ZOMORPH capsules 10mg, 30mg, 60mg, 100mg, 200mg

• Morphine sulphate BP 10mg

• Morphine sulphate BP 30mg

• Morphine sulphate BP 60mg

• Morphine sulphate BP 100mg

• Morphine sulphate BP 200mg

Sustained-release capsules.

Severe chronic pain and/or pain resistant to other analgesics, in particular pain associated with cancer.

Route of administration : orally.

As directed by a medical practitioner.

Recommended dosage

Adults: Recommended dosage is one capsule twice daily, at 12-hourly intervals.

Elderly: As with all narcotics, a reduction in dosage may be advisable in the elderly, as appropriate.

Children: Not recommended.

The capsules should not be chewed and should normally be swallowed whole.

The dosage varies according to the severity of pain and the previous analgesic treatments received by the patient.

If the pain persists, or if the patient develops tolerance to morphine, the dosage may be increased by prescribing the 10mg, 30mg, 60mg, 100mg and 200mg capsules in various combinations or alone to obtain the desired relief.

Patients previously treated with immediate-release oral morphine should receive the same daily dose of sustained-release capsules, but in two divided doses at 12-hourly intervals.

Patients previously treated with parenteral morphine should be given a sufficiently increased dosage to compensate for any reduction of the analgesic effect associated with oral administration. The dosage should be adjusted to meet the individual requirements of each patient.

For patients who cannot swallow the capsules, their contents can be administered directly in semi-solid food (puree, jam, yoghurt) or via gastric or gastrostomy tubes of a diameter of more than 16 F.G. with an open distal end or lateral pores. It is sufficient to rinse the tube with 30ml to 50ml of water.

Respiratory impairment, acute abdominal syndrome of unknown origin, severely impaired liver function, cranial trauma and raised intracranial pressure, convulsive state, acute alcoholic intoxication and delirium tremens, children, risk of paralytic ileus, known hypersensitivity to any of the ingredients contained in Zomorph, concurrent treatment with MAO (MAO = monoamine oxidase) inhibitors or within two weeks of their use.

Caution should be exercised:

- in elderly subjects, in patients with impaired hepatic and/or renal functions, in patients with hypothyroidism or hypoadrenalism, in patients in a state of shock or with asthma. The dose of Zomorph should be reduced, or its use should be avoided in cases of hepatic or renal failure.

- in patients suffering from the following conditions: hypotension, convulsive disorders, dependence (severe withdrawal symptoms if withdrawn abruptly) and prostatic hypertrophy.

Urinary retention may occur in patients with urethral disease or prostatic hypertrophy.

Concomitant use of alcohol and Zomorph may increase the undesirable effects of Zomorph; concomitant use should be avoided.

As serious and sometimes fatal reactions have occurred following administration of pethidine to patients receiving monoamine oxidase inhibitors, pethidine and related drugs are contra-indicated in patients taking monoamine oxidase inhibitors or within 14 days of stopping such treatment; morphine and other opioid analgesics should be given with extreme caution.

The depressant effects of opioid analgesics are enhanced by depressants of the central nervous system such as alcohol, anaesthetics, antipsychotics, anxyolitics, hypnotics and sedatives, tricyclic antidepressants and phenothiazines.

Cyclizine may counteract the haemodynamic benefits of opioids.

Opioid analgesics with some antagonist activity, such as buprenorphine, butorphanol, nalbuphine or pentazocine may precipitate withdrawal symptoms in patients who have recently used pure agonists such as morphine. The actions of opioids may in turn affect the activities of other compounds. For instance, their gastro-intestinal effects may delay absorption as with mexiletine or may be counteractive as with metoclopramide, domperidone and possibly cisapride.

Plasma concentrations of morphine are possibly increased by ritonavir.

Alcohol may enhance the pharmacodynamic effects of Zomorph; concomitant use should be avoided.

Since this product rapidly crosses the placental barrier, it should not be used during the second stage of labour or in premature delivery because of the risk of secondary respiratory depression in the newborn infant. If the mother is addicted, a withdrawal syndrome is observed in the newborn infant characterised by: convulsions, irritability, vomiting, increased mortality. As with all drugs, it is not advisable to administer morphine during pregnancy.

Because of the decrease in vigilance induced by this drug, attention is drawn to the possible dangers incurred by drivers of vehicles or machine operators.

The most common side effects at usual doses are nausea, constipation, confusion and occasionally vomiting.

Other possible effects include: urticaria, pruritus, rashes, decreased libido or potency, mood changes, drowsiness, dry mouth, sweating, headache, facial flushing, vertigo, bradycardia, tachycardia, palpitations, postural hypotension, dysphoria, hypotension, hypothermia, miosis, dysuria, sedation or excitation (particularly in elderly subjects in whom delirium and hallucinations may occur), increased intracranial pressure which may aggravate existing cerebral disorders, increased pressure in the main bile duct and urinary retention in cases of prostatic adenoma or urethral stenosis. Mild respiratory depression occurs even at therapeutic doses. In the event of overdosage it may be severe, serious or even fatal. Physical and psychic dependence may appear after administration of therapeutic doses for periods of 1 to 2 weeks. Some cases of dependence have been observed after only 2 to 3 days.

Withdrawal syndrome: this may occur a few hours after withdrawal of a prolonged treatment, and is maximal between the 36^th and 72^nd hours.

Symptoms include respiratory depression, extreme miosis, hypotension, hypothermia, coma. Treatment is by intravenous injection of naloxone 0.4mg, repeated every 2 to 3 minutes if necessary, or by an infusion of 2mg in 500ml of normal saline or 5% dextrose (0.004mg/ml).

In subjects dependent on morphine-like drugs, withdrawal symptoms may occur following injection of a high dose of naloxone. It should therefore be injected in gradually increasing doses to such subjects.

Morphine is an opioid analgesic. It acts mainly on the central nervous system and smooth muscle.

Morphine exerts an analgesic action, and affects psychomotor behaviour: depending on the dose administered, it induces sedation (> 1cg) or, in some cases, excitation (< 1cg). At high doses, greater than those required to produce analgesia, it induces somnolence and sleep.

Absorption

This is a sustained-release form, which makes twice-daily oral administration possible. Morphine is immediately absorbed from the digestive tract following oral administration. The maximum serum concentrations of morphine are obtained in 2 to 4 hours.

Distribution

The percentage of binding to plasma proteins after absorption is low (about 34%). There is no clearly defined correlation between the plasma concentration of morphine and the analgesic effect.

Metabolism

A considerable quantity of morphine is metabolised by the liver to glucuronides, which undergo enterohepatic recirculation.

Excretion

The product is eliminated essentially in the urine, by glomerular filtration, mainly as glucuronides. A small amount (less than 10%) is eliminated in the faeces.

None stated.

Sucrose, maize starch, polyethylene glycol 4000, ethyl-cellulose, cetyl alcohol, sodium lauryl sulphate, dibutyl sebacate, talc, gelatin, iron oxide ink (E172), titanium dioxide (E171) (for the 10mg, 30mg, 60mg and 100mg strengths), quinoline yellow (E104) (only for the 10mg strength), erythrosine (E127) (only for the 30mg strength), sunset yellow (E 110) (only for the 60mg strength).

Not applicable.

36 months.

Store below 25°C in a dry place protected from heat.

Blister packs (aluminium/PVC).

Boxes of 14, 30 and 60 capsules.

Not all pack sizes may be marketed.

Not applicable.

Archimedes Pharma UK Limited

250 South Oak Way

Green Park

Reading

Berkshire

RG2 6UG

UK

10mg: PL 12406/0028

30mg: PL 12406/0029

60mg: PL 12406/0030

100mg: PL 12406/0031

200mg: PL 12406/0032

16 July 2010 (10mg, 30mg)

17 July 2010 (60mg, 100mg & 200mg)

22 July 2011

ZomCapAll-SPC06

UK/ZC/11/006

OCT 2011