Special Warning : אזהרת שימוש

4.3   Special warnings and precautions for use
Especially careful monitoring by the physician and possibly dose reduction is needed in case of: - opioid dependence
- disturbances of consciousness
- conditions associated with a disturbance of the respiratory centre and of the respiratory function or where such disturbances must be avoided
- cor pulmonale
- conditions with increased intracranial pressure unless ventilation is performed - hypotension in the setting of hypovolaemia
- prostatic hyperplasia with residual urine (risk of bladder rupture due to urinary retention)
- obstruction or spasms of urinary tracts
- diseases of biliary ducts
- obstructive and inflammatory bowel diseases
- phaeochromocytoma
- pancreatitis
- hypothyroidism
-   epilepsia or increased propensity to seizures.

In case of an opioid overdose respiratory depression is the most important risk.
The use of morphine can be associated with physical dependence. Discontinuation after repeated use or application of an opioid antagonist can provoke typical signs of withdrawal (withdrawal syndrome).

Opioid Use Disorder (abuse and dependence) and withdrawal (abstinence) syndrome Tolerance and physical and/or psychological dependence may develop upon repeated administration of opioids such as Oramorph 20 mg/ml.
Repeated use of Oramorph 20 mg/ml can lead to Opioid Use Disorder (OUD). A higher dose and longer duration of opioid treatment, can increase the risk of developing OUD. Abuse or intentional misuse of Oramorph 20 mg/ml may result in overdose and/or death. The risk of developing OUD is increased in patients with a personal or a family history (parents or siblings) of substance use disorders (including alcohol use disorder), in current tobacco users or in patients with a personal history of other mental health disorders (eg. major depression, anxiety and personality disorders).
Before initiating treatment with Oramorph 20 mg/ml and during the treatment, treatment goals and a discontinuation plan should be agreed with the patient (see section 4.2). Before and during treatment the patient should also be informed about the risks and signs of OUD. If these signs occur, patients should be advised to contact their physician.
Patients will require monitoring for signs of drug-seeking behavior (e.g. too early requests for refills). This includes the review of concomitant opioids and psycho-active drugs (like benzodiazepines). For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered.
Symptoms can be minimised with adjustments of dose or dosage form, and gradual withdrawal of morphine. For individual symptoms, see section 4.8

Therapeutic administration in patients with chronic pain is associated with a markedly reduced risk of psychological dependence and has to be assessed in a different light.

Morphine has an abuse potential similar to other strong agonist opioids, and should be used with particular caution in patients with a history of alcohol or drug abuse.

Compared to patients not undergoing surgery the use of Oramorph® 20 mg/ml is associated with an increased risk of ileus or respiratory depression during the postoperative phase and should therefore be administered with caution in patients before and after surgery.

Due to the analgesic effect of morphine serious intraabdominal complications such as bowel perforation can be masked.

Adrenal insufficiency
Opioid analgesics may cause reversible adrenal insufficiency requiring monitoring and glucocorticoid replacement therapy. Symptoms of adrenal insufficiency may include e.g. nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or low blood pressure.

In case of pre-existing adrenocortical insufficiency (e.g. Morbus Addison) plasma concentrations of cortisol should be monitored and possibly corticoids should be substituted.

Acute chest syndrome (ACS) in patients with sickle cell disease (SCD) Due to a possible association between ACS and morphine use in SCD patients treated with morphine during a vaso-occlusive crisis, close monitoring for ACS symptoms is warranted.

Oramorph® 20 mg/ml must not be used in children under 3 years of age.

Decreased Sex Hormones and increased prolactin
Long-term use of opioid analgesics may be associated with decreased sex hormone levels and increased prolactin. Symptoms include decreased libido, impotence or amenorrhea. Due to its mutagenic properties, morphine should be given to males with procreative potential and to females with childbearing potential only if effective contraceptive measures are guaranteed (see section 4.6).

Hyperalgesia that does not respond to a further dose increase of morphine may occur in particular in high doses. A morphine dose reduction or change in opioid may be required.

Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs Concomitant use of Oramorph® 20 mg/ml and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death.
Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Oramorph® 20 mg/ml concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.
The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5).

Sleep-related breathing disorders
Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage.

Severe cutaneous adverse reactions (SCARs)
Acute generalized exanthematous pustulosis (AGEP), which can be life-threatening or fatal, has been reported in association with morphine treatment. Most of these reactions occurred within the first 10 days of treatment. Patients should be informed about the signs and symptoms of AGEP and advised to seek medical care if they experience such symptoms.
If signs and symptoms suggestive of these skin reactions appear, morphine should be withdrawn and an alternative treatment considered.

Hepatobiliary disorders
Morphine may cause dysfunction and spasm of the sphincter of Oddi, thus raising intrabiliary pressure and increasing the risk of biliary tract symptoms and pancreatitis.


Plasma concentrations of morphine may be reduced by rifampicin. The analgesic effect of morphine should be monitored and doses of morphine adjusted during and after treatment with rifampicin.

Within the first day of concomitant P2Y12 inhibitor and morphine treatment, reduced efficacy of P2Y12 inhibitor treatment has been observed (see section 4.5).

The use of Oramorph® 20 mg/ml can lead to positive results of doping tests.





Effects on Driving

4.7   Effects on ability to drive and use machines
Morphine can impair the attentiveness and the capability to react to such an extent that the ability to drive or to use machines is impaired or inexistent.
This is to be expected especially upon initiation of treatment, dose increase and change in medication as well as in combination with alcohol or the use of sedatives.
The assessment of the individual situation in each case has to be done by the treating physician.
During a stable therapeutic regimen driving is not prohibited generally.