TRAMED TABLETS

Indications

• Mild to moderate pain
• Dysmenorrhea
• Postoperative pain
• Osteoarthritis
• Rheumatoid arthritis

Dosage

Children: For

Adults: The usual adult dose is 500 mg initially, followed by 250 mg every 8 hours as needed. The maximum daily dose should not exceed 2000 mg.

Mechanism of action

Mefenamic acid exerts its therapeutic effect by inhibiting the cyclooxygenase (COX) enzymes, which are responsible for the conversion of arachidonic acid to prostaglandins. By reducing prostaglandin production, mefenamic acid decreases inflammation, pain, and fever. This inhibition primarily occurs through the non-selective blockade of COX-1 and COX-2 isoforms.

Pharmacodynamics

The pharmacodynamics of mefenamic acid involve its analgesic, anti-inflammatory, and antipyretic properties. The drug is effective in reducing pain and inflammation due to its ability to lower prostaglandin levels, which play a key role in the inflammatory response. Mefenamic acid tends to have a rapid onset of action, typically within 1 to 2 hours after administration, and its effects can last for several hours, providing relief from pain.

Pharmacokinetics

Mefenamic acid is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 2 to 4 hours after oral administration. The drug is extensively metabolized in the liver, primarily through glucuronidation, leading to the formation of active and inactive metabolites. It has a relatively long half-life of about 2 to 4 hours, and it is excreted mainly in the urine, both as unchanged drug and as metabolites. The pharmacokinetics can be influenced by factors such as age, liver function, and concurrent medications.

Contra-indications

• Hypersensitivity to mefenamic acid or any of its excipients
• Active or history of peptic ulcer disease
• Severe heart failure
• History of gastrointestinal bleeding or perforation
• Severe hepatic impairment
• Severe renal impairment

Adverse effects

• Gastrointestinal disturbances (nausea, vomiting, diarrhea, constipation)
• Headache
• Dizziness
• Rash
• Elevated liver enzymes
• Renal impairment
• Anaphylactic reactions
• Increased risk of cardiovascular events

Interactions

• Increased exposure when used with regorafenib (severe interaction)

Precautions

• Use with caution in patients with a history of gastrointestinal disorders
• Monitor renal function in patients with compromised renal function
• Caution in patients with cardiovascular diseases
• Caution in the elderly, who may be more susceptible to adverse effects

Pregnancy

Mefenamic acid should be avoided during pregnancy, especially in the third trimester due to risks of fetal cardiovascular effects and potential complications.

Breast-feeding

Use with caution; mefenamic acid is excreted in breast milk, but significant effects on the nursing infant are not expected.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Capsules
• Tablets
• Oral suspension

Indications

• Heavy menstrual bleeding (menorrhagia)
• Postoperative bleeding
• Traumatic bleeding
• Bleeding in dental procedures
• Coagulation disorders (e.g., hemophilia)
• Nosebleeds (epistaxis)
• Preventing bleeding in patients undergoing surgery

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations for paediatric patients.

Adults: Refer to the BNF for specific dosing recommendations for adults based on the condition being treated.

Mechanism of action

Tranexamic acid exerts its effects by competitively inhibiting the binding of plasminogen to fibrin, thus preventing the conversion of plasminogen to plasmin. This inhibition decreases fibrinolysis, leading to increased stability of the fibrin clot and reduced bleeding. The drug acts primarily on the fibrinolytic system, impacting coagulation by maintaining clot integrity.

Pharmacodynamics

The pharmacodynamics of tranexamic acid involves its role as an antifibrinolytic agent. By stabilizing the fibrin clot, it reduces the rate of clot breakdown and consequently decreases blood loss. The onset of action is relatively rapid, with peak plasma concentrations occurring within 1 to 3 hours after administration. The duration of effect can vary depending on the dosage and route of administration.

Pharmacokinetics

Tranexamic acid is well absorbed when administered orally or intravenously, with bioavailability of approximately 30% when taken orally. It is widely distributed throughout the body, with a volume of distribution ranging from 1 to 2 L/kg. The drug is primarily eliminated unchanged through the kidneys, with a half-life of about 2 hours. Renal impairment can significantly affect the clearance of tranexamic acid, necessitating dosage adjustments in such patients.

Contra-indications

• Active thromboembolic disease
• Severe renal impairment
• Hypersensitivity to tranexamic acid or any of its components

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Dizziness
• Headache
• Visual disturbances
• Thromboembolic events

Interactions

• Anticoagulants (may increase risk of thrombosis)
• Hormonal contraceptives (may increase risk of thromboembolism)
• Other antifibrinolytics (increased risk of adverse effects)

Precautions

• Use with caution in patients with a history of thromboembolic disease
• Monitor renal function in patients with renal impairment
• Ensure adequate hydration to reduce risk of renal complications

Pregnancy

Tranexamic acid should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Animal studies have shown adverse effects.

Breast-feeding

Tranexamic acid is excreted in breast milk. Use with caution and consider the benefits and risks.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Tablets
• Injectable solution