Ketorolac Tromethamine

S01B - Antiinflammatory agents ATC S01BC05 Small molecule approved 1989 Oral Parenteral Topical Black-box warning

🧬 Cross-allergy: NSAIDs

JFDA label: Acular LS Eye Drops

⚠ Black-Box Warning

immune system toxicity — ChEMBL drug_warning (Black Box Warning) | United States
gastrointestinal toxicity — ChEMBL drug_warning (Black Box Warning) | United States
cardiotoxicity — ChEMBL drug_warning (Black Box Warning) | United States
neurotoxicity — ChEMBL drug_warning (Black Box Warning) | United States
vascular toxicity — ChEMBL drug_warning (Black Box Warning) | United States
respiratory toxicity — ChEMBL drug_warning (Black Box Warning) | United States
Black Box Warning — ChEMBL drug_warning (Black Box Warning) | United States
Ketorolac tromethamine, a nonsteroidal anti-inflammatory drug (NSAID), is indicated for the short-term (up to 5 days in adults) management of moderately severe acute pain that requires analgesia at th

Mechanism of Action

Inhibitor of Cyclooxygenase — Cyclooxygenase inhibitor

Target	Action	Gene / class
Cyclooxygenase efficacy	INHIBITOR

Indications

Approved

Acute Pain — pain
Cataract — cataract
Eye Pain — Ocular pain
Inflammation — inflammation
Pain — pain

Off-label

Back Pain
Heart Diseases
Kidney Calculi
Macular Edema
Migraine Disorders
Pulpitis
Renal Colic
Shoulder Impingement Syndrome

Contraindications

Source: openFDA

(See also Boxed WARNING .) Ketorolac tromethamine is contraindicated in patients with previously demonstrated hypersensitivity to ketorolac tromethamine. Ketorolac tromethamine is contraindicated in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation and in patients with a history of peptic ulcer disease or gastrointestinal bleeding. Ketorolac tromethamine should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS – Anaphylactoid Reactions , and PRECAUTIONS – Pre-existing Asthma ). Ketorolac tromethamine is contraindicated as prophylactic analgesic before any major surgery. Ketorolac tromethamine is contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ). Ketorolac tromethamine is contraindicated in patients with advanced renal impairment or in patients at risk for renal failure due to volume depletion (see WARNINGS for correction of volume depletion). Ketorolac tromethamine is contraindicated in labor and delivery because, through its prostaglandin synthesis inhibitory effect, it may adversely affect fetal circulation and inhibit uterine musculature, thus increasing the risk of uterine hemorrhage. Ketorolac tromethamine inhibits platelet function and is, therefore, contraindicated in patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding (see WARNINGS and PRECAUTIONS ). Ketorolac tromethamine is contraindicated in patients currently receiving aspirin or NSAIDs because of the cumulative risks of inducing se Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (4)

Rare Bradycardia · Cardiac disorder · Cardiac failure · Palpitations

Vascular disorders (6)

Common Retinal haemorrhage

Rare Bleeding time prolonged · Flushing · Haematoma · Hypertension · Hypotension

Nervous system disorders (6)

Very Common Headache

Common Dizziness · Somnolence

Rare Convulsion · Meningitis aseptic · Paraesthesia

Hepatobiliary disorders (5)

Rare Hepatic failure · Hepatitis · Hepatobiliary disease · Jaundice cholestatic · Liver function test abnormal

Renal and urinary disorders (7)

Rare Blood creatinine increased · Haematuria · Nephrotic syndrome · Pollakiuria · Renal failure acute · Urinary retention · Urinary tract disorder

Blood and lymphatic system disorders (3)

Rare Haemolytic uraemic syndrome · Leukopenia · Thrombocytopenia

Immune system disorders (3)

Rare Anaphylactic shock · Hypersensitivity · Immune system disorder

Metabolism and nutrition disorders (2)

Rare Hyperkalaemia · Hyponatraemia

Gastrointestinal disorders (23)

Very Common Dyspepsia · Gastrointestinal pain · Nausea

Common Diarrhoea

Uncommon Vomiting

Rare Abdominal pain · Colitis · Constipation · Decreased appetite · Dry mouth · Flatulence · Gastrointestinal disorder · Gastrointestinal haemorrhage · Gastrointestinal perforation · Haematemesis · Melaena · Oesophagitis · Pancreatitis · Pancreatitis acute · Peptic ulcer · Rectal haemorrhage · Stomatitis · Thirst

Skin and subcutaneous tissue disorders (15)

Rare Angioedema · Dermatitis · Dermatitis exfoliative · Erythema multiforme · Hyperhidrosis · Pruritus · Purpura · Rash · Rash maculo-papular · Skin disorder · Stevens-Johnson syndrome · Toxic epidermal necrolysis · Urticaria · Vascular purpura · Wound haemorrhage

Musculoskeletal and connective tissue disorders (3)

Rare Connective tissue disorder · Musculoskeletal discomfort · Myalgia

Psychiatric disorders (7)

Rare Abnormal dreams · Agitation · Anxiety · Euphoric mood · Hallucination · Insomnia · Mental disorder

Eye disorders (5)

Common Eye burns · Eye pain

Uncommon Eye oedema

Rare Eye disorder · Visual impairment

Ear and labyrinth disorders (5)

Rare Deafness · Ear disorder · Hearing impaired · Tinnitus · Vertigo

Reproductive system and breast disorders (2)

Rare Breast disorder · Infertility female

Infections and infestations (1)

Rare Infection

Investigations (4)

Rare Blood urea increased · Body temperature increased · Thinking abnormal · Weight increased

General disorders and administration site conditions (34)

Common Corneal deposits · Cystoid macular oedema · Oedema

Uncommon Conjunctival hyperaemia · Corneal infiltrates

Rare Anaphylactoid reaction · Angiopathy · Asthenia · Azotaemia · Chest pain · Crohn's disease · Discomfort · Disturbance in attention · Dysgeusia · Eructation · Extrapyramidal disorder · Flank pain · Gastritis · Hyperkinesia · Injection site reaction · Malnutrition · Mediastinal disorder · Mental disability · Mouth ulceration · Nephritis · Nervous system disorder · Nervousness · Oliguria · Pallor · Psychotic disorder · Tension · Tongue disorder · Tongue oedema · Urethral disorder

Respiratory, thoracic and mediastinal disorders (7)

Rare Asthma · Bronchospasm · Dyspnoea · Epistaxis · Laryngeal oedema · Pulmonary oedema · Tubulointerstitial nephritis

Injury, poisoning and procedural complications (1)

Common Injury

Dosing

Source: openFDA

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 intravenous or intramuscular 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 intravenous or intramuscular dosing of ketorolac tromethamine. See package insert for ketorolac tromethamine tablets for transition from intravenous or intramuscular dosing of ketorolac tromethamine (single- or multiple-dose) to multiple-dose oral ketorolac tromethamine. Note: Oral formulation should not be given as an initial dose. Use minimum effective dose for the individual patient. Total duration of treatment in adult patients: the combined duration of use of intravenous or intramuscular dosing of ketorolac tromethamine and oral ketorolac tromethamine is not to exceed 5 days. Ketorolac Tromethamine Injection Ketorolac tromethamine injection may be used as a single or multiple dose on a regular or “prn” schedule for the management of moderately severe, acute pain that requires analgesia at the opioid level, usually in a postoperative setting. Hypovolemia should be corrected prior to the administration of ketorolac tromethamine (see WARNINGS – Renal Effects ). Patients should be switched to alternative analgesics as soon as possible, but ketorolac tromethamine therapy is not to exceed 5 days. When administering ketorolac tromethamine injection, the intravenous bolus must be given over no less than 15 seconds. The intramuscular administration should be given slowly and deeply into the muscle. The analgesic effect begins in ~30 minutes with maximum effect in 1 to 2 hours after dosing intravenous or intramuscular. Duration of analgesic effect is usually 4 to 6 hours. Single-Dose Treatment: The following regimen should be limited to single administration use only Intramuscular 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. Intravenous 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 (Intravenous or Intramuscular) 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): The recommended dose is 15 mg ketorolac tromethamine injection every 6 hours. The maximum daily dose for these populations should not exceed 60 mg. For breakthrough pain, do not increase the dose or the frequency of ketorolac tromethamine. Consideration should be given to supplementing these regimens with low doses of opioids “prn” unless otherwise contraindicated. Pharmaceutical Information for Ketorolac Tromethamine Injection Ketorolac tromethamine injection should not be mixed in a small volume (e.g., in a syringe) with morphine sulfate, meperidine hydrochloride, promethazine hydrochloride or hydroxyzine hydrochloride; this will result in precipitation of ketorolac from solution. NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Warnings & Precautions

Source: openFDA

Boxed Warning

Ketorolac tromethamine, a nonsteroidal anti-inflammatory drug (NSAID), is indicated for the short-term (up to 5 days in adults) management of moderately severe acute pain that requires analgesia at the opioid level. Oral ketorolac tromethamine is indicated only as continuation treatment following intravenous or intramuscular dosing of ketorolac tromethamine, if necessary. The total combined duration of use of oral ketorolac tromethamine and ketorolac tromethamine injection should not exceed 5 days. Ketorolac tromethamine is not indicated for use in pediatric patients and it is NOT indicated for minor or chronic painful conditions. Increasing the dose of ketorolac tromethamine beyond the label recommendations will not provide better efficacy but will increase the risk of developing serious adverse events. GASTROINTESTINAL RISK • Ketorolac tromethamine can cause peptic ulcers, gastrointestinal bleeding and/or perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Therefore, ketorolac tromethamine is CONTRAINDICATED in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation, and in patients with a history of peptic ulcer disease or gastrointestinal bleeding. Elderly patients are at greater risk for serious gastrointestinal events (see WARNING S ). 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 ). • Ketorolac tromethamine is CONTRAINDICATED in the setting of coronary artery bypass graft (CABG) surgery (see CONTRAINDICATIONS and WARNINGS ). RENAL RISK • Ketorolac tromethamine is CONTRAINDICATED in patients with advanced renal impairment and in patients at risk for renal failure due to volume depletion (see WARNINGS ). RISK OF BLEEDING • Ketorolac tromethamine inhibits platelet function and is, therefore, CONTRAINDICATED in patients with suspected or confirmed cerebrovascular bleeding, patients with hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding (see WARNINGS and PRECAUTIONS ). Ketorolac tromethamine is CONTRAINDICATED as prophylactic analgesic before any major surgery. HYPERSENSITIVITY • Hypersensitivity reactions, ranging from

Warnings & Precautions

(See also Boxed WARNING .) The total combined duration of use of oral ketorolac tromethamine and intravenous or intramuscular dosing of ketorolac tromethamine is not to exceed 5 days in adults. Ketorolac tromethamine is not indicated for use in pediatric patients. The most serious risks associated with ketorolac tromethamine are: Gastrointestinal Effects – Risk of Ulceration, Bleeding and Perforation: Ketorolac tromethamine is contraindicated in patients with previously documented peptic ulcers and/or gastrointestinal (GI) bleeding. Ketorolac tromethamine can cause serious GI adverse events including bleeding, ulceration and perforation, of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with ketorolac tromethamine. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Minor upper gastrointestinal problems, such as dyspepsia, are common and may also occur at any time during NSAID therapy. The incidence and severity of gastrointestinal complications increases with increasing dose of, and duration of treatment with ketorolac tromethamine. Do not use ketorolac tromethamine for more than five days. However, even short-term therapy is not without risk. In addition to past history of ulcer disease, other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids, or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population. To minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of ketorolac tromethamine until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered. NSAIDs should be given with care to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn’s disease) as their conditi

Pregnancy & Lactation

Pregnancy

Lactation

Contraindicated Hale L5 RID 0.18%

Maternal

Chemistry & Properties

Formula	C19H24N2O6
Molecular weight	376.41 g/mol
IUPAC name	2-amino-2-(hydroxymethyl)propane-1,3-diol;5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid
CAS	74103-07-4
PubChem CID	84003
InChIKey	`BWHLPLXXIDYSNW-UHFFFAOYSA-N`
logP	2.29
Polar surface area	59.3 Å²
H-bond acceptors / donors	3 / 1
Drug-likeness (QED)	0.86
Lipinski violations	0

SMILES

NC(CO)(CO)CO.O=C(c1ccccc1)c1ccc2n1CCC2C(=O)O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	2.122 h
Volume of distribution	0.097 L/kg
Protein binding	96.7%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C9	Substrate	—

Receptor binding (top 2)

Target	Action	Affinity
COX-1	Binding	pKi 8.1
COX-2	Binding	pKi 7.0

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)NTCP (Inhibitor)OAT1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCTN2 (Inhibitor)P-gp (Inhibitor)OAT1 (Substrate)OAT3 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Acalabrutinib	major
Acetylsalicylic acid	major
Apixaban	major
Betrixaban	major
Cabozantinib	major
Celecoxib	major
Dalteparin	major
Danaparoid	major
Dasatinib	major
Deferasirox	major
Desirudin	major
Diatrizoate	major
Diclofenac	major
Dicoumarol	major
Drotrecogin alfa	major
Edoxaban	major
Enoxaparin	major
Everolimus	major
Flurbiprofen	major
Fondaparinux	major
Ibritumomab tiuxetan	major
Ibrutinib	major
Ibuprofen	major
Iodipamide	major
Iodixanol	major
Iohexol	major
Iopamidol	major
Iopromide	major
Iothalamic acid	major
Ioversol	major
Ioxilan	major
Leflunomide	major
Methotrexate	major
Omacetaxine mepesuccinate	major
Panobinostat	major
Pentoxifylline	major
Ponatinib	major
Prasugrel	major
Ramucirumab	major
Regorafenib	major

Showing 40 of 100+.

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Acular LS Eye Drops	Ophthalmic Solution 0.4 %	5 ml	Arab Company for Medical & Agricultural Products	4.100
Ketomax	Ampoule 30 mg/1 ml	10 amp	Amman Pharmaceutical Industries Co	6.250
Acuvail	Vial 4.5 mg/ml	0.4 ml	Arab Company for Medical & Agricultural Products	7.570