For the use of a Registered Medical Practitioner, Hospital or a Laboratory only
KETOROLAC TROMETHAMINE INJECTION IP 30 mg/ml (For IM/IV injection use
only)
KETOWELL INJECTION
COMPOSITION
Each ml contains:
Ketorolac Tromethamine IP 30 mg
Sodium Chloride BP 4.35 mg
Alcohol (95%) equ. to Absolute Alcohol BP 11.5% v/v
Water for Injections BP q.s.
DESCRIPTION
A clear, colorless to slightly pale-yellow colored solution.
PHARMACODYNAMIC
Pharmacotherapeutic group: Antiinflammatory and antirheumatic products, acetic acid
derivatives and related substances.
ATC code M01AB15
Ketorolac is a potent analgesic agent of the non-steroidal, anti-inflammatory class (NSAID).
It is not an opioid and has no known effects on opioid receptors. Its mode of action is to
inhibit the cyclo-oxygenase enzyme system and hence prostaglandin synthesis, and it
demonstrates a minimal anti-inflammatory effect at its analgesic dose.
PHARMACOKINETICS
IM: Following intramuscular administration, ketorolac trometamol will rapidly and
completely be absorbed, a mean peak plasma concentration of 2.2µ g/ml occurring an
average of 50 minutes after a single 30mg dose.
IV: Intravenous administration of a single 10mg dose of ketorolac trometamol results in a
mean peak plasma concentration of 2.4µ g/ml occurring an average of 5.4 minutes after
dosing, with a terminal plasma elimination half-life of 5.1 hours, an average volume of
distribution of 0.15 l/kg, and a total plasma clearance of 0.35ml/min/kg.
The pharmacokinetics of ketorolac in man following single or multiple doses are linear.
Steady-state plasma levels are achieved after dosing every six hours for one day. No changes
in clearance occurred with chronic dosing. The primary route of excretion of ketorolac and its
metabolites is renal: 91.4% (mean) of a given dose being found in the urine and 6.1% (mean)
in the faeces.
More than 99% of the ketorolac in plasma is protein-bound over a wide concentration range.
THERAPEUTIC INDICATION
Ketorolac Tromethamine 30 mg/ml solution for injection is indicated for the short-term
management of moderate to severe acute post-operative pain.
Treatment should only be initiated in hospitals. The maximum duration of treatment is two
days.
DOSAGE AND ADMINISTRATION
Ketorolac is for administration by intramuscular or bolus intravenous injection. Bolus
intravenous doses should be given over no less than 15 seconds. Toradol should not be used
for epidural or spinal administration.
The time to onset of analgesic effect following both IV and IM administration is similar and
is approximately 30 minutes, with maximum analgesia occurring within one to two hours.
The median duration of analgesia is generally four to six hours.
Dosage should be adjusted according to the severity of the pain and the patient response.
The administration of continuous multiple daily doses of ketorolac intramuscularly or
intravenously should not exceed two days because adverse events may increase with
prolonged usage. There has been limited experience with dosing for longer periods since the
vast majority of patients have transferred to oral medication, or no longer require analgesic
therapy after this time.
Undesirable effects may be minimized by using the lowest effective dose for the shortest
duration necessary to control symptoms.
Adults The recommended initial dose of Ketorolac is 10 mg, followed by 10 to 30 mg every
four to six hours as required. In the initial post-operative period, Ketorolac may be given as
often as every two hours if needed. The lowest effective dose should be given. A total daily
dose of 90 mg for non-elderly and 60 mg for the elderly, renally-impaired patients and
patients less than 50 kg should not be exceeded. The maximum duration of treatment should
not exceed two days. Reduce dosage in patients under 50 kg.
Elderly
The elderly are at increased risk of the serious consequences of adverse reactions. If an
NSAID is considered necessary, the lowest effective dose should be used and for the shortest
possible duration. The patient should be monitored regularly for GI bleeding during NSAID
therapy. A total daily dose of 60 mg should not be exceeded.
Paediatric population
Safety and efficacy in children have not been established. Therefore, Ketorolac is not
recommended for use in children under 16 years of age.
Renal impairment
Contra-indicated in moderate to severe renal impairment; reduce dosage in lesser impairment
(not exceeding 60 mg/day IV or IM).
Special dosage instructions
Opioid analgesics (e.g. morphine, pethidine) may be used concomitantly, and may be
required for optimal analgesic effect in the early post-operative period when pain is most
severe. Ketorolac does not interfere with opioid binding and does not exacerbate opioid-
related respiratory depression or sedation. When used in association with Ketorolac
ampoules, the daily dose of opioid is usually less than that normally required. However,
opioid side-effects should still be considered, especially in day-case surgery. Method of
administration Ketorolac is for administration by intramuscular or bolus intravenous
injection. Bolus intravenous doses should be given over no less than 15 seconds. Toradol
should not be used for epidural or spinal administration.
Do not use Ketorolac Ampoules if particulate matter is present.
Ketorolac is compatible with normal saline, 5% dextrose, Ringer's, lactated Ringer's or
Plasmalyte solutions. Compatibility of Ketorolac with other drugs is unknown.
OVERDOSE
Symptoms and signs
Single overdoses of Ketorolac have been variously associated with abdominal pain, nausea,
vomiting, hyperventilation, peptic ulcers and/or erosive gastritis and renal dysfunction which
have resolved after discontinuation of dosing.
Gastrointestinal bleeding may occur. Hypertension, acute renal failure, respiratory depression
and coma may occur after the ingestion of NSAIDs but are rare.
Headache, epigastric pain, disorientation, excitation, drowsiness, dizziness, tinnitus and
fainting have also been observed.
Rare cases of diarrhoea and occasional convulsions have been reported. Anaphylactoid
reactions have been reported with therapeutic ingestion of NSAIDs and may occur following
an overdose.
Treatment
Patients should be managed by symptomatic and supportive care following NSAIDs
overdose. There are no specific antidotes. Dialysis does not significantly clear ketorolac from
the blood stream.
Within one hour of ingestion of a potentially toxic amount, activated charcoal should be
considered. Alternatively, in adults, gastric lavage should be considered within one hour of
ingestion of a potentially life-threatening overdose.
Good urine output should be ensured. Renal and liver function should be closely monitored.
Patients should be observed for at least four hours after ingestion of potentially toxic
amounts. Frequent or prolonged convulsions should be treated with intravenous diazepam.
Other measures may be indicated by the patient's clinical condition.
CONTRAINDICATION
Ketorolac is contraindicated in patients with previously demonstrated hypersensitivity to
Ketorolac, any of its excipients, or other NSAIDs and patients in whom aspirin or other
prostaglandin synthesis inhibitors induce allergic reactions (severe anaphylactic-like reactions
have been observed in such patients). Such reactions have included asthma, rhinitis,
angioedema, or urticaria.
Ketorolac is also contraindicated in
those with a history of asthma
children under 16 years of age.
Ketorolac is contraindicated in patients with active or a history of gastrointestinal bleeding or
perforation, related to previous NSAIDs therapy. Active or history of recurrent peptic
ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
As with other NSAIDs, Ketorolac is contraindicated in patients with severe heart failure,
hepatic failure and renal failure.
Ketorolac is contraindicated in patients with moderate or severe renal impairment (serum
creatinine >160 µ mol/l) or in patients at risk for renal failure due to volume depletion or
dehydration.
Ketorolac is contraindicated in pregnancy, labour, delivery or lactation.
Ketorolac is contra-indicated as prophylactic analgesia before surgery due to inhibition of
platelet aggregation and is contra-indicated intra-operatively because of the increased risk of
bleeding.
Ketorolac inhibits platelet function and is, therefore, contraindicated in patients with
suspected or confirmed cerebrovascular bleeding, patients who have had operations with a
high risk of haemorrhage or incomplete haemostasis and those at high risk of bleeding such
as those with haemorrhagic diatheses, including coagulation disorders.
It is also contraindicated in patients on anticoagulants, including warfarin and low dose
heparin (2500 – 5000 units 12 hourly).
Ketorolac is contraindicated in patients currently receiving ASA or other NSAIDs (including
cyclooxygenase-2 selective inhibitors).
Ketorolac Solution for injection is contraindicated for neuraxial (epidural or intrathecal)
administration due to its alcohol content.
The combination of Ketorolac with oxpentifylline is contraindicated. Concurrent treatment
with ketorolac and probenecid or lithium salts is contraindicated.
Ketorolac is contra-indicated in patients with the complete or partial syndrome of nasal
polyps, angioedema or bronchospasm.
WARNING AND PRECAUTIONS
If patient have heart problems, previous stroke or think that they might be at risk of these
conditions (for example if they have high blood pressure, diabetes or high cholesterol or are a
smoker) Doctor should know about the treatment before using this medicine.
Doctor should take history weather patient have a surgery of the stomach or intestinal tract
before receiving/taking/using ketorolac, as ketorolac can sometimes worsen wound healing in
your gut after surgery.
Doctor or nurse should check before giving ketorolac if any of the following apply:
They are elderly (are more likely to suffer problems).
Problems with kidneys or liver.
High blood pressure.
Problems with the blood vessels (arteries) anywhere in the body.
Too much fat (lipid) in the blood (hyperlipidaemia).
An autoimmune condition, such as ‘systemic lupus erythematosus’ (SLE, which causes
joint pain, skin rashes and fever) and colitis or Crohn’s disease (conditions causing
inflammation of the bowel, bowel pain, diarrhoea, vomiting and weight loss). If any of
the above apply to you, or if you are not sure, talk to your doctor or nurse before you are
given Toradol.
PREGNANCY, LACTATION, FERTILITY AND ABILITY TO DRIVE
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a
baby, ask your doctor or pharmacist for advice before taking this medicine.
You should not be given Ketorolac during the first 6 months of pregnancy unless absolutely
necessary and advised by your doctor. If you need treatment during this period or while you
are trying to get pregnant, the lowest dose for the shortest time possible should be used.
You should not be given Ketorolac if you are in the last 3 months of pregnancy as it could
harm your unborn child or cause problems at delivery. It can cause kidney and heart problems
in your unborn baby. It may affect your and your baby’s tendency to bleed and cause labour
to be later or longer than expected.
If you are given more than a few days from 20 weeks of pregnancy onward, Ketorolac can
cause kidney problems in your unborn baby that may lead to low levels of amniotic fluid that
surrounds the baby (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in
the heart of the baby.
If you need treatment for longer than a few days, your doctor may recommend additional
monitoring. Toradol may make it more difficult to become pregnant. You should inform your
doctor if you are planning to become pregnant or if you have problems becoming pregnant.
You must not be given Ketorolac injection if you are pregnant, in labour or are breast-
feeding.
ABILITY TO DRIVE
Ketorolac may make you tired, drowsy, dizzy, have problems with your balance or eyesight,
depressed or have difficulty sleeping. Talk to your doctor if any of these happen to you and
do not drive or use any tools or machines.
DRUG INTERACTION
Patient must not be given, If patient is taking any of the following medicines:
Other NSAIDs, like aspirin, ibuprofen or diclofenac.
Medicines to stop your blood clotting, like warfarin, heparin or clopidogrel.
Oxpentifylline (for your circulation).
Probenecid (for gout).
Lithium (for mental health problems).
If the patient is taking any of the below medicine the consultation of the doctor must be taken
before taking Ketorolac.
An ‘ACE inhibitor’ or other medicine for high blood pressure, like cilazapril, enalapril or
propranolol. • A diuretic (water tablet) (for high blood pressure), like furosemide.
A ‘cardiac glycoside’ (for heart problems), like digoxin.
A steroid (for swelling and inflammation), like hydrocortisone, prednisolone and
dexamethasone.
A ‘quinolone antibiotic’ (for infections), like ciprofloxacin or moxifloxacin.
Certain medicines for mental health problems ‘SSRIs’, like fluoxetine or citalopram.
Methotrexate (used to treat skin problems, arthritis or cancer).
Ciclosporin or tacrolimus (for skin problems or after an organ transplant).
Zidovudine (used to treat AIDS and HIV infections).
Mifepristone (used to end pregnancy or to bring on labour if the baby has died).
ADVERSE EFFECTS
Gastro-intestinal disorders: Peptic ulcers, ulcers, perforation or GI bleeding, Nausea,
vomiting diarrhoea, constipation, dyspepsia, abdominal pain / discomfort, melaena,
haematemesis, stomatitis, ulcerative stomatitis, eructation, flatulence, oesophagitis,
gastrointestinal ulceration, rectal bleeding, pancreatitis, dry mouth, fullness, exacerbation of
colitis and Crohn's disease have been reported following administration. Less frequently,
gastritis has been observed.
Infection: meningitis aseptic with symptoms such as stiff neck, headache, nausea, vomiting,
fever or disorientation.
Blood and Lymphatic System Disorders: thrombocytopenia. Additionally, purpura,
neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia have been observed.
Immune System Disorders: anaphylactoid reactions, anaphylactoid reactions like
anaphylaxis, hypersensitivity reactions such as bronchospasm flushing, rash, hypotension,
laryngeal oedema.
These may also occur in individuals with a history of angioedema, bronchospastic reactivity
(e.g. asthma and nasal polyps).
Metabolic and Nutrition Disorders: anorexia, hyperkalaemia, hyponatraemia.
Psychiatric Disorders: abnormal thinking, depression, insomnia, anxiety, nervousness,
psychotic reactions, abnormal dreams, hallucinations, euphoria, concentration ability
impaired, drowsiness. Confusion and stimulation have been observed.
Nervous system disorders: headache, dizziness, convulsions, paresthesia, hyperkinesias,
taste abnormality.
Eye Disorders: abnormal vision, visual disturbances, optic neuritis.
Ear Disorders: tinnitus, hearing loss, vertigo.
Renal and Urinary Disorders: acute renal failure, increased urinary frequency, interstitial
nephritis, nephrotic syndrome, urinary retention, oliguria, haemolytic uremic syndrome, flank
pain (with or without haematuria +- azotemia). As with other drugs that inhibit renal
prostaglandin synthesis signs of renal impairment, such as, but not limited to elevations of
creatinine and potassium can occur after one dose of Ketorolac IV.
Cardiac Disorders: palpitations, bradycardia, cardiac failure.
Vascular disorders: hypertension, hypotension, haematoma, flushing, pallor, postoperative
wound haemorrhage.
Clinical trial and epidemiological data suggest that use of coxibs and some NSAIDs
(particularly at high doses) may be associated with a small increased risk of arterial
thrombotic events (for example myocardial infarction or stroke). Although ketorolac has not
shown to increase thrombotic events, such as myocardial infarction, there are insufficient data
to exclude such a risk with ketorolac.
Reproductive System and Breast Disorders: female infertility.
Respiratory, Thoracic and Mediastinal Disorders: asthma, dyspnoea, pulmonary oedema.
Additionally, epistaxis has been observed.
Hepatobiliary Disorders: hepatitis, cholestatic jaundice, liver failure.
Skin and Subcutaneous Tissue Disorders: exfoliative dermatitis, maculopapular rash,
pruritus, urticaria, purpura, angioedema, sweating, bullous reactions including Stevens-
Johnson syndrome and toxic epidermal necrolysis (very rare). Additionally, erythema
multiforme and skin photosensitivity has been observed.
Musculoskeletal and Connective Tissue Disorders: myalgia, functional disorder.
General Disorders and Administration Site Condition: excessive thirst, asthenia, oedema,
injection site reactions and pain, fever, chest pain. Additionally, malaise, fatigue and weight
gain has been observed.
Investigations: bleeding time prolonged, serum urea increased, creatinine increased,
abnormal liver function tests.
PRESENTATION
KETOWELL Injection are supplied in 1 ml amber, Type I USP ampoule.
STORAGE AND OTHER INFORMATION
Store in a cool and dry place. Protect from light.
Store at below 30°C temperature.
Caution: Not to be used if container is found leaking or solution is hazy or contain any
visible solid particles. Keep this medicine out of the sight and reach of children.
