Allopurinol 300mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Allopurinol 300mg Tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 300mg Allopurinol Ph. Eur.
For a full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Tablet.
Appearance: White, circular, biconvex tablet with 242 and single breakline on one face and company logo on reverse or plain on reverse.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Allopurinol acts as a xanthine oxidase inhibitor in the management of conditions where urate/ uric acid deposition has occurred (e.g. gouty arthritis, skin tophi, nephrolithiasis) or may occur (e.g. treatment of malignancy potentially leading to acute uric acid nephropathy).
The main clinical conditions where urate/uric acid deposition may occur are: idiopathic gout; uric acid lithiasis; acute uric acid nephropathy; neoplastic disease and myeloproliferative disease with high cell turnover rates, in which high urate levels occur either spontaneously, or after cytotoxic therapy; certain enzyme disorders which lead to overproduction of urate, for example: hypoxanthine-guanine phosphoribosyltransferase, including Lesch-Nyhan syndrome; glucose-6-phosphatase including glycogen storage disease; phosphoribosylpyrophosphate synthetase, phosphoribosylpyrophosphate amidotransferase; adenine phosphoribosyltransferase.
Allopurinol is indicated for management of 2,8-dihydroxyadenine (2,8-DHA) renal stones related to deficient activity of adenine phosphoribosyltransferase.
Allopurinol is indicated in the prophylaxis and treatment of calcium oxalate renal lithiasis in patients with raised serum or urinary uric acid, when fluid dietary and similar measures have failed.
Posology and Method of Administration
4.2
Adults: Initially 100mg daily as a single dose, after food, to reduce the risk of adverse reactions, gradually increased over one to three weeks according to the plasma or urinary uric acid concentration, to about 300mg daily; the usual maintenance dose is 200mg to 600mg, rarely 900mg daily, divided into doses of not more than 300mg. Extra caution should be exercised if renal function is poor (see Dosage in renal impairment). The following dosage schedules are suggested:
o 100mg to 200mg daily in mild conditions o 300mg to 600mg daily in moderately severe conditions o 700mg to 900mg daily in severe conditions
o If dosage on a mg/kg bodyweight basis is required, 2 to 10 mg/kg bodyweight/day should be used.
Children under 15 years: Use in children is rarely indicated, except in neoplastic conditions (e.g. leukaemia) and certain enzyme disorders (e.g. Lesch-Nyhan syndrome), 10mg to 20mg per kg of bodyweight daily up to a maximum of 400mg daily.
Dosage in the elderly: In the absence of specific data, the lowest dosage which produces satisfactory urate reduction should be used. Particular attention should be paid to advice in Dosage in renal impairment and Section 4.4.
Dosage in renal impairment: Since allopurinol and its metabolites are excreted by the kidney, impaired renal function may lead to retention of the drug/ and or its metabolites with consequent prolongation of plasma half-lives. In severe renal insufficiency, it may be advisable to use less than 100mg per day or to use single doses of 100mg at longer intervals than one day.
If facilities are available to monitor plasma oxipurinol concentrations, the dose should be adjusted to maintain plasma oxipurinol levels below 100 micromol/litre (15.2mg/litre).
Allopurinol and its metabolites are removed by renal dialysis. If dialysis is required two or three times a week consideration should be given to an alternative dosage schedule of 300mg-400 mg Allopurinol immediately after each dialysis with none in the interim.
Dosage in hepatic impairment: Reduced doses should be used in patients with hepatic impairment. Periodic liver function tests are recommended during the early stages of therapy.
Treatment of high urate turnover conditions, e.g. neoplasia, Lesch- Nyhan syndrome: It is advisable to correct existing hyperuricaemia and/or hyperuricosuria with allopurinol before starting cytotoxic therapy. It is important to ensure adequate hydration to maintain optimum diuresis and to attempt alkalisation of urine to increase solubility of urinary urate/uric acid. Dosage of allopurinol should be at the lower end of the recommended dosage schedule.
If urate nephropathy or other pathology has compromised renal function, the advice given in Dosage in renal impairment should be followed.
These steps may reduce the risk of xanthine and/or oxipurinol deposition complicating the clinical situation. See also Section 4.5 and 4.8.
Monitoring advice: The dosage should be adjusted by monitoring serum urate concentrations and urinary urate/uric acid levels at appropriate intervals.
Instructions for use: Allopurinol may be taken orally once a day after a meal. It is well tolerated, especially after food. Should the daily dosage exceed 300mg and gastrointestinal intolerance be manifested, a divided dosage regimen may be appropriate.
4.3 Contraindications
Allopurinol should not be administered to individuals known to be hypersensitive to allopurinol or any of the excipients.
4.4 Special Warnings and precautions for use
Allopurinol should be withdrawn immediately when a skin rash or other evidence of sensitivity occurs as this could result in more serious hypersensitivity reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis (see Section 4.8 - Immune system disorders and Skin and subcutaneous tissue disorders).
Hypersensitivity syndrome, SJS and TEN
Allopurinol hypersensitivity reactions can manifest in many different ways, including maculopapular exanthema, hypersensitivity syndrome (also known as DRESS) and SJS/TEN. These reactions are clinical diagnoses, and their clinical presentations remain the basis for decision making. If such reactions occur at any time during treatment, allopurinol should be withdrawn immediately. Rechallenge should not be undertaken in patients with hypersensitivity syndrome and SJS/TEN. Corticosteroids may be beneficial in overcoming hypersensitivity skin reactions.
HLA-B*5801 allele
The HLA-B*5801 allele has been shown to be associated with the risk of developing allopurinol related hypersensitivity syndrome and SJS/TEN. The frequency of the HLA-B*5801 allele varies widely between ethnic populations: up to 20% in Han Chinese population, about 12% in the Korean population and 1-2% in individuals of Japanese or European origin. The use of genotyping as a screening tool to make decisions about treatment with allopurinol has not been established. If the patient is a known carrier of HLA-B*5801, the use of allopurinol may be considered if the benefits are thought to exceed risks. Extra vigilance for signs of hypersensitivity syndrome or SJS/TEN is required and the patient should be informed of the need to stop treatment immediately at the first appearance of symptoms (see section 4.8).
The dose should be reduced in the presence of severe hepatic or renal disorder.
Patients under treatment for hypertension or cardiac insufficiency, for example with diuretics or ACE inhibitors, may have some concomitant impairment of renal function and allopurinol should be used with care in this group.
Asymptomatic hyperuricaemiaper se is not an indication for allopurinol treatment. If other clinical conditions suggest a need for allopurinol the drug must be introduced at low dosage (50mg to 100mg per day) to reduce the risk of adverse reactions and the dosage increased only if the serum urate response is unsatisfactory. At the first signs of intolerance allopurinol should be withdrawn immediately and permanently.
Acute gouty attacks: Allopurinol treatment should not be started until an acute attack of gout has completely subsided, as further attacks may be precipitated.
In the early stages of treatment with Allopurinol (as with uricosuric agents), an acute attack of gouty arthritis may be precipitated. It is therefore advisable to give prophylactic treatment with a suitable anti-inflammatory agent or colchicine (0.5mg three times daily) for at least one month.
If acute attacks develop in patients receiving allopurinol, treatment should continue at the same dosage while the acute attack is treated with a suitable anti-inflammatory agent.
Xanthine desposition: In conditions where the rate of urate formation is greatly increased (e.g. malignant disease and its treatment; Lesch-Nyhan syndrome), the absolute concentration of xanthine in urine may rarely rise sufficiently to allow deposition in the urinary tract. This risk may be minimised by adequate hydration to achieve optimal urine dilution. Xanthine crystals have been seen in muscle tissue of patients receiving Alopurinol, but this appears to have no clinical significance.
Impactation of uric acid renal stones: Adequate therapy with allopurinol will lead to dissolution of large renal pelvic uric acid stones, with the remote possibility of impaction in the ureter.
Lactose intolerance: This medicinal product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Coumarin anticoagulants
Allopurinol prolongs the elimination half-life of Warfarin and other courmarin anti-coagulants under experimental conditions but there is no evidence that this has any clinical significance. All patients receiving anticoagulants must be carefully monitored.
Azathioprine and 6-mercaptopurine
Azathioprine is metabolised to 6-mercaptopurine, which is inactivated by the action of xanthine oxidase. When azthioprine or 6-mercaptpurine is given concurrently with allopurinol, only one quarter of the usual dose of azthioprine or 6-mercaptpurine should be given because inhibition of xanthine oxidase will prolong their activity.
Vidarabine (Adenine arabinoside)
The plasma half-life of adenine arabinoside may be increased in the presence of allopurinol with the risk of enhanced toxicity. When the two products are used concomitantly extra vigilance is necessary, to recognise enhanced toxic effects.
Salicylates and uricosuric agents
Oxipurinol, the major active metabolite of allopurinol, is excreted by the kidney in a similar way to urate. Hence, drugs with uricosuric activity such as probenecid or large doses of salicylates may accelerate the excretion of oxipurinol. This may decrease the therapeutic activity of allopurinol.
Chlorpropamide
If allopurinol is given concomitantly with chlorpropamide when renal function is poor, there may be an increased risk of prolonged hypoglycaemic activity because allopurinol and chlorpropamide may compete for excretion in the renal tubule.
Phenytoin
Allopurinol may inhibit hepatic oxidation of phenytoin but the clinical significance has not been demonstrated.
Theophylline
Inhibition of the metabolism of theophylline has been reported. The mechanism of the interaction may be explained by xanthine oxidase being involved in the biotransformation of theophylline in man. Theophylline levels should be measured when patients start or increase their dose of allopurinol.
Ampicillin/Amoxicillin
An increase in frequency of skin rash has been reported among patients receiving ampicillin or amoxicillin concurrently with allopurinol compared to patients who are not receiving both drugs. The cause of the reported association has not been established. However, it is recommended that in patients receiving allopurinol an alternative to ampicillin or amoxicillinis used where available.
Cyclophosphamide, doxorubicin, bleomycin, procarbazine, mechloroethamine Enhanced bone marrow suppression by cyclophosphamide and other cytotoxic agents has been reported among patients with neoplastic disease (other than leukaemia), in the presence of allopurinol. However, in a well-controlled study of patients treated with cyclophosphamide, doxorubicin, bleomycin, procarbazine and/or mechloroethamine (chlormethine hydrochloride) allopurinol did not appear to increase the toxic reaction of these cytotoxic agents.
Capecitabine
Allopurinol may decrease the activity of capecitabine.
Ciclosporin
Reports suggest that the plasma concentration of ciclosporin may be increased during concomitant treatment with allopurinol. The possibility of enhanced ciclosporin toxicity should be considered if the drugs are co-administered.
Didanosine
In healthy volunteers and HIV patients receiving didanosine, plasma didanosine Cmax and AUC values were approximately doubled with concomitant allopurinol treatment (300mg daily) without affecting terminal half-life. Co-administration of these two drugs is generally not recommended. If concomitant use is unavoidable, a dose reduction of didanosine may be required, and patients should be closely monitored.
Antacids
Allopurinol may fail to reduce the blood-uric-acid concentrations when given at the same time as aluminium hydroxide. Intake of antacids and allopurinol should be separated by 3 hours.
Ace inhibitors
Concurrent use of allopurinol and ACE inhibitors may lead to an increased risk of haematological reactions such as leucopenia, especially if there is preexisting renal failure.
4.6 Fertility, pregnancy and lactation
There are limited data from the use of allopurinol in pregnant women. There is a single case report implicating allopurinol in fetal malformation, possibly through inhibition of purine metabolism. High dose intraperitoneal allopurinol in mice has been associated with fetal abnormalities but extensive animal studies with oral allopurinol have shown none (see section 5.3)
Use in pregnancy only when there is no safer alternative and when the disease itself carries risk for the mother or unborn child.
Reports indicate that allopurinol and oxipurinol are excreted in human breast milk. Concentrations of 1.4mg/litre allopurinol and 53.7mg/litre oxipurinol have been demonstrated in breast milk from women taking allopurinol 300mg/day. However, there are no data concerning the effects of allopurinol or its metabolites on the breastfed baby.
4.7 Effects on ability to drive and use machines
Since adverse reactions such as somnolence, vertigo and ataxia have been reported in patients receiving allopurinol, patients should exercise caution before driving, using machinery or participating in dangerous activities until they are reasonably certain that allopurinol does not adversely affect performance.
4.8 Undesirable Effects
For this product there is no modern clinical documentation which can be used as support for determining the frequency of undesirable effects. Undesirable effects may vary in their incidence depending on the dose received and also when given in combination with other therapeutic agents.
The frequency categories assigned to the adverse drug reactions below are estimates. For most reactions, suitable data for calculating incidence are not available. Adverse drug reactions identified through post-marketing surveillance were considered to be rare or very rare. The following convention has been used for the classification of frequency:
Very common: Common: Uncommon: Rare:
Very rare:
> 1/10 (> 10%)
> 1/100 and <1/10 (> 1% and < 10%)
> 1/1,000 and <1/100 (> 0.1% and < 1%)
> 1/10,000 and <1/1,000 (> 0.01% and < 0.1%) < 1/10,000 (< 0.01%)
Adverse reactions from the use of allopurinol are usually rare and mostly minor. The incidence is higher in the presence of renal and/or hepatic disorder.
Infections and infestations Very rare: Furunculosis
Blood and lymphatic system disorders
Very rare: Agranulocytosis, aplastic anaemia, thrombocytopenia
Frequency not known: leucopenia, eosinophilia, haemolytic anaemia
Very rare reports have been received of thrombocytopenia, agranulocytosis and aplastic anaemia, particularly in individuals with impaired renal and/or hepatic function, reinforcing the need for particular care in this group of patients.
Skin and subcutaneous tissues disorders Common: Rash
Rare: Steven-Johnson syndrome/toxic epidermal necrolysis
Very rare: Angioedema, fixed drug eruption, alopecia, discoloured hair, DRESS
Syndrome (Drug Rash with Eosinophilia and Systemic Symptoms)
The most common side effect of allopurinol is skin rash and may occur at any time during treatment. Rashes are generally maculopapular or pruritic, sometimes scaly or purpuric and rarely exfoliative, such as Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). Allopurinol should be withdrawn immediately should such reactions occur.
After recovery from mild reactions, Allopurinol may, if desired, be re-introduced at a small dose (e.g. 50mg/day) and gradually increased. If the rash recurs, Allopurinol should be permanently withdrawn as more severe hypersensitivity may occur (see Immune system disorders).
The clinical diagnosis of SJS/TEN remains the basis for decision-making. If such reactions occur at any time during treatment, allopurinol should be withdrawn immediately and permanently.
Angioedema has been reported to occur with and without signs and symptoms of a more generalised hypersensitivity reaction.
Immune System Disorders
Uncommon: Hypersensitivity reactions
Very rare: Angioimmunoblastic lymphadenopathy
Serious hypersensitivity reactions, skin reactions associated with exfoliation, fever, lymphadenopathy, arthralgia and/or eosinophilia resembling the Stevens-Johnson and/or toxic epidermal necrolysis occur rarely (See Skin and subcutaneous tissue disorders). Associated vasculitis and tissue response may produce hepatitis, leucocytosis, interstitial nephritis and, very rarely epilepsy.
Very rarely acute anaphylactic shock has been reported. Such reactions may occur at any time during treatment. Allopurinol should be withdrawn immediately and permanently.
A delayed multi-organ hypersensitivity disorder (known as hypersensitivity syndrome or DRESS) with fever, rashes, vasculitis, lymphadenopathy, pseudo lymphoma, arthralgia, leucopenia, eosinophilia, hepato-splenomegaly, abnormal liver function tests and vanishing bile duct syndrome (destruction and disappearance of the intrahepatic bile ducts) occurring in various combinations. Other organs may also be affected (e.g. liver, lungs, kidneys, pancreas, myocardium, and colon). If such reactions do occur, it may be at any time during treatment, allopurinol should be withdrawn immediately and permanently.
When generalised hypersensitivity reactions have occurred, renal and/or hepatic disorder has usually been present particularly when the outcome has been fatal (see section 4.4).
Corticosteroids may be beneficial in overcoming hypersensitivity skin reactions. When generalised hypersensitivity reactions have occurred, a renal and/or hepatic disorder has usually been present, particularly when the outcome has been fatal. Angioimmunoblastic Lymphadenopathy has been described rarely following the biopsy of a generalised lymphadenopathy. It is reversible on withdrawal of allopurinol.
Metabolism and nutrition disorders
Very rare: Diabetes mellitus, hyperlipidaemia
Psychiatric disorders Very rare: Depression
Nervous system disorders
Very rare: Coma, paralysis, ataxia, neuropathy, paraesthesiae, somnolence,
headache, taste perversion Frequency not known: dizziness
Eye disorders
Very rare: Cataract, visual disorder, macular changes
Ear and labyrinth disorders Very rare: Vertigo
Cardiac disorders
Very rare: Angina, bradycardia
Frequency not known: vasculitis
Vascular disorders Very rare: Hypertension
Gastrointestinal disorder Uncommon: Vomiting, nausea
Very rare: Recurrent haematemesis, steatorrhoea, stomatitis, changed bowel habit
Frequency not known: diarrhoea, abdominal pain,
In early clinical studies, nausea and vomiting were reported. Further reports suggest that this reaction is not a significant problem and can be avoided by taking allopurinol after meals.
Hepatobillary disorders
Uncommon: Asymptomatic increases in liver function tests
Rare: Hepatitis (including hepatic necrosis and granulomatous hepatitis)
Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity.
Renal and Urinary disorders Very rare: Haematuria, uraemia
Frequency not known: nephrolithiasis
Reproductive system and breast disorders
Very rare: Male infertility, erectile dysfunction, gynaecomastia
Frequency not known: nocturnal emissions
General disorders and administration site conditions Very rare: Oedema, general malaise, asthenia, fever
Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity reaction (see Immune system disorders).
4.9 Overdose
Accidental or deliberate ingestion of up to 5g of allopurinol, or very rarely 20g, has been reported.
Symptoms and signs include nausea, vomiting, diarrhoea, headache, somnolence, abdominal pain and dizziness. Recovery followed general supportive measures. The most likely reaction would be gastrointestinal intolerance. Massive absorption may lead to considerable inhibition of xanthine oxidase activity. However, this should have no untoward effects unless 6-mercaptopurine, adenine arabinoside and/or azathioprine are being taken concomitantly.
Treatment
The benefit of gastric decontamination is uncertain. Consider activated charcoal (charcoal dose: 50 g for adults; 1 g/ kg for children) if the patient presents within 1 hour of ingestion of more than 50 mg/kg. If more than 50 mg/kg has been ingested check U&Es and LFTs.
Adequate hydration to maintain optimum diuresis facilitates excretion of allopurinol and its metabolites. Haemodialysis may be utilised, if considered necessary.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Preparation inhibiting uric acid production ATC Code: M04AA01
Allopurinol has no other important effects in man other than through inhibition of xanthine oxidase. Allopurinol and its main metabolite oxipurinol lower the level of uric acid in plasma and urine by inhibition of xanthine oxidase, the enzyme catalyzing the oxidation of hypoxanthine to xanthine and xanthine to uric acid. In addition to the inhibition of purine catabolism in some but not all hyperuricaemic patients, de novo purine biosynthesis is depressed via feedback inhibition of hypoxanthine-guanine phosphoribosyltransferase. Other metabolites of allopurinol include allopurinol-riboside and oxipurinol-7 riboside.Lowering uric acid concentrations in tissues leads to gradual dissolution of gouty tophi and halts the progression of gouty arthritis.
Acute attacks of gout may be precipitated by allopurinol in the initial stages of the treatment and this possibility should be covered by the use of a non-steroidal antiinflammatory drug. The urinary excretion of xanthine is increased and in patients with very high uric acid production rates xanthine stones may be formed in the urine. This is very unusual and the risk can be minimised by alkalising the urine and increasing the fluid intake.
5.2 Pharmacokinetic Properties
Allopurinol is active when given orally and is rapidly absorbed from the upper gastrointestinal tract. Studies have detected allopurinol in the blood 30-60 minutes after dosing. Estimates of bioavailability vary from 67% to 90%. Peak plasma levels of allopurinol generally occur approximately 1.5 hours after oral administration of Allopurinol, but fall rapidly and are barely detectable after 6 hours. Peak levels of oxipurinol generally occur 3-5 hours after oral administration of Allopurinol and are much more sustained.
Allopurinol is negligibly bound by plasma proteins and therefore variations in protein binding are not thought to significantly alter clearance. The apparent volume of distribution of allopurinol is approximately 1.6 litre/kg which suggests relatively extensive uptake by tissues. Tissue concentrations of allopurinol have not been reported in humans, but it is likely that allopurinol and oxipurinol will be present in the highest concentrations in the liver and intestinal mucosa where xanthine oxidase activity is high.
Approximately 20% of the ingested allopurinol is excreted in the faeces. Elimination of allopurinol is mainly by metabolic conversion to oxipurinol by xanthine oxidase and aldehyde oxidase, with less than 10% of the unchanged drug excreted in the urine. Allopurinol has a plasma half-life of about 1 to 2 hours.
Oxipurinol is a less potent inhibitor of xanthine oxidase than allopurinol, but the plasma halflife of oxipurinol is far more prolonged. Estimates range from 13 to 30 hours in man. Therefore effective inhibition of xanthine oxidase is maintained over a 24 hour period with a single daily dose of Allopurinol. Patients with normal renal function will gradually accumulate oxipurinol until a steady-state plasma oxipurinol concentration is reached. Such patients, taking 300 mg of allopurinol per day will generally have plasma oxipurinol concentrations of 5-10mg/litre.
Oxipurinol is eliminated unchanged in the urine but has a long elimination half-life because it undergoes tubular reabsorption. Reported values for the elimination half-life range from 13.6 hours to 29 hours. The large discrepancies in these values may be accounted for by variations in study design and/or creatinine clearance in the patients.
Pharmacokinetics in patients with renal impairment
Allopurinol and oxipurinol clearance is greatly reduced in patients with poor renal function resulting in higher plasma levels in chronic therapy. Patients with renal impairment, where creatinine clearance values were between 10 and 20ml/min, showed plasma oxipurinol concentrations of approximately 30mg/litre after prolonged treatment with 300mg allopurinol per day. This is approximately the concentration which would be achieved by doses of 600mg/day in those with normal renal function. A reduction in the dose of Allopurinol is therefore required in patients with renal impairment.
Pharmacokinetics in elderly patients
The kinetics of the drug is not likely to be altered other than due to deterioration in renal function (see Pharmocokinetics in patients with renal impairment).
5.3 Preclinical safety data
A. Mutagenicity
Cytogenetic studies show that allopurinol does not induce chromosome aberrations in human blood cells in vitro at concentrations up to 100 micrograms/ml and in vivo at doses up to 600 mg/day for mean period of 40 months.
Allopurinol does not produce nitraso compounds in vitro or affect lymphocyte transformation in vitro.
Evidence from biochemical and other cytological investigations strongly suggests that allopurinol has no deleterious effects on DNA at any stage of the cell cycle and is not mutagenic.
B. Carcinogenicity
No evidence of carcinogenicity has been found in mice and rats treated with allopurinol for up to 2 years.
C. Teratogenicity
One study in mice receiving intraperitoneal doses of 50 or 100 mg/kg on days 10 or 13 of gestation resulted in foetal abnormalities, however in a similar study in rats at 120 mg/kg on day 12 of gestation no abnormalities were observed. Extensive studies of high oral doses of allopurinol in mice up to 100 mg/kg/day, rats up to 200 mg/kg/day and rabbits up to 150 mg/kg/day during days 8 to 16 of gestation produced no teratogenic effects.
An in vitro study using foetal mouse salivary glands in culture to detect embryotoxicity indicated that allopurinol would not be expected to cause embryotoxicity without also causing maternal toxicity.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate Maize starch Povidone Crospovidone Magnesium stearate
6.2 Incompatibilities
None known.
6.3 Shelf life 3 years
6.4 Special precautions for storage
Do not store above 25°C.
Keep the container tightly closed. Store in the original container.
6.5 Nature and contents of container
Polypropylene securitainer fitted with low-density polyethylene caps.
Pack sizes: 28,100,500 and 1000 tablets. Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Athlone Pharmaceuticals Limited
Ballymurray
Roscommon
County Roscommon
Ireland
8 MARKETING AUTHORISATION NUMBER(S)
PL 30464/0008
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
24/04/2008
10 DATE OF REVISION OF THE TEXT
26/03/2013