Utracet Tablet 37.5mg+325mg

Product Information

UTRACET

UTRACET® (Tramadol HCl and Paracetamol)

Presentation

UTRACET tablet: Light yellow, oval-shaped, having ‘ ‘ engraved on one side, film-coated tablet; each tablet contains Tramadol HCl

BP 37.5mg and Paracetamol BP 325mg

Indications

UTRACET (Tramadol HCl and Paracetamol) tablets are indicated for the symptomatic treatment of moderate to severe pain. The use of

UTRACET (Tramadol HCl and Paracetamol) tablet should be restricted to patients whose moderate to severe pain is considered to

require a combination of Tramadol and Paracetamol.

Dosage and administration

Adults and adolescents (12 years and older): The dose should be individually adjusted according to intensity of pain and response

of the patient. An initial dose of 2 UTRACET (Tramadol HCl and Paracetamol) tablets (Tramadol HCl 75mg and Paracetamol 650mg) is

recommended. Additional doses can be taken as needed, not exceeding 8 tablets (equivalent to Tramadol 300mg and Paracetamol

2600mg) per day. The dosing interval should not be less than six hours. UTRACET (Tramadol HCl and Paracetamol) tablet should under

no circumstances be administered for longer than is strictly necessary. If repeated use or long-term treatment with UTRACET

(Tramadol HCl and Paracetamol) tablet is required as a result of the nature and severity of the illness, then regular monitoring

should take place (with breaks in the treatment, where possible), to assess whether continuation of the treatment is necessary.

Children: The effective and safe use of UTRACET (Tramadol HCl and Paracetamol) tablet has not been established in children below

the age of 12 years. Treatment is therefore not recommended in this population.

Elderly patients: The usual dosages may be used although it should be noted that in volunteers aged over 75 years the elimination

half life of Tramadol was increased by 17% following oral administration. In patients over 75 years old, it is recommended that

the minimum interval between doses should be not less than 6 hours, due to the presence of Tramadol. Renal insufficiency: Because

of the presence of Tramadol, the use of UTRACET (Tramadol HCl and Paracetamol) tablet is not recommended in patients with severe

renal insufficiency (creatinine clearance < 10ml/min). In cases of moderate renal insufficiency (creatinine clearance between

10 and 30ml/min), the dosing should be increased to 12-hourly intervals. As Tramadol is removed only very slowly by haemodialysis

or by haemofiltration, post dialysis administration to maintain analgesia is not usually required.

Hepatic insufficiency: In patients with severe hepatic impairment UTRACET (Tramadol HCl and Paracetamol) tablet should not be

used. In moderate cases prolongation of the dosage interval should be carefully considered. Method of administration: Oral use.

UTRACET tablets must be swallowed whole, with a sufficient quantity of liquid. They must not be broken or chewed.

Contra-indications, warnings, etc.

Contra-indication: Tramadol HCl and Paracetamol tablet is contra-indicated in patients with hypersensitivity to Tramadol and or

Paracetamol; acute intoxication with alcohol, hypnotic drugs, centrally-acting analgesics, opioids or psychotropic drugs; who are

receiving monoamine oxidase inhibitors or within two weeks of their withdrawal; severe hepatic impairment and epilepsy

not controlled by treatment.

Warnings: In adults and adolescents 12 years and older: The maximum dose of Tramadol HCl and Paracetamol is Tramadol 300mg and

Paracetamol 2600mg which should not be exceeded. In order to avoid inadvertent overdose, patients should be advised not to exceed

the recommended dose and not to use any other Paracetamol or Tramadol HCl containing products concurrently without the advice of a

doctor. In severe renal insufficiency (creatinine clearance < 10ml/mm), Tramadol HCl and Paracetamol tablet is not recommended. In

patients with severe hepatic impairment Tramadol HCl and Paracetamol tablet should not be used. The hazards of Paracetamol

overdose are greater in patients with non-cirrhotic alcoholic liver disease. In moderate cases prolongation of dosage interval

should be carefully considered. In severe respiratory insufficiency, Tramadol HCl and Paracetamol tablet is not recommended.

Tramadol is not suitable as a substitute in opioid-dependent patients. Although it is an opioid agonist, Tramadol cannot suppress

morphine withdrawal symptoms. Convulsions have been reported in Tramadol-treated patients susceptible to seizures or taking other

medications that lower the seizure threshold, especially selective serotonin re-uptake inhibitors, tricyclic

antidepressants, antipsychotics, centrally acting analgesics or local anaesthesia. Epileptic patients controlled by a treatment or

patients susceptible to seizures should be treated with Tramadol HCl and Paracetamol only if there are compelling circumstances.

Convulsions have been reported in patients receiving Tramadol at the recommended dose levels. The risk may be increased when doses

of Tramadol exceed the recommended upper dose limit. Concomitant use of opioid agonists-antagonists (Nalbuphine, Buprenorphine,

Pentazocine) is not recommended.

Precaution: Tramadol HCl and Paracetamol combination should be used with caution in opioid dependent patients, or in patients with

cranial trauma, in patients prone to convulsive disorder, biliary tract disorders, in a state of shock, in an altered state of

consciousness for unknown reasons, with problems affecting the respiratory center or the respiratory function, or with

an increased intracranial pressure. Paracetamol in overdosage may cause hepatic toxicity in some patients. At therapeutic doses,

Tramadol has the potential to cause withdrawal symptoms. Rarely, cases of dependence and abuse have been reported. Symptoms of

withdrawal reactions, similar to those occurring during opiate withdrawal may occur. In one study, use of Tramadol during general

anaesthesia with enflurane and nitrous oxide was reported to enhance intra-operative recall. Until further information is

available, use of Tramadol during light planes of anaesthesia should be avoided. Effects on ability to drive and use machines:

Tramadol may cause drowsiness or dizziness, which may be enhanced by alcohol or other CNS depressants. If affected, the patient

should not drive or operate machinery.

Use in Pregnancy and Lactation: Pregnancy: It should not be used during pregnancy. Data regarding Paracetamol: Epidemiological

studies in human pregnancy have shown no ill effects due to Paracetamol used in the recommended dosages. Data regarding Tramadol:

Tramadol should not be used during pregnancy as there is inadequate evidence available to assess the safety of Tramadol in

pregnant women. Tramadol administered before or during birth does not affect uterine contractility. In neonates it may induce

changes in the respiratory rate which are usually not clinically relevant. Long-term treatment during pregnancy may lead to

withdrawal symptoms in the new born after birth, as a consequence of habituation. Lactation: It should not be ingested during

breast feeding. Data regarding Paracetamol: Paracetamol is excreted in breast milk but not in a clinically significant amount.

Available published data do not contra-indicate breast feeding by women using single ingredient medicinal products containing

only Paracetamol. Data regarding Tramadol: Tramadol and its metabolites are found in small amounts in human breast milk. An infant

could ingest about 0.1% of the dose given to the mother. Tramadol should not be ingested during breast feeding.

Drug interactions: Concomitant use is contraindicated with: MAO Inhibitors – Risk of serotoninergic syndrome: diarrhoea,

tachycardia, sweating, trembling, confusion, even coma. In case of recent treatment with MAO inhibitors, a delay of two weeks

should occur before treatment with Tramadol. Concomitant use is not recommended with: Alcohol – Alcohol increases the sedative

effect of opioid analgesics. The effect on alertness can make driving of vehicles and the use of machines dangerous. Carbamazepine

and other enzyme inducers – Risk of reduced efficacy and shorter duration due to decreased plasma concentrations of Tramadol.

Opioid agonists-antagonists (Buprenorphine, Nalbuphine, Pentazocine) – Decrease of the analgesic effect by competitive blocking

effect at the receptors, with the risk of occurrence of withdrawal syndrome. Concomitant use which needs to be taken into

consideration: In isolated cases there have been reports of serotonin syndrome in a temporal connection with the therapeutic use

of Tramadol in combination with other serotoninergic medicines such as selective serotonin reuptake inhibitors (SSRIs) and

triptans. Signs of serotonin syndrome may be for example, confusion, agitation, fever, sweating, ataxia, hyperreflexia, myoclonus

and diarrohoea. Other opioid derivatives (including antitussive drugs and substitutive treatments), benzodiazepines

and barbiturates – Increase risk of respiratory depression which can be fatal in cases of overdose. Other central nervous system

depressants, such as other opioid derivatives (including antitussive drugs and substitutive treatments), Barbiturates,

Benzodiazepines, other anxiolytics, hypnotics, sedative antidepressants, sedative antihistamines, neuroleptics, centrally-acting

antihypertensive drugs, Thalidomide and Baclofen – these drugs can cause increased central depression. The effect on alertness can

make driving of vehicles and the use of machines dangerous. As medically appropriate, periodic evaluation of prothrombin time

should be performed when Tramadol and Paracetamol with Warfarin like compounds are administered concurrently due to reports

of increased INR. Medicinal products reducing the seizure threshold, such as Bupropion, serotonin reuptake inhibitor

antidepressants, tricyclic antidepressants and neuroleptics. Concomitant use of Tramadol with these drugs can increase the risk of

convulsions. The speed of absorption of Paracetamol may be increased by Metoclopramide or Domperidone and absorption reduced

by Cholestyramine. In a limited number of studies the pre-or postoperative application of the antiemetic 5-HT3 antagonist

Ondansetron increased the requirement of Tramadol in patients with postoperative pain.

Side effects: The most commonly reported undesirable effects during the clinical trials performed with the Tramadol and

Paracetamol tablet were nausea, dizziness and somnolence, observed in more than 10% of the patients. Cardiovascular system

disorders: Uncommon – Hypertension, palpitations, tachycardia, arrhythmia. Central and peripheral nervous system disorders:

Very common – Dizziness, somnolence. Common – Headache trembling. Uncommon – Involuntary muscular contractions, paraesthesia,

tinnitus. Rare – Ataxia, convulsions. Psychiatric disorders: Common – Confusion, mood changes (anxiety, nervousness, euphoria),

sleep disorders. Uncommon – Depression, hallucinations, nightmares, amnesia. Rare – Drug dependence. Very rare – Abuse. Vision

disorders: Rare – Blurred vision. Respiratory system disorders: Uncommon – Dyspnoea. Gastro-intestinal disorders: Very common –

Nausea. Common – Vomiting, constipation, dry mouth, diarrhea, abdominal pain, dyspepsia, flatulence. Uncommon – dysphagia,

melena. Liver and billiary system disorders: Uncommon – hepatic transminases increase. Skin and appendages disorders: Common –

Sweating, pruritus. Uncommon – dermal reactions. Urinary system disorders: Uncommon – Abuminuria, micturition disorders (dysuria

and urinary retention). Body as a whole: Uncommon – Shivers, hot flushes, thoracic pain. Although not observed during clinical

trials, the occurrence of the following undesirable effects known to be related to the administration of Tramadol, of Paracetamol

cannot be excluded. Side effects associated with Tramadol: Postural hypotension, bradycardia, collapse. Tramadol has revealed rare

alternations of warfarin effect, including elevation of prothrombin times. Rare cases: Changes in appetite, motor weakness, and

respiratory depression. Psychic side-effects may occur following administration of Tramadol which vary individually in intensity

and nature (depending on personality and duration of medication). These include changes in mood, (usually elation occasionally

dysphoria), changes in activity (usually suppression occasionally increase) and changes in cognitive and sensorial capacity (e.g.

decision behavior perception disorders).Worsening asthma has been reported though a causal relationship has not been established.

Symptoms of withdrawal reactions, similar to those occurring during opiate withdrawal may occur as follows: agitation, anxiety,

nervousness, insomnia, hyperkinesias, tremor and gastrointestinal systems. Other systems that have very rarely been seen if

Tramadol HCl is discontinued abruptly include: panic attacks, severe anxiety, hallucinations, paraesthesia, tinnitus and unusual

CNS symptoms. Side effects associated Paracetamol: Adverse effects of Paracetamol are rare but hypersensitivity including skin

rash may occur. There have been reports of blood dyscrasias including thrombocytopenia, and agranulocytosis, but they were

not necessarily causally related to Paracetamol. There have been several reports that suggest that Paracetamol may produce

hyperprothrombenimia when administered with Warfarin-like compounds. In other studies, prothrombin time did not change.

Overdose: In case of overdose, the symptoms may include the signs and symptoms of toxicity of Tramadol or Paracetamol or of both

these active ingredients. Symptoms of overdose from Tramadol: In principle on intoxication with Tramadol, symptoms similar to

those of other centrally acting analgesics (opioids) are to be expected. These include in particular, miosis, vomiting,

and cardiovascular collapse, consciousness disorders up to coma, convulsions and respiratory depression up to respiratory arrest.

Symptoms of overdose from Paracetamol: An overdose is of particular concern in young children. Symptoms of Paracetamol overdosage

in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours

after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may

progress to encephalopathy, coma and death. Acute renal failure with tubular necrosis may develop even in the absence of severe

liver damage. Cardiac arrhythmia and pancreatic have been reported. Liver damage is possible in adults who have taken Paracetamol

7.5-10 g or more. It is considered that quantities of a toxic metabolic (usually adequately detoxified by glutathione when normal

doses of Paracetamol are ingested), become irreversibly bound to liver tissue. Emergency treatment: Transfer immediately to a

specialised unit. Maintain respiratory and circulatory functions. Prior to starting treatment, a blood sample should be taken as

soon as possible after overdose in order to measure the plasma concentration of Paracetamol and Tramadol and in order to perform

hepatic tests. Perform hepatic tests at the start (of overdose) and repeat every 24 hours. An increase in hepatic enzymes (ASAT,

ALAT) is usually observed, which normalizes after one or two weeks. Empty the stomach by causing the patient to vomit (when the

patient is conscious) by irritation or gastric lavage. Supportive measures such as maintaining the patency of the airway and

maintaining cardiovascular function should be instituted; naloxone should be used to reverse respiratory depression; fits can be

controlled with diazepam. Tramadol is minimally eliminated from the serum by haemodialysis or haemofiltration. Therefore treatment

of acute intoxication with Tramadol and Paracetamol tablet with haemodialysis or haemofiltration alone is not suitable

for detoxification. Immediate treatment is essential in the management of Paracetamol overdose. Despite a lack of significant

early symptoms, patients should be referred to hospital urgently for immediate medical attention and any adult or adolescent who

had ingested around 7.5 g or more of Paracetamol in the preceding 4 hours or any child who has ingested 150 mg/kg of Paracetamol

in the preceding 4 hours should undergo gastric lavage. Paracetamol concentrations in blood should be measured later than 4 hours

after overdose in order to be able to assess the risk of developing liver damage (via the Paracetamol overdose nomogram).

Administration of oral methionine or intravenous N-acetylcysteine (NAC) which may have a beneficial effect up to at least 48 hours

after the overdose, may be required. Administration of intravenous NAC is most beneficial when initiated within 8 hours of

overdose ingestion. However, NAC should still be given if the time to presentation is greater than 8 hours after overdose and

continued for a full course of therapy. NAC treatment should be started immediately when massive overdose is suspected. General

supportive measures must be available. Irrespective of the reported quantity of Paracetamol ingested, the antidote for

Paracetamol, NAC, should be administered orally or intravenously, as quickly as possible, if possible, within 8 hours following

the overdose.

Pharmaceutical precautions

Store in a cool and dry place, protected from light.

Packaging quantities

UTRACET tablet: Cartons containing 30 tablets in blisters.