Feldene Transdermal Patch Side Effects


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Feldene transdermal patch Feldene Feldene / piroxicam/ Fentanyl transdermal patches

Feldene, which is also known as piroxicam, is a member of the oxicam group of nonsteroidal anti-inflammatory drugs (NSAIDs). It has been marketed in the U.S. since 1982 and has been associated with a substantial increased risk of Stevens-Johnson syndrome, similar to Daypro. Piroxicam has been approved for the treatment of rheumatoid arthritis (RA) and osteoarthritis (OA). The drug has an extremely long half-life (time it takes for the blood plasma concentration of the drug to be reduced by one-half), which means that the amount of drug available for therapeutic (and toxic) effect is greater in the blood stream for a longer period of time, which increases its propensity to cause toxic reactions, such as Stevens Johnson syndrome or toxic epidermal necrolysis. The main concern is bullous drug reactions-erythema multiforme(EM), Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). NSAIDs have played an increasing role in the etiology of TEN and it may be that drugs with a longer serum half-life carry a higher risk. In pre-marketing and post-marketing studies of a new drug, careful attention should be paid to the nature of the side-effects, as a high rate of mild reactions belonging to the EM spectrum may be indicative of higher risks of SJS and TEN. [1]
[1] Roujeau, J.C., “Clinical Aspects of Skin reactions to NSAIDs,” Scandinavian Journal of Rheumatology (Suppl. 65); 131-134, 1987.
American Family Physician: Serious and life-threatening drug eruptions - Cover Story

Drug eruptions are common diseases. Although most of these conditions are benign and self-limited when use of the responsible drug is discontinued, several subtypes of drug eruptions are characterized by significant morbidity and mortality. The more dangerous types include erythroderma, leukocytoclastic vasculitis, anticonvulsant hypersensitivity syndrome, Stevens-Johnson syndrome and toxic epidermal necrolysis. Relatively few medications are repeatedly implicated in the pathogenesis of severe reactions. Prompt recognition of drug eruptions and early intervention are necessary to prevent the serious consequences of this group of iatrogenic diseases.

As options for pharmacotherapy continue to expand, so does the frequency of iatrogenic disease. Adverse reactions to medications are common, with a reported incidence of 10 to 20 percent in hospitalized patients.(1)(2)(3)(4)(5) Although less well documented, the rate of outpatient visits related to adverse drug reactions has been estimated to be as high as one per 40 visits to general practitioners.(1)
Cutaneous eruptions are one of the most frequent presentations of adverse drug reactions. Maculopapular, morbilliform and urticarial eruptions are the most common types and usually resolve without incident when the responsible medication is discontinued.(6)(7)(8) However, several less common cutaneous reactions are associated with significant morbidity and mortality.(1)(6)(9) Medications that are most frequently implicated in serious drug eruptions are listed in Table 1.

TABLE 1 Medications That Can Cause Serious Cutaneous Drug Eruptions

Allopurinol (Zyloprim)
Nonsteroidal anti-inflammatory drugs
Thiol medications
Bumetanide (Bumex)
Captopril (Capoten)
Furosemide (Lasix)
Penicillamine (Cuprimine)
Piroxicam (Feldene)
Thiazide diuretics
An awareness of cross-reactivity between medications is important, since patients often take multiple drugs concurrently and more than one medication may be responsible for the reaction. An example of this situation involves the diverse thiol (sulfhydryl-containing) medications (Table 1), which are often used simultaneously for unrelated indications.
Prompt recognition and early intervention are critical in minimizing the morbidity and mortality associated with severe cutaneous drug reactions.

Erythroderma, or exfoliative dermatitis, is defined as diffuse inflammation of all or most of the cutaneous surface. Erythroderma has a male predominance and an average age of onset in the sixth decade.(10)(11) The etiology of erythroderma generally falls into one of five categories: (1) preexisting dermatoses (e.g., psoriasis), (2) drug eruptions, (3) underlying malignancy, (4) miscellaneous factors (e.g., acquired immunodeficiency syndrome) and (5) idiopathic causes.(10)(11)(12) Drug-induced erythroderma accounts for 10 to 20 percent of cases in most series.(11)(12) Antiepileptic, antihypertensive and antibiotic medications are frequently implicated, but many drugs, including topical preparations, may be a possible cause.(10)(11)

Exfoliative dermatitis presents as generalized erythema and desquamation (Figure 1), often associated with pruritus, fever and chills.(10)(11) Lymphadenopathy is frequently noted, and hepatosplenomegaly is present in a minority of patients.(10)(11) Complications of exfoliative dermatitis may include high-output cardiac failure due to expanded circulation, hypothermia and hyperpyrexia, and a negative nitrogen balance.(13)


Leukocytosis, eosinophilia, mild anemia and abnormal serum protein electrophoresis may be present.(10)(11)(13) Skin biopsy often has nonspecific findings but may reveal a preexisting dermatosis or show changes consistent with mycosis fungoides.(10)

The mechanism by which erythroderma develops in patients using topical medications is an irritant or allergic contact dermatitis. The pathogenesis of exfoliative dermatitis secondary to systemic medications is less clear.(10) Treatment of drug-induced erythroderma includes discontinuation of the medication, daily baths, emollients, antihistamines and topical or systemic corticosteroids.(10)(13) Although the reported mortality rates for erythroderma have ranged from 8 percent to 64 percent, patients with drug-induced erythroderma have a much more favorable prognosis, with full recovery in the majority of cases.(10)(13)

Leukocytoclastic Vasculitis

Leukocytoclastic vasculitis, or allergic vasculitis, is the most common of the serious drug eruptions. Although leukocytoclastic vasculitis may have several etiologies, the factors most frequently implicated are medications, infections and immune-complex diseases.(14)(15)



SUBJECT: Analysis and recommendations for Agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk

Executive Summary

Following a thorough review of the available data we have reached the following conclusions regarding currently approved COX-2 selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs)1 and the risk of adverse cardiovascular (CV) events:2

• The three approved COX-2 selective NSAIDs (i.e., celecoxib, rofecoxib, and valdecoxib) are associated with an increased risk of serious adverse CV events compared to placebo. The available data do not permit a rank ordering of these drugs with regard to CV risk.

• Data from large long-term controlled clinical trials that have included a comparison of COX-2 selective and non-selective NSAIDs do not clearly demonstrate that the COX-2 selective agents confer a greater risk of serious adverse CV events than non-selective NSAIDs.



The eruption of vasculitis usually begins in dependent areas, such as the lower extremities in ambulatory patients or the posterior thorax and sacrum in nonambulatory patients. The first lesions to appear are blanching erythematous macules, which may rapidly become elevated and purpuric (Figure 2), and occasionally bullous. Pruritus, pain and dependent edema are variably present. Systemic signs such as fever, arthralgias, myalgias, arthritis and abdominal pain may occur.(16) In severe cases, vasculitis may affect renal, gastrointestinal, pulmonary, cardiac and central nervous systems.(16)


Biopsy of an early skin lesion shows neutrophilic infiltration and fibrinoid necrosis of the walls of blood vessels, as well as leukocytoclasia.(14)(16) Direct immunofluorescence most commonly reveals deposition of IgM, complement or fibrin around dermal blood vessels.(14) Laboratory abnormalities may include hematuria, proteinuria and uremia, as well as elevated serum creatinine levels and erythrocyte sedimentation rates.

Leukocytoclastic vasculitis is a classic type III hypersensitivity reaction, in which immune complexes are deposited in postcapillary venules, with resultant complement activation and neutrophil recruitment.(14)(16) Release of lysosomal enzymes from neutrophils leads to vessel damage and the resultant clinicopathologic findings.

Many medications have been implicated in the etiology of leukocytoclastic vasculitis, but some drugs cause this reaction more frequently.(1)(16) These drugs include penicillins, thiazide diuretics, sulfonamides, nonsteroidal anti-inflammatory drugs (NSAIDs) and quinidine.(1)(16)

The evaluation of a patient with leukocytoclastic vasculitis should include a complete history, physical examination and laboratory tests, including a complete blood count, assessment of renal function, urinalysis and stool testing for occult blood. Further testing, as dictated by the preliminary clinical or laboratory findings, may be appropriate if no drug is implicated.

Potentially responsible medications must be promptly discontinued. For patients with extracutaneous involvement, treatment with systemic corticosteroids, azathioprine (Imuran), methotrexate or cyclophosphamide (Cytoxan) may be necessary.(15)(16) Patients whose vasculitis is limited to the skin may need only topical care or may require treatment with systemic corticosteroids, sulfones, colchicine or, rarely, azathioprine.(15)(16) Prognosis is related to the presence or absence of systemic involvement.

Anticonvulsant Hypersensitivity Syndrome

The anticonvulsant hypersensitivity syndrome, also known as the phenytoin (Dilantin) pseudolymphoma syndrome, is a rare complication that occurs with the use of antiepileptic medications, most commonly phenytoin. Carbamazepine (Tegretol) and phenobarbital have also been reported to cause a similar reaction.(17)(18)

In most cases, hypersensitivity develops three weeks to three months after initiation of therapy, which is much later than the time at which is much later than the time at which most drug reactions occur.(19)(20) The cardinal features of anticonvulsant hypersensitivity syndrome are high spiking fever, rash, lymphadenopathy and hepatitis.(17)(19)(20) Although a maculopapular erythematous eruption (Figure 3) is the most common cutaneous presentation, diffuse pustulation or erythroderma is not uncommon.(17) Edema, especially facial or acral, is a frequent finding (Figure 4).(17)(18) Lymphadenopathy may be localized or diffuse.(20)


Laboratory investigations commonly reveal leukocytosis with frequent eosinophilia, as well as elevated serum transaminase values. Histopathology of skin and lymph nodes may vary from a reactive pattern to frank lymphomatous changes.(19)(20)(21)

It has been postulated that this syndrome occurs as a result of a delayed hypersensitivity reaction.(17)(22) Treatment includes discontinuation of the medication, with careful substitution necessary because of the high rate of cross-reactivity between anticonvulsant medications.(17)(18)(20) Systemic corticosteroids have been anecdotally reported to be effective in more extensive cases of anticonvulsant hypersensitivity syndrome.(17)