TIVORBEX- indomethacin capsule
Iroko Pharmaceuticals, LLC
WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS
Cardiovascular Thrombotic Events
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [see Warnings and Precautions (5.1) ].
TIVORBEX is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications (4) and Warnings and Precautions (5.1)].
Gastrointestinal Bleeding, Ulceration, and Perforation
NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events [see Warnings and Precautions (5.2) ].
1 INDICATIONS AND USAGE
TIVORBEX is indicated for treatment of mild to moderate acute pain in adults.
2 DOSAGE AND ADMINISTRATION
2.1 General Dosing Instructions
Carefully consider the potential benefits and risks of TIVORBEX and other treatment options before deciding to use TIVORBEX. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5) ].
For treatment of mild to moderate acute pain, the dosage is 20 mg three times daily or 40 mg two or three times daily.
2.2 Non-Interchangeability with Other Formulations of Indomethacin
Different dose strengths and formulations of oral indomethacin are not interchangeable. This difference should be taken into consideration when changing strengths or formulations.
3 DOSAGE FORMS AND STRENGTHS
TIVORBEX (indomethacin) Capsules 20 mg � dark blue body and light blue cap (imprinted IP-201 on the body and 20 mg on the cap in white ink).
TIVORBEX (indomethacin) Capsules 40 mg � dark blue body and blue cap (imprinted IP-202 on the body and 40 mg on the cap in white ink).
4 CONTRAINDICATIONS
TIVORBEX is contraindicated in the following patients:
Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to indomethacin or any components of the drug product [see Warnings and Precautions (5.7, 5.9)]
History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions (5.7, 5.8)]
In the setting of coronary artery bypass graft (CABG) surgery.
ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
Cardiovascular Thrombotic Events [see Warnings and Precautions (5.1) ]
GI Bleeding, Ulceration and Perforation [see Warnings and Precautions (5.2) ]
Hepatotoxicity [see Warnings and Precautions (5.3) ]
Hypertension [see Warnings and Precautions (5.4) ]
Heart Failure and Edema [see Warnings and Precautions (5.5) ]
Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.6) ]
Anaphylactic Reactions [see Warnings and Precautions (5.7) ]
Serious Skin Reactions [see Warnings and Precautions (5.9) ]
Hematologic Toxicity
OVERDOSAGE
Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care. Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression, and coma have occurred, but were rare [see Warnings and Precautions (5.1, 5.2, 5.4,5.6)].
Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. Consider emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg of body weight in pediatric patients) and/or osmotic cathartic in symptomatic patients seen within four hours of ingestion or in patients with a large overdosage (5 to 10 times the recommended dosage). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.
For additional information about overdosage treatment contact a poison control center (1-800-222-1222).
11 DESCRIPTION
TIVORBEX (indomethacin) capsule is a nonsteroidal anti-inflammatory drug, available as hard gelatin capsules of 20 mg and 40 mg for oral administration. The chemical name is 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid. The molecular weight is 357.8. Its molecular formula is C19 H16 ClNO4
Indomethacin is a white to yellow crystalline powder. It is practically insoluble in water and sparingly soluble in alcohol. Indomethacin has a pKa of 4.5 and is stable in neutral or slightly acidic media and decomposes in strong alkali.
The inactive ingredients in TIVORBEX include: lactose monohydrate, sodium lauryl sulfate, microcrystalline cellulose, croscarmellose sodium and sodium stearyl fumarate. The capsule shells contain gelatin, titanium dioxide, and dyes FD&C blue #1, FD&C blue #2 and FD&C red #40. The imprinting on the gelatin capsules is white edible ink. The 20 mg capsules have a dark blue body imprinted with IP-201 and light blue cap imprinted with 20 mg in white ink. The 40 mg capsules have a dark blue body imprinted with IP-202 and blue cap imprinted with 40 mg in white ink.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Indomethacin has analgesic, anti-inflammatory, and antipyretic properties.
The mechanism of action of TIVORBEX, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).
Indomethacin is a potent inhibitor of prostaglandin synthesis in vitro. Indomethacin concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because indomethacin is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.