FDA Approvals: Ammonul, VIGIV, TQ-1017

Yael Waknine

February 24, 2005

Feb. 24, 2005 -- The U.S. Food and Drug Administration (FDA) has approved sodium phenylacetate plus sodium benzoate intravenous injection for rescue treatment of patients with urea cycle disorder in hyperammonemic crisis; a vaccinia-specific immunoglobulin G intravenous injection for the treatment of smallpox vaccine complications; and a secure-release once-daily formulation of tramadol for the management of HIV-related neuropathic pain.

Sodium Phenylacetate plus Sodium Benzoate Injection (Ammonul) for UCD Crisis Rescue

On Feb. 17, the FDA approved sodium phenylacetate plus sodium benzoate 10%/10% intravenous injection (Ammonul, made by Ucyclyd Pharma, a subsidiary of Medicis Pharmaceutical Corp.) for adjunctive use in the treatment of acute hyperammonemia and associated encephalopathy in patients with urea cycle disorder (UCD).

The product scavenges ammonia directly from the bloodstream, bypassing the enzyme-deficient urea cycle in patients with UCD. It is intended for use as rescue therapy for patients who progress into hyperammonemic crisis.

Adverse events reported with sodium phenylacetate/sodium benzoate therapy include rare occurrences of vomiting, hyperglycemia, hypokalemia, convulsions, and mental impairment.

Sodium phenylacetate plus sodium benzoate injection previously received orphan drug status for this indication.

Vaccinia-Specific IgG Injection (VIGIV) for Complications of Smallpox Vaccination

On Feb. 18, the FDA approved a human plasma--derived antibody product (Vaccinia Immune Globulin Intravenous; VIGIV, made by DynPort Vaccine Company, LLC) for the treatment and modification of certain rare complications of smallpox vaccination.

Patients at risk for vaccinia infection include those with eczema or other skin conditions and those with a suppressed immune system due to disease or medication. The product is not intended for use in treating common and self-limiting adverse events related to smallpox vaccine, such as sore arm, fever, and body rash.

The injection contains purified vaccinia-specific immunoglobulin G (IgG) antibodies derived from pooled human plasma collected from donors immunized with the Dryvax smallpox vaccine (made by Wyeth Laboratories, Inc.) and is intended to boost a patient's immune response to the vaccinia virus.

Indications include aberrant vaccinia infections induced by accidental implantation in eyes (except in cases of isolated keratitis), mouth, and other areas where the infection would constitute a special hazard; eczema vaccinatum; progressive vaccinia; and severe generalized vaccinia.

The product is also indicated for use in treating vaccinia infections in patients with highly active or extensive eczematous skin lesions or skin conditions (burns, impetigo, varicella-zoster, or poison ivy).

The approval was based on the results of a study showing the product's efficacy in raising serum antibody concentrations to be similar to those of a previously licensed intramuscular formulation (Vaccinia Immune Globulin Intramuscular; VIGIM, made by Baxter Healthcare Corp. in 1994).

Safety and tolerability of the antibody product were confirmed in a study involving 111 healthy volunteers. Adverse events were mild to moderate in severity and included headache, hives, and other rashes.

Once-Daily Secure-Release Tramadol (Orphan Drug TQ-1017) for HIV-Related Neuropathic Pain

On Feb. 17, the FDA approved orphan drug status for a once-daily secure-release formulation of tramadol (TQ-1017, made by TheraQuest Biosciences, LLC) for the management of HIV-related neuropathic pain.

According to a company news release, the extended-release formulation incorporates several deterrents for abuse. The product cannot be crushed for inhalation or to obtain rapid euphoria from high blood levels when swallowed. In addition, extraction of tramadol using common solvents is difficult.

Short-acting tramadol 50-mg tablets (Ultram, made by Ortho-McNeil Pharmaceuticals, Inc.) are approved by the FDA for the management of moderate to moderately severe pain in adults.

A once-daily formulation of tramadol (made by Labopharm, Inc., and marketed by Sanofi-Aventis) was recently approved in France.

Reviewed by Gary D. Vogin, MD


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