TARGIN Prolonged-release tablet Ref.[50686] Active ingredients: Naloxone Oxycodone Oxycodone and Naloxone

Posology

The analgesic efficacy of Targin is equivalent to oxycodone hydrochloride prolonged-release formulations.

The dosage should be adjusted to the intensity of pain and the sensitivity of the individual patient. Unless otherwise prescribed, these tablets should be administered as follows:

Adults

The usual starting dose for an opioid naïve patient is 10 mg/5 mg of oxycodone hydrochloride/naloxone hydrochloride at 12 hourly intervals.

Lower strengths are available to facilitate dose titration when initiating opioid therapy and for individual dose adjustment.

Patients already receiving opioids may be started on higher doses depending on their previous opioid experience.

The maximum daily dose of these tablets is 160 mg oxycodone hydrochloride and 80 mg naloxone hydrochloride. The maximum daily dose is reserved for patients who have previously been maintained on a stable daily dose and who have become in need of an increased dose. Special attention should be given to patients with compromised renal function and patients with mild hepatic impairment if an increased dose is considered. For patients requiring higher doses, administration of supplemental prolonged-release oxycodone hydrochloride at the same time intervals should be considered, taking into account the maximum daily dose of 400 mg prolonged-release oxycodone hydrochloride. In the case of supplemental oxycodone hydrochloride dosing, the beneficial effect of naloxone hydrochloride on bowel function may be impaired.

After complete discontinuation of therapy with these tablets with a subsequent switch to another opioid a worsening of the bowel function can be expected.

Some patients taking these prolonged-release tablets according to a regular time schedule require immediate-release analgesics as rescue medication for breakthrough pain Targin is aprolonged-release formulation and therefore not intended for the treatment of breakthrough pain. For the treatment of breakthrough pain, a single dose of “rescue medication” should approximate one sixth of the equivalent daily dose of oxycodone hydrochloride. The need for more than two “rescues” per day is usually an indication that the dosage requires upward adjustment. This adjustment should be made every 1-2 days in steps of 5 mg/2.5 mg twice daily, or where necessary 2.5 mg/1.25 mg or 10 mg/5 mg oxycodone hydrochloride/ naloxone hydrochloride until a stable dose is reached. The aim is to establish a patient-specific twice daily dose that will maintain adequate analgesia and make use of as little rescue medication as possible for as long as pain therapy is necessary. Slightly elevated (dose corrected) peak plasma concentrations should be taken into account when the 2.5mg/1.25 mg tablet is used (see section 5.2).

Targin is taken at the determined dosage twice daily according to a fixed time schedule. While symmetric administration (the same dose mornings and evenings) subject to a fixed time schedule (every 12 hours) is appropriate for the majority of patients, some patients, depending on the individual pain situation, may benefit from asymmetric dosing tailored to their pain pattern. In general, the lowest effective analgesic dose should be selected.

In non-malignant pain therapy, daily doses of up to 40 mg/20 mg oxycodone hydrochloride/naloxone hydrochloride are usually sufficient, but higher doses may be needed.

For doses not realisable/practicable with this strength other strengths of this medicinal product are available.

Elderly patients

As for younger adults the dosage should be adjusted to the intensity of the pain and the sensitivity of the individual patient.

Patients with impaired hepatic function

A clinical trial has shown that plasma concentrations of both oxycodone and naloxone are elevated in patients with hepatic impairment. Naloxone concentrations were affected to a higher degree than oxycodone (see section 5.2). The clinical relevance of a relative high naloxone exposure in hepatic impaired patients is yet not known. Caution must be exercised when administering these tablets to patients with mild hepatic impairment (see section 4.4). In patients with moderate and severe hepatic impairment Targin is contraindicated (see section 4.3).

Patients with impaired renal function

A clinical trial has shown that plasma concentrations of both oxycodone and naloxone are elevated in patients with renal impairment (see section 5.2). Naloxone concentrations were affected to a higher degree than oxycodone. The clinical relevance of a relative high naloxone exposure in renal impaired patients is yet not known. Caution should be exercised when administering these tablets to patients with renal impairment (see section 4.4).

Paediatric population

The safety and efficacy of Targin in children aged below 18 years has not been established. No data are available

Duration of use

These tablets should not be administered for longer than absolutely necessary. If long-term pain treatment is necessary in view the nature and severity of the illness, careful and regular monitoring is required to establish whether and to what extent further treatment is necessary. When the patient no longer requires opioid therapy, it may be advisable to taper the dose gradually (see section 4.4).

Method of administration

Oral use.

These prolonged-release tablets are taken in the determined dosage twice daily in a fixed time schedule.

The prolonged-release tablets may be taken with or without food with sufficient liquid. These tablets must be swallowed whole, and not broken, chewed or crushed (see section 4.4).

Symptoms of intoxication

Depending on the history of the patient, an overdose of Targin may be manifested by symptoms that are either triggered by oxycodone (opioid receptor agonist) or by naloxone (opioid receptor antagonist).

Symptoms of oxycodone overdose include miosis, respiratory depression, somnolence progressing to stupor, skeletal muscle flaccidity, bradycardia as well as hypotension. Coma, non-cardiogenic pulmonary oedema and circulatory failure may occur in more severe cases and may lead to a fatal outcome.

Symptoms of a naloxone overdose alone are unlikely.

Therapy of intoxication

Withdrawal symptoms due to an overdose of naloxone should be treated symptomatically in a closely-supervised environment.

Clinical symptoms suggestive of an oxycodone overdose may be treated by 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 necessary. It is also possible to apply an infusion of 2 mg naloxone hydrochloride in 500 ml of 0.9% sodium chloride or 5% dextrose (0.004 mg/ml naloxone). The infusion should be run at a rate aligned to the previously administered bolus doses and to the patient’s response.

Consideration may be given to gastric lavage.

Supportive measures (artificial ventilation, oxygen, vasopressors and fluid infusions) should be employed, as necessary, to manage the circulatory shock accompanying an overdose. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation. Artificial ventilation should be applied if necessary. Fluid and electrolyte metabolism should be maintained.

3 years.

Do not store above 25°C.

Child resistant PVC/aluminium foil blisters:

Pack sizes: 10, 14, 20, 28, 30, 50, 56, 60, 98 or 100 tablets.

Hospital pack: 100 (10 × 10) tablets.

HDPE bottles with a child-resistant PP closure:

Pack size: 100 tablets

Not all pack sizes and container types may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.