Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use
Repeated use can cause tolerance and dependence. Caution in use should be exercised and a reduction in dose may be advisable in the elderly and in the following cases:

•          Hypotension
•          Hypothyroidism
•          Depressed respiratory reserve
•          Prostatic hypertrophy
•          Hepatic or renal impairment (avoid or reduce dose)
•          Convulsive disorders
•          Asthma (avoid during attack)
•          Adrenocortical insufficiency
•          Urethral stricture
•          Inflammatory or obstructive bowel disorders 
Opioids such as morphine should either be avoided in patients with biliary disorders or they should be given with an antispasmodic.
Morphine can cause an increase in intrabiliary pressure as a result of effects on the sphincter of Oddi. Therefore, in patients with biliary tract disorders morphine may exacerbate pain (use in biliary colic is a contraindication, see 4.3).
In patients given morphine after cholecystectomy, biliary pain has been induced. Abrupt withdrawal from persons physically dependent on them precipitates a withdrawal syndrome, the severity of which depends on the individual, the drug used, the size and frequency of the dose and the duration of drug use. Great caution should be exercised in patients with a known tendency or history of drug abuse.
Palliative care - in the control of pain in terminal illness, these conditions should not necessarily be a deterrent to use.
Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs:
Concomitant use of Morphine Sulfate 1mg/ml Solution for Injection 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 Morphine Sulfate 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).
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.
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.
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
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.
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.
Dependence and withdrawal (abstinence) syndrome

Use of opioid analgesics may be associated with the development of physical and/or psychological dependence or tolerance. The risk increases with the time the drug is used, and with higher doses.
Symptoms can be minimised with adjustments of dose or dosage form, and gradual withdrawal of morphine. For individual symptoms, see section 4.8.
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.

Morphine Martindale contains sodium
Morphine Martindale 10 mg/ml
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

Morphine Martindale 20 mg/ml
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

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

Effects on Driving

4.7   Effects on ability to drive and use machines
Morphine causes drowsiness so patients should avoid driving or operating machinery.
This medicine can impair cognitive function and can affect a patient’s ability to drive safely. When prescribing this medicine, patients should be told:
•   The medicine is likely to affect your ability to drive •   Do not drive until you know how the medicine affects you