Diclofenac-Misoprostol

Diclofenac/Misoprostol is a combination of prescription medicines used for the treatment of osteoarthritis and rheumatoid arthritis.

• Diclofenac/Misoprostol  is available under the following different brand names: Arthrotec

Adult dosage

Tablet

• 50mg/200mcg
• 75mg/200mcg

Osteoarthritis

Adult dosage

• 50 mg/200 mcg: 1 tab orally three times daily; not to exceed 200 mcg misoprostol/dose or 800 mcg/day
• 75mg/200mcg: 1 tab orally three times daily; not to exceed 200 mcg misoprostol/dose or 800 mcg/day

Rheumatoid Arthritis

Adult dosage

• 50 mg/200 mcg: 1 tab orally three or four times daily; not to exceed 200 mcg misoprostol/dose or 800 mcg/day
• 75mg/200mcg: 1 tab orally three or four times daily; not to exceed 200 mcg misoprostol/dose or 800 mcg/day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of the Diclofenac/Misoprostol include:

• diarrhea,
• stomach pain,
• nausea,
• upset stomach,
• gas,
• vaginal bleeding or spotting,
• heavy menstrual flow, and
• menstrual cramps
• unusual vaginal bleeding.

Serious side effects of the Diclofenac/Misoprostol include:

• severe ongoing stomach discomfort or diarrhea,
• feeling very thirsty or hot,
• unable to urinate,
• heavy sweating, and
• hot and dry skin

Rare side effects of the Diclofenac/Misoprostol include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Diclofenac/Misoprostol has severe interactions with no other drugs.
• Diclofenac/Misoprostol has serious interactions with at least 21 other drugs.
• Diclofenac/Misoprostol has moderate interactions with at least 268 other drugs.
• Diclofenac/Misoprostol has minor interactions with at least 101 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity drugs or related products
• Perioperative pain in the setting of coronary artery bypass graft (CABG) surgery; active gastrointestinal bleeding
• Patients who have experienced asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Diclofenac/Misoprostol?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Diclofenac/Misoprostol?”

Cautions

• Women of childbearing potential (see mfr's package insert for restrictions)
• Avoid pregnancy during & for at least 1 month after treatment
• May cause blurred vision, drowsiness, dizziness
• Transaminase elevation observed with chronic use
• Hypokalemia may occur when administered with drugs capable of inducing hyperkalemia; the risk may increase in diabetics, renal disease, the elderly
• NSAIDs reported to cause serious skin reactions including exfoliative dermatitis, Stevens-Johnson syndrome
• May increase the risk of aseptic meningitis, especially in patients with mixed connective tissue disorders and systemic lupus erythematous
• Severe bronchospasm may occur in patients with asthma
• Use caution in hepatic impairment, porphyria (avoid if possible), hypertension, renal impairment
• Avoid the use of diclofenac/Misoprostol with concomitant NSAIDs including COX inhibitors
• Use the lowest effective dose in patients with known cardiovascular (CV) disease or risk factors for CV
• Concurrent use of aspirin with NSAIDs in mitigating CV thrombotic events not shown conclusively; increased risk of serious GI adverse reactions likely
• Use caution in patients with hypertension; monitor blood pressure closely during the initiation of NSAID treatment and throughout therapy
• Fluid retention and edema may occur with therapy; use with caution in patients with heart failure
• Serious gastrointestinal adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal may occur
• Renal papillary necrosis and other renal injuries reported with NSAID long-term therapy
• Toxic epidermal necrolysis, reported with NSAID use, especially within the first month of therapy; discontinue use at the first appearance of skin rash
• The use of NSAIDs may diminish the ability to diagnose conditions associated with pain or inflammation
• Anemia reported with NSAID use; monitor
• Use caution in patients with coagulation disorders or receiving anticoagulants; NSAIDs inhibit platelet aggregation
• Not for administration to patients with aspirin-sensitive asthma; use caution in patients with preexisting asthma
• NSAIDs may diminish the antihypertensive effect of ACE-inhibitors
• Not recommended in patients with advanced renal disease
• Drug-induced hepatotoxicity is reported in the first month, and may occur within 1-6 months, but can occur at any time during therapy
• GI bleeding
  • Serious gastrointestinal adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal may occur
  • Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than the 10-fold increased risk of developing a GI bleed compared to patients without these risk factors
  • Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, antiplatelet drugs (such as aspirin), anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status; most postmarketing reports of fatal GI events occurred in elderly or debilitated patients; additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding
• Hepatotoxicity
  • Meaningful elevations (ie, more than 3 times the ULN) of aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) reported
  • Because serious GI bleeding, hepatotoxicity and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a complete blood count (CBC) and a chemistry profile periodically
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)
  • Drug reactions reported in patients taking NSAIDs; some of these events have been fatal or life-threatening; DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling
  • Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis; sometimes symptoms of DRESS may resemble an acute viral infection
  • Eosinophilia is often present; because this disorder is variable in its presentation, other organ systems not noted here may be involved
  • Early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident; if such signs or symptoms are present, discontinue therapy and evaluate the patient immediately

Pregnancy and Lactation

• The 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 after 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 an increased pre-and post-implantation loss; if a woman becomes pregnant while taking a drug combination, discontinue the drug and advise the woman of the potential risks to her and the 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, induce labor, and 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 the 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
  • The 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
  • 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 the 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 the mechanism of action, NSAIDs may delay or prevent the 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
• 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 the mother’s clinical need for therapy, and any potential adverse effects on the breastfed infant from therapy or underlying maternal conditioned