Special Warning : אזהרת שימוש

Warnings
Drug Dependence
Hydromorphone, like all opioid analgesics, may cause physical dependence whereby the body adapts itself to the drug. This involves physiological changes which explain two phenomena frequently seen with long-term opioid treatment: tolerance and the withdrawal syndrome.

Tolerance is defined as the need to administer a higher dose of the opioid to maintain the same level of analgesia. For most patients, the first indication of tolerance is a decrease in the duration of analgesia for a given dose and the appearance of breakthrough pain.
Tolerance may be confused with an increase in the pain intensity of the disease itself (which is the most common reason an increase in dosage is indicated). Irrespective of the underlying cause, it is recommended that the dose be increased and the patient re-titrated until the pain is again controlled.

Withdrawal symptoms, sometimes called the opioid abstinence syndrome, are those manifested by a patient upon cessation of treatment or rapid reduction of dosage.

If a reduction in dosage is required, the opioid abstinence syndrome can usually be avoided by gradually decreasing the dosage in the following fashion. Half the prior daily dosage should be given for the first 2 days. This should be reduced by 25% every 2 days thereafter, until the total dosage is 30 mg/day in oral morphine equivalents. The drug may be discontinued after 2 days at this dosage level.

Physical dependence does not imply psychological dependence. Psychological dependence is a pattern of compulsive drug use characterized by a craving for an opioid and the need to use the opioid for effects other than pain relief. This type of dependence is extremely rare in patients taking opioids for the relief of severe pain. This must not be confused with the behavior of patients whose pain is inadequately treated, who will also manifest drug-seeking behavior. For these patients titration to pain-controlling dosage is required.

Head Injury
Because of the tendency of hydromorphone to produce respiratory depression and its capacity to elevate cerebrospinal fluid pressure, it should be used with extreme caution, if at all, in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure since both of these adverse reactions may be markedly exaggerated.
Opioid agonists like hydromorphone may interfere with evaluation of CNS functions, especially relative to consciousness levels, pupillary changes, and respiratory depression, thereby masking the clinical course of patients with head injuries. In such cases, hydromorphone must be used with extreme caution and only when it is absolutely essential.


Paralytic Ileus
Palladone SR capsules should not be used where there is the possibility of paralytic ileus occurring. Should paralytic ileus be suspected or occur during use, Palladone SR capsules should be discontinued immediately.

Cordotomy
Patients about to undergo cordotomy or other pain-relieving surgical procedures should be transferred to immediate release hydromorphone prior to surgery. If further treatment with Palladone SR capsules is indicated then the dosage should be adjusted to the new post- operative requirement.

Asthma and other Respiratory Conditions
Hydromorphone should be used with extreme caution, if at all, in patients with acute asthma, chronic obstructive pulmonary disease or cor-pulmonale, a decreased respiratory reserve (as in emphysema, kyphoscoliosis or severe obesity), hypoxia or hypercapnia.
Even therapeutic doses of opioids may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea.

Cardiovascular Effects
Opioids may produce orthostatic hypotension in ambulatory patients. Opioids may also cause severe hypotension in individuals whose ability to maintain their blood pressure has already been compromised by depleted blood volume or concurrent administration of other drugs such as phenothiazines or certain anesthetics.

Use in Pregnancy and Labor
Hydromorphone crosses the placental barrier. Because of possible adverse effects on fetal development, hydromorphone is not recommended for use during pregnancy. Use during labor is not recommended (see Contraindications). It may lead to respiratory depression, especially in the premature neonate.

Use in Breastfeeding
It is not known whether hydromorphone is excreted in human milk. However, because many drugs are excreted in human milk and because of the potential for adverse effects in infants, nursing should be discontinued if hydromorphone is absolutely indicated.

Use in Pediatrics
Hydromorphone is not recommended for use in children under 12 years.

Use in the Elderly
Hydromorphone should be used with caution in the elderly. The elderly may require a lower dosage than adults to achieve adequate analgesia. Some elderly patients may be sensitive to the respiratory depressant effect of hydromorphone and should be monitored closely during therapy initiation and any subsequent dosage increase.

Adverse Reactions

The most serious adverse reactions to hydromorphone are respiratory depression and, to a lesser degree, circulatory depression, respiratory arrest, shock and cardiac arrest.
The most frequent adverse reactions include lightheadedness, dizziness, miosis, drowsiness, sedation, constipation, nausea, vomiting and sweating. Other adverse reactions include mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, euphoria, confusion, dysphoria, psychic dependence, mood changes, weakness, dry mouth, biliary tract spasm, ureteral spasm, spasm of vesical sphincters and urinary retention, hesitancy oliguria, decreased libido, pruritus and urticaria.
In some individuals, hydromorphone may cause less constipation or emesis than morphine preparations. When nausea and vomiting or constipation are troublesome, Palladone SR capsules can be readily combined with anti-emetics or laxatives.

Precautions
Use with caution in patients with Addison’s disease, cardiac arrhythmia, cardiovascular disease, cerebral arteriosclerosis, history of drug abuse or dependence, ulcerative colitis, gall bladder and hepato-renal impairment, prostatic hypertrophy, urethral stricture, respiratory disease, hypothyroidism, convulsive disorders, and acute alcoholism. The administration of opioids may obscure the diagnosis or clinical course of patients with acute abdominal conditions.

Palladone SR capsules are not recommended in the first 24 hours post-operatively. After this time, they should be used with caution particularly following abdominal surgery.
Opioid agonist-induced increase in intraluminal pressure may endanger surgical anastomosis.

Persons who perform potentially hazardous tasks requiring mental alertness and/or physical coordination should be warned about possible CNS adverse effects (e.g. driving may be affected). As with all opioids, a reduction in dosage may be advisable in the elderly and in debilitated patients (see Warnings).

Effects on Driving