Treatment of vomiting and nausea with minimum dose of olanzapine
Compositions, devices, and methods for transdermal administration of olanzapine and uses thereof, e.g., to treat nausea and vomiting.
1. A method for preventing or reducing the frequency and/or intensity of vomiting (emesis) and/or nausea associated with chemotherapy, comprising: administering olanzapine transdermally in an amount greater than about 2 mg and less than about 8 mg per day in combination with a fatty alcohol, a fatty ester, or a combination thereof in a drug-in-adhesive formulation, wherein an average flux rate of olanzapine of at least 3 μg/cm 2 /hr is achieved continuously throughout a period of at least 3 days after administration.
2. The method of claim 1 , wherein said transdermal administration provides a plasma concentration of olanzapine i) 24 hours after administration of at least about 7 μg/L, ii) 48 hours after administration of greater than about 11 μg/L, and iii) 60 hours after administration of greater than about 15 μg/L.
3. The method of claim 1 , wherein said transdermal administration provides a plasma concentration of olanzapine 24 hours after administration of at least about 6 μg/L and achieves a steady state plasma concentration of olanzapine of about 16-24 μg/L for a period beginning at a time 24 hours after administration and continuing for at least about 2 days.
4. The method of claim 1 , wherein said transdermal administration provides a plasma concentration of olanzapine 24 hours after administration of at least about 8 μg/L and achieves a steady state plasma concentration of olanzapine of about 18-22 μg/L for a period beginning at a time 24 hours after administration and continuing for at least about 2 days.
5. The method of claim 1 wherein sedation resulting from said administering is essentially unchanged relative to an olanzapine oral dose of about 2 mg.
6. The method of claim 1 , wherein the chemotherapy is emetogenic cancer chemotherapy.
7. The method of claim 1 , wherein transdermally administering comprises applying to skin of a human subject a composition, the composition comprising: (i) at least about 40 wt % of a pressure-sensitive adhesive; (ii) between about 3-15 wt % of the fatty ester, the fatty alcohol, or a combination thereof; and (iii) between about 1-20 wt % olanzapine.
8. The method of claim 1 comprising: transdermally administering olanzapine to a subject in need thereof in a dose ranging from 2.0 mg to 6.0 mg daily.
9. The method of claim 1 comprising: transdermally administering olanzapine to a subject in need thereof, wherein the method achieves an AUC of olanzapine ranging from 1000 to 2500 μg/L/h.
10. The method of claim 1 comprising: transdermally administering olanzapine to a subject in need thereof, wherein the method achieves a mean Cmax ranging from 5 to 20 μg/L.
11. The method of claim 1 comprising: transdermally administering olanzapine to a subject in need thereof, wherein the method achieves an AUC of olanzapine of between 20% and 80% of the AUC obtained from a standard of care treatment.