DUEXIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DUEXIS (DUEXIS).
DUEXIS is a combination of ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin synthesis, and famotidine, a histamine H2-receptor antagonist that decreases gastric acid secretion. Famotidine mitigates the risk of NSAID-induced gastric ulcers.
| Metabolism | Ibuprofen is primarily metabolized by CYP2C9, with minor contributions from CYP2C8. Famotidine is metabolized via the liver with minimal first-pass effect, but specific CYP enzymes are not significantly involved; elimination is mainly renal. |
| Excretion | Ibuprofen: ~1% unchanged in urine, 14% as conjugated metabolites, remainder as oxidative metabolites; <1% excreted in feces. Famotidine: 65-70% unchanged in urine, 30-35% metabolized hepatic; <10% fecal. |
| Half-life | Ibuprofen: 2-4 hours (terminal); requires every 6-8 hour dosing. Famotidine: 2.5-3.5 hours (normal renal function); prolonged to 20 hours or more in severe renal impairment (CrCl < 30 mL/min). |
| Protein binding | Ibuprofen: >99% bound to albumin. Famotidine: 15-20% bound to plasma proteins. |
| Volume of Distribution | Ibuprofen: 0.1-0.2 L/kg. Famotidine: 1.0-1.5 L/kg. |
| Bioavailability | Ibuprofen: 80-100% oral. Famotidine: 40-50% oral. |
| Onset of Action | Pain relief: 30-60 minutes after oral administration. Antipyretic effect: 1-2 hours. |
| Duration of Action | Pain relief: 4-6 hours. Antipyretic: 6-8 hours. Acid suppression with famotidine: up to 12 hours. |
| Molecular Weight | Ibuprofen: 206.28 Da; Famotidine: 337.46 Da. Combined drug product: note separate molecular weights. |
One tablet (800 mg ibuprofen/26.6 mg famotidine) orally three times daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in patients with CrCl <30 mL/min. For CrCl 30-60 mL/min: maximum dose one tablet twice daily. |
| Liver impairment | No specific adjustment recommended, but caution in severe hepatic impairment (Child-Pugh C) due to potential hepatotoxicity. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | Use lowest effective dose; consider increased risk of gastrointestinal bleeding and renal impairment; monitor renal function. |
| 1st trimester | Avoid; risk of miscarriage and cardiac defects (first trimester use of NSAIDs is associated with increased risk of miscarriage and congenital malformations, particularly cardiac defects). Also, NSAIDs may interfere with implantation. |
| 2nd trimester | Use only if clearly needed; risk of oligohydramnios and fetal renal dysfunction (NSAIDs can cause premature closure of the ductus arteriosus and oligohydramnios due to fetal renal effects). |
| 3rd trimester | Contraindicated; risk of premature closure of ductus arteriosus and persistent pulmonary hypertension of the newborn. Use is contraindicated during third trimester. |
Clinical note
Comprehensive clinical and safety monograph for DUEXIS (DUEXIS).
| Placental transfer | Both ibuprofen and famotidine cross the placenta. Ibuprofen: known to cross placenta, fetal serum concentrations reach up to 10% of maternal levels. Famotidine: crosses placenta, achieving cord blood concentrations similar to maternal plasma. |
| Breastfeeding |
■ FDA Black Box Warning
NSAIDs increase the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use and in patients with cardiovascular risk factors. DUEXIS is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery. NSAIDs also cause an increased risk of serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal.
| Serious Effects |
History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsActive peptic ulcer disease or gastrointestinal bleedingKnown hypersensitivity to ibuprofen, famotidine, or any component of the productThird trimester of pregnancySevere heart failure (NYHA class III-IV)Coronary artery bypass graft (CABG) surgery perioperative painSevere renal impairment (CrCl <30 mL/min)
| Precautions | Cardiovascular thrombotic events; gastrointestinal bleeding, ulceration, and perforation; hypertension; congestive heart failure; renal toxicity; anaphylactic reactions; skin reactions (e.g., Stevens-Johnson syndrome); hematologic effects (e.g., thrombocytopenia); interaction with aspirin; masking of fever and inflammation; pregnancy risk (avoid in third trimester); renal papillary necrosis. |
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| DUEXIS contains ibuprofen and famotidine. Ibuprofen is excreted into breast milk in very low amounts and is considered compatible with breastfeeding. Famotidine is also excreted into breast milk but in low concentrations; it is generally considered safe. Monitor infant for gastrointestinal effects. |
| Lactation Rating | L2 (Safer) for both components according to LactMed; generally considered compatible. |
| Teratogenic Risk | DUEXIS (ibuprofen/famotidine) contains ibuprofen, an NSAID. Avoid during third trimester due to risk of premature closure of ductus arteriosus and oligohydramnios. First and second trimester use associated with increased risk of cardiac defects and gastroschisis; use only if clearly needed. |
| Fetal Monitoring | Monitor amniotic fluid volume via ultrasound if used in third trimester; fetal echocardiography for ductal patency if prolonged use after 30 weeks gestation; maternal renal function and blood pressure. |
| Fertility Effects | Ibuprofen may impair female fertility by inhibition of prostaglandin synthesis, potentially delaying ovulation or causing reversible infertility. Discontinue in women attempting to conceive if fertility issues. |
| Food/Dietary | No specific food interactions. However, taking with food or milk may reduce GI upset. Avoid alcohol as it may increase risk of GI bleeding. |
| Clinical Pearls | DUEXIS is a fixed-dose combination of ibuprofen (NSAID) and famotidine (H2RA) designed to reduce the risk of NSAID-associated gastric ulcers. The famotidine component does not provide adequate protection against duodenal ulcers. Not interchangeable with separate ibuprofen and famotidine due to differing pharmacokinetics. Contraindicated in patients with history of aspirin-exacerbated respiratory disease, peripartum pain (risk of premature ductus arteriosus closure), and severe renal impairment. Advise patients to avoid concurrent use of other NSAIDs including OTC ibuprofen. |
| Patient Advice | Take with food or milk to reduce stomach upset. · Avoid taking other NSAIDs (e.g., aspirin, naproxen) or famotidine-containing products unless directed by your doctor. · Report signs of gastrointestinal bleeding: black/tarry stools, coffee-ground vomit, abdominal pain. · Can cause drowsiness or dizziness; avoid driving until you know how it affects you. · Do not use if you are pregnant or planning to become pregnant due to risk of fetal harm. · Store at room temperature away from moisture and heat. |