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« on: June 23, 2007, 01:40:07 pm » |
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April 26, 2007 — The US Food and Drug Administration (FDA) has approved a 200-mg/5-mL formulation of cefixime oral suspension to facilitate pediatric dosing and enhance therapeutic compliance; a new indication for Rh0(D) immune globulin intravenous (human) injection, allowing its use to raise platelet counts in patients with chronic immune thrombocytopenia purpura; and protein C concentrate (human) injection for the prevention and treatment of venous thrombosis and purpura fulminans in patients with severe congenital protein C deficiency.
Cefixime 200-mg/5-mL Oral Suspension (Suprax) Facilitates Pediatric Dosing
On April 10, the FDA approved a 200-mg/5-mL formulation of cefixime oral suspension (Suprax; Lupin Pharmaceuticals Ltd) for the treatment of infections caused by susceptible strains of designated microorganisms.
Compared with the previously approved 100-mg/5-mL suspension, the new formulation allows parents to administer fewer teaspoons per dose of the antibiotic to their children and is expected to provide increased convenience and therapeutic compliance.
According to a company news release, commercial shipments of the product have already commenced.
Cefixime oral suspension is a cephalosporin antibiotic indicated for the treatment of uncomplicated urinary tract infections, otitis media, pharyngitis and tonsillitis, acute bronchitis and acute exacerbations of chronic bronchitis, and uncomplicated gonorrhea.
The recommended dose of cefixime in pediatric patients is 8 mg/kg/day; children weighing more than 50 kg and those older than 12 years should receive the recommended adult dose (400 mg/day).
Rh0(D) Immune Globulin Intravenous (Human) (Rhophylac) for Chronic ITP
On March 26, the FDA approved a new indication for Rh0(D) immune globulin intravenous (human) injection (Rhophylac; CSL Behring [formerly ZLB Behring]), allowing its use to raise platelet counts in Rho(D)-positive, nonsplenectomized adult patients with chronic immune thrombocytopenia purpura (ITP).
Also known as idiopathic thrombocytopenic purpura, ITP usually results from the production of autoantibodies that coat platelets and cause their elimination from the blood. It is characterized by low platelet counts (< 30 × 109/L), petechiae, and mucosal bleeding, often accompanied by fatigue.
Although not fully understood, Rh0(D) immune globulin's mechanism of action is thought to involve the formation of Rh0(D) immune globulin red blood cell complexes that are preferentially removed by the reticuloendothelial system, particularly the spleen; the resulting Fc membrane receptor blockade serves to spare antibody-coated platelets.
Approval of the ITP indication was based on data from an open-label, single-group, multicenter trial of 98 patients with platelet counts of 30 × 109/L or less who received a single 250-IU (50-µg)/kg intravenous dose of Rh0(D) immune globulin injection. The primary endpoint was defined as an increase in platelet count of greater than 20 × 109/L from baseline and the achievement of a platelet count of 30 × 109/L or greater by day 15.
Results showed that this goal was achieved by 66.3% (95% confidence interval, 56.5% - 74.9%) of patients overall — success rates in subgroups determined by baseline platelet count (× 109/L) were 39.5% (? 10); 78.6% (> 10 - 20); 88.9% (> 20 - 30); and 80.0% (> 30). The median time to response was 3 days and median duration of response was 22 days (secondary endpoints).
Furthermore, 55.1% of patients exceeded this response, achieving an increase in platelet counts to 50 × 109/L or greater by day 15; subgroup rates ranged from 26.3% (baseline ? 10 × 109/L) to 100% (baseline > 30 × 109/L).
During the study, 88% (95% confidence interval, 76% - 94%) of 50 patients with bleeding at baseline demonstrated an overall regression of hemorrhage; the percentage of patients without bleeding increased to a maximum of 70.4% on day 8.
The most commonly reported adverse events associated with use of Rh0(D) immune globulin therapy for ITP included chills (34.7%), pyrexia/increased body temperature (30.6%), increased blood bilirubin levels (21.4%), and headache (11.2%). Intravascular hemolytic reaction occurred in 2 patients who subsequently recovered completely.
Rh0(D) immune globulin injection must be administered intravenously in ITP patients; the recommended 250-IU (50-µg)/kg dose should be infused at a rate of 2 mL per 15 to 60 seconds.
The FDA advises that patients receiving Rh0(D) immune globulin be monitored for signs and symptoms of intravascular hemolysis, including back pain, shaking chills, fever, and hemoglobinuria. Complications of the condition include clinically compromising anemia, acute renal insufficiency, and, very rarely, disseminated intravascular coagulation and death.
Rh0(D) immune globulin injection previously was approved for intravenous or intramuscular use to suppress rhesus (Rh) isoimmunization in nonsensitized Rh0(D)-negative women with an Rh-incompatible pregnancy, including routine antepartum and postpartum Rh prophylaxis and Rh prophylaxis in cases of obstetric complication or invasive procedures during pregnancy. It also is indicated for the suppression of Rh isoimmunization in Rh0(D)-negative individuals transfused with Rho(D)-positive red blood cells or blood components containing Rh0(D)-positive red blood cells.
Protein C Injection (Ceprotin) for Patients With Severe Congenital Deficiency
On March 30, the FDA approved protein C concentrate (human) lyophilized powder for injectable solution (Ceprotin; Baxter Healthcare Corp) for the prevention and treatment of venous thrombosis and purpura fulminans in pediatric and adult patients with severe congenital protein C deficiency. Orphan drug status was also granted for this indication, which currently affects less than 20 individuals in the United States.
"This product offers much-needed treatment for the small number of patients with severe inherited protein C deficiency," said Jesse Goodman, MD, MPH, director of the FDA's Center for Biologics Evaluation and Research, in an FDA news release. "If left untreated, clotting may result in blindness, severe brain damage, multi-organ failure and death for these patients."
The FDA's approval was based on a priority review of data from a multicenter, open-label, nonrandomized, phase 2/3 study in 18 patients (9 male) aged newborn to 25.7 years. Results showed that the biologic product was effective for 94% of purpura fulminans episodes; the remaining 6% required dose adjustments and treatment was deemed "effective with complications."
When compared with a historical control group, use of protein C for purpura fulminans episodes was found to be more effective than other options such as fresh frozen plasma or conventional anticoagulants. It also yielded a decrease in the number and size of skin lesions, healing nonnecrotic and necrotic lesions after a median of 4 and 11 days, respectively. Inadequate data were available for the treatment of warfarin-induced skin necrosis.
No blood clotting complications were observed in the 7 patients who received protein C as a preventive measure prior to surgery or anticoagulation therapy or in 8 patients who received the biologic product as a long-term preventive measure. The most commonly reported adverse events were hypersensitivity reactions (itching and rash) and lightheadedness. Hemothorax, hypotension, hyperhydrosis, fever, and restlessness have been reported during postapproval use.
The recommended regimen of protein C injection for acute episodes and short-term prophylaxis of events is 100 to 120 IU/kg (initial dose) followed by 3 doses of 60 to 80 IU/kg every 6 hours, adjusted to maintain a target peak protein C activity of 100%. After the acute episode is resolved, the same dose should be used to maintain a protein C activity level above 25% for the remainder of the treatment period. The maintenance dose for short-term prophylaxis ranges from 45 to 60 IU/kg given every 6 or 12 hours. For long-term prophylaxis, patients should receive 45 to 60 IU/kg every 12 hours.
The FDA notes that patients following low sodium/renal impairment diets should be informed that the maximum daily dose of protein C injection contains greater than 200 mg of sodium.
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
http://www.rhophylac4itp.com/includes/rhophylacitpPI.pdf
http://www.fda.gov/cber/label/protbax033007LB.pdf
Source: http://www.medscape.com/viewarticle/555732?src=mp
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