphenazone/acetaminophen (Rx)

    Brand and Other Names:Midrin
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    Dosing & Uses

    AdultPediatric

    Dosage Forms & Strengths

    isometheptene/dichloralphenazone/acetaminophen

    capsule: Schedule IV

    • 65mg/100mg/325mg

    Migraine Headache

    2 capsules PO at onset of headache, then 1 capsule PO q1hr until headache relieved up to a cumulative dose of 5 capsules/12 hr

    Tension Headache

    1-2 capsules PO q4hr; not to exceed 8 capsules/24 hr

    Safety and efficacy not established

    Next:

    Interactions

    Interaction Checker

    and isometheptene/dichloralphenazone/acetaminophen

    No Results

       activity indicator 
      No Interactions Found
      Interactions Found

      Contraindicated

        Serious - Use Alternative

          Significant - Monitor Closely

            Minor

              All Interactions Sort By:
               activity indicator 

              Contraindicated (5)

              • isocarboxazid

                isocarboxazid, isometheptene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hypertension, V tach.

              • linezolid

                linezolid, isometheptene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hypertension, V tach.

              • phenelzine

                phenelzine, isometheptene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hypertension, V tach.

              • selegiline transdermal

                selegiline transdermal, isometheptene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hypertension, V tach.

              • tranylcypromine

                tranylcypromine, isometheptene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hypertension, V tach.

              Serious - Use Alternative (3)

              • lonafarnib

                acetaminophen will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

              • metoclopramide intranasal

                dichloralphenazone, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

              • pexidartinib

                acetaminophen and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

              Monitor Closely (11)

              • apalutamide

                apalutamide will decrease the level or effect of acetaminophen by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.

              • atogepant

                acetaminophen will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • avapritinib

                acetaminophen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • axitinib

                acetaminophen increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • bupivacaine implant

                acetaminophen, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

              • busulfan

                acetaminophen increases levels of busulfan by decreasing metabolism. Use Caution/Monitor. Use of acetaminophen prior to (< 72 hours) or concurrently with busulfan may result in decreased clearance of busulfan due to acetaminophen-induced decreases in glutathione levels.

              • cenobamate

                cenobamate, dichloralphenazone. Either increases effects of the other by sedation. Use Caution/Monitor.

              • dapsone topical

                acetaminophen increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia .

              • droxidopa

                isometheptene and droxidopa both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. May increase risk for supine hypertension

              • eltrombopag

                eltrombopag increases levels of acetaminophen by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

              • midazolam intranasal

                midazolam intranasal, dichloralphenazone. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

              Minor (50)

              • acetazolamide

                acetazolamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • albiglutide

                albiglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

              • antithrombin alfa

                acetaminophen increases effects of antithrombin alfa by unknown mechanism. Minor/Significance Unknown.

              • antithrombin III

                acetaminophen increases effects of antithrombin III by unknown mechanism. Minor/Significance Unknown.

              • argatroban

                acetaminophen increases effects of argatroban by unknown mechanism. Minor/Significance Unknown.

              • bemiparin

                acetaminophen increases effects of bemiparin by unknown mechanism. Minor/Significance Unknown.

              • bivalirudin

                acetaminophen increases effects of bivalirudin by unknown mechanism. Minor/Significance Unknown.

              • carbamazepine

                carbamazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • cholestyramine

                cholestyramine decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

              • clonazepam

                clonazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • colestipol

                colestipol decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

              • dalteparin

                acetaminophen increases effects of dalteparin by unknown mechanism. Minor/Significance Unknown.

              • diazepam

                diazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • disulfiram

                disulfiram will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

              • enoxaparin

                acetaminophen increases effects of enoxaparin by unknown mechanism. Minor/Significance Unknown.

              • ethanol

                ethanol will decrease the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

                ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown.

              • ethosuximide

                ethosuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • felbamate

                felbamate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • fondaparinux

                acetaminophen increases effects of fondaparinux by unknown mechanism. Minor/Significance Unknown.

              • fosphenytoin

                fosphenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • gabapentin

                gabapentin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • gabapentin enacarbil

                gabapentin enacarbil decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • green tea

                green tea increases effects of acetaminophen by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical, due to caffeine content).

              • heparin

                acetaminophen increases effects of heparin by unknown mechanism. Minor/Significance Unknown.

              • isoniazid

                isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown.

              • lacosamide

                lacosamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • lamotrigine

                lamotrigine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • levetiracetam

                levetiracetam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • liraglutide

                liraglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

              • lorazepam

                lorazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • methsuximide

                methsuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • metoclopramide

                metoclopramide increases levels of acetaminophen by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

              • metronidazole

                metronidazole will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

              • oxcarbazepine

                oxcarbazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • oxybutynin

                oxybutynin decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

              • oxybutynin topical

                oxybutynin topical decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

              • oxybutynin transdermal

                oxybutynin transdermal decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

              • phenindione

                acetaminophen increases effects of phenindione by unknown mechanism. Minor/Significance Unknown.

              • phenobarbital

                phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • phenytoin

                phenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • primidone

                primidone decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • protamine

                acetaminophen increases effects of protamine by unknown mechanism. Minor/Significance Unknown.

              • rifabutin

                rifabutin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • rifampin

                rifampin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • rufinamide

                rufinamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • ruxolitinib

                acetaminophen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              • tiagabine

                tiagabine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • topiramate

                topiramate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • valproic acid

                valproic acid decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • zonisamide

                zonisamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism increase levels of hepatotoxic metabolites.

              Previous
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              Adverse Effects

              Frequency Not Defined

              Rash

              Transient dizziness

              Previous
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              Warnings

              Contraindications

              Hypersensitivity

              Hepatitis or severe hepatic/renal impairment

              Glaucoma

              Severe renal impairment

              Hypertension

              Heart disease

              Hepatic impairment

              Within 14 days of MAO inhibitors

              Cautions

              Risk of hepatotoxicity higher in alcoholics, or with use of more than one acetaminophen-containing product

              Acetaminophen: Risk for rare, but serious skin reactions that can be fatal; these reactions include Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP); symptoms may include skin redness, blisters and rash

              G6PD deficiency

              May cause sedation; avoid driving car or operating machinery

              May increase respiratory depressant effects; caution with head injury, COPD, or other conditions with decreased respiratory drive

              Controlled substance (dichloralphenazone); may cause tolerance/dependence

              Caution in cardiovascular disease, hepatic impairment, G6PD deficiency

              Previous
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              Pregnancy & Lactation

              Pregnancy category: C

              Lactation: Excreted in breast milk; caution advised

              Dichloralphenazone: prodrug of chloral hydrate and phenazone; trichloroethanol (active metabolite of chloral hydrate), acetaminophen, and phenazine are excreted in breast milk

              According to the American Academy of Pediatrics, chloral hydrate and acetaminophen are compatible with breastfeeding

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

              Previous
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              Pharmacology

              Mechanism of Action

              Isometheptene: Elicits sympathomimetic effect; constricts dilated cerebral/cranial arterioles

              Dichloralphenazone: Elicits mild sedative effect; reduces emotional response to painful stimulus

              Acetaminophen: Inhibitis prostaglandin sythesis in CNS and may block peripheral pain impulse generation; acts on hypothalamus to antipyresis

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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              View explanations for tiers and restrictions
              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
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              QL Quantity Limits
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