The FDA has approved a fixed-dose combination of lumacaftor and ivacaftor (Orkambi – Vertex) for oral treatment of cystic fibrosis (CF) in patients ≥12 years old who are homozygous for the F508del mutation. About 50% of patients in the US with CF are homozygous for the F508del (also called Phe508del) mutation. This is the first approved indication for lumacaftor; ivacaftor is available alone as Kalydeco for treatment of CF in patients ≥2 years old with other mutations. Orkambi is the first drug to be approved in the US for treatment of patients with the F508del...

Trovafloxacin (Trovan - Pfizer) and its prodrug alatrofoxacin (Trovan IV) are new fluroroquinolones marketed for an unusually wide variety of infections, including oral and intravenous treatment of nosocomial and community-acquired pneumonia, acute ecerbations of chronic bronchitis, acute sinusitis, complicate intra-abdominal and pelvic infections, diabetic foot infection, uncomplicated urinary tract infection, prostatitis, cervicitis and uncomplicated gonorrhea.

Ceritinib (Zykadia – Novartis), an oral tyrosine kinase inhibitor, has received accelerated approval from the FDA for treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib (Xalkori). It is the second tyrosine kinase inhibitor to be approved for ALK-positive metastatic NSCLC; crizotinib was the first. Translocations of the ALK gene are found in about 5% of lung cancers; they occur predominantly in nonsmokers with adenocarcinoma.

The February 14th issue of The Medical Letter reviewed natalizumab (Tysabri - Biogen Idec), a new monoclonal antibody that was granted accelerated approval because it decreased the number of relapses in patients with multiple sclerosis. On February 28th, the FDA issued a Public Health Advisory announcing that marketing of the drug had been suspended because 2 patients who had been treated with natalizumab for more than 2 years had developed progressive multifocal leukoencephalopathy, a rare, often fatal disease...

Erlotinib (Tarceva) is the second oral epidermal growth factor receptor (EGFR) inhibitor to become available in the US for treatment of advanced refractory NSCLC. In clinical trials, erlotinib produced a response rate of only 8.9%, but increased median survival from 4.7 to 6.7 months. Patients who had never smoked and those with EGFR-positive tumors survived longer. Erlotinib is generally well tolerated; diarrhea and rash are the most common adverse effects.

The FDA has approved Apadaz (KemPharm), a short-acting, fixed-dose combination of benzhydrocodone and acetaminophen, for short-term management (≤14 days) of acute pain severe enough to require an opioid and for which alternative treatment options are inadequate. Benzhydrocodone is a prodrug of hydrocodone. Fixed-dose combinations of short-acting hydrocodone and acetaminophen or ibuprofen have been available for years and are the most abused opioid products in the US. Apadaz was developed under the presumption that inclusion of the inactive prodrug would reduce the potential for...

The injectable glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide, which was approved by the FDA as Mounjaro for treatment of type 2 diabetes in 2022, has now been approved as Zepbound (Lilly) for chronic weight management in adults who have a BMI ≥30 kg/m2 or a BMI ≥27 kg/m2 and at least one weight-related comorbidity. The injectable GLP-1 receptor agonists liraglutide (Saxenda) and semaglutide (Wegovy) are approved for chronic weight management in patients ≥12 years...

Voriconazole (Vfend -- Pfizer), an antifungal triazole structurally related to fluconazole (Diflucan) with a spectrum of action similar to that of itraconazole, has been approved by the FDA for primary treatment of invasive aspergillosis and for refractory infection with Scedosporium apiospermum (the asexual form of Pseudallescheria boydii) or Fusarium spp.

An injectable extended-release formulation of the opioid-receptor antagonist naltrexone (Vivitrol - Alkermes/Cephalon) has been approved by the FDA for once-monthly use, along with psychosocial support, to maintain abstinence from alcohol. Naltrexone inhibits the rewarding effects of alcohol. Oral naltrexone (Revia, and others) has been approved for treatment of alcohol dependence since 1994, but poor adherence has limited its effectiveness. In the new extended-release (XR) formulation, naltrexone is encapsulated in polylactide-co-glycolide microspheres (similar to absorbable suture material)...

Panitumumab (Vectibix - Amgen), a fully human IgG₂ monoclonal antibody that inhibits the epidermal growth factor receptor (EGFR), has been approved by the FDA for treatment of patients with EGFR-expressing metastatic colorectal cancer that has progressed despite standard chemotherapy. It is the second monoclonal antibody EGFR inhibitor to be approved for metastatic colorectal cancer; cetuximab (Erbitux), a human-murine chimeric IgG₁ monoclonal antibody, was approved in 2004.