Menactra available for young children; FDA approves vandetanib

July 15, 2011

On April 22, 2011, Menactra was granted FDA approval for use in infants and toddlers as young as 9 months of age.

Key Points

Quadrivalent meningococcal (groups A, C, Y, and W-135)polysaccharide diptheria toxoid conjugate vaccine

(Menactra, Sanofi Pasteur)

In 2005, the Menactra vaccine became the first quadrivalent meningococcal (groups A, C, Y, and W-135) conjugate vaccine available in the United States for people 11 to 55 years of age. It was subsequently approved in 2007 for use in children 2 to 10 years of age. On April 22, 2011, Menactra was granted FDA approval for use in infants and toddlers as young as 9 months of age. This is the first FDA approval of a meningococcal vaccine for this age group.

Efficacy. The efficacy of Menactra in infants and toddlers was assessed in one phase 2 and three phase 3 single-blind, controlled, U.S. multicenter trials enrolling more than 3,300 subjects. Menactra was administered using a 2-dose schedule, starting in children as young as 9 months. These studies demonstrated that Menactra produced a significant immune response against the meningococcal serogroups included in the vaccine. In 1 of these studies, the proportion of infants and toddlers achieving a human serum bactericidal assay (SBA-H) titer of at least 1:8 (the primary determinant of efficacy in this study) was 95.6%, 100%, 96.4%, and 86.4% for the A, C, Y, and W-135 serogroups, respectively, at 30 days after the second dose of Menactra.

Safety. The most common adverse events in infants and toddlers 9 and 12 months of age (occurring in ≥10% of study participants) were injection site tenderness (37.4%), erythema (30.2%) and swelling (16.8%), irritability (56.8%), abnormal crying (33.3%), drowsiness (30.2%), appetite loss (30.2%), vomiting (14.1%), and fever (12.2%). Guillain-Barré syndrome (GBS) has been reported following Menactra administration.

Dosing. Menactra is administered in children 9 through 23 months of age as a series of two 0.5-mL intramuscular injections given 3 months apart. Studies show that the measles-mumps-rubella-varicella vaccine and the pneumococcal conjugate vaccine can be administered concomitantly with Menactra.

Patients experiencing a severe allergic reaction after a previous dose of Menactra, a meningococcal capsular polysaccharide-, diphtheria toxoid- or CRM197-containing vaccine, or those with a history of GBS, should not receive Menactra.

Oral kinase inhibitor

(Vandetanib, AstraZeneca)

On April 6, 2011, FDA approved vandetanib for the treatment of progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.

Efficacy. Vandetanib's efficacy was established in a single, double-blind, placebo-controlled study involving 331 patients [vandetanib 300 mg (n=231) versus placebo (n=100)] with unresectable locally advanced or metastatic medullary thyroid cancer. Efficacy was measured by the patients' progression-free survival (PFS). Statistically significant improvements in PFS were observed in patients randomly assigned to vandetanib [59 of 231 (26%)] compared to placebo [41 of 100 (41%)] (HR=0.35; 95% CI, 0.24 to 0.53; P<.0001).

Safety. The most common adverse reactions (occurring in >20%) seen with vandetanib were diarrhea, rash, acne, nausea, hypertension, headache, fatigue, decreased appetite, and abdominal pain. Laboratory abnormalities (occurring in >20%) included decreased calcium, increased ALT, and decreased glucose. The use of vandetanib has resulted in Stevens-Johnson syndrome, interstitial lung disease, ischemic cerebrovascular events, hemorrhage, heart failure, hypothyroidism, and reversible posterior leukoencephalopathy syndrome. In addition, Torsades de pointes, ventricular tachycardia, and sudden death have been reported. QT interval prolongation has been reported in a concentration-dependant manner with the use of vandetanib [~35 ms for the 300-mg dose]. In addition, 36% of patients receiving vandetanib experienced >60 ms increase in the QT interval, and 4.3% of patients had a QTc >500 ms. Vandetanib treatment should not be started in patients whose QTc interval is >450 ms. If the QTc rises above 500 ms, vandetanib use should be interrupted until QTc returns to <450 ms, then resume at reduced dose.

Dosing. The recommended daily dose for vandetanib is 300 mg taken once daily (with or without food). Patients should continue to take vandetanib until they are no longer benefiting from treatment or an unacceptable toxicity occurs. A reduced starting dose of 200 mg should be given to patients with moderate and severe renal impairment.

Pregnancy should be avoided during treatment and for at least 4 months after treatment when the patient is taking vandetanib because it could cause fetal harm. Reduced drug levels of vandetanib may be found with the concomitant use of strong CYP 3A4 inducers and therefore should be avoided.

Vandetanib is available only through a restricted distribution program.

Craig I. Coleman is associate professor of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Conn., and director of the Pharmcoeconomics and Outcomes Studies Group, Hartford Hospital.