Arthrofen 50 Tablet

Arthrofen 50 Tablet is used for: Rheumatoid arthritis, Osteoarthritis, Joint and muscular pains

Oral Osteoarthritis 50 mg/200 mcg, 75mg/200mcg: 1 tab PO three times daily; not to exceed 200 mcg misoprostol/dose or 800 mcg/day A dosage of diclofenac higher than 150 mg/day is not recommended. Rheumatoid Arthritis 50 mg/200 mcg, 75mg/200mcg: 1 tab PO three or four times daily; not to exceed 200 mcg misoprostol/dose or 800 mcg/day A dosage of diclofenac higher than 200 mg/day is not recommended. If not tolerated may reduce frequency to twice daily Three times daily dose of misoprostol is more protective than when given twice daily

Safety & efficacy not established

RENAL IMPAIRMENT Avoid if possible or use with caution. Avoid in severe impairment. Dose adjustments The lowest effective dose should be used for the shortest possible duration. Monitoring In renal impairment monitor renal function; sodium and water retention may occur and renal function may deteriorate, possibly leading to renal failure. Diclofenac and misoprostol are primarily excreted by the kidneys. Long-term administration of NSAIDs has resulted in renal toxicity. Correct volume status in dehydrated or hypovolemic patients prior to initiating Diclofenac and misoprostol. Monitor renal function, especially during concomitant use of ACE inhibitors or ARBs. Also, monitor renal function in patients with hepatic impairment. Avoid the use of Diclofenac and misoprostol in patients with advanced renal disease. If use cannot be avoided in patients with advanced renal disease, use the lowest dosage for the shortest duration, monitor the patient’s renal function and monitor for clinical signs of worsening renal function

Swallow tablet whole, do not chew or crush Do not take with antacids

Known hypersensitivity to diclofenac sodium, misoprostol, or any components of the drug product Pregnancy In the setting of CABG surgery Active gastrointestinal bleeding History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs

Administration of misoprostol, a component of Diclofenac Sodium + Misoprostol, to pregnant women can cause uterine rupture, abortion, premature birth, or birth defects. Uterine rupture has occurred when misoprostol was administered in pregnant women to induce labor or an abortion. Diclofenac Sodium + Misoprostol is contraindicated in pregnancy and is not recommended in women of childbearing potential. Patients must be advised of the abortifacient property and warned not to give the drug to others. Increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. Diclofenac Sodium + Misoprostol is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal and can occur at any time and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk. Embryo-Fetal Toxicity with NSAIDs: Use of NSAIDs, including diclofenac in women at about 20 weeks gestation and later in pregnancy may cause oligohydramnios/fetal renal dysfunction and premature closure of the fetal ductus arteriosus. Hepatotoxicity: Inform patients of warning signs and symptoms of hepatotoxicity. Discontinue if abnormal liver tests persist or worsen or if clinical signs and symptoms of liver disease develop. Hypertension: Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure. Heart Failure and Edema: Avoid in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure. Renal Toxicity: Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia. Avoid in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function. Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs. Exacerbation of Asthma Related to Aspirin Sensitivity: Contraindicated in patients with aspirin-sensitive asthma. Monitor patients with preexisting asthma (without aspirin sensitivity). Serious Skin Reactions: Discontinue at first appearance of skin rash or other signs of hypersensitivity. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Discontinue and evaluate clinically. Hematologic Toxicity: Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia.

Pregnancy Not recommended in women of childbearing potential; if prescribed, patient must be advised of abortifacient property and warned not to give drug to others; advise females to inform their healthcare provider of a known or suspected pregnancy Drug combination is contraindicated in pregnant women; there are no adequate and well-controlled studies in pregnant women; however, there is information available about the active drug components diclofenac sodium and misoprostol Administration of misoprostol to pregnant women can cause abortion, premature birth, birth defects or uterine rupture; congenital anomalies sometimes associated with fetal death have been reported subsequent to unsuccessful use of misoprostol as an abortifacient, but the drug’s teratogenic mechanism has not been demonstrated Use of NSAIDS, including diclofenac can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment There are clinical considerations when misoprostol and diclofenac are used in pregnant women In reproduction studies with pregnant rabbits, there were no skeletal or visceral malformations when the combination of diclofenac sodium and misoprostol was administered during organogenesis at doses less than the maximum recommended human doses (MRHD); however, embryotoxicity was observed at this exposure Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization In animal studies, administration of prostaglandin synthesis inhibitors such as diclofenac, resulted in increased pre-and post-implantation loss; if a woman becomes pregnant while taking drug combination, discontinue drug and advise the woman of the potential risks to her and to a fetus Maternal adverse reactions Misoprostol may produce uterine contractions, uterine bleeding, and expulsion of the products of conception; misoprostol has been used to ripen the cervix, to induce labor, and to treat postpartum hemorrhage, outside of its approved indication A major adverse effect of these uses is hyperstimulation of the uterus; uterine rupture, amniotic fluid embolism, severe bleeding, shock, and maternal death have been reported when misoprostol was administered to pregnant women to induce labor to induce abortion beyond the eighth weeks of pregnancy Higher doses of misoprostol, including the 100 mcg tablet, may increase the risk of complications from uterine hyperstimulation; the drug combination, which contains 200 mcg of misoprostol, is likely to have a greater risk of uterine hyperstimulation than the 100 mcg tablet of misoprostol Abortions caused by misoprostol may be incomplete; cases of amniotic fluid embolism, which resulted in maternal and fetal death, have been reported with use of misoprostol during pregnancy Severe vaginal bleeding, retained placenta, shock, and pelvic pain have also been reported; these women were administered misoprostol vaginally and/or orally over a range of doses; if a woman is or becomes pregnant while taking this drug, the drug should be discontinued and the patient apprised of the potential hazard to the fetus Drug combination is contraindicated in pregnant women Fetal toxicity Misoprostol may endanger pregnancy (may cause abortion) and thereby cause harm to the fetus when administered to a pregnant woman; use of misoprostol for the induction of labor in the third trimester was associated with uterine hyperstimulation with resulting changes in the fetal heart rate (fetal bradycardia) and fetal death (misoprostol is not approved for this use) NSAIDs can cause premature closure of the fetal ductus arteriosus at about 30 weeks gestation and later in pregnancy and at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue treatment and follow up according to clinical practice Labor or delivery There are no studies on the effects of drug combination or diclofenac during labor or delivery; in animal studies, NSAIDS, including diclofenac, are known to inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth; In humans, some case reports and studies have associated misoprostol with risk of stillbirth, uterine hyperstimulation, perineal tear, amniotic fluid embolism, severe bleeding, shock, uterine rupture and death The risk of uterine rupture associated with misoprostol use in pregnancy may occur at any gestational age, and increases with advancing gestational ages and with prior uterine surgery, including cesarean delivery; grand multiparity also appears to be a risk factor for uterine rupture Infertility Based on mechanism of action, NSAIDs, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women Animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation; small studies in women have also shown a reversible delay in ovulation in women treated with NSAIDs; consider withdrawal of NSAIDs, in women who have difficulties conceiving or who are undergoing investigation of infertility Animal data In reproduction studies with pregnant rabbits, there were no skeletal or visceral malformations when drug combination was administered during organogenesis at doses less than maximum recommended human doses (MRHD); however, embryotoxicity was observed at this exposure Based on animal data, prostaglandins have been shown to have important role in endometrial vascular permeability, blastocyst implantation, and decidualization; in animal studies, administration of prostaglandin synthesis inhibitors such as diclofenac, resulted in increased pre-and post-implantation loss; if a woman becomes pregnant while receiving therapy, discontinue drug and advise woman of potential risks to her and to a fetus In animal studies, NSAIDs are known to inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth Lactation No lactation studies conducted; however, limited published literature reports that diclofenac and active metabolite of misoprostol are present in breast milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

Drugs that Interfere with Hemostasis (e.g. warfarin, aspirin, SSRIs/SNRIs): Monitor patients for bleeding who are concominantly taking Diclofenac Sodium + Misoprostol with drugs that interfere with hemostasis. Concomitant use of Diclofenac Sodium + Misoprostol and analgesic doses of aspirin is not generally recommended ACE inhibitors, Angiotensin Receptor Blockers (ARB), or Beta-Blockers: Concomitant use with Diclofenac Sodium + Misoprostol may diminish the antihypertensive effect of these drugs. Monitor blood pressure ACE Inhibitors and ARBs: Concomitant use with Diclofenac Sodium + Misoprostol in elderly, volume depleted, or those with renal impairment may result in deterioration of renal function. In such high risk patients, monitor for signs of worsening renal function Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics. Monitor patients to assure diuretic efficacy including antihypertensive effects Digoxin: Concomitant use with Diclofenac Sodium + Misoprostol can increase serum concentration and prolong half-life of digoxin. Monitor serum digoxin levels Antacids: Antacids reduce the bioavailability of Misoprostol. Antacids may also delay absorption of Diclofenac Sodium. Magnesium-containing antacids exacerbate misoprostol-associated diarrhea Methotrexate: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Intervention: During concomitant use of Diclofenac Sodium + Misoprostol and methotrexate, monitor patients for methotrexate toxicity Cyclosporine: Concomitant use of diclofenac and cyclosporine may increase cyclosporine’s nephrotoxicity. Intervention: During concomitant use of Diclofenac Sodium + Misoprostol and cyclosporine, monitor patients for signs of worsening renal function Corticosteroids: Concomitant use of corticosteroids with diclofenac may increase the risk of GI ulceration or bleeding Contraindicated (0) Serious (5) aluminum hydroxide/magnesium carbonate aluminum hydroxide/magnesium trisilicate citric acid/glucono-delta-lactone/magnesium carbonate magnesium gluconate oxytocin

Side effects of Diclofenac Sodium + Misoprostol : >10% Rash including erythematous, rash macular and maculo-papular (18%),Pyrexia (15%),Urticaria (13%),Flushing (13%) 1-10% Hypertension (10%),Hyperhydrosis (8%),Decreased oxygen saturation (8%),Cough (8%),Tachypnea (8%),Tachycardia (8%),Urticaria (8%),Anaphylaxis (7%),Chest discomfort (7%),Muscle twitching (7%),Erythema (5%),Vomiting (5%),Rigors (5%),Pallor (5%),Cyanosis (5%),Agitation (5%),Tremor (5%),Myalgia (5%),Flushing (5%),Peripheral edema (3%),Pruritus (3%),Rash, papular (3%),Throat tightness (3%) <1% Fatigue,Malaise,Chills,Edema,Atrial fibrillation,Congestive heart failure,Myocardial infarction,Phlebitis,Vasculitis,Syncope,Dysphagia,Enteritis,Peptic ulcer,Vaginitis,Breast pain,Dysmenorrhea,Uterine cramping,Ulcerative stomatitis,Impotence,Perineal pain,Glycosuria,Alopecia

Diclofenac: Inhibits cyclooxygenase-1 (COX-1) & -2 (COX-2), thereby inhibiting prostaglandin synthesis; has anti-inflammatory, antipyresis, and analgesic properties. Misoprostol: Replaces protective prostaglandins consumed by prostaglandin-inhibiting therapies (NSAID-induced ulcers).

Arthrofen 50 50mg + 200mcg Tablet manufactured by Healthcare Pharmaceuticals Ltd.. Its generic name is Diclofenac Sodium + Misoprostol. Arthrofen 50 is availble in Bangladesh. Farmaco BD drug index information on Arthrofen 50 Tablet is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.