REDUCED DOSE INTRAVENOUS ACETAMINOPHEN

• US 20170157071A1
• Filed: 02/17/2017
• Published: 06/08/2017
• Est. Priority Date: 11/13/2007
• Status: Active Grant

• Current Assignee: Mallinckrodt Hospital Products IP Ltd. (Mallinckrodt plc)
• Original Assignee: Mallinckrodt Ip (Mallinckrodt plc)
• Inventors: Royal, Mike Allan, Breitmeyer, James Bradley
• Granted Patent: US 9,987,238 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

Described herein are compositions and methods for intravenous administration of acetaminophen at a single dose level of less than about 1000 mg for the treatment or prevention of pain (e.g., postoperative pain) and/or fever.

Claims

1-75. -75. (canceled)

76. A method of treating pain in a human subject, in need thereof, weighing at least 50 kg comprising:

administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising about 500 mg to about 750 mg of acetaminophen; and

repeating the administration at least once every four hours;

wherein the pharmaceutical composition is administered to the subject intravenously; and

wherein the therapeutic effect of the pharmaceutical composition is comparable to the standard of care treatment of 1000 mg of acetaminophen administered orally every 6 hours.

77. The method of claim 76, wherein subject is administered less than 4 grams of acetaminophen over a twenty-four hour period.

78. The method of claim 76, wherein the pharmaceutical composition is administered to the subject at least six times in a period of 24 hours.

79. The method of claim 76, wherein the pharmaceutical composition comprises about 600 mg to about 700 mg of acetaminophen.

80. The method of claim 76, wherein the pharmaceutical composition comprises about 650 mg of acetaminophen.

81. The method of claim 76, wherein the pharmaceutical composition further comprises at least one antioxidant.

82. The method of claim 81, wherein the antioxidant is cysteine hydrochloride monohydrate.

83. The method of claim 76, wherein the pharmaceutical composition further comprises a buffering agent.

84. The method of claim 83, wherein the buffering agent is selected from the group consisting of a pharmaceutically acceptable salt or acid of citrate, phosphate, acetate, glutamate, tartate, benzoate, lactate, histidine or other amino acids, gluconate, malate, succinate, formate, proprionate, carbonate, and any combinations thereof

85. The method of claim 83, wherein the buffering agent is disodium phosphate dehydrate.

86. The method of claim 76, wherein the pharmaceutical composition has a pH between about 4 to about 8.

87. The method of claim 76, wherein the pharmaceutical composition has a pH between about 5 to about 6.

88. The method of claim 76, wherein the pharmaceutical composition has an osmolarity of between about 200 mOsm/L to about 400 mOms/L.

89. The method of claim 76, wherein the pharmaceutical composition further comprises an isotonicity agent.

90. The method of claim 89, wherein the isotonicity agent is selected from the group consisting of:

dextrose, mannitol, and lactose.

91. The method of claim 89, wherein the isotonicity agent is mannitol.

92. The method of claim 76, wherein the pharmaceutical composition is a lyophilized powder.

93. The method of claim 92, wherein the lyophilized powder is reconstituted in solution prior to administration.

94. The method of claim 76, wherein the pharmaceutical composition is intravenously administered to the subject over about 5 minutes to about 30 minutes.

95. The method of claim 76, wherein the pharmaceutical composition is intravenously administered to the subject over about 15 minutes.