Duexis for Rheumatoid Arthritis & Osteoarthritis: Drug Warnings

Generic drug: ibuprofen and famotidine

Brand name: Duexis

What is Duexis (ibuprofen and famotidine), and how does it work?

Duexis (ibuprofen and famotidine) is a prescription medicine used to treat the symptoms of Rheumatoid Arthritis and Osteoarthritis. Duexis may be used alone or with other medications.

Duexis belongs to a class of drugs called NSAIDs.

It is not known if Duexis is safe and effective in children.

What are the side effects of Duexis?

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.
Duexis 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.

Duexis may cause serious side effects including:

sneezing,
runny or stuffy nose,
wheezing,
trouble breathing,
swelling in your face or throat,
fever,
sore throat,
burning eyes,
skin pain,
red or purple skin rash with blistering and peeling,
chest pain spreading to your jaw or shoulder,
sudden numbness or weakness on one side of the body,
slurred speech,
leg swelling,
shortness of breath,
changes in your vision,
first sign of any skin rash (no matter how mild),
headache,
neck stiffness,
increased sensitivity to light,
nausea,
vomiting,
confusion,
drowsiness,
severe headache,
blurred vision,
pounding in your neck or ears,
little or no urination,
swelling,
rapid weight gain,
loss of appetite,
stomach pain (upper right side),
tiredness,
itching,
dark urine,
clay-colored stools,
yellowing of the skin or eyes (jaundice),
pale skin,
unusual tiredness,
lightheadedness,
cold hands and feet,
bloody or tarry stools, and
coughing up blood or vomit that looks like coffee grounds

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

The most common side effects of Duexis include:

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 Duexis. 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 Duexis?

Carefully consider the potential benefits and risks of Duexis and other
treatment options before deciding to use Duexis. Use ibuprofen at the lowest
effective dosage for the shortest duration consistent with individual
patient treatment goals.
The recommended daily dose of Duexis (ibuprofen and
famotidine) 800 mg/26.6 mg is a single tablet administered orally three times
per day.
Duexis tablets should be swallowed whole, and should not
be cut to supply a lower dose. Do not chew, divide, or crush tablets.
Patients should be instructed that if a dose is missed,
it should be taken as soon possible. However, if the next scheduled dose is
due, the patient should not take the missed dose, and should be instructed to
take the next dose on time. Patients should be instructed not to take 2 doses
at one time to make up for a missed dose.
Do not substitute Duexis with the single-ingredient
products of ibuprofen and famotidine.

What drugs interact with Duexis?

See Table 3 for clinically significant drug interactions
with ibuprofen.

Table 3: Clinically Significant Drug Interactions with
Ibuprofen and Famotidine

Drugs That Interfere with Hemostasis

Clinical Impact:

Ibuprofen and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of ibuprofen 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 Duexis 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:
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:
Concomitant use of Duexis and analgesic doses of aspirin is not
generally recommended because of the increased risk of bleeding. Duexis is not a substitute for low dose aspirin for cardiovascular protection.

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 Duexis and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained.
During concomitant use of Duexis 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 Duexis 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 ibuprofen with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin.

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

Lithium

Clinical Impact:
NSAIDs have produced elevations of 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 Duexis and lithium, monitor patients for signs of lithium toxicity.

Methotrexate

Clinical Impact:
Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction).

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

Cyclosporine

Clinical Impact:
Concomitant use of ibuprofen and cyclosporine may increase cyclosporine’s nephrotoxicity.

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

NSAIDs and Salicylates

Clinical Impact:
Concomitant use of ibuprofen 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 Duexis with other NSAIDs or salicylates is not recommended.

Pemetrexed

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

Intervention:

During concomitant use of Duexis 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 permetrexed 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.

Drugs Dependent on Gastric pH for Absorption

Clinical Impact
Because famotidine lowers intra-gastric acidity, this may result in reduced absorption and loss of efficacy of concomitant drugs.

Intervention
Concomitant administration of Duexis is not recommended with dasatinib, delavirdine mesylate, cefditoren, and fosamprenavir.
For administration instructions of other drugs whose absorption is dependent on gastric pH, refer to their prescribing information (e.g., atazanavir, erlotinib, ketoconazole, itraconazole, nilotinib, ledipasvir/sofosbuvir, and rilpivirine).

Tizanidine (CYP1A2 Substrate)

Clinical Impact
Famotidine is considered a weak CYP1A2 inhibitor and may lead to substantial increases in blood concentrations of tizanidine, a CYP1A2 substrate.

Intervention
Avoid concomitant use with Duexis.
If concomitant use is necessary, monitor for hypotension, bradycardia or excessive drowsiness.
Refer to the full prescribing information for tizanidine.

QUESTION

The term arthritis refers to stiffness in the joints.
See Answer

Is Duexis safe to use while pregnant or breastfeeding?

Use of NSAIDs, including Duexis, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus.
Avoid use of NSAIDs, including Duexis, in pregnant women starting at 30 weeks of gestation (third trimester).
There are no adequate and well-controlled studies of Duexis in pregnant women.
No studies have been conducted with the use of Duexis in lactating women.
Limited data from published literature report famotidine is present in human milk in low amounts.
Published literature also reports the presence of ibuprofen in human milk in low amounts. No information is available on the effects of famotidine or ibuprofen on milk production or on a breastfed infant.