ARTHROTEC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ARTHROTEC (ARTHROTEC).
Arthrotec is a combination of diclofenac, a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin synthesis, and misoprostol, a synthetic prostaglandin E1 analog that protects the gastric mucosa by increasing mucus and bicarbonate secretion, enhancing mucosal blood flow, and promoting epithelial repair.
| Metabolism | Diclofenac is primarily metabolized by CYP2C9 (major) and CYP3A4 (minor) via hydroxylation and glucuronidation, followed by renal excretion. Misoprostol is rapidly de-esterified to misoprostol acid, the active metabolite, which undergoes further oxidation and glucuronidation, with renal excretion. |
| Excretion | Renal: ~95% as metabolites (diclofenac: ~65% as glucuronide conjugates; misoprostol: ~80% as inactive metabolites). Biliary/fecal: <5%. |
| Half-life | Diclofenac: ~2 hours (range 1-4 h); misoprostol: 20-40 minutes (acid metabolite 1.5 h). No accumulation with repeated dosing. |
| Protein binding | Diclofenac: >99.5% (primarily albumin); misoprostol: 80-90% (albumin). |
| Volume of Distribution | Diclofenac: 0.17-0.55 L/kg (widely distributed, crosses placenta); misoprostol: not well characterized (estimated 2-3 L/kg). |
| Bioavailability | Diclofenac: ~50% (oral, immediate-release); misoprostol: 70-80% (oral, extensively metabolized). |
| Onset of Action | Oral: diclofenac analgesia within 1 h; misoprostol cytoprotection within 30 min. |
| Duration of Action | Diclofenac: 6-8 h (immediate-release); misoprostol: 3-6 h (gastric protection lasts up to 6 h). |
One tablet (diclofenac 50 mg / misoprostol 200 mcg) orally twice daily with food.
| Dosage form | TABLET, DELAYED RELEASE |
| Renal impairment | GFR 30-59 mL/min: no adjustment; GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh class A: no adjustment; class B or C: use with caution, consider dose reduction of diclofenac; not recommended in severe hepatic impairment. |
| Pediatric use | Not recommended for pediatric patients; safety and efficacy not established. |
| Geriatric use | Initiate at lowest effective dose; monitor renal function and gastrointestinal bleeding risk; start with one tablet daily if required. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ARTHROTEC (ARTHROTEC).
| Breastfeeding | Diclofenac is excreted into breast milk in low amounts (M/P ratio ~0.017 for diclofenac; misoprostol's active metabolite M/P ratio unknown). Misoprostol may cause diarrhea in infants. Use not recommended due to potential adverse effects in nursing infants. |
| Teratogenic Risk | ARTHROTEC contains diclofenac (NSAID) and misoprostol. Misoprostol is a known abortifacient and teratogen. First trimester: Risk of Möbius syndrome, cranial nerve palsy, and limb defects. Second/third trimester: Misoprostol can cause uterine rupture, premature labor, and fetal death. NSAIDs may cause premature ductus arteriosus closure and oligohydramnios. Pregnancy category X - contraindicated in pregnancy. |
■ FDA Black Box Warning
NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. Arthrotec is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery. 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.
| Serious Effects |
["Known hypersensitivity to diclofenac, misoprostol, or other NSAIDs","History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs","Setting of CABG surgery","Pregnancy (misoprostol is contraindicated due to abortifacient properties)","Active gastrointestinal bleeding or peptic ulcer disease","Advanced renal disease (unless dialysis is ongoing)"]
| Precautions | ["Cardiovascular: increased risk of thromboembolic events, myocardial infarction, and stroke; avoid in patients with recent CABG.","Gastrointestinal: serious GI adverse events including bleeding, ulceration, and perforation; use with caution in patients at risk.","Renal: may cause renal toxicity; avoid in patients with advanced renal disease.","Hepatic: may cause elevations in liver enzymes and liver injury; monitor LFTs.","Fetal toxicity: misoprostol can induce labor and cause fetal harm; contraindicated in pregnancy.","Hypertension: can worsen or induce hypertension.","Anaphylactoid reactions: may occur; avoid in patients with aspirin allergy.","Hematologic: may cause anemia; monitor hemoglobin."] |
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| Fetal Monitoring | If exposure occurs, monitor for uterine contractions, fetal heart rate, amniotic fluid index (oligohydramnios), and ductus arteriosus patency (fetal echocardiography after 32 weeks). Assess for maternal gastrointestinal bleeding or uterine hyperstimulation. |
| Fertility Effects | NSAIDs may impair female fertility by inhibiting prostaglandin synthesis, affecting ovulation and implantation. Misoprostol can cause uterine contractions and cervical softening, potentially interfering with implantation. Reversible upon discontinuation. |
| Food/Dietary | Take with food or milk to minimize gastrointestinal irritation. Avoid alcohol as it increases risk of GI bleeding. |
| Clinical Pearls | ARTHROTEC is a fixed-dose combination of diclofenac (NSAID) and misoprostol (PGE1 analog) indicated for osteoarthritis and rheumatoid arthritis in patients at high risk for NSAID-induced gastric ulcers. Misoprostol reduces gastric acid secretion and increases mucus and bicarbonate production, but can cause diarrhea, abdominal cramps, and uterine contractions. Contraindicated in pregnancy due to abortifacient properties. Use lowest effective dose; monitor renal function, blood pressure, and signs of GI bleeding. |
| Patient Advice | Take with food to reduce GI upset. · Avoid alcohol and other NSAIDs (e.g., ibuprofen, naproxen) while taking this medication. · Inform all healthcare providers you are taking Arthrotec. · Do not use if pregnant or planning pregnancy; misoprostol can cause miscarriage. Use effective contraception. · Report black/tarry stools, severe abdominal pain, vomiting blood, or chest pain immediately. · This medication can cause diarrhea, especially at start of therapy; stay hydrated. |