Nalorex

1. Name Of The Medicinal Product

NALOREX 50mg Film-Coated Tablets

2. Qualitative And Quantitative Composition

Naltrexone hydrochloride 50 mg per tablet.

3. Pharmaceutical Form

Pale yellow, film coated, capsule-shaped tablet debossed on one side with 'R11' and scored and debossed with '50' on the other side.

4. Clinical Particulars

4.1 Therapeutic Indications

Nalorex is indicated as an adjunctive prophylactic therapy in the maintenance of detoxified, formerly opioid-dependent patients.

4.2 Posology And Method Of Administration

Route of administration - oral.

Nalorex treatment should be initiated in a drug addiction centre and supervised by suitably qualified physicians.

The initial dose of Nalorex should be 25 mg (half a tablet) followed by 50 mg (one tablet) daily.

A three-times-a-week dosing schedule may be considered if it is likely to result in better compliance e.g. 100 mg on Monday, 100 mg on Wednesday and 150 mg on Friday.

Treatment with Nalorex should be considered only in patients who have remained opioid-free for a minimum of 7-10 days.

Narcan® (Naloxone hydrochloride) challenge is recommended to minimise the chance of a prolonged withdrawal syndrome precipitated by Nalorex (see also Warnings).

As Nalorex is an adjunctive therapy and full recovery from opioid dependence is variable, no standard duration of treatment can be recommended; an initial period of three months should be considered. However, prolonged administration may be necessary.

Use in Children

Safe use in children has not been established.

Use in Elderly

There is no experience of use in the elderly.

4.3 Contraindications

Nalorex should not be given to patients with acute hepatitis or liver failure.

Nalorex should not be given to patients currently dependent on opioids since an acute withdrawal syndrome may ensue.

Nalorex should not be used in conjunction with an opioid-containing medication.

Nalorex should not be given to patients who are hypersensitive to it.

4.4 Special Warnings And Precautions For Use

It is not uncommon for opioid abusing individuals to have impaired liver function.

Liver function test abnormalities have been reported in obese and elderly patients taking naltrexone who have no history of drug abuse. Liver function tests should be carried out both before and during treatment.

Since NALOREX is extensively metabolised by the liver and excreted predominantly in the urine, caution should be observed in administering the drug to patients with impaired hepatic or renal function. Liver function tests should be carried out both before and during treatment.

A withdrawal syndrome may be precipitated by NALOREX in opioid dependent patients; signs and symptoms may develop within 5 minutes and last up to 48 hours. Treatment should be symptomatic and may include opioid administration.

Narcan (Naloxone Hydrochloride) challenge is recommended to screen for presence of opioid use; a withdrawal syndrome precipitated by Narcan will be of shorter duration than one precipitated by Nalorex.

The recommended procedure is as follows:

-	i.v. injection of 0.2 mg Narcan
-	if after 30 seconds no adverse reactions occur, a further i.v. injection of 0.6 mg Narcan may be administered
-	continue to observe the patient for withdrawal effects for a further 30 minutes.

If doubt exists that the patient is opioid-free, the challenge may be repeated with a Narcan dose of 1.6 mg.

If there is no evidence of a reaction, Nalorex administration may be initiated with 25 mg by mouth (half a tablet).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Concomitant administration of Nalorex with an opioid-containing medication should be avoided. Patients should be warned that attempts to overcome the blockade may result in acute opioid intoxication which may be life threatening. In an emergency requiring opioid analgesia an increased dose of opioid may be required to control pain. The patient should be closely monitored for evidence of respiratory depression or other adverse symptoms and signs.

4.6 Pregnancy And Lactation

Animal studies do not suggest a teratogenic effect. Because of absence of documented clinical experience Nalorex should only be given to pregnant or breast-feeding women when, in the judgement of the attending physician, the potential benefits outweigh the possible risks.

4.7 Effects On Ability To Drive And Use Machines

Nalorex may impair the mental and/or physical abilities required for performance of potentially hazardous tasks such as driving a car or operating machinery.

4.8 Undesirable Effects

The following adverse reactions have been reported before and during naltrexone medication:

•	an incidence of more than 10% in detoxified opioid abusers: difficulty sleeping, anxiety, nervousness, abdominal pain/cramps, nausea and/or vomiting, low energy, joint and muscle pain, and headache;
•	an incidence of less than 10%: loss of appetite, diarrhoea, constipation, increased thirst, increased energy, feeling down, irritability, dizziness, skin rash, delayed ejaculation, decreased potency, chills, chest pain, increased sweating and increased lacrimation.

Occasional liver function abnormalities have also been reported. One case of reversible idiopathic thrombocytopenic purpura has occurred in a patient taking Nalorex.

4.9 Overdose

There is no clinical experience with NALOREX overdose in patients. There was no evidence of toxicity in volunteers receiving 800 mg/day for seven days, however, in case of overdose, patients should be monitored and treated symptomatically in a closely supervised environment.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Naltrexone is a specific, high affinity, long acting competitive antagonist at opioid receptors. It has negligible opioid agonist activity. Tolerance does not develop with prolonged use.

5.2 Pharmacokinetic Properties

Naltrexone is rapidly absorbed after oral administration. It is metabolised by the liver and excreted primarily in the urine, less than 5% is excreted in the faeces. Naltrexone has an elimination half-life of four hours. The major metabolite 6-beta-naltrexol has an elimination half-life of 12.9 hours.

5.3 Preclinical Safety Data

Nalorex is well established in medical use. Preclinical data is broadly consistent with clinical experience.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose Monohydrate

Microcrystalline Cellulose

Crospovidone

Silica, Colloidal Anhydrous

Magnesium Stearate

Pale Yellow Opadry

Pale Yellow Opadry contains hypromellose, macrogol, polysorbate 80 and colouring agents titanium dioxide (E171) and yellow and red iron oxides (E172).

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

36 months

6.4 Special Precautions For Storage

Do not store above 25°C. .

6.5 Nature And Contents Of Container

White opaque PVC/PE/Aclar blister or white opaque PVC/Aclar/PVC blister with aluminium foil in packs of 28 tablets.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Bristol-Myers Squibb Pharmaceuticals Limited

Uxbridge Business Park

Sanderson Road, Uxbridge,

Middlesex, UB8 1DH

8. Marketing Authorisation Number(S)

PL 11184/0104

9. Date Of First Authorisation/Renewal Of The Authorisation

31 July 1992 / 10 October 2005

10. Date Of Revision Of The Text

August 2009