CELECOXIB – SULFONAMIDE ALLERGY

After conversation with several patients, physicians, and pharmacists, it has come to our attention that many are unaware of a celecoxib (Celebrex) contraindication. Per the package label, celecoxib is contraindicated in patients with a documented allergic-type reaction to sulfonamides. 

Levalbuterol is approved for the treatment of asthma. Levalbuterol is the R-enantiomer of racemic albuterol. In a single dose, double blinded, crossover study, adult patients with mild-to-moderate asthma received levalbuterol (in doses of 0.31 mg, 0.62 mg, 1.25 mg), albuterol and placebo. Each patient was treated with each drug and dose on five separate days. Based on pulmonary function tests, 0.62 mg levalbuterol was equivalent to 2.5 mg racemic albuterol and had fewer side effects. In a single dose crossover study, 43 children with asthma were treated with four of seven treatments. They were randomized to receive racemic albuterol (1.25 mg or 2.5 mg), levalbuterol (0.16mg, 0.31 mg, 0.63 mg, 1.25 mg) or placebo. The best results were obtained with the 1.25 mg levalbuterol dosage, however, the 0.31 and 0.63 mg levalbuterol groups and the 2.5 mg racemic albuterol doses were effective in providing adequate improvements in FEV-1 for a minimum of four hours. The contraindications, warnings and precautions are the same with levalbuterol as they are with albuterol. The drug is rated as FDA Pregnancy Category C. Levalbuterol should be used with caution in nursing mothers. Plasma levels of levalbuterol after inhalation are very low, but it is not known if this agent is excreted in breast milk. The adverse effects associated with levalbuterol are similar to those reported with racemic albuterol. In addition, the risk of tachyphylaxis may be reduced with levalbuterol. The incidence of certain beta-adrenergic adverse effects (e.g. Tremor, nervousness) was slightly less in the levalbuterol group as compared to the other treatment groups. The usual starting dose for patients greater than 12 years of age is 0.63 mg administered three times daily, every 6 to 8 hours by nebulization. Patients with more severe asthma or patients who do not respond adequately may require a dosage of 1.25 mg three times per day.

Thalidomide is approved for the treatment of cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). It is also indicated for the prevention and suppression of the cutaneous manifestations of erythema nodosum leprosum. It is currently used for several other purposes, including aphthous ulcers, AIDS related and cancer related cachexia, HIV/AIDS progression, Kaposi’s sarcoma and glioma. Thalidomide is an immunomodulator with sedative and anti-inflammatory activity. It’s activity in the treatment of ENL may be related to its selective inhibition of the production of tumor necrosis factor alpha (TNF-a), which is elevated in patients with ENL. It may also stimulate the proliferation of suppressor T lymphocytes. The mean time to peak plasma concentration ranges from 2.9 to 5.7 hours. Oral absorption has a wide degree of variability and may be related to the poor solubility of thalidomide in aqueous media. The mean half-life is 3.7 to 5.5 hours. The major route of elimination is non-renal as only 0.6% of the drug is excreted in the urine. Thalidomide, a glutamic acid derivative, has been shown to inhibit in vitro angiogenesis, the process of formation of new blood vessels.

Thalidomide is contraindicated in patients who have hypersensitivity to this agent or other ingredients, in women of child bearing potential (unless they meet specified conditions) and sexually mature males. These conditions include but are not limited to:

• Understanding and reliably carry out instructions
• Capability of complying with mandatory contraceptive measures, pregnancy testing and patient registration
• Received both oral and written warnings of hazards of the risk of possible contraceptive failure and need to use two reliable forms of contraception simultaneously
• Understanding of these factors is presented in writing at least two months prior to initiating therapy
• A negative pregnancy test within 24 hours prior to beginning therapy
• If minor patient, parent must read S.T.E.P.S. materials and agree to ensure compliance

The S.T.E.P.S. program is a system of registration and consent that must be completed prior to initiating therapy. The physician, patient and pharmacy must be registered with Celgene Corp. Thalidomide can cause severe birth defects and is categorized as Pregnancy Category X.

Peripheral neuropathy is a common and potentially severe and sometimes irreversible side effect of thalidomide therapy and may occur in up to 70% of patients. Reductions in white blood cell counts, including neutropenia have also been reported during thalidomide therapy and treatment should not be started if an absolute neutrophil count of less than 750/mm³ is recorded. The most common adverse effects include somnolence, dizziness and rash. Increased appetite, weight gain, headache, bradycardia, loss of libido, edema of the face and limbs, nausea, pruritis, eosinophilia and leukopenia have also been reported. Thalidomide enhances the activity of barbiturates, alcohol, chlorpromazine and reserpine. It should be used with caution with other CNS depressants. Amphetamines and methylphenidate will antagonize its sedative activity. Medications associated with neuropathy (i.e.: amiodarone, cisplatin, didanosine, paclitaxel) should be used with caution in patients receiving thalidomide.

For the treatment of ENL, thalidomide should be initiated at 100 to 300 mg daily, administered with water, preferably at bedtime and at least one hour after the evening meal.

Hydrogen peroxide solution as it may inactivate the papain. Papain may also be inactivated by the salts of heavy metals such as lead, mercury and silver. Contact with medications containing these metals should be avoided. Terramycin, aureomycin and chloromycetin may inhibit protein degradation.

Apply Accuzyme directly to the wound, cover with appropriate dressing and secure into place. Daily or twice daily applications are preferred. Irrigate the wound at each dressing change to remove any accumulation of liquefied necrotic material.