FDA Safety Labeling Changes: Hectorol, Mevacor, Pulmicort Respules

Yael Waknine

September 28, 2005

Sept. 28, 2005 ( updated Oct. 6, 2005) -- The U.S. Food and Drug Administration (FDA) approved safety labeling revisions in June to advise that doxercalciferol dose reductions are recommended in patients who develop treatment-related hypercalcemia or hyperphosphatemia; concurrent administration of cytochrome P-450 3A4 inhibitors or danazol with lovastatin is linked to an increased risk of myopathy/rhabdomyolysis; and budesonide inhalation therapy does not alter the effectiveness of varicella vaccination in children aged one to eight years.

Doxercalciferol Injection (Hectorol) Dose Reductions for High Calcium/Phosphate Levels

On June 22, the FDA approved safety labeling revisions for doxercalciferol injection (Hectorol, made by Bone Care International) to advise of treatment recommendations for hypercalcemia and hyperphosphatemia secondary to its use.

According to the FDA, the serum calcium multiplied by serum phosphorus (Ca x P) product should be maintained below 55 mg 2/dL 2 in patients with chronic kidney disease.

If hypercalcemia occurs during therapy, doses of doxercalciferol and/or calcium-containing phosphate binders should be decreased. Should hyperphosphatemia occurs, the doxercalciferol dose should be decreased and/or that of phosphate binders increased.

Doxercalciferol injection is indicated for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.

Lovastatin (Mevacor) Drug Interactions Linked to Increased Risk of Myopathy, Rhabdomyolysis

On June 13, the FDA approved safety labeling revisions for lovastatin (Mevacor tablets, made by Merck & Co., Inc.) to advise of certain drug interactions that increase the risk of myopathy/rhabdomyolysis associated with its use.

As with other HMG-CoA reductase inhibitors, lovastatin may cause myopathy that presents as muscle pain, tenderness, or weakness with creatine kinase levels greater than 10 times the upper limit of normal. Myopathy may also take the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred.

Because lovastatin is a substrate for the cytochrome P-450 isoform 3A4 (CYP 3A4) enzyme, concomitant administration of potent CYP 3A4 inhibitors results in elevated HMG-CoA plasma activity levels and an increased risk of these adverse events.

Use of lovastatin in conjunction with itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, or large quantities of grapefruit juice (>1 quart daily) should be avoided.

Concomitant use of danazol may also increase the risk of myopathy/rhabdomyolysis, particularly at higher doses of lovastatin, and the risk-benefit ratio of such therapy should be carefully evaluated on an individual basis. In patients receiving both drugs, the dose of lovastatin should not exceed 20 mg per day.

Lovastatin is indicated for the treatment of dyslipidemia to reduce the risk of atherosclerotic vascular disease.

Budesonide (Pulmicort Respules) Does Not Interfere With Varicella Vaccination

Editor's note: This section has been corrected to show that the safety labeling change was to include the findings of a clinical trial.

An open-label, nonrandomized study has found that budesonide inhalation suspension (Pulmicort Respules, made by AstraZeneca Pharmaceuticals) does not alter the effectiveness of varicella vaccination in children aged one to eight years. In the study, a total of 243 asthma patients were treated with either budesonide respules or nonsteroidal asthma therapy. The results showed that the rate of developing seroprotective antibody titers was similar between the groups. In addition, no one receiving budesonide inhalation therapy developed chicken pox.

Although immunosuppressant doses of steroids are known to increase the risks of varicella and measles infection, there had been no previous studies evaluating the effect of inhaled steroids on the clinical course of chicken pox and measles.

Budesonide inhalation suspension is indicated for the maintenance treatment of asthma and as prophylactic therapy in children aged 12 months to eight years.

Reviewed by Gary D. Vogin, MD


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