Posology : מינונים

2 DOSAGE AND ADMINISTRATION

General Dosing Information
Morphine sulphate preservative-free Injection is intended for IV, epidural or intrathecal administration.
Rapid IV injection of most opioid analgesics has caused chest wall rigidity, anaphylactoid reactions, severe respiratory depression, hypotension, peripheral circulatory collapse, and cardiac arrest. It is recommended that when an opioid analgesic must be given intravenously, dosage should be reduced and a dilute solution should be injected slowly over a period of several minutes.
The patient usually should be lying down and should remain recumbent for a period of time to minimize side effects such as hypotension, dizziness, lightheadedness, nausea and vomiting. If these side effects occur in an ambulatory patient, they may be relieved if the patient lies down. An opioid antagonist and equipment for artificial ventilation should be available.

Epidural or intrathecal administration of opioid analgesics should be performed only by physicians experienced in these techniques. Solutions containing a preservative must not be injected via these routes. Resuscitative equipment and medications, including a specific antagonist (naloxone HCl injection) should be immediately available for management of respiratory depression or other complications that may arise from inadvertent intrathecal or intravascular administration. Also, facilities for adequate monitoring of the patient’s respiratory status must be available for 24 hours after each dose since delayed respiratory depression may occur (see Warnings and Precautions).

For epidural or intrathecal administration, injection into the lumbar area may be preferred because of the increased risk of respiratory depression with injection into the thoracic area. Also, the epidural route is preferred, whenever possible, because of the increased risk of respiratory depression with intrathecal administration (see Warnings and Precautions).

Prior to epidural administration, proper placement of the needle or catheter in the epidural space must be verified. Aspiration to check for blood or cerebrospinal fluid may be performed; however, the fact that intravascular administration is possible even when aspiration for blood is negative must be kept in mind.

Alternatively, administration of 5 ml (3 ml for obstetrical patients) of preservative-free 1.5% lidocaine hydrochloride with epinephrine 1:200,000 injection may be used to verify placement in the epidural space.
Tachycardia occurring after injection of the test medication indicates that the medication has entered the circulation; sudden onset of segmental anesthesia indicates that the medication has been administered intrathecally.


Following epidural or intrathecal injection of an opioid analgesic, administration of low doses of naloxone via continuous IV infusion for 24 hours may decrease the incidence of potential side effects without interfering with the analgesic effectiveness of the medication.

For the correct and effective use of morphine it is critical to adjust the dosing regimen for each patient individually according to the severity of pain, the patient’s metabolism and condition, previous history of analgesic therapy, concurrent medications and response to morphine. The following dosage recommendations are, therefore, only suggested approaches to what is actually a series of clinical decisions in the management of pain of an individual patient.

IV Dosage
Adults
For IV administration, the initial dose is 4-10 mg of morphine sulphate/70 kg injected slowly over 4-5 minutes in adults.

Children
IV doses of 0.05-0.1 mg/kg body weight have been injected slowly in children.

In patients with exceptionally severe pain or in those who are tolerant to the analgesic effect of opiate agonists, it may be necessary to exceed the usual dosage. Patients vary greatly in their analgesic requirements and titration to achieve the desired therapeutic effect while minimizing side effects should be emphasized.

In the immediate postoperative period following surgical procedures associated with severe pain e.g. abdominal surgery, it is often preferable to administer opioids on a regular time schedule (round-the-clock) rather than on an as-needed basis after pain recurs. This avoids a delay between the recurrence of pain and onset of analgesia, causing needless suffering an adverse medical consequences for the patient. (For morphine, the dosing schedule is often every 4 hours.) It may be acceptable late in the postoperative course to switch to an as-needed schedule, as the patient’s analgesic requirements diminish.

Epidural and Intrathecal Dosage
The usual initial epidural dose for injection in adults is 5 mg morphine sulphate preservative-free in the lumbar region, which may provide adequate pain relief for up to 24 hours. If adequate pain relief is not achieved within 1 hour after administration of the initial dose, additional epidural doses may be given carefully in 1 to 2 mg increments at intervals sufficient to assess efficacy, but generally no more than 10 mg total should be administered by epidural injection daily. Pain relief generally occurs within 15-60 minutes and persists for about 16-24 hours (range: 4-36 hours) after a single, effective epidural dose of morphine. For continuous epidural infusion when the device is not implanted surgically, an initial dosage of 2-4 mg per 24 hours has been recommended; epidural dosage may be increased by 1-2 mg daily if adequate relief is not achieved initially.

The intrathecal dosage of morphine sulphate is usually 1/10 that of the epidural dosage. A single 0.2 to 1 mg intrathecal dose may provide adequate relief for up to 24 hours in adults who are not tolerant to opiates.
(Caution: this is only 0.2 to 1 ml of the 1 mg/ml potency. Do not inject intrathecally more than 1 ml of the 1 mg/ml potency.) Use in the lumbar area only is recommended.

Repeated intrathecal doses of the drug are not recommended except to establish initial intrathecal dosage when continuous intrathecal infusion is contemplated; if additional morphine therapy is necessary for patients who are not candidates for continuous intrathecal infusion, alternative routes of administration should be considered.

In debilitated or geriatric patients, epidural or intrathecal administration should be undertaken only with extreme caution, using relatively small doses.

Safety and efficacy of epidural or intrathecal administration in children have not been determined, and usage in this population is not recommended.

Important Dosage and Administration Instructions
Safety and Handling Instructions:
Morphine Injections 1 mg/ml is supplied in sealed ampoules. Accidental dermal exposure should be treated by the removal of any contaminated clothing and rinsing the affected area with water.
Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use, if the solution is discolored in any other way, or if it contains a precipitate.
Morphine Injections 1 mg/ml is intended for single use only. Protect from light, discard any unused portion. Do not heat-sterilize.
Initial Dosage
The starting dose of Morphine Injections 1 mg/ml must be individualized.
Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see Warnings and Precautions (5.3)].
Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment experience and response, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.3)].
Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with Morphine Injections 1 mg/ml and adjust the dosage accordingly [see Warnings and Precautions (5.2)].

Discontinuation of Morphine Injections 1 mg/ml
When a patient who has been treated with a regimen of opioid analgesics including Morphine Injections 1 mg/ml regularly and may be physically dependent or no longer requires therapy with Morphine Injections 1 mg/ml, taper the dose gradually while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Do not abruptly discontinue Morphine Injections 1 mg/ml in a physically-dependent patient [see Warnings and Precautions (5.16), Drug Abuse and Dependence (9.3)].