TARGIN® Prolonged Release Tablets 10mg/5mg

Therapeutic indications

The management of moderate to severe chronic pain unresponsive to non-opioid analgesics.

The opioid antagonist naloxone is added to counteract opioid-induced constipation by blocking the action of oxycodone at opioid receptors locally in the gut.

Contraindications

• Hypersensitivity to the active substances or to any of the excipients,
• Any situation where opioids are contraindicated,
• Severe respiratory depression with hypoxia and/or hypercapnoea,
• Severe chronic obstructive pulmonary disease,
• Cor pulmonale,
• Severe bronchial asthma,
• Non-opioid induced paralytic ileus,
• Moderate to severe hepatic impairment.

Posology and method of administration

Posology

Analgesia

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, Targin ® 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 of Targin ® depending on their previous opioid experience.

Targin ® 5 mg/2.5 mg is intended for dose titration when initiating opioid therapy and individual dose adjustment.

The maximum daily dose of Targin ® 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 of Targin® 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 of Targin ®, 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 Targin ® with a subsequent switch to another opioid a worsening of the bowel function can be expected.

Some patients taking Targin ® according to a regular time schedule require immediate-release analgesics as "rescue" medication for breakthrough pain. Targin ® is a prolonged-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 dose of Targin ® 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 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.

A single dose of Targin® greater than 40mg/20mg or a total daily dose greater than 80mg/40mg is only for use in patients in whom tolerance to an opioid of comparable potency has been established. Patients considered opioid tolerant are those receiving, for one week or longer, at least 60mg oral morphine/day, 25mcg transdermal fentanyl/hour, 30mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25mg oral oxymorphone/day, or an equianalgesic dose of another opioid.

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 (refer to Pharmacokinetic Properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). The clinical relevance of a relative high naloxone exposure in hepatic impaired patients is yet not known. Caution must be exercised when administering Targin ® to patients with mild hepatic impairment (refer to Special Warnings and Precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). In patients with moderate and severe hepatic impairment Targin ® is contraindicated (refer to Contraindications).

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 (refer to Pharmacokinetic Properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). 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 Targin ® to patients with renal impairment (refer to Special Warnings and Precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Paediatric population

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

Method of administration

Oral use.

Targin ® is 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. Targin ® must be swallowed whole, and not broken or chewed or crushed.

Duration of use

Targin ® should not be administered for longer than absolutely necessary. If long-term pain treatment is necessary in view of the nature and severity of the illness, careful and regular monitoring is required to establish whether and to what extent further treatment is necessary.

Analgesia

When the patient no longer requires opioid therapy, it may be advisable to taper the dose gradually (refer to Special Warnings and Precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).