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Mundipharma Pharmaceuticals Limited - Formerly Napp Laboratories

Millbank House, Arkle Road, Sandyford, Dublin 18, Ireland
Telephone: +353 1 206 3800
Medical Information e-mail: info@mundipharma.ie


Summary of Product Characteristics last updated on medicines.ie: 15/03/2017
SPC PALLADONE Capsules


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1. NAME OF THE MEDICINAL PRODUCT

Palladone 1.3 mg and 2.6 mg capsules


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2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Palladone 1.3 mg capsules contain hydromorphone hydrochloride 1.30 mg equivalent to 1.16 mg hydromorphone.

Palladone 2.6 mg capsules contain hydromorphone hydrochloride 2.60 mg equivalent to 2.32 mg hydromorphone.

Excipients with known effect:

Each Palladone 1.3 mg capsule contains 39.35 mg of lactose.

Each Palladone 2.6 mg capsule contains 78.70 mg of lactose.

For the full list of excipients, see section 6.1.


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3. PHARMACEUTICAL FORM

Capsule, hard (capsule).

Palladone capsules 1.3 mg are gelatin capsules with clear uncoloured caps and opaque orange bodies, containing white to off-white spherical pellets. The capsule is marked HNR 1.3.

Palladone capsules 2.6 mg are gelatin capsules with clear uncoloured bodies and opaque red caps, containing white to off-white spherical pellets. The capsule is marked HNR 2.6.


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4. CLINICAL PARTICULARS

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4.1 Therapeutic indications

For the relief of severe pain


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4.2 Posology and method of administration

Method of administration

Oral use

The capsules can be swallowed whole or opened and their contents sprinkled on to cold soft food.

Posology

Adults and adolescents over 12 years:

The dosage is dependent upon the severity of the pain and the patient's previous history of analgesic requirements. 1.3 mg of hydromorphone hydrochloride has an efficacy equivalent to 10 mg of morphine sulphate given orally. 1.3 mg and 2.6 mg capsules are available. Treatment should normally be started at a dosage of 1.3 mg or 2.6 mg hydromorphone hydrochloride 4 hourly. Increasing severity of pain will require increased dosage of hydromorphone using 1.3 mg and 2.6 mg capsules alone or in combination with prolonged release hydromorphone products to achieve the desired relief.

Elderly

As with adults, the elderly should be dose-titrated with Palladone capsules in order to achieve adequate analgesia. It should be noted however, that the elderly may require a lower dosage than adults to achieve adequate analgesia.

Paediatric population

Not recommended for use in children under 12 years.

Patients with renal and hepatic impairment

These patients may require lower doses than other patient groups to achieve pain control. Patients should be carefully titrated to clinical effect.


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4.3 Contraindications

Hypersensitivity to hydromorphone or to any of the excipients listed in section 6.1. Significant respiratory depression with hypoxia or elevated carbon dioxide levels in the blood, severe chronic obstructive airways disease, coma, acute abdomen, paralytic ileus, concurrent administration of mono-amine oxidase inhibitors or within two weeks of discontinuation of their use.


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4.4 Special warnings and precautions for use

The major risk of opioid excess is respiratory depression. Use with caution in opioid dependent patients and in patients with head injury (due to the risk of increased intracranial pressure), convulsive disorders, alcoholism, delirium tremens, toxic psychosis, hypotension with hypovolaemia, disorders of consciousness, diseases of the biliary tract, biliary or ureteric colic, pancreatitis, obstructive and inflammatory bowel disorders, prostatic hypertrophy, adrenocortical insufficiency (e.g. Addison's disease), hypothyroidism, chronic obstructive airways disease, reduced respiratory reserve, in the debilitated elderly and in patients with severely impaired renal or hepatic function (see Section 4.2). In patients in whom caution is required, a reduced dosage may be advisable.

Patients may develop tolerance to the drug with chronic use and require progressively higher doses to maintain pain control. There may also be cross-tolerance with other opioids. Prolonged use of this product may lead to physical dependence and a withdrawal syndrome may occur upon abrupt cessation of therapy. When a patient no longer requires therapy with hydromorphone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

Hydromorphone has an abuse profile similar to other strong opioid agonists. Hydromorphone may be sought and abused by people with latent or manifest addiction disorders. There is potential for development of psychological dependence (addiction) to opioid analgesics, including hydromorphone. Palladone capsules should be used with particular care in patients with a history of alcohol and drug abuse.

Abuse of oral dosage forms by parenteral administration can be expected to result in serious adverse events, which may be fatal.

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

Palladone should not be used where there is the possibility of paralytic ileus occurring. Should paralytic ileus be suspected or occur during use, hydromorphone treatment must be discontinued immediately.

Palladone capsules should be used with caution preoperatively and within 24 hours postoperatively. After this time, they should be used with caution particularly following abdominal surgery.

Patients about to undergo additional pain relieving procedures (e.g. surgery, plexus blockade) should not receive hydromorphone for 4 hours prior to the intervention. If further treatment with Palladone is indicated then the dosage should be adjusted to the new post-operative requirement.

It should be emphasised that patients, once titrated to an effective dose of a certain opioid, should not be changed to other opioid analgesic preparations without clinical assessment and careful retitration as necessary. Otherwise a continuous analgesic action is not ensured.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption, should not take this medicine.


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4.5 Interaction with other medicinal products and other forms of interaction

Centrally acting drugs such as tranquillisers, anaesthetics (e.g. barbiturates), hypnotics and sedatives, neuroleptics, antidepressants, antiemetics, antihistaminic drugs and other opioids or alcohol may enhance the CNS depressant effects of either drug, e.g. sedation, respiratory depression etc.

Concurrent administration of hydromorphone and mono-amine oxidase inhibitors or within two weeks of discontinuation of their use must be avoided.

No formal studies of drug interaction with Palladone capsules have been performed.


4.6 Fertility, pregnancy and lactation

Palladone capsules are not recommended in pregnancy or in the breast-feeding mother.

Pregnancy

No clinical data on exposed pregnancies are available.

Animal studies revealed no teratogenic effects at doses that give exposure greater than those expected in humans (see Section 5.3). Animal studies revealed no evidence of an effect on fertility or reproductive parameters at oral doses as high as 5 mg/kg/day. Peri-natal toxicity was noted in rats treated with 2 and 5 mg/kg/day.

Palladone capsules should not be used during pregnancy and labour due to impaired uterine contractility and the risk of neonatal respiratory depression. Prolonged use of hydromorphone during pregnancy can result in neonatal withdrawal syndrome.

Lactation

No data are available on the use of hydromorphone during lactation. Palladone capsules should therefore not be used in breast-feeding mothers, otherwise breast-feeding should be stopped.


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4.7 Effects on ability to drive and use machines

Hydromorphone may impair the ability to drive and use machines. This is particularly likely at the initiation of treatment with hydromorphone, after dose increase or product rotation and if hydromorphone is combined with alcohol or other CNS depressant agents. Patients stabilised on a specific dosage will not necessarily be restricted. Therefore, patients should consult with their physician as to whether driving or the use of machinery is permitted.


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4.8 Undesirable effects

The following frequency categories form the basis for classification of the undesirable effects:

Very common: 1/10

Common: 1/100 to < 1/10

Uncommon: 1/1000 to < 1/100

Rare: 1/10000 to < 1/1000

Very rare: < 1/10000

Not known: cannot be estimated from the available data

Very common

Common

Uncommon

Rare

Not known

Immune system disorders

Anaphylactic reactions

Hypersensitivity reactions (including oropharyngeal swelling)

Metabolism and nutrition disorders

Decreased appetite

Psychiatric disorders

Anxiety

Confusional state

Insomnia

Agitation

Depression

Euphoric mood

Hallucination

Nightmares

Aggression

Drug dependence

Dysphoria

Nervous system disorders

Dizziness

Somnolence

Headache

Tremor

Myoclonus

Paraesthesia

Sedation

Lethargy

Convulsions

Dyskinesia

Hyperalgesia (see section 4.4)

Eye disorders

Visual impairment

Miosis

Cardiac disorders

Bradycardia

Palpitations

Tachycardia

Vascular disorders

Hypotension

Flushing

Respiratory, thoracic and mediastinal disorders

Dyspnoea

Respiratory depression

Bronchospasm

Gastrointestinal disorders

Constipation

Nausea

Abdominal pain

Dry mouth

Vomiting

Dyspepsia

Diarrhoea

Dysgeusia

Paralytic ileus

Hepatobiliary disorders

Hepatic enzymes increased

Elevation of pancreatic enzymes

Skin and subcutaneous tissue disorders

Pruritus

Hyperhidrosis

Rash

Urticaria

Renal and urinary disorders

Urgency

Urinary retention

Reproductive system and breast disorders

Decreased libido

Erectile dysfunction

General disorders and administration site conditions

Asthenia

Drug withdrawal syndrome*

Fatigue

Malaise

Peripheral oedema

Drug tolerance

Neonatal drug withdrawal sydrome

* A withdrawal syndrome may occur and include symptoms such as agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal symptoms.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via;

HPRA Pharmacovigilance,

Earlsfort Terrace,

IRL - Dublin 2;

Tel: +353 1 6764971;

Fax: +353 1 6762517.

Website: www.hpra.ie;

E-mail: medsafety@hpra.ie.


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4.9 Overdose

Signs of hydromorphone toxicity and overdose include miotic pupils, bradycardia, respiratory depression, hypotension, somnolence progressing to stupor and coma. Circulatory failure and deepening coma may occur in more severe cases and may lead to a fatal outcome.

In unconscious patients with respiratory arrest intubation and assisted respiration may be required. Naloxone 0.8 mg should be administered intravenously. This should be repeated at 2-3 minute intervals as necessary, or by an infusion of 2 mg in 500 ml of sodium chloride solution or 5% w/v glucose solution (0.004 mg ml-1). The infusion should be run at a rate relative to the previous bolus administered and should be in accordance with the patient's response. Respiration should be assisted if necessary. Fluid and electrolyte levels should be maintained.

Close monitoring (at least for 24 hours) is required, since the effect of the opioid antagonist is shorter than that of hydromorphone, so that repeated occurrence of the signs of overdose like respiratory insufficiency are to be expected.


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5. PHARMACOLOGICAL PROPERTIES

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5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Opioid analgesic; natural opium alkaloid.

ATC code: N02A A03.

Like morphine, hydromorphone is a μ1 selective full opioid agonist. The pharmaceutical actions of hydromorphone and morphine do not differ significantly. Hydromorphone and related opioids produce their major effects on the central nervous system and bowel. The effects are primarily analgesic, anxiolytic, antitussive and sedative. Moreover, mood swings, respiratory depression, reduced gastrointestinal motility, nausea, vomiting and alteration of the endocrine and vegetative nervous system may occur.

There have been no long term clinical studies with Palladone capsules.

Endocrine System

Opioids may influence the hypothalamic-pituitary-adrenal or -gonadal axes. Some changes that can be seen include an increase in serum prolactin, and decreases in plasma cortisol and testosterone. Clinical symptoms may be manifest from these hormonal changes.

Hepatobiliary System

Opioids may induce biliary spasm.

Other Pharmacologic System

Preclinical studies indicate various effects of opioids on components of the immune system; the clinical significance of these findings is unknown. Whether hydromorphone, a semisynthetic opioid, has immunological effects similar to natural opioids is unknown.


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5.2 Pharmacokinetic properties

Hydromorphone is absorbed from the gastrointestinal tract and undergoes pre-systemic elimination resulting in a mean oral bioavailability of about 32 % (range 17 – 62%). It is metabolised and excreted in the urine mainly as conjugated hydromorphone, dihydroisomorphine and dihydromorphine.


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5.3 Preclinical safety data

Reproductive and Development Toxicity

No effects have been observed on male or female fertility or sperm parameters in rats at oral hydromorphone doses as high as 5 mg/kg/day (30 mg/m2/day or 1.4 times the expected human dose on a surface area basis).

Hydromorphone was not teratogenic in pregnant rats nor rabbits given oral doses during the major period of organ development. Reduced foetal development was observed in rabbits at 50 mg/kg (the developmental no-effect level dose of 25 mg/kg or 380 mg/m2 at a drug exposure, AUC, approximately 4 times that expected in humans). No evidence of foetal toxicity was observed in rats at oral hydromorphone doses as high as 10 mg/kg (308 mg/m2 at an AUC approximately 1.8 times that expected in humans). Evidence of a teratogenic effect in mice and hamsters has been reported in literature.

A pre- and post-natal study in rats showed that there was an increase in pup mortality at 2 and 5 mg/kg/day and reduced body weight gain in the early postnatal period, associated with maternal toxicity. No effects on continued pup development or reproductive performance were observed.

Carcinogenicity

Hydromorphone was non-genotoxic in a bacterial mutation test, in the in vitro human lymphocyte chromosome aberration assay and the in vivo mouse micronucleus assay, but positive in mouse lymphoma assay with metabolic activation. Similar findings have been reported with other opioid analgesics.

Long term carcinogenicity studies have not been performed.


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6. PHARMACEUTICAL PARTICULARS

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6.1 List of excipient(s)

Capsule contents:

Microcrystalline cellulose

Lactose anhydrous

Capsule shells:

Gelatin

Erythrosine (E127)

Iron oxide yellow (E172)

Titanium dioxide (E171)

Sodium laurilsulfate

Black printing ink containing:

Shellac

Propylene glycol

Iron oxide (E172)


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6.2 Incompatibilities

Not applicable.


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6.3 Shelf life

2 years.


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6.4 Special precautions for storage

Do not store above 25°C. Store in the original package.


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6.5 Nature and contents of container

PVC/PVdC blister packs with aluminium backing foil containing 56 capsules.


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6.6 Special precautions for disposal and other handling

No special requirements.


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7. MARKETING AUTHORISATION HOLDER

Mundipharma Pharmaceuticals Limited

Millbank House

Arkle Road

Sandyford

Dublin 18

Ireland


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8. MARKETING AUTHORISATION NUMBER(S)

PA 1688/007/001-002


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9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 07 December 1995

Date of last renewal: 05 April 2009


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10. DATE OF REVISION OF THE TEXT

21 February 2017



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Active Ingredients

 
   Hydromorphone Hydrochloride