Remopain

REMOPAIN®

Injection IV/IM

:: COMPOSITION ::

Each ampoule (1 mL) contains : Ketorolac tromethamine 10 mgEach ampoule (1 mL)

contains : Ketorolac tromethamine 30 mg

:: PHARMACOLOGY ::

Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID). It acts on

cyclooxigenase route, inhibits prostaglandins synthesis and may be considered a strong
analgesic, both peripherally and centrally, besides having anti-inflammatory and
antipyretic effects. Ketorolac reduce the mild to severe pain at emergency cases,
musculosceletal pain, post minor or major operative, renal cholic & pain in cancer at
adults or children. Ketorolac has analgesic efficacy equivalent to morphine or pethidin.
Initial analgesic effects of ketorolac may be slower, but the duration longer than opioid.
Combination therapy of ketorolac and opioid may reduce 25-50% of opioid needs. And
for some patients, this case is accompanied by decreasing side effects which is induced by
opioid, faster normalization of gastrointestinal tract function and shorter hospital stay.

:: PHARMACOKINETCS ::

Bioavailability has been reported to range from 80-100% following oral administration. T
max occurs within 30-60 minutes after oral or parenteral administration. Food decreases
the absorption rate, but not the extent of oral absorption. 99% of the ketorolac in plasma is
protein-bound, volume distribution (Vd) < 0.3 L/kg. Ketorolac is metabolised in liver, and
excreted through renal. The metabolites doesn’t have significant analgesic activity. The
elimination terminal half-life of ketorolac (t ½b) is ± 5 hours In geriatric patients,
absorption of ketorolac and plasma protein bound does not affect substantially, but the
plasma clearance is decreased (CL) (t ½b= 6-7 hours).In patients with renal impairment
the plasma clearance is decreased, it prolongs t½b (9-10 hours).Patients with alcoholic
cirrhosis shows a little increase of t½b and T max.

:: INDICATIONS ::

Ketorolac is indicated for the short-term (≤ 5 days) management of moderate and severe
acute pain that requires analgesia at the opioid level.
:: CONTRAINDICATIONS ::

Patients with known hypersensitivity to Ketorolac tromethamine or in patients in whom

aspirin or other NSAIDS induce serious allergic manifestations.Patients with acute peptic
ulcer, patients with recent gastrointestinal bleeding or perforation and in patients with a
history of peptic ulcer disease or gastrointestinal bleeding.Patients with severe renal
impairment or patients at high risk of renal failure.In labor and delivery, it may adversely
affect fetal circulation and inhibit uterine contraindications, thus increasing the risk of
uterine hemorrhage.Nursing mother because of the potential adverse effects of
prostaglandin inhibiting drugs on neonates.Hemostasis disorders.Patients with suspected
or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis and
those at high risk of bleeding.Patients in concomitant use of other NSAIDs and
probenecid. Ketorolac is contraindicated for neuraxial (epidural or intrathecal)
administration.

:: DOSAGE and ADMINISTRATION ::

Longterm treatment of ketorolac IV and IM should not exceed 5 days.Hypovolemia

should be corrected prior to the administration of ketorolac tromethamine.The IV bolus
must be given over no less than 15 seconds.The IM administration should be given deeply
and slowly into the muscle.The analgesic effect begins in 30 minutes with maximum
effect occurring in 1-2 hours after dosing IV or IM. The duration of analgesic effect is
usually 4-6 hours.For breakthrough pain, do not increase the dose or the frequency of
ketorolac tromethamine. Consideration should be given to supplementing these regiments
with low doses of opioids unless otherwise contraindicated.For the short-term
management of pain, an initial IM ketorolac tromethamine loading dose is recommended
of 30 mg or 60 mg, and if necessary therapy is then continued with 15 mg or 30 mg
administered every 6 hours. The maximum daily dose is 120 mg, but if needed, the dose
can be increased up to 150 mg in the first day of treatment. A 30 mg (IM) dose is optimal
dose for relieving moderate postoperative pain. For those with severe pain, a 90 mg dose
should be given.

≥ 65 years of age with renal

Single dose IM/IV < 65 years of age impairment and/or weight < 50
kg
IM 1 x 60 mg 1 x 30 mg
IV 1 x 30 mg 1 x 30 mg
Repeated
≥ 65 years of age, damaged kidney
administration IM or < 65 years of age
or weight < 50 kg
IV
30 mg every 6 hours, 15 mg every 6 hours, maximum
IM and IV
maximum 120 mg daily. 60 mg daily.
:: WARNINGS and PRECAUTIONS ::

• Should be used cautiously in patients receiving anticoagulant therapy and patients

with hemophilia.
• Haematological effects : Ketorolac inhibits thrombocyte aggregation and prolong
bleeding time. Because of that ketorolac should not be used before surgery and use
with caution if there is hemostasis disturbances.
• Should be used with caution in patients with cardiac decompensation, acute renal
failure, hypertension or other conditions associated with fluid retention.
• Ketorolac tromethamine should be used with caution in patients with impaired
hepatic function or patients with history of hepatic desease.
• Hepatic effects : Ketorolac therapy increases hepatic enzymes and in hepatic
disease patients, severe hepatic risk reaction may occur. Administration of
ketorolac should be discontinued if abnormality of hepatic function test occurs
after ketorolac administration.

• Ketorolac tromethamine is not recommended for children under 16 years (Safety

and efficacy have not been established).

:: SIDE EFFECTS ::

Side effect incidence increases proportionally with increasing dose of ketorolac. Severe
complications are caused by ketorolac therapy like ulcer, bleeding and gastrointestinal
perforation, post operative bleeding, acute renal failure, anaphylactic and anaphylactoid
reactions and hepatic failure must be keep on guard. Complications NSAID may be
serious, especially if administration of ketorolac out of recommended dose.The adverse
reactions listed below are reported as probably related to ketorolac in clinical trials.

:: INCIDENCE > 1% ::

Percentage incidence were reported in 3% or more patients.

• Body as a whole : Edema (4%)

• Cardiovascular effects: Hypertension
• Dermatologic : pruritus, rash
• Gastrointestinal : Nausea (12%), dyspepsia (12%), gastrointestinal pain (13%),
diarrhoea (7%), constipation, flatulence, gastrointestinal fullness, vomiting,
stomatitis.
• Hemic and lymphatic : purpura
• Central Nervous system : Cephalgia (17%), drowsiness (6%), dizziness(7%),
swelling.
 • Pain on injection site were reported by 2% patients at study with multiple doses.

:: INCIDENCE ≤ 1% ::

• Body as a whole: Increasing in weight, fever, infections, asthenia.

• Cardiovascular : Palpitations, pale, syncope.
• Dermatologic : Urticaria.
• Gastrointestinal : Gastritis, rectal bleeding, belch, anorexia, appetite increasing.
• Hemic and lymphatic : Epistaxis, anemia, eosinophilia.
• Nervous system : Tremor, abnormal dream, hallucinations, euphoria,
extrapyramidal symptoms, vertigo, paresthesia, depression, insomnia, nervousness,
excessive thirst, dry mouth, abnormal vision, difficult to concentrate, hyperkinesis,
stupor.
• Respiratory : Dyspnea, lung oedema, rhinitis, cough.
• Five senses : abnormal taste, abnormal vision, blurred vision, tinnitus, deaf.

• Urogenital : Hematuria, proteinuria, oliguria, urine retention, polyuria, increased

urinary frequency.

:: DRUG INTERACTION ::

There are no significant interactions between ketorolac and warfarin or heparin. Should be
used with cautiously and strictly monitored if administration of ketorolac for patients with
anticoagulant therapy.Combination of ketorolac tromethamine and other NSAIDs is not
recommended, because it would increase side effects potency.
Ketorolac Effects
interactions
Warfarin Protein binding of warfarin may be decreased slightly from
99.5% to 99.3%. It doesn’t change significantly
pharmacokinetics or pharmacodynamics profile. Protein
binding of ketorolac doesn’t change.
Heparin Prolong average bleeding time (placebo : 5.1 minutes; heparin:
6.0 minutes; heparin + ketorolac : 6.4 minutes).
Digoxin Protein binding of digoksin and ketorolac do not change.
Salicylate Protein binding of ketorolac was decreased from 99.2% to
97.5%, which would represent a potential two-fold increase in
plasma concentrations of unbound drug.
Ibuprofen Protein-binding doesn’t change.
Naproxen Protein-binding doesn’t change.
 Piroxicam Protein-binding doesn’t change.
Acetaminophen Protein-binding doesn’t change.
Phenytoin Protein-binding doesn’t change.
Tolbutamide Protein-binding doesn’t change.
Furosemide Reduced diuretic response 20% (Mean sodium and urinary
output decreased 17%).
Probenecid Results in decreased clearance of ketorolac and significant
increases in ketorolac plasma levels (Total AUC increases ± 3
fold from 5.4 to 17.8 µg/hour/mL, t½ terminal increase ± 2 fold
from 6.6 to 15.1 hours. Concomitant use of ketorolac and
probenecid is contraindicated.
Lithium Inhibition of renal lithium clearance, leading to an increase in
plasma lithium concentration.
Methotrexate Methotrexate clearance is decreased, so that enhancing the
toxicity of methotrexate (because of NSAID). The effect of
Ketorolac on methotrexate clearance has not been studied.
Non-depolarizing Concomitant use of ketorolac and muscle relaxants have not
muscle relaxants formally studied, so that it must be used with caution.
ACE inhibitors Renal impairment risk will be increased, especially in volume-
depleted patients.
Antiepilectic drugs Convulsion attack is occurred (sporadic cases)
(phenytoin,
carbamazepine)
Psychoactive drugs Hallucinations
(fluoxetine, tiotixen,
alprazolam)
Morphine No detrimental interactions are observed. Do not mix ketorolac
and morphine in the same syringe.
There are no reports of combination between ketorolac and anti infections, antiemetic,
laxative, sedative, anxiolitic, corticosteroid, bronchodilator or hormon.No evidence (in
animal or human studies) which shows that ketorolac induces or inhibits hepatic enzymes
capable of metabolizing itself or other drugs.

:: PRESENTATION and REGISTRATION NUMBER ::

Remopain injection : Box, 5 ampoules 10 mg/mL @ 1 mL; Reg.No.

DKL0305032943A1Remopain injection : Box, 5 ampoules 30 mg/mL @ 1 mL; Reg.No.
DKL0305032943B1