In the US, Healon is a member of the drug class ophthalmic surgical agents and is used to treat Ophthalmic Viscoelastic Agent.
Hyaluronic Acid sodium salt (a derivative of Hyaluronic Acid) is reported as an ingredient of Healon in the following countries:
International Drug Name Search
Pulmicort® LS Inhaler, 50 micrograms per actuation, pressurised inhalation suspension.
Pulmicort LS Inhaler contains budesonide, 50 micrograms per actuation (puff).
For excipients see 6.1.
Pulmicort LS Inhaler is a pressurised inhalation suspension. The suspension is delivered via a pressurised metered dose inhaler (pMDI).
Pulmicort LS inhaler may also be administered via the Nebuhaler®.
Pulmicort LS Inhaler is recommended in patients with bronchial asthma.
Adults: 200 micrograms twice daily, in the morning and in the evening. During periods of severe asthma, the daily dosage can be increased up to 1600 micrograms.
In patients whose asthma is well controlled, the daily dose may be reduced below 400 micrograms, but should not go below 200 micrograms.
The dose should be reduced to the minimum needed to maintain good asthma control.
Children: 50 to 400 micrograms to be given twice daily. During periods of severe asthma, the daily dose can be increased up to 800 micrograms.
The dose should be reduced to the minimum needed to maintain good asthma control.
Elderly: Dosage as for adults.
Patients maintained on oral glucocorticosteroids
Pulmicort Inhaler may permit replacement or significant reduction in the dosage of oral glucocorticosteroids while maintaining asthma control. For further information on the withdrawal of oral corticosteroids, see section 4.4
Instructions for the correct use of Pulmicort LS Inhaler:
Note: It is important to instruct the patient
• To carefully read the instructions for use in the patient information leaflet, which is packed with each inhaler.
• To shake the inhaler thoroughly before each actuation, in order to mix the contents of the inhaler properly.
• To breathe in slowly and deeply through the mouthpiece and to release the dose whilst continuing to breathe in.
On actuation of Pulmicort LS Inhaler, a suspension of the substance is pumped out of the canister at a high velocity. When the patient inhales through the mouthpiece at the same time as releasing a dose, the substance will follow the inspired air into the airways.
History of hypersensitivity to budesonide or any of the excipients. No other specific contraindications are known, but special care is needed in patients with lung tuberculosis, fungal and viral infections in the airways.
Patients not dependent on steroids: Treatment with the recommended doses of Pulmicort LS Inhaler usually gives a therapeutic benefit within 7 days. However, certain patients may have an excessive collection of mucous secretion in the bronchi, which reduces penetration of the active substance into the airways. In these cases, a short course of oral corticosteroids (usually 1 to 2 weeks) should be given in addition to the aerosol. After the course of the oral drug, the inhaler alone should be sufficient therapy. Exacerbations of asthma caused by bacterial infections are usually controlled by appropriate antibiotic treatment and possibly increasing the Pulmicort LS Inhaler dosage or, if necessary, by giving systemic steroids.
Steroid-dependent patients: Transfer of patients dependent upon oral steroids to treatment with Pulmicort LS Inhaler demands special care, mainly due to the slow restitution of the disturbed hypothalamic-pituitary function, caused by extended treatment with oral corticosteroids. When the Pulmicort LS Inhaler treatment is initiated, the patient should be in a relatively stable phase. Pulmicort LS Inhaler is then given in combination with the previously used oral steroid dose, for about 10 days.
After this period of time, the reduction of the oral corticosteroid dose can be started, with a dose reduction corresponding to about 1 mg prednisolone per day, every week. The oral dose is thus reduced to the lowest level which, in combination with Pulmicort LS Inhaler, gives a stable respiratory capacity.
In many cases, it may eventually be possible to completely substitute the oral steroid with Pulmicort LS Inhaler, but other cases may have to be maintained on a low steroid dosage.
Some patients may experience unease during the withdrawal period due to a decreased steroid effect. The physician may have to explain the reason for the Pulmicort LS Inhaler treatment in order to encourage the patient to continue. The length of time needed for the body to regain its natural production of corticosteroid in sufficient amounts is often extensive. Prolonged treatment with high doses of inhaled corticosteroids, particularly higher than the recommended doses, may result in clinically significant adrenal suppression. Additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.
During transfer from oral therapy to Pulmicort LS Inhaler, a generally lower systemic steroid action will be experienced which may result in the appearance of allergic or arthritic symptoms such as rhinitis, eczema, and muscle and joint pain. Specific treatment should be initiated for these conditions. A general insufficient glucocorticosteroid effect should be suspected if, in rare cases, symptoms such as tiredness, headache, nausea and vomiting should occur. In these cases a temporary increase in the dose of oral glucocorticosteroids is sometimes necessary.
As with other inhalation therapy, paradoxical bronchospasm may occur, with an immediate increase in wheezing after dosing. If a severe reaction occurs, treatment should be reassessed and an alternative therapy instituted if necessary.
Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma.
It is important, therefore, that the dose of inhaled corticosteroid is titrated to the lowest dose at which effective control of asthma is maintained.
It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly monitored. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of inhaled corticosteroid, if possible, to the lowest dose at which effective control of asthma is maintained. In addition, consideration should be given to referring the patient to a paediatric respiratory specialist.
If patients find short-acting bronchodilator treatment ineffective, or they need more inhalations than usual, medical attention must be sought. In this situation consideration should be given to the need for or an increase in their regulartherapy, e.g., higher doses of inhaled budesonide, the addition of a long-acting beta agonist or a course of oral glucocorticosteroid.
Reduced liver function may affect the elimination of glucocorticosteroids. The plasma clearance following an intravenous dose of budesonide however was similar in cirrhotic patients and in healthy subjects. After oral ingestion systemic availability of budesonide was increased by compromised liver function due to decreased first pass metabolism. The clinical relevance of this to treatment with Pulmicort is unknown as no data exist for inhaled budesonide, but increases in plasma levels and hence an increased risk of systemic adverse effects could be expected.
In vivo studies have shown that oral administration of ketoconazole and itraconazole (known inhibitors of CYP3A4 activity in the liver and in the intestinal mucosa) causes an increase in the systemic exposure to budesonide. Concomitant treatment with ketoconazole and itraconazole or other potent CYP3A4 inhibitors should be avoided (see section 4.5 Interactions). If this is not possible, the time interval between administration of the interacting drugs should be as long as possible. A reduction in the dose of budesonide should also be considered.
The metabolism of budesonide is primarily mediated by CYP3A4, one of the cytochrome p450 enzymes. Inhibitors of this enzyme, e.g. ketoconazole and itraconazole, can therefore increase systemic exposure to budesonide, (see Section 4.4 Special Warnings and Special Precautions for Use and Section 5.2 Pharmacokinetic Properties). Other potent inhibitors of CYP3A4 are also likely to markedly increase plasma levels of budesonide.
Data on approximately 2000 exposed pregnancies indicate no increased teratogenic risk associated with the use of inhaled budesonide. In animal studies, glucocorticosteroids have been shown to induce malformations (see Section 5.3). This is not likely to be relevant for humans given recommended doses, but therapy with inhaled budesonide should be regularly reviewed and maintained at the lowest effective dose.
The administration of budesonide during pregnancy requires that the benefits for the mother be weighed against the risk for the foetus. Inhaled glucocorticosteroids should be considered in preference to oral glucocorticosteroids because of the lower systemic effects at the doses required to achieve similar pulmonary responses. There is no information regarding the passage of budesonide into breast milk.
Pulmicort LS Inhaler does not affect ability to drive or use machines.
Clinical trials, literature reports and post-marketing experience suggest that the following adverse drug reactions may occur:
|
|
|
|
The candida infection in the oropharynx is due to drug deposition. Advising the patient to rinse the mouth out with water after each dosing will minimise the risk. The incidence should be less with the Nebuhaler®, as this reduces oral deposition.
As with other inhalation therapy, paradoxical bronchospasm may occur in very rare cases (see Section 4.4).
Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma. The effect is probably dependent on dose, exposure time, concomitant and previous steroid exposure, and individual sensitivity.
The only harmful effect that follows inhalation of large amounts of the drug over a short period is suppression of hypothalamic-pituitary-adrenal (HPA) function. No special emergency action needs to be taken. Treatment with Pulmicort LS Inhaler should be continued at the recommended dose to control the asthma.
Budesonide is a glucocorticosteroid which possesses a high local
anti-inflammatory action, with a lower incidence and severity of adverse effects than those seen with oral corticosteroids
Pharmacotherapeutic group: Other drugs for obstructive airway diseases, inhalants, glucocorticoids. ATC Code: RO3B A02.
Topical anti-inflammatory effect
The exact mechanism of action of glucocorticosteroids in the treatment of asthma is not fully understood. Anti-inflammatory actions, such as inhibition of inflammatory mediator release and inhibition of cytokine-mediated immune response are probably important.
A clinical study in asthmatics comparing inhaled and oral budesonide at doses calculated to achieve similar systemic bioavailability demonstrated statistically significant evidence of efficacy with inhaled but not oral budesonide compared with placebo. Thus, the therapeutic effect of conventional doses of inhaled budesonide may be largely explained by its direct action on the respiratory tract.
In a provocation study pre-treatment with budesonide for four weeks has shown decreased bronchial constriction in immediate as well as late asthmatic reactions.
Onset of effect
After a single dose of orally inhaled budesonide, delivered via dry powder inhaler, improvement of the lung function is achieved within a few hours. After therapeutic use of orally inhaled budesonide delivered via dry powder inhaler, improvement in lung function has been shown to occur within 2 days of initiation of treatment, although maximum benefit may not be achieved for up to 4 weeks.
Airway reactivity
Budesonide has also been shown to decrease airway reactivity to histamine and methacholine in hyper-reactive patients.
Exercise-induced asthma
Therapy with inhaled budesonide has effectively been used for prevention of exercise-induced asthma.
Growth
Limited data from long term studies suggest that most children and adolescents treated with inhaled budesonide ultimately achieve their adult target height. However, an initial small but transient reduction in growth (approximately 1 cm) has been observed. This generally occurs within the first year of treatment (see section 4.4).
HPA axis function
Studies in healthy volunteers with inhaled budesonide (administered as a dry powder via Turbohaler) have shown dose-related effects on plasma and urinary cortisol. At recommended doses, Pulmicort Turbohaler, causes less effect on the adrenal function than prednisolone 10mg, as shown by ACTH tests.
Budesonide is a glucocorticosteroid with high local anti-inflammatory effect.
Budesonide undergoes extensive biotransformation in the liver, to metabolites of low glucocorticosteroid activity. The glucocorticosteroid activity of the major metabolites 6β-hydroxybudesonide and 16α-hydroxyprednisolone, is less than 1% of that of budesonide. The metabolism of budesonide is primarily mediated by CYP3A4, one of the cytochrome p450 enzymes.
In a study, 100 mg ketoconazole taken twice daily, increased plasma levels of concomitantly administered oral budesonide (single dose of 10 mg) on average, by 7.8-fold. Information about this interaction is lacking for inhaled budesonide, but marked increases in plasma levels could be expected.
About 10% of the dose is deposited in the lungs. Of the fraction of budesonide which is swallowed, approximately 90% is inactivated at first passage through the liver. The maximal plasma concentration after inhalation of 1 mg budesonide is about 2.1 nmol/L and is reached after about 10 minutes.
The acute toxicity of budesonide is low and of the same order of magnitude and type as that of the reference glucocorticosteroids studied (beclomethasone dipropionate, fluocinolone acetonide).
Results from subacute and chronic toxicity studies show that the systemic effects of budesonide are less severe than, or similar to, those observed after administration of the other glucocorticosteroids, e.g. decreased body-weight gain and atrophy of lymphoid tissues and adrenal cortex.
An increased incidence of brain gliomas in male rats, in a carcinogenicity study, could not be verified in a repeat study in which the incidence of gliomas did not differ between any of the groups on active treatment (budesonide, prednisolone, triamcinolone acetonide) and the control groups.
Liver changes (primary hepatocellular neoplasms) found in male rats in the original carcinogenicity study were noted again in the repeat study with budesonide, as well as with the reference glucocorticosteroids. These effects are most probably related to a receptor effect and thus represent a class effect.
Available clinical experience shows no indication that budesonide, or other glucocorticosteroids, induce brain gliomas or primary hepatocellular neoplasms in man.
In animal reproduction studies, corticosteroids such as budesonide have been shown to induce malformations (cleft palate, skeletal malformations). However, these animal experimental results do not appear to be relevant in humans at the recommended doses.
Animal studies have also identified an involvement of excess prenatal glucocorticosteroids, in increased risk for intrauterine growth retardation, adult cardiovascular disease and permanent changes in glucocorticoid receptor density, neurotransmitter turnover and behaviour at exposures below the teratogenic dose range.
Sorbitan trioleate, trichlorofluoromethane, dichlorotetrafluoroethane, dichlorodifluoromethane.
None known.
24 months
Do not store above 30˚C.
Do not puncture or expose the canister to high temperatures (40ºC) or direct sunlight, even when empty.
Aluminium canister containing 200 metered doses of budesonide, fitted with a valve to deliver 50 micrograms budesonide per actuation. The canister fits into a plastic adaptor made of polypropylene, with a removable cover made of polypropylene or polyethylene.
See Section 4.2 Posology and Method of Administration.
AstraZeneca UK Ltd.,
600 Capability Green,
Luton, LU1 3LU, UK.
PL 17901/0159
28th June 2002
4th April 2004
Ammonia and Ipecacuanha Mixture BP 1999
Ammonium Hydrogen Carbonate 100.0 mg per 5ml dose
Ipecacuanha Tincture BP 1999 0.15 ml per 5 ml dose
For full list of excipients, see 6.1
Oral solution.
A dark brown liquid
For the symptomatic relief of productive coughs.
Oral.
Dose and dosage schedule
Adults, the elderly and children over 12 years: 10- 20ml, repeated after 4 hours if required. Not more than 4 doses to be taken in any 24 hours.
Contraindicated in patients with known sensitivity to ipecacuanha, ammonium salts or any of the other ingredients. Contraindicated in patients with hepatic or renal impairment, cardiovascular disorders, patients in shock or at risk from seizures.
Do not exceed the stated dose.
If symptoms persist consult your doctor.
Keep all medicines away from children.
Discard any unused mixture 2 months after opening.
None known.
As with all medicines, use should be avoided during pregnancy, especially in the first trimester, and in lactation unless recommended by a doctor.
No or negligible influence.
Large doses of ipecacuanha or ammonium salts may cause nausea and vomiting, however, these effects would not be expected to occur when this preparation is taken at the recommended dose.
Large doses of ammonium salts irritate the gastric mucosa and may result in nausea and vomiting. Excessive doses of ammonium salts may give rise to hepatic encephalopathy, however, this effect is unlikely to occur after oral administration.
Large doses of ipecacuanha irritate the gastro-intestinal tract and may give rise to persistent bloody vomiting, and diarrhoea.
Absorption of emetine, which is most likely if vomiting does not occur after emetic doses of ipecacuanha, may have adverse effects on the heart, such as conduction abnormalities or myocardial infarction. These, combined with dehydration due to vomiting may cause vasomotor collapse followed by death. Chronic abuse of ipecacuanha may result in cardiotoxicity and myopathy due to the accumulation of emetine, and recovery may be prolonged due to its slow elimination.
After acute overdosage of ipecacuanha, activated charcoal should be given to delay absorption, followed by gastric lavage if necessary. Excessive vomiting should be controlled by administration of an anti-emetic and fluid and electrolyte imbalance corrected if necessary.
Overdose with this preparation is unlikely to occur due to the low concentrations of the active ingredients present.
R05C A04 – Cough and cold preparations, expectorants
Ammonium Hydrogen Carbonate is an expectorant used to aid relief of productive coughs.
Ipecacuanha is an expectorant, and in larger doses an emetic.
Ammonium Hydrogen Carbonate is metabolised to produce urea and free bicarbonate.
Emetine, one of the major alkaloids of ipecacuanha is excreted or metabolised slowly, it has been detected in urine 40 – 60 days after discontinuation of treatment.
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
Liquorice Liquid Extract
Camphor Water Concentrated
Anise Water Concentrated
Chloroform
Purified Water
None known.
18 months unopened.
2 months after first opening.
Store below 25°C. Discard any unused mixture 2 months after opening.
200 ml: Amber glass bottle with plastic 28mm tamper evident child resistant closure with EPE /Saranex liner.
None.
Thornton & Ross Ltd
Linthwaite Laboratories
Huddersfield
HD7 5QH
PL 00240/6458R
15th June 1988
01/05/2011
ANDROPATCH 5 mg / 24 hours Transdermal Patch
Testosterone
Andropatch contains a medicine called testosterone.
Andropatch is used to replace testosterone in men who have low or no natural testosterone (called hypogonadism).
This may be caused by:
Testosterone helps the penis and testicles to develop normally. It allows men to produce sperm and keep their sex drive. They also need testosterone to grow body hair and to develop their bones and muscles. It also makes their voice deepen.
Signs of low testosterone may include the following:
Do not use Andropatch if:
If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before using Andropatch.
Before you use Andropatch, tell your doctor or pharmacist if:
If you are elderly the doctor may discuss with you the effect of testosterone on your prostate. You may need regular checks of your prostate.
If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before using Andropatch. Even so your doctor may still want you to use Andropatch and will advise you about your medicine.
Please tell your doctor or pharmacist if you are taking, or have recently taken any other medicines, including medicines obtained without a prescription. This includes herbal medicines. This is because Andropatch can affect the way some medicines work. Also some medicines can affect the way Andropatch works.
In particular tell your doctor or pharmacist if you are taking any of the following:
If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before using Andropatch.
You must not use Andropatch if you are a woman.
It has not been tested in women and if you are pregnant, it may be harmful to unborn babies.
Do not breast-feed while using Andropatch.
Always use Andropatch exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.
The usual starting dose is one patch each night. Look at the label on the pack to see how many patches your doctor would like you to use each day.
You can put the patch on your back, stomach, upper arms or thighs.
Some people prefer to choose an area of their body that will be covered by their clothes.
If you put on too many patches by mistake, take off the extra ones as soon as you realise. Do not put these extra patches back in their pouches. Get rid of them as outlined above (See point 6: Removing your patch).
If you have any further questions on the use of this product, ask your doctor or pharmacist.
Like all medicines, Andropatch can cause side effects, although not everybody gets them. The following side effects may happen with this medicine.
Most patients get some redness, itching, burning, hardness or rashes on their skin where the patch has been at some time during their treatment. This usually disappears within 10 days of removing the patch. If the redness and itching are a particular problem, your pharmacist or doctor may be able to recommend a cream which will help. You can avoid or reduce these problems by putting your patch in a different place each day.
Sometimes a more severe skin reaction can occur causing a blister like a burn where the patch has been. If this happens remove the patch straight away and tell your doctor as soon as possible. The blisters may produce sores that take a few weeks to heal and may leave a scar.
Other side effects caused by testosterone include:
Men having testosterone have also sometimes had:
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
The other ingredients are ethanol, purified water, glycerol (E422), glycerol mono-oleate, methyl laurate, carbomer copolymer B and sodium hydroxide (E524).
Andropatch 5 mg is an oval, beige, patch. Each patch comes in a protective pouch. Andropatch 5 mg is available in packs of 30 transdermal patches.
Components of the patch: silicone-coated polyester liner, acrylic adhesive/silicone-coated PET laminate, peelable LDPE/aluminium/polyester film, microporous HMWPE (high molecular weight polyethylene) film. Backing film: inner layer of EVA, Surlyn and metallised polyethylene. Outer layer: polyethylene layer, pigmented with alcohol resistant beige ink to form a beige, plastic film.
Marketing Authorisation Holder:
Manufacturer:
Other formats:
To listen to or request a copy of this leaflet in Braille, large print or audio please call, free of charge: 0800 198 5000 (UK Only)
Please be ready to give the following information:
Product Name Andropatch 5 mg
Reference number 10592/0106
This is a service provided by the Royal National Institute of the Blind.
Patient reminder chart
Make sure you change the position of your patches each day. Do not put a patch in the same place on your body twice in the same week. A patient reminder chart can be used to help you remember where you have put your patches each day, and this can be found at the end of your package leaflet.
You can put Andropatch on your back, stomach, upper arms or thighs.
Andropatch is a registered trademark of the GlaxoSmithKline group of companies
© 2007 GlaxoSmithKline group of companies
Leaflet date: August 2007.
200234-03
Arthrotec 50 modified-release tablets.
Each tablet consists of a gastro-resistant core containing 50mg diclofenac sodium surrounded by an outer mantle containing 200mcg misoprostol.
Excipient(s):
Each tablet contains 13 mg lactose monohydrate.
For a full list of excipients, see section 6.1.
Modified-release tablet.
White, round, biconvex tablets marked
Arthrotec 50 is indicated for patients who require the non-steroidal anti-inflammatory drug diclofenac together with misoprostol.
The diclofenac component of Arthrotec 50 is indicated for the symptomatic treatment of osteoarthritis and rheumatoid arthritis. The misoprostol component of Arthrotec 50 is indicated for patients with a special need for the prophylaxis of NSAID-induced gastric and duodenal ulceration
Adults
One tablet to be taken with food, two or three times daily. Tablets should be swallowed whole, not chewed.
Elderly/Renal Impairment/Hepatic Impairment
No adjustment of dosage is necessary in the elderly or in patients with hepatic impairment or mild to moderate renal impairment as pharmacokinetics are not altered to any clinically relevant extent. Nevertheless patients with renal or hepatic impairment should be closely monitored (see section 4.4 and section 4.8).
Children
The safety and efficacy of Arthrotec 50 in children has not been established.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
Arthrotec 50 is contraindicated in:
- Patients with active peptic ulcer/haemorrhage or perforation or who have active GI bleeding or other active bleedings e.g. cerebrovascular bleedings.
- Pregnant women and in women planning a pregnancy.
- Patients with a known hypersensitivity to diclofenac, aspirin, other NSAIDs, misoprostol, other prostaglandins, or any other ingredient of the product.
- Patients in whom attacks of asthma, urticaria or acute rhinitis are precipitated by aspirin or other non-steroidal anti-inflammatory agents.
- Treatment of peri-operative pain in the setting of coronary bypass graft (CABG) surgery.
- Patients with severe renal and hepatic failure.
- Patients with severe heart failure.
Warnings
The use of diclofenac/misoprostol with concomitant NSAIDs including COX-2 inhibitors should be avoided.
Use in pre-menopausal women (see also section 4.3))
Arthrotec 50 should not be used in pre-menopausal women unless they use effective contraception and have been advised of the risks of taking the product if pregnant (see section 4.6). The label will state: 'Not for use by pre-menopausal women unless using effective contraception'.
Precautions
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).
•Renal/Cardiac/Hepatic
In patients with renal, cardiac or hepatic impairment caution is required since the use of NSAIDs may result in deterioration of renal function. In the following conditions Arthrotec 50 should be used only in exceptional circumstances and with close clinical monitoring: advanced cardiac failure, advanced kidney failure, advanced liver disease, severe dehydration.
Diclofenac metabolites are eliminated primarily by the kidneys (see section 5.2). The extent to which the metabolites may accumulate in patients with renal failure has not been studied. As with other NSAIDs, metabolites of which are excreted by the kidney, patients with significantly impaired renal function should be more closely monitored.
In rare cases, NSAIDs, including diclofenac/misoprostol, may cause interstitial nephritis, glomerulitis, papillary necrosis and the nephrotic syndrome. NSAIDs inhibit the synthesis of renal prostaglandin which plays a supportive role in the maintenance of renal perfusion in patients whose renal blood flow and blood volume are decreased. In these patients, administration of an NSAID may precipitate overt renal decompensation, which is typically followed by recovery to pretreatment state upon discontinuation of NSAID therapy. Patients at greatest risk of such a reaction are those with congestive heart failure, liver cirrhosis, nephrotic syndrome and overt renal disease. Such patients should be carefully monitored while receiving NSAID therapy.
Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.
As with all NSAIDS, diclofenac/misoprostol can lead to the onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of cardiovascular events. NSAIDs, including diclofenac/misoprostol, should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of therapy with diclofenac/misoprostol and throughout the course of therapy.
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with diclofenac after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Clinical trial and epidemiological data suggest that use of diclofenac, particularly at high dose (150mg daily) and in long term treatment may be associated with a small increased risk of serious arterial thrombotic events (for example myocardial infarction or stroke).
Physicians and patients should remain alert for the development of such events, even in the absence of previous cardiovascular symptoms. Patients should be informed about the signs and/or symptoms of serious cardiovascular toxicity and the steps to take if they occur (see section 4.3).
•Blood system/Gastrointestinal
NSAIDs, including diclofenac/misoprostol, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. When GI bleeding or ulceration occurs in patients receiving diclofenac/misoprostol, the treatment should be withdrawn. These events can occur at any time during treatment, with or without warning symptoms or in patients with a previous history of serious GI events.
Patients most at risk of developing these types of GI complications with NSAIDs are those treated at higher doses, the elderly, patients with cardiovascular disease, patients using concomitant aspirin, or patients with a prior history of, or active, gastrointestinal disease, such as ulceration, GI bleeding or inflammatory conditions.
Therefore, diclofenac/misoprostol should be used with caution in these patients and commence on treatment at the lowest dose available (see section 4.3).
Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment. Caution should be advised in patients receiving concomitant medicines which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5).
Arthrotec 50, in common with other NSAIDs, may decrease platelet aggregation and prolong bleeding time. Extra supervision is recommended in haematopoietic disorders or in conditions with defective coagulation or in patients with a history of cerebrovascular bleeding.
Caution is required in patients suffering from ulcerative colitis or Crohn's Disease as these conditions may be exacerbated (see section 4.8).
Care should be taken in elderly patients and in patients treated with corticosteroids, other NSAIDs, or anti-coagulants (see section 4.5).
•Skin Reactions
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs, including diclofenac/misoprostol (see section 4.8). Patients appear to be at highest risk for these events early in the course of therapy, the onset of the event occurring in the majority of cases within the first month of treatment. Diclofenac/misoprostol should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity
• Hypersensitivity
NSAIDs may precipitate bronchospasm in patients suffering from, or with a history of, bronchial asthma or allergic disease.
•Long-term treatment
All patients who are receiving long-term treatment with NSAIDs should be monitored as a precautionary measure (e.g. renal, hepatic function and blood counts). During long-term, high dose treatment with analgesic/anti-inflammatory drugs, headaches can occur which must not be treated with higher doses of the medicinal product.
Arthrotec may mask fever and thus an underlying infection.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
NSAIDs may attenuate the natriuretic efficacy of diuretics due to inhibition of intrarenal synthesis of prostaglandins. Concomitant treatment with potassium-sparing diuretics may be associated with increased serum potassium levels, hence serum potassium should be monitored.
Because of their effect on renal prostaglandins, cyclo-oxygenase inhibitors such as diclofenac can increase the nephrotoxicity of ciclosporin. There is a possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Steady state plasma lithium and digoxin levels may be increased and ketoconazole levels may be decreased.
Pharmacodynamic studies with diclofenac have shown no potentiation of oral hypoglycaemic and anticoagulant drugs. However as interactions have been reported with other NSAIDs, caution and adequate monitoring are, nevertheless advised (see statement on platelet aggregation in Precautions).
Because of decreased platelet aggregation caution is also advised when using Arthrotec 50 with anti-coagulants. NSAIDs may enhance the effects of anti-coagulants, such as warfarin, antiplatelet agents, such as aspirin, and serotonin re-uptake inhibitors (SSRIs) thereby increasing the risk of gastrointestinal bleeding (see section 4.4).
Cases of hypo and hyperglycaemia have been reported when diclofenac was associated with antidiabetic agents.
Caution is advised when methotrexate is administered concurrently with NSAIDs because of possible enhancement of its toxicity by the NSAID as a result of increase in methotrexate plasma levels.
Concomitant use with other NSAIDs or with corticosteroids may increase the frequency of side effects generally.
Anti-hypertensives including diuretics, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists (AIIA): NSAIDs can reduce the efficacy of diuretics and other antihypertensive drugs.
In patients with impaired renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the co-administration of an ACE inhibitor or an AIIA with a cyclo-oxygenase inhibitor can increase the deterioration of the renal function, including the possibility of acute renal failure, which is usually reversible. The occurrence of these interactions should be considered in patients taking diclofenac/misoprostol with an ACE inhibitor or an AIIA.
Antacids may delay the absorption of diclofenac. Magnesium-containing antacids have been shown to exacerbate misoprostol-associated diarrhoea.
Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.
NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
Pregnancy
Arthrotec 50 is contraindicated in pregnant women and in women planning a pregnancy because misoprostol induces uterine contractions and is associated with abortion, premature birth, and foetal death. Use of misoprostol has been associated with birth defects. Also diclofenac may cause premature closure of the ductus arteriosus.
Women of childbearing potential should not be started on diclofenac/misoprostol until pregnancy is excluded, and should be fully counseled on the importance of adequate contraception while undergoing treatment. If pregnancy is suspected, use of the product should be discontinued.
Lactation
Misoprostol is rapidly metabolised in the mother to misoprostol acid, which is biologically active and is excreted in breast milk. Diclofenac is excreted in breast milk in very small quantities. In general, the potential effects on the infant from any exposure to misoprostol and its metabolites via breast feeding are unknown. However, diarrhoea is a recognised side effect of misoprostol and could occur in infants of nursing mothers. Arthrotec 50 should therefore not be administered to nursing mothers.
Patients who experience dizziness or other central nervous system disturbances while taking NSAIDs should refrain from driving or operating machinery.
In the table below the incidence of adverse drug reactions reported in controlled clinical studies where Arthrotec was administered to more than 2000 patients are listed. Additionally, adverse drug reactions reported during post-marketing surveillance are whose frequency cannot be estimated from the available data, such as spontaneous reports, have been listed at frequency 'unknown'. The most commonly observed adverse events are gastrointestinal in nature.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 Symptoms of aseptic meningitis (stiff neck, headache, nausea, vomiting, fever or impaired consciousness) have been reported during treatment with NSAIDs. Patients suffering from autoimmune disease (e.g. lupus erythematosus, mixed connective tissue disorders) seem to be more susceptible.
2 Diarrhoea is usually mild to moderate and transient and can be minimised by taking Arthrotec 50 with food and by avoiding the use of predominantly magnesium-containing antacids.
3 GI perforation or bleeding can sometimes be fatal, particularly in the elderly (see section 4.4).
4 Serious skin reactions, some of them fatal, have been reported very rarely (see section 4.4).
5 Especially in patients with hypertension or impaired renal function (see section 4.4).
Given the lack of precise and/or reliable denominator and numerator figures, the spontaneous adverse event reporting system through which post marketing safety data are collected does not allow for a medically meaningful frequency of occurrence of any undesirable effects.
With regard to the relative frequency of reporting of adverse reactions during post marketing surveillance, the undesirable effects at the gastrointestinal level were those received most frequently by the MAH (approximately 45% of all case reports in the company safety database) followed by cutaneous/hypersensitivity-type reactions, which is in agreement with the known side effects profile of the NSAIDs drug class.
Clinical trial and epidemiological data suggest that use of diclofenac, particularly at high doses (150 mg daily) and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).
The toxic dose of Arthrotec 50 has not been determined and there is no experience of overdosage. Intensification of the pharmacological effects may occur with overdosage. Management of acute poisoning with NSAIDs essentially consists of supportive and symptomatic measures. It is reasonable to take measures to reduce absorption of any recently consumed drug by forced emesis, gastric lavage or activated charcoal.
Pharmacotherapeutic group (ATC code): M01BX
Arthrotec 50 is a non-steroidal, anti-inflammatory drug which is effective in treating the signs and symptoms of arthritic conditions.
This activity is due to the presence of diclofenac which has been shown to have anti-inflammatory and analgesic properties.
Arthrotec 50 also contains the gastroduodenal mucosal protective component misoprostol which is a synthetic prostaglandin E1 analogue that enhances several of the factors that maintain gastroduodenal mucosal integrity.
The pharmacokinetic profiles of diclofenac and misoprostol administered as Arthrotec 50 are similar to the profiles when the two drugs are administered as separate tablets and there are no pharmacokinetic interactions between the two components.
Diclofenac sodium is completely absorbed from the gastrointestinal (GI) tract after fasting oral administration. Only 50 % of the absorbed dose is systemically available due to first pass metabolism. Peak plasma levels are achieved in 2 hours (range 1-4 hours), and the area-under-the plasma-concentration curve (AUC) is dose proportional within the range of 25 mg to 150 mg. The extent of diclofenac sodium absorption is not significantly affected by food intake.
The terminal half-life is approximately 2 hours. Clearance and volume of distribution are about 350 ml/min and 550 ml/kg, respectively. More than 99 % of diclofenac sodium is reversibly bound to human plasma albumin, and this has been shown not to be age dependent.
Diclofenac sodium is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Approximately 65 % of the dose is excreted in the urine and 35 % in the bile. Less than 1 % of the parent drug is excreted unchanged.
Misoprostol is rapidly and extensively absorbed, and it undergoes rapid metabolism to its active metabolite, misoprostol acid, which is eliminated with an elimination t½ of about 30 minutes. No accumulation of misoprostol acid was found in multiple-dose studies, and plasma steady state was achieved within 2 days. The serum protein binding of misoprostol acid is less than 90 %. Approximately 70 % of the administered dose is excreted in the urine, mainly as biologically inactive metabolites.
In co-administration studies in animals, the addition of misoprostol did not enhance the toxic effects of diclofenac. The combination was also shown not to be teratogenic or mutagenic. The individual components show no evidence of carcinogenic potential.
Misoprostol in multiples of the recommended therapeutic dose in animals has produced gastric mucosal hyperplasia. This characteristic response to E-series prostaglandins reverts to normal on discontinuation of the compound.
Arthrotec 50 tablets contain:
Core:
Lactose monohydrate
microcrystalline cellulose
maize starch
povidone K-30
magnesium stearate
Mantle/Coat:
cellulose acetate phthalate
diethyl phthalate
methylhydroxpropylcellulose
crospovidone
hydrogenated castor oil
colloidal silicon dioxide
microcrystalline cellulose
Not applicable.
Arthrotec 50 has a shelf-life of 3 years when stored in cold-formed blisters.
Store in a dry place. Do not store above 25oC.
Arthrotec 50 is presented in cold formed aluminium blisters in pack sizes of 6, 7, 56, 60, 84, 100, 120 and 140 (supplied as 14 packs of 10 tablets shrink wrapped together) tablets.
Not all pack sizes may be marketed.
No Special requirements.
Pharmacia Limited
Ramsgate Road
Sandwich
Kent
CT13 9NJ
United Kingdom
PL 00032/0396
Date of first authorisation: 15 April 2002
Date of last renewal: 23 January 2007
September 2009
POM
Ref: AE 8_0
Vomex A Kinder-Suppositorien may be available in the countries listed below.
Dimenhydrinate is reported as an ingredient of Vomex A Kinder-Suppositorien in the following countries:
International Drug Name Search
