Zipsor Side Effects

Generic name: diclofenac

Note: This document contains side effect information about diclofenac. Some of the dosage forms listed on this page may not apply to the brand name Zipsor.

Some side effects of Zipsor may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to diclofenac: for solution oral, oral capsule, oral delayed release tablet, oral powder for reconstitution, oral tablet, oral tablet extended release

Get emergency medical help if you have any of these signs of an allergic reaction while taking diclofenac (the active ingredient contained in Zipsor) hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using diclofenac and call your doctor at once if you have a serious side effect such as:

• chest pain, weakness, shortness of breath, slurred speech, problems with vision or balance;

• black, bloody, or tarry stools;

• coughing up blood or vomit that looks like coffee grounds;

• swelling or rapid weight gain, urinating less than usual or not at all;

• nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• bruising, severe tingling, numbness, pain, muscle weakness;

• neck stiffness, chills, increased sensitivity to light, purple spots on the skin, and/or seizure (convulsions); or

• severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Less serious side effects of diclofenac may include:

• upset stomach, mild heartburn or stomach pain, diarrhea, constipation bloating, gas;

• dizziness, headache, nervousness;

• skin itching or rash;

• blurred vision; or

• ringing in your ears.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to diclofenac: compounding powder, oral capsule, oral delayed release tablet, oral powder for reconstitution, oral tablet, oral tablet extended release

Gastrointestinal

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

Colonic strictures, ulcerations, and bleeding 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.

Gastrointestinal side effects have been reported in up to 10% of patients. The most common side effects, despite the use of an enteric coated formulation, have included gastric upset or discomfort. Diarrhea, nausea, vomiting, and constipation have been reported in 3% to 9% of patients. Gastric ulcer (0.79%), peptic ulceration (with or without bleeding and perforation) (0.16% to 0.34%), duodenal ulcer (0.33%), anastomotic ulcer (0.01%), obstruction (0.01%), small bowel ulceration, pseudomembranous colitis, colonic strictures, and ileocolitis have been reported.

Hepatic

Elevations in serum transaminases three times normal values have been reported in up to 2% of patients during the first 2 months of diclofenac (the active ingredient contained in Zipsor) 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 have been reported in the literature. Autopsies in these cases revealed massive hepatic necrosis and cholestasis. Diclofenac-induced hepatitis may be a result of a hypersensitivity 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.

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 injury is most likely to occur in older females in the first 6 months of use.

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.

A 56-year-old man with chronic renal failure and liver cirrhosis developed transient anuria after being administered a single oral 100 mg dose of diclofenac (the active ingredient contained in Zipsor)

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.

Renal side effects have included rare reports of nephrotic syndrome, interstitial nephritis, renal papillary necrosis, acute renal failure, urinary frequency, nocturia, proteinuria, and hematuria. A case of transient anuria has been reported.

Dermatologic

A pruritic maculopapular eruption with hives, erythema, and vomiting developed in a 57-year-old female one hour after treatment with diclofenac (the active ingredient contained in Zipsor) 100 mg orally for gonarthrosis. After treatment with dexchlorpheniramine, symptoms subsided. Upon rechallenge with diclofenac 75 mg as well as desensitization attempts with increasing diclofenac doses, the patient developed similar symptoms as well as hypotension, conjunctivitis, and mild dyspnea which were resolved with dexchlorpheniramine, corticosteroids, and subcutaneous epinephrine.

A 34-year-old female with pubic pain after delivery experienced nicolau syndrome after an intramuscular dose of diclofenac on the upper outer quadrant of the right buttock. Immediately after the injection, the patient complained of an intense pain of the right buttock radiating to the posterior side of the leg. She was diagnosed with nicolau syndrome and administered treatment. She was completely healed after four months.

Dermatologic side effects have included rash (1% to 3%), pruritus (1% to 3%), eczema, alopecia, bullous eruptions, allergic purpura, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Severe pustular psoriasis has been reported. At least one case of pruritic maculopapular eruption has been reported, in addition to a case of nicolau syndrome.

Hematologic

Autoimmune hemolytic anemia and thrombocytopenia 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 have been reported, 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 (the active ingredient contained in Zipsor) when used for analgesia after adenotonsillectomy.

Hematologic side effects have included anemia, leukopenia, thrombocytopenia, hemolytic anemia, spontaneous bruising associated with increased bleeding times, purpura, agranulocytosis, and aplastic anemia. Blood dyscrasias are usually reversible upon cessation of diclofenac, although rare fatalities are reported. Postoperative hemorrhage has also been reported.

Musculoskeletal

A 44-year-old man with recurring knee pain treated himself with diclofenac (the active ingredient contained in Zipsor) 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.

Musculoskeletal side effects including at least one case of rhabdomyolysis have been reported.

Hypersensitivity

Hypersensitivity side effects including urticaria, rash, angioedema, bronchospasm, anaphylactoid reactions, and anaphylaxis have been reported in approximately 0.5% of patients.

A 44-year-old male with gout experienced urticarial rash coincident with diclofenac therapy. He was administered a 75 mg diclofenac tablet approximately 10 hours prior to presentation to the hospital. A diagnosis of anaphylaxis was made. He was treated with IV fluids, steroids, antihistamines and intramuscular epinephrine. He was discharged from the hospital one day after presentation.

Metabolic

Hyperkalemic quadriparesis in a 76-year-old woman who had received diclofenac (the active ingredient contained in Zipsor) sodium 100 mg/ day for 10 months for the treatment of gouty arthritis was reversed upon discontinuation of diclofenac therapy and the emergency treatment of the hyperkalemia with dextrose, insulin, and intravenous calcium gluconate.

Metabolic side effects have included rare reports of azotemia, hypoglycemia, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and a case report of diclofenac-induced porphyria. At least one case of hyperkalemic quadriparesis has also been reported.

Nervous system

Aseptic meningitis was reported in a 42-year-old female following two weeks of therapy with diclofenac (the active ingredient contained in Zipsor) 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.

Nervous system side effects including headache, drowsiness, dizziness, insomnia, and tremor have been uncommonly reported. In addition, aseptic meningitis has been reported.

Cardiovascular

Cardiovascular side effects have included myocardial infarction (0.74%), ischemic cerebrovascular stroke (0.81%), unstable angina pectoris (0.31%), peripheral venous thrombosis (0.16%), pulmonary embolism (0.15%), sudden cardiac death (0.14%), transient ischemic attack (0.13%), peripheral arterial thrombosis (0.03%), cardiac thrombus (0.02%), resuscitated cardiac arrest (0.01%), and cerebrovascular venous thrombosis (0.01%). Fluid retention and edema which may be important in patients with heart failure have been reported. In addition, blood pressure may be elevated by diclofenac (the active ingredient contained in Zipsor) which may have clinical relevance in patients with comorbid illnesses. Heart rate suppression has been reported.

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.

Evidence suggests that extensive use of diclofenac substantially increases the risk (by around twofold) of acute myocardial infarction in patients with no prior strong risk factors.

Psychiatric

Psychiatric side effects have included rare reports of depression, anxiety, irritability, nightmares, and psychotic reactions.

Other

Other side effects have included tinnitus, taste disturbance, and reversible hearing loss.

Ocular

Ocular side effects including peripheral corneal infiltrates and photosensitivity have been reported.

A 37-year-old physician receiving therapy for back pain experienced peripheral corneal infiltrates coincident with diclofenac therapy. The adverse event occurred two days after initiation of therapy at three different times. The peripheral corneal infiltrates resolved completely within 7 days, at each event, after discontinuation of therapy.

Diclofenac eye drops (0.1%) may cause transient stinging or burning.

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