Pentazocine Tablets USP 25mg Taj Pharma

1.NAME OF THE MEDICINAL PRODUCT
Pentazocine Tablets USP 25mg Taj Pharma.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains
Pentazocine Hydrochloride USP                 25mg
Excipients                                                       q.s.
Lactose monohydrate                                200mg
For the full list of excipients, see section 6.1

3. PHARMACEUTICAL FORM
White uncoated tablets.
White, circular, biconvex uncoated tablets

4. CLINICAL PARTICULARS

4.1 Therapeutic indications
1. For the treatment of constipation.
2. For the treatment of hepatic encephalopathy (HE); hepatic coma.

4.2 Posology and method of administration
Posology

Adults

The usual initial dosage is 50mg every four hours after meals, but dosage is best tailored to the individual patient and to the degree of pain within the range 25-100mg every three to four hours.

Elderly

Since impaired renal of hepatic function is often associated with ageing, elderly patients may require smaller doses of pentazocine.

Paediatric population

Children 6-12 years: 25mg every three to four hours as required.

Children under 6 years: Not recommended.

Method of administration

For oral us

4.3 Contraindications
– Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

– Pentazocine should not be administered to patients with established respiratory depression, especially in the presence of cyanosis and excessive bronchial secretion

– Acute alcoholism

– Acute bronchial asthma

– Heart failure secondary to chronic lung disease

– Porphyria

– Raised intracranial pressure, head injuries or pathological brain conditions where clouding of the sensorium is undesirable..

4.4 Special Warnings and precautions for use
Pentozocine can both depress as well as elevate blood pressure possibly through the release of endogenous catecholamines.

Particular caution should be observed in patients with phaeochromocytoma, in the acute phase following myocardial infarction when it may increase pulmonary and systemic arterial pressure and vascular resistance, and in other clinical situations where alterations of vascular resistance and blood pressure might be particularly undesirable.

Caution should be exercised when administering high doses of pentazocine to patients who have suffered a recent myocardial infarction due to increases in heart rate and blood pressure.

Pentazocine should be given with caution to patients with severely impaired renal or hepatic function and in elderly patients, who may additionally be especially sensitive to the effects of opioids, as both conditions may lead to an increase in bioavailability of pentazocine and call for a reduction in dosage.

Administer with caution to patients previously on large doses of narcotics.

Cautions should be observed in patients who are prone to seizures.

Patients taking other opioids should be treated cautiously and pentazocine should not be used on patients already dependent on other opioids since the weak opioid antagonistic effects of pentazocine may provoke withdrawal symptoms.

Caution should also be observed in patients with hypothyroidism, adrenocortical insufficiency, prostatic hypertrophy, inflammatory or obstructive bowel disorders , cholecystitis, pancreatitis or other unidentified abdominal pain.

When pentazocine is prescribed for chronic use, the physician should take precautions to avoid any unnecessary increase in dose by the patient since prolonged use of high doses of pentazocine may produce a dependence.

Patients with a history of drug abuse should be closely supervised when receiving pentazocine.

Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs:

Concomitant use of Pentazocine and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Pentazocine concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of 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).

Some opioids can cause CNS excitation or depression. Pentazocine, like most other strong analgesics, should not be used in patients who are receiving monoamine oxidase inhibitors or who have received them within the past 14 days. (see section 4.5) Opioids can be taken after two weeks of MAOI’s discontinuation

After long term treatment (> 3 months) of analgesics with use every second day or more frequently, headache may develop or aggravate. Headache caused by overuse of analgesics (MOH – medication-overuse headache) should not be treated by increasing the dose. In such cases the use of analgesics should be discontinued in consultation with a doctor.

DEPENDENCE LIABILITY

There have been rare reports of mild withdrawal symptoms in the new-born after prolonged maternal use of pentazocine during pregnancy. This abstinence syndrome of pentazocine is not typical of opiate dependence. Symptoms include mild abdominal cramps, nausea, vomiting, nervousness or restlessness, dizziness, fever and chills, but are mild compared with opiate withdrawal symptoms. Withdrawal of pentazocine from such patients has caused few problems only occasionally requiring treatment with tranquillisers. It should be emphasised that the majority of patients reported to have become dependant on pentazocine had previously been dependant on opiates or had misused other drugs.

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction
Monoamine oxidase inhibitors may enhance the opioid effects of pentazocine and the agents may interact through their respective effects on catecholamine breakdown and release.

Pentazocine, should not be used in patients who are receiving monoamine oxidase inhibitors or who have received them within the past 14 days (see section 4.4).

Agents with sedative action, including phenothiazines tricyclic antidepressants and ethyl alcohol can enhance the central depressant effects of pentazocine which are opposed by respiratory stimulants such as doxapram.

Tobacco smoking appears to enhance the metabolic clearance rate of

Pentazocine reducing the clinical effectiveness of a standard dose of pentazocine.

Pentazocine can antagonise the effects of stronger opioid agonists such as diamorphine (heroin) and morphine, and may provoke withdrawal symptoms if given to narcotic addicts and is itself antagonised by naloxone.

Sedative medicines such as benzodiazepines or related drugs:

The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dose and duration of concomitant use should be limited (see section 4.4).

4.6 Fertility, Pregnancy and lactation
Pregnancy
There is no epidemiological evidence for the safety of pentazocine in human pregnancy but it has been widely used for many years without apparent ill consequences. Doses which produce maternal toxicity in rats have caused harmful effects in the foetus.

Pentazocine can rapidly cross the placental barrier and enter the foetal circulation and has the potential to cause opioid effects including central depression and abstinence syndrome in the foetus and newborn infant. It does not appear to have significant adverse effects on uterine function at parturition. Nonetheless, careful consideration should be given to the use of pentazocine during pregnancy, particularly during the first trimester, or at term. Special attention should be paid to clinical monitoring of the newborn, particularly premature infants, if pentazocine has been used during labour.

Breast-feeding
Pentazocine is excreted in very small amounts in breast milk. Caution should therefore be observed in administering pentazocine to breast- feeding mothers, particularly of infants at risk.

It is recommended that infants of nursing mothers who are receiving high doses of pentazocine, should be appropriately monitored.

4.7 Effects on ability to drive and use machines
As pentazocine may produce sedation, dizziness and occasionally euphoria, patients should be warned against the performance of potentially hazardous tasks such as driving a car or operating machinery; alcohol may potentiate the sedative effect.

This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:

The medicine is likely to affect your ability to drive
Do not drive until you know how the medicine affects you
It is an offence to drive while under the influence of this medicine
However, you would not be committing an offence (called ‘statutory defence’) if:

– The medicine has been prescribed to treat a medical or dental problem and

– You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and

– It was not affecting your ability to drive safely

4.8 Undesirable Effects
In chronic usage, care should be exercised to avoid any unnecessary increase in dosage since prolonged use of high dosage of pentazocine may produce dependence.

At normal therapeutic dosed, side effects are generally of a minor nature. Sedation and drowsiness, the most common effect, is less than that associated with morphine.

The most frequent side effects are light-headedness, dizziness, sedation, nausea, vomiting, and sweating.

The following side effects have also been reported.

Cardiovascular disorders: transient hypertension, tachycardia, bradycardia, hypotension, circulatory depression, palpitations.

Nervous system disorders: hallucinations may occur occasionally, dysphoria, disturbances of vision, headache, disorientation, mood changes, nightmares, insomnia, paraesthesia, syncope, euphoria, grand mal convulsions, raised intracranial pressure, confusion, muscle tremor thought disturbances.

Immune system disorders: oedema of the face, flushed skin including facial plethora, skin rashes, urticaria, dermatitis including pruritus, chills and allergic reactions.

Gastrointestinal disorders: constipation, dry mouth, ureteric or biliary spasm, abdominal pain

Blood and lymphatic system disorders: depression of the white blood cell count, especially granulocyctes, which is usually reversible, moderate transient eosinophillia.

Eye disorders: miosis, disturbances of vision.

Respiratory, thoracic and mediastinal disorders: respiratory depression.

Skin and subcutaneous system disorders: toxic epidermal necrolysis.

Renal and urinary disorders: urinary retention, ureteric tract spasm.

Pregnancy, puerperium and perinatal conditions: alterations in rate or strength of uterine contractions during labour.

Reproductive system and breast disorders: decreased libido or potency.

General disorders and administration site conditions: hypothermia.

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
The symptoms of pentazocine overdose will resemble those of morphine and other opioids. They may therefore include somnolence, respiratory depression hypotension, hypertension, tachycardia, hallucinations, or seizures. Circulatory failure and deepening coma may occur in more severe cases, as may convulsions, particularly in patients who have also ingested other CNS depressants such as alcohol, sedatives/hypnotics or antihistamines. Adequate measures to maintain ventilation and general circulatory support should be employed.

Gastric lavage and gastric aspiration should be considered where appropriate.

For respiratory depression due to overdosage or unusual sensitivity to pentazocine, parenteral naloxone is a specific and effective antagonist. Initial dose of 0.4 to 0.2mg of naloxone are recommended, repeated at 2-3 minute intervals if needed, up to a total of 10mg. Anti-convulsant therapy may be necessary

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Benzomorphan derivatives

Pentozocine is an opioid analgesic with actions and uses similar to those of morphine. It also has antagonist activity. It is used for the relief of moderate to severe pain. Its analgesic effect declines more rapidly than that of morphine.

5.2 Pharmacokinetic properties
Absorption
Pentazocine is absorbed from the gastro-intestinal tract.

Distribution
Following administration by mouth, peak plasma concentrations are reached in 1 to 3 hours and the half-life is reported to be 2 to 3 hours. After intramuscular injection, peak plasma concentrations are reached in 15 minutes to 1 hour.

Pentazocine diffuses across the placenta.

Biotransformation
Pentazocine is metabolised in the liver.

Elimination
Only a small proportion of the dose administered appears unchanged in the urine.

5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients
Also contains: crospovidone, lactose, magnesium stearate, polyvidone, microcrystalline cellulose (E460).

6.2 Incompatibilities
None known.

6.3 Shelf life
Three years from the date of manufacture.

6.4 Special precautions for storage
Store below 25°C in a dry place.

6.5 Nature and contents of container
The product containers are rigid injection moulded polypropylene or injection blow-moulded polyethylene tablet containers with polyfoam wad or polyethylene ullage filler and snap-on polyethylene lids; in case any supply difficulties should arise the alternative is amber glass bottles with screw caps and polyfoam wad or cotton wool. An alternative closure for polyethylene containers is a polypropylene, twist on, push down and twist off child-resistant, tamper-evident lid.

The product may also be supplied in blister packs in cartons:
a) Carton: Printed carton manufactured from white folding box board.
b) Blister pack: (i) 250µm white rigid PVC. (ii) Surface printed 20µm hard temper aluminium foil with 5-7g/M²PVC and PVdC compatible heat seal lacquer on the reverse side.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling
Not applicable.

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Package leaflet: Information for the patient

Pentazocine Tablets USP 25mg Taj Pharma

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 any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

What is in this leaflet
1. What Pentazocine tablets is and what it is used for
2. Before you are given Pentazocine tablets
3. How you will be given Pentazocine tablets
4. Possible side effects
5. How Pentazocine tablets is stored
6. Further Information

1. What Pentazocine tablets is and what it is used for
Pentazocine tablets belong to a group of medicines called analgesics and are used for the relief of moderate to severe pain.

2. Before you are given Pentazocine tablets
Do not take Pentazocine tablets if:
• you are allergic (hypersensitive) to Pentazocine, analgesics or to any of the other ingredients of this medicine (listed in section 6)
• you suffer from heart problems due to lung disease
• you suffer from any brain conditions (including raised pressure in the skull) or head injury
• you suffer from asthma, lung disease or have breathing difficulties, especially if you have blue discoloration of the skin (cyanosis) or cough up a lot of phlegm
• you suffer from alcoholism or are a heavy drinker
• you have porphyria (a group of rare inherited or acquired disorders where there is a problem with the production of haem (used to make haemoglobin in red blood cells) within the body)

Warnings and precautions
• taking a pain reliever regularly for a long time may lead to a dependence (addiction)
• taking a pain reliever too often or for too long can make headaches develop or worsen. Headaches caused by overuse of medicine should not be treated by increasing the dose.

Talk to your doctor before taking Pentazocine tablets:
• if you suffer from phaeochromocytoma (untreated tumour of the adrenal gland)
• if you have suffered a recent heart attack due to increases in heart rate and blood pressure
• if you suffer from severe kidney or liver problems
• if you are elderly, as you may be especially sensitive to the effects of Pentazocine
• if you have ever suffered from drug dependency or abuse
• if you have a history of or suffer from fits or seizures
• if you take other analgesic medicines (See “Other medicines and Pentazocine”)
• if you have an underactive thyroid gland (hypothyroidism)
• if you have a condition in which the adrenal glands do not produce adequate amounts of steroid hormones (adrenocortical insufficiency)
• if you suffer from inflammation (swelling) of the prostate (prostatic hypertrophy)
• if you suffer from inflammatory or obstructive bowel disorders
• if you suffer from swelling (inflammation) of the gallbladder (cholecystitis)
• if you suffer from inflammation of the pancreas (pancreatitis)
• if you suffer from unexplained stomach pain
• if you are taking medicines used to treat major depressive episodes, known as Monoamine Oxidase Inhibitors (MAOIs) (See “Other medicines and Pentazocine”). Treatment with Pentazocine should only be started 2 weeks after discontinuing treatment with an MAOI

Other medicines and Pentazocine tablets
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription. This includes herbal medicines.

Medicines which may interact with or be affected by Pentazocine:
• Antidepressant medicines known as Monoamine Oxidase Inhibitors (MAOI) in the past 2 weeks
– Medicines which make you sleepy including: Phenothiazines such as trifluoperazine, used to treat anxiety, mental disorders, feeling and/or being sick (nausea, vomiting)
– Tricyclic antidepressants, used to treat depression such as amitriptyline
– Medicines used to improve breathing ability such as doxapram (respiratory stimulants)
• Tobacco smoking may decrease the effectiveness of Pentazocine
• Strong pain relievers such as diamorphine (heroin), morphine and naloxone
• Concomitant use of Pentazocine and sedative medicines such as benzodiazepines or related drugs increases the risk of drowsiness, difficulties in breathing (respiratory depression), coma and may be lifethreatening. Because of this, concomitant use should only be considered when other treatment options are not possible. However if your doctor does prescribe Pentazocine 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.

Taking Pentazocine tablets with food and drink and alcohol
• These tablets should be taken after meals.
• Do not drink alcohol while you are taking these tablets. If you drink alcohol whilst taking this medicine the sedative effect may be enhanced.

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 for advice before taking this medicine.

Pregnancy
• Careful consideration should be given to the use of Pentazocine during pregnancy particularly during the first trimester (first 3 months) or at full term (end of pregnancy).
• Regular use during pregnancy may cause withdrawal symptoms in the newborn. Symptoms may include stomach cramps, feeling sick, being sick, restlessness, dizziness, fever and chills.
• Clinical monitoring of the newborn, particularly premature infants, is necessary if Pentazocine has been used during labour.

Breast-feeding
• Pentazocine is passed into breast milk, but in very small amounts. It is advisable to avoid taking Pentazocine whilst breastfeeding.

Driving and using machines
Pentazocine tablets may cause sedation, dizziness and occasionally euphoria. Make sure you are not affected before you drive or operate machinery. The medicine can affect your ability to drive as it may make you sleepy or dizzy.

Do not drive while taking this medicine until you know how it affects you.
• It is an offence to drive if this medicine affects your ability to drive.
• However, you would not be committing an offence if:
– The medicine has been prescribed to treat a medical or dental problem and
– You have taken it according to the instructions given by the prescriber or in the information provided with the medicine and
– It was not affecting your ability to drive safely

Talk to your doctor or pharmacist if you are not sure whether it is safe for you to drive while taking this medicine.

Pentazocine tablets contain lactose
If you have been told you have an intolerance to some sugars, contact your doctor before taking this medicine.

3. How you will be given Pentazocine tablets
Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

Swallow the tablets with water, after meals.

The recommended dose is:
• Adults: the usual starting dose is 2 tablets every four hours. Dosage should be within the range of 25-100mg every three to four hours.
• Children 6-12 years: 25mg every 3 to 4 hours as required.
• Children under 6 years: not recommended.
• Elderly: your doctor may give you a lower dose.
• Patients with liver or kidney problems: your doctor may reduce your dose.

If you take more Pentazocine tablets than you should
If you accidentally take too many tablets, contact your doctor or nearest hospital emergency department immediately for advice. Remember to take this leaflet or any remaining tablets with you.

Symptoms of overdose include: sleepiness or drowsiness (somnolence), slower or weaker breathing (respiratory depression), low/high blood pressure (hypotension/hypertension), faster heartbeat (tachycardia), seeing or hearing things that are not real (hallucinations), or fits (seizures, convulsions). Poor circulation and unconsciousness or coma may occur in more severe cases.

If you forget to take Pentazocine tablets
Do not take a double dose to make up for a forgotten dose. If you forget to take a dose take it as soon as you remember it and then take the next dose at the right time.

If you stop taking the Pentazocine tablets
• It is important that you keep taking Pentazocine for as long as your doctor has told you to.
• If you stop taking the tablets you may develop the following withdrawal symptoms: mild stomach cramps, feeling sick (nausea) or being sick (vomiting), nervousness or restlessness, dizziness, fever and chills.
• Long-term use of Pentazocine, particularly in high doses, can lead to dependence.

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

4. Possible Side Effects
Like all medicines, Pentazocine tablets can cause side effects, although not everybody gets them.

Seek medical advice immediately if you develop the following symptoms:
• Allergic reactions (swelling of the face, throat or tongue, difficulty breathing or dizziness)
• Frequent wheezing, breathlessness, abdominal pain, diarrhoea, fever, cough and rashes due to an increase in certain white blood cells (eosinophillia)
• Severe blistering of the skin, mouth, eyes and genitals (toxic epidermal necrolysis) Side effects (most frequent)
• Feeling sick (nausea) or being sick (vomiting)
• Feeling tired or drowsy
• Light-headedness
• Dizziness
• Sweating

Other side effects (frequency not known)
• High blood pressure (hypertension) or low blood pressure (hypotension)
• Slow heartbeat (bradycardia) or fast heartbeat (tachycardia)
• Feeling your heartbeat (palpitations)
• Poor circulation
• Seeing or hearing things that are not real (hallucinations). May occur occasionally
• Feeling depressed or discontented (dysphoria)
• Visual disturbances
• Headache
• Feeling disorientated
• Mood changes
• Nightmares
• Difficulty sleeping (insomnia)
•Tingling or numbness in the hands or feet (paraesthesia)
• Fainting (syncope)
• Intense feeling of well-being or elation (euphoria)
• Fits (seizures)
• Increased pressure in the skull
• Confusion
• Thought disturbances
• Reddening of the face (flushing)
• Skin rashes
• Skin rashes with the formation of wheals (urticaria)
• Skin rash or inflammation (dermatitis)
• Severe itching (pruritus)
• Constipation
• Dry mouth
• Pain in lower back or stomach (may be caused by a spasm of the ureter or bile duct)
• Depression of the white blood cell count, which is usually reversible
• Extremely small pupils of the eyes (miosis)
• Breathing more slowly or weakly than usual (respiratory depression)
• Muscle tremor
• Chills
• Low body temperature (hypothermia)
• Difficulty passing urine
• Changes in the rate or strength of uterine contractions during labour
• Lack of sexual desire (decreased libido)

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

5. How Pentazocine tablets is stored
Keep out of the sight and reach of children.
Store below 25°C in a dry place.
Do not use Pentazocine tablets after the expiry date stated on the label/carton/bottle.
The expiry date refers to the last day of that month. 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 to protect the environment

6. Further information

What Pentazocine tablets contains
• The active substance (the ingredient that makes the tablets work) is pentazocine hydrochloride.
Each tablet contains
Pentazocine Hydrochloride USP                 25mg
Excipients                                                       q.s.
Lactose monohydrate                                200.00mg

The other ingredients are lactose, magnesium stearate, polyvidone, microcrystalline cellulose (E460), crospovidone.

What Pentazocine tablets looks like and contents of the pack
Pentazocine tablets are white, circular, biconvex uncoated tablets.
Pack sizes are 28 tablets.