Oruvail 150mg Capsules

1. Name Of The Medicinal Product

Oruvail 150

2. Qualitative And Quantitative Composition

Ketoprofen 150mg

3. Pharmaceutical Form

Controlled release capsules

4. Clinical Particulars

4.1 Therapeutic Indications

Oruvail is recommended in the management of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute articular and peri-articular disorders, (bursitis, capsulitis, synovitis, tendinitis), cervical spondylitis, low back pain (strain, lumbago, sciatica, fibrositis), painful musculo-skeletal conditions, acute gout, dysmenorrhoea and control of pain and inflammation following orthopaedic surgery.

Oruvail reduces joint pain and inflammation and facilitates increase in mobility and functional independence. As with other non-steroidal anti-inflammatory agents, it does not cure the underlying disease.

4.2 Posology And Method Of Administration

Adults: 100 - 200mg once daily, depending on patient weight and on severity of symptoms.

The maximum daily dose is 200mg. The balance of risks and benefits should be carefully considered before commencing treatment with 200mg daily, and higher doses are not recommended (see also section 4.4).

Elderly: The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.

Paediatric dosage not established.

Oruvail capsules are for oral administration. To be taken preferably with or after food.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).

4.3 Contraindications

Ketoprofen is contraindicated in patients who have a history of hypersensitivity reactions such as bronchospasm, asthmatic attacks, rhinitis, angioedema, urticaria or other allergic-type reactions to ketoprofen, any other ingredients in this medicine, ASA or other NSAIDs. Severe, rarely fatal, anaphylactic reactions have been reported in such patients (see section 4.8 Undesirable effects).

Ketoprofen is contraindicated in patients with hypersensitivity to any of the excipients of the drug.

Ketoprofen is also contraindicated in the third trimester of pregnancy.

Ketoprofen is contraindicated in the following cases:

- severe heart failure

- active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding)

- history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy

- haemorrhagic diathesis

- severe hepatic insufficiency

- severe renal insufficiency

- third trimester of pregnancy

4.4 Special Warnings And Precautions For Use

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2 Posology and method of administration, and GI and cardiovascular risks below).

The use of ketoprofen with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5 Interactions).

Elderly:

The elderly have an increased risk of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation which may be fatal (see Section 4.2 Posology and method of administration).

Cardiovascular, Renal and Hepatic impairment:

At the start of treatment, renal function must be carefully monitored in patients with heart impairment, heart failure, liver dysfunction, cirrhosis and nephrosis, in patients receiving diuretic therapy, in patients with chronic renal impairment, particularly if the patient is elderly. In these patients, administration of ketoprofen may induce a reduction in renal blood flow caused by prostaglandin inhibition and lead to renal decomposition. (see Section 4.3 Contra-indications).

NSAIDs have also been reported to cause nephrotoxicity in various forms and this can lead to interstitial nephritis, nephrotic syndrome and renal failure.

In patients with abnormal liver function tests or with a history of liver disease, transaminase levels should be evaluated periodically, particularly during long-term therapy. Rare cases of jaundice and hepatitis have been described with ketoprofen.

Cardiovascular and cerebrovascular effects

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.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long-term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for ketoprofen.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ketoprofen after careful consideration. Similar consideration should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

Respiratory disorders:

Patients with asthma combined with chronic rhinitis, chronic sinusitis, and/or nasal polyposis have a higher risk of allergy to aspirin and/or NSAIDs than the rest of the population. Administration of this medicinal product can cause asthma attacks or bronchospasm, particularly in subjects allergic to aspirin or NSAIDs (see section 4.3).

Gastrointestinal bleeding, ulceration and perforation:

GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.

Some epidemiological evidence suggests that ketoprofen may be associated with a high risk of serious gastrointestinal toxicity, relative to some other NSAIDs, especially at high doses (see also section 4.2 and 4.3).

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAlD doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in the elderly. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4.5).

NSAIDs should only be given with care to patients with a history of gastrointestinal disease (e.g. ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see Section 4.8 Undesirable effects).

Patients with a history of gastrointestinal 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 medications which could increase the risk of ulceration or bleeding, such as corticosteroids, or anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see Section 4.5).

When GI bleeding or ulceration occurs in patients receiving ketoprofen, the treatment should be withdrawn.

SLE and mixed connective tissue disease:

In patients with systemic lupus erythematosis (SLE) and mixed connective tissue disorders, there may be an increased risk of aseptic meningitis (see Section 4.8 Undesirable effects).

Female fertility:

The use of ketoprofen, as with other NSAIDs, may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulty conceiving or who are undergoing investigation of infertility, withdrawal of ketoprofen should be considered.

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. Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Treatment should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Infectious disease:

As with other NSAIDs, in the presence of an infectious disease, it should be noted that the anti-inflammatory, analgesic and the antipyretic properties of ketoprofen may mask the usual signs of infection progression such as fever.

Visual disturbances:

If visual disturbances such as blurred vision occur, treatment should be discontinued.

Patients with active or a past history of peptic ulcer.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Anticoagulants (heparin and warfarin) and platelet aggregation inhibitors (i.e. ticlopidine, clopidogrel):

Increased risk of bleeding (see section 4.4).

If coadministration is unavoidable, patient should be closely monitored.

Lithium:

Risk of elevation of lithium plasma levels, sometimes reaching toxic levels due to decreased lithium renal excretion. Where necessary, plasma lithium levels should be closely monitored and the lithium dosage levels adjusted during and after NSAIDs therapy.

Other analgesics/NSAIDs (including cyclooxygenase-2 selective inhibitors) and high dose salicylates:

Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects, particularly gastrointestinal ulceration and bleeding. (see Section 4.4 Special warnings and precautions for use).

Methotrexate:

Serious interactions have been recorded after the use of high dose methotrexate with NSAIDs, including ketoprofen, due to decreased elimination of methotrexate. At doses greater than 15mg/week:

Increased risk of haematologic toxicity of methotrexate, particularly if administered at high doses (> 15 mg/week), possibly related to displacement of protein-bound methotrexate and to its decreased renal clearance. At doses lower than 15mg/week: During the first weeks of combination treatment, full blood count should be monitored weekly. If there is any alteration of the renal function or if the patient is elderly, monitoring should be done more frequently.

Mifepristone:

NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.

Pentoxifylline:

There is an increased risk of bleeding. More frequent clinical monitoring and monitoring of bleeding time is required.

Antihypertensive agents (beta-blockers, angiotensin converting enzyme inhibitors, diuretics):

Risk of decreased antihypertensive potency (inhibition of vasodilator prostaglandins by NSAIDs).

Diuretics:

Risk of reduced diuretic effect. Patients and particularly dehydrated patients taking diuretics are at a greater risk of developing renal failure secondary to a decrease in renal blood flow caused by prostaglandin inhibition. Such patients should be rehydrated before initiating coadministration therapy and renal function monitored when the treatment is started (see section 4.4 Special warnings and precautions for use).

Cardiac glycosides:

NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

Ciclosporin:

Increased risk of nephrotoxicity, particularly in elderly subjects.

Corticosteroids:

Increased risk of gastrointestinal ulceration or bleeding. (see Section 4.4 Special warnings and precautions for use).

Quinolone antibiotics:

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.

Tacrolimus:

Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus, particularly in elderly subjects.

Thrombolytics:

Increased risk of bleeding.

Probenecid:

Concomitant administration of probenecid may markedly reduce the plasma clearance of ketoprofen.

Anti-platelet agents and Selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding (section 4.4 Special warnings and precautions for use).

ACE inhibitors and Angiotensin II Antagonists:

In patients with compromised renal function (e.g. dehydrated patients or elderly patients the co-administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclooxygenase may result in further deterioration of renal function, including possible acute renal failure.

Zidovudine:

Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

4.6 Pregnancy And Lactation

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, ketoprofen should not be given unless clearly necessary. If ketoprofen is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

- renal dysfunction, which may progress to renal failure with oligo-hydroamniosis; the mother and the neonate, at the end of the pregnancy, to:

- possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.

- Inhibition of uterine contractions resulting in delayed or prolonged labour.

Consequently, ketoprofen is contraindicated during the third trimester of pregnancy.

Lactation

No data are available on excretion of ketoprofen in human milk. Ketoprofen is not recommended in nursing mothers.

4.7 Effects On Ability To Drive And Use Machines

Patients should be warned about the potential for somnolence, dizziness or convulsions, drowsiness, fatigue and visual disturbances and be advised not to drive or operate machinery if these symptoms occur.

4.8 Undesirable Effects

The following CIOMS frequency rating is used, when applicable:

Very common (

The following adverse reactions have been reported with Ketoprofen in adults:

Blood and lymphatic system disorders

- rare: haemorrhagic anaemia, anaemia due to bleeding

- not known: agranulocytosis, thrombocytopenia, bone marrow failure, neutropenia

Immune system disorders

- rare: anaphylactic reactions (including shock)

Psychiatric disorders

- not known: mood altered

Nervous system disorders

- uncommon: headache, dizziness, somnolence

- rare: paraesthesia

- not known: convulsions, dysgeusia, depression, confusion, hallucinations, vertigo, malaise, drowsiness, reports of aseptic meningitis (especially in patients with existing auto-immune disorders such as systemic lupus erythematosis, mixed connective tissue disease) with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation (see section 4.4 Special warnings and precautions for use).

Eye disorders

- rare: visual disturbances such as blurred vision (see section 4.4 Special warnings and precautions for use)

- not known: optic neuritis

Ear and labyrinth disorders

- rare: tinnitus

Cardiac disorders

- not known: heart failure, oedema

Vascular disorders

- not known: hypertension, vasodilatation

Respiratory, thoracic and mediastinal disorders

- rare: asthma, asthmatic attack

- not known: bronchospasm (particularly in patients with known hypersensitivity to ASA and other NSAIDs), rhinitis, non-specific allergic reactions, dyspnoea

Gastrointestinal disorders

- common: dyspepsia, nausea, abdominal pain, vomiting

- uncommon: constipation, diarrhoea, flatulence, gastritis

- rare: stomatitis, peptic ulcer

- very rare: pancreatitis (very rare reports of pancreatitis have been noted with NSAIDs)

- not known: exacerbation of colitis and Crohn's disease, gastrointestinal haemorrhage and perforation, gastralgia, melaena, haematemesis

Gastrointestinal bleeding may sometimes be fatal, particularly in the elderly (see section 4.4 Special warnings and precautions for use).

Hepatobiliary disorders

- rare: hepatitis, transaminases increased, elevated serum bilirubin due to hepatitis disorders

- not known: abnormal liver function, jaundice

Skin and subcutaneous disorders

- uncommon: rash, pruritis

- not known: photosensitivity reactions, alopecia, urticaria, angioedema, bullous eruption including Stevens-Johnson syndrome and toxic epidermal necrolysis, exfoliative and bullous dermatoses (including epidermal necrolysis, erythema multiforme), purpura

Renal and urinary disorders

- not known: renal failure acute, tubulointerstitial nephritis, nephritic syndrome, renal function tests abnormal

General disorders and administration site conditions

- uncommon: oedema, fatigue

- not known: headache, taste perversion

Investigations

- rare: weight increased

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with an increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4 Special warnings and precautions for use).

In all cases of major adverse effects Oruvail should be withdrawn at once.

4.9 Overdose

Symptoms

Cases of overdose have been reported with doses up to 2.5g of ketoprofen. In most instances, the symptoms observed have been benign and limited to lethargy, drowsiness, nausea, vomiting and epigastric pain. Headache, rarely diarrhoea, disorientation, excitation, coma, dizziness, tinnitus, fainting, occasionally convulsions may also occur. Adverse effects seen after overdose with propionic acid derivatives such as hypotension, bronchospasm and gastro-intestinal haemorrhage should be anticipated.

In cases of significant poisoning, acute renal failure and liver damage are possible.

If renal failure is present, haemodialysis may be useful to remove circulating medicinal product.

Therapeutic measures:

There are no specific antidotes to ketoprofen overdosages. In cases of suspected massive overdosages, a gastric lavage is recommended and symptomatic and supportive treatment should be instituted to compensate for dehydration, to monitor urinary excretion and to correct acidosis, if present.

Owing to the slow release characteristics of Oruvail, it should be expected that ketoprofen will continue to be absorbed for up to 16 hours after ingestion.

Within one hour of ingestion, consideration should be given to administering activated charcoal in an attempt to reduce absorption of slowly-released ketoprofen.

Alternatively, in adults, gastric lavage, aimed at recovering pellets that may still be in the stomach, should be considered if the patient presents within 1 hour of ingesting a potentially toxic amount.

It should be possible to identify the pellets in the gastric contents. Correction of severe electrolyte abnormalities may need to be considered.

Good urine output should be ensured.

Renal and liver function should be closely monitored.

Patients should be observed for at least four hours after ingestion of potentially toxic amounts.

Frequent or prolonged convulsions should be treated with intravenous diazepam.

The benefit of gastric decontamination is uncertain.

Other measures may be indicated by the patient's clinical condition.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Ketoprofen overall has the properties of a potent non-steroidal anti-inflammatory agent. It has the following pharmacological effects:

Anti-inflammatory

It inhibits the development of carageenan-induced abscesses in rats at 1mg/kg, UV-radiation induced erythema in guinea pigs at 6mg/kg. It is also a potent inhibitor of PGE₂ and PFG_2∝ synthesis in guinea pig and human chopped lung preparations.

Analgesic

Ketoprofen effectively reduced visceral pain in mice caused by phenyl benzoquinone or by bradykinin following p.o. Administration at about 6mg/kg.

Antipyretic

Ketoprofen (2 and 6mg/kg) inhibited hyperthermia caused by s.c injection of brewer's yeast in rats and, at 1mg/kg hyperthermia caused by i.v. administration of anticoagulant vaccine to rabbits.

Ketoprofen at 10mg/kg i.v. did not affect the cardiovascular, respiratory, central nervous system or autonomic nervous systems.

5.2 Pharmacokinetic Properties

Ketoprofen is slowly but completely absorbed from Oruvail capsules. Maximum plasma concentration occurs after 6 - 8 hours. It declines thereafter with a half-life of about 8 hours. There is no accumulation on continued daily dosing. Ketoprofen is very highly bound to plasma protein.

5.3 Preclinical Safety Data

No additional data of relevance to the prescriber

6. Pharmaceutical Particulars

6.1 List Of Excipients

Pellets

Sugar spheres

Colloidal anhydrous silica

Shellac

Ethylcellulose

Talc

Capsule shell-body

Gelatin

Erythrosine (E127)

Capsule shell – cap

Gelatin

Titanium dioxide (E171)

Erythrosine (E127)

6.2 Incompatibilities

None stated

6.3 Shelf Life

36 months

6.4 Special Precautions For Storage

Store below 25°C in a dry place and protect from light.

6.5 Nature And Contents Of Container

UPVC/Aluminium foil blister or UPVC coated with PVDC aluminium foil blister containing 28 capsules

6.6 Special Precautions For Disposal And Other Handling

None stated.

7. Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS

United Kingdom

8. Marketing Authorisation Number(S)

PL 04425/0598

9. Date Of First Authorisation/Renewal Of The Authorisation

09/01/2007

10. Date Of Revision Of The Text

11 May 2011

LEGAL CATEGORY

POM

Alkeran injection 50 mg (Laboratories Genopharm)

1. Name Of The Medicinal Product

Alkeran 50 mg Injection

2. Qualitative And Quantitative Composition

Melphalan Hydrochloride BP equivalent to 50 mg mephalan per vial.

3. Pharmaceutical Form

Freeze-dried powder for injection.

4. Clinical Particulars

4.1 Therapeutic Indications

Alkeran Injection, at conventional intravenous dosage, is indicated in the treatment of multiple myeloma and ovarian cancer.

Alkeran Injection, at high intravenous dosage, is indicated, with or without haematopoietic stem cell transplantation, for the treatment of multiple myeloma and childhood neuroblastoma.

Alkeran Injection, administered by regional arterial perfusion, is indicated in the treatment of localised malignant melanoma of the extremities and localised soft tissue sarcoma of the extremities.

In the above indications, Alkeran may be used alone or in combination with other cytotoxic drugs.

4.2 Posology And Method Of Administration

Parenteral administration:

Alkeran Injection is for intravenous use and regional arterial perfusion only. Alkeran Injection should not be given without haematopoietic stem cell rescue at doses of above 140 mg/m².

For intravenous administration, it is recommended that Alkeran Injection solution is injected slowly into a fast-running infusion solution via a swabbed injection port.

If direct injection into a fast-running infusion is not appropriate, Alkeran Injection solution may be administered diluted in an infusion bag.

Alkeran is not compatible with infusion solutions containing dextrose and it is recommended that only sodium chloride intravenous infusion 0.9% w/v is used.

When further diluted in an infusion solution, Alkeran has reduced stability and the rate of degradation increases rapidly with rise in temperature. If Alkeran is infused at a room temperature of approximately 25°C, the total time from preparation of the injection solution to the completion of infusion should not exceed 1.5 hours.

Should any visible turbidity or crystallisation appear in the reconstituted or diluted solutions, the preparation must be discarded.

Care should be taken to avoid possible extravasation of Alkeran and in cases of poor peripheral venous access, consideration should be given to use of a central venous line.

If high dose Alkeran Injection is administered with or without autologous bone marrow transplantation, administration via a central venous line is recommended.

For regional arterial perfusion, the literature should be consulted for detailed methodology.

Multiple myeloma: Alkeran Injection is administered on an intermittent basis alone, or in combination with other cytotoxic drugs. Administration of prednisone has also been included in a number of regimens.

When used as a single agent, a typical intravenous Alkeran dosage schedule is 0.4 mg/kg body weight (16 mg/m² body surface area) repeated at appropriate intervals (e.g. once every 4 weeks), provided there has been recovery of the peripheral blood count during this period.

High-dose regimens generally employ single intravenous doses of between 100 and 200 mg/m² body surface area (approximately 2.5 to 5.0 mg/kg body weight), but haematopoietic stem cell rescue becomes essential following doses in excess of 140 mg/m² body surface area. Hydration and forced diuresis are also recommended.

Ovarian adenocarcinoma: When used intravenously as a single agent, a dose of 1 mg/kg body weight (approximately 40 mg/m² body surface area) given at intervals of 4 weeks has often been used.

When combined with other cytotoxic drugs, intravenous doses of between 0.3 and 0.4 mg/kg body weight (12 to 16 mg/m² body surface area) have been used at intervals of 4 to 6 weeks.

Advanced neuroblastoma: Doses of between 100 and 240 mg/m² body surface area (sometimes divided equally over 3 consecutive days) together with haematopoietic stem cell rescue, have been used either alone or in combination with radiotherapy and/or other cytotoxic drugs.

Malignant melanoma: Hyperthermic regional perfusion with Alkeran has been used as an adjuvant to surgery for early malignant melanoma and as palliative treatment for advanced but localised disease. The scientific literature should be consulted for details of perfusion technique and dosage used. A typical dose range for upper extremity perfusions is 0.6-1.0 mg/kg bodyweight and for lower extremity perfusions is 0.8-1.5 mg/kg body weight.

Soft tissue sarcoma: Hyperthermic regional perfusion with Alkeran has been used in the management of all stages of localised soft tissue sarcoma, usually in combination with surgery. A typical dose range for upper extremity perfusions is 0.6-1.0 mg/kg body weight and for lower extremity perfusions is 1-1.4 mg/kg body weight.

Use in Children

Alkeran, at conventional dosage, is only rarely indicated in children and dosage guidelines cannot be stated.

High dose Alkeran Injection, in association with haematopoietic stem cell rescue, has been used in childhood neuroblastoma and dosage guidelines based on body surface area, as for adults, may be used.

Use in the elderly

Although Alkeran is frequently used at conventional dosage in the elderly, there is no specific information available relating to its administration to this patient sub-group.

Experience in the use of high dose Alkeran in elderly patients is limited. Consideration should therefore be given to ensure adequate performance status and organ function, before using high dose Alkeran Injection in elderly patients.

Dosage in renal impairment

Alkeran clearance, though variable, may be decreased in renal impairment.

Currently available pharmacokinetic data do not justify an absolute recommendation on dosage reduction when administering Alkeran Tablets to patients with renal impairment, but it may be prudent to use a reduced dosage initially until tolerance is established.

When Alkeran Injection is used at conventional intravenous dosage (16-40 mg/m² body surface area), it is recommended that the initial dose should be reduced by 50% and subsequent dosage determined according to the degree of haematological suppression.

For high intravenous doses of Alkeran (100 to 240 mg/m² body surface area), the need for dose reduction depends upon the degree of renal impairment, whether haematopoietic stem cells are re-infused, and therapeutic need. Alkeran Injection should not be given without haematopoietic stem cell rescue at doses of above 140 mg/m².

As a guide, for high dose Alkeran treatment without haematopoietic stem cell rescue in patients with moderate renal impairment (creatinine clearance 30 to 50 ml/min) a dose reduction of 50% is usual. High dose Alkeran (above 140 mg/m²) without haematopoietic stem cell rescue should not be used in patients with more severe renal impairment.

High dose Alkeran with haematopoietic stem cell rescue has been used successfully even in dialysis dependent patients with end-stage renal failure. The relevant literature should be consulted for details.

4.3 Contraindications

Alkeran should not be given to patients who have suffered a previous hypersensitivity reaction to melphalan.

4.4 Special Warnings And Precautions For Use

Alkeran is a cytotoxic drug, which falls into the general class of alkylating agents. It should be prescribed only by physicians experienced in the management of malignant disease with such agents. As with all high dose chemotherapy, precautions should be taken to prevent tumour lysis syndrome.

Immunisation using a live organism vaccine has the potential to cause infection in immunocompromised hosts. Therefore, immunisations with live organism vaccines are not recommended.

Since Alkeran is myelosuppressive, frequent blood counts are essential during therapy and the dosage should be delayed or adjusted if necessary.

Alkeran Injection solution can cause local tissue damage, should extravasation occur and consequently, it should not be administered by direct injection into a peripheral vein. It is recommended that Alkeran Injection solution is administered by injecting slowly into a fast-running intravenous infusion via a swabbed injection port, or via a central venous line.

In view of the hazards involved and the level of supportive care required, the administration of high dose Alkeran Injection should be confined to specialist centres, with the appropriate facilities and only be conducted by experienced clinicians.

In patients receiving high dose Alkeran Injection, consideration should be given to the prophylactic administration of anti-infective agents and the administration of blood products as required.

Consideration should be given to ensure adequate performance status and organ function before using high dose Alkeran Injection. Alkeran Injection should not be given without haematopoietic stem cell rescue at doses of above 140 mg/m².

As with all cytotoxic chemotherapy, adequate contraceptive precautions should be practised when either partner is receiving Alkeran.

Safe handling of Alkeran

The handling of Alkeran formulations should follow guidelines for the handling of cytotoxic drugs according to the Royal Pharmaceutical Society of Great Britain Working Party on the handling of cytotoxic drugs.

Monitoring

Since Alkeran is a potent myelosuppressive agent, it is essential that careful attention should be paid to the monitoring of blood counts, to avoid the possibility of excessive myelosuppression and the risk of irreversible bone marrow aplasia. Blood counts may continue to fall after treatment is stopped, so at the first sign of an abnormally large fall in leukocyte or platelet counts, treatment should be temporarily interrupted. Alkeran should be used with caution in patients who have undergone recent radiotherapy or chemotherapy in view of increased bone marrow toxicity.

Renal Impairment

Alkeran clearance may be reduced in patients with renal impairment who may also have uraemic marrow suppression. Dose reduction may therefore be necessary (see Posology and Method of Administration). See Undesirable Effects for elevation of blood urea.

Mutagenicity

Melphalan is mutagenic in animals and chromosome aberrations have been observed in patients being treated with the drug.

Carcinogenicity

Melphalan, in common with other alkylating agents, has been reported to be leukaemogenic. There have been reports of acute leukaemia occurring after melphalan treatment for diseases such as amyloid, malignant melanoma, multiple myeloma, macroglobulinaemia, cold agglutinin syndrome and ovarian cancer.

A comparison of patients with ovarian cancer who received alkylating agents with those who did not, showed that the use of alkylating agents, including melphalan, significantly increased the incidence of acute leukaemia.

The leukaemogenic risk must be balanced against the potential therapeutic benefit when considering the use of melphalan.

Effects on Fertility

Alkeran causes suppression of ovarian function in premenopausal women resulting in amenorrhoea in a significant number of patients.

There is evidence from some animal studies that Alkeran can have an adverse effect on spermatogenesis. Therefore, it is possible that Alkeran may cause temporary or permanent sterility in male patients.

The label for the product will contain the following statements:

Keep out of the reach of children.

Store below 30° C

Do not refrigerate.

Protect from light

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Vaccinations with live organism vaccines are not recommended in immunocompromised individuals (see Warnings and Precautions).

Nalidixic acid together with high-dose intravenous melphalan has caused deaths in children due to haemorrhagic entercolitis.

Impaired renal function has been described in bone marrow transplant patients who received high dose intravenous melphalan and who subsequently received ciclosporin to prevent graft-versus-host disease.

4.6 Pregnancy And Lactation

The teratogenic potential of Alkeran has not been studied. In view of its mutagenic properties and structural similarity to known teratogenic compounds, it is possible that melphalan could cause congenital defects in the offspring of patients treated with the drug.

The use of melphalan should be avoided whenever possible during pregnancy, particularly during the first trimester. In any individual case, the potential hazard to the foetus must be balanced against the expected benefit to the mother.

Mothers receiving Alkeran should not breastfeed.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

For this product there is no modern clinical documentation which can be used as support for determining the frequency of undesirable effects. Undesirable effects may vary in their incidence depending on the indication and dose received and also when given in combination with other therapeutic agents.

The following convention has been utilised for the classification of frequency:- Very common

Blood and Lymphatic System Disorders
Very common:	bone marrow depression leading to leucopenia, thrombocytopenia and anaemia
Rare:	haemolytic anaemia
Immune System Disorders
Rare:	allergic reactions (see Skin and Subcutaneous Tissue Disorders)

Allergic reactions to melphalan such as urticaria, oedema, skin rashes and anaphylactic shock have been reported uncommonly following initial or subsequent dosing, particularly after intravenous administration. Cardiac arrest has also been reported rarely in association with such events.

Respiratory, Thoracic and Mediastinal Disorders
Rare:	interstitial pneumonitis and pulmonary fibrosis (including fatal reports)
Gastrointestinal Disorders
Very common:	nausea, vomiting and diarrhoea; stomatitis at high dose
Rare:	stomatitis at conventional dose

The incidence of diarrhoea, vomiting and stomatitis becomes the dose-limiting toxicity in patients given high intravenous doses of melphalan in association with autologous bone marrow transplantation. Cyclophosphamide pretreatment appears to reduce the severity of gastro-intestinal damage induced by high-dose melphalan and the literature should be consulted for details.

Hepatobiliary Disorders
Rare:	hepatic disorders ranging from abnormal liver function tests to clinical manifestations such as hepatitis and jaundice; veno-occlusive disease following high dose treatment
Skin and Subcutaneous Tissue Disorders
Very common:	alopecia at high dose
Common:	alopecia at conventional dose
Rare:	maculopapular rashes and pruritus (see Immune System Disorders)
Musculoskeletal and Connective Tissue Disorders
Injection, following isolated limb perfusion:
Very common:	muscle atrophy, muscle fibrosis, myalgia, blood creatine phosphokinase increased.
Common:	compartment syndrome
Not known:	muscle necrosis, rhabdomyolysis
Renal and Urinary Disorders
Common:	temporary significant elevation of the blood urea has been seen in the early stages of melphalan therapy in myeloma patients with renal damage
General Disorders and Administration Site Conditions
Very common:	subjective and transient sensation of warmth and/or tingling

4.9 Overdose

Gastro-intestinal effects, including nausea, vomiting and diarrhoea are the most likely signs of acute oral overdosage. The immediate effects of acute intravenous overdosage are nausea and vomiting. Damage to the gastro-intestinal mucosa may also ensue and diarrhoea, sometimes haemorrhagic, has been reported after overdosage. The principal toxic effect is bone marrow suppression, leading to leucopenia, thrombocytopenia and anaemia.

General supportive measures, together with appropriate blood and platelet transfusions, should be instituted if necessary and consideration given to hospitalisation, antibiotic cover, the use of haematological growth factors.

There is no specific antidote. The blood picture should be closely monitored for at least four weeks following overdosage until there is evidence of recovery.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Melphalan is a bifunctional alkylating agent. Formation of carbonium intermediates from each of the two bis-2-chloroethyl groups enables alkylation through covalent binding with the 7-nitrogen of guanine on DNA, cross-linking the two DNA strands and thereby preventing cell replication.

5.2 Pharmacokinetic Properties

Absorption

The absorption of oral melphalan is highly variable with respect to both the time to first appearance of the drug in plasma and peak plasma concentration.

In studies of the absolute bioavailability of melphalan the mean absolute bioavailability ranged from 56 to 85%.

Intravenous administration can be used to avoid variability in absorption associated with myeloablative treatment.

Distribution

Melphalan is moderately bound to plasma proteins with reported percent binding ranging from 69% to 78%. There is evidence that the protein binding is linear in the range of plasma concentrations usually achieved in standard dose therapy, but that the binding may become concentration-dependent at the concentrations observed in high-dose therapy. Serum albumin is the major binding protein, accounting for about 55 to 60% the binding, and 20% is bound to α₁-acid glycoprotein. In addition, melphalan binding studies have revealed the existence of an irreversible component attributable to the alkylation reaction with plasma proteins.

Following administration of a two-minute infusion of doses ranging from 5 to 23 mg/m² body surface area (approximately 0.1 to 0.6 mg/kg bodyweight) to 10 patients with ovarian cancer or multiple myeloma, the mean volumes of distribution at steady state and central compartment were 29.1 ± 13.6 litres and 12.2 ± 6.5 litres, respectively.

In 28 patients with various malignancies who were given doses of between 70 and 200 mg/m² body surface area as a 2- to 20-min infusion, the mean volumes of distribution at steady state and central compartment were, respectively, 40.2 ± 18.3 litres and 18.2 ± 11.7 litres.

Melphalan displays limited penetration of the blood-brain barrier. Several investigators have sampled cerebrospinal fluid and found no measurable drug. Low concentrations (~10% of that in plasma) were observed in a single high-dose study in children.

Metabolism

In vivo and in vitro data suggest that spontaneous degradation rather than enzymatic metabolism is the major determinant of the drug's half-life in man.

Elimination

In 13 patients given oral melphalan at 0.6 mg/kg bodyweight, the plasma mean terminal elimination half-life was 90 ± 57 min with 11% of the drug being recovered in the urine over 24 h.

In 8 patients given a single bolus dose of 0.5 to 0.6 mg/kg bodyweight, the composite initial and terminal half-lives were reported to be 7.7 ± 3.3 min and 108 ± 20.8 min, respectively. Following injection of melphalan, monohydroxymelphalan and dihydroxymelphalan were detected in the patients' plasma, reaching peak levels at approximately 60 min and 105 min, respectively. A similar half-life of 126 ± 6 min was seen when melphalan was added to the patients' serum in vitro (37C), suggesting that spontaneous degradation rather than enzymic metabolism may be the major determinant of the drug's half-life in man.

Following administration of a two-minute infusion of doses ranging from 5 to 23 mg/m² body surface area (approximately 0.1 to 0.6 mg/kg bodyweight) to 10 patients with ovarian cancer or multiple myeloma, the pooled initial and terminal half-lives were, respectively, 8.1 ± 6.6 min and 76.9 ± 40.7 min. A mean clearance of 342.7 ± 96.8 ml/min was recorded.

In 15 children and 11 adults given high-dose i.v. melphalan (140 mg/m² body surface area) with forced diuresis, the mean initial and terminal half-lives were found to be 6.5 ± 3.6 min and 41.4 ± 16.5 min, respectively. Mean initial and terminal half-lives of 8.8 ± 6.6 min and 73.1 ± 45.9 min, respectively, were recorded in 28 patients with various malignancies who were given doses of between 70 and 200 mg/m² body surface area as a 2- to 20-min infusion. The mean clearance was 564.6 ± 159.1 ml/min.

Following hyperthermic (39C) perfusion of the lower limb with 1.75 mg/kg bodyweight, mean initial and terminal half-lives of 3.6 ± 1.5 min and 46.5 ± 17.2 min, respectively, were recorded in 11 patients with advanced malignant melanoma. A mean clearance of 55.0 ± 9.4 ml/min was recorded.

Special Patient Populations

• Renal impairment

Melphalan clearance may be decreased in renal impairment (see Dosage and Administration - Renal impairment and Warnings and Precautions - Renal impairment).

• Elderly

No correlation has been shown between age and melphalan clearance or with melphalan terminal elimination half-life (see Dosage and Administration).

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SmPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Hydrochloric Acid Ph.Eur.

Povidone K12 Ph.Eur.

Water for Injections BP

6.2 Incompatibilities

None known.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Store below 30° C

Protect from light

Do not refrigerate.

6.5 Nature And Contents Of Container

Clear, neutral glass vial and bromobutyl rubber stopper with an aluminium collar.

Pack size: 50 mg

6.6 Special Precautions For Disposal And Other Handling

Preparation of Alkeran Injection Solution:

Alkeran Injection should be prepared at room temperature (approximately 25°C), by reconstituting the freeze-dried powder with the solvent-diluent provided.

It is important that both the freeze-dried powder and the solvent provided are at room temperature before starting reconstitution. Warming the diluent in the hand may aid reconstitution. 10 ml of this vehicle should be added quickly, as a single quantity into the vial containing the freeze dried powder, and immediately shaken vigorously (for approximately 1 minute) until a clear solution, without visible particles, is obtained. Each vial must be reconstituted individually in this manner. The resulting solution contains the equivalent of 5 mg per ml anhydrous melphalan and has a pH of approximately 6.5.

Alkeran Injection solution has limited stability and should be prepared immediately before use. Any solution unused after one hour should be discarded according to standard guidelines for handling and disposal of cytotoxic drugs.

The reconstituted solution should not be refrigerated as this will cause precipitation.

7. Marketing Authorisation Holder

Laboratoires GENOPHARM

ZI de l'Esplanade

2, rue Niels Bohr

F – 77400 Saint-Thibault-des-Vignes

8. Marketing Authorisation Number(S)

PL 26946/0001

9. Date Of First Authorisation/Renewal Of The Authorisation

18 January 2004

10. Date Of Revision Of The Text

September 2010

11 LEGAL STATUS

POM

Lidocaine/Benzalkonium Cream

Pronunciation: LYE-doe-kane/BEN-zal-KOE-nee-um
Generic Name: Lidocaine/Benzalkonium
Brand Name: Examples include A + D Cracked Skin Relief and Dr. Scholl's Cracked Heel Relief

Lidocaine/Benzalkonium Cream is used for:

Relieving pain and itching caused by minor cuts, scrapes, and burns. It may also be used as first aid treatment to help prevent skin infection.

Lidocaine/Benzalkonium Cream is an antiseptic and anesthetic combination. It works by cleansing the wound. It also stops nerves from transmitting painful impulses to the brain.

Do NOT use Lidocaine/Benzalkonium Cream if:

• you are allergic to any ingredient in Lidocaine/Benzalkonium Cream or to similar medicines (eg, amide-type local anesthetics)


• you have signs of infection (eg, oozing, warmth, pain) or tissue damage in the affected area

Contact your doctor or health care provider right away if any of these apply to you.

Before using Lidocaine/Benzalkonium Cream:

Some medical conditions may interact with Lidocaine/Benzalkonium Cream. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to any anesthetic medicine


• if you have heart, liver, or kidney problems; diabetes; or poor circulation


• if the affected area is an animal bite, a burn, or a deep wound (eg, puncture wound), or if there is redness or swelling in the affected area

Some MEDICINES MAY INTERACT with Lidocaine/Benzalkonium Cream. Because little, if any, of Lidocaine/Benzalkonium Cream is absorbed into the blood, the risk of it interacting with another medicine is low.

Ask your health care provider if Lidocaine/Benzalkonium Cream may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Lidocaine/Benzalkonium Cream:

Use Lidocaine/Benzalkonium Cream as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Wash your hands before and immediately after using Lidocaine/Benzalkonium Cream, unless your hands are part of the treated area.


• Wash and completely dry the affected area. Apply a thin layer of Lidocaine/Benzalkonium Cream to the affected area. Gently rub the medicine in until it is evenly distributed.


• If you miss a dose of Lidocaine/Benzalkonium Cream, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.

Ask your health care provider any questions you may have about how to use Lidocaine/Benzalkonium Cream.

Important safety information:

• Lidocaine/Benzalkonium Cream may cause harm if it is swallowed. If you may have taken it by mouth, contact your poison control center or emergency room right away.


• Lidocaine/Benzalkonium Cream is for external use only. Do not get it in your eyes or on the inside of your nose or mouth. If you get Lidocaine/Benzalkonium Cream in your eyes, rinse them immediately with cool water.


• Lidocaine/Benzalkonium Cream may cause a numbing effect at the application site. Do not scratch, rub, or expose the area to extreme hot or cold temperatures until the numbness is gone.


• Do not apply Lidocaine/Benzalkonium Cream over large areas of the body, to open wounds, or to blistered or infected skin without first checking with your doctor.


• Do not use more often than recommended or use for longer than 7 days without checking with your doctor.


• If you symptoms do not get better within 7 days or if they get worse, check with your doctor.


• Talk with your doctor before you use any other medicines or cleansers on your skin.


• Different brands of Lidocaine/Benzalkonium Cream may have different dosing instructions for CHILDREN. Follow the dosing instructions on the package labeling. If your doctor has given you instructions, follow those. If you are unsure of the dose to give to a child, check with your doctor or pharmacist.


• PREGNANCY and BREAST-FEEDING: It is not known if Lidocaine/Benzalkonium Cream can cause harm to the fetus. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Lidocaine/Benzalkonium Cream while you are pregnant. It is not known if Lidocaine/Benzalkonium Cream is found in breast milk after topical use. If you are or will be breast-feeding while you use Lidocaine/Benzalkonium Cream, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Lidocaine/Benzalkonium Cream:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Minor redness or swelling at the application site.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); excessive irritation; signs of infection in the affected area (eg, warmth, oozing, pain).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Lidocaine/Benzalkonium Cream may be harmful if swallowed.

Proper storage of Lidocaine/Benzalkonium Cream:

Store Lidocaine/Benzalkonium Cream at room temperature, between 59 and 86 degrees F (15 and 30 degrees C), in a tightly closed container. Store away from heat, moisture, and light. Keep Lidocaine/Benzalkonium Cream out of the reach of children and away from pets.

General information:

• If you have any questions about Lidocaine/Benzalkonium Cream, please talk with your doctor, pharmacist, or other health care provider.


• Lidocaine/Benzalkonium Cream is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Discard unused medicine and packaging in the trash out of the reach of children and pets.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Lidocaine/Benzalkonium Cream. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Lidocaine/Benzalkonium resources

• Lidocaine/Benzalkonium Use in Pregnancy & Breastfeeding
• Lidocaine/Benzalkonium Drug Interactions
• Lidocaine/Benzalkonium Support Group
• 1 Review for Lidocaine/Benzalkonium - Add your own review/rating

Compare Lidocaine/Benzalkonium with other medications

• Bacterial Skin Infection

Amprolium Hydrochloride

Amprolium Hydrochloride may be available in the countries listed below.

Ingredient matches for Amprolium Hydrochloride

Amprolium

Amprolium Hydrochloride (BANM) is also known as Amprolium (Rec.INN)

International Drug Name Search

Glossary

BANM	British Approved Name (Modified)
Rec.INN	Recommended International Nonproprietary Name (World Health Organization)

Click for further information on drug naming conventions and International Nonproprietary Names.

Amilin

Amilin may be available in the countries listed below.

Ingredient matches for Amilin

Amitriptyline

Amitriptyline hydrochloride (a derivative of Amitriptyline) is reported as an ingredient of Amilin in the following countries:

• Bangladesh


• Iceland

International Drug Name Search

Alendronic Acid 70mg (Actavis UK Ltd)

Alendronic Acid 70mg Tablets

Alendronic acid (as sodium trihydrate)

Please read this leaflet carefully before you start to take your tablets.

• It contains important information.



• It is particularly important to read the section “How to take your tablets”.



• If you are not sure about anything, or want to know more, ask your doctor or a pharmacist.



• Keep this leaflet safe, as you may want to read it again.

About Your Tablets

Your tablets are called Alendronic Acid 70mg Tablets.

They are part of a group of drugs known as bisphosphonates.

What Is In Your Tablets

Each tablet contains:

• Alendronic acid 70mg (as sodium trihydrate) (active ingredient); and



• Cellactose 80, croscarmellose sodium, colloidal anhydrous silica and magnesium stearate (inactive ingredients).

Alendronic Acid 70mg Tablets are white, round, biconvex tablets, marked with ‘70’ on one side and plain on the other side.

Alendronic Acid 70mg Tablets are supplied in blister packs of 2, 4 and 12 tablets. Not all pack sizes may be marketed.

Who makes your tablets

The marketing authorisation holder is

Actavis Group PTC ehf

Reykjavikurvegi

76-78, 220 Hafnarfjordur

Iceland

The manufacturer and distributor is

Actavis

Barnstaple

EX32 8NS

UK

What your tablets do

Alendronic acid belongs to a group of medicines called bisphosphonates.

Alendronic acid prevents the loss of bone (osteoporosis) in women that occurs after the menopause, and helps to rebuild bone. Osteoporosis if untreated can result in fractures (broken bones) of the spine and hips, and alendronic acid can reduce the risk of the fractures occurring.

Before You Take Your Tablets

Do not take Alendronic Acid 70mg Tablets and tell your doctor if;

• you have certain disorders of the oesophagus (sometimes called the gullet and is the tube that connects your mouth with your stomach)



• you are unable to stand or sit upright for at least 30 minutes



• you are allergic to any of the ingredients



• your doctor has told you that you have low blood calcium



• you are or think you may be pregnant



• you are breast-feeding.

Alendronic acid should not be given to children.

Please tell your doctor or pharmacist before you start to take Alendronic Acid 70mg Tablets if you;

• suffer from kidney problems



• have any allergies



• have any swallowing or digestive problems



• have an intolerance to some sugars e.g. lactose



• are taking any other medicines including ones you have bought yourself without prescription.

Can you take Alendronic acid with other medicines?

Alendronic acid can interact with food, drinks and other medicines which you take by mouth, and it is important to follow the advice given under the heading “How to take your tablets”. You should always tell your doctor about all medicines you are taking or plan to take,
including any obtained without prescription.

How To Take Your Tablets

Alendronic Acid 70mg Tablets are to be taken by mouth once a week.

It is important that you carefully follow the instructions on how to take your tablets.

Choose a day of the week to take your tablet that best fits with your normal schedule. Every week, take one Alendronic Acid 70mg Tablet on your chosen day.

After getting up for the day and before taking your first food, beverage or other medicine, swallow your Alendronic Acid 70mg Tablet with a full glass of plain water (not less than 200ml or 7 fl. oz).

Do not take your tablet with mineral water, coffee, tea or fruit juice.

Do not chew your tablet or allow it to dissolve in your mouth.

After swallowing your tablet do not lie down, stay fully upright (sitting, standing or walking) for at least 30 minutes, and do not lie down until after your first food of the day.

Do not take Alendronic acid at bedtime or before getting up for the day.

If you develop difficulty or pain upon swallowing, chest pain, or new or worsening heartburn, stop taking Alendronic acid and contact your doctor.

After swallowing your Alendronic Acid 70mg Tablet, wait at least 30 minutes before taking your first food, beverage, or other medication of the day, including antacids, calcium supplements and vitamins.Alendronic acid is effective only if taken when your stomach is empty.

If you miss a dose, just take one Alendronic Acid 70mg Tablet on the morning after your remember. Do not take two tablets on the same day.

The following week return to taking one tablet once a week, as originally scheduled on your chosen day.

It is important that you continue taking Alendronic acid for as long as your doctor prescribes the medicine.

What to do if you take too many tablets

It is important not to take too many tablets. If you have taken too many tablets drink a full glass of milk and contact your doctor or hospital Accident and Emergency department immediately. Do not make yourself vomit, and do not lie down.

What unwanted effects could Alendronic Acid 70mg Tablets have?

While taking Alendronic Acid 70mg Tablets you may have some side effects. Tell your doctor if you suffer from any of the following:

• irritation or ulceration of the oesophagus (the tube that connects your mouth with your stomach), which can cause chest pain, heartburn, difficulty or pain upon swallowing and/or scarring leading to narrowing of the oesophagus.These reactions may occur if patients do not drink a full glass of water with alendronic acid and/or if they lie down less than 30 minutes after taking alendronic acid or before their first food of the day. Oesophageal reactions may worsen if patients continue to take alendronic acid after developing symptoms suggesting irritation of the oesophagus.



• stomach/abdominal pain, dyspepsia, constipation, diarrhoea, flatulence, feeling full or bloated, nausea and vomiting and black and/or bloody stools.



• some patients may experience bone, muscle or joint pain, (rarely, with flu-like symptoms or fever), headache or rarely a rash (occasionally made worse by sunlight), itching, eye pain, diminished or hazy vision and/or see black floating spots.



• rarely stomach or other peptic ulcers have occurred. It is not known whether or not these were caused by treatment with Alendronic acid.



• very rarely severe skin reactions have occurred. Allergic reactions such as hives or, rarely, more severe allergic reactions have occurred. If you experience swelling of the face, lips, tongue and/or throat, possibly causing difficulty in breathing or swallowing, you should go to your local Accident and Emergency department immediately as this may be due to a severe allergic reaction which can be life threatening.



• mouth ulcers have occurred when the tablets have been chewed or sucked.

If you feel unwell in any other way, tell your doctor as soon as you can.

Alendronic acid should not affect your ability to drive or operate machinery.

Looking After Your Tablets

Keep all tablets out of the sight and reach of children.

No special storage conditions are required for this medicine.

Do not take the tablets after the expiry date.You should take any tablets that are out of date or which you no longer need back to your pharmacist.

These tablets are only for you. Only a doctor can prescribe them for you. Never give them to anyone else as it may harm them, even if their symptoms are the same as yours.

PL number 30306/0032

This leaflet was written in November 2007.

Actavis

Barnstaple

EX32 8NS

UK

Anodesyn Ointment

1. Name Of The Medicinal Product

Anodesyn Ointment

Care Haemorrhoid Relief Ointment

Sainsburys Haemorrhoid Relief Ointment

Tesco Haemorrhoid Relief Ointment

2. Qualitative And Quantitative Composition

Allantoin 0.5% w/w.

Lidocaine Hydrochloride 0.5% w/w.

For excipients, see 6.1

3. Pharmaceutical Form

A soft white translucent ointment.

4. Clinical Particulars

4.1 Therapeutic Indications

For the symptomatic relief of pain and irritation associated with external haemorrhoids.

4.2 Posology And Method Of Administration

Route of administration: For external application.

Adults & the elderly.

For external piles, wash the affected area with tepid water, dry and apply the ointment with gauze or lint.

Repeat as required, do not use for more than 7 days unless advised by your doctor.

Children.

Not recommended for children.

4.3 Contraindications

Hypersensitivity to any of the ingredients, especially lidocaine.

4.4 Special Warnings And Precautions For Use

Anodesyn Ointment / Care Haemorrhoid Relief Ointment / Sainsburys Haemorrhoid Relief Ointment/Tesco Haemorrhoid Relief Ointment is intended for use for short periods and should not be used for longer than 7 days without medical advice. Patients should be instructed to seek medical advice if they experience persistent pain or bleeding from the anus, especially where associated with a change in bowel habit, if the stomach is distended or if they are losing weight.

Avoid contact with the eyes.

The label will state:

Keep all medicines out of the reach and sight of children.

If symptoms persist for more than 7 days consult your doctor.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No clinically significant drug interactions known.

4.6 Pregnancy And Lactation

The safety of Anodesyn Ointment / Care Haemorrhoid Relief Ointment / Sainsburys Haemorrhoid Relief Ointment/Tesco Haemorrhoid Relief Ointment in pregnancy and lactation has not been assessed, but it is thought unlikely to constitute a hazard, though caution should be exercised during the first trimester.

Lidocaine crosses the placenta and is distributed into breast milk.

4.7 Effects On Ability To Drive And Use Machines

No or negligible influence.

4.8 Undesirable Effects

Hypersensitivity to any of the ingredients, especially lidocaine.

4.9 Overdose

Accidental ingestion may result in anaesthesia of the upper respiratory tract, nausea, vomiting and abdominal discomfort. Ingestion of very large quantities could result in CNS and cardiovascular toxicity. Treatment should be symptomatic and supportive.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

C05A X - Other antihaemorrhoidals for topical use

Lidocaine has a local anaesthetic action, relieving pain and discomfort in the affected areas.

Allantoin is claimed to promote healing.

5.2 Pharmacokinetic Properties

No data available.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

White Soft Paraffin

Wool Fat

Purified Water

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

Three years.

6.4 Special Precautions For Storage

Store at or below 25°C.

6.5 Nature And Contents Of Container

A collapsible 25g aluminium tube, internally lacquered with a latex welt and HPDE screw cap. Supplied with a nozzle and packed in a carton.

6.6 Special Precautions For Disposal And Other Handling

None stated

7. Marketing Authorisation Holder

Thornton & Ross Limited

Linthwaite

Huddersfield

West Yorkshire

HD7 5QH

United Kingdom

8. Marketing Authorisation Number(S)

PL 00240/0072

9. Date Of First Authorisation/Renewal Of The Authorisation

2 December 2002 / 29 September 2003

10. Date Of Revision Of The Text

23/1/2008

11 DOSIMETRY (IF APPLICABLE)

Not Applicable

12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS (IF APPLICABLE)

Not Applicable