Dosing & Uses
Dosing Forms & Strengths
acetaminophen/caffeine/isometheptene
tablet
- 325mg/20mg/65mg
Migraine Headache
1 or 2 tablets PO at onset of headache, then 1 tablet hourly until relieved; not to exceed 5 tablets/12 hr
Tension Headache
1-2 tablets PO q4hr; not to exceed 8 tablets/24 hr
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (8)
- fezolinetant
caffeine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors
- isocarboxazid
isocarboxazid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.
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.
linezolid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode. - phenelzine
phenelzine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.
phenelzine, isometheptene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hypertension, V tach. - procarbazine
procarbazine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Caffeine can produce severe hypertensive crises or dangerous cardiac arrhythmias if administered to patients taking a MAOI. All preparations containing caffeine should be used sparingly.
- selegiline transdermal
selegiline transdermal, isometheptene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hypertension, V tach.
- selegiline transdermal
selegiline transdermal increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.
- tranylcypromine
tranylcypromine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.
tranylcypromine, isometheptene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hypertension, V tach.
Serious - Use Alternative (9)
- bupropion
caffeine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.
- dipyridamole
caffeine decreases effects of dipyridamole by pharmacodynamic antagonism. Contraindicated.
- givosiran
givosiran will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- iobenguane I 131
caffeine will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.
- 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.
- ozanimod
ozanimod increases toxicity of caffeine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.
- 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.
- pretomanid
acetaminophen, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.
- regadenoson
caffeine decreases effects of regadenoson by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid methylxanthines for 12 hours before regadenoson administration.
Monitor Closely (189)
- albuterol
albuterol and caffeine both decrease sedation. Use Caution/Monitor.
- alfentanil
alfentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- alprazolam
alprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- amitriptyline
amitriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- amobarbital
amobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- amoxapine
amoxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- 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.
- arformoterol
arformoterol and caffeine both decrease sedation. Use Caution/Monitor.
- aripiprazole
aripiprazole increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- armodafinil
armodafinil and caffeine both decrease sedation. Use Caution/Monitor.
- 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.
- azelastine
azelastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- belladonna and opium
belladonna and opium increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- benperidol
benperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- benzphetamine
caffeine and benzphetamine both decrease sedation. Use Caution/Monitor.
- brompheniramine
brompheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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.
- buprenorphine buccal
buprenorphine buccal increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- 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.
- butabarbital
butabarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- butalbital
butalbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- butorphanol
butorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- carbinoxamine
carbinoxamine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- chloral hydrate
chloral hydrate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- chlordiazepoxide
chlordiazepoxide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- chlorpheniramine
chlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- chlorpromazine
chlorpromazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- cinnarizine
cinnarizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- ciprofloxacin
ciprofloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. The hepatic metabolism of caffeine may be decreased by ciprofloxacin; pharmacologic effects of caffeine may be increased.
- clemastine
clemastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- clomipramine
clomipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- clonazepam
clonazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- clorazepate
clorazepate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- clozapine
clozapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- codeine
codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- cyclizine
cyclizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- cyproheptadine
cyproheptadine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dapsone topical
acetaminophen increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia .
- deferasirox
deferasirox increases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- desipramine
desipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dexchlorpheniramine
dexchlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dexfenfluramine
caffeine and dexfenfluramine both decrease sedation. Use Caution/Monitor.
- dexmedetomidine
dexmedetomidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dexmethylphenidate
caffeine and dexmethylphenidate both decrease sedation. Use Caution/Monitor.
- dextroamphetamine
caffeine and dextroamphetamine both decrease sedation. Use Caution/Monitor.
- dextromoramide
dextromoramide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- diamorphine
diamorphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- diethylpropion
caffeine and diethylpropion both decrease sedation. Use Caution/Monitor.
- difenoxin hcl
difenoxin hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dimenhydrinate
dimenhydrinate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- diphenhydramine
diphenhydramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- diphenoxylate hcl
diphenoxylate hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dipipanone
dipipanone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dobutamine
dobutamine and caffeine both decrease sedation. Use Caution/Monitor.
- dopamine
caffeine and dopamine both decrease sedation. Use Caution/Monitor.
- dopexamine
dopexamine and caffeine both decrease sedation. Use Caution/Monitor.
- doxepin
doxepin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- droperidol
droperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- 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
caffeine 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.
- ephedrine
ephedrine and caffeine both decrease sedation. Use Caution/Monitor.
- epinephrine
epinephrine and caffeine both decrease sedation. Use Caution/Monitor.
- epinephrine inhaled
caffeine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
- epinephrine racemic
epinephrine racemic and caffeine both decrease sedation. Use Caution/Monitor.
- esketamine intranasal
esketamine intranasal, caffeine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- estazolam
estazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- ethanol
ethanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- ethinylestradiol
ethinylestradiol will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- exenatide injectable solution
exenatide injectable solution will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.
- exenatide injectable suspension
exenatide injectable suspension will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.
- fenfluramine
caffeine and fenfluramine both decrease sedation. Use Caution/Monitor.
- fexinidazole
fexinidazole will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- finerenone
acetaminophen will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.
- flibanserin
acetaminophen will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.
- fluphenazine
fluphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- flurazepam
flurazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- fluvoxamine
fluvoxamine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- formoterol
formoterol and caffeine both decrease sedation. Use Caution/Monitor.
- green tea
green tea increases effects of caffeine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of CNS stimulation due to caffeine component of green tea. Caution advised.
- guselkumab
guselkumab, caffeine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.
- haloperidol
haloperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- hydromorphone
hydromorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- hydroxyzine
hydroxyzine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- iloperidone
iloperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- imatinib
imatinib decreases levels of acetaminophen by decreasing hepatic clearance. Modify Therapy/Monitor Closely. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation (Ki value of 58.5 micro-M) at therapeutic levels; avoid chronic acetaminophen therapy with imatinib; if occasional acetaminophen administered, do not exceed 1300 mg/day.
- imipramine
imipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- isavuconazonium sulfate
acetaminophen will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- isoniazid
isoniazid will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.
- isoproterenol
isoproterenol and caffeine both decrease sedation. Use Caution/Monitor.
- ivacaftor
acetaminophen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .
- ketotifen, ophthalmic
ketotifen, ophthalmic increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- lemborexant
acetaminophen will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.
- letermovir
letermovir increases levels of caffeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- levalbuterol
levalbuterol and caffeine both decrease sedation. Use Caution/Monitor.
- levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of acetaminophen by unknown mechanism. Use Caution/Monitor.
acetaminophen increases levels of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by decreasing hepatic clearance. Use Caution/Monitor. Coadministration of ascorbic acid and certain combined hormonal contraceptives (CHCs) containing EE may increase plasma EE concentrations, possibly by inhibition of conjugation. - levorphanol
levorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- levothyroxine
caffeine decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Caffeine (a sympathomimetic) concomitantly used with oral levothyroxine may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
- lisdexamfetamine
caffeine and lisdexamfetamine both decrease sedation. Use Caution/Monitor.
- lixisenatide (DSC)
lixisenatide (DSC) will decrease the level or effect of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. GLP1 agonists delay gastric emptying, which may affect absorption of concomitantly administered oral medications. No effects on acetaminophen Cmax and Tmax were observed when acetaminophen was administered 1 hr before lixisenatide. When administered 1 or 4 hr after lixisenatide, acetaminophen Cmax was decreased by 29% and 31% respectively and median Tmax was delayed by 2 and 1.75 hr, respectively.
- lofepramine
lofepramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- lofexidine
lofexidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- lomitapide
acetaminophen increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.
- loprazolam
loprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- lorazepam
lorazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- lormetazepam
lormetazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- loxapine
loxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- loxapine inhaled
loxapine inhaled increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- maprotiline
maprotiline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- marijuana
marijuana increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- melatonin
melatonin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- meperidine
meperidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- meprobamate
meprobamate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- metaproterenol
metaproterenol and caffeine both decrease sedation. Use Caution/Monitor.
- methadone
methadone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- methamphetamine
caffeine and methamphetamine both decrease sedation. Use Caution/Monitor.
- methotrexate
caffeine decreases effects of methotrexate by pharmacodynamic antagonism. Use Caution/Monitor.
- methylenedioxymethamphetamine
caffeine and methylenedioxymethamphetamine both decrease sedation. Use Caution/Monitor.
- methylphenidate
caffeine increases effects of methylphenidate by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.
- midazolam
midazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- midazolam intranasal
acetaminophen will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.
- midodrine
caffeine and midodrine both decrease sedation. Use Caution/Monitor.
- mipomersen
mipomersen, acetaminophen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.
- mirtazapine
mirtazapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- modafinil
caffeine and modafinil both decrease sedation. Use Caution/Monitor.
- morphine
morphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- motherwort
motherwort increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- moxonidine
moxonidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- nabilone
nabilone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- nalbuphine
nalbuphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- norepinephrine
norepinephrine and caffeine both decrease sedation. Use Caution/Monitor.
- nortriptyline
nortriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- olanzapine
olanzapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- opium tincture
opium tincture increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- oxazepam
oxazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- oxycodone
oxycodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- oxymorphone
oxymorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- paliperidone
paliperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- papaveretum
papaveretum increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- pefloxacin
pefloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- pentazocine
pentazocine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- pentobarbital
pentobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- perphenazine
perphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- phendimetrazine
caffeine and phendimetrazine both decrease sedation. Use Caution/Monitor.
- phenobarbital
phenobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- phentermine
caffeine and phentermine both decrease sedation. Use Caution/Monitor.
- phenylephrine
caffeine and phenylephrine both decrease sedation. Use Caution/Monitor.
- phenylephrine PO
caffeine and phenylephrine PO both decrease sedation. Use Caution/Monitor.
- pholcodine
pholcodine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- pimozide
pimozide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- pirbuterol
pirbuterol and caffeine both decrease sedation. Use Caution/Monitor.
- primidone
primidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- prochlorperazine
prochlorperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- promethazine
promethazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- propylhexedrine
caffeine and propylhexedrine both decrease sedation. Use Caution/Monitor.
- protriptyline
protriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- quazepam
quazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- quetiapine
quetiapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- rasagiline
rasagiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.
- risperidone
risperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- rucaparib
rucaparib will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.
- salmeterol
salmeterol and caffeine both decrease sedation. Use Caution/Monitor.
- scullcap
scullcap increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- secobarbital
secobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- selegiline
selegiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.
- shepherd's purse
shepherd's purse increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- solriamfetol
caffeine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
- stiripentol
stiripentol, caffeine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.
- sufentanil
sufentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- tapentadol
tapentadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- tazemetostat
acetaminophen will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- temazepam
temazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- terbutaline
terbutaline and caffeine both decrease sedation. Use Caution/Monitor.
- teriflunomide
teriflunomide decreases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- tetracaine
tetracaine, acetaminophen. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.
- thioridazine
thioridazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- thiothixene
thiothixene increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- tinidazole
acetaminophen will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- topiramate
topiramate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- tramadol
tramadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- trazodone
trazodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- triazolam
triazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- triclofos
triclofos increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- trifluoperazine
trifluoperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- trimipramine
trimipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- triprolidine
triprolidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- warfarin
acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.
- xylometazoline
caffeine and xylometazoline both decrease sedation. Use Caution/Monitor.
Minor (87)
- acetazolamide
acetazolamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- adenosine
caffeine decreases effects of adenosine by pharmacodynamic antagonism. Minor/Significance Unknown.
- albiglutide
albiglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- amantadine
amantadine, caffeine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.
- American ginseng
American ginseng increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.
- amobarbital
amobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. 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.
- armodafinil
armodafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. 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.
- butabarbital
butabarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- butalbital
butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- calcium acetate
caffeine decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.
- calcium carbonate
caffeine decreases levels of calcium carbonate by increasing renal clearance. Minor/Significance Unknown.
- calcium chloride
caffeine decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.
- calcium citrate
caffeine decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.
- calcium gluconate
caffeine decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.
- carbamazepine
carbamazepine will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
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.
- cigarette smoking
cigarette smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- cimetidine
cimetidine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- clonazepam
clonazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- clotrimazole
clotrimazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
- 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.
- eucalyptus
eucalyptus increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
- felbamate
felbamate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- fluconazole
fluconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
- 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.
- grapefruit
grapefruit increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
- green tea
green tea increases effects of acetaminophen by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical, due to caffeine content).
- guarana
guarana increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.
- heparin
acetaminophen increases effects of heparin by unknown mechanism. Minor/Significance Unknown.
- isoniazid
isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown.
- itraconazole
itraconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
- ketoconazole
ketoconazole increases levels of caffeine by decreasing metabolism. 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.
- levoketoconazole
levoketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
- 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.
- mexiletine
mexiletine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- miconazole vaginal
miconazole vaginal increases levels of caffeine by decreasing 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.
- peginterferon alfa 2a
peginterferon alfa 2a will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- pentobarbital
pentobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. 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.
phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown. - phenytoin
phenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- pipemidic acid
pipemidic acid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- posaconazole
posaconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
- primidone
primidone decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
primidone will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown. - protamine
acetaminophen increases effects of protamine by unknown mechanism. Minor/Significance Unknown.
- rifampin
rifampin will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. 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.
- ruxolitinib topical
acetaminophen will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- sage
sage increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
- secobarbital
secobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- smoking
smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- thiamine
caffeine decreases levels of thiamine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Coffee, tea are high in anti-thiamine factors.
- tiagabine
tiagabine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- tobacco use
tobacco use will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- 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.
- verapamil
verapamil will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- voriconazole
voriconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
- yerba mate
yerba mate increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.
- zileuton
zileuton will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- zonisamide
zonisamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism increase levels of hepatotoxic metabolites.
Adverse Effects
Frequency Not Defined
Rash
Transient dizziness
Warnings
Black Box Warnings
Medication errors and hepatotoxicity with acetaminophen
- Take care when prescribing, preparing, and administering acetaminophen to avoid dosing errors which could result in accidental overdose and death
In particular, be careful to ensure that
- The dose in milligrams (mg) and milliliters (mL) is not confused
- The dosing is based on weight for patients <50 kg
- Infusion pumps are properly programmed
- The total daily dose of acetaminophen from all sources does not exceed maximum daily limits
- 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 the maximum daily limits, and often involve more than one acetaminophen-containing product
Contraindications
Glaucoma
Severe renal disease
Severe hypertension
Organic heart disease
Severe hepatic disease
Coadministration or within 2 weeks of MAOIs
Cautions
Cautions with history of hypertension, peripheral vascular disease, and after recent cardiovascular events
Acetaminophen
- Reports of acute liver failure, at times resulting in liver transplant and death; most of the cases of liver injury are associated with doses exceeding 4 g/day, and often involve >1 acetaminophen-containing product (see Black Box Warnings)
- 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
- Postmarketing reports of hypersensitivity and anaphylaxis
Pregnancy & Lactation
Pregnancy Category: C Lactation: Unknown if distributed in human breast milk
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.Pharmacology
Mechanism of Action
Acetaminophen: Nonnarcotic analgesic; reduces the perception of pain impulses originating from dilated cerebral vessels
Caffeine: Cranial vasoconstrictor; enhances vasoconstrictor effect of isometheptene; also used as a central stimulant for relief of headache
Isometheptene: Sympathomimetic amine that acts by constricting dilated cranial and cerebral arterioles, thus reducing the stimuli that lead to vascular headaches
Images
Formulary
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Adding plans allows you to:
- View the formulary and any restrictions for each plan.
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