Ingredient matches for CortaGel
Hydrocortisone is reported as an ingredient of CortaGel in the following countries:
- United States
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Hydrocortisone is reported as an ingredient of CortaGel in the following countries:
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Falcol may be available in the countries listed below.
Aceclofenac is reported as an ingredient of Falcol in the following countries:
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Isimig may be available in the countries listed below.
Frovatriptan succinate monohydrate (a derivative of Frovatriptan) is reported as an ingredient of Isimig in the following countries:
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Ranitidine 50mg/2ml Solution for Injection and Infusion
Each one ml of solution contains 25mg ranitidine as ranitidine hydrochloride. Each 2ml ampoule contains 50mg ranitidine.
For a full list of excipients, see section 6.1.
Solution for Injection and Infusion
Clear, colourless solution.
Ranitidine Solution for Injection is indicated for the treatment of duodenal ulcer, benign gastric ulcer, post - operative ulcer, and of Zollinger - Ellison Syndrome.
In the management of conditions where reduction of gastric secretion and acid output is desirable, such as reflux oesphagitis.
As prophylaxis against:
• gastrointestinal haemorrhage from stress ulceration in seriously ill patients
• recurrent haemorrhage in patients with bleeding peptic ulcers
• acid aspiration (Mendelson's Syndrome) before anaesthesia in patients at risk, particularly obstetric patients during labour.
Children (6 months to 18 years)
• short term treatment of peptic ulcer
• treatment of gastro-oesophageal reflux, including reflux oesophagitis and symptomatic relief of gastro-oesophageal reflux disease.
For intravenous or intramuscular injection or, after dilution, for intravenous infusion. Whenever solution and container permit, parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration.
Adults (including elderly) and adolescents (12 years and older)
Ranitidine Solution for Injection may be given as:
• a slow intravenous injection (over at least two minutes) of 50 mg, after dilution to a volume of 20 ml per 50 mg dose. This dose may be repeated every six to eight hours
• an intermittent intravenous infusion at a rate of 25 mg per hour for two hours. The infusion may be repeated at six to eight hour intervals
• an intramuscular injection of 50 mg (2ml) every six to eight hours.
In the prophylaxis of haemorrhage from stress ulceration in seriously ill patients or the prophylaxis of recurrent haemorrhage in patients bleeding from peptic ulceration, parenteral administration may be continued until oral feeding commences. Patients considered to be still at risk may then be treated orally with tablets 150 mg twice daily.
In the prophylaxis of upper gastro-intestinal haemorrhage from stress ulceration in seriously ill patients a priming dose of 50 mg as a slow intravenous injection followed by a continuous intravenous infusion of 0.125 - 0.250 mg/kg/hr may be preferred.
In patients considered at risk of developing acid aspiration (Mendelson's) syndrome, Ranitidine Solution for Injection 50 mg may be given intramuscularly or by slow intravenous injection (over 2 minutes), 45 to 60 minutes before induction of general anaesthesia.
Children (6 months to 11 years)
See section 5.2 Pharmacokinetic Properties – Special Patient Populations
Ranitidine Injection may be given as a slow (over 2 minutes) i.v. injection up to a maximum of 50mg every 6 to 8 hours.
Peptic Ulcer Acute Treatment and Gastro-Oesophageal Reflux
Intravenous therapy in children with peptic ulcer disease is indicated only when oral therapy is not possible.
For acute treatment of peptic ulcer disease and gastro-oesophageal reflux in paediatric patients, Ranitidine injection may be administered at doses that have been shown to be effective for these diseases in adults and effective for acid suppression in critically ill children. The initial dose (2.0 mg/kg or 2.5 mg/kg, maximum 50 mg) may be administered as a slow intravenous infusion over 10 minutes, either with a syringe pump followed by a 3 ml flush with normal saline over 5 min, or following dilution with normal saline to 20 ml. Maintenance of pH> 4.0 can be achieved by intermittent infusion of 1.5 mg/kg every 6 h to 8 h. Alternatively treatment can be continuous, administering a loading dose of 0.45 mg/kg followed by a continuous infusion of 0.15 mg/kg/hr.
Prophylaxis of stress ulceration in seriously ill patients
The recommended dose for prophylaxis of stress ulceration is 1mg/kg (maximum 50 mg) every 6h to 8h.
Alternatively treatment can be continuous, administering 125 - 250 micrograms/kg/hr as continuous infusion.
Neonates (under 1 month)
See Section 5.2 Pharmacokinetic Properties – Special Patient Populations.
Renal Impairment
Accumulation of ranitidine with resulting elevated plasma concentrations will occur in patients with severe renal impairment (creatinine clearance less than 50ml/min). It is recommended in such patients that Ranitidine Solution for Injection be administered in doses of 25mg.
Hypersensitivity to the active substance(s) or to any of the excipients.
Treatment with a histamine H2-antagonist may mask the symptoms associated with carcinoma of the stomach and may therefore delay diagnosis of the condition. Where gastric ulcer is suspected, the possibility of malignancy should be excluded before therapy with ranitidine is started.
Ranitidine is excreted via the kidney and so plasma levels of the drug are increased in patients with severe renal impairment. The dosage should be adjusted as detailed in Section 4.2 Posology and Method of Administration.
Asystole and bradycardia in association with rapid administration of ranitidine has been reported rarely, usually in patients with factors predisposing to cardiac rhythm disturbances. Recommended rates of administration should not be exceeded.
It has been reported that the use of higher than recommended doses of intravenous H2-antagonists has been associated with rises in liver enzymes when treatment has been extended beyond five days.
Although clinical reports of acute intermittent porphyria associated with ranitidine administration have been rare and inconclusive, ranitidine should be avoided in patients with a history of this condition.
In patients such as the elderly, persons with chronic lung disease, diabetes or the immunocompromised, there may be an increased risk of developing community acquired pneumonia. A large epidemiological study showed an increased risk of developing community acquired pneumonia in current users of H2 receptor antagonists versus those who had stopped treatment, with an observed adjusted relative risk increase of 1.63 (95% CI, 1.07–2.48).
Ranitidine has the potential to affect the absorption, metabolism or renal excretion of other drugs. The altered pharmacokinetics may necessitate dosage adjustment of the affected drug or discontinuation of treatment
Interactions occur by several mechanisms including:
1) Inhibition of cytochrome P450-linked mixed function oxygenase system:
Ranitidine, at blood levels produced by standard doses, does not inhibit or interact significantly with the hepatic cytochrome P450-linked mixed function oxygenase system.
Accordingly, ranitidine in usual therapeutic doses, does not potentiate the actions of drugs which are inactivated by this enzyme; these include diazepam, lidocaine, phenytoin, propranolol and theophylline .
There have been reports of altered prothrombin time with coumarin anticoagulants (e.g. warfarin). Due to the narrow therapeutic index, close monitoring of increased or decreased prothrombin time is recommended during concurrent treatment with ranitidine.
2) Competition for renal tubular secretion:
Since ranitidine is partially eliminated by the cationic system, it may affect the clearance of other drugs eliminated by this route. High doses of ranitidine (e.g. such as those used in the treatment of Zollinger-Ellison syndrome) may reduce the excretion of procainamide and N-acetylprocainamide resulting in increased plasma level of these drugs.
3) Alteration of gastric pH:
The bioavailability of certain drugs may be affected. This can result in either an increase in absorption (e.g. triazolam, midazolam, glipizide) or a decrease in absorption (e.g. ketoconazole, atazanavir, delaviridine, gefitnib).
Ranitidine crosses the placenta but therapeutic doses administered to obstetric patients in labour or undergoing caesarean section have been without any adverse effect on labour, delivery or subsequent neonatal progress. Ranitidine is also excreted in human breast milk. Like other drugs, ranitidine should only be used during pregnancy or lactation if considered essential by a physician.
None known.
The following convention has been utilised for the classification of undesirable effects: very common (
Blood & Lymphatic System Disorders
Unknown: Blood count changes (leucopenia, thrombocytopenia). These are usually reversible. Agranulocytosis or pancytopenia, sometimes with marrow hypoplasia or marrow aplasia.
Immune System Disorders
Uncommon: Hypersensitivity reactions (urticaria, angioneurotic oedema, fever, bronchospasm, hypotension and chest pain).
Unknown: Anaphylactic shock
These events have been reported after a single dose.
Psychiatric Disorders
Very Rare: Depression.
Unknown: Reversible mental confusion and hallucinations.
These have been reported predominantly in severely ill and elderly patients.
Nervous System Disorders
Common: Headache (sometimes severe) and dizziness..
Unknown: Reversible involuntary movement disorders
Eye Disorders
Uncommon: Reversible blurred vision.
There have been reports of blurred vision, which is suggestive of a change in accommodation.
Cardiac Disorders
Unknown: As with other H2 receptor antagonists bradycardia and A-V Block.
Vascular Disorders
Unknown: Vasculitis.
Gastrointestinal Disorders
Common: Diarrhoea.
Unknown: Acute pancreatitis.
Hepatobiliary Disorders
Very Rare: Transient and reversible changes in liver function tests.
Unknown: Hepatitis (hepatocellular, hepatocanalicular or mixed) with or without jaundice, these were usually reversible.
Skin and Subcutaneous Tissue Disorders
Uncommon: Skin Rash.
Unknown: Erythema multiforme, alopecia.
Musculoskeletal and Connective Tissue Disorders
Unknown: Musculoskeletal symptoms such as arthralgia and myalgia.
Renal and Urinary Disorders
Unknown: Acute interstitial nephritis.
Reproductive System and Breast Disorders
Unknown: Reversible impotence. Breast symptoms and breast conditions (such as gynaecomastia and galactorrhoea).
The safety of ranitidine has been assessed in children aged 0 to 16 years with acid-related disease and was generally well tolerated with an adverse event profile resembling that in adults. There are limited long term safety data available, in particular regarding growth and development.
Ranitidine is very specific in action and accordingly, no particular problems are expected following overdosage with the drug. Symptomatic and supportive therapy should be given as appropriate. Ranitidine may be removed by haemodialysis.
Pharmacotherapeutic group: drugs for peptic ulcer and gastro-oesophageal reflux disease. H2– receptor antagonist.
ATC code: A02B A02
Ranitidine is a specific, rapidly acting histamine H2-antagonist. It inhibits basal and stimulated secretion of gastric acid, reducing both the volume, and the acid and pepsin content of the secretion.
The clinical data available mentions the use of ranitidine in children to prevent stress ulcers. No direct evidence for prevention of stress ulcers is available. Treatment for these patients is based on the observation that pH is below 4 after administration of ranitidine. The value of this surrogate parameter in children with stress ulcers remains to be established.
Absorption of ranitidine after intramuscular injection is rapid and peak plasma concentrations are usually achieved within 15 minutes of administration. Ranitidine is not extensively metabolised. The elimination of the drug is primarily by tubular secretion. The elimination half-life of ranitidine is 2-3 hours. In studies with 150mg 3H-ranitidine, 93% of an intravenous dose was excreted in urine and 5% in faeces. Analysis of urine excreted in the first 24 hours after dosing showed that 70% of the intravenous dose was eliminated unchanged. About 6% of the dose is excreted in the urine as the N-oxide, 2% as desmethyl ranitidine and 1-2% as the furoic acid analogue.
Special Patient Populations
Children/infants (6 months and above)
Limited pharmacokinetic data show that there were no significant differences in half-life (range for children 3 years and above: 1.7 - 2.2 h) and plasma clearance (range for children 3 years and above: 9 - 22 ml/min/kg) between children and healthy adults receiving intravenous ranitidine when correction is made for body weight. Pharmacokinetic data in infants is extremely limited but appears to be in line with that for older children.
Neonates (under 1 month)
Limited pharmacokinetic data from term babies undergoing treatment with Extracorporeal Membrane Oxygenation (EMCO) suggests that plasma clearance following iv administration may be reduced (1.5-8.2 ml/min/kg) and the half-life increased in the new-born. Clearance of ranitidine appeared to be related to the estimated glomerular filtration rate in the neonates.
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
Potassium dihydrogen phosphate
Disodium hydrogen phosphate dihydrate
Sodium chloride
Water for Injections
None
2 years
Do not store above 25°C. Keep ampoules in the outer carton in order to protect from light.
2 ml solution in amber, type 1 glass ampoules.
Pack size: 5 ampoules
Ranitidine Injection has been shown to be compatible with the following intravenous infusion fluids:
Sodium Chloride 0.9% w/v
Dextrose 5% w/v
Sodium Chloride 0.18% w/v and Dextrose 4% w/v
Sodium Bicarbonate 4.2% w/v
Hartmann's solution
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless preparation of solutions has taken place in controlled and validated aseptic conditions.
All solutions of Ranitidine Solution for Injection should be discarded after use.
Beacon Pharmaceuticals Ltd
85 High Street
Tunbridge Wells
Kent TN1 1YG
UK
PL 18157/0019
21 October 2008
01 September 2010
Itaka may be available in the countries listed below.
Sildenafil is reported as an ingredient of Itaka in the following countries:
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Remestyp may be available in the countries listed below.
Terlipressin is reported as an ingredient of Remestyp in the following countries:
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Bronchialpastillen VA mit Codein may be available in the countries listed below.
Codeine phosphate hemihydrate (a derivative of Codeine) is reported as an ingredient of Bronchialpastillen VA mit Codein in the following countries:
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Etoral Cream may be available in the countries listed below.
Ketoconazole is reported as an ingredient of Etoral Cream in the following countries:
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Tetracycline complex with sodium metaphosphate (a derivative of Tetracycline) is reported as an ingredient of Tetrin in the following countries:
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Minims Stains may be available in the countries listed below.
Fluorescein sodium (a derivative of Fluorescein) is reported as an ingredient of Minims Stains in the following countries:
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Efedrin SAD may be available in the countries listed below.
Ephedrine hydrochloride (a derivative of Ephedrine) is reported as an ingredient of Efedrin SAD in the following countries:
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Ropinirol Orion may be available in the countries listed below.
Ropinirole hydrochloride (a derivative of Ropinirole) is reported as an ingredient of Ropinirol Orion in the following countries:
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Isosorbide Mononitrate is reported as an ingredient of Ismo Retard in the following countries:
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Isoniazid is reported as an ingredient of Isoniac in the following countries:
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Chemicetina may be available in the countries listed below.
Chloramphenicol is reported as an ingredient of Chemicetina in the following countries:
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In the US, Repaglinide (repaglinide systemic) is a member of the drug class meglitinides and is used to treat Diabetes, Type 2.
US matches:
Rec.INN
A10BX02
0135062-02-1
C27-H36-N2-O4
452
Oral antidiabetic agent, meglitinide (glinide)
(+)-2-Ethoxy-α-[[(S)-α-isobutyl-o-piperidinobenzyl]carbamoyl]-p-toluic acid
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Glossary
| BAN | British Approved Name |
| DCF | Dénomination Commune Française |
| IS | Inofficial Synonym |
| OS | Official Synonym |
| PH | Pharmacopoeia Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
Talohexal may be available in the countries listed below.
Citalopram hydrobromide (a derivative of Citalopram) is reported as an ingredient of Talohexal in the following countries:
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Glizide may be available in the countries listed below.
Gliclazide is reported as an ingredient of Glizide in the following countries:
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Tosidrin may be available in the countries listed below.
Dihydrocodeine tartrate (a derivative of Dihydrocodeine) is reported as an ingredient of Tosidrin in the following countries:
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Livocab Nasal may be available in the countries listed below.
Levocabastine hydrochloride (a derivative of Levocabastine) is reported as an ingredient of Livocab Nasal in the following countries:
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Intragel may be available in the countries listed below.
Hyaluronic Acid sodium salt (a derivative of Hyaluronic Acid) is reported as an ingredient of Intragel in the following countries:
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Alopurinol Teva may be available in the countries listed below.
Allopurinol is reported as an ingredient of Alopurinol Teva in the following countries:
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Edimox may be available in the countries listed below.
Acetazolamide is reported as an ingredient of Edimox in the following countries:
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Alfuzosin Sandoz may be available in the countries listed below.
Alfuzosin hydrochloride (a derivative of Alfuzosin) is reported as an ingredient of Alfuzosin Sandoz in the following countries:
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Gabapentine CristerS may be available in the countries listed below.
Gabapentin is reported as an ingredient of Gabapentine CristerS in the following countries:
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Losartan Acostlabs may be available in the countries listed below.
Losartan potassium salt (a derivative of Losartan) is reported as an ingredient of Losartan Acostlabs in the following countries:
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Pantoprazol Novafarm may be available in the countries listed below.
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Fluvoxaminemaleaat Katwijk may be available in the countries listed below.
Fluvoxamine maleate (a derivative of Fluvoxamine) is reported as an ingredient of Fluvoxaminemaleaat Katwijk in the following countries:
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Flunixin N-Vet may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Flunixin meglumine (a derivative of Flunixin) is reported as an ingredient of Flunixin N-Vet in the following countries:
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Brivox may be available in the countries listed below.
Brivudine is reported as an ingredient of Brivox in the following countries:
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Acetilcisteina may be available in the countries listed below.
Acetilcisteina (DCIT) is known as Acetylcysteine in the US.
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Glossary
| DCIT | Denominazione Comune Italiana |
Cremicort H1 may be available in the countries listed below.
Hydrocortisone is reported as an ingredient of Cremicort H1 in the following countries:
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Flécaïnide Teva may be available in the countries listed below.
Flecainide acetate (a derivative of Flecainide) is reported as an ingredient of Flécaïnide Teva in the following countries:
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Indometacine CF may be available in the countries listed below.
Indometacin is reported as an ingredient of Indometacine CF in the following countries:
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Melorem may be available in the countries listed below.
Meloxicam is reported as an ingredient of Melorem in the following countries:
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Linkosol may be available in the countries listed below.
Lincomycin is reported as an ingredient of Linkosol in the following countries:
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Axidexa may be available in the countries listed below.
Dexamethasone 21-(disodium phosphate) (a derivative of Dexamethasone) is reported as an ingredient of Axidexa in the following countries:
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Clotrimazolo EG may be available in the countries listed below.
Clotrimazole is reported as an ingredient of Clotrimazolo EG in the following countries:
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Cytocristin may be available in the countries listed below.
Vincristine sulfate (a derivative of Vincristine) is reported as an ingredient of Cytocristin in the following countries:
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Geniceral may be available in the countries listed below.
Idebenone is reported as an ingredient of Geniceral in the following countries:
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Clarute may be available in the countries listed below.
Diltiazem hydrochloride (a derivative of Diltiazem) is reported as an ingredient of Clarute in the following countries:
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Biocolchid may be available in the countries listed below.
Thiocolchicoside is reported as an ingredient of Biocolchid in the following countries:
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Aldometil may be available in the countries listed below.
Methyldopa is reported as an ingredient of Aldometil in the following countries:
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Bal-Lanz may be available in the countries listed below.
Lansoprazole is reported as an ingredient of Bal-Lanz in the following countries:
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Ciclavix may be available in the countries listed below.
Aciclovir is reported as an ingredient of Ciclavix in the following countries:
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Kipres may be available in the countries listed below.
Montelukast sodium salt (a derivative of Montelukast) is reported as an ingredient of Kipres in the following countries:
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Baklofen may be available in the countries listed below.
Baclofen is reported as an ingredient of Baklofen in the following countries:
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Biotin beta may be available in the countries listed below.
Biotin is reported as an ingredient of Biotin beta in the following countries:
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Piracetam CF may be available in the countries listed below.
Piracetam is reported as an ingredient of Piracetam CF in the following countries:
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Messelfenil may be available in the countries listed below.
Metamizole sodium anhydrous (a derivative of Metamizole) is reported as an ingredient of Messelfenil in the following countries:
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Claire may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Clenbuterol hydrochloride (a derivative of Clenbuterol) is reported as an ingredient of Claire in the following countries:
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In the US, Xylose is a member of the drug class miscellaneous uncategorized agents.
Lactulose is reported as an ingredient of Xylose in the following countries:
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Cinedil may be available in the countries listed below.
Cinnarizine is reported as an ingredient of Cinedil in the following countries:
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ratio-Indometacin may be available in the countries listed below.
Indometacin is reported as an ingredient of ratio-Indometacin in the following countries:
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Caltrioject may be available in the countries listed below.
Calcitriol is reported as an ingredient of Caltrioject in the following countries:
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Histaloc may be available in the countries listed below.
Promethazine hydrochloride (a derivative of Promethazine) is reported as an ingredient of Histaloc in the following countries:
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Klopidogrel Arrow may be available in the countries listed below.
Clopidogrel besilate (a derivative of Clopidogrel) is reported as an ingredient of Klopidogrel Arrow in the following countries:
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Kind may be available in the countries listed below.
Levocetirizine is reported as an ingredient of Kind in the following countries:
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Antox may be available in the countries listed below.
Ciprofloxacin is reported as an ingredient of Antox in the following countries:
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Hyso may be available in the countries listed below.
Scopolamine is reported as an ingredient of Hyso in the following countries:
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Kenalgesic may be available in the countries listed below.
Ketorolac tromethamine (a derivative of Ketorolac) is reported as an ingredient of Kenalgesic in the following countries:
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Ambroxol Sandoz may be available in the countries listed below.
Ambroxol hydrochloride (a derivative of Ambroxol) is reported as an ingredient of Ambroxol Sandoz in the following countries:
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Cardiject may be available in the countries listed below.
Dobutamine hydrochloride (a derivative of Dobutamine) is reported as an ingredient of Cardiject in the following countries:
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In some countries, this medicine may only be approved for veterinary use.
In the US, Chloromycetin (chloramphenicol ophthalmic) is a member of the drug class miscellaneous antibiotics and is used to treat Anthrax, Bacterial Infection, Brucellosis, Cholera, Glanders, Meningitis, Ornithosis, Plague, Psittacosis, Rabbit Fever and Rickettsial Infection.
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Chloramphenicol is reported as an ingredient of Chloromycetin in the following countries:
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Chloramphenicol succinate sodium (a derivative of Chloramphenicol) is reported as an ingredient of Chloromycetin in the following countries:
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Glossary
| SPC | Summary of Product Characteristics (UK) |
Paroxetine Topgen may be available in the countries listed below.
Paroxetine hydrochloride (a derivative of Paroxetine) is reported as an ingredient of Paroxetine Topgen in the following countries:
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Facicam may be available in the countries listed below.
Piroxicam is reported as an ingredient of Facicam in the following countries:
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Ephedrine HCl Berlico may be available in the countries listed below.
Ephedrine hydrochloride (a derivative of Ephedrine) is reported as an ingredient of Ephedrine HCl Berlico in the following countries:
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In the US, Cognex (tacrine systemic) is a member of the drug class cholinesterase inhibitors and is used to treat Alzheimer's Disease.
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Laurimic may be available in the countries listed below.
Fenticonazole nitrate (a derivative of Fenticonazole) is reported as an ingredient of Laurimic in the following countries:
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Rec.INN
0027060-91-9
C19-H18-Cl-F-N2-O3
376
Anxiolytic agent
Sedative agent
Benzodiazepine derivative
Oxazolo[3,2-d][1,4]benzodiazepin-6(5H)-one, 10-chloro-11b-(2-fluorophenyl)-2,3,7,11b-tetrahydro-7-(2-hydroxyethyl)-
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Glossary
| IS | Inofficial Synonym |
| JAN | Japanese Accepted Name |
| OS | Official Synonym |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Flutiamik may be available in the countries listed below.
Finasteride is reported as an ingredient of Flutiamik in the following countries:
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Caloidal may be available in the countries listed below.
Calcium is reported as an ingredient of Caloidal in the following countries:
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Benzyl Nicotinate may be available in the countries listed below.
Benzyl Nicotinate (JAN) is also known as Nicotinic Acid (Rec.INN)
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Glossary
| JAN | Japanese Accepted Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Gabax may be available in the countries listed below.
Gabapentin is reported as an ingredient of Gabax in the following countries:
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Rozex Cream
Metronidazole Ph. Eur 0.75% w/w
Cream
Indicated in the treatment of inflammatory papules, pustules and erythema of rosacea
For topical administration only.
The average period of treatment is three to four months. The recommended duration of treatment should not be exceeded. However, if a clear benefit has been demonstrated, continued therapy for a further three to four months period may be considered by the prescribing physician depending on the severity of the condition. In clinical studies, topical metronidazole therapy for rosacea has been continued for up to 2 years. In the absence of a clear clinical improvement, therapy should be stopped.
Adults: Rozex Cream should be applied in a thin layer to the affected areas of the skin twice daily, morning and evening. Areas to be treated should be washed with a mild cleanser before application. Patients may use non-comedogenic and non-astringent cosmetics after application of Rozex Cream.
Elderly: The dosage recommended in the elderly is the same as that recommended in adults.
Children: Not recommended. Safety and efficacy have not been established.
Contraindicated in individuals with a history of hypersensitivity to Metronidazole, or other ingredients of the formulation.
Contact with mucous membranes should be avoided.
Rozex Cream has been reported to cause lacrimation of the eyes, therefore, contact with the eyes should be avoided. If a reaction suggesting local irritation occurs patients should be directed to use the medication less frequently or discontinue use temporarily and to seek medical advice if necessary. Metronidazole is a nitroimidazole and should be used with care in patients with evidence of, or history of, blood dyscrasia. Exposure of treated sites to ultraviolet (e.g. solarium, sun-lamp) or strong sunlight (including sun-bathing) should be avoided during use of metronidazole. Unnecessary and prolonged use of this medication should be avoided.
Evidence suggests that metronidazole is carcinogenic in certain animal species. There is no evidence to date of a carcinogenic effect in human (see section 5.3).
Interaction with systemic medication is unlikely because absorption of metronidazole following cutaneous application of Rozex Cream is low. Nevertheless, it should be mentioned that disulfiram-like reactions have been reported in a small number of patients taking metronidazole and alcohol concomitantly. Oral metronidazole has been reported to potentiate the effect of warfarin and other coumarin anticoagulants, resulting in a prolongation of prothrombin time. The effect of topical metronidazole on prothrombin is not known. However, very rare cases of modification of the INR values have been reported with concomitant use of Rozex and coumarin anticoagulants.
There is no experience to date with the use of Rozex Cream in pregnancy. In case of oral administration, metronidazole crosses the placental barrier and rapidly enters the foetal circulation. No foetotoxicity was observed after oral metronidazole in either rats or mice. However because animal reproduction studies are not always predictive of human response and since oral metronidazole has been shown to be a carcinogen in some rodents this drug should be used in pregnancy only if clearly needed.
After oral administration, Metronidazole is excreted in breast milk in concentrations similar to those found in the plasma. Even though Metronidazole blood levels from topical administration are significantly lower than those achieved after oral administration, in nursing mothers a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Based upon the pharmacodynamic profile and clinical experience performance related to driving and using machines should not be affected.
Because of the minimal absorption of metronidazole and consequently its insignificant plasma concentration after topical administration, the adverse experiences reported with the oral form of the drug have not been reported with Rozex Cream. Adverse reactions reported with Rozex Cream have been only local and mild.
The following spontaneous adverse experiences have been reported, and within each system organ class, are ranked by frequency, using the following convention:
Very common (
Common (
Uncommon (
Rare (
Very rare (<1/10,000), including isolated reports
Skin and subcutaneous tissue disorders:
Common: dry skin, erythema, pruritus, skin discomfort (burning, pain of skin/stinging), skin irritation, worsening of rosacea.
Unknown frequency: contact dermatitis
Nervous System disorders:
Uncommon: hypothesia, paraesthesia, dysgeusia (metallic taste)
Gastrointestinal disorders:
Uncommon: nausea
Watery eyes have been reported if applied too closely to this area.
No data exists about overdosage in humans. Acute oral toxicity studies with a topical gel formulation containing 0.75% w/w metronidazole in rats have shown no toxic action with doses of up to 5 g of finished product per kilogram body weight, the highest dose used. This dose is equivalent to the oral intake of 12 tubes of 30g packaging Rozex Cream for an adult weighing 72 kg, and 2 tubes of Cream for a child weighing 12 kg.
Metronidazole is an antiprotozoal and antibacterial agent which is active against a wide range of pathogenic micro-organisms. The mechanisms of action of metronidazole in rosacea are unknown but available evidence suggests that the effects may be antibacterial and/or anti-inflammatory.
Metronidazole is rapidly and nearly totally absorbed after oral administration. The drug is not significantly bound to serum proteins and distributes well to all body compartments with the lowest concentration found in the fat. Metronidazole is excreted primarily in the urine as parent drug, oxidative metabolites and conjugates.
Bioavailability studies with a topical 1g application of Rozex Cream to the face of normal subjects resulted in mean maximum serum concentrations of 32.9ng/ml (range 14.8 to 54.4ng/ml) which is approximately 100 times less than those attained after a single oral dose of 250 mg (mean Cmax = 7248ng/ml; range 4270 – 13970ng/ml). The peak concentration occurred between 0.25 – 4 hours after oral dosing, and 6 to 24 hours after cutaneous application of Rozex Cream.
Following topical application of Rozex Cream, serum concentrations of the major metabolite (the hydroxymetabolite 2-hydroxymethylmetronidazole) were below the quantifiable limit of the assay (<9.6ng/ml) at most of the time points, ranging to a maximum of 17.5ng/ml peak concentration between 8 and 24 hours after application. In comparison, the peak concentration following a 250mg oral dose ranged from 626 to 1788ng/ml between 4 and 12 hours after dosing.
The extent of exposure (Area under the curve, AUC) from a 1g application of metronidazole administered topically was 1.36% of the AUC of a single oral 250mg metronidazole dose (mean + 912.7ng.hr/ml and approximately 67207ng.ml/hr respectively).
No evidence for a primary dermal irritation was observed in rabbits following a single 24-hour cutaneous application of Rozex Cream to abraded and non-abraded skin, under occlusion.
Metronidazole has shown mutagenic activity in several in vitro bacterial assay systems. In addition, a dose-response increase in the frequency of micronuclei was observed in mice after intraperitoneal injection and an increase in chromosome aberrations have been reported in patients with Crohn's disease who were treated with 200 to 1200mg/day of oral metronidazole for 1 to 24 months. However, the preponderance of evidence from these studies suggests that although metronidazole has a potential for producing mutations, this should not occur in well oxygenated mammalian cells, i.e., under normal aerobic conditions.
The carcinogenicity of metronidazole by the oral route of administration has been evaluated in rats, mice and hamsters. These studies showed that oral metronidazole caused an increased incidence of pulmonary tumours in mice and possibly other tumours, including liver tumours, in the rat. Conversely, two lifetime studies in hamsters produced negative results. Moreover, one study showed a significant enhancement of UV-induced skin tumours in hairless mice treated with metronidazole intraperitoneally (15μg per g body weight and per day for 28 weeks).
Although the significance of these results to the cutaneous use of metronidazole for the treatment of rosacea is unclear, patients should be advised to avoid or minimise exposure of metronidazole cream-treated sites to sun. After several decades of systemic use, no evidence has been published to suggest that metronidazole is associated with carcinogenic potential in humans.
Emulsifying Wax, Benzyl alcohol, Isopropyl palmitate, Glycerol, Sorbitol 70% (non-crystallising), lactic acid and/or Sodium Hydroxide, Purified Water.
None known
Rozex Cream has a shelf life when unopened of 36 months
Store at a temperature not exceeding 25°C. Do not refrigerate.
Aluminium tubes with epoxy phenolic lining, fitted with white polypropylene screw caps; pack sizes: 30g, 40g & 50g
Replace cap tightly after use.
Galderma (UK.) Limited
Meridien House
69-71 Clarendon Road
Watford
Herts.
WD17 1DS
UK
PL 10590/0028
18th June 1997
December 2010
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