CONTIROXIN 40 MG PROLONGED-RELEASE TABLETS - summary of medicine characteristics

Summary of medicine characteristics - CONTIROXIN 40 MG PROLONGED-RELEASE TABLETS

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Contiroxin 40 mg Prolonged-release Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each prolonged-release tablet contains 40 mg oxycodone hydrochloride corresponding to 35.9 mg oxycodone.

Excipient(s) with known effect:

Each prolonged-release tablet contains a maximum of 12 mg sucrose.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Prolonged-release tablet

Orange, biconvex, oblong prolonged-release tablets with a breakline on both sides.

The prolonged-release tablets can be divided into equal doses.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Severe pain, which can be adequately managed only with opioid analgesics Oxycodone Hydrochloride prolonged-release tablets are indicated in adults and adolescents aged 12 years and older.

4.2 Posology and method of administration

Posology

The dose should be adjusted to the intensity of the pain and the sensitivity of the individual patient.

For doses not practicable with this medicinal product other strengths are available.

Adults and adolescents (12 years of age and older)

Starting dose

The usual starting dose for an opioid naïve patient is 10 mg oxycodone hydrochloride per dose at intervals of 12 hours. Some patients may benefit from a starting dose of 5 mg to minimise the incidence of adverse reactions.

Patients already receiving opioids may start treatment with higher doses of Oxycodone Hydrochloride prolonged-release tablets taking into account their experience with former opioid therapies.

10 to 13 mg oxycodone hydrochloride correspond to approximately 20 mg of morphine sulphate, both in the prolonged-release formulation.

Dose adjustment

Some patients who take Oxycodone Hydrochloride Prolonged-release Tablets following a fixed schedule need rapid release analgesics as rescue medication in order to control breakthrough pain. Oxycodone Hydrochloride Prolonged-release Tablets is not intended for therapy ofbreakthrough pain. The single dose of the rescue medication should amount to 1/6 of the equianalgesic daily dose of Oxycodone Hydrochloride Prolonged-release Tablets. Use of the rescue medication more than twice daily indicates that the dose of Oxycodone Hydrochloride Prolonged-release Tablets needs to be increased. The dose should not be adjusted more often than once every 1–2 days until a stable 12 hourly administration has been achieved.

Following a dose increase from 10 mg to 20 mg oxycodone hydrochloride taken every 12 hours dose adjustments should be made in steps of approximately one third of the daily dose until the desired effect is obtained. The aim is a patient-specific 12 hourly dose that will maintain adequate analgesia with acceptable undesirable effects and as little rescue medication as possible as long as pain control is necessary.

Even administration (the same dose in the morning and in the evening) following a fixed schedule (every 12 hours) is appropriate for the majority of the patients. For some patients it may be beneficial to arrange the doses unevenly. In general, the lowest effective analgesic dose should be chosen.

For the treatment of non malignant pain a daily dose of 40 mg oxycodone hydrochloride is generally sufficient; but higher doses may be necessary.

Patients with cancer-related pain may require doses of 80 to 120 mg oxycodone hydrochloride, which in individual cases can be increased to up to 400 mg.

Duration of administration

Oxycodone should not be used for longer than necessary. If long-term treatment is necessary due to the type and severity of the illness careful and regular monitoring is required to determine whether and to what extent treatment should be continued.

Discontinuation of treatment

When a patient no longer requires therapy with oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

Elderly patients

A dose adjustment is usually not necessary in elderly patients without clinically manifest impairment of hepatic or renal function.

Patients with renal or hepatic impairment

The dose initiation should follow a conservative approach in these patients. The recommended adult starting dose should be reduced by 50% (for example a total daily dose of 10 mg of oxycodone hydrochloride orally in opioid naïve patients), and each patient should be titrated to adequate pain control according to their clinical situation. In such cases oxycodone hydrochloride 5 mg prolonged-release tablets can be used.

Other , patients at risk

Patients with low body weight or slow metabolisers, who are opioid naïve should initially receive half the dose usually recommended for adults.

Therefore, 10 mg of oxycodone hydrochloride per dose at intervals of 12 hours may not be suitable as a starting dose and in such cases oxycodone hydrochloride 5 mg prolonged-release tablets can be used.

Children under 12 years of age

Oxycodone hydrochloride prolonged-release tablets are not recommended for use in children under 12 years of age due to insufficient data on safety and efficacy.

Method of administration

Oral use.

Oxycodone hydrochloride prolonged-release tablets should be taken twice daily based on a fixed schedule at the dose determined.

The Oxycodone hydrochloride prolonged-release tablets may be taken with or without food with sufficient liquid.

Oxycodone hydrochloride prolonged-release tablets can be divided into equal halves. However, the tablets must not be further broken, crushed or chewed.

4.3 Contraindications

hypersensitivity to the active substance or to any of the excipients listed in section 6.1

severe respiratory depression with hypoxia

elevated carbon dioxide levels in the blood (hypercarbia)

severe chronic obstructive lung disease

cor pulmonale

severe bronchial asthma

paralytic ileus

4.4 Special warnings and precautions for use

The major risk of opioid excess is respiratory depression.

Caution should be exercised in

elderly or debilitated patients,

patients with severe impairment of pulmonary function, impaired hepatic or renal function,

patients with myxedema,

hypothyroidism,

Addison’s disease,

prostatic hypertrophy,

toxic psychosis,

alcoholism, delirium tremens, known opioid dependence,

diseases of the biliary tract,

pancreatitis,

obstructive and inflammatory bowel disorders,

head injury (due to risk of increased intracranial pressure),

hypotension,

hypovolaemia,

epilepsy or predisposition to convulsions,

in patients taking sedative medicinal products such as benzodiazepines or other centrally depressant active substances including alcohol (see also section 4.5)

in patients taking MAO inhibitors or within 2 weeks of discontinuation of their use (see also section 4.5)

With the occurrence or suspicion of paralytic ileus, oxycodone should be immediately discontinued.

Risk from concomitant use of sedative medicinal products such as benzodiazepines or related medicinal products

Concomitant use of oxycodone and sedative medicinal products such as benzodiazepines or related medicinal products may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicinal products should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe oxycodone concomitantly with sedative medicinal products, 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).

Tolerance and dependence

The patient may develop tolerance to the active substance with chronic use and require progressively higher doses to maintain pain control. Prolonged use of this medicinal 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 oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal. Withdrawal symptoms may include yawning, mydriasis, lacrimation, rhinorrhoea, tremor, hyperhidrosis, anxiety, agitation, convulsions, insomnia or myalgia.

Hyperalgesia that will not respond to a further dose increase of oxycodone may occur particularly in high doses. An oxycodone dose reduction or change to an alternative opioid may be required.

Abuse and misuse

Oxycodone has an abuse profile similar to other strong agonist opioids. Oxycodone 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 oxycodone. Oxycodone Hydrochloride Prolonged-release Tablets 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.

To avoid damage to the controlled-release properties of the prolonged-release tablets, the Oxycodone Hydrochloride prolonged-release tablets must not be broken, chewed or crushed. The administration of broken, chewed or crushed tablets leads to rapid release and absorption of a potentially fatal dose of oxycodone (see section 4.9). However, the tablets can be divided into equal halves (see sections 3 and 4.2).

Surgical procedures

Oxycodone Hydrochloride prolonged-release tablets are not recommended for pre-operative use or within the first 12–24 hours post-operatively. Depending on the type and extent of surgery, the anaesthetic procedure selected, other comedication and the individual condition of the patient, the exact timing for initiating postoperative treatment with Oxycodone Hydrochloride Prolonged-release Tablets depends on a careful risk-benefit assessment for each individual patient.

As with all opioid preparations, oxycodone-containing medicinal products should be used with caution following abdominal surgery as opioids are known to impair intestinal motility and should not be used until the physician is assured of normal bowel function.

Paediatric population

Oxycodone Hydrochloride Prolonged-release Tablets is not recommended for use in children below the age of 12 years due to insufficient data on safety and efficacy.

Alcohol

Concomitant use of alcohol and Oxycodone Hydrochloride Prolonged-release Tablets may increase the undesirable effects of oxycodone; concomitant use should be avoided.

Endocrine system

Opioids such as oxycodone 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.

This medicinal product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product.

4.5 Interaction with other medicinal products and other forms of interaction Sedative medicinal products such as benzodiazepines or related medicinal products:

The concomitant use of opioids with sedative medicinal products such as benzodiazepines or related medicinal products increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dose and duration of concomitant use should be limited (see section 4.4).

CNS depressant active substances are for example sedatives (including benzodiazepines), hypnotics, phenothiazines, neuroleptics, antidepressants, antihistamines, antiemetics or other opioids.

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

Concomitant administration of oxycodone with serotonin agents, such as a Selective Serotonin Re-uptake Inhibitor (SSRI) or a Serotonin Norepinephrine Re-uptake Inhibitor (SNRI) may cause serotonin toxicity. The symptoms of serotonin toxicity may include mental-status changes (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g. hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea). Oxycodone should be used with caution and the dose may need to be reduced in patients using these medicinal products.

Medicinal products with anticholinergic effects (e.g. tricyclic antidepressants, antihistamines, antiemetics, psychotropic medicinal products, muscle relaxants, medicinal products against Morbus Parkinson) may intensify the anticholinergic adverse drug reactions of oxycodone, such as constipation, dry mouth or dysfunction of urinary excretion.

Oxycodone should be used with caution in patients administered MAOinhibitors or who have received MAO-inhibitors during the last two weeks.

A clinically relevant decrease or increase of INR (International Normalised Ratio) has been observed in individual cases in simultaneous use of oxycodone and coumarin anticoagulants.

Oxycodone is metabolised mainly by CYP3A4, with a contribution from

CYP2D6. The activities of these metabolic pathways may be inhibited or induced by various co-administered medicinal products or dietary elements. In the following paragraphs these interactions are explained in detail.

CYP3A4 inhibitors, such as macrolide antibiotics (e.g. clarithromycin, erythromycin or telithromycin), azol-antifungals (e.g. ketoconazole, voriconazole, itraconazole, or posaconazole), protease inhibitors (e.g. boceprevir, ritonavir, indinavir, nelfinavir or saquinavir), cimetidine and grapefruit juice may cause a reduced clearance of oxycodone that could cause an increase of the plasma concentrations of oxycodone. Therefore the oxycodone dose may need to be adjusted accordingly.

Some specific examples of CYP3A4 enzyme inhibition are provided as follows:

Itraconazole, a potent CYP3A4 inhibitor, administered 200 mg orally for five days, increased the AUC of oral oxycodone. On average, the AUC was approximately 2.4 times higher (range 1.5 – 3.4).

Voriconazole, a CYP3A4 inhibitor, administered 200 mg twice-daily for four days (400 mg given as first two doses), increased the AUC of oral oxycodone. On average, the AUC was approximately 3.6 times higher (range 2.7 – 5.6).

Telithromycin, a CYP3A4 inhibitor, administered 800 mg orally for four days, increased the AUC of oral oxycodone. On average, the AUC was approximately 1.8 times higher (range 1.3 – 2.3).

Grapefruit juice, a CYP3A4 inhibitor, administered as 200 ml three times a day for five days, increased the AUC of oral oxycodone. On average, the AUC was approximately 1.7 times higher (range 1.1 – 2.1).

CYP3A4 inducers, such as rifampicin, carbamazepin, phenytoin or St John's wort may induce the metabolism of oxycodone and cause an increased clearance of oxycodone that could cause a reduction of the plasma concentrations of oxycodone. The oxycodone dose may need to be adjusted accordingly.

Some specific examples of CYP3A4 enzyme induction are provided as follows:

St John’s wort, a CYP3A4 inducer, administered as 300 mg three times a day for fifteen days, reduced the AUC of oral oxycodone. On average, the AUC was approximately 50% lower (range 37–57%).

Rifampicin, a CYP3A4 inducer, administered as 600 mg once-daily for seven days, reduced the AUC of oral oxycodone. On average, the AUC was approximately 86% lower.

Medicinal products that inhibit CYP2D6 activity, such as paroxetine or quinidine, may cause decreased clearance of oxycodone which could lead to an increase in oxycodone plasma concentrations.

4.6 Fertility, pregnancy and lactation

Use of this medicinal product should be avoided to the extent possible in patients who are pregnant or lactating.

Pregnancy

There are limited data from the use of oxycodone in pregnant women. Oxycodone passes the placenta. Infants born to mothers who have received opioids during the last 3 to 4 weeks before giving birth should be monitored for respiratory depression. Withdrawal symptoms may be observed in the newborn of mothers undergoing treatment with oxycodone.

Breastfeeding

Oxycodone may be excreted into breast milk and may cause sedation and respiratory depression in the. breast-fed infant. Therefore, oxycodone should, not be used in breast-feeding mothers.

Fertility

Human data are not available. Studies in rats have not shown any effects upon fertility (see section 5.3).

4.7 Effects on ability to drive and use machines

Oxycodone may impair the ability to drive and use machines. This is particularly likely at the initiation of treatment with oxycodone, after dose increase or product rotation and if oxycodone is combined with other CNS depressant agents. Patients stabilised on a specific dose will not necessarily be restricted. Therefore, the physician should decide whether the patient is allowed to drive or use machinery.

This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. 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

It is an offence to drive while under the influence of this medicine

However, you would not be committing an offence (called ‘statutory defence’) if:

o The medicine has been prescribed to treat a medical or dental

problem and

o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and o It was not affecting your ability to drive safely.

4.8 Undesirable effects

Due to its pharmacological properties oxycodone can cause respiratory depression, miosis, bronchial spasm and spasm of the smooth muscles and may suppress the cough reflex.

The most frequently reported undesirable effects are nausea (especially at the beginning of treatment) and constipation.

Respiratory depression is the chief hazard of an opioid overdose and occurs most commonly in elderly or debilitated patients.

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

Very common (>1/10)

Common (>1/100 to <1/10)

Uncommon (>1/1,000 to <1/100)

Rare (>1/10,000 to <1/1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data)

Infections and infestations

Rare: herpes simplex

Immune system disorders

Uncommon: hypersensitivity

Not known: anaphylactic responses, anaphylactoid reactions

Metabolism and nutrition disorders

Common: decreased appetite up to loss of appetite

Uncommon: dehydration

Rare:

increased appetite

Psychiatric disorders

Common: anxiety, confusional state, depression, decreased activity,

restlessness, psychomotor hyperactivity, nervousness, insomnia, abnormal thinking

Uncommon: agitation, affect lability, euphoric mood, perception disturbances such as hallucinations, derealisation; decreased libido, drug dependence (see section 4.4)

Not known: aggression

Nervous system disorders

Very common: somnolence, sedation, dizziness, headache

Common: tremor, lethargy

Uncommon: amnesia, convulsion (especially in persons with epileptic

disorder or predisposition to convulsions), concentration impaired, migraine, hypertonia, involuntary muscle contractions, hypoaesthesia, coordination disturbances, speech disorder, syncope, paraesthesia, dysgeusia

Not known: hyperalgesia

Eye disorders

Uncommon: visual impairment, miosis

Ear and labyrinth disorders

Uncommon: hearing impaired, vertigo

Cardiac disorders

Uncommon: tachycardia, palpitations (in the context of withdrawal syndrome)

Vascular disorders

Uncommon: vasodilatation

Rare: hypotension, orthostatic hypotension

Respiratory, thoracic and mediastinal disorders

Common: dyspnoea, bronchospasm

Uncommon: respiratory depression, dysphonia, cough

Gastrointestinal disorders

Very common: constipation, vomiting, nausea

Common: abdominal pain, diarrhoea, dry mouth, hiccups, dyspepsia

Uncommon: mouth ulceration, stomatitis, dysphagia, flatulence, eructation, ileus

Rare: melaena, tooth disorders, gingival bleeding

Not known: dental caries

Hepatobiliary disorders

Uncommon: increased hepatic enzymes

Not known: cholestasis, biliary colic

Skin and subcutaneous tissue disorders

Very common: pruritus

Common: skin reaction/rash, hyperhidrosis

Uncommon: dry skin

Rare: urticaria

Renal and urinary disorders

Common: dysuria, micturition urgency

Uncommon: urinary retention

Reproductive system and breast disorders

Uncommon: erectile dysfunction, hypogonadism

Not known: amenorrhoea

General disorders and administration site conditions

Common: asthenic conditions, fatigue

Uncommon: chills, drug withdrawal syndrome, pain (e.g. chest pain),

malaise, oedema, peripheral oedema, drug tolerance, thirst

Rare: weight increase, weight decrease

Not known: drug withdrawal syndrome neonatal

Injury, poisoning and procedural complications

Uncommon: injuries from accidents

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 the Yellow Card Scheme

(www.mhra.gov.uk/yellowcard) or search for MHRA Yellow Card in Google play or Apple App store.

4.9 Overdose

Symptoms of intoxication

Acute overdose with oxycodone can be manifested by respiratory depression, somnolence progressing up to stupor or coma, hypotonia, miosis, bradycardia, hypotension, lung oedema and death.

Therapy of intoxication

A patent airway must be maintained. The pure opioid antagonists such as naloxone are specific antidotes against symptoms from opioid overdose. Other supportive measures should be employed as needed.

Opioid antagonists: Naloxone (e.g. 0.4 to 2 mg intravenously). Administration should be repeated at 2 to 3 minute intervals as necessary, or by an infusion of 2 mg in 500 ml of 0.9% sodium chloride or 5% dextrose (0.004 mg/ml naloxone). The infusion should be run at a rate related to the previously administered bolus doses and should be in accordance with the patient’s response.

Other supportive measures: including artificial ventilation, oxygen, vasopressors, and fluid infusions in the management of circulatory shock accompanying overdose. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation. Fluid and electrolyte metabolism should be maintained.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Analgesics; Natural opium alkaloids

ATC code: N02AA05

Oxycodone shows an affinity to kappa, mu and delta opioid receptors in the brain, spinal cord and peripheral organs. It acts at these receptors as an opioid agonist without an antagonistic effect. The therapeutic effect is mainly analgesic and sedative. Compared to rapid-release oxycodone, given alone or in combination with other substances, oxycodone prolonged-release tablets provide pain relief for a markedly longer period without increased occurrence of undesirable effects.

Endocrine system

See section 4.4.

Gastrointestinal system

Opioids may induce spasm of the sphincter of Oddi.

5.2 Pharmacokinetic properties

Absorption

The absorption of oxycodone from oxycodone prolonged-release tablets could be calculated biphasic with an initially relatively rapid half-life of 0.6 hours accounting for a minority of the active substance, and a slower half-life of 6.9 hours accounting for the majority of the active substance.

To avoid damage to the controlled-release properties of the prolonged-release tablets, the oxycodone prolonged-release tablets must not be broken, chewed or crushed. The administration of broken, chewed or crushed tablets leads to rapid release and absorption of a potentially fatal dose of oxycodone (see section 4.9). However, the tablets can be divided into equal halves (see sections 3. and 4.2).

The relative bioavailability of Prolonged-release oxycodone is comparable to that of rapid release oxycodone with maximum plasma concentrations being achieved after approximately 4.5–7 hours after intake of the prolonged-release tablets compared to 1 to 1.5 hours. Peak plasma concentrations and oscillations of the concentrations of oxycodone from the prolonged-release and rapid-release formulations are comparable when given at the same daily dose at intervals of 12 and 6 hours respectively.

A fat-rich meal before the intake of the tablets does not affect the maximum concentration or the extent of absorption of oxycodone.

The absolute bioavailability of oxycodone is approximately two thirds relative to parenteral administration.

Distribution

In steady state, the volume of distribution of oxycodone amounts to 2.6 l/kg; plasma protein binding to 38–45%; the elimination half-life to 4 to 6 hours and plasma clearance to 0.8 l/min. The elimination half-life of oxycodone from prolonged-release tablets is 4 to 5 hours with steady state values being achieved after a mean of 1 day.

Biotransformation:

Oxycodone is metabolised to noroxycodone and oxymorphone in the intestine and liver via the P450 cytochrome system, as well as to several glucuronide conjugates. In vitro studies suggest that therapeutic doses of cimetidine probably have no relevant effect on the formation of noroxycodone. In man, quinidine reduces the production of oxymorphone while the pharmacodynamic properties of oxycodone remain largely unaffected. The contribution of the metabolites to the overall pharmacodynamic effect is irrelevant.

Elimination

Oxycodone and its metabolites are excreted via urine and faeces. Oxycodone crosses the placenta and is found in breast milk.

Linearity/non-linearity

The 20, 40 and 80 mg prolonged-release tablets are bioequivalent in a dose proportional manner with regard to the amount of active substance absorbed as well as comparable with regard to the rate of absorption.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.

Oyxcodone showed no effect on fertility and early embryonic development in male and female rats in doses of up to 8 mg/kg body weight and induced no malformation in rats in doses of up to 8 mg/kg and in rabbits in doses of 125 mg/kg bodyweight. However, in rabbits, when individual fetuses were used in statistical evaluation, a dose related increase in developmental variations was observed (increased incidences of 27 presacral vertebrae, extra pairs of ribs). When these parameters were statistically evaluated using litters, only the incidence of 27 presacral vertebrae was increased and only in the 125 mg/kg group, a dose level that produced severe pharmacotoxic effects in the pregnant animals. In a study on pre- and postnatal development in rats F1 body weights were lower at 6 mg/kg/d when compared to body weights of the control group at doses which reduced maternal weight and food intake (NOAEL 2 mg/kg body weight). There were neither effects on physical, reflexological, and sensory developmental parameters nor on behavioural and reproductive indices.

There were no effects on F2 generation.

Long-term studies on carcinogenicity have not been performed.

PHARMACEUTICAL PARTICULARSPHARMACEUTICAL PARTICULARS

6.1

List of excipients

Tablet core:

Sugar spheres (sucrose, maize starch)

Hypromellose

Macrogol 6000

Talc

Ethyl cellulose

Hydroxypropylcellulose

Propylene glycol

Magnesium stearate

Microcrystalline cellulose

Colloidal anhydrous silica

Tablet coating: Hypromellose Talc

Macrogol 6000

Titanium dioxide (E 171)

Iron oxide yellow (E 172)

Iron oxide red (E 172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

4 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Alu/PVC/PVDC blister with child-resistant closure.

Pack sizes:

10, 20, 28, 30, 40, 50, 56, 60, 100 and 112 prolonged-release tablets

HDPE bottles with child-resistant PP twist-off caps