ASQUE TABLET:
Tramadol Hydrochloride B.P 37.5 mg.
Paracetamol I.P 325 mg.
Caffeine 30 mg.
Taurine 250 mg.

RATIONALE FOR COMBINATION

1 Tramadol represents an excellent Multimodal Analgesic.
2 Paracetamol often analgesic or antipyretic of choice in patients in whom salicylates or NSAIDs arecontraindicated. Such patients include asthmatics and patients with a history of peptic ulcer. Its use is generally preferred in the elderly.
3 Caffeine stimulates fat burning in endurance activities and thereby helps to use fat stores in the body to provide energy and to preserve the glycogen. This means that caffeine intake during endurance activities results in a more efficient supply of energy and especially in extended exertion it leads to a significant improvement in performance and endurance.
4 Caffeine consumption is known for its stimulating effect on psychological and physiological functions – concentration, reaction speed and alertness are improved.
5 Taurine aids the movement of potassium, sodium, calcium and magnesium in and out of cells and thus helps to activate the body (Provides energy).
6 Taurine acts as an antioxidant and protects against toxicity to various substances. Supplementation with Taurine has been shown to prevent oxidative stress induced by exercise.
7 As liver is the major site for transsulfuration and taurine synthesis, hepatic dysfunction can adversely affect sulfur amino acid status.
8 Dose ratio of tramadol and paracetamol in combination ensures the best possible synergy. For synergistic analgesic effect this fixed ratio is really the one to select.
9 Combination of these different pharmacological effects produces effective analgesia (analgesic synergy) without synergy in side effects. Tramadol represents an excellent multimodal analgesic.
10 Tramadol and Paracetamol are well known, very well researched and with excellent safety profile to what else is available.
11 The combination produces a rapid onset of analgesia with Tramadol contributing to the long duration of action. The combination is more efficacious than the individual components alone.
12 With effective analgesia patients will have improved mobility and quicker rehabilitation.
   

CLINICAL PHARMACOLOGY PHARMACODYNAMICS TRAMADOL

Tramadol is a synthetic centrally acting analgesic. Tramadol is used orally as an analgesic for the relief of moderate to moderately severe pain. Comparative and non-comparative clinical studies have shown that tramadol is an effective analgesic agent in the treatment of moderately severe acute or chronic pain including post-operative gynaecologic and obstetric pain, as well as pain of various other origins including cancer. The drug acts as an opiate agonist apparently by selective activity at µ opioid receptors. Tramadol inhibits reuptake of certain monoamines (norepinephrine, serotonin) which appears to contribute to the drug’s analgesic effect.

PARACETAMOL

Paracetamol, a para-aminophenol derivative, has analgesic and antipyretic properties and weak anti-inflammatory activity. Paracetamol is often the analgesic or antipyretic of choice especially in patients in whom salicylates or other NSAIDS are contraindicated. Such patients include asthmatics or those with a history of peptic ulcer. Its use is generally preferred in elderly patients. Paracetamol is used in the management of mild to moderate pain. Paracetamol may also be used as an adjunct to opioids in the management of severe pain such as cancer pain.

CAFFEINE

Caffeine is a methylxanthine which like theophylline inhibits the enzyme phosphodiesterase and has an antagonistic effect at central adenosine receptors. It is a stimulant of CNS particularly the higher centres and it can produce a condition of wakefulness and increased mental activity. It may also stimulate the respiratory centre increasing the rate and depth of respiration. Caffeine facilitates the performance of muscular work and increases the total work which can be performed by a muscle.

FUNCTIONS OF CAFFEINE IN THE BODY

  • Caffeine consumption is known for its stimulating effect of psychological and physiological functions – concentration, reaction speed and alertness are improved.
  • Caffeine stimulates fat burning during endurance activities and thereby helps to use fat stores in the body to provide energy and to preserve the glycogen. This means that Caffeine intake during endurance activities results in a more efficient supply of energy and especially in extended exertion it leads to a significant improvement in performance and endurance.

TAURINE

Taurine is derivative of the sulfur containing amino acid, Cysteine. Taurine is one of the few known naturally occurring sulfonic acids. It is often called an amino acid but as it lacks a carboxyl group it is not strictly an amino acid. It acts as an anti-oxidant and protects against toxicity of various substances. Supplementation with taurine has been shown to prevent oxidative stress induced by exercise. Taurine aids the movement of potassium, sodium, calcium and magnesium in and out of cells and helps generate nerve impulse and activate the body. The action of taurine on the cardiovascular system is highly complex and has not yet been fully investigated. There is proof however that taurine both inhibits cardiac arrhythmias and lowers blood pressure. Taurine contributes to the maintenance of the electrolytic balance. It has been shown to have a protective effect on cells especially on leucocytes and neurons. Based on its antioxidative role, its effect on inflammation, connective tissue generation, taurine has recently been proposed as a wound healing agent. Taurine has a positive effect on patients with cardiac disorders.

PHARMACOKINETICS

TRAMADOL
Tramadol is readily absorbed following oral administration but is subject to first pass metabolism. Tramadol is metabolized in the liver. Tramadol is excreted mainly in the urine predominantly as metabolites. Tramadol is widely distributed. The elimination half life following oral administration is about 6 hours.

PARACETAMOL
Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 10 to 60 minutes after oral administration. Paracetamol is distributed into most body tissues. The elimination half-life of Paracetamol varies from about 1 to 3 hours. Paracetamol is metabolized predominantly in the liver and excreted in the urine.

CAFFEINE
Caffeine is absorbed readily after oral administration and is widely distributed throughout the body. Caffeine passes readily into CNS and saliva. In adults Caffeine is metabolized almost completely in the liver and is excreted 1% unchanged in the urine. Elimination half lives are approximately 3 to 7 hours in adults.

INDICATIONS

ASQUE is indicated for the management of moderate to moderately severe acute or chronic pain including:-
1 OSTEOARTHRITIC PAIN.
2 SEVERE LOWER BACK PAIN.
3 REHABILITATION AFTER SPORTS INJURY/DAY CASE SURGERY.
4 POST OPERATIVE PAIN – GYNAECOLOGIC, OBSTETRIC, ONCOLOGIC, DENTAL SURGERY AND GENERAL SURGERY.
5 FRACTURE.
6 NEUROPATHIC PAIN.
7 DENTAL PAIN.
8 CANCER PAIN.

CONTRAINDICATIONS

1 HYPERSENSITIVTY.
2 CNS DEPRESSANTS – Alcohol, Opioid Analgesics, Psychotropics.

ADVERSE DRUG REACTIONS

Generally the combination is well tolerated. Commonly reported adverse effects were nausea (In 26% after 7 days), dizziness, dry mouth, fatigue and dyspepsia.

PRECAUTIONS AND WARNINGS

1 The combination should be given with caution in patients taking Selective Serotonin Reuptake Inhibitors (SSRI), Tricyclic Antidepressants, Opioid Agonists.
2 Should be given with caution in patients at Seizure risks - Epilepsy, Head Injury and Metabolic Disorders.
3 Should be used with caution and in reduced dosage in patients receiving CNS depressants.
4 The combination should be used with caution in patients with increased intracranial pressure and head injury.

DOSAGE AND ADMINISTRATION

The combination should be administered orally. ADULTS AND ADOLESCENTS (17 years and above)

MODERATE OR MODERATELY SEVERE PAIN

Initial Dose 1 – 2 tablets
Maintenance Dose 1-2 tablets every 4-6 hours.

Daily Dosage not to exceed 6 tablets or as directed by physician.

GERIATRICS

1 or 2 tablets every 4-6 hours as needed in patients with normal renal and hepatic functions.
75 yrs and older - Dosage not to exceed 6 Tablets /Day.

DOSAGE IN RENAL AND HEPATIC IMPAIRMENT

Dosage Reduced by decreasing frequency of administration in patients with GFR (Glomerular Filteration Rate) < 30 ml/min – 1 or 2 tablets every 12 hours.
Not to exceed 200 mg/day (Tramadol).
Hepatic Cirrhosis - 1 tablet every 12 hours.

PAEDIATRIC

Safety and Efficacy of the combination in children less than 16 years not established.

PREGNANCY AND LACTATION

Safe use of the combination not established and should be used only if potential benefits justify potential risk to foetus. The combination not recommended in:-
  • Obstetrical Pre-Operative Medication.
  • Post Delivery Analgesia.

PRESENTATION

Strip of 10 tablets.

Contact : Mr.Adiga
Telephone : 91-80-23154770/23156757
E-mail : pmt@afdil.com