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Arthrotec

Arthrotec (Diclofenac Sodium, Misoprostol) side effects drug center

 

PROFESSIONAL

CONSUMER

SIDE EFFECTS

 

Arthrotec Side Effects Center

What Is Arthrotec?

Arthrotec (diclofenac sodium/misoprostol) is a combination non-steroidal anti-inflammatory drug (NSAID) and a prostaglandin that protects the stomach from irritating effects of NSAIDs used to treat osteoarthritis and rheumatoid arthritis in people at high risk for developing stomach or intestinal ulcers. Arthrotec is available in generic form.

What Are Side Effects of Arthrotec?

Common side effects of Arthrotec include diarrhea and upset stomach or stomach pain within a few weeks after you start taking this medication, and usually last for about 1 week. Other side effects of Arthrotec include:

  • nausea,
  • bloating,
  • gas,
  • dizziness,
  • drowsiness,
  • headache,
  • blurred vision,
  • ringing in your ears, or
  • unusual vaginal bleeding.

Tell your doctor if you have serious side effects of Arthrotec including:

  • difficult or painful swallowing,
  • swelling of the hands or feet,
  • sudden or unexplained weight gain,
  • vision changes,
  • mental/mood changes (e.g., depression),
  • fast or pounding heartbeat,
  • persistent or severe headache,
  • fainting,
  • menstrual problems/irregular periods,
  • unusual tiredness,
  • easy bruising or bleeding,
  • signs of infection (e.g., fever, persistent sore throat),
  • changes in the amount of urine, or
  • unexplained stiff neck.

Dosage for Arthrotec

For the relief of rheumatoid arthritis and osteoarthritis, the recommended dose of Arthrotec is 50 mg diclofenac sodium/200 mcg misoprostol or 75 mg diclofenac sodium/200 mcg misoprostol.

What Drugs, Substances, or Supplements Interact with Arthrotec?

Arthrotec may interact with blood thinners, cyclosporine, digoxin, diuretics (water pills), insulin or oral diabetes medicine, lithium, methotrexate, phenobarbital, steroids, aspirin or other NSAIDs, or ACE inhibitors. Tell your doctor all medications you use.

Arthrotec During Pregnancy and Breastfeeding

Arthrotec must not be used during pregnancy. It can harm the fetus and mother. Use birth control while taking this medication. This medication passes into breast milk. However, this drug is unlikely to harm a nursing infant. Consult your doctor before breastfeeding.

Additional Information

Our Arthrotec (diclofenac sodium/misoprostol) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Arthrotec Consumer Information

Get emergency medical help if you have signs of an allergic reaction (sneezing, runny or stuffy nose, hives, wheezing or trouble breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Get emergency medical help if you have signs of a heart attack or stroke: chest pain spreading to your jaw or shoulder, sudden numbness or weakness on one side of the body, slurred speech, feeling short of breath.

Stop using this medicine and call your doctor at once if you have:

  • the first sign of any skin rash, no matter how mild;
  • shortness of breath (even with mild exertion);
  • swelling or rapid weight gain;
  • signs of stomach bleeding--bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;
  • liver problems--loss of appetite, stomach pain (upper right side), tiredness, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
  • kidney problems--little or no urination, swelling in your feet or ankles, feeling tired or short of breath; or
  • low red blood cells (anemia)--pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet.

Common side effects may include:

  • abnormal vaginal bleeding;
  • heartburn, indigestion stomach pain, gas;
  • nausea, vomiting;
  • diarrhea, constipation; or
  • dizziness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Arthrotec (Diclofenac Sodium, Misoprostol)

 

Arthrotec Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

  • Cardiovascular Thrombotic Events [see WARNINGS AND PRECAUTIONS]
  • GI Bleeding, Ulceration and Perforation [see WARNINGS AND PRECAUTIONS]
  • Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
  • Hypertension [see WARNINGS AND PRECAUTIONS]
  • Heart Failure and Edema [see WARNINGS AND PRECAUTIONS]
  • Renal Toxicity and Hyperkalemia [see WARNINGS AND PRECAUTIONS]
  • Anaphylactic Reactions [see WARNINGS AND PRECAUTIONS]
  • Serious Skin Reactions [see WARNINGS AND PRECAUTIONS]
  • Hematologic Toxicity [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reaction information for ARTHROTEC is derived from multinational controlled clinical trials in over 2,000 patients receiving ARTHROTEC 50 or ARTHROTEC 75, as well as from blinded, controlled trials of diclofenac sodium delayed-release tablets and misoprostol tablets.

Gastrointestinal

GI disorders had the highest reported incidence of adverse reactions for patients receiving ARTHROTEC. These events were generally minor, but led to discontinuation of therapy in 9% of patients on ARTHROTEC and 5% of patients on diclofenac sodium. For GI ulcer rates, [see Clinical Studies].

GI disorder ARTHROTEC Diclofenac Sodium
Abdominal pain 21% 15%
Diarrhea 19% 11%
Dyspepsia 14% 11%
Nausea 11% 6%
Flatulence 9% 4%

ARTHROTEC can cause more abdominal pain, diarrhea, and other GI symptoms than diclofenac alone.

Diarrhea and abdominal pain developed early in the course of therapy, and were usually self-limited (resolved after 2 to 7 days). Rare instances of profound diarrhea leading to severe dehydration have been reported in patients receiving misoprostol. Patients with an underlying condition such as inflammatory bowel disease, or those in whom dehydration, were it to occur, would be dangerous, should be monitored carefully if ARTHROTEC is prescribed. The incidence of diarrhea can be minimized by administering ARTHROTEC with food and by avoiding coadministration with magnesium-containing antacids.

Gynecological

Gynecological disorders previously reported with misoprostol use have also been reported for women receiving ARTHROTEC (see below). Postmenopausal vaginal bleeding may be related to administration of ARTHROTEC. If it occurs, diagnostic workup should be undertaken to rule out gynecological pathology [see BOX WARNING, CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

Elderly

Overall, there were no significant differences in the safety profile of ARTHROTEC in over 500 patients 65 years of age or older compared with younger patients.

Other adverse experiences reported occasionally with ARTHROTEC, diclofenac or other NSAIDs, or misoprostol are:

Body as a whole: asthenia, fatigue, malaise.

Central and peripheral nervous system: dizziness, drowsiness, headache, insomnia, paresthesia, vertigo.

Digestive: anorexia, appetite changes, constipation, dry mouth, dysphagia, esophageal ulceration, esophagitis, eructation, gastritis, gastroesophageal reflux, GI neoplasm benign, peptic ulcer, tenesmus, vomiting.

Female reproductive disorders: breast pain, dysmenorrhea, menstrual disorder, menorrhagia, vaginal hemorrhage.

Hemic and lymphatic system: epistaxis, leukopenia, melena, purpura, decreased hematocrit.

Metabolic and nutritional: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, dehydration, hyponatremia.

Musculoskeletal system: arthralgia, myalgia.

Psychiatric: anxiety, concentration impaired, depression, irritability.

Respiratory system: asthma, coughing, hyperventilation.

Skin and appendages: alopecia, eczema, pemphigoid reaction, photosensitivity, sweating increased, pruritus.

Special senses: taste perversion, tinnitus.

Renal and urinary disorders: ysuria, nocturia, polyuria, proteinuria, urinary tract infection.

Vision: diplopia.

Postmarketing Experience

The following adverse reactions have been identified during post approval of ARTHROTEC, diclofenac or misoprostol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliable estimate their frequency or establish a causal relationship to drug exposure.

Body as a whole: death, fever, infection, sepsis, chills, edema.

Cardiovascular system: arrhythmia, atrial fibrillation, congestive heart failure, hypertension, hypotension, increased creatine phosphokinase (CPK), increased lactate dehydrogenase (LDH), myocardial infarction, palpitations, phlebitis, premature ventricular contractions, syncope, tachycardia, vasculitis.

Central and peripheral nervous system: coma, convulsions, hyperesthesia, hypertonia, hypoesthesia, meningitis, migraine, neuralgia, somnolence, stroke, tremor.

Congenital, familial and genetic disorders: birth defects.

Digestive: enteritis, GI bleeding, glossitis, heartburn, hematemesis, hemorrhoids, intestinal perforation, stomatitis and ulcerative stomatitis.

Female reproductive disorders: intermenstrual bleeding, leukorrhea, vaginitis, uterine cramping, uterine hemorrhage.

Hemic and lymphatic system: agranulocytosis, anemia, aplastic anemia, coagulation time increased, ecchymosis, eosinophilia, hemolytic anemia, leukocytosis, lymphadenopathy, pancytopenia, pulmonary embolism, rectal bleeding, thrombocythemia, thrombocytopenia.

Hypersensitivity: angioedema, laryngeal/pharyngeal edema, urticaria.

Liver and biliary system: abnormal hepatic function, bilirubinemia, liver failure, pancreatitis, hepatitis, jaundice.

Male reproductive disorders: impotence, perineal pain.

Metabolic and nutritional: blood urea nitrogen (BUN) increased, glycosuria, gout, hypercholesterolemia, hyperglycemia, hyperuricemia, hypoglycemia, periorbital edema, porphyria, weight changes, fluid retention.

Pregnancy, puerperium and perinatal conditions: abnormal uterine contractions, uterine rupture/perforation, retained placenta, amniotic fluid embolism, incomplete abortion, premature birth, fetal death.

Psychiatric: confusion, disorientation, dream abnormalities, hallucinations, nervousness, paranoia, psychotic reaction.

Reproductive system and breast disorders: female fertility decreased.

Respiratory system: dyspnea, pneumonia, respiratory depression.

Skin and appendages: acne, bruising, erythema multiforme, exfoliative dermatitis, pruritus ani, rash, skin ulceration, Stevens-Johnson syndrome, toxic epidermal necrolysis, cutaneous reactions (bullous eruption).

Special senses: hearing impairment, taste loss.

Renal and urinary disorders: cystitis, hematuria, interstitial nephritis, micturition frequency, nephrotic syndrome, oliguria, papillary necrosis, renal failure, glomerulonephritis membranous, glomerulonephritis minimal lesion, glomerulonephritis.

Vision: amblyopia, blurred vision, conjunctivitis, glaucoma, iritis, lacrimation abnormal, night blindness, vision abnormal.

DRUG INTERACTIONS

See Table 1 for clinically significant drug interactions with diclofenac and misoprostol.

Table 1: Clinically Significant Drug Interactions with Diclofenac and Misoprostol

Drugs That Interfere with Hemostasis
Clinical Impact:
  • Diclofenac and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of diclofenac and anticoagulants have anincreased risk of serious bleeding compared to the use of either drug alone.
  • Serotonin release by platelets plays an important role in hemostasis Case-control and cohort epidemiological studies showed that concomitant useof drugs that interfere with serotonin reuptake and an NSAID may potentiatethe risk of bleeding more than an NSAID alone.
Intervention: Monitor patients with concomitant use of ARTHROTEC with anticoagulants(e.g., warfarin), antiplatelet drugs (e.g., aspirin), SSRIs, and SNRIs for signs ofbleeding [see WARNINGS AND PRECAUTIONS].
Aspirin
Clinical Impact: Controlled clinical studies showed that the concomitant use of NSAIDs andanalgesic doses of aspirin does not produce any greater therapeutic effect thanthe use of NSAIDs alone. In a clinical study, the concomitant use of an NSAIDand aspirin was associated with a significantly increased incidence of GIadverse reactions as compared to use of the NSAID alone [see WARNINGS AND PRECAUTIONS].
Intervention: Concomitant use of ARTHROTEC and analgesic doses of aspirin is notgenerally recommended because of the increased risk of bleeding [see WARNINGS AND PRECAUTIONS].

ARTHROTEC is not a substitute for low dose aspirin for cardiovascularprotection.
ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers
Clinical Impact:
  • NSAIDs may diminish the antihypertensive effect of ACE inhibitors, ARBs,or beta-blockers (including propranolol).
  • In patients who are elderly, volume-depleted (including those on diuretictherapy), or have renal impairment, co-administration of an NSAID withACE inhibitors or ARBs may result in deterioration of renal function,including possible acute renal failure. These effects are usually reversible.
Intervention:
  • The concomitant administration of these drugs should be done with caution.Patients should be adequately hydrated and the clinical need to monitor therenal function should be assessed at the beginning of the concomitanttreatment and periodically thereafter.
  • During concomitant use of ARTHROTEC and ACE inhibitors, ARBs, orbeta-blockers, monitor blood pressure to ensure that the desired bloodpressure is obtained.
  • During concomitant use of ARTHROTEC and ACE inhibitors or ARBs inpatients who are elderly, volume-depleted, or have impaired renal function,monitor for signs of worsening renal function [see WARNINGS AND PRECAUTIONS].
Diuretics
Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDsreduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazidediuretics in some patients. This effect has been attributed to the NSAIDinhibition of renal prostaglandin synthesis.
Intervention: During concomitant use of ARTHROTEC with diuretics, observe patients forsigns of worsening renal function, in addition to assuring diuretic efficacyincluding antihypertensive effects [see WARNINGS AND PRECAUTIONS].
Digoxin
Clinical Impact The concomitant use of diclofenac with digoxin has been reported to increasethe serum concentration and prolong the half-life of digoxin.
Intervention: During concomitant use of ARTHROTEC and digoxin, monitor serum digoxinlevels.
Lithium
Clinical Impact: NSAIDs have produced elevations in plasma lithium levels and reductions inrenal lithium clearance. The mean minimum lithium concentration increased15%, and the renal clearance decreased by approximately 20%. This effect hasbeen attributed to NSAID inhibition of renal prostaglandin synthesis.
Intervention: During concomitant use of ARTHROTEC and lithium, monitor patients forsigns of lithium toxicity.
Methotrexate
Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk formethotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction).
Intervention: During concomitant use of ARTHROTEC and methotrexate, monitor patientsfor methotrexate toxicity.
Cyclosporine
Clinical Impact: Concomitant use of diclofenac and cyclosporine may increase cyclosporine’snephrotoxicity.
Intervention: During concomitant use of ARTHROTEC and cyclosporine, monitor patientsfor signs of worsening renal function.
NSAIDs and Salicylates
Clinical Impact: Concomitant use of diclofenac with other NSAIDs or salicylates (e.g.,diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase inefficacy [see WARNINGS AND PRECAUTIONS].
Intervention: The concomitant use of ARTHROTEC with other NSAIDs or salicylates is notrecommended.
Pemetrexed
Clinical Impact: Concomitant use of diclofenac and pemetrexed may increase the risk ofpemetrexed-associated myelosuppression, renal, and GI toxicity (see thepemetrexed prescribing information).
Intervention: During concomitant use of ARTHROTEC and pemetrexed, in patients withrenal impairment whose creatinine clearance ranges from 45 to 79 mL/min,monitor for myelosuppression, renal and GI toxicity.

Avoid ARTHROTEC for a period of two days before, the day of, and two daysfollowing administration of pemetrexed.
Antacids
Clinical Impact Antacids reduce the bioavailability of misoprostol acid. Antacids may alsodelay absorption of diclofenac. Magnesium-containing antacids exacerbatemisoprostol-associated diarrhea.
Intervention: Concomitant use of ARTHROTEC and magnesium-containing antacids is notrecommended
Corticosteroids
Clinical Impact: Concomitant use of corticosteroids with diclofenac may increase the risk of GIulceration or bleeding.
Intervention Monitor patients with concomitant use of ARTHROTEC with corticosteroidsfor signs of bleeding [see WARNINGS AND PRECAUTIONS].
CYP2C9 Inhibitors or Inducers
Clinical Impact: Diclofenac is metabolized by cytochrome P450 enzymes, predominantly byCYP2C9. Co-administration of diclofenac with CYP2C9 inhibitors (e.g.,voriconzaole) may enhance the exposure and toxicity of diclofenac [see CLINICAL PHARMACOLOGY] whereas co-administration with CYP2C9inducers (e.g., rifampin) may lead to compromised efficacy of diclofenac.
Intervention: CYP 2C9 inhibitors: When concomitant use of CYP2C9 inhibitors is necessary,the total daily dose of diclofenac should not exceed the lowest recommendeddose of ARTHROTEC 50 twice daily [see DOSAGE AND ADMINISTRATION].

CYP2C9 inducers: A dosage adjustment may be warranted whenARTHROTEC is administered with CYP2C9 inducers. Administer the separateproducts of misoprostol and diclofenac if a higher dose of diclofenac is deemednecessary.

Read the entire FDA prescribing information for Arthrotec (Diclofenac Sodium, Misoprostol)

&Copy; Arthrotec Patient Information is supplied by Cerner Multum, Inc. and Arthrotec Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.