ALTREX (film coated tablet)
(and dosage form):
ALTREX (film coated tablet)
Each tablet contains naltrexone hydrochloride 50 mg as active ingredient.
List of excipients: Crosspovidone, hydroxypropyl methylcellulose, lactose monohydrate, macrogol/polyethylene glycol, magnesium stearate, microcrystalline cellulose, polysorbate 80, purified water, red iron oxide, silicon dioxide, titanium dioxide, yellow iron oxide.
A 1.3.2 Narcotic analgesic and sedatives: Opioid antagonist
Naltrexone is an opioid antagonist. It blocks the effects of opioids by competitive binding at opioid receptors. The administration of naltrexone is not associated with the development of tolerance or dependence. Naltrexone will precipitate withdrawal symptoms in subjects physically dependent on opioids
Although naltrexone is well absorbed orally, it is subject to significant first pass metabolism. It is extensively metabolised in the liver and the major metabolite is 6-beta-naltrexol. Naltrexone and its metabolites are excreted mainly in the urine. Less than 1% of an oral dose of naltrexone is excreted unchanged. Peak plasma levels of both naltrexone and 6-beta-naltrexol occur within one hour of dosing and naltrexone is 20% bound to plasma proteins over the therapeutic dose range.
The mean elimination half-life (T½) values for naltrexone and 6-beta-naltrexol are 4 hours and 13 hours respectively.
ALTREX is indicated:
As an adjunct in the prophylactic maintenance therapy of detoxified, formerly opioid dependent patients.
ALTREX has not been shown to provide any therapeutic benefit except as part of an appropriate plan of management for opiod addictions.
ALTREX is contra-indicated in:
Patients receiving opioid analgesics.
Patients currently dependent on opioids.
Patients in acute opioid withdrawal (see WARNINGS).
Any individual who has failed the naloxone challenge test or who has a positive urine screen for opioids.
Any individual with a history of hyper-sensitivity to ALTREX (naltrexone) or any other ingredient stated under Composition.
Any individual with acute hepatitis or liver failure (see WARNINGS).
Pregnancy and lactation. (see PREGNANCY AND LACTATION)
ALTREX may cause hepatocellular injury when given in high doses. ALTREX is contraindicated in acute hepatitis or liver failure. Its use in patients with active liver disease or hepatic impairment must be carefully considered in light of its hepatotoxic effects.
Patients should be warned of the risk of hepatic injury and advised to stop the use of ALTREX and seek medical attention if they experience symptoms of acute hepatitis.
Although no cases of hepatic failure due to ALTREX administration have been reported, doctors are advised to consider this as a possible risk of treatment.
Patients with renal impairment should be carefully monitored when taking ALTREX.
Unintended Precipitation of Abstinence:
Patients must be opioid-free for a minimum of 7 to 10 days before starting ALTREX in order to prevent occurrence of an acute abstinence syndrome, or exacerbation of a pre-existing abstinence syndrome. Since the absence of an opioid in the urine is often not sufficient proof that a patient is opioid free, it is advised that a naloxone challenge should be employed. The naloxone challenge test is described under DOSAGE AND DIRECTIONS FOR USE.
Attempt to overcome blockade:
While ALTREX is a potent antagonist with a prolonged pharmacologic effect (24 to 72 hours), the blockade produced by ALTREX is surmountable. This poses a potential risk to individuals who attempt, on their own, to overcome the blockade by administering large amounts of exogenous opioids. This may be very dangerous and may lead to a fatal overdose. Injury may arise because the plasma concentration of exogenous opioids attained immediately following their acute administration may be sufficient to overcome the competitive receptor blockade. As a consequence, the patient may be in immediate danger of suffering life-endangering opioid intoxication (e.g. respiratory arrest, circulatory collapse). Patients should be told of the serious consequences of trying to overcome the opiate blockade (see Special Precautions).
There is also the possibility that a patient who had been treated with ALTREX will respond to lower doses of opioids than previously used, particularly if taken in such a manner that high plasma concentrations remain in the body beyond the time that ALTREX exerts its therapeutic effects. This could result in potentially life-threatening opioid intoxication (respiratory compromise or arrest, circulatory collapse, etc.). Patients should be aware that they may be more sensitive to lower doses of opioids after ALTREX treatment is discontinued.
ALTREX should be discontinued at least 48 hours before elective surgery involving opiod analgesics.
Ultra rapid opioid withdrawal:
Safe use of ALTREX in rapid opiate detoxification programs has not been established (see Side effects and Special Precautions).
The safe use of ALTREX in patients younger than 18 years old has not been established. (see DOSAGE AND DIRECTIONS FOR USE)
The risk of suicide is increased in patients with substance abuse with or without concomitant depression. This risk is not abated by the treatment with ALTREX (see Side Effects).
Interaction studies between ALTREX and medicines other than opiates have not been performed. Caution is advised if the concomitant administration of ALTREX and other medicines is required.
The effect of concomitant use of ALTREX and disulfiram is unknown, and the concomitant use of two potentially hepatotoxic medications is not ordinarily recommended.
Lethargy and somnolence have been reported following doses of ALTREX and thioridazine.
Administration of ALTREX to a patient dependent on opioid agents will precipitate withdrawal symptoms within 5 minutes of ALTREX administration, which can persist for up to 48 hours (refer to Special Precautions).
Patients taking ALTREX may not benefit from opioid containing medicines, such as cough and cold preparations, anti-diarrhoeal preparations and opioid analgesics. In an emergency situation when opioid analgesia must be administered to a patient receiving ALTREX, the amount of opioid required may be greater than usual, and the resulting respiratory depression may be deeper and more prolonged (see Special Precautions). The patient should be closely monitored for evidence of respiratory depression or other adverse symptoms and signs.
PREGNANCY AND LACTATION
Safety and/or efficacy during pregnancy and lactation have not been established.
DOSAGE AND DIRECTIONS FOR USE
DO NOT ATTEMPT TREATMENT WITH ALTREX UNLESS, IN THE MEDICAL JUDGMENT OF THE PRESCRIBING DOCTOR, THERE IS NO REASONABLE POSSIBILITY OF OPIOID USE WITHIN THE PAST 7 10 DAYS. IF THERE IS ANY QUESTION OF OCCULT OPIOID DEPENDENCE, PERFORM A NALOXONE CHALLENGE TEST (see below) AND DO NOT INITIATE ALTREX THERAPY UNTIL THE NALOXONE CHALLENGE IS NEGATIVE.
ALTREX should be initiated in an addiction centre and supervised by suitably qualified doctors.
Treatment of opioid dependence:
Treatment should be initiated, with an initial dose of 25 mg (half a tablet) the first day. If no withdrawal signs occur, the dosage may be increased to 50 mg daily thereafter.
Alternative dosing schedules:
Once treatment has been initiated with ALTREX, 50 mg every 24 hours will produce adequate clinical blockade of the actions of parenterally administered opioids (i.e., this dose will block the effect of a 25 mg intravenous heroin challenge). A flexible approach to a dosing regimen may need to be employed in cases of supervised administration. Thus, patients may receive 50 mg ALTREX every weekday with a 100 mg dose on Saturday; 100 mg every other day; or 150 mg every third day. The degree of blockade produced by ALTREX may be reduced by these extended dosing intervals.
There may be a higher risk of hepatocellular injury with single doses above 50 mg, and use of higher doses and extended dosing intervals should balance the possible risks against the probable benefits (see WARNINGS).
Naloxone challenge test
The naloxone challenge test should not be performed in a patient showing clinical signs or symptoms of opioid withdrawal, or in a patient whose urine contains opioids. The naloxone challenge test may be administered by either the intravenous or subcutaneous routes.
The recommended procedure is as follows:
Intravenous: Inject 0,2 mg naloxone. Observe for 30 seconds for signs or symptoms of withdrawal. If no evidence of withdrawal, inject 0,6 mg of naloxone. Observe for an additional 30 minutes. If doubt exists that the patient is opioid-free, the challenge may be repeated with a naloxone dose of 1,6 mg.
Administer 0,6 mg of naloxone. Observe for 20 minutes for signs and symptoms of withdrawal.
Interpretation of the challenge: Monitor vital signs and observe the patient for signs and symptoms of opioid withdrawal. These may include, but are not limited to: nausea, vomiting, dysphoria, yawning, sweating, tearing, rhinorrhoea, stuffy nose, craving for opioids, poor appetite, abdominal cramps, sense of fear, skin erythema, disrupted sleep patterns, fidgeting, uneasiness, poor ability to focus, mental lapses, muscle aches or cramps, pupiliary dilation, piloerection, fever, changes in blood pressure, pulse or temperature, anxiety, depression, irritability, backache, bone or joint pains, tremors, sensations of skin crawling or involuntary muscle contraction (twitching). If signs or symptoms of withdrawal appear, the test is positive and no additional naloxone should be administered.
If the test is positive, do NOT initiate ALTREX therapy.
Repeat the challenge in 24 hours. If the test is negative and no other contra-indications are present, ALTREX therapy may be initiated. If there is any doubt about the result of the test, withhold ALTREX and repeat the challenge after 24 hours.
The safe use of ALTREX in patients younger than 18 years old has not been established. (see WARNINGS)
SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Infections and infestations
Inguinal pain, swollen glands.
Nervous system disorders
Nervousness, dizziness, headache, irritability, difficulty sleeping, low energy, increased energy.
Head pounding, yawning, somnolence.
Abdominal pain/cramps; nausea and/or vomiting; diarrhoea; constipation.
Excessive gas; haemorrhoids; ulcer; dry mouth.
Musculoskeletal and connective tissue disorders
Joint and muscle pain.
Painful shoulders, legs or knees; tremors; twitching.
Metabolism and nutritional disorders
Loss of appetite; increased thirst.
Increased appetite; weight loss; weight gain.
Skin and subcutaneous tissue disorders
Skin rash, increased sweating.
Oily skin; pruritus; acne; athletes foot; cold sores; alopecia.
Reproductive system and breast disorders
Delayed ejaculation; decreased potency.
Increased or decreased sexual interest.
Respiratory, thoracic and mediastinal disorders
Nasal congestion, rhinorrhoea; sneezing; sore throat; excess mucus or phlegm; sinus; heavy breathing; hoarseness; cough and shortness of breath.
Non-specific ECG changes; palpitations; tachycardia.
Blood and lymphatic system disorders
Phlebitis; increased blood pressure, oedema, epistaxis.
Renal and urinary disorders
Increased frequency of, or discomfort during urination.
Anxiety, mood swings.
Depression; paranoia; fatigue; restlessness; confusion; disorientation; hallucinations; nightmares, suicidal ideas, attempted suicide, agitation, euphoria.
Blurred vision; burning; light sensitive; swollen; aching; strained eyes, increased lacrimation.
Clogged ears; aching; tinnitus.
General disorders and administrative site conditions
When reversal of ALTREX blockade is required:
In an emergency situation in patients receiving full blocking doses of ALTREX, a suggested management plan is use of non-opioid analgesics or general anaesthesia, regional analgesia or conscious sedation with a benzodiazepine.
The amount of opioid required may be greater than usual in a situation requiring opioid analgesia, and a prolonged and deeper respiratory depression is expected. This may be prevented by using a rapid acting opioid analgesic which minimises the duration of respiratory depression. The amount of analgesic administered should be titrated to the needs of the patient. Non-receptor mediated actions may occur and should be expected (e.g. facial swelling, itching, generalised erythema, or bronchoconstriction) presumably due to histamine release.
The patient should be monitored closely irrespective of the medicine chosen to reverse ALTREX blockade. The reversal of ALTREX blockade should only take place in a setting equipped and staffed for cardiopulmonary resuscitation managed by appropriately trained personnel.
Accidentally precipitated withdrawal:
The accidental ingestion of ALTREX leading to severe opioid withdrawal syndromes have been reported in opioid-dependent individuals. Withdrawal symptoms appeared within five minutes of ingestion of ALTREX and can last for up to 48 hours. Symptoms of withdrawal include: mental status changes including confusion, somnolence, visual hallucinations, significant fluid losses from vomiting and diarrhoea (intravenous fluid administration may be required). In all cases patients were closely monitored and therapy with non-opioid medications was tailored to meet individual requirements.
Use of ALTREX does not eliminate or diminish withdrawal symptoms. Numerous adverse events are known to be associated with withdrawal. If ALTREX is initiated early in the abstinence process, it will not preclude the patients experience of the full range of signs and symptoms that would be experienced if ALTREX had not been started.
Patients with renal impairment:
As ALTREX and its primary metabolite are excreted primarily in the urine, caution is recommended in administering the medicine to patients with renal impairment.
Patients with hepatic impairment:
Special caution should be exercised when ALTREX is administered to patients with liver disease. It is also suggested that alterations in ALTREX bioavailability are related to liver disease severity.
Medicine-related hepatic injury should always be suspected, if the occurrence of liver damage induced by ALTREX is to be detected at the earliest possible time. Evaluations, using appropriate batteries of tests to detect liver injury are recommended at a frequency appropriate to the clinical situation and the dose of ALTREX.
ALTREX contains lactose. Patients with rare hereditary problems of galactose intolerance, the lapp lactase deficiency, or glucose-galactose malabsorption, should not take ALTREX.
Ability to drive or use machinery
ALTREX can cause dizziness, blurred vision, somnolence and other side-effects that may affect the patients ability to drive and operate machinery. Patients should refrain from driving and operating machinery until they know how ALTREX affects them.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
There is limited clinical experience with ALTREX overdosage in humans. There was no evidence of toxicity in patients receiving 800 mg/day for seven days.
In view of the lack of actual experience in the treatment of ALTREX overdose, patients should be treated symptomatically and supportively in a closely supervised environment. Doctors should contact a poison information centre for the most up-to-date information.
When reversal of overdose of ALTREX is required, refer to Special Precautions.
Yellow film coated capsule-shaped tablet with a convex surface, debossed with a 50 and a full bisect between the 5 and 0 on one side, and 1170 debossed on the other side.
ALTREX is packed into white plastic (HDPE) containers and a white plastic ribbed Child Resistant cap with a foil seal. Pack sizes are 30 and 100 tablets.
Store at or below 25°C.
The container must be kept tightly closed.
KEEP OUT OF REACH OF CHILDREN.
NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION
Pharmaplan (Pty) Ltd.
106 16th Road
DATE OF PUBLICATION OF THE PACKAGE INSERT
27 July 2012
New addition to this site: May 2014
Source: Pharmaceutical Industry
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