Tapentadol 50mg Tablets Taj Pharma

Tapentadol 50mg Tablets Taj Pharma

1. Name of the medicinal product

Tapentadol 50mg tablets Taj Pharma

2. Qualitative and quantitative composition

Each  tablet contains 50mg Tapentadol (as hydrochloride).

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Film coated tablet

4. Clinical particulars

4.1 Therapeutic indications

Tapentadol is indicated for the management of severe chronic pain in adults, which can be adequately managed only with opioid analgesics.

4.2 Posology and method of administration

Posology

The dosing regimen should be individualised according to the severity of pain being treated, the previous treatment experience and the ability to monitor the patient.

Tapentadol should be taken twice daily, approximately every 12 hours.

Initiation of therapy

Initiation of therapy in patients currently not taking opioid analgesics

Patients should start treatment with single doses of 50mg Tapentadol as  tablet administered twice daily.

Initiation of therapy in patients currently taking opioid analgesics

When switching from opioids to Tapentadol and choosing the initial dose, the nature of the previous medicinal product, administration and the mean daily dose should be taken into account. This may require higher initial doses of Tapentadol for patients currently taking opioids compared to those not having taken opioids before initiating therapy with Tapentadol.

Titration and maintenance

After initiation of therapy the dose should be titrated individually to a level that provides adequate analgesia and minimises undesirable effects under the close supervision of the prescribing physician.

Experience from clinical trials has shown that a titration regimen in increments of 50mg Tapentadol as  tablet twice daily every 3 days was appropriate to achieve adequate pain control in most of the patients.

Total daily doses of Tapentadol greater than 500mg Tapentadol have not yet been studied and are therefore not recommended.

Discontinuation of treatment

Withdrawal symptoms could occur after abrupt discontinuation of treatment with Tapentadol (see section 4.8). When a patient no longer requires therapy with Tapentadol, it is advisable to taper the dose gradually to prevent symptoms of withdrawal.

Renal Impairment

In patients with mild or moderate renal impairment a dosage adjustment is not required (see section 5.2).

Tapentadol has not been studied in controlled efficacy trials in patients with severe renal impairment, therefore the use in this population is not recommended (see sections 4.4 and 5.2).

Hepatic Impairment

In patients with mild hepatic impairment a dosage adjustment is not required (see section 5.2).

Tapentadol should be used with caution in patients with moderate hepatic impairment. Treatment in these patients should be initiated at the lowest available dose strength, i.e. 50mg Tapentadol as  tablet, and not be administered more frequently than once every 24 hours. At initiation of therapy a daily dose greater than 50mg Tapentadol as  tablet is not recommended. Further treatment should reflect maintenance of analgesia with acceptable tolerability (see sections 4.4 and 5.2).

Tapentadol has not been studied in patients with severe hepatic impairment and therefore, use in this population is not recommended (see sections 4.4 and 5.2).

Elderly patients (persons aged 65 years and over)

In general, a dose adaptation in elderly patients is not required. However, as elderly patients are more likely to have decreased renal and hepatic function, care should be taken in dose selection as recommended (see sections 4.2 and 5.2).

Paediatric Patients

The safety and efficacy of Tapentadol in children and adolescents below 18 years of age has not yet been established. Therefore Tapentadol is not recommended for use in this population.

Method of administration

Tapentadol has to be taken whole, not divided or chewed, to ensure that the  mechanism is maintained. Tapentadol should be taken with sufficient liquid. Tapentadol can be taken with or without food.

The shell (matrix) of the Tapentadol tablet may not be digested completely and therefore it can be eliminated and seen in the patient’s stool. However, this finding has no clinical relevance, since the active substance of the tablet will have already been absorbed.

4.3 Contraindications

TAPENTADOL is contraindicated

• in patients with hypersensitivity to Tapentadol or to any of the excipients listed in section 6.1.
• in situations where active substances with mu-opioid receptor agonist activity are contraindicated, i.e. patients with significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment), and patients with acute or severe bronchial asthma or hypercapnia
• in any patient who has or is suspected of having paralytic ileus
• in patients with acute intoxication with alcohol, hypnotics, centrally acting analgesics, or psychotropic active substances (see section 4.5)

4.4 Special warnings and precautions for use

Potential for Abuse and Addiction/ Dependence Syndrome

Tapentadol has a potential for abuse and addiction. This should be considered when prescribing or dispensing Tapentadol in situations where there is concern about an increased risk of misuse, abuse, addiction, or diversion.

All patients treated with active substances that have mu-opioid receptor agonist activity should be carefully monitored for signs of abuse and addiction.

Risk from concomitant use of sedating medicinal products such as benzodiazepines or related substances

Concomitant use of Tapentadol and sedating medicinal products such as benzodiazepines or related substances may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedating medicinal products should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Tapentadol concomitantly with sedating medicinal products, the reduction of dose of one or both agents should be considered and the duration of the concomitant treatment should be as short as possible.

The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5).

Respiratory Depression

At high doses or in mu-opioid receptor agonist sensitive patients, Tapentadol may produce dose-related respiratory depression. Therefore, Tapentadol should be administered with caution to patients with impaired respiratory functions. Alternative non-mu-opioid receptor agonist analgesics should be considered and Tapentadol should be employed only under careful medical supervision at the lowest effective dose in such patients. If respiratory depression occurs, it should be treated as any mu-opioid receptor agonist-induced respiratory depression (see section 4.9).

Head Injury and Increased Intracranial Pressure

Tapentadol should not be used in patients who may be particularly susceptible to the intracranial effects of carbon dioxide retention such as those with evidence of increased intracranial pressure, impaired consciousness, or coma. Analgesics with mu-opioid receptor agonist activity may obscure the clinical course of patients with head injury. Tapentadol should be used with caution in patients with head injury and brain tumors.

Seizures

Tapentadol has not been systematically evaluated in patients with a seizure disorder, and such patients were excluded from clinical trials. However, like other analgesics with mu-opioid agonist activity Tapentadol is not recommended in patients with a history of a seizure disorder or any condition that would put the patient at risk of seizures. In addition, tapentadol may increase the seizure risk in patients taking other medicinal products that lower the seizure threshold (see section 4.5).

Renal Impairment

Tapentadol has not been studied in controlled efficacy trials in patients with severe renal impairment, therefore the use in this population is not recommended (see section 4.2 and 5.2).

Hepatic Impairment

Subjects with mild and moderate hepatic impairment showed a 2-fold and 4.5-fold increase in systemic exposure, respectively, compared with subjects with normal hepatic function. Tapentadol should be used with caution in patients with moderate hepatic impairment (see section 4.2 and 5.2), especially upon initiation of treatment.

Tapentadol has not been studied in patients with severe hepatic impairment and therefore, use in this population is not recommended (see sections 4.2 and 5.2).

Use in Pancreatic/Biliary Tract Disease

Active substances with mu-opioid receptor agonist activity may cause spasm of the sphincter of Oddi. Tapentadol should be used with caution in patients with biliary tract disease, including acute pancreatitis.

Mixed opioid agonists/antagonists

Care should be taken when combining Tapentadol with mixed mu-opioid agonist/antagonists (like pentazocine, nalbuphine) or partial mu-opioid agonists (like buprenorphine). In patients maintained on buprenorphine for the treatment of opioid dependence, alternative treatment options (like e.g. temporary buprenorphine discontinuation) should be considered, if administration of full mu-agonists (like Tapentadol) becomes necessary in acute pain situations. On combined use with buprenorphine, higher dose requirements for full mu-receptor agonists have been reported and close monitoring of adverse events such as respiratory depression is required in such circumstances.

Tapentadol  tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption, should not take this medicinal product.

4.5 Interaction with other medicinal products and other forms of interaction

Sedative medicines such as benzodiazepines or related drugs

The concomitant use of Tapentadol with sedating medicinal products such as benzodiazepines or other respiratory or CNS depressants (other opioids, antitussives or substitution treatments, barbiturates, antipsychotics, H1-antihistamines, alcohol) increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. Therefore, when a combined therapy of Tapentadol with a respiratory or CNS depressant is contemplated, the reduction of dose of one or both agents should be considered and the duration of the concomitant use should be limited (see section 4.4).

Mixed opioid agonists/antagonists

Care should be taken when combining Tapentadol with mixed mu-opioid agonist/antagonists (like pentazocine, nalbuphine) or partial mu-opioid agonists (like buprenorphine) (see also section 4.4).

Tapentadol can induce convulsions and increase the potential for selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, antipsychotics and other medicinal products that lower the seizure threshold to cause convulsions.

There have been reports of serotonin syndrome in a temporal connection with the therapeutic use of Tapentadol in combination with serotoninergic medicinal products such as selective serotonin re-uptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants.

Serotonin syndrome is likely when one of the following is observed:

• Spontaneous clonus
• Inducible or ocular clonus with agitation or diaphoresis
• Tremor and hyperreflexia
• Hypertonia and body temperature > 38°C and inducible ocular clonus.

Withdrawal of the serotoninergic medicinal products usually brings about a rapid improvement. Treatment depends on the nature and severity of the symptoms.

The major elimination pathway for Tapentadol is conjugation with glucuronic acid mediated via uridine diphosphate transferase (UGT) mainly UGT1A6, UGT1A9 and UGT2B7 isoforms. Thus, concomitant administration with strong inhibitors of these isoenzymes (e.g. ketoconazole, fluconazole, meclofenamic acid) may lead to increased systemic exposure of Tapentadol (see section 5.2).

For patients on Tapentadol treatment, caution should be exercised if concomitant drug administration of strong enzyme inducing drugs (e.g. rifampicin, phenobarbital, St John’s Wort (hypericum perforatum)) starts or stops, since this may lead to decreased efficacy or risk for adverse effects, respectively

Treatment with Tapentadol should be avoided in patients who are receiving monoamine oxidase (MAO) inhibitors or who have taken them within the last 14 days due to potential additive effects on synaptic noradrenaline concentrations which may result in adverse cardiovascular events, such as hypertensive crisis.

4.6 Fertility, pregnancy and lactation

Pregnancy

There is very limited amount of data from the use in pregnant women.

Studies in animals have not shown teratogenic effects. However, delayed development and embryotoxicity were observed at doses resulting in exaggerated pharmacology (mu-opioid-related CNS effects related to dosing above the therapeutic range). Effects on the postnatal development were already observed at the maternal NOAEL (see section 5.3).

Tapentadol should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Labour and Delivery

The effect of Tapentadol on labour and delivery in humans is unknown. Tapentadol is not recommended for use in women during and immediately before labour and delivery. Due to the mu-opioid receptor agonist activity of Tapentadol, new-born infants whose mothers have been taking Tapentadol should be monitored for respiratory depression.

Lactation

There is no information on the excretion of Tapentadol in human milk. From a study in rat pups suckled by dams dosed with Tapentadol it was concluded that Tapentadol is excreted via milk (see section 5.3). Therefore, a risk to the suckling child cannot be excluded. Tapentadol should not be used during breast feeding.

4.7 Effects on ability to drive and use machines

Tapentadol may have major influence on the ability to drive and use machines, because it may adversely affect central nervous system functions (see section 4.8). This has to be expected especially at the beginning of treatment, when any change of dosage occur as well as in connection with the use of alcohol or tranquilisers (see section 4.4). Patients should be cautioned as to whether driving or use of machines is permitted.

4.8 Undesirable effects

The adverse drug reactions that were experienced by patients in the placebo controlled trials performed with Tapentadol were predominantly of mild and moderate severity. The most frequent adverse drug reactions were in the gastrointestinal and central nervous system (nausea, dizziness, constipation, headache and somnolence).

The table below lists adverse drug reactions that were identified from clinical trials performed with Tapentadol and from post-marketing environment. They are listed by class and frequency. Frequencies are defined as very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

Clinical trials performed with Tapentadol with patient exposure up to 1 year have shown little evidence of withdrawal symptoms upon abrupt discontinuations and these were generally classified as mild, when they occurred. Nevertheless, physicians should be vigilant for symptoms of withdrawal (see section 4.2) and treat patients accordingly should they occur.

The risk of suicidal ideation and suicides committed is known to be higher in patients suffering from chronic pain. In addition, substances with a pronounced influence on the monoaminergic system have been associated with an increased risk of suicidality in patients suffering from depression, especially at the beginning of treatment. For Tapentadol data from clinical trials and post-marketing reports do not provide evidence for an increased risk.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

Symptoms

Human experience with overdose of Tapentadol is very limited. Preclinical data suggest that symptoms similar to those of other centrally acting analgesics with mu-opioid receptor agonist activity are to be expected upon intoxication with Tapentadol. In principle, these symptoms include, referring to the clinical setting, in particular miosis, vomiting, cardiovascular collapse, consciousness disorders up to coma, convulsions and respiratory depression up to respiratory arrest.

Management

Management of overdose should be focused on treating symptoms of mu-opioid agonism. Primary attention should be given to re-establishment of a patent airway and institution of assisted or controlled ventilation when overdose of Tapentadol is suspected.

Pure opioid receptor antagonists such as naloxone are specific antidotes to respiratory depression resulting from opioid overdose. Respiratory depression following an overdose may outlast the duration of action of the opioid receptor antagonist. Administration of an opioid receptor antagonist is not a substitute for continuous monitoring of airway, breathing, and circulation following an opioid overdose. If the response to opioid receptor antagonists is suboptimal or only brief in nature, an additional dose of antagonist (e.g. naloxone) should be administered as directed by the manufacturer of the product.

Gastrointestinal decontamination may be considered in order to eliminate unabsorbed active substance. Gastrointestinal decontamination with activated charcoal or by gastric lavage may be considered within 2 hours after intake. Before attempting gastrointestinal decontamination, care should be taken to secure the airway.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Analgesics; opioids; other opioids

Tapentadol is a strong analgesic with µ-agonistic opioid and additional noradrenaline reuptake inhibition properties. Tapentadol exerts its analgesic effects directly without a pharmacologically active metabolite.

Tapentadol demonstrated efficacy in preclinical models of nociceptive, neuropathic, visceral and inflammatory pain; efficacy has been verified in clinical trials with Tapentadol  tablets in non-malignant nociceptive and neuropathic chronic pain conditions as well as chronic tumour-related pain. The trials in pain due to osteoarthritis and chronic low back pain showed similar analgesic efficacy of Tapentadol to a strong opioid used as a comparator. In the trial in painful diabetic peripheral neuropathy Tapentadol separated from placebo which was used as comparator.

Effects on the cardiovascular system: In a thorough human QT trial, no effect of multiple therapeutic and supratherapeutic doses of Tapentadol on the QT interval was shown. Similarly, Tapentadol had no relevant effect on other ECG parameters (heart rate, PR interval, QRS duration, T-wave or U-wave morphology).

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with TAPENTADOL in all subsets of the paediatric population in severe chronic pain (see section 4.2 for information on paediatric use).

Post-marketing data

Two post-marketing studies were performed to address the practical use of Tapentadol.

The efficacy of Tapentadol  tablets has been verified in a multicenter, randomized, double blind parallel-group trial with patients suffering from low back pain with a neuropathic component (KF5503/58). Reductions in average pain intensity were similar in the Tapentadol treatment group and the comparator treatment group i.e. receiving a combination of Tapentadol  tablets and pregabalin immediate release tablets.

In an open-label, multicenter, randomized trial with patients having severe chronic low back pain with a neuropathic component (KF5503/60), Tapentadol  tablets were associated with significant reductions in average pain intensity.

5.2 Pharmacokinetic properties

Absorption

Mean absolute bioavailability after single-dose administration (fasting) of Tapentadol is approximately 32% due to extensive first-pass metabolism. Maximum serum concentrations of Tapentadol are observed at between 3 and 6 hours after administration of  tablets.

Dose proportional increases for AUC have been observed after administration of the  tablets over the therapeutic dose range.

A multiple dose trial with twice daily dosing using 86mg and 172mg Tapentadol administered as  tablets showed an accumulation ratio of about 1.5 for the parent active substance which is primarily determined by the dosing interval and apparent half-life of Tapentadol. Steady state serum concentrations of Tapentadol are reached on the second day of the treatment regimen.

Food Effect

The AUC and C_max increased by 8% and 18%, respectively, when  tablets were administered after a high-fat, high-calorie breakfast. This was judged to be without clinical relevance as it falls into the normal inter-subject variability of Tapentadol PK parameters. TAPENTADOL may be given with or without food.

Distribution

Tapentadol is widely distributed throughout the body. Following intravenous administration, the volume of distribution (Vz) for Tapentadol is 540 +/- 98 l. The serum protein binding is low and amounts to approximately 20%.

Metabolism

In humans, the metabolism of Tapentadol is extensive. About 97% of the parent compound is metabolised. The major pathway of Tapentadol metabolism is conjugation with glucuronic acid to produce glucuronides. After oral administration approximately 70% of the dose is excreted in urine as conjugated forms (55% glucuronide and 15% sulfate of Tapentadol). Uridine diphosphate glucuronyl transferase (UGT) is the primary enzyme involved in the glucuronidation (mainly UGT1A6, UGT1A9 and UGT2B7 isoforms). A total of 3% of active substance is excreted in urine as unchanged active substance. Tapentadol is additionally metabolised to N-desmethyl Tapentadol (13%) by CYP2C9 and CYP2C19 and to hydroxy Tapentadol (2%) by CYP2D6, which are further metabolised by conjugation. Therefore, active substance metabolism mediated by cytochrome P450 system is of less importance than glucuronidation.

None of the metabolites contributes to the analgesic activity.

Elimination

Tapentadol and its metabolites are excreted almost exclusively (99%) via the kidneys. The total clearance after intravenous administration is 1530 +/- 177 ml/min. Terminal half-life is on average 5-6 hours after oral administration.

Special populations

Elderly patients

The mean exposure (AUC) to Tapentadol was similar in a trial with elderly subjects (65-78 years of age) compared to young adults (19-43 years of age), with a 16% lower mean C_max observed in the elderly subject group compared to young adult subjects.

Renal Impairment

AUC and C_max of Tapentadol were comparable in subjects with varying degrees of renal function (from normal to severely impaired). In contrast, increasing exposure (AUC) to Tapentadol-O-glucuronide was observed with increasing degree of renal impairment. In subjects with mild, moderate, and severe renal impairment, the AUC of Tapentadol-O-glucuronide are 1.5-, 2.5-, and 5.5-fold higher compared with normal renal function, respectively.

Hepatic Impairment

Administration of Tapentadol resulted in higher exposures and serum levels to Tapentadol in subjects with impaired hepatic function compared to subjects with normal hepatic function. The ratio of Tapentadol pharmacokinetic parameters for the mild and moderate hepatic impairment groups in comparison to the normal hepatic function group were 1.7 and 4.2, respectively, for AUC; 1.4 and 2.5, respectively, for Cmax; and 1.2 and 1.4, respectively, for t1/2. The rate of formation of Tapentadol-O-glucuronide was lower in subjects with increased liver impairment.

Pharmacokinetic Interactions

Tapentadol is mainly metabolised by glucuronidation, and only a small amount is metabolised by oxidative pathways.

As glucuronidation is a high capacity/low affinity system, which is not easily saturated even in disease, and as therapeutic concentrations of active substances are generally well below the concentrations needed for potential inhibition of glucuronidation, any clinically relevant interactions caused by glucoronidation are unlikely to occur. In a set of drug-drug interaction trials using paracetamol, naproxen, acetylsalicylic acid and probenecid, a possible influence of these active substances on the glucuronidation of Tapentadol was investigated. The trials with probe active substances naproxen (500mg twice daily for 2 days) and probenecid (500mg twice daily for 2 days) showed increases in AUC of Tapentadol by 17% and 57%, respectively. Overall, no clinically relevant effects on the serum concentrations of Tapentadol were observed in these trials.

Furthermore, interaction trials of Tapentadol with metoclopramide and omeprazole were conducted to investigate a possible influence of these active substances on the absorption of Tapentadol. These trials also showed no clinically relevant effects on Tapentadol serum concentrations.

In vitro studies did not reveal any potential of Tapentadol to either inhibit or induce cytochrome P450 enzymes. Thus, clinically relevant interactions mediated by the cytochrome P450 system are unlikely to occur.

Plasma protein binding of Tapentadol is low (approximately 20%). Therefore, the likelihood of pharmacokinetic drug-drug interactions by displacement from the protein binding site is low.

5.3 Preclinical safety data

Tapentadol was not genotoxic in bacteria in the Ames test. Equivocal findings were observed in an in vitro chromosomal aberration test, but when the test was repeated the results were clearly negative. Tapentadol was not genotoxic in vivo, using the two endpoints of chromosomal aberration and unscheduled DNA synthesis, when tested up to the maximum tolerated dose. Long-term animal studies did not identify a potential carcinogenic risk relevant to humans.

Tapentadol had no influence on male or female fertility in rats but there was reduced in utero survival at the high dose. It is not known whether this was mediated via the male or the female. Tapentadol showed no teratogenic effects in rats and rabbits following intravenous and subcutaneous exposure. However, delayed development and embryotoxicity were observed after administration of doses resulting in exaggerated pharmacology (mu-opioid related CNS effects related to dosing above the therapeutic range). After intravenous dosing in rats reduced in utero survival was seen. In rats Tapentadol caused increased mortality of the F1 pups that were directly exposed via milk between days 1 and 4 postpartum already at dosages that did not provoke maternal toxicities. There were no effects on neurobehavioral parameters.

Excretion into breast milk was investigated in rat pups suckled by dams dosed with Tapentadol. Pups were dose-dependently exposed to Tapentadol and Tapentadol O-glucuronide. It was concluded that Tapentadol is excreted in milk.

6. Pharmaceutical particulars

6.1 List of excipients

Tablet core (all doses):

Hypromellose Microcrystalline cellulose Colloidal anhydrous silica Magnesium stearate

Tablet coat:

Hypromellose Lactose monohydrate Talc Macrogol Propylene glycol, Titanium dioxide Yellow iron oxide Red iron oxide, Black iron oxide

6.2 Incompatibilities

Not applicable

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

PVC/PVDC-aluminium/paper/PET blisters

Packs with 7, 10, 14, 20, 24, 28, 30, 40, 50, 54, 56, 60, 90, 100  tablets.

PVC/PVDC aluminium/paper/PET perforated unit-dose blisters

Packs with 10, 14, 20, 28, 30, 50, 56, 60, 90, 100  tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

7. Manufactured By:
   Taj Pharmaceuticals Ltd.
   at: Plot. No. 220, Mahagujarat
   Industrial Estate, At & Post-Moraiya,
   Tal-Sanand, Dist- Ahmedabad Gujarat (India)

Tapentadol 50mg Tablets

Tapentadol

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet (see section 4).

What is in this leaflet:

1. What Tapentadol  is and what it is used for
   2. What you need to know before you take  Tapentadol
   3. How to take  Tapentadol
   4. Possible side effects
   5. How to store  Tapentadol
   6. Contents of the pack and other information
2. What Tapentadol  is and what it is used for

The full name of your medicine is ‘ Tapentadol   50mg. It is referred to as ‘ Tapentadol  ’ in the rest of this leaflet.

Tapentadol – the active substance in  Tapentadol   – is a strong painkiller which belongs to the class of opioids.  Tapentadol   is used in adults for the treatment of severe long-term pain that can only be adequately managed with an opioid painkiller.

2. What you need to know before you take Tapentadol

Do not take  Tapentadol  

• if you are allergic to tapentadol or any of the other ingredients of this medicine (listed in section 6)
• if you have asthma or if your breathing is dangerously slow or shallow (respiratory depression, hypercapnia)
• if you have no bowel movement as shown by severe constipation and bloating which may be accompanied by pain or discomfort in the lower stomach
• if you have poisoning with alcohol, sleeping pills, pain relievers or medicines that affect mood and emotions (see ‘Other medicines and Tapentadol  ’)

Warnings and precautions

Talk to your doctor or pharmacist before taking  Tapentadol   if you:

• have slow or shallow breathing
• suffer from increased pressure in the brain or are not fully conscious
• have had a head injury or brain tumors
• suffer from liver or kidney problems (see ‘How to take Tapentadol  ’)
• suffer from a pancreatic disease including inflammation of the pancreas (pancreatitis) or disease of the bile duct (biliary tract disease)
• are taking medicines referred to as mixed opioid agonist/antagonists (e.g., pentazocine, nalbuphine) or partial mu-opioid agonists (e.g. buprenorphine)
• have a tendency towards epilepsy or fits or if you are taking other medicines known to increase the risk of seizures because the risk of a fit may increase.
• have a tendency to abuse medicines or if you are dependent on medicines, as Tapentadol ER may lead to addiction. In this case, you should only take these tablets for short periods of time and under strict medical supervision.

Other medicines and  Tapentadol  

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Your doctor will tell you which medicines are safe to take with  Tapentadol  .

• The risk of side effects increases if you are taking medicines which may cause convulsions (fits), such as certain antidepressants or antipsychotics. The risk of having a fit may increase if you take Tapentadol   at the same time. Your doctor will tell you whether  Tapentadol is suitable for you.
• Concomitant use of Tapentadol   and sedative medicines such as benzodiazepines or related drugs (certain sleeping pills or tranquillizers (e.g. barbiturates) or pain relievers such as opioids, morphine and codeine (also as cough medicine), antipsychotics, H1-antihistamines, alcohol) increases the risk of drowsiness, difficulties in breathing (respiratory depression), coma and may be life-threatening. Because of this, concomitant use should only be considered when other treatment options are not possible. However if your doctor does prescribe  Tapentadol   together with sedative medicines the dose and duration of concomitant treatment should be limited by your doctor. Please tell your doctor about all sedative medicines you are taking, and follow your doctor’s dose recommendation closely. It could be helpful to inform friends or relatives to be aware of the signs and symptoms stated above. Contact your doctor when experiencing such symptoms.
• If you are taking a type of medicine that affects serotonin levels (e.g. certain medicines to treat depression), speak to your doctor before taking Tapentadol   as there have been cases of “serotonin syndrome”. Serotonin syndrome is a rare, but life-threatening condition. The signs include involuntary, rhythmic contractions of muscles, including the muscles that control movement of the eye, agitation, excessive sweating, tremor, exaggeration of reflexes, increased muscle tension and body temperature above 38°C. Your doctor can advise you on this.
• Tapentadol   may not work as well if taken with opioid like medicines (e.g. those containing pentazocine, nalbuphine or buprenorphine). Tell your doctor if you are currently being treated with one of these medicines.
• Taking Tapentadol   with products (e.g. rifampicin, phenobarbital or St John’s Wort) that affect the enzymes required to remove  Tapentadol   from the body, may affect how well  Tapentadol   works or may cause side effects. The effects may occur especially when the other medication is started or stopped.
• Tapentadol   should not be taken together with monoamine oxidase inhibitors (MAOIs – certain medicines for the treatment of depression). Tell your doctor if you are taking MAO inhibitors or have taken these during the last 14 days.

Please keep your doctor informed about all medicines you are taking.

Taking  Tapentadol   with food, drink and alcohol

Do not drink alcohol whilst you are taking  Tapentadol  , because some side effects such as drowsiness may be increased. You can take  Tapentadol   with or without food.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Do not take  Tapentadol  :

• if you are pregnant, unless your doctor has instructed you to do so
• if you become pregnant during treatment with Tapentadol  . Check with your doctor.
• during childbirth, as it could lead to dangerously slow or shallow breathing (respiratory depression) in the newborn
• if you are breast-feeding, as it may pass into the breast milk.

Driving and using machines

If you feel drowsy, dizzy, have blurred vision or a slow reaction time whilst taking  Tapentadol  , then do not drive, use tools or machinery.

Any such effects are more likely to occur when you start taking  Tapentadol  , when the dose of  Tapentadol   is changed, or when you drink alcohol or take tranquilizers.

Please ask your doctor before driving a car or using machinery.

 Tapentadol   contains lactose.

Lactose is a type of sugar. If you have been told by your doctor that you have an intolerance to some sugars, talk to your doctor before taking this medicine.

3. How to take Tapentadol

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Your doctor will change the dose and time between doses of  Tapentadol   according to your pain level and your needs. Generally, the lowest pain-relieving dose should be taken.

Adults

The usual dose is 1 tablet every 12 hours.

Daily doses of  Tapentadol   greater than 500mg  tapentadol are not recommended.

Your doctor may prescribe a different, more appropriate dose or timing of dosing, if this is necessary for you. If you feel that the effect of these tablets is too strong or weak, talk to your doctor or pharmacist.

How and when should you take  Tapentadol  

Tapentadol   is for oral use.

Swallow the tablets with a glass of water. You may take the tablets either on an empty stomach or with food. Do not chew, break or crush the tablet, as it may result in overdose due to quick release of tapentadol in your body.

The empty shell of the tablet may not be digested completely and thus be seen in stool. This should not worry you, since the drug (active substance) of the tablet has already been absorbed in your body and what you see is just the empty shell.

How long should you take  Tapentadol  

Do not take the tablets for longer than your doctor has told you.

Elderly patients

In elderly patients (above 65 years) usually no dose adjustment is necessary. However, your doctor may adjust your dose or time between doses if required.

Patients with liver or kidney problems (insufficiency)

Do not take  Tapentadol   if you have severe liver or kidney problems.

If you have moderate liver problems, your doctor will adjust your dose or time between doses.

If you have mild liver problems or mild to moderate kidney problems, a dose adjustment is not required.

Children and adolescents

Tapentadol   is not recommended for children and adolescents below the age of 18 years.

If you take more  Tapentadol   than you should

Taking too much  Tapentadol   may be life-threatening.

Immediate medical advice should be sought in the event of an overdose, even if you feel well.

Very high doses of  Tapentadol   may cause the following:

• pin-point pupils in the eyes
• being sick (vomiting)
• drop in blood pressure
• fast heart beat
• altered consciousness, collapse or deep unconsciousness (coma)
• epileptic fits
• dangerously slow or shallow breathing or stopping breathing.

If you forget to take  Tapentadol  

If you forget to take the tablets, your pain is likely to return. Do not take a double dose to make up for a forgotten dose; simply continue taking the tablets as before.

If you stop taking  Tapentadol  

If you interrupt or stop treatment too soon, your pain is likely to return. If you wish to stop treatment, please tell your doctor first before stopping treatment.

Generally there will be no withdrawal effects when treatment is stopped. However, on uncommon occasions, people who have been taking the tablets for some time may feel unwell if they suddenly stop taking them.

Symptoms may be:

• feeling restless, irritable, anxious, weak or sick (nausea), loss of appetite, being sick (vomiting), diarrhoea
• watery eyes, runny nose, increase in size of the pupils in the eyes (dilated pupils)
• difficulty in sleeping, yawning
• sweating, shivering
• muscle or joint pain, backache, abdominal cramps
• increase in blood pressure, breathing or heart rate.

If you experience any of these complaints after stopping  Tapentadol  , please contact your doctor.

Do not stop taking this medicine unless your doctor tells you to. If your doctor wants you to stop taking your tablets, he/she will tell you how to do this. This may include a gradual reduction of the dose.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Important side effects or symptoms to look out for and what to do if you are affected:

• This medicine may cause allergic reactions including swelling beneath the skin, hives, and in severe cases difficulty breathing, a fall in blood pressure, collapse, or shock (uncommon). Symptoms may be wheeziness, difficulty breathing, swelling of the eyelids, face or lips, or rash or itching, which may cover your whole body.
• Another serious side effect is a condition where you breathe more slowly or weakly than expected (rare). It mostly occurs in elderly and weak patients.

If you are affected by these important side effects contact a doctor immediately.

Other side effects that may occur:

Very common (may affect more than 1 in 10 people)

• feeling sick (nausea)
• constipation
• dizziness, drowsiness, headache.

Common (may affect up to 1 in 10 people)

• decreased appetite, anxiety, being sick (vomiting), diarrhoea, indigestion
• sleep problem, tiredness or exhaustion (fatigue), feeling of weakness, trembling, muscle twitches, shortness of breath
• feeling depressed, nervousness, restlessness, lack of attention
• feeling hot (flushing), increased sweating, feeling of body temperature change, dry areas like nostrils, mouth, lips, eyelids, ears, genitals and anus
• itching, rash
• water retention (oedema).

Uncommon (may affect up to 1 in 100 people)

• weight loss
• low awareness of time, place or identity (disorientation), confusion, excitable (agitated), disturbances in perception, abnormal dreams, forgetfulness, mental impairment
• very happy (euphoria), less consciousness, fainting, sedation, feeling unsteady, difficulty in speaking, numbness
• abnormal sensations of the skin (e.g. tingling, prickling), skin reactions (hives)
• abnormal vision
• faster or slower heart beat, palpitations, low blood pressure
• stomach discomfort, delay in passing urine, passing urine more often than usual
• sexual dysfunction
• drug withdrawal effects (see ‘If you stop taking Tapentadol ’)
• feeling strange, irritable.

Rare (may affect up to 1 in 1,000 people)

• addiction
• thinking abnormal, epileptic fits, near fainting, uncoordinated, feeling drunk or relaxed
• delayed emptying of the stomach (impaired gastric emptying).

Unknown

• Delirium

In general, the likelihood of having suicidal thoughts and behaviour is increased in patients suffering from chronic pain. In addition, certain medicines for the treatment of depression (which have an impact on the neurotransmitter system in the brain) may increase this risk, especially at the beginning of treatment. Although tapentadol also affects neurotransmitters, data from human use of tapentadol do not provide evidence for an increased risk.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

5. How to store Tapentadol

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and the blister. The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What  Tapentadol   contains

The active ingredient is tapentadol.

Tapentadol   50mg  tablet contains 50mg  tapentadol (as hydrochloride).

The other ingredients are:

• Tablet core: hypromellose, microcrystalline cellulose, colloidal anhydrous silica, magnesium stearate.
• tablet coat: hypromellose, lactose monohydrate, talc, macrogol, propylene glycol, titanium dioxide.

What  Tapentadol   looks like and contents of the pack

•  Tapentadol   50mg  tablets

Tapentadol   are packed in blisters.

7. Manufactured By:
   Taj Pharmaceuticals Ltd.
   at: Plot. No. 220, Mahagujarat
   Industrial Estate, At & Post-Moraiya,
   Tal-Sanand, Dist- Ahmedabad Gujarat (India)