SYMBRAVO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SYMBRAVO (SYMBRAVO).
Symbravo is a combination of ibuprofen (a nonsteroidal anti-inflammatory drug) and famotidine (a histamine H2-receptor antagonist). Ibuprofen inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis, which mediates inflammation, pain, and fever. Famotidine reduces gastric acid secretion by blocking histamine H2 receptors, mitigating NSAID-induced gastrointestinal injury.
| Metabolism | Ibuprofen is primarily metabolized via hepatic cytochrome P450 (CYP) 2C9 and CYP2C8 to inactive hydroxylated metabolites. Famotidine undergoes minimal hepatic metabolism, with approximately 70% excreted unchanged in the urine. |
| Excretion | Urine (primarily as metabolites; <5% unchanged for formoterol, ~10% for budesonide), feces (biliary elimination of metabolites, ~60-70% for budesonide). |
| Half-life | Budesonide: 2-4 hours (terminal). Formoterol: 10 hours (terminal). Clinical context: Twice-daily dosing for asthma maintenance. |
| Protein binding | Budesonide: 85-90% (albumin). Formoterol: 61-64% (albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Budesonide: 3-4 L/kg (extensive tissue distribution). Formoterol: 4-5 L/kg (wide distribution). |
| Bioavailability | Inhalation: Budesonide ~39% (lung deposition), Formoterol ~46% (lung deposition). Oral bioavailability <10% for both. |
| Onset of Action | Inhalation: Budesonide 1-2 weeks for clinical effect; Formoterol 1-3 minutes for bronchodilation. |
| Duration of Action | Budesonide: 12-24 hours (anti-inflammatory). Formoterol: 12 hours (bronchodilation). Clinical note: Twice-daily dosing. |
1 capsule (6 mg vortioxetine / 10 mg bupropion) or (6 mg vortioxetine / 15 mg bupropion) or (12 mg vortioxetine / 15 mg bupropion) or (18 mg vortioxetine / 15 mg bupropion) orally once daily, with or without food. Titrate based on efficacy and tolerability.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh C). Use with caution in moderate impairment (Child-Pugh B); maximum recommended dose is 6 mg vortioxetine / 15 mg bupropion once daily. No dose adjustment needed for mild impairment (Child-Pugh A). |
| Pediatric use | Safety and efficacy have not been established in pediatric patients (<18 years). Not recommended. |
| Geriatric use | No specific dose adjustment recommended for elderly patients (≥65 years) based on pharmacokinetic data. However, clinical experience is limited, and doses should be titrated with caution due to increased sensitivity and potential for comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SYMBRAVO (SYMBRAVO).
| Breastfeeding | Olmesartan is excreted in rat milk but human data are lacking; amlodipine is excreted in human milk with an estimated infant dose of ~1% of maternal weight-adjusted dose; hydrochlorothiazide is excreted in breast milk with milk-to-plasma ratio approximately 1.0. Due to potential for adverse effects on the nursing infant (e.g., electrolyte disturbances, hypotension), use during breastfeeding is not recommended. Consider alternative antihypertensive therapy. |
| Teratogenic Risk | SYMBRAVO (olmesartan/amlodipine/hydrochlorothiazide) is contraindicated in pregnancy. Drugs acting directly on the renin-angiotensin system can cause fetal renal dysfunction, oligohydramnios, and skull ossification defects when used in the second and third trimesters. First trimester exposure is associated with a low but measurable risk of teratogenicity, primarily cardiovascular and central nervous system malformations. Hydrochlorothiazide can cause electrolyte disturbances and neonatal thrombocytopenia. |
■ FDA Black Box Warning
NSAIDs increase the 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. Symbravo is contraindicated for treatment of perioperative pain in coronary artery bypass graft (CABG) surgery.
| Serious Effects |
["Hypersensitivity to ibuprofen, famotidine, or any component of the formulation","History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs","Perioperative pain in the setting of coronary artery bypass graft (CABG) surgery","Advanced renal disease","History of GI bleeding or perforation related to previous NSAID therapy","Active peptic ulcer disease or GI bleeding"]
| Precautions | ["Cardiovascular risk: Increased risk of serious thrombotic events, myocardial infarction, stroke; caution in patients with cardiovascular disease or risk factors","Gastrointestinal risk: NSAIDs increase risk of serious GI adverse events including bleeding, ulceration, and perforation; famotidine reduces but does not eliminate risk","Renal effects: Dose-dependent reduction in renal blood flow, risk of acute renal failure in patients with impaired renal function","Hepatic effects: Elevations of liver enzymes, rare cases of severe hepatic reactions","Anaphylactoid reactions: Can occur without prior exposure","Hypertension: May aggravate hypertension or lead to new-onset hypertension","Heart failure: Can precipitate fluid retention and decompensation"] |
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| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN), electrolytes (especially potassium and sodium), and fetal growth (ultrasound). If inadvertent exposure occurs after the first trimester, perform serial ultrasound assessments for oligohydramnios and fetal renal function. Consider monitoring fetal heart rate. Assess for neonatal hypotension, hyperkalemia, and renal dysfunction postpartum. |
| Fertility Effects | ACE inhibitors and angiotensin receptor blockers have been associated with reduced fertility in animal studies. In humans, no specific data on SYMBRAVO; however, antihypertensive therapy in general may affect erectile function or libido in males. No known direct effect on female fertility. |