Liquid pharmaceutical formulations of palonosetron
The present invention relates to shelf-stable liquid formulations of palonosetron for reducing chemotherapy and radiotherapy induced emesis with palonosetron. The formulations are particularly useful in the preparation of intravenous and oral liquid medicaments.
1. A pharmaceutical single-use, unit-dose formulation for intravenous administration to a human to reduce the likelihood of cancer chemotherapy-induced nausea and vomiting, comprising a 5 mL sterile aqueous solution, said solution comprising:
a) palonosetron hydrochloride in an amount of 0.25 mg based on the weight of its free base,
b) optionally a chelating agent, and
c) a tonicifying agent in an amount sufficient to make said solution isotonic, wherein said formulation is stable at 24 months when stored at room temperature.
2. The pharmaceutical formulation of claim 1 , wherein said solution is buffered at a pH of 5.0±0.5.
3. The pharmaceutical formulation of claim 1 , wherein said tonicifying agent is mannitol.
4. The pharmaceutical formulation of claim 3 , wherein said mannitol is in an amount from 10 mg/mL to 80 mg/mL.
5. The pharmaceutical formulation of claim 4 , wherein said mannitol is in an amount of 41.5 mg/mL.
6. The pharmaceutical formulation of claim 1 , wherein said formulation comprises a chelating agent.
7. The pharmaceutical formulation of claim 6 , wherein said chelating agent is EDTA.
8. The pharmaceutical formulation of claim 7 , wherein said EDTA is in an amount of from 0.005 mg/mL to 1.0 mg/mL.
9. The pharmaceutical formulation of claim 8 , wherein said EDTA is in an amount of 0.5 mg/mL.
10. The pharmaceutical formulation of claim 1 , wherein said solution further comprises a citrate buffer.
11. The pharmaceutical formulation of claim 10 , wherein said citrate buffer is at a concentration of 20 millimolar.
12. A method for reducing the likelihood of cancer chemotherapy-induced nausea and vomiting, comprising intravenously administering to a human in need thereof the pharmaceutical formulation of claim 1 , wherein said intravenous administration to said human occurs before the start of the cancer chemotherapy.
13. The method of claim 12 , wherein said intravenous administration to said human occurs over a period of time of 10 to 60 seconds.
14. The method of claim 12 , wherein said intravenous administration reduces the likelihood of acute nausea and vomiting in said human.
15. The method of claim 12 , wherein said intravenous administration reduces the likelihood of delayed nausea and vomiting in said human.
16. A pharmaceutical single-use, unit-dose formulation for intravenous administration to a human to reduce the likelihood of cancer chemotherapy-induced nausea and vomiting, comprising a 5 mL sterile aqueous solution, said solution comprising:
a) palonosetron hydrochloride in an amount of 0.25 mg based on the weight of its free base,
b) optionally a chelating agent, and
c) a tonicifying agent in an amount sufficient to make said solution isotonic, wherein said formulation is stable at 18 months when stored at room temperature.