JURNISTA Prolonged-release tablet Ref.[50341] Active ingredients: Hydromorphone

Posology

As with other opioid analgesics, safe and effective administration of JURNISTA to patients with pain depends upon a comprehensive assessment of the patient. The nature of the pain as well as the concurrent medical status of the patient will affect selection of the dose. Owing to the varied response observed to opioids between individuals, it is recommended that all patients be started at a conservative dose of opioid therapy and titrated to an adequate level of analgesia, balanced with an acceptable level of adverse reaction(s).

As with any strong opioid, appropriate prophylaxis for known adverse reactions (for example constipation) should be considered.

JURNISTA should not be taken more than once every 24 hours.

Patients currently not routinely receiving opioids

Initiation of therapy: The starting dose of JURNISTA in most patients should be 8 mg administered once every 24 hours and should not exceed 8 mg. Some patients may benefit from an initial titration dose of 4 mg administered once every 24 hours to improve tolerability.

Titration and Maintenance: After initiation of therapy, dose adjustments may be necessary to obtain the patient’s best balance between pain relief and undesirable effects. The dose may be titrated upwards, if required in increments of either 4 or 8 mg depending on response and supplementary analgesic requirements. Note the dosage should not be titrated more frequently than every fourth dose (for example, if the first dose is given on a Monday, the dosage could be increased no earlier than the fourth dose, on Thursday) (see Individualisation of dosage and maintenance of therapy for further information).

Because it may be more time consuming to titrate a patient to adequate analgesia using a controlled release opioid preparation, it may be advisable to begin treatment with conventional immediate release preparations (e.g. immediate release hydromorphone or immediate release morphine) and then convert to the appropriate total daily dose of JURNISTA. For conversion please use the conversion table.

Patients currently receiving opioids regularly

In patients currently taking opioid analgesics, the starting dose of JURNISTA should be based on the prior daily opioid dose, using standard equianalgesic ratios. For opioids other than morphine, first the equivalent total daily dose of morphine should be estimated, then the table below should be used to determine the equivalent total daily dose of JURNISTA.

Conversion Table: Multiplication Factors for Converting the Daily Dose of Prior Opioids to the Daily Dose of JURNISTA (mg/day Prior Opioid x Factor = mg/day JURNISTA):

No fixed conversion ratio is likely to be satisfactory in all patients, due to individual patient and formulation differences. Therefore, conversion to the recommended starting dose of JURNISTA followed by close patient monitoring and titration is advised.

Dosages should be rounded down to the closest dose of JURNISTA available in 4 mg increments (4, 8, 16, 32, 64 mg tablets), as clinically indicated.

All other around-the-clock opioid analgesic medicinal products should be discontinued when JURNISTA therapy is initiated.

JURNISTA can also be safely used with usual doses of non-opioid analgesics and analgesic adjuvants.

Supplemental analgesia

In addition to once-daily JURNISTA therapy, supplemental breakthrough pain medication in the form of immediate release preparations (eg immediate release hydromorphone or immediate release morphine) could be made available to all patients with chronic pain. For conversion the conversion table should be used. Individual supplemental doses of immediate release hydromorphone or immediate release morphine should generally not exceed 10% to 25% of the 24 hour JURNISTA dose (see table below).

Recommended Starting Dose for Supplemental Rescue Medication:

Individualisation of dosage and maintenance of therapy

After initiation of therapy with JURNISTA, dose adjustments may be necessary to obtain the patient’s best balance between pain relief and opioid-related undesirable effects.

If the pain increases in severity or analgesia is inadequate, a gradual increase in dosage may be required. In order to allow the effects of the dose change to stabilise, the dosage should be increased no more frequently than every fourth dose (for example, if the first dose is given on a Monday, the dosage could be increased no earlier than the fourth dose, on Thursday). As a guideline, dosage increases of 25%-100% of the current daily dose of JURNISTA should be considered for each titration step.

Once patients become stable on once-daily JURNISTA therapy, the dose may be continued for as long as pain relief is necessary. The continued need for around-the-clock opioid therapy and adjustments in therapy should be reassessed periodically as appropriate.

Missed dose

If the patient did not take the regularly scheduled dose of JURNISTA, the patient should be instructed to take the next dose immediately and start a new 24-hour regimen.

Cessation of therapy

In patients who are physically dependent on opioids and receiving daily administration of hydromorphone, abrupt discontinuation of treatment with JURNISTA will result in abstinence (“withdrawal”) syndrome. If cessation of therapy with JURNISTA is indicated, patients should therefore have their JURNISTA dose reduced by 50% every 2 days until the lowest possible dose is reached, at which time therapy may be safely discontinued. If signs of withdrawal appear, tapering should be stopped. The dose should be slightly increased until the signs and symptoms of opioid withdrawal disappear. Tapering should then begin again but with longer periods of time between each hydromorphone dose reduction, or before converting to an equianalgesic dose of another opioid to continue tapering.

Use in the elderly

The medical status of the elderly patient is often complex. Therefore, the treatment with hydromorphone should be initiated cautiously, and the initial dose should be reduced (see section 5.2).

Renal impairment

Following single-dose administration of hydromorphone immediate-release tablets, the following results were observed in clinical studies:

• In patients with moderate renal insufficiency (creatinine clearance of 40-60 ml/min), exposure (plasma AUC) to hydromorphone was approximately 2-times higher than in those with normal renal function and elimination half-life was unaltered.
• In patients with severe renal insufficiency (creatinine clearance <30 ml/min), exposure (plasma AUC) to hydromorphone was approximately 4-times greater than in those with normal renal function and elimination half-life 3-times longer.

Therefore, patients with moderate renal insufficiency should be started on a reduced dose and closely monitored during dose titration. In patients with severe renal insufficiency an increased dosing interval should also be considered and these patients should in addition be monitored during maintenance therapy.

Hepatic impairment

Following single-dose administration of hydromorphone immediate-release tablets, the following results were observed in clinical studies:

• In patients with moderate hepatic insufficiency (scoring 7-9 on Child-Pugh rating scale) both exposure (plasma AUC) and peak plasma concentrations of hydromorphone were approximately 4-times higher compared with healthy controls and elimination half-life was unaltered.

Therefore, patients with moderate hepatic insufficiency should be started on a reduced dose and closely monitored during dose titration.

Paediatric population

The safety and efficacy of JURNISTA in children and adolescents below 18 years of age have not been established. No data are available. JURNISTA is not recommended for use in this population.

Method of administration

Patients should be instructed to swallow the JURNISTA tablet whole with a glass of water, at approximately the same time each day, and never to chew, divide, or crush it. JURNISTA may be taken with or without food (see section 5.2).

JURNISTA overdose is characterized by respiratory depression, drowsiness which progresses to stupor and coma, musculoskeletal flaccidity, cold skin, contracted pupils and, at times, tachycardia and hypotension. In cases of severe overdose, apnea, circulatory collapse, cardiac arrest and death may occur.

In the treatment of overdose, primary attention should be given to the reestablishment of adequate respiratory exchange keeping the airway open and instituting assisted or controlled ventilation. Supportive measures (including oxygen and vasopressors) should be used to manage the shock and pulmonary oedema which potentially accompany overdose. Cardiac arrest and arrhythmias may require cardiac massage or defibrillation.

In cases of severe overdose, specific antidotes such as naloxone and nalmefene should be used to manage respiratory depression (see the prescribing information for the specific opioid antagonist for details of proper use). The effect of naloxone is relatively short. Therefore, the patient should be carefully monitored until respiration has stabilised. JURNISTA will release hydromorphone for approximately 24 hours. This should be taken into account in determining the treatment. Opioid antagonists should not be given in the absence of clinically significant respiratory depression, or circulatory depression because of opioids. Opioid antagonists should be administered with caution to patients suspected to be physically dependent on hydromorphone, since rapid reversal of an opioid, including hydromorphone, may precipitate symptoms of withdrawal.

2 years.

Do not store above 25°C.

PVC/Aclar aluminium blisters.

Pack sizes of 7, 10, 14, 20, 28, 30, 35, 40, 50, 56, 60, 100 tablets.

Not all pack sizes may be marketed.

No special requirements.