Treximet (sumatriptan/naproxen) for Migraines: Drug Warnings

Generic drug: sumatriptan and naproxen sodium

Brand name: Treximet

What is Treximet (sumatriptan and naproxen sodium), and how does it work?

Treximet (sumatriptan and naproxen sodium) is a prescription medicine used to treat the symptoms of Migraine Headache. Treximet may be used alone or with other medications.

Treximet belongs to a class of drugs called NSAIDs; Serotonin 5-HT-Receptor Agonists.

It is not known if Treximet is safe and effective in children younger than 12 years of age.

What are the side effects of Treximet?

WARNING

RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS

Cardiovascular Thrombotic Events

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of
serious cardiovascular thrombotic events, including myocardial infarction
and stroke, which can be fatal. This risk may occur early in treatment and
may increase with duration of use.
Treximet is contraindicated in the setting of coronary artery bypass
graft (CABG) surgery.

Gastrointestinal Bleeding, Ulceration, and Perforation

NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse
events including bleeding, ulceration, and perforation of the stomach or
intestines, which can be fatal. These events can occur at any time during
use and without warning symptoms. Elderly patients and patients with a prior
history of peptic ulcer disease and/or GI bleeding are at greater risk for
serious GI events.

Treximet may cause serious side effects including:

hives,
difficulty breathing,
swelling of your face, lips, tongue, or throat,
severe skin reaction,
fever,
sore throat,
burning eyes,
skin pain,
red or purple skin rash with blistering and peeling,
pain spreading to your jaw or shoulder,
sudden numbness or weakness on one side of the body,
slurred speech,
shortness of breath,
numbness, tingling, pale or blue-colored appearance in your fingers or toes,
leg cramps,
burning, coldness, or heavy feeling in your legs,
severe headache,
blurred vision,
pounding in your neck or ears,
seizure,
swelling,
rapid weight gain,
little or no urination,
swelling of your feet or ankles,
tiredness,
loss of appetite,
stomach pain (upper right side),
tiredness,
itching,
dark urine,
clay-colored stools,
yellowing of the skin or eyes (jaundice),
pale skin,
bloody or tarry stools,
coughing up blood,
vomit that looks like coffee grounds,
sudden severe stomach pain (especially after eating),
vomiting,
constipation,
bloody diarrhea,
weight loss,
agitation,
hallucinations,
fever,
sweating,
shivering,
fast heart rate,
muscle stiffness,
twitching,
loss of coordination,
nausea,
vomiting, and
diarrhea

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Treximet include:

dizziness,
drowsiness,
weakness,
tiredness,
irregular heartbeats,
numbness or tingling in your fingers or toes,
dry mouth,
heartburn,
nausea,
feeling hot,
tight muscles, and
pain or pressure in your chest or throat

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Treximet. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is the dosage for Treximet?

Dosage In Adults

The recommended dosage for adults is 1 tablet of Treximet 85/500 mg. Treximet 85/500 mg contains a dose of sumatriptan higher than the lowest effective dose. The choice of the dose of sumatriptan, and of the use of a fixed combination such as in
Treximet 85/500 mg should be made on an individual basis, weighing the possible benefit of a higher dose of sumatriptan with the potential for a greater risk of adverse reactions.

The maximum recommended dosage in a 24-hour period is 2 tablets, taken at least 2 hours apart.
The safety of treating an average of more than 5 migraine headaches in adults in a 30-day period has not been established.
Use the lowest effective dosage for the shortest duration consistent
with individual patient treatment goals.

Dosage In Pediatric Patients 12 To 17 Years Of Age

The recommended dosage for pediatric patients 12 to 17 years of age is 1 tablet of
Treximet 10/60 mg.
The maximum recommended dosage in a 24-hour period is 1 tablet of
Treximet 85/500 mg.
The safety of treating an average of more than 2 migraine headaches in pediatric patients in a 30-day period has not been established.
Use the lowest effective dosage for the shortest duration consistent
with individual patient treatment goals.

Dosing In Patients With Hepatic Impairment

Treximet is contraindicated in patients with severe hepatic impairment.
In patients with mild to moderate hepatic impairment, the recommended
dosage in a 24-hour period is 1 tablet of Treximet 10/60 mg.
Use the lowest effective dosage for the shortest duration consistent
with individual patient treatment goals.

Administration Information

Treximet may be administered with or without food. Tablets should not be split, crushed, or chewed.

What drugs interact with Treximet?

Clinically Significant Drug Interactions With Treximet

See Table 3 for clinically significant drug interactions with NSAIDs or Sumatriptan

Table 3. Clinically Significant Drug Interactions with naproxen or sumatriptan

Ergot-Containing Drugs

Clinical Impact:
Ergot-containing drugs have been reported to cause prolonged vasospastic reactions.

Intervention:
Because these effects may be additive, coadministration of
Treximet and ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) within 24 hours of each other is contraindicated.

Monoamine Oxidase-A Inhibitors

Clinical Impact:
MAO-A inhibitors increase systemic exposure of orally administered sumatriptan by 7-fold.

Intervention:
The use of Treximet in patients receiving MAO-A inhibitors is contraindicated.

Other 5-HT Agonists

Clinical Impact:
5-HT₁ agonist drugs can cause vasospastic effects.

Intervention:
Because these effects may be additive, coadministration of
Treximet and other 5 HT₁ agonists (e.g., triptans) within 24 hours of each other is contraindicated.

Drugs That Interfere with Hemostasis

Clinical Impact:

Naproxen and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of naproxen and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone.
Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone.

Intervention:
Monitor patients with concomitant use of Treximet with
anticoagulants (e.g., warfarin), antiplatelet agents (e.g.,
aspirin), selective serotonin reuptake inhibitors (SSRIs), and
serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of
bleeding.

Aspirin

Clinical Impact:
A pharmacodynamic (PD) study has demonstrated an interaction in
which lower dose naproxen (220mg/day or 220mg twice daily)
interfered with the antiplatelet effect of low-dose
immediate-release aspirin, with the interaction most marked during
the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the PD study due to the longer washout period.
Controlled clinical studies showed that the concomitant use of
NSAIDs and analgesic doses of aspirin does not produce any greater
therapeutic effect than the use of NSAIDs alone. In a clinical
study, the concomitant use of an NSAID and aspirin was associated
with a significantly increased incidence of GI adverse reactions as
compared to use of the NSAID alone.

Intervention:
Because there may be an increased risk of cardiovascular events following discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics where appropriate.
Concomitant use of Treximet and analgesic doses of aspirin
is not generally recommended because of the increased risk of
bleeding.

Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome

Clinical Impact:
Cases of serotonin syndrome have been reported during
coadministration of triptans and SSRIs, SNRIs, TCAs, and MAO
inhibitors.

Intervention:
Discontinue Treximet if serotonin syndrome is suspected.

ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-blockers

Clinical Impact:

NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol).
In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible.

Intervention:

During concomitant use of Treximet and ACE-inhibitors, ARBs,
or beta-blockers, monitor blood pressure to ensure that the
desired blood pressure is obtained.
During concomitant use of Treximet and ACE-inhibitors or
ARBs in patients who are elderly, volume-depleted, or have
impaired renal function, monitor for signs of worsening renal
function.

Diuretics

Clinical Impact:
Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis.

Intervention:
During concomitant use of Treximet with diuretics, observe
patients for signs of worsening renal function, in addition to
assuring diuretic efficacy including antihypertensive effects.

Digoxin

Clinical Impact:
The concomitant use of naproxen with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin.

Intervention:
During concomitant use of Treximet and digoxin, monitor serum digoxin levels.

Lithium

Clinical Impact:
NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis.

Intervention:
During concomitant use of Treximet and lithium, monitor patients for signs of lithium toxicity.

Methotrexate

Clinical Impact:
Concomitant administration of some NSAIDs with high-dose methotrexate therapy has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity. Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction).

Intervention:
During concomitant use of Treximet and methotrexate, monitor patients for methotrexate toxicity.

Cyclosporine

Clinical Impact:
Concomitant use of NSAIDs and cyclosporine may increase cyclosporine's nephrotoxicity.

Intervention:
During concomitant use of Treximet and cyclosporine, monitor patients for signs of worsening renal function.

NSAIDs and Salicylates

Clinical Impact:
Concomitant use of naproxen with other NSAIDs or salicylates
(e.g., diflunisal, salsalate) increases the risk of GI toxicity,
with little or no increase in efficacy.

Intervention:
The concomitant use of naproxen with other NSAIDs or salicylates is not recommended.

Pemetrexed

Clinical Impact:
Concomitant use of NSAIDs and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information).

Intervention:

During concomitant use of Treximet and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity. NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a period of two days before, the day of, and two days following administration of pemetrexed.
In the absence of data regarding potential interaction between pemetrexed and NSAIDs with longer half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration.

Probenecid

Clinical Impact:
Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly. The clinical significance of this is unknown.

Intervention:
Reduce the frequency of administration of Treximet when given concurrently with probenecid.

Drug/Laboratory Test Interactions

Blood Tests

Naproxen may decrease platelet aggregation and prolong bleeding time. This effect should be kept in mind when bleeding times are determined.

Urine Tests

The administration of naproxen sodium may result in increased urinary values for 17-ketogenic steroids because of an interaction between the drug and/or its metabolites with m-di-nitrobenzene used in this assay.
Although 17-hydroxy-corticosteroid measurements (Porter-Silber test) do not appear to be artificially altered, it is suggested that therapy with naproxen be temporarily discontinued 72 hours before adrenal function tests are performed if the Porter-Silber test is to be used.

Naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid (5HIAA).

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Is Treximet safe to use while pregnant or breastfeeding?

Use of NSAIDs, including Treximet, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.
Because of these risks, limit dose and duration of Treximet use between about 20 and 30 weeks of gestation, and avoid
Treximet use at about 30 weeks of gestation and later in pregnancy.
Both active components of Treximet, sumatriptan and naproxen, have been reported to be secreted in human milk.
Because of the potential for serious adverse reactions in nursing infants from
Treximet, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.