ALEVE-D SINUS & COLD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALEVE-D SINUS & COLD (ALEVE-D SINUS & COLD).
Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2), reducing prostaglandin synthesis. Pseudoephedrine is a sympathomimetic amine that acts as a decongestant via alpha-adrenergic receptor agonism in the nasal mucosa.
| Metabolism | Naproxen is primarily metabolized by CYP2C9 and to a lesser extent by CYP1A2. Pseudoephedrine is partially metabolized by CYP450 enzymes (likely CYP2D6) and is primarily excreted unchanged in urine. |
| Excretion | Renal elimination: naproxen ~95% (mostly as unconjugated naproxen and 6-O-desmethyl naproxen), pseudoephedrine ~70-90% unchanged. Biliary/fecal: minor (<5% for each). |
| Half-life | Naproxen: 12-17 hours (clinical: twice daily dosing); pseudoephedrine: 4-6 hours (clinical: every 4-6 hours). |
| Protein binding | Naproxen: >99% bound to albumin; pseudoephedrine: negligible binding (<20%). |
| Volume of Distribution | Naproxen: 0.16 L/kg (low, indicates plasma/tissue distribution); pseudoephedrine: 2.6-3.3 L/kg (extensive tissue distribution). |
| Bioavailability | Naproxen: oral ~95%; pseudoephedrine: oral ~100%. |
| Onset of Action | Naproxen: oral 1-2 hours; pseudoephedrine: oral 30 minutes. |
| Duration of Action | Naproxen: 8-12 hours; pseudoephedrine: 4-6 hours. |
| Molecular Weight | Naproxen: 230.26 Da; Pseudoephedrine: 165.23 Da |
Naproxen 220 mg (as naproxen sodium) and pseudoephedrine HCl 120 mg orally every 12 hours; maximum 2 doses per 24 hours.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 30-59 mL/min: not recommended; GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B or C: contraindicated due to naproxen component. |
| Pediatric use | Not recommended for children under 12 years of age. For ages 12-17: same as adult dose (naproxen 220 mg/pseudoephedrine 120 mg) every 12 hours, maximum 2 doses in 24 hours. |
| Geriatric use | Avoid use in elderly due to increased risk of gastrointestinal bleeding, renal impairment, and cardiovascular events; use lowest effective dose for shortest duration if necessary, with monitoring. |
| 1st trimester | Avoid. Naproxen and pseudoephedrine are generally contraindicated in the first trimester due to potential teratogenicity and risk of spontaneous abortion. Naproxen may be associated with cardiovascular malformations and pseudoephedrine may increase risk of gastroschisis. |
| 2nd trimester | Avoid. Naproxen is contraindicated in the second trimester due to risk of premature closure of the ductus arteriosus and oligohydramnios. Pseudoephedrine may cause uterine vasoconstriction and reduced placental perfusion. |
| 3rd trimester | Contraindicated. Naproxen crosses placenta and may cause premature closure of the ductus arteriosus, oligohydramnios, and neonatal renal impairment. Pseudoephedrine may lead to fetal tachycardia and hypertension. |
Clinical note
Comprehensive clinical and safety monograph for ALEVE-D SINUS & COLD (ALEVE-D SINUS & COLD).
| Placental transfer | Naproxen: Crosses placenta (>50% of maternal serum concentration at term). Pseudoephedrine: Crosses placenta; fetal/maternal ratio approximately 0.7. |
| Breastfeeding |
■ FDA Black Box Warning
Naproxen carries a black box warning for increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Risk increases with duration of use and in patients with cardiovascular risk factors. Also, naproxen is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Serious Effects |
Hypersensitivity to naproxen, pseudoephedrine, or any componentHistory of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDsPerioperative pain in the setting of coronary artery bypass graft (CABG) surgeryActive peptic ulcer disease or gastrointestinal bleedingSevere renal impairment (CrCl < 30 mL/min)Severe hepatic impairmentSevere uncontrolled hypertensionCoronary artery diseaseConcurrent use of MAOIs or within 14 days of MAOI therapyNarrow-angle glaucomaUrinary retentionHyperthyroidismPheochromocytoma
| Precautions | Cardiovascular risk (increased risk of thrombosis, MI, stroke, hypertension exacerbation), gastrointestinal risk (bleeding, ulceration, perforation), renal toxicity, hepatic effects, anaphylactoid reactions, asthma exacerbation, and use in pregnancy (avoid in third trimester). |
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| Naproxen is excreted into breast milk in low concentrations, but its long half-life and potential for adverse effects in neonates (e.g., gastrointestinal bleeding, renal impairment) warrant caution. Pseudoephedrine is excreted into breast milk and may cause irritability and sleep disturbances in infants. The American Academy of Pediatrics considers pseudoephedrine compatible with breastfeeding, but the combination with naproxen is not recommended due to lack of safety data. |
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | First trimester: NSAIDs (naproxen) associated with increased risk of cardiac defects and gastroschisis; pseudoephedrine may be associated with gastroschisis and small intestinal atresia. Second trimester: NSAIDs risk of fetal renal impairment and oligohydramnios; pseudoephedrine may cause fetal tachycardia. Third trimester: NSAIDs risk of premature closure of ductus arteriosus, pulmonary hypertension, oligohydramnios, and fetal/neonatal renal dysfunction; pseudoephedrine may cause neonatal irritability and tachycardia. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and signs of fluid retention. Fetal monitoring includes ultrasound for oligohydramnios, ductus arteriosus assessment (Doppler echocardiography) in third trimester, and fetal growth scans. |
| Fertility Effects | NSAIDs (naproxen) may impair female fertility by inhibiting prostaglandin synthesis affecting ovulation; effect is reversible upon discontinuation. Pseudoephedrine has no known significant effect on fertility. |
| Food/Dietary |
| Avoid high-tyramine foods (aged cheeses, cured meats, fermented products) due to risk of hypertensive crisis with pseudoephedrine. Take naproxen with food or milk to reduce GI upset. Avoid excessive caffeine. |
| Clinical Pearls | Aleve-D Sinus & Cold contains naproxen 220 mg (NSAID) and pseudoephedrine 120 mg (sympathomimetic). Avoid in patients with uncontrolled hypertension, CAD, or MAOI use within 14 days. Naproxen increases bleeding risk; caution with anticoagulants. Pseudoephedrine can cause urinary retention in BPH. Limit caffeine intake to reduce additive CNS stimulation. |
| Patient Advice | Do not take with other products containing NSAIDs or pseudoephedrine. · Avoid alcohol to reduce risk of GI bleeding. · Use with caution if you have high blood pressure, heart disease, or glaucoma. · Do not use for more than 7 days for cold symptoms. · Discontinue and seek medical attention if symptoms worsen or new symptoms occur. |