FDA Safety Labeling Changes: Norditropin, Agrylin, and Lac-Hydrin

Yael Waknine

February 24, 2005

Feb. 24, 2005 — The U.S. Food and Drug Administration (FDA) approved in November and December 2004 revisions to safety labeling to advise healthcare professionals of the following changes: use of somatropin injection is contraindicated in the presence of active neoplasia or proliferative/preproliferative diabetic retinopathy, and pituitary and other brain tumors should be ruled out prior to initiation of somatropin therapy; dose reductions are required when prescribing anagrelide for patients with moderate hepatic impairment; sun exposure should be avoided for areas of the skin treated with ammonium lactate 12% cream.

Somatropin Injection (Norditropin) Contraindicated in Presence of Active Neoplasia

On Nov. 1, the FDA approved revisions to the safety labeling for somatropin [rDNA origin] injection (Norditropin Cartridges, made by Novo Nordisk Pharmaceuticals, Inc.) to advise of contraindications and warnings associated with its use.

Use of somatropin injection is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients, including histidine, poloxamer 188, phenol, and mannitol.

Somatropin injection should not be used to promote growth in patients with closed epiphyses.

Somatropin therapy is contraindicated in the presence of active neoplasia. Preexisting neoplasia should be inactive and treatment complete prior to initiation of somatropin therapy; therapy should be discontinued upon recurrence.

Because growth hormone deficiency may be an early sign of pituitary and other brain tumors, these should be ruled out prior to somatropin therapy initiation. The FDA notes that somatropin should not be used in patients with any evidence of progression or recurrence of an underlying lesion occupying intracranial space. Somatropin use has not been linked to an increased rate of tumor recurrence.

Somatropin use is also contraindicated in patients with proliferative or preproliferative diabetic retinopathy.

Somatropin injection is indicated for long-term replacement therapy in adults with confirmed growth hormone deficiency of either adult or childhood onset, and in children with growth failure due to inadequate secretion of endogenous growth hormone.

Anagrelide (Agrylin) Dose Reductions Required in Hepatic Impairment

On Dec. 17, the FDA approved revisions to the safety labeling for anagrelide HCl (Agrylin capsules, made by Shire Pharmaceutical Development, Inc.) to warn that dose reductions are required when prescribing the product for patients with moderate hepatic impairment.

The warning was based on the results of a pharmacokinetic study showing that total exposure (AUC) to anagrelide was increased eightfold in patients with moderate hepatic impairment.

The FDA notes that anagrelide has not been studied in patients with severe hepatic impairment and that its use in this population is contraindicated.

In patients with moderate hepatic impairment, anagrelide therapy should be initiated at a reduced dose of 0.5 mg/day (normal: 2 mg/day in divided doses) and be maintained for a minimum of one week with careful monitoring for adverse cardiovascular effects. As with anagrelide regimens for patients with normal hepatic function, incremental dose increases should not exceed 0.5 mg/day in any one week.

The FDA recommends that potential risks and benefits of anagrelide therapy be assessed prior to initiation of anagrelide therapy in patients with mild to moderate hepatic impairment.

Anagrelide is indicated for the treatment of thrombocythemia secondary to myeloproliferative disorders to reduce platelet count and the risk of thrombosis, and to improve associated symptoms such as thrombohemorrhagic events.

Avoid Sun Exposure for Skin Treated With Ammonium Lactate 12% Cream (Lac-Hydrin)

On Dec. 13, the FDA approved revisions to the safety labeling for ammonium lactate 12% cream (Lac-Hydrin, made by Bristol-Myers Squibb Co.) to advise of contraindications and warnings associated with its use.

Use of ammonium lactate cream is contraindicated in patients with a history of sensitivity to the active ingredient or other product excipients, including cetyl alcohol, glycerin, glyceryl stearate, laureth-4, light mineral oil, magnesium aluminum silicate, methylcellulose, methyl and propyl parabens, PEG-100 stearate, polyoxyl 40 stearate, and propylene glycol.

The FDA warns that sun exposure should be avoided or minimized for skin areas treated with ammonium lactate cream. Treatment should be discontinued if hypersensitivity develops.

Although clinical studies and postmarketing experience have not identified age-related differences in response to therapy, the FDA advises caution in selecting doses of ammonium lactate cream for elderly patients.

Ammonium lactate 12% cream is indicated for the treatment of ichthyosis vulgaris and xerosis.

Reviewed by Gary D. Vogin, MD

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