Applies to diclofenac / misoprostol: oral tablet enteric coated.

Serious side effects

Along with its needed effects, diclofenac / misoprostol may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking diclofenac / misoprostol:

More common

• Stomach pain

Less common

• Black, tarry stools
• bladder pain
• bloody or cloudy urine
• burning feeling in the chest or stomach
• burning while urinating
• chest pain, discomfort, or tightness
• chills
• cough
• deep or fast breathing with dizziness
• difficult, burning, or painful urination
• difficulty swallowing
• dizziness
• double vision
• feeling of constant movement of self or surroundings
• fever
• frequent urge to urinate
• heartburn
• increased sensitivity of the skin to sunlight
• increased volume of pale, dilute urine
• indigestion
• itching, skin rash
• lightheadedness
• longer or heavier menstrual periods
• lower back or side pain
• nosebleed
• numbness of the feet, hands, and around the mouth
• pain or burning in the throat
• pain with swallowing
• redness or other discoloration of the skin
• seeing double
• sensation of spinning
• severe sunburn
• sores, ulcers, or white spots on the lips or in the mouth
• sore throat
• stomach upset or tenderness
• swollen glands
• unusual bleeding or bruising
• unusual tiredness or weakness
• vaginal bleeding
• vomiting with or without blood

Incidence not known

• Ankle, knee, or great toe joint pain
• anxiety
• black, tarry stools
• bleeding gums
• blindness
• blistering, peeling, or loosening of the skin
• bloating or swelling of the face, arms, hands, lower legs, or feet
• bluish color of the skin
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• burning, dry, or itching eyes
• cloudy or dark urine
• decreased frequency or amount of urine
• decreased vision
• diarrhea
• difficulty in speaking
• dilated neck veins
• discharge, excessive tearing
• dizziness, fainting, or lightheadedness when getting up suddenly from a lying or sitting position
• drowsiness
• excessive muscle tone
• eye pain
• fainting
• fast, irregular, pounding, or racing heartbeat or pulse
• general feeling of illness
• headache, severe and throbbing
• hoarseness
• inability to move the arms, legs, or facial muscles
• inability to speak
• increased sensitivity to pain or touch
• increased thirst
• irregular, fast or slow, or shallow breathing
• joint pain, stiffness, or swelling
• large, hive-like swelling on the pain, face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals
• light-colored stools
• lightheadedness
• loss of appetite
• loss of consciousness
• muscle stiffness, tension, or tightness
• nausea
• nervousness
• night blindness
• pain or discomfort in the arms, jaw, back, or neck
• pains in the stomach, side, or abdomen, possibly radiating to the back
• pain, warmth, or burning in the fingers, toes, and legs
• pale or blue lips, fingernails, or skin pale skin
• pinpoint red spots on the skin
• pounding in the ears
• problems with vision or hearing
• rapid weight gain
• red skin lesions, often with a purple center
• redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid
• redness or soreness of the skin
• seizures
• severe stomach cramping
• slow heartbeat
• slow speech
• sneezing
• sores, welts, or blisters
• stiff neck or back
• tremor
• trouble breathing
• unusual bleeding or bruising
• unusual weight gain or loss
• upper right stomach pain
• uterine cramping and bleeding
• vomiting of material that looks like coffee grounds, severe and continuing
• yellow eyes or skin

Other side effects

Some side effects of diclofenac / misoprostol may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Belching
• excess air or gas in the stomach or bowels
• full feeling
• passing gas

Less common

• Breast pain
• change in or loss of taste
• confusion about identity, place, and time
• constipation
• continuing ringing or buzzing or other unexplained noise in the ears
• decreased concentration
• depression
• difficulty in moving
• dry mouth
• frequent urge to defecate
• increased clear or white vaginal discharge
• irritability
• itching of the vagina or genital area
• lack or loss of strength
• loss or thinning of hair
• pain during sexual intercourse
• seeing, hearing, or feeling things that are not there
• straining while passing stool
• thick, white vaginal discharge with no odor or with a mild odor
• trouble sleeping

Incidence not known

• Blemishes on the skin
• decreased interest in sexual intercourse
• inability to have or keep an erection
• loss in sexual ability, desire, drive, or performance
• pimples
• sleepiness or unusual drowsiness

For Healthcare Professionals

Applies to diclofenac / misoprostol: oral delayed release tablet, oral tablet.

General

The highest reported incidences of adverse events for this drug were gastrointestinal and included abdominal pain, diarrhea, dyspepsia, nausea, and flatulence.^[Ref]

Gastrointestinal

NSAIDs including this drug, can cause serious gastrointestinal (GI) events which can occur at any time, with or without warning. For patients who develop a serious upper GI event, only about 20% were symptomatic. Upper GI ulcers, gross bleeding, or perforation occurred in approximately 1% of patients treated with NSAIDs for 3 to 6 months and 2% to 4% of patients treated for 1 year. Patients with a prior history of peptic ulcer disease and/or GI bleeding had a greater than 10-fold increased risk for developing a GI bleed than patients with neither of these risk factors.^[Ref]

Diclofenac-misoprostol:

Very common (10% or more): Abdominal pain (21%), diarrhea (19%), dyspepsia (14%), nausea (11%)

Common (1% to 10%): Flatulence, gastritis, vomiting, eructation, constipation, peptic ulcer

Uncommon (0.1% to 1%): Stomatitis

Rare (less than 0.1%): Esophageal ulceration, esophagitis, gastroesophageal reflux, heartburn, hematemesis, melena, gall bladder disorder

Frequency not reported: Pancreatitis

Postmarketing reports: Gastrointestinal (GI) perforation, GI bleeding, melena, colitis, Crohn's disease, esophageal disorder, mouth ulceration, tongue edema, dry mouth

Diclofenac:

Very common (10% or more): Abdominal pain (15%), diarrhea (11%), dyspepsia (11%), nausea (11%)

Common (1% to 10%): Flatulence, nausea^[Ref]

Cardiovascular

Uncommon (0.1% to 1%): Hypertension, chest pain, edema, palpitation, syncope

Rare (less than 0.1%): Arrhythmia, atrial fibrillation, hypotension, myocardial infarction, premature ventricular contractions, tachycardia, vasculitis, phlebitis

Frequency not reported: Cardiac failure, palpitations^[Ref]

Clinical trials of several cyclooxygenase (COX)-2 selective and nonselective NSAIDs of up to 3 years duration have shown an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs appear to have a similar risk. There is no consistent evidence that concurrent use of aspirin mitigates this increased risk and may be associated with an increased risk of serious gastrointestinal events.^[Ref]

Hepatic

Common (1% to 10%): Alanine aminotransferase increased, aspartate aminotransferase increased

Rare (less than 0.1%): Hepatitis, jaundice, abnormal hepatic function

Frequency not reported: Liver failure

Postmarketing reports: Hepatitis fulminant, blood bilirubin increased^[Ref]

Elevations to greater than 3 x ULN of ALT occurred in about 1.6% (n=2184) of patients receiving diclofenac-misoprostol at some point during treatment. These increases were generally transient and returned to within normal range upon discontinuation of therapy. In an open-labeled trial among patients receiving NSAIDs, a higher incidence of transaminase elevations were observed in patients receiving diclofenac compared with other NSAIDs.^[Ref]

Hypersensitivity

Rare (less than 0.1%): Allergic reactions

Frequency not reported: Angioedema, laryngeal/pharyngeal edema, urticaria

Postmarketing reports: Anaphylaxis^[Ref]

Dermatologic

Common (1% to 10%): Erythema multiforme, rash, pruritus

Uncommon (0.1% to 1%): Purpura, urticaria

Rare (less than 0.1%): Angioedema, increased sweating, acne

Postmarketing reports: Toxic epidermal necrolysis, Stevens-Johnson syndrome, dermatitis exfoliative, dermatitis bullous, Henoch Schonlein purpura, mucocutaneous rash, rash vesicular, photosensitivity reaction, alopecia^[Ref]

Renal

Frequency not reported: Renal failure, glomerulonephritis membranous, glomerulonephritis minimal lesion

Postmarketing reports: Acute renal failure, renal papillary necrosis, nephritis, interstitial nephrotic syndrome, proteinuria^[Ref]

Hematologic

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, the NSAID effect on platelet function is quantitatively less, of shorter duration, and reversible.^[Ref]

Uncommon (0.1% to 1%): Thrombocytopenia

Rare (less than 0.1%): Agranulocytosis, anemia, aplastic anemia, coagulation time increased, ecchymosis, eosinophilia, hemolytic anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, decreased hematocrit^[Ref]

Metabolic

Rare (less than 0.1%): Anorexia, appetite changes, dehydration, hyperglycemia, hypoglycemia, hyponatremia, weight changes, gout, hypercholesterolemia, porphyria^[Ref]

Nervous system

Common (1% to 10%): Headache, dizziness

Rare (less than 0.1%): Drowsiness, headache, hyperesthesia, hypertonia, hypoesthesia, insomnia, meningitis, migraine, neuralgia, paresthesia, somnolence, stroke, tremor, confusion

Frequency not reported: Coma

Postmarketing reports: Convulsions, memory disturbance, taste disturbance^[Ref]

Psychiatric

Common (1% to 10%): Insomnia

Rare (less than 0.1%): Anxiety, impaired concentration, depression, dream abnormalities, hallucinations, irritability, nervousness, paranoia, psychotic reaction

Postmarketing reports: Mood changes, nightmares^[Ref]

Other

Rare (less than 0.1%): Asthenia, fatigue, fever, malaise, chills, hearing impairment, tinnitus, speech disorder^[Ref]

Genitourinary

Misoprostol may cause abortion. It has been used outside of its approved indications to ripen the cervix, to induce labor, and to treat postpartum hemorrhage, however a major adverse effect of these uses is hyperstimulation of the uterus. Uterine rupture, amniotic fluid embolism, and severe genital bleeding have been reported.^[Ref]

Diclofenac-misoprostol:

Rare (less than 0.1%): Vaginitis, menstrual disorder, menorrhagia, dysmenorrhea, intermenstrual bleeding, cystitis, dysuria, nocturia

Frequency not reported: Impotence, perineal pain

Postmarketing reports: Intrauterine death, uterine rupture, incomplete abortion, abnormal uterine contractions, retained placenta, dysuria, urine abnormal

Misoprostol:

Frequency not reported: Hyperstimulation of the uterus, amniotic fluid embolism resulting in maternal and fetal death, severe vaginal bleeding, retained placenta, pelvic pain, uterine rupture^[Ref]

Ocular

Rare (less than 0.1%): Amblyopia, blurred vision, conjunctivitis, diplopia, glaucoma, iritis, lacrimation abnormal, night blindness, abnormal vision, eye pain^[Ref]

Respiratory

Rare (less than 0.1%): Coughing, dyspnea, hyperventilation, pneumonia, respiratory depression, pharyngitis, increased sputum

Postmarketing reports: Asthma, pneumonitis, dyspnea^[Ref]

Immunologic

Frequency not reported: Infection, sepsis

Postmarketing reports: Aseptic meningitis^[Ref]

Musculoskeletal

Rare (less than 0.1%): Arthralgia, myalgia, leg cramps^[Ref]