isometheptene/dichloralphenazone/acetaminophen (Rx)

Brand and Other Names:Midrin
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Dosing & Uses

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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

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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.

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            Adverse Effects

            Frequency Not Defined

            Rash

            Transient dizziness

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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

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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.

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

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            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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