COMPOSITION

Acupain TM : Each tablet contains Ketorolac tromethamine USP 10 mg.

PHARMACOLOGICAL INFORMATION

Pharmacological Action

Acupain TM is a nonsteroidal anti-inflammatory drug which, when administered systemically, has demonstrated analgesic, anti-inflammatory and anti-pyretic activity.

Mechanism of Action

Ketorolac works by inhibiting prostaglandin synthesis. It inhibits the synthesis of prostaglandins in body tissues by inhibiting cyclooxygenase (COX). Both (COX-1) and (COX-2) have been identified that, they catalyze the formation of prostaglandins in the arachidonic acid pathway. Ketorolac, achieves its effects by acting on the enzyme Cox, which converts arachidonic acid to endoperoxides, the precursors of prostaglandins, prostacyclin and thromboxanes.

PHARMACOKINETICS

Absorption:

After oral dosing, ketorolac is rapidly and almost, completely absorbed. Bioavailability is quoted at 81-100 %. Oral administration of Ketorolac after a high-fat meal resulted in decreased peak and delayed time-to-peak concentrations of ketorolac tromethamine by about 1 hour. Antacids did not affect the extent of absorption.

Distribution:

The mean apparent volume (Vß) of ketorolac tromethamine was approximately 13 liters. The ketorolac tromethamine racemate has been shown to be highly protein bound (99%). Nevertheless, even plasma concentrations as high as 10 mg/mL will only occupy approximately 5% of the albumin binding sites. Ketorolac tromethamine is excreted in human milk.

Metabolism:

Ketorolac tromethamine is largely metabolized in the liver. The metabolic products are hydroxylated and conjugated forms of the parent drug. The products of metabolism and some unchanged drug are excreted in the urine.

Elimination:

The principal route of elimination of ketorolac and its metabolites is renal. About 92% of a given dose is found in the urine, approximately 40% as metabolites and 60% as unchanged ketorolac. Approximately 6% of a dose is excreted in the feces.

CLINICAL INFORMATION

Indication and Uses

Ketorolac tromethamine is indicated for the short-term management of moderately severe, acute pain that requires analgesia at the opioid level, usually in a postoperative setting.

Dosage and Administration

Ketorolac tablets are recommended for short-term use only (up to 7 days) and are not recommended for chronic use. 10 mg every 4 to 6 hours as required. Doses exceeding 40 mg per day are not recommended. For patients receiving parenteral Ketorolac tromethamine, and who are converted to Ketorolac tromethamine oral tablets, the total combined daily dose should not exceed 90 mg (60 mg for the elderly, renally impaired patients and patients less than 50 kg) and the oral component should not exceed 40 mg on the day the change of formulation is made. Patients should be converted to oral treatment as soon as possible.

Use in Pregnancy & Lactation

Pregnant woman: ketorolac tromethamine is not recommended for use during pregnancy and should be used only when the potential benefit justify, the possible risk of fetus. Ketorolac tromethamine should not be used during late pregnancy or during labor or delivery, since inhibitors of prostaglandin synthesis may have adverse effects on the fetal cardiovascular system (e.g. premature closure of the ductus arteriosus) and on uterine contraction.

Lactating mother: Because ketorolac is distributed into milk, and because of the potential adverse effects of prostaglandin-inhibiting drugs in neonates, the drug should not be used m nursing women.

Dosage in Renal Impairment

Prostaglandins E2 and I2 have renal vasodilatory actions in conditions of impaired renal blood flow. NSAIDs will block this effect and increase the risk of renal damage. Patient with established renal impairment have substantially reduce clearance of ketorolac and require lower dose and careful monitoring as delayed clearance in such patients results in increase blood level of the drug which, because of its high protein binding , is not readily eliminated by dialysis.

Dosage in hepatic Impairment

The need for ketorolac tromethamine dosage adjustment in patients with hepatic impairment has not been fully determined, but evidence from patients with liver cirrhosis suggests that modification may not be necessary. Pending further accumulation of data, caution should be exercised when the drug is used in patients with hepatic impairment.

Side Effects

Most commonly- reported side effects are, gastrointestinal symptoms with dyspepsia, gastrointestinal pain, nausea, and vomiting occurring in 3-9% of patients. Such symptoms probably necessitate discontinuation of the drug as they may herald more serious pathology.

Contraindications

Ketorolac tromethamine is contraindicated in patients having hypersensitivity to this drug or other NSAIDs and those patients in whom aspirin or other prostaglandin synthesis inhibitors induce allergic reactions. It is also contraindicated in a history of peptic ulcer, gastro-intestinal bleeding, severe renal impairment or history of asthma. Ketorolac tromethamine 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. It is also contraindicated during pregnancy, labor, delivery or lactation.

Precaution

Patients over the age of 65 years may be at a greater risk of experiencing adverse events than younger patients. Ketorolac tromethamine can cause gastro-intestinal irritation, ulcers or bleeding in patients with or without a history of previous symptoms. Bronchospasm may be precipitated in patients with a history of asthma. Since ketorolac tromethamine and its metabolites are excreted primarily by the kidney, patients with moderate to severe impairment of renal function (serum creatinine greater than 160 micromole/l) should not receive. Fluid retention and edema have been reported with the use of Ketorolac tromethamine.

Drug Interactions

Ketorolac tromethamine should not be used with other NSAIDs or in patients receiving aspirin because of the potential for additive side-effects. Care should be taken when administering Ketorolac tromethamine with anti-coagulants since co-administration may cause an enhanced anti-coagulant effect. Ketorolac tromethamine and other non-steroidal anti-inflammatory drugs can reduce the anti-hypertensive effect of beta-blockers and may increase the risk of renal impairment when administered concurrently with ACE inhibitors, particularly in volume depleted patients. Caution is advised when methotrexate is administered concurrently, since some prostaglandin synthesis inhibiting drugs have been reported to reduce the clearance of methotrexate, and thus possibly enhance its toxicity. Probenecid should not be administered concurrently with ketorolac tromethamine because of increases in ketorolac plasma level and half-life.

Overdose and Treatment

Symptoms following acute NSAIDs overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare.

Patients should be managed by symptomatic and supportive care following a NSAIDs overdose. There are no specific antidotes. Emesis and/or activated charcoal (60 g to 100 g in adults, 1g/kg to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large oral overdose (5 to 10 times the usual dose).

PHARMACEUTICAL INFORMATION

Storage Conditions

Store in a cool and dry place away from light. Keep out of reach of children.

Presentation & Packaging

Acupain TM : Each commercial box containing 30 tablets in Alu-PVC blister pack.