Tonoflex-P Tablets

                                Tonoflex-P

                  (Tramadol HCI + Paracetamol)

Composition:

Each film coated tablet contains:

Tramadol HCI Ph. Eur.......37.5mg

Paracetamol BP..... ..............32.5mg

Clinical Pharmacology:

Mode of Action

Tramadol is a centrally acting synthetic analgesic compound whose analgesic profile can be attributed to the binding of parent and 0-demethylated (M1) metabolites to opioid receptors as well as the weak inhibition of neuronal re-uptake of noradrenaline and serotonin. Paracetamol also has centrally acting analgesic effects

PHARMACOKINETICS:
Tramadol is well absorbed after oral adminstration, reaching peak activity in 2 to 3 hours. Oral absorption of paracetamol following co-administration of tramadol and paracetamol, gives a peak plasma concentration of paracetamol within one hour and is not affected by co-administration with tramadol Tramadol and paracetamol are both extensively metabolised in tha liver. Approximately 30% of tramadol is excteted unchanged in the urine. Tramadol and its metabolites are eliminated primarily by the kidney. The plasme elimination half-lives of tramadol and its M1 metabolite are approximate 6 and 7 hours respectively. Paracetamol is eliminated from the body primarily by fomation of glucuronidr and sulfate conjugates in a dose-dependent manner. The half-life of paracetamol is about 2-3 hours in adults. Less than 9% of paracetamol is excreted  unchanged in the urine

INDICATIONS:
Tonoflex-P tablets are indicated for short term (Less than 5 days) management of acute pain

WARNINGS:
dosages in excess of those recommended may cause severe liver damage. Patients suffering from liver or kidney disease should take paracetamol containing products under medical supervision

serious Skin Reactions
Rarely, acetaminophen (paracetamol) may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidemal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity

Seizures
Seizures have been reported in patiens receiving tramadol at dosages within the recommended dosage range. The risk of seizures is enhanced in patients exceeding the recommended dose, or in patients taking tricyclic anti-depressants or other tricyclic e.g.promethazine, selective serotonin re-uptake inhibitors, MAO-inhibitors and neuroleptics

Drug Abuse and Dependence
Although tramadol has a low dependence potential, tolerance, psychic and physical dependence of the morphine-type may develop with long-tem use

Effects on Ability to Drive or Operate Machinery
Tramadol may affect reactions to the extent that driving ability and the ability and the ability to operate machinery may be impired. This applies particularly in cinjunction with other psychotropic medicines including alcohol

DOSAGE AND ADMINISTRATION:
To be used in adults and children over 16 years of age. Do not exceed the recommend dose

Acute Pain
2 tablets every 4 or 6 hours as needed for pain relief. Do not exceed 8 teblets per day

Renal Impairment
In patients with creatinine clearance less than 30ml/min, it is recommended that the dosing interval be increased not to exceed 2 tablets every 12 hours

PRECAUTIONS:

Pregnancy
Teratogenic Effect: pregnancy Category C
Safety during pregnancy and lactation has not been established. Tremadol has been show to cross the placenta

Children
Safety and efficacy have not been established

Elderly
Use with caution, reflecting the greater frequency of hepatic, renal, or cardiac function, and of concomitant disease and multiple drug therapy.