Amsacrine Lactate may be available in the countries listed below.
Amsacrine Lactate (BANM) is also known as Amsacrine (Prop.INN)
International Drug Name Search
Glossary
| BANM | British Approved Name (Modified) |
| Prop.INN | Proposed International Nonproprietary Name (World Health Organization) |
LMX 4
Lidocaine 4%w/w Cream
Lidocaine 4%w/w
For excipients, see 6.1
Cream
A white to off-white yellowish cream
Local anaesthetic for topical use to produce surface anaesthesia of the skin prior to venous cannulation or venipuncture.
For cutaneous use only.
Adults, including elderly, and children over one month of age.
Apply 1g to 2.5g of cream onto the skin to cover a 2.5cm x 2.5cm (6.25cm2) area where venous cannulation or venipuncture will occur. No more than 1g of cream should be applied to infants below the age of 1 year. 1g of cream equates to approximately 5cm of cream squeezed from the 5g tube or 3.5cm from the 30g tube.
The cream should remain undisturbed and the area can be covered with an occlusive dressing to prevent disturbance or interference by the patient or other external factors. Adequate anaesthesia should be obtained after 30 minutes, but the LMX4 Cream may be applied for up to 5 hours under a dressing. Prior to starting the procedure, the LMX 4 Cream should be removed using a clean gauze swab and the site for venous cannulation or venipuncture prepared in the usual manner. The procedure should be initiated approximately 5 minutes after the cream has been removed. Maximum application time for 1 month upto 3 month infant should not exceed 60 minutes. Maximum application time for 3 month upto 12 month infant should not exceed 4 hours. Maximum application for 12 month infant – adult should not exceed 5 hours.
Hypersensitivity to the active substance, or any of the amide-type local anaesthetics, or any of the excipients.
For external use only.
Avoid contact with eyes.
Do not apply to irritated skin or if excessive irritation develops. If condition worsens, or if symptoms persist unaltered for more than seven days or clear up and occur again within only a few days, discontinue use of this product and consult a doctor.
Do not use in large quantities, particularly over raw or blistered areas.
LMX 4 contains propylene glycol which may cause skin irritation.
LMX 4 has not been applied to wounds, mucous membranes or in areas of atopic dermatitis as there are no clinical data in relation to these.
Anaesthetic efficacy during the heel lancing of neonates has not been studied.
Application of lidocaine to larger areas or for longer times than those recommended could result in sufficient absorption of lidocaine resulting in serious adverse effects.
Studies in laboratory animals (guinea pigs) have shown that lidocaine has an ototoxic effect when instilled into the middle ear. In these same studies, animals exposed to lidocaine in the external auditory canal only showed no abnormality. Lidocaine should not be used in any clinical situation in which its penetration or migration beyond the tympanic membrane into the middle ear is possible.
Dermal application of lidocaine may cause transient local blanching followed by transient erythema.
PRECAUTIONS
General: Repeated doses of lidocaine may increase blood levels of lidocaine. Lidocaine should be used with caution in patients who may be more sensitive to the systemic effects of lidocaine including acutely ill, debilitated, or elderly patients.
Lidocaine coming in contact with the eye should be avoided because animal studies have demonstrated severe eye irritation. Also the loss of protective reflexes can permit corneal irritation and potential abrasion. Absorption of lidocaine in conjunctival tissues has not been determined. If eye contact occurs, immediately wash out the eye with water or saline and protect the eye until sensation returns.
Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to lidocaine; however, lidocaine should be used with caution in patients with a history of drug sensitivities, especially if the etiologic agent is uncertain. Patients with severe hepatic disease, because of their inability to metabolize local anaesthetics normally, are at greater risk of developing toxic plasma concentrations of lidocaine.
When lidocaine is used, the patient should be aware that the production of dermal analgesia may be accompanied by the block of all sensations in the treated skin. For this reason, the patient should avoid inadvertent trauma to the treated area by scratching, rubbing, or exposure to extreme hot or cold temperatures until complete sensation has returned.
Lidocaine has bactericidal and antiviral properties in concentrations above 0.5%. For this reason, the results of intra-cutaneous injections of live vaccines (such as BCG vaccination) should be monitored.
Lidocaine should be used with caution in patients receiving Class I anti-arrhythmic drugs (such as tocainide and mexiletine) since the toxic effects are additive and generally synergistic.
The risk of additional systemic toxicity should be considered when large doses of LMX 4 are applied to patients already using other local anaesthetics.
There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, lidocaine should be used during pregnancy only if clearly needed.
Lidocaine is not contraindicated in labour and delivery. Should LMX 4 be used concomitantly with other products containing lidocaine, total doses contributed by all formulations must be considered.
Lidocaine can cross the placental barrier.
Lidocaine is excreted in human milk. Therefore, caution should be exercised when LMX 4 is administered to a nursing mother since the milk:plasma ratio of lidocaine is 0.4.
None known.
Common side effects (>1/100) can include irritation, redness, itching, or rash.
In rare cases local anaesthetics have been associated with allergic reactions including anaphylactic shock.
Corneal irritation after accidental eye exposure.
Overdose with LMX 4 cream is unlikely but signs of systemic toxicity would be consistent with those of lidocaine.
An indication of systemic toxicity may include blurred vision, dizziness or drowsiness, difficulty breathing, trembling, chest pain, or irregular heartbeat.
Anaesthetics for topical use, lidocaine, ATC Code: D04A B 01
Lidocaine applied to intact skin provides dermal analgesia by a release of lidocaine from the cream into the epidermal and dermal layers of the skin, and by the accumulation of lidocaine in the vicinity of pain receptors and nerve endings. Lidocaine is an amide-type local anaesthetic agent which stabilises neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anaesthetic action. The onset, depth and duration of dermal analgesia provided by lidocaine depend primarily on the duration of application. LMX 4 may cause transient peripheral vasoconstriction followed by transient vasodilation at the application site.
The amount of lidocaine systemically absorbed is directly related to both the duration of application and to the area over which it is applied. It is not known if it is metabolized into the skin. Lidocaine is metabolized rapidly by the liver to a number of metabolites including monoethylglycinexylidide (MEGX) and glycinexylidide (GX), both of which have pharmacologic activity similar to, but less potent to that of lidocaine. The metabolite, 2,6-xylidine, has unknown pharmacologic activity but is carcinogenic in rats. Following intravenous administration, MEGX and GX concentrations in serum range from 11 to 36% and from 5 to 11% of concentrations, respectively. The half-life of lidocaine elimination from the plasma following IV administration is approximately 65 to 150 minutes (mean 110, ±24 SD, n=13). This half-life may be increased in cardiac or hepatic dysfunction. More than 98% of an absorbed dose of can be recovered in the urine as metabolites or parent drug. The systemic clearance is 10 to 20 mL/min/kg (mean 13, ±3 SD, n=13).
When applied topically to intact skin, the absorption of lidocaine is very low. Increased absorption is therefore to be expected when applied to mucosa or previously damaged skin.
The maximum plasma level of active ingredient was very low (0.3 µg/ml or less) in a study investigating the application of LMX 4 in children of different ages. It was well below the toxically effective plasma level of ingredients.
The mutagenic potential of lidocaine HCl has been tested in the Ames Salmonella/mammalian microsome test and by analysis of structural chromosome aberrations in human lymphocytes in vitro, and by mouse micronucleus test in vivo. There was no indication in these tests of any mutagenic effects. The mutagenicity of 2,6-xylidine, a metabolite of lidocaine, has been studied in different tests with mixed results. The compound was found to be weakly mutagenic in the Ames test only under metabolic activation conditions. In addition, 2,6-xylidine was observed to be mutagenic at the thymidine kinase locus, with or without activation, and induced chromosome aberrations and sister chromatic exchanges at concentrations at which the drug precipitated out of the solution (1.2 mg/ml). No evidence of genotoxicity was found in the in vivo assays measuring unscheduled DNA synthesis in rat hepatocytes, chromosome damage in polychromatic erythrocytes or preferential killing of DNA repair-deficient bacteria in liver, lung, kidney, testes and blood extracts from mice. However, covalent binding studies of DNA from liver and ethmoid turbinates in rats indicate that 2,6-xylidine may be genotoxic under certain conditions in vivo.
Benzyl Alcohol
Carbomers
Cholesterol
Phospholipon 80H (Hydrogenated Soy Lecithin)
Polysorbate 80 (Tween 80)
Propylene Glycol
Trolamine
Vitamin E Acetate
Purified Water
Not applicable
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Do not store above 25°C.
The pack sizes are 5g and 30g.
Both packs comprise of an aluminium tube with an epoxyphenolic internal lacquer, fitted with a polypropylene cap.
The following packaging options are approved but not all of these packaging options may be marketed:
1) A carton containing one 5g tube.
2) A carton containing five 5g tubes.
3) A carton containing one 5g tube with two Tegaderm® occlusive dressings.
4) A carton containing five 5g tubes with ten Tegaderm® occlusive dressings.
5) A carton containing one 30g tube.
No special requirements
Ferndale Pharmaceuticals Ltd
12 York Place
Leeds
LS1 2DS
United Kingdom
PL 20685/0034
20/11/2007
15/03/2011
Anti-Pulgas may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Dimpylate is reported as an ingredient of Anti-Pulgas in the following countries:
International Drug Name Search
innohep® 10,000 IU/ml and innohep® Syringe 10,000 IU/ml
Tinzaparin sodium 10,000 anti-Factor Xa IU/ml
Solution for injection
For the prevention of thromboembolic events, including deep vein thrombosis, in patients undergoing general and orthopaedic surgery.
For the prevention of clotting in the extracorporeal circuit during haemodialysis in patients with chronic renal insufficiency.
For prevention of thromboembolic events:
Administration is by subcutaneous injection.
Adults at low to moderate risk, e.g. patients undergoing general surgery:
3,500 anti-Factor Xa IU two hours before surgery and then once daily for 7 to 10 days post-operatively.
Adults at high risk, e.g. patients undergoing orthopaedic surgery:
In this high risk group the recommended dose is either a fixed dose of 4,500 anti-Factor Xa IU given 12 hours before surgery followed by a once daily dose, or 50 anti-Factor Xa IU/kilogram body weight 2 hours before surgery followed by a once daily dose for 7 to 10 days post-operatively.
For haemodialysis:
The dose of innohep® should be given into the arterial side of the dialyser or intravenously. The dialyser can be primed by flushing with 500-1000 ml isotonic sodium chloride (9 mg/ml) containing 5,000 anti-Factor Xa IU innohep® per litre.
Patients with chronic renal insufficiency:
a) Short-term haemodialysis (up to 4 hours)
A bolus dose of 2,000-2,500 anti-Factor Xa IU into the arterial side of the dialyser (or intravenously).
b) Long-term haemodialysis (more than 4 hours)
A bolus dose of 2,500 anti-Factor Xa IU into the arterial side of the dialyser (or intravenously) followed by 750 anti-Factor Xa IU/hour infused into the extracorporeal circuit.
Dosage adjustment
The bolus innohep® dose may be adjusted (increased or decreased) by 250-500 anti-Factor Xa IU until a satisfactory response is obtained.
Additional innohep® (500-1,000 anti-Factor Xa IU) may be given if concentrated red cells or blood transfusions (which may increase the likelihood of clotting in the dialyser) are given during dialysis or additional treatment beyond the normal dialysis duration is employed.
Dose monitoring
Determination of plasma anti-Factor Xa may be used to monitor the innohep® dose during haemodialysis. Plasma anti-Factor Xa, one hour after dosing should be within the range 0.4 - 0.5 IU/ml.
Use in the elderly
No dose modifications are necessary.
Use in children
There is no experience of use in children.
• Known hypersensitivity to constituents.
• Current or history of heparin-induced thrombocytopenia.
• Generalised or local haemorrhagic tendency, including uncontrolled severe hypertension, severe liver insufficiency, active peptic ulcer, acute or subacute septic endocarditis, intracranial haemorrhage, or injuries and operations on the central nervous system, eyes and ears, and in women with abortus imminens.
• The innohep® 10,000 IU/ml vial formulation contains 10 mg/ml of the preservative benzyl alcohol. This formulation must not be given to premature babies or neonates.
The innohep® 10,000 IU/ml syringe formulation does not contain the preservative benzyl alcohol.
• An epidural anaesthesia during birth in pregnant women treated with low molecular weight heparin is contraindicated (see section 4.6).
• In patients receiving heparin for treatment rather than prophylaxis, locoregional anaesthesia in elective surgical procedures is contra-indicated because the use of heparin may be very rarely associated with epidural or spinal haematoma resulting in prolonged or permanent paralysis.
Care should be taken when innohep® is administered to patients with increased risk of bleeding complications.
In patients undergoing peridural or spinal anaesthesia or spinal puncture, the prophylactic use of heparin may be very rarely associated with epidural or spinal haematoma resulting in prolonged or permanent paralysis. The risk is increased by the use of a peridural or spinal catheter for anaesthesia, by the concomitant use of drugs affecting haemostasis such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors or anticoagulants, and by traumatic or repeated puncture.
In decision making on the interval between the last administration of heparin at prophylactic doses and the placement or removal of a peridural or spinal catheter, the product characteristics and the patient profile should be taken into account. Subsequent dose should not take place before at least four hours have elapsed. Re-administration should be delayed until the surgical procedure is completed.
Should a physician decide to administer anti-coagulation in the context of peridural or spinal anaesthesia, extreme vigilance and frequent monitoring must be exercised to detect any signs and symptoms of neurologic impairment, such as back pain, sensory and motor deficits and bowel or bladder dysfunction. Patients should be instructed to inform immediately a nurse or a clinician if they experience any of these.
innohep® should not be administered by intramuscular injection due to the risk of haematoma.
Due to increased bleeding risk care should be taken when giving concomitant intramuscular injections, lumbar puncture and similar procedures.
innohep® should be used with caution in patients with hypersensitivity to heparin or to other low molecular weight heparins.
As there is a risk of antibody-mediated heparin-induced thrombocytopenia, platelet counts should be measured in patients receiving heparin treatment for longer than 5 days and the treatment should be stopped immediately in those who develop thrombocytopenia.
As with other low molecular weight heparins, in some patients undergoing surgical procedures (especially orthopaedic) or presenting with a concomitant inflammatory process, the administration of innohep® has coincided with an asymptomatic increase of platelet count, which in many cases subsided during continued administration. If an increase in platelet count occurs, evaluation of the benefit/risk of continuing therapy for that patient should be made.
Care should be taken when innohep® is administered to patients with kidney insufficiency who are undergoing general or orthopaedic surgery. In such cases a dose reduction should be considered.
Heparin can suppress adrenal secretion of aldosterone leading to hyperkalaemia, particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, a raised plasma potassium or taking potassium-sparing drugs. The risk of hyperkalaemia appears to increase with duration of therapy but is usually reversible. Plasma potassium should be measured in patients at risk before starting heparin therapy and monitored regularly thereafter particularly if treatment is prolonged beyond about 7 days.
The innohep® 10,000 IU/ml vial formulation contains the preservative benzyl alcohol 10 mg/ml. This should be administered with caution to infants and children up to 3 years old, as there is a risk that benzyl alcohol may cause toxic reactions and allergic reactions (anaphylactoid) in this age group (see section 4.3 for premature babies and neonates).
Drugs affecting platelet function or the coagulation system should in general not be given concomitantly with innohep® (see section 4.5).
Prosthetic heart valves:
There have been no adequate studies to assess the safe and effective use of tinzaparin sodium in preventing valve thrombosis in patients with prosthetic heart valves; therefore no dosage recommendations can be given. High doses of tinzaparin sodium (175 IU/kg) may not be sufficient prophylaxis to prevent valve thrombosis in patients with prosthetic heart valves. The use of tinzaparin sodium cannot be recommended for this purpose.
The anticoagulant effect of innohep® may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system, e.g. platelet aggregation inhibitors, thrombolytic agents, salicylates, non-steroidal anti-inflammatory drugs, vitamin K antagonists, dextrans, activated protein C.
innohep® does not appear to interact with other drugs used widely in chronic renal failure, including vitamin B supplements, aluminium hydroxide, calcium supplements, alfacalcidol, ranitidine, vitamin C supplements, ferrous sulphate, folic acid, nifedipine, erythropoietin and azatadine.
Pregnancy
No transplacental passage of innohep® was found (assessed by anti-Factor Xa and anti-Factor IIa activity) in patients given a dose of 35 to 40 anti-Factor Xa IU/kg in the second trimester of pregnancy. In rabbits, no transplacental passage of anti-Factor Xa or anti-Factor IIa activity was observed after doses of 1750 anti-Factor Xa IU/kg. Toxicological studies in rats have shown no embryotoxic or teratogenic effects, although a lower birthweight was found.
Although these animal studies show no hazard, as a precaution innohep® should not be used in pregnancy unless no safer alternative is available.
As benzyl alcohol may cross the placenta, the use of innohep® formulations containing benzyl alcohol should be avoided during pregnancy.
The use of innohep® in women with abortus imminens is contraindicated (see section 4.3).
Prosthetic heart valves:
Therapeutic failures and maternal death have been reported in pregnant women with prosthetic heart valves on full anti-coagulant doses of low molecular weight heparins. In the absence of clear dosing, efficacy and safety information in this circumstance, tinzaparin sodium is not recommended for use in pregnant women with prosthetic heart valves.
Lactation
It is not known whether innohep® is excreted in breast milk. However, patients are advised to stop breast-feeding while receiving innohep®.
innohep® has no or negligible influence on the ability to drive or use machines.
Based on reports from clinical trials the frequency rate of all adverse reactions is 17.6%. The most frequently reported undesirable effects are bleeding events, injection site reactions, various skin reactions, reversible thrombocytopenia, allergic reactions, headache and reversible increase in liver enzymes.
Based on pooled study results, from a clinical trial programme where 3167 patients received innohep®, local reactions following subcutaneous administration such as irritation, bruising, pain and ecchymosis were identified in approximately 3.7 % of patients. The overall bleeding risk was approximately 11 % while the risk of major bleeding was approximately 0.5%. Reversible thrombocytopenia was seen in approximately 0.6 % of patients.
A list of undesirable effects is given below. Where frequencies are given, these are based on the clinical trial data, using the stated frequency classification. Where the term 'Not known' is given, these effects are derived from spontaneous reports.
Frequency classification:
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Overdose of innohep® may be complicated by haemorrhage. With recommended dosages there should be no need for an antidote but in the event of accidental administration of an overdose, the effect of innohep® can be reversed by intravenous administration of 1% protamine sulphate solution.
The dose of protamine sulphate required for neutralisation should be accurately determined by titrating with the patient's plasma.
Studies in healthy volunteers indicate that 65-80% of the anti-Xa activity is neutralised by protamine sulphate 1 mg/100 anti-Xa IU of innohep®. A return of innohep® anti-Xa, anti-IIa and APTT activities are seen 3 hours after its reversal probably due to continuous absorption of innohep® from the s.c. depot. It may therefore be necessary to give protamine sulphate intermittently or as a continuous infusion to achieve and maintain neutralisation of s.c. innohep® for at least 24 hours. Potential side-effects of protamine sulphate must be considered and patients carefully observed.
Transfusion of fresh plasma may be used, if necessary. Plasma anti-Factor Xa and anti-Factor IIa activity should be measured during the management of overdose situations.
innohep® is an antithrombotic agent. It potentiates the inhibition of several activated coagulation factors, especially Factor Xa, its activity being mediated via antithrombin III.
The pharmacokinetics/pharmacodynamic activity of innohep® is monitored by anti-Factor Xa activity.
innohep® has a bioavailability of around 90% following a subcutaneous injection. The absorption half-life is 200 minutes, peak plasma activity being observed after 4 to 6 hours. The elimination half-life is about 90 minutes.
The half-life of innohep® in patients with renal insufficiency given a bolus intravenous dose of 2,500 anti-Factor Xa IU is about 2.5 hours.
There is a linear dose response relationship between plasma activity and the dose administered.
There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
innohep® 10,000 IU/ml:
Benzyl alcohol
Sodium acetate
Sodium hydroxide
Water for injections
innohep® Syringe 10,000 IU/ml:
Sodium acetate
Water for injections
As pH adjuster: sodium hydroxide
innohep® should not be mixed with any other injection.
innohep® 10,000 IU/ml:
2 years.
innohep® Syringe 10,000 IU/ml:
3 years.
Do not store above 25°C.
innohep® 10,000 IU/ml:
2 ml glass vial containing 10,000 anti-Factor Xa IU/ml in packs of 10 vials.
innohep® Syringe 10,000 IU/ml:
A prefilled unit dose syringe with needle safety device containing:
2,500 anti-Factor Xa IU in 0.25 ml
3,500 anti-Factor Xa IU in 0.35 ml
4,500 anti-Factor Xa IU in 0.45 ml
in packs of 10 syringes.
innohep® 10,000 IU/ml:
The vial should be discarded 14 days after first use.
innohep® Syringe 10,000 IU/ml:
Contains no preservative, any portion of the contents not used at once should be discarded with the syringe.
LEO Laboratories Limited
Longwick Road
Princes Risborough
Bucks HP27 9RR
innohep® 10,000 IU/ml: PL 00043/0205
innohep® Syringe 10,000 IU/ml: PL 00043/0204
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1 September 2011
POM
Amoxycillin Sandoz may be available in the countries listed below.
Amoxicillin trihydrate (a derivative of Amoxicillin) is reported as an ingredient of Amoxycillin Sandoz in the following countries:
International Drug Name Search
Bradoral may be available in the countries listed below.
Domiphen Bromide is reported as an ingredient of Bradoral in the following countries:
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Acétylcysteine EG may be available in the countries listed below.
Acetylcysteine is reported as an ingredient of Acétylcysteine EG in the following countries:
International Drug Name Search
