Arthrotec Side Effects

Generic Name: diclofenac / misoprostol

Note: This page contains information about the side effects of diclofenac / misoprostol. Some of the dosage forms included on this document may not apply to the brand name Arthrotec.

Not all side effects for Arthrotec may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to diclofenac / misoprostol: oral tablet, oral tablet enteric coated

In addition to its needed effects, some unwanted effects may be caused by diclofenac / misoprostol. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking diclofenac / misoprostol:

Less common
  • Black, tarry stools
  • bleeding or crusting sores on the lips
  • blood in the urine or stools
  • bruises or red spots on the skin
  • chest pain
  • chills
  • confusion
  • continuing thirst
  • convulsions (seizures)
  • cough or hoarseness
  • disorientation
  • drowsiness
  • fainting
  • fever with or without chills
  • fluid retention
  • general feeling of illness
  • heartburn or indigestion
  • increased blood pressure
  • increased heart rate
  • increased weight gain
  • irregular heartbeat
  • itching of the skin
  • large, flat, blue or purplish patches on the skin
  • lightheadedness or dizziness
  • lower back or side pain
  • mental depression
  • muscle cramps
  • nausea
  • painful or difficult urination
  • pounding heartbeat
  • psychotic reaction
  • rectal bleeding
  • seeing, hearing, or feeling things that are not there
  • severe headache
  • severe liver reactions
  • severe stomach pain, cramping, or burning
  • shortness of breath, troubled breathing, tightness in the chest, or wheezing
  • skin rash
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • stiff neck or back
  • sudden decrease in the amount of urine
  • swelling or tenderness in the upper stomach
  • swelling of the face, fingers, feet, or lower legs
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • vomiting of material that looks like coffee grounds
  • yellow eyes or skin
Rare
  • Changes in facial skin color
  • fast or irregular breathing
  • puffiness or swelling of the eyelids or around the eyes

If any of the following symptoms of overdose occur while taking diclofenac / misoprostol, get emergency help immediately:

Symptoms of overdose
  • Diarrhea
  • fever
  • slow heartbeat
  • stomach pain
  • trembling or shaking

Some of the side effects that can occur with diclofenac / misoprostol may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Gas
Less common
  • Abnormal vision
  • acne
  • change in sense of taste
  • decreased appetite
  • decrease in sexual ability
  • dry mouth
  • irritability or nervousness
  • loss of hair
  • muscle pain
  • tingling, burning, or prickling sensations
  • trouble with swallowing
  • vaginal bleeding

For Healthcare Professionals

Applies to diclofenac / misoprostol: oral tablet

Gastrointestinal

In one safety review, gastrointestinal bleeding was reported in 0.16% and 0.17% of patients following short-term (duration not defined) and long-term (up to 58 weeks) treatment with diclofenac, respectively. Peptic ulceration occurred in 0.16 and 0.34% of patients, respectively. The manufacturer reports a higher incidence, 2 to 4%, of serious gastrointestinal events in patients treated with diclofenac for up to 1 year.

Colonic strictures, ulcerations, and bleeding associated with diclofenac use have been reported in the literature. Several authors have speculated that the enteric, or "delayed release", form of diclofenac may be at fault, as tablet fragments have been found at the site of the pathology.

Patients with a history of serious gastrointestinal events or alcohol abuse are at increased risk for severe gastrointestinal side effects. Diclofenac-misoprostol should be used with caution in these patients.[Ref]

Gastrointestinal (GI) side effects have been reported the most frequently. These have included abdominal pain (21%), diarrhea (19%), dyspepsia (14%), nausea (11%) and flatulence (9%). Diarrhea and constipation may occur early in the course of therapy, are self-limited and disappear within two to seven days. Other gastrointestinal effects include anorexia, appetite changes, constipation, dry mouth, dyspepsia, enteritis, esophageal ulceration, esophagitis, eructation, gastritis, gastroesophageal reflux, GI bleeding, GI neoplasm benign, glossitis, heartburn, hematemesis, hemorrhoids, intestinal perforation, peptic ulcer, stomatitis and ulcerative stomatitis, tenesmus, pseudomembranous colitis, colonic strictures, ileocolitis, and vomiting.

Gastrointestinal side effects, including diarrhea (up to 40%), abdominal pain (up to 20%), nausea (3.2%), flatulence, and dyspepsia, are commonly associated with misoprostol therapy.[Ref]

Hepatic

Hepatic side effects have included elevations in serum transaminases in up to 15% of patients as well as rare cases of hepatitis, jaundice, and fatal fulminant hepatitis. Liver failure and pancreatitis have also been reported. Liver injury is most likely in older females in the first 6 months of use.[Ref]

Elevations in serum transaminases three times normal values are reported in up to 2% of patients during the first 2 months of diclofenac therapy. Elevations eight times normal values occurred in 1% of patients over 2 to 6 months of therapy. In one review of 26 cases of diclofenac-induced hepatitis, the authors found a correlation between the cumulative diclofenac dose and severity of liver damage as well as the logarithm of the peak and mean transaminase levels. Elevations in serum transaminases are generally reversible upon cessation of diclofenac therapy.

Fatal cases of fulminant hepatitis during diclofenac therapy are reported in the literature. Autopsies in these cases revealed massive hepatic necrosis and cholestasis. Diclofenac-induced hepatitis may be a result of a hypersensitivity reaction in some cases. Three reported cases had features of autoimmune chronic active hepatitis, with accompanying positive ANA titers. Eosinophilia, maculopapular rash, fever, and lymphadenopathy have also been present in some cases.[Ref]

Renal

Diclofenac may impair the ability of the kidney to cope with low renal blood flow states due to inhibition of prostaglandin-dependent afferent arteriolar vasodilation. Renal function may be further compromised in patients with heart failure, hypovolemia, cirrhosis, nephrotic syndrome, or hypoalbuminemia. Additional risk factors for diclofenac-induced renal insufficiency are advanced age and concomitant use of diuretics or ACE inhibitors.

A case-control study suggested that patients who consumed 5000 or more pills containing NSAIDs during their lifetime may be at increased risk of end-stage renal disease.[Ref]

Renal side effects have included cystitis, nephrotic syndrome, interstitial nephritis, renal papillary necrosis, acute renal failure, urinary frequency, nocturia, proteinuria, and hematuria.[Ref]

Dermatologic

Dermatologic side effects have included acne, alopecia, bruising, eczema, erythema multiforme, exfoliative dermatitis, pemphigoid reaction, photosensitivity, pruritus, pruritus ani, rash, skin ulceration, Stevens-Johnson, sweating increased, toxic epidermal necrolysis. In addition, severe pustular psoriasis has been reported.[Ref]

Hematologic

Hematologic side effects have included agranulocytosis, anemia, aplastic anemia, coagulation time increased, ecchymosis, eosinophilia, epistaxis, hemolytic anemia, leukocytosis, leukopenia, lymphadenopathy, melena, pancytopenia, pulmonary embolism, purpura, rectal bleeding, thrombocythemia, and thrombocytopenia. Blood dyscrasias are usually reversible upon cessation of diclofenac, although rare fatalities are reported.

Hematologic abnormalities are uncommon during misoprostol therapy, but include thrombocytopenia purpura, anemia, abnormal differential, and increases in ESR.[Ref]

Autoimmune hemolytic anemia and thrombocytopenia during diclofenac therapy have been associated with the development of autoantibodies as well as drug- or metabolite-dependent antibodies, implicating a drug hypersensitivity. Evidence of the dyscrasia may be preceded by other signs of hypersensitivity such as rash, pruritus, and fever. In one case, diclofenac-induced thrombocytopenic purpura was accompanied by renal and hepatic toxicity.

Agranulocytosis and aplastic anemia during diclofenac therapy are reported as well, and have resulted in patient death despite proper management.

A disproportionate amount of postoperative hemorrhage requiring operative intervention has been reported with the use of diclofenac when used for analgesia after adenotonsillectomy.[Ref]

Musculoskeletal

Musculoskeletal side effects have included arthralgia and myalgia.[Ref]

A 44-year-old man with recurring knee pain treated himself with diclofenac 75 mg intramuscularly for 6 days followed by 75 mg orally three times a day for seven days. During the last three days of diclofenac treatment, he became anorexic and complained of nausea, epigastric pain and developed erythematous pruritic eruptions over his back, abdomen, chest, face and scalp. He denied use of other medications or any drug allergies. Serum LDH, SGOT, SGPT were all elevated. His muscle strength gradually decreased. Serum CPK levels peaked at 83,770 units/L 11 days following diclofenac cessation. The patient was diagnosed with erythema multiforme and rhabdomyolysis due to diclofenac. Six months following cessation of diclofenac, the patient was asymptomatic and strength was normal.[Ref]

Hypersensitivity

Hypersensitivity side effects have included anaphylactoid reactions, and anaphylaxis, angioedema, laryngeal or pharyngeal edema, and urticaria.[Ref]

Metabolic

Metabolic side effects have included increases in alkaline phosphatase and BUN, dehydration, glycosuria, gout, hypercholesterolemia, hyperglycemia, hyperuricemia, hypoglycemia, hyponatremia, periorbital edema, porphyria, chills, and weight changes.[Ref]

Nervous system

Aseptic meningitis was reported in a 42-year-old female following two weeks of therapy with diclofenac 50 mg three times a day. CSF eosinophilia was present in the absence of peripheral eosinophilia, a finding similar to that seen with other cases of NSAID-induced aseptic meningitis. The patient's symptoms spontaneously resolved over 48 hours following the discontinuation of diclofenac.[Ref]

Nervous system side effects have included coma, convulsions, dizziness, drowsiness, headache, hyperesthesia, hypertonia, hypoesthesia, insomnia, meningitis, migraine, neuralgia, paresthesia, somnolence, tremor and vertigo.[Ref]

Cardiovascular

Nonsteroidal anti-inflammatory drugs (NSAIDs) may elevate blood pressure and increase the risk for the initiation of antihypertensive therapy. Furthermore, NSAIDs may antagonize the blood pressure lowering effect of antihypertensive medications in patients already being treated with antihypertensive drugs.[Ref]

Cardiovascular side effects have included arrhythmia, atrial fibrillation, congestive heart failure, hypertension, hypotension, increased CPK, increased LDH, myocardial infarction, palpitations, phlebitis, premature ventricular contractions, syncope, tachycardia, and vasculitis. In addition, blood pressure may be elevated by diclofenac which may have clinical relevance in patients with comorbid illnesses.[Ref]

Psychiatric

Psychiatric side effects of diclofenac include rare reports of depression, anxiety, irritability, nightmares, and psychotic reactions.[Ref]

Other

Other diclofenac side effects include tinnitus, blurred vision, taste disturbance, reversible hearing loss, dry eyes, scotoma, night blindness, and amblyopia. Diclofenac eye drops (0.1%) may cause transient stinging or burning.

A case of misoprostol-induced fever has been reported in the literature.[Ref]

Genitourinary

Postmenopausal bleeding may occur in patients treated with misoprostol. It is recommended that patients who develop postmenopausal bleeding undergo gynecological evaluation to rule out non-drug related pathology.

A 25-year-old female developed stress urinary incontinence after one month of misoprostol therapy. The patient was rechallenged with misoprostol with symptoms recurring after 7 days of therapy. Urodynamic studies revealed a deficiency in urethral resistance while on misoprostol.[Ref]

Genitourinary side effects have included dysmenorrhea, dysuria, hematuria, intermenstrual bleeding, leukorrhea, menstrual disorder, menorrhagia, micturition frequency, nocturia, and vaginal hemorrhage. Also, impotence and perineal pain have been reported.[Ref]

Ocular

Ocular side effects have included amblyopia, blurred vision, conjunctivitis, diplopia, glaucoma, iritis, abnormal lacrimation, night blindness, and abnormal vision.[Ref]

Respiratory

Respiratory side effects have included asthma, coughing, dyspnea, hyperventilation, pneumonia, and respiratory depression.[Ref]

References

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56. Codding C, Targoff IN, McCarty GA "Aseptic meningitis in association with diclofenac treatment in a patient with systemic lupus erythematosus." Arthritis Rheum 34 (1991): 1340-1

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