A fixed-dose combination (FDC) analgesic and anti-inflammatory agent (Naproxen) with a prokinetic antiemetic (Domperidone). Naproxen is a non-steroidal anti-inflammatory drug (NSAID) of the propionic acid class, providing potent anti-inflammatory, analgesic, and antipyretic effects. Domperidone is a dopamine D2 and D3 receptor antagonist, acting as a peripheral antiemetic and gastroprokinetic agent. This combination is primarily used for conditions where pain/inflammation is accompanied by nausea or delayed gastric emptying, such as migraine, dysmenorrhea, and musculoskeletal pain. The FDC was banned in India in 2013 due to safety concerns regarding irrational combinations and potential cardiac risks from domperidone, but it was subsequently revoked for certain combinations. Prescribers must exercise caution and adhere to strict indications.
Adult: One tablet (Naproxen 500mg + Domperidone 10mg) twice daily, preferably with food. The dose should be the lowest effective for the shortest possible duration. For migraine, use at onset of attack.
Note: Take with a full glass of water, with food or milk to minimize gastric irritation. Do not crush or chew. Swallow whole. Do not lie down for at least 10 minutes after taking the tablet. Maintain adequate fluid intake. Do not take for more than 10 days for pain or 3 days for fever unless directed by a physician.
Naproxen exerts its effects by non-selectively inhibiting both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. This inhibition reduces the synthesis of prostaglandins (PGs) and thromboxanes from arachidonic acid. The reduction in prostaglandins (particularly PGE2) at the site of injury mediates its anti-inflammatory, analgesic, and antipyretic effects. Domperidone acts as a selective peripheral dopamine D2 and D3 receptor antagonist. It blocks these receptors in the chemoreceptor trigger zone (CTZ) outside the blood-brain barrier, exerting an antiemetic effect. It also blocks dopamine receptors in the upper gastrointestinal tract, leading to increased lower esophageal sphincter pressure, enhanced gastric peristalsis, and improved gastroduodenal coordination, which accelerates gastric emptying.
Pregnancy: Pregnancy Category C (first and second trimester) for Naproxen. Category not assigned for Domperidone. Avoid in third trimester (Category D for NSAIDs) due to risk of premature closure of ductus arteriosus, oligohydramnios, and prolonged labor. Domperidone is excreted in animal milk; human data limited. Use only if potential benefit justifies potential fetal risk. Preferably avoid.
Driving: May cause dizziness, drowsiness, or blurred vision. Patients should not drive or operate machinery if they experience these effects.
| Anticoagulants (Warfarin, Acenocoumarol) | Increased risk of bleeding due to platelet inhibition and potential displacement from protein binding by Naproxen. | Major |
| Anti-platelets (Aspirin, Clopidogrel) | Additive risk of GI bleeding. | Major |
| Other NSAIDs (including COX-2 inhibitors) or corticosteroids (Prednisolone) | Increased risk of GI ulceration/bleeding and nephrotoxicity. | Major |
| ACE Inhibitors (Ramipril, Enalapril), ARBs (Losartan), Diuretics (Furosemide) | Reduced antihypertensive efficacy; increased risk of renal impairment due to Naproxen inhibiting prostaglandin-mediated renal blood flow. | Major |
| Lithium | Naproxen can decrease renal clearance of Lithium, leading to toxicity. | Major |
| Methotrexate | Naproxen may reduce renal clearance of Methotrexate, increasing risk of bone marrow suppression and GI toxicity. | Major |
| SSRIs (Fluoxetine, Sertraline) | Increased risk of upper GI bleeding. | Moderate |
| Potent CYP3A4 Inhibitors (Ketoconazole, Fluconazole, Clarithromycin, Ritonavir) | Markedly increase Domperidone plasma levels, significantly raising the risk of QTc prolongation and cardiac arrhythmias. CONTRAINDICATED. | Major |
| Anticholinergics (Dicyclomine, Atropine) | May antagonize the gastroprokinetic effect of Domperidone. | Moderate |
| Dopaminergic agents (Levodopa, Bromocriptine) | Domperidone may antagonize their peripheral effects (e.g., on GI motility). | Moderate |
| QT-prolonging drugs (Amiodarone, Sotalol, Fluoroquinolones, Tricyclic Antidepressants) | Additive risk of QTc prolongation and arrhythmias with Domperidone. | Major |
Same composition (Naproxen (500mg) + Domperidone (10mg)), different brands: