Update on Drugs and Drug News: September-October 2013

Dabrafenib mesilate capsule

Tafinlar™
GlaxoSmithKline Inc.

In July 2013, Health Canada approved this BRAF kinase inhibitor as a monotherapy oral treatment for unresectable melanoma or metastatic melanoma in adult patients whose tumors express the BRAF V600E gene mutation. Dabrafenib is not indicated for treating patients with wild-type BRAF melanoma. A validated test to identify BRAF V600 mutation status is required to determine treatment eligibility. Dabrafenib inhibits certain mutated BRAF kinases that activate the BRAF pathway and drive tumor cell growth.

Trametinib dimethyl sulfoxide tablet

Mekinist™
GlaxoSmithKline Inc.

In July 2013, Health Canada approved this first-in-class MEK1/ MEK2 inhibitor as a monotherapy oral treatment for unresectable or metastatic melanoma in adult patients with BRAF V600E or V600K mutations. These mutations must be detected by a validated companion diagnostic to confirm treatment eligibility. It is not indicated for patients who have received prior BRAF inhibitor therapy. Trametinib specifically binds to and inhibits MEK 1 and 2, resulting in inhibition of growth factor-mediated cell signalling and cellular proliferation in various cancers.

Vismodegib capsule

Erivedge®
Curis, Inc./Roche

The European Commission has granted conditional approval to this hedgehog pathway inhibitor in July 2013 for the treatment of adult patients with symptomatic metastatic basal cell carcinoma (BCC) or locally advanced BCC inappropriate for surgery or radiotherapy. The drug is administered orally once-daily.

In July 2013, the US FDA issued a Drug Safety Communication to healthcare professionals recommending ketoconazole oral tablets (Nizoral®) should no longer be used as a first-line treatment for any fungal infection due to the potential risk for severe liver damage, adrenal insufficiency, and drug interactions. Ketoconazole tablets should be used only for the treatment of certain life-threatening mycoses when the potential benefits outweigh the risks and alternative therapeutic options are not available or tolerated. The updated drug label for ketoconazole tablets will include:

• Use in Candida and dermatophyte infections is no longer indicated and should be used only when other antifungal drugs are not available or tolerated by the patient
• Not indicated for the treatment of fungal infections of the skin or nails
• Contraindicated in patients with acute or chronic liver disease

Topical formulations of ketoconazole, including creams, shampoos, foams, and gels, have not been associated with liver damage, adrenal problems, or drug interactions.

In August 2013, the US FDA issued a warning to consumers and healthcare professionals that acetaminophen is associated with rare but severe and potentially fatal skin reactions. The agency cited three published reports in which individuals developed Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP) following acetaminophen administration. From 1969 to 2012, a search of the FDA Adverse Event Reporting System database identified 91 cases of SJS/TEN and 16 cases of AGEP, which resulted in 67 hospitalizations and 12 deaths. The labels of prescription drug products containing acetaminophen will be required to indicate the risk for serious skin reactions. The FDA will also request that manufacturers add a warning about serious skin reactions to the product labels of over-the-counter acetaminophen drug products.