Drug addiction is a complex but treatable brain disease. It is characterized by compulsive drug craving, seeking, and use that persist even in the face of severe adverse consequences. For many people, drug addiction becomes chronic, with relapses possible even after long periods of abstinence. In fact, relapse to drug abuse occurs at rates similar to those for other well-characterized, chronic medical illnesses such as diabetes, hypertension, and asthma. As a chronic, recurring illness, addiction may require repeated treatments to increase the intervals between relapses and diminish their intensity, until abstinence is achieved. Through treatment tailored to individual needs, people with drug addiction can recover and lead productive lives.

The ultimate goal of drug addiction treatment is to enable an individual to achieve lasting abstinence, but the immediate goals are to reduce drug abuse, improve the patient's ability to function, and minimize the medical and social complications of drug abuse and addiction. Like people with diabetes or heart disease, people in treatment for drug addiction will need to change behavior to adopt a more healthful lifestyle.

In 2004, approximately 22.5 million Americans aged 12 or older needed treatment for substance (alcohol or illicit drug) abuse and addiction. Of these, only 3.8 million people received it. (NSDUH 2004)

Untreated substance abuse and addiction add significant costs to families and communities, including those related to violence and property crimes, prison expenses, court and criminal costs, emergency room visits, healthcare utilization, child abuse and neglect, lost child support, foster care and welfare costs, reduced productivity, and unemployment.

The latest estimate for the costs to society of illicit drug abuse alone is $181 billion (2002). When combined with alcohol and tobacco costs, they exceed $500 billion including healthcare, criminal justice, and lost productivity. Successful drug abuse treatment can help reduce this cost; crime; and the spread of HIV/AIDS, hepatitis, and other infectious diseases. It is estimated that for every dollar spent on addiction treatment programs, there is a $4 to $7 reduction in the cost of drug-related crimes. With some outpatient programs, total savings can exceed costs by a ratio of 12:1.
Basis for Effective Treatment
Scientific research since the mid-1970s shows that treatment can help many people change destructive behaviors, avoid relapse, and successfully remove themselves from a life of substance abuse and addiction. Recovery from drug addiction is a long-term process and frequently requires multiple episodes of treatment. Based on this research, key principles have been identified that should form the basis of any effective treatment program:

No single treatment is appropriate for all individuals.

Treatment needs to be readily available.

Effective treatment attends to multiple needs of the individual, not just his or her drug addiction.

An individual’s treatment and services plan must be assessed often and modified to meet the person’s changing needs.

Remaining in treatment for an adequate period of time is critical for treatment effectiveness.

Counseling and other behavioral therapies are critical components of virtually all effective treatments for addiction.

For certain types of disorders, medications are an important element of treatment, especially when combined with counseling and other behavioral therapies.

Addicted or drug-abusing individuals with coexisting mental disorders should have both disorders treated in an integrated way.

Medical management of withdrawal syndrome is only the first stage of addiction treatment and by itself does little to change long-term drug use.

Treatment does not need to be voluntary to be effective.

Possible drug use during treatment must be monitored continuously.

Treatment programs should provide assessment for HIV/AIDS, hepatitis B and C, tuberculosis, and other infectious diseases, and should provide counseling to help patients modify or change behaviors that place themselves or others at risk of infection.

As is the case with other chronic, relapsing diseases, recovery from drug addiction can be a long-term process and typically requires multiple episodes of treatment, including "booster" sessions and other forms of continuing care.

Effective Treatment Approaches
Medication and behavioral therapy, alone or in combination, are aspects of an overall therapeutic process that often begins with detoxification, followed by treatment and relapse prevention. Easing withdrawal symptoms can be important in the initiation of treatment; preventing relapse is necessary for maintaining its effects. And sometimes, as with other chronic conditions, episodes of relapse may require a return to prior treatment components. A continuum of care that includes a customized treatment regimen, addressing all aspects of an individual's life, including medical and mental health services, and followup options (e.g., community- or family-based recovery support systems) can be crucial to a person’s success in achieving and maintaining a drug-free lifestyle.

Medications can be used to help with different aspects of the treatment process.

Withdrawal: Medications offer help in suppressing withdrawal symptoms during detoxification. However, medically assisted withdrawal is not in itself "treatment"—it is only the first step in the treatment process. Patients who go through medically assisted withdrawal but do not receive any further treatment show drug abuse patterns similar to those who were never treated.

Treatment: Medications can be used to help re-establish normal brain function and to prevent relapse and diminish cravings throughout the treatment process. Currently, we have medications for opioid (heroin, morphine) and tobacco (nicotine) addiction, and are developing others for treating stimulant (cocaine, methamphetamine) and cannabis (marijuana) addiction.

Methadone and buprenorphine, for example, are effective medications for the treatment of opiate addiction. Acting on the same targets in the brain as heroin and morphine, these medications block the drug's effects, suppress withdrawal symptoms, and relieve craving for the drug. This helps patients to disengage from drug-seeking and related criminal behavior and be more receptive to behavioral treatments.

Buprenorphine: This is a relatively new and important treatment medication. NIDA-supported basic and clinical research led to the development of buprenorphine (Subutex or, in combination with naloxone, Suboxone), and demonstrated it to be a safe and acceptable addiction treatment. While these products were being developed in concert with industry partners, Congress passed the Drug Addiction Treatment Act (DATA 2000), permitting qualified physicians to prescribe narcotic medications (Schedules III to V) for the treatment of opioid addiction. This legislation created a major paradigm shift by allowing access to opiate treatment in a medical setting rather than limiting it to specialized drug treatment clinics. To date, nearly 10,000 physicians have taken the training needed to prescribe these two medications, and nearly 7,000 have registered as potential providers.

Behavioral Treatments help patients engage in the treatment process, modify their attitudes and behaviors related to drug abuse, and increase healthy life skills. Behavioral treatments can also enhance the effectiveness of medications and help people stay in treatment longer.

Outpatient behavioral treatment encompasses a wide variety of programs for patients who visit a clinic at regular intervals. Most of the programs involve individual or group drug counseling. Some programs also offer other forms of behavioral treatment such as:

Cognitive Behavioral Therapy, which seeks to help patients recognize, avoid, and cope with the situations in which they are most likely to abuse drugs.

Multidimensional Family Therapy, which addresses a range of influences on the drug abuse patterns of adolescents and is designed for them and their families.

Motivational Interviewing, which capitalizes on the readiness of individuals to change their behavior and enter treatment.

Motivational Incentives (contingency management), which uses positive reinforcement to encourage abstinence from drugs.

Residential treatment programs can also be very effective, especially for those with more severe problems. For example, therapeutic communities (TCs) are highly structured programs in which patients remain at a residence, typically for 6 to 12 months. Patients in TCs may include those with relatively long histories of drug addiction, involvement in serious criminal activities, and seriously impaired social functioning. TCs are now also being designed to accommodate the needs of women who are pregnant or have children. The focus of the TC is on the re-socialization of the patient to a drug-free, crime-free lifestyle.

Treatment within the criminal justice system can succeed in preventing an offender's return to criminal behavior, particularly when treatment continues as the person transitions back into the community. Studies show that treatment does not need to be voluntary to be effective. Research from the Substance Abuse and Mental Health Services Administration suggests that treatment can cut drug abuse in half, reduce criminal activity up to 80 percent, and reduce arrests up to 64 percent.

NIDA

1. NAME OF THE MEDICINAL PRODUCT

NALOREX®

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

No special precautions for storage

6.5 Nature and contents of container

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

6.6 Instructions for use, handling and disposal

Not applicable.

7. MARKETING AUTHORISATION HOLDER

Bristol-Myers Squibb Pharmaceuticals Limited

Uxbridge Business park

Sanderson Road

Uxbridge

Middlesex, UB8 1DH