Posology : מינונים

4.2   Posology and method of administration

For the correct and effective use of morphine it is critical to adjust the dosing regimen for each patient individually. The following dosage recommendations are, therefore, only suggested approaches to what is actually a series of clinical decisions in the management of the pain of an individual patient.
The dosage of morphine is individualized according to the severity of the pain, the patient's age and metabolism, previous history of analgesic therapy, and response to morphine.
The correct dosage for any individual patient is that which is sufficient to control pain with no, or tolerable, side effects for a full 12 hours.
MCR should be taken on a regular 12-hourly schedule, at the minimum dose required to achieve acceptable analgesia. For patients who experience end-of-dosing failure, an 8-hourly schedule may be employed.
MCR tablets should be swallowed whole and not chewed, crushed, dissolved or broken. Taking broken, chewed or crushed tablets could lead to the release of a toxic dose of morphine.
The MCR formulation is designed to embody release characteristics appropriate to a 12-hour dosing interval. In adjusting dosing requirements, it is recommended that the dosing interval never be extended beyond 12 hours, because the administration of inappropriately-large single doses may lead to acute overdosage.

It is recommended that patients receiving MCR be supplied with a concurrent prescription for immediate-release morphine, which is then readily available to the patient if breakthrough pain is experienced.
Initial Dose and Titration
In opioid-naive patients, for ease of titration, it is recommended that the initial daily dosage of morphine be established using morphine immediate-release tablets (MIR) using a 4-hourly schedule. The total daily dose should then be divided into two and administered as MCR tablets 12-hourly.
Because of the difficulty of titrating MCR, opioid-naive patients who are started directly on MCR therapy should initially receive a conservative dose of 10-20 mg, 12-hourly, in order to avoid overdosage. The majority of patients will then require an upward titration.
Most patients are controlled on 30-100 mg of MCR 12-hourly. However, smaller doses such as 10 mg 12-hourly may be adequate in some patients, while higher doses may be needed in others. As there is no upper limit to the amount of morphine that may be given in intractable oncologic pain, the quantity administered should be that which produces adequate analgesia.
During the course of treatment the patient may experience breakthrough pain due to an increase in the level of pain or the development of tolerance to the drug. If this breakthrough pain occurs often, an increase in the dosage may be required. If other measures to relieve pain (e.g., nerve blocks) are employed, the morphine dosage should be reduced to an appropriate level.
Conversion from other Opioid Analgesics
Patients who have previously received other opioids to control their pain may be started directly on MCR therapy using the conversion table below:

Oral                      Parenteral morphine                                     1                        3 methadone                                   1.5                       3 pethidine                                   0.1                       0.4 pentazocine                                  0.17                     0.5 codeine                                      0.15 oxycodone                                    1 buprenorphine                               35 nalbuphine                                                            3 1    Calculate the total daily dosage of each opioid (mg)
2     Multiply by the conversion factor shown (this gives the daily total in oral morphine equivalents)
3     Divide by two and administer MCR tablets 12-hourly
4     If the patient is receiving more than one opioid, the morphine equivalents of each opioid should be summed to give the total daily dosage of morphine.


The conversion table is only meant to serve as a guide. In all circumstances, the patient's response following conversion from other opioids must be carefully monitored and the dosage of MCR adjusted accordingly. To reduce the dangers of overdosage the conversion factors have been estimated conservatively for use in one direction - from other opioids to MCR. For this reason the table should not be used where the intention is to convert from MCR to other drugs. The conservative nature of the factors presented means that it is likely that further upward titration may be necessary.


Conversion between MCR and MIR
When converting between these forms, the total daily dosage of morphine should remain the same.


Therefore, when changing from MCR to MIR, the total daily dosage of MCR should be divided into 6 daily doses of MIR.
When changing from MIR to MCR, the total daily dosage of MIR should be divided into two and administered as MCR 12-hourly.


Conversion from Parenteral Morphine to MCR
A 1:3 ratio of parenteral to oral morphine equivalence is suggested. This ratio is conservative and may underestimate the amount of morphine required. If this is the case, the dose of MCR can be gradually increased to achieve acceptable analgesia.


Children:
For children with severe cancer pain, a starting dose in the range of 0.2 to 0.8 mg morphine per kg body weight 12 hourly is recommended. Doses should then be titrated as for adults. Since the controlled release tablets must be swallowed whole, and not broken, chewed, dissolved or crushed, only children who are able to swallow the tables in whole, can use MCR tables.


Post-operative pain:
MCR tablets are not recommended in the first 24 hours post-operatively or until normal bowel function has returned; thereafter it is suggested that the following dosage schedule be observed at the physician's discretion:
1. MCR 10 tablets (1-2 tablets) 12 hourly to patients under 70 kg.
2. MCR 30 tablets 12 hourly to patients over 70 kg.
3. Elderly - a reduction in dosage may be advisable in the elderly.
4. Children - not recommended.


Supplemental parenteral morphine may be given if required but with careful attention to the total dosages of morphine, and bearing in mind the prolonged effects of morphine in this controlled release formulation.