Active ingredients: Oxycodone (Oxycodone hydrochloride), Naloxone (naloxone hydrochloride)
Targin 5mg / 2.5mg prolonged release tablets
Targin 10mg / 5mg prolonged release tablets
Targin 20mg / 10mg prolonged release tablets
Targin 40mg / 20mg prolonged release tablets
Why is Targin used? What is it for?
You have been prescribed Targin for the treatment of severe pain, which can only be adequately treated with opioid analgesics. Naloxone hydrochloride is added to counter constipation.
How Targin works
Targin contains two medicines: oxycodone hydrochloride and naloxone hydrochloride. Oxycodone hydrochloride is responsible for the pain suppression of Targin and is a potent analgesic (pain reliever) belonging to the opioid group.
The second active ingredient of Targin, naloxone hydrochloride, acts against constipation. Bowel dysfunction (constipation) is a typical undesirable effect in treatment with opioid pain relievers.
Targin is an extended-release tablet, which means that the active ingredients it contains are released over a long period of time. Their action lasts for 12 hours.
Contraindications When Targin should not be used
DO NOT use Targin
- if you are allergic (hypersensitive) to "oxycodone hydrochloride, naloxone hydrochloride or any of the other ingredients of this medicine (listed in section 6),
- if breathing is unable to supply enough oxygen to the blood, and to eliminate the carbon dioxide produced (respiratory depression),
- if you have severe lung disease associated with narrowing of the airways (chronic obstructive pulmonary disease or COPD),
- if you have a condition known as cor pulmonale. In this condition, the right side of the heart becomes enlarged, as a result of an increase in pressure within the blood vessels in the lung etc. (eg as a consequence of COPD - see above),
- if you suffer from severe bronchial asthma,
- if you have paralytic ileus (a type of intestinal obstruction) not caused by opioids,
- if you have moderate or severe liver dysfunction.
Precautions for use What you need to know before you take Targin
Talk to your doctor or pharmacist before taking Targin
- in case of elderly or debilitated (weak) patients
- if you suffer from paralytic ileus (a type of intestinal obstruction) caused by opioids
- if you have kidney failure
- if you suffer from mild hepatic insufficiency
- if you have severe lung insufficiency (e.g. reduced breathing capacity)
- if you have myxedema (a thyroid disorder with dry, cold and swollen skin - swelling - in the areas of the face and limbs)
- if your thyroid gland does not produce enough hormones (thyroid failure or hypothyroidism)
- if your adrenal glands are not producing enough hormones (adrenal insufficiency, or Addison's disease)
- if you have mental disorders accompanied by a (partial) loss of sense of reality (psychosis) due to alcohol or intoxication with other substances (substance-induced psychosis)
- if you suffer from gallstones
- if your prostate gland is abnormally enlarged (prostatic hypertrophy)
- if you suffer from alcoholism or delirium tremens
- if your pancreas is inflamed (pancreatitis)
- if you have low blood pressure (hypotension)
- if you have high blood pressure (hypertension)
- if you have pre-existing cardiovascular disease
- if you have ever had a head injury (due to the risk of increased intracranial pressure)
- if you suffer from epilepsy or are prone to fits
- if you are also taking MAO inhibitors (used to treat depression or Parkinson's disease), eg. medicines containing tranylcypromine, phenelzine, isocarboxazid, moclobemide, linezolid.
Tell your doctor if any of the above has happened in the past. Also tell your doctor if you get any of the above while you are taking Targin.
The most serious effect of an opioid overdose is respiratory depression (slow, shallow breathing). This can also cause a drop in oxygen levels in the blood, resulting in possible fainting etc.
For those who carry out sporting activities: the use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.
There is no clinical evidence in patients with cancer associated with peritoneal metastases or with onset of bowel obstruction and in advanced stage of digestive and pelvic cancer. Therefore, the use of Targin is not recommended in these patients.
Children and adolescents
This medicine should not be given to children or adolescents under the age of 18 as its safety and benefits have not yet been proven.
How to use Targin correctly.
If severe diarrhea occurs at the start of treatment, this may be due to the effect of naloxone. It can be a sign that bowel function is returning to normal. Diarrhea can occur in the first 3 - 5 days of treatment. If diarrhea persists after 3-5 days, or gives you cause for concern, contact your doctor.
When switching to Targin, if you are using high doses of another opioid, withdrawal symptoms may initially occur, such as agitation, sweating and muscle aches. If such symptoms occur, close medical monitoring may be required.
Tell your doctor that you are taking Targin if you are going to have surgery.
You can become tolerant of Targin if you use it for a long time. This means that a higher dose may be needed to achieve the desired pain relief. In addition, long-term use of Targin can lead to physical dependence. Withdrawal symptoms may occur if treatment is stopped too abruptly (agitation, sweating attacks, muscle aches). If you no longer need treatment, you should reduce the daily dose gradually, under the supervision of your doctor.
The active substance oxycodone hydrochloride alone has an abuse profile similar to other strong opioids (strong analgesics). There is the possibility of developing a psychological dependence. Medicines that contain oxycodone hydrochloride should be avoided in patients with past or present abuse of alcohol, drugs or medicines.
Residues of the prolonged-release tablet can be found in the faeces. Do not be alarmed, as the active ingredients (oxycodone hydrochloride and naloxone hydrochloride) have already been released in the stomach and intestines, and absorbed into your body.
Incorrect use of Targin
You must swallow the tablet whole, so as not to affect the slow release of oxycodone hydrochloride from the tablet. The tablets must not be broken, chewed or crushed. Swallowing broken, chewed or crushed tablets may result in the absorption of a lethal dose of oxycodone hydrochloride (see below: If you take more Targin than you should).
Targin is not suitable for the treatment of opioid withdrawal.
You should never abuse Targin, particularly if you are addicted to substances such as heroin, morphine or methadone, severe withdrawal symptoms are similar if you abuse Targin as it contains naloxone. Pre-existing withdrawal symptoms may worsen.
You should not use Targin prolonged-release tablets improperly by dissolving and injecting them (for example into a blood vessel). In particular, they contain talc, which can locally cause tissue destruction (necrosis) and changes in lung tissue (lung granuloma). Such abuse can also have other serious consequences and can be fatal.
For those who carry out sporting activities: the use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.
Interactions Which drugs or foods may change the effect of Targin
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
If you take Targin at the same time as alcohol or medicines that affect brain function, the risk of side effects is increased. In this case, the undesirable effects of Targin can be enhanced. For example, tiredness / sleepiness may occur, or respiratory depression (slow, shallow breathing) may worsen.
Examples of medicines that affect brain function include:
- other powerful pain relievers (opioids)
- sleep medicines and tranquilizers (sedatives, hypnotics)
- antidepressants
- medicines used to treat allergies, car sickness or nausea (antiemetics or antihistamines)
- other medicines that affect the nervous system (phenothiazines, neuroleptics).
Tell your doctor if you are taking:
- medicines that decrease the ability of the blood to clot (coumarin derivatives), the clotting time may be speeded up or slowed down
- antibiotics of the macrolide class (e.g. clarithromycin)
- azole antifungals (e.g. ketoconazole)
- ritonavir and other protease inhibitors (used to treat HIV)
- rifampicin (used to treat tuberculosis)
- carbamazepine (used to treat fits, fits or convulsions and in some pain conditions)
- phenytoin (used to treat fits, fits or convulsions)
No interactions are expected between Targin and paracetamol, acetylsalicylic acid or naltrexone.
Targin with food, drink and alcohol
Drinking alcohol while taking Targin may cause drowsiness or increase the risk of serious side effects such as shortness of breath with the risk of respiratory depression and loss of consciousness.
It is recommended not to drink alcohol while taking Targin. Medicines containing oxycodone hydrochloride should be avoided in patients with a past or present history of alcohol and drug abuse.
You should avoid drinking grapefruit juice when taking Targin.
Warnings It is important to know that:
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy
The use of Targin should be avoided as much as possible during pregnancy. If used for prolonged periods during pregnancy, oxycodone hydrochloride can lead to withdrawal symptoms in newborns. If oxycodone hydrochloride is given during childbirth, respiratory depression (breathing slow and superficial) in the newborn.
Feeding time
Breastfeeding should be discontinued during treatment with Targin. Oxycodone hydrochloride passes into breast milk. It is not known whether naloxone hydrochloride also passes into breast milk. Therefore, a risk to the suckling child cannot be excluded particularly following intake. of multiple doses of Targin.
Driving and using machines
Targin may affect the ability to drive or use machines. In particular, this is more likely to happen at the start of Targin therapy, after a dose increase or after switching from a different medicine. However, these side effects disappear once you have stabilized the dose of Targin. doctor if you can drive or use machines.
Targin contains lactose
This medicine contains lactose (milk sugar). If you have been told by your doctor that you have an "intolerance to some sugars, contact your doctor before taking Targin.
Dose, Method and Time of Administration How to use Targin: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
In the absence of a different medical prescription, the recommended dose is:
Adults
The recommended starting dose of Targin is one 10 mg oxycodone hydrochloride / 5 mg naloxone hydrochloride prolonged-release tablet every 12 hours.
Your doctor will decide how much Targin you should take each day and how to distribute the daily dosage between morning and evening. He / she will also decide on any dose adjustments that may be needed during treatment. The dose will be adjusted according to the level of pain and individual sensitivity. You should be given the lowest dose needed for pain relief. If you have already been treated with opioids, treatment with Targin can be started at a higher dose. The maximum daily dose of Targin is 80 mg of oxycodone hydrochloride and 40 mg of naloxone hydrochloride. If you need a higher dose, your doctor may give you higher doses of oxycodone hydrochloride without naloxone hydrochloride.
The maximum daily dose of oxycodone hydrochloride should not exceed 400 mg. The benefit of naloxone hydrochloride on intestinal activity may be reduced with higher doses of oxycodone hydrochloride administered without further doses of naloxone hydrochloride.
If you switch from Targin to another opioid pain medicine your bowel function will likely get worse.
If you feel pain between two doses of Targin, you may need a pain reliever that works quickly. Targin is not suitable for this. In this case, consult your doctor.
If you have the impression that the effect of Targin is too strong or too weak, talk to your doctor or pharmacist.
Renal or hepatic impairment
If you suffer from impaired kidney function or mild impairment in function
liver disease, your doctor will prescribe Targin for you with particular caution. If you have moderate or severe hepatic impairment, Targin should not be used (see also section 2 "Do not take Targin ..." and "Take special care with Targin ...").
Children and adolescents under 18 years of age
Targin has not yet been studied in children and adolescents under 18 years of age. Its safety and efficacy have not been demonstrated in children and adolescents. For this reason, the use of Targin in children and adolescents under 18 years of age is not recommended.
Elderly patients
In general, no dose adjustment is necessary in elderly patients with normal kidney and / or liver function.
Method of administration
Swallow Targin whole without chewing, with an adequate amount of liquid (1⁄2 glass of water). You can take the prolonged-release tablets with or without food. Take Targin every 12 hours, according to a fixed schedule ( eg 8 am and 8 pm) The prolonged-release tablets should not be divided, chewed or crushed.
Duration of use
In general, you should not take Targin for longer than necessary. If you have been taking Targin for a long time, your doctor should check regularly if you still need Targin.
Overdose What to do if you have taken too much Targin
If you take more Targin than you should If you have taken more than the prescribed dose of Targin, you must inform your doctor immediately.
An overdose can cause:
- constricted pupils
- slow, shallow breathing (respiratory depression)
- a state similar to narcosis (drowsiness, even unconsciousness)
- low muscle tone (hypotonia)
- reduced pulse rate
- drop in blood pressure.
In severe cases, loss of consciousness (coma), accumulation of fluid in the lungs and circulatory collapse can occur, which in some cases can be fatal.
Situations that require a high level of vigilance, such as driving, should be avoided.
If you forget to take Targin
Or if you take a lower dose than prescribed, you may not feel any analgesic effect.
If you forget to take your dose, please follow the instructions below:
- If you have to take your next usual dose in 8 hours or more: take the forgotten prolonged-release tablet right away, then continue with your normal prescription schedule.
- If you have to take your next usual dose in less than 8 hours: take the forgotten Targin prolonged-release tablet. Then wait at least 8 hours before taking your next Targin tablet, trying to return to the original prescription schedule (eg 8 am and 8 pm). Do not take more than one Targin prolonged-release tablet in any one period. 8 hours.
Do not take a double dose to make up for a forgotten tablet.
If you stop taking Targin
Do not stop taking Targin without consulting your doctor.If you do not need further treatment, you should reduce your daily dosage gradually after talking to your doctor. This will prevent withdrawal symptoms such as agitation, sweating attacks and muscle pain.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Targin
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following frequency data are used to evaluate side effects:
Important side effects or signs to look for, and what to do if they occur:
If you notice any of the following important side effects, please consult your nearest doctor immediately.
Slow, shallow breathing (respiratory depression) is the main danger of an opioid overdose. It mainly occurs in elderly and debilitated (weak) patients. Opioids can also cause a severe drop in blood pressure in predisposed patients.
common
- abdominal pain
- constipation
- diarrhea
- dry mouth
- indigestion
- vomiting (feeling sick)
- feeling unwell
- flatulence
- reduced appetite up to loss of appetite
- feeling dizzy or "dizzy"
- headache
- hot flashes
- general weakness
- itch
- skin reactions / rash
- sweating
- dizziness
- difficulty sleeping
- drowsiness
Uncommon
- abdominal bloating
- abnormal thoughts
- anxiety
- confusion
- depression
- nervousness
- chest tightness especially if you already have coronary heart disease
- decrease in blood pressure
- withdrawal symptoms such as agitation
- fainting
- palpitations
- bilar colic
- chest pain
- feeling bad in general
- ache
- swelling in the hands, ankles or feet
- weight loss
- difficulty concentrating
- impaired language
- tremors
- breathing difficulties
- restlessness
- chills
- increased liver enzymes
- increase in arterial pressure
- a runny nose
- cough
- hypersensitivity / allergic reactions
- accident injuries
- increased urge to urinate
- muscle cramps
- muscle spasms
- muscular pain
- vision problems
- seizures (especially in people with epileptic disorders or predisposition to seizures)
Rare
- increased heart rate
- dental alterations
- yawns
- weight gain
Not known
- euphoria
- severe sleepiness
- erectile dysfunction
- nightmares
- hallucinations
- shallow breathing
- difficulty urinating
- tingling in the hands and feet
- belching
The active ingredient oxycodone hydrochloride, if not in combination with naloxone hydrochloride, has the following side effects:
Oxycodone can cause breathing problems (respiratory depression), reduction in the pupil diameter of the eye, bronchial muscle cramps and smooth muscle cramps, and depression of the cough reflex.
common
- altered mood and personality changes (for example, depression, sense of extreme happiness)
- decrease in activity
- increased activity
- difficulty urinating
- hiccup
Uncommon
- impaired concentration ability
- migraine
- taste abnormalities
- increased muscle tension
- involuntary muscle contractions
- drug addiction
- ileus
- dry skin
- drug tolerance
- reduced sensitivity to pain or touch
- abnormal coordination
- voice changes (dysphonia)
- water retention
- hearing difficulties
- mouth ulcers
- difficulty swallowing
- inflamed gums
- perception disturbances (e.g. hallucinations, derealization)
- reduced sex drive
- redness of the skin
- dehydration
- agitation
- thirst
Rare
- itchy rash (hives)
- herpes simplex
- increased appetite
- black (tarry) stools
- bleeding in the gums
Not known
- generalized acute allergic reactions (anaphylactic reactions)
- absence of menstruation
- problems with the flow of bile
If you get any of the side effects, including those not listed in this leaflet, talk to your doctor or pharmacist.
Expiry and Retention
Keep out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the outer label and blister after "EXP". The expiry date refers to the last day of that month.
Store Targin 5 mg / 2.5 mg in the original package in order to protect from light.
Do not store above 25 ° C.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Targin contains
- The active ingredients are: oxycodone hydrochloride and naloxone hydrochloride
Targin 5mg / 2.5mg
1 prolonged-release tablet contains 5 mg of oxycodone hydrochloride equivalent to 4.5 mg of oxycodone. 2.73 mg of naloxone hydrochloride dihydrate, equivalent to 2.5 mg of naloxone
Targin 10mg / 5mg
1 prolonged-release tablet contains 10 mg of oxycodone hydrochloride equivalent to 9 mg of oxycodone. 5.45 mg of naloxone hydrochloride dihydrate, equivalent to 5.0 mg of naloxone hydrochloride or 4.5 of naloxone
Targin 20mg / 10mg
1 prolonged-release tablet contains 20 mg of oxycodone hydrochloride equivalent to 18 mg of oxycodone. 10.9 mg of naloxone hydrochloride dihydrate, equivalent to 10.0 mg of naloxone hydrochloride or 9 mg of naloxone
Targin 40mg / 20mg
1 prolonged-release tablet contains 40 mg of oxycodone hydrochloride equivalent to 36 mg of oxycodone. 21.8 mg of naloxone hydrochloride dihydrate, equivalent to 20.0 mg of naloxone or 18 mg of naloxone.
The other ingredients are:
Tablet core:
(Targin 5 mg / 2.5 mg)
Hydroxypropylcellulose,
(Targin 10 mg / 5 mg, 20 mg / 10 mg and 40 mg / 20 mg)
Povidone K30,
ethyl cellulose, stearyl alcohol, lactose monohydrate, talc, magnesium stearate,
Tablet coating:
(Targin 5 mg / 2.5 mg)
Polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, brilliant blue FCF aluminum lake
(E133)
(Targin 10 mg / 5 mg)
Polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc.
(Targin 20 mg / 10 mg)
Polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, red iron oxide (E172).
(Targin 40 mg / 20 mg)
Polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc iron oxide yellow (E172)
What Targin looks like and contents of the pack
Targin 5 mg / 2.5 mg prolonged release tablets are blue, oblong with a film-coated label marked "OXN" on one side and "5" on the other.
Targin 10 mg / 5 mg prolonged-release tablets are white, oblong with a film-coated label marked "OXN" on one side and "10" on the other.
Targin prolonged-release 20mg / 10mg tablets are pink, oblong with a film-coated label marked "OXN" on one side and "20" on the other.
Targin 40mg / 20mg prolonged-release tablets are yellow, oblong with a film-coated label marked "OXN" on one side and "40" on the other.
Targin prolonged-release tablets are available in packs of 10, 14, 20, 28, 30, 50, 56, 60, 98 and 100.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
TARGIN PROLONGED-RELEASE TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Targin 5 mg / 2.5 mg
Each prolonged-release tablet contains 5 mg of oxycodone hydrochloride equivalent to 4.5 mg of oxycodone, and 2.73 mg of naloxone hydrochloride dihydrate equivalent to 2.5 mg of naloxone hydrochloride and 2.25 mg of naloxone.
Targin 10 mg / 5 mg
Each prolonged-release tablet contains 10 mg of oxycodone hydrochloride equivalent to 9.0 mg of oxycodone, and 5.45 mg of naloxone hydrochloride dihydrate equivalent to 5.0 mg of naloxone hydrochloride and 4.5 mg of naloxone.
Targin 20 mg / 10 mg
Each prolonged-release tablet contains 20 mg of oxycodone hydrochloride equivalent to 18.0 mg of oxycodone, and 10.9 mg of naloxone hydrochloride dihydrate equivalent to 10.0 mg of naloxone hydrochloride and 9.0 mg of naloxone.
Targin 40 mg / 20 mg
Each prolonged-release tablet contains 40 mg of oxycodone hydrochloride equivalent to 36.0 mg of oxycodone, and 21.8 mg of naloxone hydrochloride dihydrate equivalent to 20.0 mg of naloxone hydrochloride and 18.0 mg of naloxone.
Targin 5 mg / 2.5 mg
Excipients: Each prolonged-release tablet contains 68.17 mg of anhydrous lactose.
Targin 10 mg / 5 mg
Excipients: Each prolonged-release tablet contains 61.04 mg of anhydrous lactose.
Targin 20 mg / 10 mg
Excipients: Each prolonged-release tablet contains 51.78 mg of anhydrous lactose.
Targin 40 mg / 20 mg.
Excipients: Each prolonged-release tablet contains 103.55 mg of anhydrous lactose.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Prolonged-release tablets.
Targin 5 mg / 2.5 mg
Blue, oblong film-coated tablets, debossed with "OXN" on one side and "5" on the other side.
Targin 10 mg / 5 mg.
White, oblong film-coated tablets debossed with "OXN" on one side and "10" on the other.
Targin 20 mg / 10 mg.
Pink, oblong film-coated tablets debossed with "OXN" on one side and "20" on the other.
Targin 40 mg / 20 mg
Yellow, oblong film-coated tablets, debossed with "OXN" on one side and "40" on the other.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Severe pain that can only be adequately managed with analgesic opioids. The opioid antagonist naloxone is added to counteract opioid-induced constipation by blocking the action of oxycodone at the opioid receptors of the gastrointestinal tract.
04.2 Posology and method of administration
Oral use
Dosage
The analgesic efficacy of Targin is equivalent to that of the prolonged release formulations of oxycodone hydrochloride.
The dose should be adjusted according to the intensity of the pain and the individual sensitivity of the patient. Without a different prescription, Targin should be administered as follows:
Adults
The usual starting dose for an opioid-naïve patient is 10 mg / 5 mg oxycodone hydrochloride / naloxone hydrochloride, at 12 hour intervals.
Patients who are already on opioid treatment may start with higher doses of Targin based on previous experience.
In case of initiation of opioid therapy or dose adjustment, Targin 5 mg / 2.5 mg dosage is indicated.
The maximum daily dose of Targin is 80 mg of oxycodone hydrochloride and 40 mg of naloxone hydrochloride.For those patients requiring higher doses of Targin, supplemental doses of prolonged-release oxycodone hydrochloride should be considered at the same time intervals, taking into account the maximum daily dose of 400 mg prolonged-release oxycodone hydrochloride. In case of supplemental dose of oxycodone hydrochloride, the beneficial effect of naloxone hydrochloride on intestinal function could be compromised.
Worsening of bowel function may occur after complete discontinuation of Targin therapy and subsequent switch to another opioid.
Some patients treated with Targin on a regular schedule may require immediate release analgesics as a "rescue drug" for the treatment of breakthrough pain. Targin is a prolonged-release formulation and therefore not indicated for the treatment of breakthrough pain.
For the treatment of breakthrough pain, a single dose of rescue medication should be 1/6 of the equivalent daily dose of oxycodone hydrochloride.
The need for more than two 'rescue medication' administrations per day is generally an indication that the dose of Targin needs increasing adjustment. This adjustment should be made every 1 to 2 days in increments of 5 mg / 2.5 mg twice daily or, where required, 10 mg / 5 mg oxycodone hydrochloride / naloxone hydrochloride until an adequate dose is reached.
The aim is to establish the specific individual dose to be taken twice a day, which maintains adequate analgesia and which uses as little as possible other "rescue medication" for as long as pain therapy is required.
Targin is taken at a certain dosage twice a day according to a regular therapeutic schedule. While symmetrical dosing (same dosing morning and evening) subject to a fixed time schedule (every 12 hours) is appropriate for most patients, some patients, based on their individual pain situation, may benefit from an adapted asymmetric dosing. the course of your pain. Generally the lowest effective analgesic dose should be chosen.
In non-malignant pain therapy, daily doses of up to 40 mg / 20 mg of oxycodone hydrochloride / naloxone hydrochloride are usually sufficient, but higher doses may be needed.
Targin 5 mg / 2.5 mg
Targin 10 mg / 5 mg
Targin 20 mg / 10 mg
Targin 40 mg / 20 mg
For doses not practicable with this posology, other posologies of this medicinal product are available.
Children and adolescents (under 18)
Targin is not recommended in children and adolescents below 18 years of age due to a lack of data on safety and efficacy.
Elderly patients
As for young adults, the dosage should be adjusted according to the intensity of pain and the sensitivity of the individual patient.
Patients with impaired liver function
A clinical study in patients with hepatic impairment has shown that plasma concentrations of both oxycodone and naloxone are elevated. Concentrations of naloxone are increased more than "oxycodone" (see section 5.2). The clinical relevance of a relatively high exposure to naloxone in patients with hepatic impairment is not yet known. Particular care should be taken when administering Targin to patients with mild hepatic impairment (see section 4.4). Targin is contraindicated in patients with moderate to severe hepatic impairment (see section 4.3).
Patients with impaired renal function.
A clinical study in patients with renal impairment has shown that plasma concentrations of both oxycodone and naloxone are elevated. Concentrations of naloxone are increased more than "oxycodone" (see section 5.2). The clinical relevance of a relatively high exposure to naloxone in patients with renal impairment is not yet known. Particular care should be taken when administering Targin to patients with renal impairment (see section 4.4).
Method of administration
Targin is taken at the established dosage twice a day according to a fixed time schedule.
The prolonged-release tablets can be taken with sufficient liquid with or without food. Targin tablets should be swallowed whole, not broken or chewed.
Duration of use
Targin should not be administered for long periods unless absolutely necessary. If long-term treatment is required based on the nature and severity of pain, careful and regular monitoring is required to determine whether and to what extent further treatment is required. If the patient no longer requires opioid therapy, it may be advisable to decrease the dose of Targin gradually (see section 4.4).
04.3 Contraindications
Hypersensitivity to active substances or to any of the excipients
All situations in which opioids are contraindicated
Severe respiratory depression with hypoxemia and / or hypercapnia
Severe obstructive pulmonary disease
Pulmonary heart,
Severe bronchial asthma
Paralytic ileus not induced by opioids
Moderate or severe hepatic impairment.
04.4 Special warnings and appropriate precautions for use
The major risk caused by opioids is respiratory depression.
Caution should be exercised when administering Targin to elderly and infirm patients, patients with opioid-induced paralytic ileus, patients with severely impaired lung function, myxedema, hypothyroidism, Addison's disease (adrenocortical insufficiency), toxic psychosis, cholelithiasis, prostate hypertrophy, alcoholism , delirium tremens, pancreatitis, hypotension, hypertension, pre-existing cardiovascular disease, head trauma (due to the risk of increased intracranial pressure), epilepsy or predisposition to seizures, or patients undergoing treatment with MAO inhibitors.
Caution should also be exercised when administering Targin to patients with mild hepatic or renal impairment. Close medical monitoring is especially necessary for patients with severe renal impairment.
Diarrhea can be considered a possible effect of naloxone.
In patients on long-term opioid treatment with high doses of opioids, switching to Targin treatment may initially lead to withdrawal syndrome. These patients may require specific attention.
Targin is not indicated for the treatment of withdrawal symptoms.
During long-term administration, the patient may develop tolerance to the drug and require higher doses to maintain the desired analgesic effect. Chronic administration of Targin can lead to physical dependence. abstinence If treatment with Targin is no longer necessary, it may be advisable to gradually reduce the daily dose in order to avoid withdrawal syndrome.
There is a potential for psychological dependence on opioid analgesics, including Targin. Targin should be used with particular care in patients with a history of alcohol and drug abuse. Oxycodone alone has a similar abuse profile to that of other potent opioid agonists.
In order not to compromise the prolonged-release characteristic of the prolonged-release tablets, the tablets must be taken whole and must not be broken, chewed or crushed. Ingesting the prolonged-release tablets by breaking, chewing or crushing them results in a faster release of the active substances and the absorption of a possible fatal dose of oxycodone (see section 4.9).
No studies on the safety and efficacy of Targin in children and adolescents under 18 years have been conducted. For this reason it is not recommended for use in children and adolescents under 18 years of age.
There is no clinical experience in patients with cancer associated with peritoneal carcinomatosis or subocclusive syndrome in advanced stages of digestive and pelvic cancers. Therefore the use of Targin is not recommended in these subjects.
Targin is not recommended for preoperative use or within 12/24 hours after surgery. Based on the type and extent of the intervention, the anesthetic procedure selected, other co-medications and the patient's individual condition, the exact time for initiating a post-operative treatment with Targin depends on a careful assessment of the risk ratio. / benefit for each individual patient.
Any abuse of Targin by drug addicts is strongly discouraged.
Abuse of Targin parenterally, intranasally or orally by individuals dependent on opioid agonists, such as heroin, morphine or methadone, produces marked withdrawal symptoms - due to the characteristics of the opioid receptor antagonist naloxone - or intensifies existing withdrawal symptoms (see section 4.9).
Targin consists of a polymer matrix, intended for oral use only. Parenteral injections for illicit use of the prolonged-release tablet components (especially talc) can cause local tissue necrosis and pulmonary granulomas or can lead to other serious and potentially fatal side effects.
The blank matrix of the prolonged-release tablet may be visible in the stool.
The use of Targin can produce positive results in doping controls.
The use of Targin as a doping agent can become dangerous to health.
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose / galactose malabsorption should not take Targin.
04.5 Interactions with other medicinal products and other forms of interaction
No interaction studies have been performed in adults.
Substances that have a CNS depressant effect (eg alcohol, other opioids, sedatives, hypnotics, antidepressants, sleep aids, phenothiazines, neuroleptics, antihistamines, antiemetics) may accentuate the CNS depressant effect (eg respiratory depression) of Targin .
Clinically relevant changes in International Normalized Ratio (INR or Quick's time) have been observed in both directions when oxycodone and coumarin anticoagulants are taken simultaneously.
In vitro metabolism studies indicate that no clinically relevant interactions are expected between oxycodone and naloxone. At therapeutic concentrations, Targin is not expected to cause clinically relevant interactions with other concomitantly administered active substances which are metabolised via the cytochromial isomers CYP1A2, CYP2A6, CYP2C9 / 19, CYP2D6, CYP2E1 and CYP3A4.
In addition, at therapeutic concentrations, the risk of clinically relevant interactions between paracetamol, acetylsalicylic acid or naltrexone and the combination of oxycodone and naloxone is minimal.
04.6 Pregnancy and lactation
Pregnancy
No data are available on the use of Targin in pregnant women and during childbirth. The limited human data on the use of oxycodone during pregnancy do not reveal an increased risk of congenital anomalies. Insufficient clinical data are available for naloxone. on exposure in pregnancy.
However, the systemic exposure of women to naloxone after use of Targin is relatively low (see section 5.2). Both naloxone and oxycodone penetrate the placenta. Animal studies have not been conducted with oxycodone and naloxone in combination (see section 5.3). Animal studies with oxycodone or naloxone administered as a single medicinal product did not reveal any teratogenic or embryotoxic effects.
Long-term administration of oxycodone during pregnancy can lead to withdrawal symptoms in the newborn. When given during childbirth, oxycodone can cause respiratory depression in the newborn.
Targin should only be used during pregnancy if the benefits outweigh any possible risks to the unborn or newborn baby.
Feeding time
Oxycodone passes into breast milk.
A milk-to-plasma concentration ratio of 3.4: 1 was measured and therefore effects of oxycodone on the infant are conceivable.
It is not known whether naloxone also enters breast milk. However after taking Targin the systemic levels of naloxone are very low (see section 5.2).
A risk to the infant cannot be excluded, particularly after the nursing mother has taken multiple doses of Targin.
Breastfeeding should be discontinued during treatment with Targin.
04.7 Effects on ability to drive and use machines
Targin may reduce the ability to drive and use machines. This is particularly likely at the start of treatment with Targin, after a dose increase or 'rotation' of the drug and if Targin is in combination with alcohol or other CNS depressant agents. Patients who have stabilized on a specific dosage do not require necessarily restrictive measures Therefore it is necessary for patients to consult their doctor to see if they can drive or use machines.
04.8 Undesirable effects
The following frequencies are the basis for assessing undesirable effects:
Very common (≥ 1/10)
Common (≥ 1/100 e
Uncommon (≥1 / 1000 and
Rare (≥ 1 / 10,000 e
Very rare (
Not known (cannot be estimated from the available data)
Within each frequency class, undesirable effects are reported in descending order of severity.
Disorders of the immune system
Uncommon: hypersensitivity
Metabolism and nutrition disorders
Common: decreased appetite leading to loss of appetite
Psychiatric disorders
Common: restlessness
Uncommon: impaired thinking, anxiety, confusion, depression, euphoria, hallucinations, insomnia, nervousness
Rare: nightmares
Disorders of the nervous system
Common: dizziness, headache,
Uncommon: attention disturbance, paraesthesia, somnolence, speech disturbances, tremor
Rare: seizures (particularly in people with epileptic disorders or predisposition to seizures), sedation, syncope
Eye disorders
Uncommon: visual disturbances
Ear and labyrinth disorders
Common: Vertigo
Cardiac pathologies
Uncommon: angina pectoris, particularly in patients with a history of coronary heart disease, palpitations
Rare: Tachycardia
Vascular pathologies
Common: decrease in blood pressure
Uncommon: increased blood pressure
Respiratory, thoracic and mediastinal disorders
Uncommon: dyspnoea, rhinorrhea, cough
Rare: incoercible yawn
Very rare: respiratory depression
Gastrointestinal disorders
Common: abdominal pain, constipation, diarrhea, dry mouth, dyspepsia, vomiting, nausea, flatulence
Uncommon: abdominal distension, belching
Rare: dental disorders
Hepatobiliary disorders
Common: increased liver enzymes
Uncommon: biliary colic
Diseases of the reproductive system and breast
Uncommon: erectile dysfunction
Skin and subcutaneous tissue disorders
Common: itching, skin reactions, hyperhidrosis
Musculoskeletal and connective tissue disorders
Uncommon: muscle spasms, muscle contractions, myalgia
Renal and urinary disorders
Uncommon: urge to urinate
Rare: urinary retention
General disorders and administration site conditions
Common: drug withdrawal syndrome, feeling hot and cold, chills, asthenia
Common: chest pain, malaise, pain, peripheral edema, weight decrease
Rare: weight gain
Injury, poisoning and procedural complications
Uncommon: accident injuries
The following additional undesirable effects are known for the active substance oxycodone hydrochloride:
Due to its pharmacological properties, oxycodone hydrochloride can cause respiratory depression, miosis, bronchospasm, smooth muscle spasms, as well as suppress the cough reflex.
Infections and infestations
Rare: herpes simplex
Disorders of the immune system
Very rare: anaphylactic reactions
Metabolism and nutrition disorders
Rare: dehydration, increased appetite
Psychiatric disorders
Common: mood alteration and personality change, reduced activity, psychomotor hyperactivity, agitation
Uncommon: perception disturbances (e.g. derealization), decreased libido
not known: drug addiction.
Nervous system disorders
Uncommon: impaired concentration, migraine, dysgeusia, hypertonia, involuntary muscle contractions, hypoesthesia, coordination abnormal
Ear and labyrinth disorders
Uncommon: impaired hearing
Vascular pathologies
Uncommon: vasodilation
Respiratory, thoracic and mediastinal disorders
Uncommon: dysphonia
Gastrointestinal disorders
Common: hiccups
Uncommon: mouth ulcerations, stomatitis
Rare: melaena, gingival bleeding, dysphagia
Very rare: ileus
Skin and subcutaneous tissue disorders
Rare: dry skin
Very rare: hives
Renal and urinary disorders
Common: dysuria
Diseases of the reproductive system and breast
Rare: amenorrhea
General disorders and administration site conditions
Uncommon: edema
Rare: thirst
Not known: drug tolerance.
04.9 Overdose
Symptoms of intoxication
Depending on the patient's history, an overdose of Targin can manifest with symptoms induced by both oxycodone (opioid receptor agonist) and naloxone (opioid receptor antagonist).
Symptoms of an oxycodone overdose include miosis, respiratory depression, somnolence progressing to coma, musculoskeletal flaccidity, bradycardia as well as hypotension. In severe cases, coma, non-cardiogenic pulmonary edema and circulatory failure can occur and can lead to a fatal outcome.
Symptoms of overdose from naloxone alone are unlikely.
Treatment of overdose
Withdrawal symptoms due to naloxone overdose should be treated symptomatically in a strictly controlled environment.
Clinical symptoms suggesting an overdose of oxycodone should be treated with the administration of opioid antagonists (e.g. naloxone hydrochloride 0.4 - 2 mg intravenously). Administration should be repeated at 2 - 3 minute intervals as clinically required.
It is also possible to apply an infusion of 2 mg of naloxone hydrochloride in 500 ml of 0.9% sodium chloride or 5% dextrose solution (0.004 mg / ml of naloxone).
The infusion should be administered at a rate corresponding by dose to the previously administered bolus doses and according to the patient's response. Gastric lavage should be considered.
Supportive measures (artificial ventilation, oxygen, vasopressors, and fluid infusion) should be employed, if necessary, to manage the circulatory shock accompanying an overdose. Cardiac arrest or arrhythmias may require heart massage or defibrillation.
If necessary, artificial ventilation should be practiced. The water and electrolyte balance must be preserved.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: natural opium alkaloids: oxycodone, combinations
ATC code: N02AA55
Oxycodone and naloxone have an affinity for the kappa, mu and delta opioid receptors of the brain, spinal cord and peripheral organs (eg the intestine).
Oxycodone acts as an opioid receptor agonist and produces pain relief by binding to endogenous opioid receptors in the CNS. Conversely, naloxone is a pure antagonist that acts on all types of opioid receptors.
Due to the marked first pass metabolism, the bioavailability of naloxone with oral administration is
Due to the local competitive antagonism of naloxone on the effect of oxycodone on the opioid receptor in the intestinal tract, naloxone reduces intestinal disturbances typical of opioid treatment.
In a 12-week, double-blind, parallel-group study of 322 patients with opioid-induced constipation, patients who were treated with oxycodone hydrochloride - naloxone hydrochloride in the last week of treatment had on average extra spontaneous bowel movement. (without laxatives), compared to patients who continued to use comparable dosages of oxycodone hydrochloride prolonged-release tablets (p
The use of laxatives in the first 4 weeks was significantly lower in the oxycodone-naloxone group than in the oxycodone monotherapy group (31% versus 55%, respectively, p
Opioids can affect the hypothalamic-pituitary-adrenal axes and gonads. Among the observed changes are an increase in serum prolactin and a decrease in the level of cortisol and testosterone in plasma. Clinical symptoms can occur due to these hormonal changes.
Preclinical studies show different effects of natural opioids on components of the immune system. The clinical relevance of these findings is unknown. It is not known whether oxycodone, a semi-synthetic opioid, has the same effects as natural opioids on the immune system.
05.2 Pharmacokinetic properties
Oxycodone hydrochloride
Absorption
Oxycodone has a high absolute bioavailability of up to 87% following oral administration.
Distribution
Once absorbed, oxycodone is distributed throughout the body. About 45% is bound to plasma proteins.
Oxycodone crosses the placenta and can be detected in breast milk.
Metabolism
Oxycodone is metabolised in the intestine and liver to noroxycodone and oxymorphone and various conjugated glucuronides. Noroxycodone, oxymorphone and noroxymorphone are produced via the cytochrome P450 system. In vitro studies indicate that therapeutic doses of cimetidine do not significantly affect noroxycodone production Quinidine reduces the production of oxymorphone in humans without substantially affecting the pharmacodynamics of oxycodone. The contribution of metabolites to the overall pharmacodynamic effect is insignificant.
Elimination
Oxycodone and its metabolites are eliminated in both urine and faeces.
Naloxone hydrochloride
Absorption
Following oral administration, naloxone has very low systemic availability (
Distribution
Naloxone crosses the placenta barrier. It is not known whether naloxone also passes into breast milk.
Metabolism and elimination
After parenteral administration, the plasma half-life is approximately one hour. The duration of action depends on the dose and route of administration, intramuscular injection produces a more prolonged effect than intravenous doses. It is metabolized in the liver and excreted in the urine. The major metabolites are naloxone glucuronide, 6 b-naloxole and its glucuronide..
Combination of oxycodone hydrochloride / naoxone hydrochloride (Targin)
The pharmacokinetic characteristics of Targin oxycodone are equivalent to those of oxycodone hydrochloride prolonged-release tablets administered in combination with naloxone hydrochloride prolonged-release tablets.
All strengths of Targin are interchangeable.
After oral administration of Targin in the maximum dose to healthy subjects, the plasma concentrations of naloxone are so low that it is not possible to perform a pharmacokinetic analysis. To conduct a pharmacokinetic analysis, naloxone-3-glucuronide is used as a surrogate, until its plasma concentration is high enough to be measured.
Overall, after ingestion of a high-fat meal, the bioavailability and maximum plasma concentration (Cmax) of oxycodone increased by an average of 16% and 30%, respectively, compared to dosing in the fasted state. evaluated as clinically not relevant, therefore Targin prolonged-release tablets can be taken with or without food (see section 4.2).
In light of the results of studies in vitro on drug metabolism, clinically relevant interactions with Targin seem unlikely.
Elderly patients
Oxycodone:
For AUC? of oxycodone, on average, c "was an increase to 118% (90% CI: 103, 135), for the elderly compared to younger volunteers. For oxycodone C, on average, c" was an increase up to 114% (90% CI: 102, 127). For Cmin of oxycodone, on average, c "was an increase of up to 128% (90% CI: 107, 152).
Naloxone:
For AUC? of naloxone, on average, c "was an increase to 182% (90% CI: 123, 270) for the elderly compared to younger volunteers. For naloxone C, on average, c" was an increase to 173 % (90% CI: 107, 280). For Cmin of naloxone, on average, c "was an increase to 317% (90% CI: 142, 708).
Naloxone-3-glucuronide:
For AUC? of naloxone-3-glucuronide, on average, c "was an increase to 128% (90% CI: 113, 147), for the elderly compared to younger volunteers. For naloxone-3-glucuronide Cmax, on average , c "was an increase to 127% (90% CI: 112, 144). For Cmin of naloxone-3-glucuronide, on average, c "was an increase to 125% (90% CI: 105, 148).
Patients with impaired hepatic function
Oxycodone:
For AUCINF of oxycodone, on average, c "was an increase to 143% (90% CI: 111, 184), 319% (90% CI: 248, 411) and 310% (90% CI: 241, 398) in subjects with mild, moderate and severe hepatic impairment, respectively, compared to healthy volunteers. For oxycodone Cmax, on average, c "was an increase to 120% (90% CI: 99, 144), to 201% (CI 90%: 166, 242) and 191% (90% CI: 158, 231) in subjects with mild, moderate and severe hepatic impairment, respectively, compared to healthy volunteers. For t½Z of oxycodone, on average, c "was an increase to 108% (90% CI: 70, 146), 176% (90% CI: 138, 215) and 183% (90% CI: 145, 221) in subjects with mild, moderate and severe hepatic impairment, respectively, compared to healthy volunteers.
Naloxone:
For AUCt of naloxone, on average, c "was an increase to 411% (90% CI: 152, 1112), 11518% (90% CI: 4259, 31149) and 10666% (90% CI: 3944, 28847) in subjects with mild, moderate and severe hepatic impairment, respectively, compared to healthy volunteers. For naloxone Cmax, on average, c "was an increase to 193% (90% CI: 115, 324), 5292% (90% CI: 3148, 8896) and 5252% (90% CI: 3124, 8830) in subjects with mild, moderate and severe hepatic impairment, respectively, compared to healthy volunteers. Due to insufficient amount of data available, the t½Z and corresponding AUCINF of naloxone were not calculated. Comparisons on the bioavailability of naloxone are therefore based on AUCt values.
Naloxone-3-glucuronide:
For AUCINF of naloxone-3-glucuronide, on average, c "was an increase to 157% (90% CI: 89, 279), 128% (90% CI: 72, 227) and 125% (90% CI: 71, 222) in subjects with mild, moderate and severe hepatic impairment, respectively, compared to healthy volunteers. For naloxone-3-glucuronide Cmax, on average, c "was an increase to 141% (90% CI: 100, 197), 118% (90% CI: 84, 166) and a decrease to 98% (90% CI: 70, 137) in subjects with mild, moderate and severe hepatic impairment, respectively, compared to healthy volunteers. For t½Z of naloxone-3-glucuronide, on average, c "was an increase to 117% (90% CI: 72, 161), a decrease to 77% (90% CI: 32, 121) and 94% ( 90% CI: 49, 139) in subjects with mild, moderate and severe hepatic impairment, respectively, compared to healthy volunteers.
Patients with impaired renal function
Oxycodone:
For AUCINF of oxycodone, on average, c "was an increase to 153% (90% CI: 130, 182), 166% (90% CI: 140, 196) and 224% (90% CI: 190, 266) in subjects with mild, moderate and severe renal impairment, respectively, compared to healthy volunteers. For oxycodone Cmax, on average, c "was an increase to 110% (90% CI: 94, 129), 135% (90% CI %: 115, 159) and 167% (90% CI: 142, 196) in subjects with mild, moderate and severe renal impairment, respectively, compared to healthy volunteers. For t½Z of oxycodone, on average, c "was an increase to 149%, 123% and 142% in subjects with mild, moderate and severe renal impairment, respectively, compared to healthy volunteers.
Naloxone:
For AUCt of naloxone, on average, c "was an increase to 2850% (90% CI: 369, 22042), 3910% (90% CI: 506, 30243) and 7612% (90% CI: 984, 58871) , in subjects with mild, moderate and severe renal impairment, respectively, compared to healthy volunteers. For naloxone Cmax, on average, c "was an increase to 1076% (90% CI: 154, 7502), 858% (CI 90%: 123, 5981) and 1675% (90% CI: 240, 11676), in subjects with mild, moderate and severe renal impairment, respectively, compared to healthy volunteers. Due to insufficient amount of data available, the t½Z values and the corresponding AUCINF value of naloxone were not calculated. Comparisons of bioavailability of naloxone are therefore based on AUCt values. The reports may have been influenced by the inability to fully characterize the plasma profiles of naloxone from healthy subjects.
Naloxone-3-glucuronide:
For AUCINF of naloxone-3-glucuronide, on average, c "was an increase to 220% (90% CI: 148, 327), 370% (90% CI: 249, 550) and 525% (90% CI: 354, 781) in subjects with mild, moderate and severe renal impairment, respectively, compared to healthy subjects. For naloxone-3-glucuronide Cmax, on average, c "was an increase to 148% (90% CI: 110, 197), 202% (90% CI: 151, 271) and 239% (90% CI: 179, 320) in subjects with mild, moderate and severe renal impairment, respectively, compared to healthy subjects. For the t½Z value of naloxone-3-glucuronide, on average, there was no significant change between renally impaired and healthy subjects.
Abuse
To avoid damage to the prolonged-release properties of the tablets, Targin tablets should not be broken, crushed or chewed as this leads to a rapid release of the active ingredients. Furthermore, naloxone, when administered intranasally, has a slower elimination rate. Both properties mean that abuse of Targin will not have the desired effect. In oxycodone-dependent rats, intravenous administration of oxycodone hydrochloride / naloxone hydrochloride in a ratio of 2: 1 produced withdrawal symptoms.
05.3 Preclinical safety data
There are no data from reproductive toxicity studies of the combination of oxycodone and naloxone.
Studies on the individual components showed that oxycodone had no effect on fertility and early embryonic development in male and female rats at doses up to 8 mg / kg body weight and did not cause malformations in rats at doses up to 8 mg / kg. and in rabbits at doses of 125 mg / kg per body weight. However, in rabbits, when single fetuses were used for statistical evaluation, an increase in dose-related developmental abnormalities (increased incidence of 27 pre-sacral vertebrae and supernumerary ribs) was observed.
When these parameters were statistically evaluated using litters, only the incidence of the 27 pre-sacral vertebrae was increased and only in the 125 mg / kg group, a dose level that produced severe pharmacotoxic effects in pregnant animals. In one pre- and post-natal development study in rats, at doses of 6 mg / kg / day F1 body weights were lower when compared to the body weight of the control group with doses that reduced maternal weight and food intake (NOAEL 2 mg / kg body weight).
There were no effects on physical, reflexological and sensory development parameters or on behavioral and reproductive indices. Standard reproductive toxicity studies with naloxone show that at high oral doses naloxone was not teratogenic and / or embryo-fetotoxic and did not affect pre / postnatal development.
At very high doses (800 mg / kg / day) naloxone caused "increased pup mortality" in the immediate postpartum period at dosages that produced significant toxicity in mother rats (eg, loss of body weight, seizures). However, in the surviving puppies, no developmental or behavioral effects were observed.
Long-term carcinogenicity studies have not been performed with oxycodone / naloxone in combination or with oxycodone as a single component. An oral carcinogenicity study in rats lasting 24 months was conducted with naloxone at doses up to 100 mg / kg / day. The results indicate that naloxone is not carcinogenic under these conditions.
Oxycodone and naloxone as single entities show clastogenic potential in in vitro tests. Similar effects were not observed, however, in in vivo tests, albeit at toxic doses. The results indicate that the mutagenic risk of Targin to humans at therapeutic concentrations can be ruled out with sufficient certainty.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Core of the tablet
Ethylcellulose,
Stearyl alcohol,
Lactose monohydrate,
Talc,
Magnesium stearate
(Targin 5 mg / 2.5 mg)
Hydroxypropylcellulose
(Targin 10 mg / 5 mg, 20 mg / 10 mg, 40 mg / 20 mg)
Povidone K30
Tablet coating:
Polyvinyl alcohol,
Titanium dioxide (E171),
Macrogol 3350,
Talc
(Targin 5 mg / 2.5 mg)
Brilliant blue FCF aluminum lake (E133)
(Targin 20/10 mg)
Red iron oxide (E172)
(Targin 40 mg / 20 mg)
Yellow iron oxide (E172))
06.2 Incompatibility
Not relevant.
06.3 Period of validity
Targin 5 mg / 2.5 mg 10 mg / 5 mg, 20 mg / 10 mg, 40 mg / 20 mg
3 years
06.4 Special precautions for storage
Do not store above 25 ° C.
Targin 5 mg / 2.5 mg
Store in the original packaging to protect from light.
06.5 Nature of the immediate packaging and contents of the package
Polyvinyl chloride blister / aluminum foil blister
10 prolonged-release tablets
14 prolonged-release tablets
20 prolonged-release tablets
28 prolonged-release tablets
30 prolonged-release tablets
50 prolonged-release tablets
56 prolonged-release tablets
60 prolonged-release tablets
98 prolonged-release tablets
100 prolonged-release tablets.
Hospital pack of 100 (10 x 10) prolonged-release tablets
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Any unused product or waste material should be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
MUNDIPHARMA PHARMACEUTICALS SRL - Via G. Serbelloni n ° 4, 20122 Milan, Italy
08.0 MARKETING AUTHORIZATION NUMBER
039586019 - "5 MG / 2,5 MG EXTENDED RELEASE TABLETS" 10 TABLETS IN PVC / AL BLISTER
039586021 - "5 MG / 2.5 MG EXTENDED RELEASE TABLETS" 14 TABLETS IN PVC / AL BLISTER
039586033 - "5 MG / 2,5 MG EXTENDED RELEASE TABLETS" 20 TABLETS IN PVC / AL BLISTER
039586045 - "5 MG / 2,5 MG EXTENDED RELEASE TABLETS" 28 TABLETS IN PVC / AL BLISTER
039586058 - "5 MG / 2.5 MG EXTENDED RELEASE TABLETS" 30 TABLETS IN PVC / AL BLISTER
039586060 - "5 MG / 2.5 MG EXTENDED RELEASE TABLETS" 50 TABLETS IN PVC / AL BLISTER
039586072 - "5 MG / 2.5 MG EXTENDED RELEASE TABLETS" 56 TABLETS IN PVC / AL BLISTER
039586084 - "5 MG / 2.5 MG EXTENDED RELEASE TABLETS" 60 TABLETS IN PVC / AL BLISTER
039586096 - "5 MG / 2.5 MG EXTENDED RELEASE TABLETS" 98 TABLETS IN PVC / AL BLISTER
039586108 - "5 MG / 2.5 MG EXTENDED RELEASE TABLETS" 100 TABLETS IN PVC / AL BLISTER
039586110 - "5 MG / 2.5 MG EXTENDED RELEASE TABLETS" 100 (10X10) TABLETS IN PVC BLISTER / IN HOSPITAL PACKAGING
039586122 - "10 MG / 5 MG EXTENDED RELEASE TABLETS" 10 TABLETS IN PVC / AL BLISTER
039586134 - "10 MG / 5 MG EXTENDED RELEASE TABLETS" 14 TABLETS IN PVC / AL BLISTER
039586146 - "10 MG / 5 MG EXTENDED RELEASE TABLETS" 20 TABLETS IN PVC / AL BLISTER
039586159 - "10 MG / 5 MG EXTENDED RELEASE TABLETS" 28 TABLETS IN PVC / AL BLISTER
039586161 - "10 MG / 5 MG EXTENDED RELEASE TABLETS" 30 TABLETS IN PVC / AL BLISTER
039586173 - "10 MG / 5 MG EXTENDED RELEASE TABLETS" 50 TABLETS IN PVC / AL BLISTER
039586185 - "10 MG / 5 MG EXTENDED RELEASE TABLETS" 56 TABLETS IN PVC / AL BLISTER
039586197 - "10 MG / 5 MG EXTENDED RELEASE TABLETS" 60 TABLETS IN PVC / AL BLISTER
039586209 - "10 MG / 5 MG EXTENDED RELEASE TABLETS" 98 TABLETS IN PVC / AL BLISTER
039586211 - "10 MG / 5 MG EXTENDED RELEASE TABLETS" 100 TABLETS IN PVC / AL BLISTER
039586223 - "10 MG / 5 MG EXTENDED RELEASE TABLETS" 100 (10X10) TABLETS IN PVC BLISTER / IN HOSPITAL PACKAGING
039586235 - "20 MG / 10 MG EXTENDED RELEASE TABLETS" 10 TABLETS IN PVC / AL BLISTER
039586247 - "20 MG / 10 MG EXTENDED RELEASE TABLETS" 14 TABLETS IN PVC / AL BLISTER
039586250 - "20 MG / 10 MG EXTENDED RELEASE TABLETS" 20 TABLETS IN PVC / AL BLISTER
039586262 - "20 MG / 10 MG PROLONGED RELEASE TABLETS" 28 TABLETS IN PVC / AL BLISTER
039586274 - "20 MG / 10 MG EXTENDED RELEASE TABLETS" 30 TABLETS IN PVC / AL BLISTER
039586286 - "20 MG / 10 MG EXTENDED RELEASE TABLETS" 50 TABLETS IN PVC / AL BLISTER
039586298 - "20 MG / 10 MG EXTENDED RELEASE TABLETS" 56 TABLETS IN PVC / AL BLISTER
039586300 - "20 MG / 10 MG EXTENDED RELEASE TABLETS" 60 TABLETS IN PVC / AL BLISTER
039586312 - "20 MG / 10 MG EXTENDED RELEASE TABLETS" 98 TABLETS IN PVC / AL BLISTER
039586324 - "20 MG / 10 MG EXTENDED RELEASE TABLETS" 100 TABLETS IN PVC / AL BLISTER
039586336 - "20 MG / 10 MG EXTENDED RELEASE TABLETS" 100 (10X10) TABLETS IN PVC BLISTER / IN HOSPITAL PACKAGE
039586348 - "40 MG / 20 MG EXTENDED RELEASE TABLETS" 10 TABLETS IN PVC / AL BLISTER
039586351 - "40 MG / 20 MG EXTENDED RELEASE TABLETS" 14 TABLETS IN PVC / AL BLISTER
039586363 - "40 MG / 20 MG EXTENDED RELEASE TABLETS" 20 TABLETS IN PVC / AL BLISTER
039586375 - "40 MG / 20 MG PROLONGED RELEASE TABLETS" 28 TABLETS IN PVC / AL BLISTER
039586387 - "40 MG / 20 MG EXTENDED RELEASE TABLETS" 30 TABLETS IN PVC / AL BLISTER
039586399 - "40 MG / 20 MG EXTENDED RELEASE TABLETS" 50 TABLETS IN PVC / AL BLISTER
039586401 - "40 MG / 20 MG PROLONGED RELEASE TABLETS" 56 TABLETS IN PVC / AL BLISTER
039586413 - "40 MG / 20 MG EXTENDED RELEASE TABLETS" 60 TABLETS IN PVC / AL BLISTER
039586425 - "40 MG / 20 MG EXTENDED RELEASE TABLETS" 98 TABLETS IN PVC / AL BLISTER
039586437 - "40 MG / 20 MG EXTENDED RELEASE TABLETS" 100 TABLETS IN PVC / AL BLISTER
039586449 - "40 MG / 20 MG EXTENDED RELEASE TABLETS" 100 (10X10) TABLETS IN PVC BLISTER / IN HOSPITAL PACKAGING
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
November 2010
10.0 DATE OF REVISION OF THE TEXT
November 2010
