KETOROLAC TROMETHAMINE

WOCKHARDT USA LLC

KETOROLAC TROMETHAMINE INJECTION USP

FULL PRESCRIBING INFORMATION: CONTENTS*

• KETOROLAC TROMETHAMINE DESCRIPTION
• CLINICAL PHARMACOLOGY
  • Pharmacodynamics
  • Pharmacokinetics
• Clinical Studies
• KETOROLAC TROMETHAMINE INDICATIONS AND USAGE
  • Acute Pain in Adult Patients
• KETOROLAC TROMETHAMINE CONTRAINDICATIONS
• WARNINGS
• PRECAUTIONS
  • General
  • Hepatic Effects
  • Hematological Effects
  • Preexisting Asthma
  • Information for patients
  • Laboratory tests
  • Drug interactions
  • Carcinogenesis, mutagenesis, impairment of fertility
  • Pregnancy
  • Nursing mothers
  • Pediatric use
• KETOROLAC TROMETHAMINE ADVERSE REACTIONS
  • Postmarketing Surveillance Study
• OVERDOSAGE
• KETOROLAC TROMETHAMINE DOSAGE AND ADMINISTRATION
• HOW SUPPLIED

FULL PRESCRIBING INFORMATION

KETOROLAC TROMETHAMINE DESCRIPTION

CLINICAL PHARMACOLOGY

Pharmacodynamics

Pharmacokinetics

Clinical Studies

KETOROLAC TROMETHAMINE INDICATIONS AND USAGE

Acute Pain in Adult Patients

KETOROLAC TROMETHAMINE CONTRAINDICATIONS

WARNINGS

PRECAUTIONS

General

Hepatic Effects

Hematological Effects

Preexisting Asthma

Information for patients

• Ketorolac tromethamine, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS: Cardiovascular Effects).
• Ketorolac tromethamine, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS: Gastrointestinal Effects- Risk of Ulceration, Bleeding, and Perforation).
• Ketorolac tromethamine, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.
• Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians.
• Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.
• Patients should be informed of the signs of an anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS).
• In late pregnancy, as with other NSAIDs, ketorolac tromethamine should be avoided because it will cause premature closure of the ductus arteriosus.

Laboratory tests

Drug interactions

digoxin, warfarin, ibuprofen, naproxen, piroxicam, acetaminophen, phenytoin tolbutamide

warfarin heparin WARNINGSPRECAUTIONS: Hematological Effects



Aspirin:

Diuretics:WARNINGS: Renal Effects

Probenecid: probenecid

Lithium:

Methotrexate:

ACE Inhibitors/Angiotensin II Receptor Antagonists: ACE inhibitors and/or angiotensin II receptor antagonists

Antiepileptic Drugs: antiepileptic drugs

Psychoactive Drugs: psychoactive drugs

Pentoxifylline: pentoxifylline

Nondepolarizing Muscle Relaxants: nondepolarizing muscle relaxants

Selective Serotonin Reuptake Inhibitors (SSRIs): selective serotonin reuptake inhibitors

Carcinogenesis, mutagenesis, impairment of fertility

Pregnancy

Teratogenic effects: Pregnancy Category C


Nonteratogenic effects




Labor and delivery
CONTRAINDICATIONS

Effects on Fertility

Nursing mothers

Pediatric use

Geriatric use (≥65 years of age)
CLINICAL PHARMACOLOGYWARNINGS: Gastrointestinal Effects- Risk of Ulceration, Bleeding, and PerforationDOSAGE AND ADMINISTRATION

KETOROLAC TROMETHAMINE ADVERSE REACTIONS

Boxed WARNING, WARNINGS, PRECAUTIONS, DOSAGE AND ADMINISTRATION


































Body as a Whole:

Cardiovascular:

Dermatologic:

Gastrointestinal:

Hemic and Lymphatic:

Metabolic and Nutritional:

Nervous System:

Reproductive, female:

Respiratory:

Special Senses:

Urogenital:



Body as a Whole:WARNINGS

Cardiovascular:

Dermatologic:

Gastrointestinal:

Hemic and Lymphatic: Boxed WARNING, WARNINGS, PRECAUTIONS

Metabolic and Nutritional:

Nervous System:

Respiratory:

Special Senses:

Urogenital:

Postmarketing Surveillance Study

Table 3 Incidence of Clinically Serious G.I. Bleeding as Related to Age, Total Daily Dose, and History of G.I. Perforation, Ulcer, Bleeding (PUB) after up to 5 Days of Treatment with Ketorolac Tromethamine Injection
A. Patients without History of PUB
Age of Patients	Total Daily Dose of Ketorolac Tromethamine Injection
	≤60 mg	>60 to 90 mg	>90 to 120 mg	>120 mg
<65 years of age	0.4%	0.4%	0.9%	4.6%
≥65 years of age	1.2%	2.8%	2.2%	7.7%
B. Patients with History of PUB
Age of Patients	Total Daily Dose of Ketorolac Tromethamine Injection
	≤60 mg	>60 to 90 mg	>90 to 120 mg	>120 mg
<65 years of age	2.1%	4.6%	7.8%	15.4%
≥65 years of age	4.7%	3.7%	2.8%	25.0%

OVERDOSAGE

Symptoms and Signs


Treatment

KETOROLAC TROMETHAMINE DOSAGE AND ADMINISTRATION

Carefully consider the potential benefits and risks of ketorolac tromethamine and other treatment options before deciding to use ketorolac tromethamine. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. In adults, the combined duration of use of IV or IM dosing of ketorolac tromethamine and oral ketorolac tromethamine is not to exceed 5 days. In adults, the use of oral ketorolac tromethamine is only indicated as continuation therapy to IV or IM dosing of ketorolac tromethamine. See package insert for ketorolac tromethamine tablets for transition from IV or IM dosing of ketorolac tromethamine (single- or multiple-dose) to multiple-dose oral ketorolac tromethamine.

Note:
Oral formulationnotas an initial dose

Use minimum effective dose

Total duration of treatment in adult patients:

Ketorolac Tromethamine Injection

WARNINGS -


Single-Dose Treatment: The Following Regimen Should Be Limited To Single Administration Use Only IM Dosing:

• Patients < 65 years of age: One dose of 60 mg.
• Patients ≥ 65 years of age, renally impaired and/or less than 50 kg (110 lbs) of body weight: One dose of 30 mg.

IV Dosing:

• Patients < 65 years of age: One dose of 30 mg.
• Patients ≥ 65 years of age, renally impaired and/or less than 50 kg (110 lbs) of body weight: One dose of 15 mg.

Multiple-Dose Treatment (IV or IM)

• Patients < 65 years of age: The recommended dose is 30 mg ketorolac tromethamine injection every 6 hours. The maximum daily dose for these populations should not exceed 120 mg.
• For patients ≥ 65 years of age, renally impaired patients (see WARNINGS), and patients less than 50 kg (110 lbs):

Pharmaceutical Information for Ketorolac Tromethamine Injection:

HOW SUPPLIED

Ketorolac Tromethamine Injection USP











*FOR IM USE ONLY
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Medication Guide for
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
(See the end of this Medication Guide for a list of prescription NSAID medicines.)

What is the most important information I should know about medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

NSAID medicines may increase the chance of a heart attack or stroke that can lead to death.

• with longer use of NSAID medicines
• in people who have heart disease

NSAID medicines should never be used right before or after a heart surgery called a "coronary artery bypass graft (CABG).”

NSAID medicines can cause ulcers and bleeding in the stomach and intestines at any time during treatment. Ulcers and bleeding:

• can happen without warning symptoms
• may cause death

The chance of a person getting an ulcer or bleeding increases with:

• taking medicines called "corticosteroids" and “anticoagulants"
• longer use
• smoking
• drinking alcohol
• older age
• having poor health

NSAID medicines should only be used:

• exactly as prescribed
• at the lowest dose possible for your treatment
• for the shortest time needed

What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

• different types of arthritis
• menstrual cramps and other types of short-term pain

Who should not take a Non-Steroidal Anti-Inflammatory Drug (NSAID)?
Do not take an NSAID medicine:

• if you had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAID medicine
• for pain right before or after heart bypass surgery

Tell your healthcare provider:

• about all of your medical conditions.
• about all of the medicines you take. NSAIDs and some other medicines can interact with each other and cause serious side effects. Keep a list of your medicines to show to your healthcare provider and pharmacist.
• if you are pregnant. NSAID medicines should not be used by pregnant women late in their pregnancy.
• if you are breastfeeding. Talk to your doctor.

What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

Serious side effects include: heart attack stroke high blood pressure heart failure from body swelling (fluid retention) kidney problems including kidney failure bleeding and ulcers in the stomach and intestine low red blood cells (anemia) life-threatening skin reactions life-threatening allergic reactions liver problems including liver failure asthma attacks in people who have asthma

Other side effects include: stomach pain constipation diarrhea gas heartburn nausea vomiting dizziness

Get emergency help right away if you have any of the following symptoms:

•  shortness of breath or trouble breathing
•  chest pain
•  weakness in one part or side of your body
•  slurred speech
•  swelling of the face or throat 

Stop your NSAID medicine and call your healthcare provider right away if you have any of the following symptoms:

• nausea
• more tired or weaker than usual
• itching
• your skin or eyes look yellow
• stomach pain
• flu-like symptoms
• vomit blood
• there is blood in your bowel movement or it is black and sticky like tar
• unusual weight gain
• skin rash or blisters with fever
• swelling of the arms and legs, hands and feet
  

Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• Aspirin is an NSAID medicine but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.
• Some of these NSAID medicines are sold in lower doses without a prescription (over -the -counter). Talk to your healthcare provider before using over -the -counter NSAIDs for more than 10 days.

NSAID medicines that need a prescription

Generic Name	Tradename
Celecoxib	Celebrex
Diclofenac	Cataflam, Voltaren, Arthrotec (combined with misoprostol)
Diflunisal	Dolobid
Etodolac	Lodine, Lodine XL
Fenoprofen	Nalfon, Nalfon 200
Flurbirofen	Ansaid
Ibuprofen	Motrin, Tab-Profen, Vicoprofen* (combined with hydrocodone), Combunox (combined with oxycodone)
Indomethacin	Indocin, Indocin SR, Indo-Lemmon, Indomethagan
Ketoprofen	Oruvail
Ketorolac	Toradol
Mefenamic Acid	Ponstel
Meloxicam	Mobic
Nabumetone	Relafen
Naproxen	Naprosyn, Anaprox, Anaprox DS, EC-Naproxyn, Naprelan, Naprapac (copackaged with lansoprazole)
Oxaprozin	Daypro
Piroxicam	Feldene
Sulindac	Clinoril
Tolmetin	Tolectin, Tolectin DS, Tolectin 600

KETOROLAC TROMETHAMINE KETOROLAC TROMETHAMINE INJECTION Product Information Product Type Human prescription drug label Item Code (Source) NDC:64679-757 Route of Administration INTRAMUSCULAR DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength KETOROLAC TROMETHAMINE KETOROLAC 15 mg Inactive Ingredients Ingredient Name Strength ALCOHOL SODIUM CHLORIDE SODIUM HYDROXIDE HYDROCHLORIC ACID water Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 1 in 1 VIAL, SINGLE-DOSE 2 1 in 1 VIAL, SINGLE-DOSE 3 1 in 1 VIAL, SINGLE-DOSE 4 NDC:64679-757-03 1 in 1 CARTON Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077942 2007-03-27

KETOROLAC TROMETHAMINE KETOROLAC TROMETHAMINE INJECTION Product Information Product Type Human prescription drug label Item Code (Source) NDC:64679-758 Route of Administration INTRAMUSCULAR DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength KETOROLAC TROMETHAMINE KETOROLAC 30 mg Inactive Ingredients Ingredient Name Strength ALCOHOL SODIUM CHLORIDE SODIUM HYDROXIDE HYDROCHLORIC ACID water Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 1 in 1 VIAL, SINGLE-DOSE 2 1 in 1 VIAL, SINGLE-DOSE 3 2 in 1 VIAL, SINGLE-DOSE 4 2 in 1 VIAL, SINGLE-DOSE 5 2 in 1 VIAL, SINGLE-DOSE 6 10 in 1 VIAL, MULTI-DOSE 7 NDC:64679-758-03 15 in 1 CARTON Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077942 2007-03-27