Nalbuphine Hydrochloride for injection 20mg/ml Taj Pharma

1 NAME OF THE MEDICINAL PRODUCT

Nalbuphine Hydrochloride 10mg/ml for injection Taj Pharma
Nalbuphine Hydrochloride 20mg/ml for injection Taj Pharma

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains
Nalbuphine hydrochloride 10mg
Excipients q.s

Each ml contains
Nalbuphine hydrochloride 20mg
Excipients q.s

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Solution for injection

4 CLINICAL PARTICULARS

Therapeutic Indications

Nalbuphine Hydrochloride 10mg/ml solution for injection is indicated for the short-term relief of moderate to severe pain. It can also be used for pre- and postoperative analgesia.

4.2 Posology and method of administration

Adults

The usual recommended dose for adults is 10 – 20mg for patients with 70 kg body weight, which is equivalent to 0.1 –

0.3mg/kg body weight. This dose may be administered intravenously, intramuscularly or subcutaneously and may be repeated after 3 to 6 hours, if necessary. The maximum single dose in adults must not exceed 20mg. The posology must be adapted to the intensity of pain and the physical status of the patient.

Children and adolescents

The usual recommended dose for children is 0,1 – 0,2mg/kg body weight. This dose may be administered intravenously, intramuscularly or subcutaneously. Intramuscular as well as subcutaneous administration might be painful and should be avoided in children.

The dose may be repeated after 3 to 6 hours, if necessary. The single maximum dose is fixed with 0,2mg nalbuphine hydrochloride per kilogram body weight.

There are no adequate data for the treatment of children younger than 1.5 years.

Elderly people

Due to increased bioavailability and decreased systemic clearance it is suggested to start with the lowest dose of nalbuphine hydrochloride.

Patients with hepatic / renal impairment

Patients with moderate and mild renal impairment may show an abnormal reaction upon standard dosages. Therefore, the product should be used with caution in these patients.

Nalbuphine hydrochloride is contraindicated in patients with hepatic disorders and severe renal impairment (see sections 4.3 and 4.4).

Nalbuphine Hydrochloride 10mg/ml solution for injection is not suitable for long term treatment. For further information see section 6.6.

4.3 Contraindications

hypersensitivity to the active substance or to any of the excipients listed in section 1
severe renal impairment
hepatic impairment
concomitant treatment with µ-agonistic opioids e.g. morphine and fentanyl (see section 5)

4.4 Special warnings and precautions for use

This medicinal product contains less than 1 mmol sodium (23mg) per dose, i.e. essentially `sodium-free´. Opioid dependence

Nalbuphine Hydrochloride 10mg/ml solution for injection may not be used as a subsitute for heroine, methadone or other opioids in dependent persons. In these cases the withdrawal symptoms may be considerably intensified.

Withdrawal symptoms, including increased pain, can occur in patients with chronic pain treated with other µ-agonistic opioids e.g. morphine and fentanyl.

Abuse of Nalbuphine Hydrochloride 10mg/ml solution for injection can lead to psychological and physical dependence. Special attention is required before treating emotionally unbalanced patients or patients with opioid-misuse in their medical history.

Head injury and increased intracranial pressure

It is possible that potent analgesics may increase intracranial pressure and so cause respiratory depression. In case of head injury, inner head injury or already existing increased intracranial pressure this effect might be intensified. In addition, potent analgesics can cause effects that may mask the course of the disease in patients with head injury. Therefore, Nalbuphine Hydrochloride 10mg/ml solution for injection must only be used if really necessary and with the utmost caution.

Renal and hepatic disorders

As Nalbuphine Hydrochloride 10mg/ml solution for injection is metabolised in the liver and eliminated renally, nalbuphine hydrochloride is contraindicated in patients with hepatic disorders and severe renal impairment (see section 4.3). Patients with moderate and mild renal impairment may show abnormal reactions upon standard dosages. Caution is required in these patients.

Obstetric use (see section 4.6)

Foetal and neonatal adverse effects reported following the administration of nalbuphine hydrochloride to the mother during labour include foetal bradycardia, respiratory depression at birth, apnoea, cyanosis, and hypotension. Some of these events have been life-threatening. Maternal administration of naloxone during labour has reversed these effects in some cases. Nalbuphine hydrochloride should only be used during labour and delivery if clearly indicated and if the potential benefit outweighs the risk to the infant. Newborns should be monitored for respiratory depression, apnoea, bradycardia and arrhythmias if Nalbuphine hydrochloride has been used.

Precautions

10mg Nalbuphine Hydrochloride 10mg/ml solution for injection causes respiratory depression comparable to that caused by 10mg morphine. Unlike morphine, there is a ceiling effect to the respiratory depressant effect of nalbuphine.

There is a ceiling for respiratory depression at a dose of approximately 30mg, and an analgetic ceiling at approximately 50mg administered during a short period. Patients with pain conditions who have a high opioid requirement should be offered an opioid with no analgetic ceiling.

Respiratory depression raised by Nalbuphine Hydrochloride 10mg/ml solution for injection may be treated with naloxone hydrochloride, if necessary. Nalbuphine Hydrochloride 10mg/ml solution for injection must be administered with great caution and in very small dosages to patients who suffer from impaired respiration (e.g. caused by other medical treatment, uremia, bronchial asthma, serious infections, cyanose or respiratory obstruction).

Nalbuphine hydrochloride should be used with caution in patients with heart insufficiency, paralytic ileus, biliary colic, epilepsy and hypothyroidism.

During administration, antagonist treatment should be available (naloxone).

4.5 Interaction with other medicinal products and other forms of interaction

Contra-indicated combinations

Pure morphine agonists (such as morphine, pethidine, dextromoramide, dihydrocodeine, dextropropoxyphene, methadone, levacethylmethadol):

Pure µ-agonists reduce analgesic effect due to competitive receptor blockage. Non recommended combinations:

Alcohol:

Alcohol potentiates the sedative effect of morphine-based analgesics.

Alcoholic beverages and medicinal products containing alcohol must be avoided.
Precautions

Other central nervous system suppressants, such as other morphine derivatives (analgesics and antitussives), sedative antidepressants, sedative H1 antihistamines, barbiturates, benzodiazepines, anxiolytics other than benzodiazepines, neuroleptics, clonidine and related substances:

These substances may cause an increased risk of respiratory depression, potentially life threatening in case of overdose.

There is no information available regarding the potential for pharmacokinetic interactions between nalbuphine and other medicinal products. Caution is recommended when nalbuphine is combined with potent enzyme inhibitors or medicinal products with a narrow therapeutic range.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are inadequate data regarding the use of nalbuphine hydrochloride in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk in humans is unknown. Pregnant women should only be treated with nalbuphine hydrochloride if the anticipated benefit to the mother exceeds the possible risk to the foetus.

As with all opioids, chronic use by the mother, particularly at the end of pregnancy may produce a withdrawal syndrome in the newborn, regardless of the dose.

As is the case with every opioid nalbuphine hydrochloride has not been studied in terms of efficacy and safety in premature labour or delivery.

When nalbuphine hydrochloride is administered to the mother directly before or during delivery, newborns should be monitored for respiratory depression, apnoea, bradycardia and arrhythmias (see section 4.4 and 4.8).

Lactation

Nalbuphine hydrochloride is excreted in breast-milk. Lactation should be discontinued for 24 hours after treatment with Nalbuphine Hydrochloride 10mg/ml solution for injection.

4.7 Effects on ability to drive and use machines

Nalbuphine Hydrochloride 10mg/ml solution for injection reduces the ability to respond and has therefore a major influence on the ability to drive and use machines. These activities have to be avoided until the effects of nalbuphine hydrochloride have subsided.

4.8 Undesirable effects

The following undesirable effects are ranked according to system organ class and to their frequency: 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)

Nervous system disorders:

Very common: Sedation

Common: Perspiration, Drowsiness, Vertigo, Dry mouth, Headache

Rare: Light numbness in the head, Nervousness, Tremor, Withdrawal symptoms, Paresthesia Very rare: Euphoria

Psychiatric disorders:

Common: Dysphoria

Very rare: Hallucination, Confusion, personality disorder trait

Respiratory, thoracic and mediastinal disorders: Rare: Respiratory difficulties

Cardiac disorders:

Very rare: Bradycardia, Tachycardia, Lung oedema.

Vascular disorders:

Very rare: Hypotension, Hypertension

Eye disorders:

Very rare: Watery eyes, Blurred vision

Immune system disorders:

Very rare: Allergic reaction

General disorders and administration site conditions: Very rare: Pain in the puncture, Flushing

Skin and subcutaneous tissue disorders: Very rare: Urticaria

Gastrointestinal disorders:
Common: Vomiting, Nausea

Pregnancy, puerperium and perinatal conditions:

Very rare: respiratory depression in newborn children, retarded circulation in newborn children.

Nalbuphine Hydrochloride 10mg/ml solution for injection can cause certain withdrawal symptoms if used in patients who exert opioids in an excessive way.

When Nalbuphine Hydrochloride 10mg/ml solution for injection is used during delivery it can raise respiratory depression and/or retarded circulation in newborn children with deleterious consequences. In these cases naloxone hydrochloride must be kept available as an antidote.

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.

Overdose

Administration of high doses of nalbuphine hydrochloride (intramuscular or intravenous) produces several symptoms of overdose – like respiratory depression, sedation, sleepiness, unconsciousness and light uncomfortableness.

Naloxone hydrochloride can be used as a specific antidote to nalbuphine hydrochloride. However, primary attention should be given to respiratory and cardiovascular function. Symptomatic and supportive therapy is mostly sufficient for slight and moderate overdosage. Oxygen, plasma volume expanders and other auxiliaries may be used, if necessary.

5 PHARMACOLOGICAL PROPERTIES

Pharmacodynamic properties

Pharmacotherapeutic group: Opioids, Morphinane derivatives

Nalbuphine hydrochloride is an opioid with kappa-agonistic and mu-antagonistic properties. Beside the essential agonistic (analgesic) effect nalbuphine hydrochloride has antagonistic effects of about a fourth of nalorfine and ten times of pentazocine.

Nalbuphine hydrochloride has minimal abuse potential and has no effect on the digestive and urinary smooth muscles. Nalbuphine hydrochloride minimally delays gastric emptying and intestinal transit. It does not induce difficulty in micturition.

5.2 Pharmacokinetic properties

In adults, the effect takes place 2 to 3 minutes after intravenous administration and less than 15 minutes after intramuscular or subcutaneous injection. The duration of action ranges from 3 to 6 hours. The half-life period is 2,93  0,795 hours.
In children of 1.5 years of age and above, the effect takes place 2 to 3 minutes after intravenous injection and 20 to 30 minutes after intramuscular or subcutaneous injection. The duration of action ranges from 3 to 4 hours. The protein binding of nalbuphine is moderate (about 50%).
Nalbuphine hydrochloride is metabolised in the liver.
There are seven metabolites that are already isolated. The most important metabolite is N- (hydroxyketocyclobutyl)-methylnornalbuphine, the other metabolites are isomers of the same and correspond to hydroxylated nalbuphine. All metabolites seem to have no particular
There is no information regarding enzymes catalysing the formation of these
Nalbuphine hydrochloride is excreted in the urine in terms of glucuronide metabolites.
No studies have been performed in patients with renal impairment or hepatic impairment.

5.3 Preclinical safety data

Reproductive toxicity studies with parenterally administered nalbuphine were performed in rats and rabbits. In a pre- and postnatal study in rats, an increase in pre- and postnatal mortality and a decrease in offspring weight were observed at high doses.

Nalbuphine hydrochloride exerted no effects on fertility in male and female rats. No teratogenic effect was observed in rats and rabbits.

6 PHARMACEUTICAL PARTICULARS

List of excipients

Citric acid, anhydrous Sodium citrate Sodium chloride

Hydrochloric acid (for pH adjustment) Water for injections

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

3 years.

The product has to be used immediately after opening.

6.4 Special precautions for storage

Do not store above 25°C.

Keep the ampoules in the outer carton in order to protect from light.

6.5 Nature and contents of container

Colourless glass, Type I.

Ampoules of 2 ml, in packages of 10 ampoules.

6.6 Special precautions for disposal and other handling

For single use only.

Only clear solutions practically free from particles should be used. The solution must be visually inspected prior to use. Any unused solution should be disposed of in accordance with local requirements.

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

Nalbuphine Hydrochloride 10 mg/ml, 20mg/ml for injection Taj Pharma

PACKAGE LEAFLET: INFORMATION FOR THE USER

Nalbuphine Hydrochloride 10 mg/ml, 20mg/ml solution for injection

nalbuphine hydrochloride

Read all of this leaflet carefully before you start using this medicine.

Keep this leaflet. You may need to read it
If you have any further questions, ask your doctor or
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or

In this leaflet:

What Nalbuphine Hydrochloride 10 mg/ml solution for injection is and what it is used for
Before you use Nalbuphine Hydrochloride 10 mg/ml solution for injection
How to use Nalbuphine Hydrochloride 10 mg/ml solution for injection
Possible side effects
How to store Nalbuphine Hydrochloride 10 mg/ml solution for injection
Further Information

WHAT Nalbuphine Hydrochloride 10 MG/ML SOLUTION FOR INJECTION IS AND WHAT IT IS USED FOR

Nalbuphine Hydrochloride 10 mg/ml solution for injection is a medicinal product that belongs to a group of pain killers (analgesics) with opioid properties.

It is used for short-term treatment of moderate to severe pain. It can also be used before or after an operation.

2. BEFORE YOU USE Nalbuphine Hydrochloride 10 MG/ML SOLUTION FOR INJECTION
Do not use Nalbuphine Hydrochloride 10 mg/ml solution for injection

if you are allergic (hypersensitive) to nalbuphine hydrochloride or any of the other ingredients of Nalbuphine Hydrochloride 10 mg/ml solution for injection (see section 6)
if you have severe renal impairment
if you have hepatic impairment
if you use other opioids

Take special care with Nalbuphine Hydrochloride 10 mg/ml solution for injection

if you suffer from head injury, inner head injury or already existing increased intracranial pressure, Nalbuphine Hydrochloride 10 mg/ml solution for injection might intensify this. It is also possible that the use of Nalbuphine Hydrochloride 10 mg/ml solution for injection in patients with head injury can disguise symptoms. if you suffer from a deranged kidney function, the dosage of Nalbuphine Hydrochloride 10 mg/ml solution for injection must then be reduced.
if Nalbuphine Hydrochloride 10 mg/ml solution for injection is administered to the mother during labour and delivery. Newborns should be monitored for respiratory depression and arrhythmias if Nalbuphine Hydrochloride 10 mg/ml solution for injection has been used.if you suffer from impaired breathing or if you get difficulties with your breathing during the treatment, your doctor may have to monitor you
if you suffer with heart failure, paralysed gut, gallbladder pains, epilepsy or reduced function of the
Abuse of Nalbuphine Hydrochloride 10 mg/ml solution for injection can lead to psychical and physical addiction and
if you are addicted on heroine, methadone or other opioid substances. Nalbuphine Hydrochloride 10 mg/ml solution for injection cannot be used as a replacement. In these cases the acute withdrawal symptoms can be considerably

Ask your doctor, if one of the above mentioned warnings applies to you or has applied to you in the past.

Using other medicines

Other medicines can have an influence on the effect of Nalbuphine Hydrochloride 10 mg/ml solution for injection.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription, herbal medicines or natural products.

Combination with specific narcotics (opioids) is not indicated. The painkilling effect might be
Alcohol and medicinal products containing alcohol must be
The use of Nalbuphine Hydrochloride 10 mg/ml solution for injection in combination with other medicines that diminish fear and anxiety (anxiolytics) or the concurrent use of Nalbuphine Hydrochloride 10 mg/ml solution for injection with narcotic analgesics (pain killers), phenothiazines (medicines used for schizophrenia) or other sedative, sleep enhancing or similar medication that affect the central nervous system can show worsening of the side effects. Your doctor must adapt the dosage of Nalbuphine Hydrochloride 10 mg/ml solution for injection or the other medicinal

Pregnancy and breast-feeding

There are insufficient data on the possible harmful effects in humans with the use of Nalbuphine Hydrochloride 10 mg/ml solution for injection in pregnancy. If Nalbuphine Hydrochloride 10 mg/ml solution for injection is administered to the mother during labour and delivery, newsborns should be monitored for respiratory depression and arrhythmias (see section 4 possible side effects).

Nalbuphine Hydrochloride 10 mg/ml solution for injection is excreted in the breast-milk. Lactation should be discontinued for 24 hours during treatment with Nalbuphine Hydrochloride 10 mg/ml solution for injection.

Ask your doctor or nurse for advice before taking any medicine.

Driving and using machines

Nalbuphine Hydrochloride 10 mg/ml solution for injection reduces your ability to react quickly. You should therefore avoid driving and using machines while you are treated with Nalbuphine Hydrochloride 10 mg/ml solution for injection. Other side effects that may occur are listed in section 4.

Important information about some of the ingredients of Nalbuphine Hydrochloride 10 mg/ml solution for injection

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially `salt-free´.

3. HOW TO USE Nalbuphine Hydrochloride 10 MG/ML SOLUTION FOR INJECTION

Nalbuphine Hydrochloride 10 mg/ml solution for injection is only used by the physician or nurse.

Posology

Adults

The common used dose for adults is 10 to 20 mg for persons with 70 kg body weight: intravenous, intramuscular or subcutaneous administration. This dose can be repeated after 3 to 6 hours, if necessary. The dosage must be adapted according to the intensity of the pain and the condition of the patient.

Children and adolescents

The usual dosage for children is 0,1 to 0,2 mg/kg body weight: intravenous, intramuscular or subcutaneous administration. This dose can be repeated after 3 to 6 hours, if necessary. The single maximum dose is defined with 0,2 mg Nalbuphine Hydrochloride hydrochloride per kilogram body weight.

Duration of treatment

The duration of treatment is specified by your doctor.

If you notice that the effect of Nalbuphine Hydrochloride 10 mg/ml solution for injection is too strong or even too weak, please ask your doctor or nurse for advice.

If you get more Nalbuphine Hydrochloride 10 mg/ml solution for injection than you should

The usage of a high dosage of Nalbuphine Hydrochloride 10 mg/ml solution for injection can cause symptoms such as respiratory depression, drowsiness or unconsciousness.

As this medicine will be given to you whilst you are in hospital, it is unlikely that you will be given too much.

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

4. POSSIBLE SIDE EFFECTS

Like all medicines, Nalbuphine Hydrochloride 10 mg/ml solution for injection can cause side effects, although not everybody gets them.

The possible side effects are ranked according to their frequency: very common (more than 1 out of 10 persons)

common (more than 1 out of 100 persons and less than 1 out of 10 persons) uncommon (more than 1 out of 1,000 persons and less than 1 out of 100 persons) rare (more than 1 out of 10,000 persons and less than 1 out of 1,000 persons) very rare (less than 1 out of 10,000 persons)

The following side effects may appear:

Very common: Sedation

Common: Sweating, sleepiness, dizziness, Dry mouth, Headache, Vomiting, sickness, decreased feeling of happiness

Rare: Light numbness in the head, nervousness, shiver, Withdrawal symptoms, disturbed feeling of the skin, Respiratory difficulties

Very rare: illusions, n, personality disorder trait, slow heartbeat, rapid heartbeat, fluid retention in the Lung, increased feeling of happiness, low blood pressure, high blood pressure, Watery eyes, Blurred vision, Allergic reaction, Pain in the puncture, reddened skin, nettle-rash, respiratory depression in newborn children, retarded circulation in newborn children

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

5. HOW TO STORE Nalbuphine Hydrochloride 10 MG/ML SOLUTION FOR INJECTION

Keep out of the reach and sight of children.

Do not use Nalbuphine Hydrochloride 10 mg/ml solution for injection after the expiry date which is stated on the ampoule and carton.The expiry date refers to the last day of that month.

Do not store above 25°C.

Keep the ampoules in the outer carton, in order to protect from light. The product has to be used immediately after first opening.

This medicinal product is for single use only. Discard any unused solution.

Do not use Nalpain 10 mg/ml if you notice discolouration, cloudiness or particles in the solution.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose medicines no longer required. These measures will help to protect the environment.

6. FURTHER INFORMATION

What Nalbuphine Hydrochloride 10 mg/ml solution for injection contains

The active substance is nalbuphine

1 ml of solution contains 10 mg nalbuphine hydrochloride.

1 ampoule of 2 ml contains 20 mg nalbuphine hydrochloride.

The other ingredients are citric acid, anhydrous sodium citrate

sodium chloride hydrochloric acid (for pH adjustment) water for injection

What Nalbuphine Hydrochloride 10 mg/ml solution for injection looks like and contents of the pack

One ampoule contains 2 ml of a clear and colourless solution for injection. Nalbuphine Hydrochloride 10 mg/ml solution for injection is available in packs with 10 ampoules.

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