Friday, October 14, 2016

Nabilone 1mg Capsules





1. Name Of The Medicinal Product



Nabilone Capsules


2. Qualitative And Quantitative Composition



Nabilone Capsules contain 1.0mg Nabilone per capsule.



3. Pharmaceutical Form



Blue and white capsules imprinted "CL 3101”.



4. Clinical Particulars



4.1 Therapeutic Indications



Nabilone is indicated for the control of nausea and vomiting, caused by chemotherapeutic agents used in the treatment of cancer, in patients who have failed to respond adequately to conventional antiemetic treatments.



4.2 Posology And Method Of Administration



Nabilone is for administration to adults only. It is not recommended for use in children younger than 18 years of age as safety and efficacy have not been established.



The usual adult dosage is 1mg or 2mg twice a day. To minimise side-effects, it is recommended that the lower starting dose is used and that the dose is increased as necessary. The first dose should be administered the night before initiation of chemotherapy, and the second dose should be given one to three hours before the first dose of the oncolytic agent is administered.



The maximum daily dose should not exceed 6mg, given in three divided doses.



Nabilone may be administered throughout each cycle of chemotherapy and, if necessary, for 48 hours after the last dose of each cycle. Data on the chronic use of nabilone are not available.



The elderly: as for adults (see 'precautions').



4.3 Contraindications



Nabilone is contra-indicated in patients with a known allergy to cannabinoid agents and when the nausea and vomiting arises from any cause other than cancer chemotherapy.



4.4 Special Warnings And Precautions For Use



As nabilone is excreted primarily by the biliary route, the drug is not recommended for use in patients with severe liver dysfunction.



Patients receiving Nabilone should be closely observed, if possible, within an inpatient setting. This is especially important during the treatment of naive patients. However, even patients experienced with cannabinoid agents may have serious untoward responses not predicted by prior uneventful exposures. Patients should be made aware of possible changes of mood and other adverse behavioural effects of the drug.



Since Nabilone can elevate supine and standing heart rates and cause postural hypotension, it should be used with caution in the elderly and in patients with hypertension and heart disease.



4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction



Nabilone should be administered with caution to patients who are taking other psychoactive drugs or CNS depressants, including alcohol, barbiturates and narcotic analgesics, or to those with a history of psychiatric disorder (including manic-depressive illness and schizophrenia). Nabilone has been shown to have an additive CNS depressant effect when given with either diazepam, secobarbitone sodium, alcohol or codeine.



4.6 Pregnancy And Lactation



Usage in pregnancy: Laboratory studies have so far shown no evidence of teratogenicity. There are no adequate and well controlled studies in pregnant women. Nabilone should be used during pregnancy only if clearly needed.



Reproduction studies performed in rats at 150 times the human dose and rabbits at 40 times the human dose revealed a dose-related reduction in litter size, an increase in the incidence of foetal resorptions, and an increase in the incidence of stillborn pups. The number of implantations was unaffected by treatment. These effects appear related to the dose-dependent reduction in maternal food intake and gain in body weight induced by Nabilone. At 150 times the maximum recommended human dose, Nabilone produced a reduction in neonatal survival that may be related to reduced milk production by mothers. Nabilone is known to have an inhibitory effect on prolactin release, which could contribute to the observed reduction in milk production. Hypothermia was also reported in the offspring of high-dose groups of female rats, which may have also contributed to reduced neonatal survival.



Nursing mothers: It is not known whether this drug is excreted in breast milk. It is not recommended that Nabilone be given to nursing mothers.



4.7 Effects On Ability To Drive And Use Machines



Nabilone may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as operating machinery or driving a car; therefore the patient should be advised accordingly. The effects of Nabilone may persist for a variable and unpredictable period of time following its oral administration. Adverse psychiatric reactions can persist for 48 to 72 hours following cessation of treatment.



4.8 Undesirable Effects



During controlled clinical trials of nabilone, virtually all patients experienced at least one adverse reaction. These included pyschotomimetic reactions.



In these trials, the commonest statistically significant adverse events (in decreasing order of incidence) were: drowsiness, vertigo/dizziness, euphoria (high), dry mouth, ataxia, visual disturbance, concentration difficulties, sleep disturbance, dysphoria, hypotension, headache and nausea.



Other reported events include confusion, disorientation, hallucinations, psychosis, depression, decreased co-ordination, tremors, tachycardia, decreased appetite and abdominal pain.



Tolerance to such CNS effects as relaxation, drowsiness and euphoria develops rapidly and is readily reversible.



Drug abuse and dependence: Nabilone is an abusable substance, capable of producing subjective side-effects, such as euphoria or "high", at therapeutic doses. Prescriptions should be limited to the amount necessary for a single cycle of chemotherapy (i.e., a few days). The physical dependence capability of Nabilone is unknown. Patients who participated in clinical trials, up to 5 days duration, showed no withdrawal symptoms on cessation of dosing.



4.9 Overdose



Signs and symptoms are an extension of the psychotomimetic and physiological effects of nabilone. Overdosage may be considered to have occurred, even at prescribed dosages, if disturbing psychiatric symptoms are present. Subsequent doses should be withheld until patients have returned to their baseline mental status; routine dosing, possibly at a lower dose, may then be resumed if clinically indicated. In controlled clinical trials, alterations in mental status, related to the use of nabilone, resolved within 72 hours without specific medical therapy. Vital signs should be monitored, since hypertension, hypotension and tachycardia have occurred.



No cases of overdosage with more than 10mg/day of Nabilone have been reported during clinical trials. Signs and symptoms to be anticipated in large overdose situations are psychotic episodes, including hallucinations and anxiety reactions, respiratory depression and coma.



Treatment: Conservative management, if possible (i.e. verbal support and comfort). In more severe cases, antipsychotic drugs may be useful, although they have not been systematically evaluated. Such patients should be closely monitored because of the potential for drug interactions (eg., additive CNS depressant effects due to Nabilone and chlorpromazine).



General supportive care is recommended. Consider giving activated charcoal to decrease absorption from the gastrointestinal tract. The use of forced diuresis, peritoneal dialysis, haemodialysis, charcoal haemoperfusion, or cholestyramine, has not been reported. Most of a dose of Nabilone is eliminated through the biliary system.



Treatment for respiratory depression and comatose state consists of symptomatic and supportive therapy. Attention should be paid to the occurrence of hypothermia. Consider fluids, inotropes and/or vasopressors for hypotension.



5. Pharmacological Properties



5.1 Pharmacodynamic Properties



Nabilone is a synthetic cannabinoid which has been shown to have significant anti-emetic activity in patients undergoing chemotherapy for malignant neoplasms. The mode of action of Nabilone has been studied in cats and dogs. Although its anti-emetic action is not yet fully understood, it is apparent that there are a number of points in the control systems of the body at which Nabilone could block the emetic mechanism.



5.2 Pharmacokinetic Properties



Absorption



Two fasted subjects were given an oral dose of 2mg 14C-nabilone. Nabilone was readily absorbed from the gastrointestinal tract. Pharmacokinetic comparison between the oral and intravenous routes of administration suggested that most of the drug was available after oral dosage. Similarly, the percentages of radioactivity in the faeces and urine were approximately sixty per cent and twenty-four per cent respectively whichever route was employed, supporting the view that most of the oral dose was absorbed.



Half-life



The plasma half-life of unchanged Nabilone in these volunteers was approximately two hours. The estimated half-life of the carbinol metabolite was somewhat longer at between five and ten hours. Total radioactivity had a half-life of approximately thirty-five hours.



Transport



The rapid disappearance of absorbed drug from the plasma has been related to extensive tissue distribution and to rapid metabolism and excretion.



Metabolism



Two metabolic pathways have been suggested. The major pathway probably involves the direct oxidation of Nabilone to produce hydroxylic and carboxylic analogues. These compounds are thought to account for the remaining plasma radioactivity when carbinol metabolites have been extracted.



Excretion



When 2mg of 14C-nabilone was administered orally, over sixty per cent of the total radioactivity was eliminated in the faeces and about twenty five per cent in the urine. The discrepancy is probably due to additive analytical errors, since respiratory 14C CO2 did not account for the remaining fifteen per cent. Comparison with intravenous administration indicated no significant differences in the excretion pattern suggesting the biliary system to be the major excretory pathway.



5.3 Preclinical Safety Data



Monkeys treated with Nabilone at doses as high as 2mg/kg/day for a year experienced no significant adverse events. This result contrasts with the finding in a planned 1-year dog study that was prematurely terminated because of deaths associated with convulsions in dogs receiving as little as 0.5mg/kg/day. The earliest deaths, however, occurred at 56 days in dogs receiving 2mg/kg/day. The unusual vulnerability of the dog is not understood; it is hypothesised, however, that the explanation lies in the fact that the dog differs markedly from other species (including humans) in its metabolism of Nabilone.



Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenicity studies have not been performed with Nabilone. The influence on fertility and reproduction at doses of 150 and 40 times the maximum recommended human dose was evaluated in rats and rabbits, respectively. In these studies there was no evidence of teratogenicity due to Nabilone. In high dose groups, however, Nabilone produced a slight decrease in mean litter size, although the number of implantations was unaffected by treatment.



6. Pharmaceutical Particulars



6.1 List Of Excipients



Povidone



Starch flowable



Indigo carmine



Red iron oxide



Titanium dioxide



Gelatin



Edible black ink



6.2 Incompatibilities



None known.



6.3 Shelf Life



Three years.



6.4 Special Precautions For Storage



Bottles: Keep tightly closed. Store at 15 - 25 ºC.



Blisters: Store at 15 - 25 ºC.



6.5 Nature And Contents Of Container



High density polyethylene bottles with screw caps or blister packs, each containing 20 capsules.



6.6 Special Precautions For Disposal And Other Handling



None



7. Marketing Authorisation Holder



Meda Pharmaceuticals Ltd.



Skyway House



Parsonage Road



Takeley



Bishop's Stortford



CM22 6PU



UK



8. Marketing Authorisation Number(S)



PL 15142/0028



9. Date Of First Authorisation/Renewal Of The Authorisation



27 March 2009



10. Date Of Revision Of The Text



June 2009




Neostigmine Methylsulphate Injection BP 2.5mg (hameln)







Read all of this leaflet carefully before you start using this medicine.



  • Keep this leaflet. You may need to read it again. In some circumstances this may not be possible if you are given this injection in an emergency. This leaflet will be kept in a safe place should you wish to read it again


  • If you have any further questions, please ask your doctor or your pharmacist.


  • This medicine has been prescribed for you personally and you should not pass it on to others. It may harm them, even if their symptoms are the same as yours.



  • 1. What Neostigmine Injection is and what it is used for

  • 2. Before you are given Neostigmine Injection

  • 3. How to use Neostigmine Injection

  • 4. Possible side effects

  • 5. Storing Neostigmine Injection

  • 6. Further information



Neostigmine Methylsulphate Injection BP 2.5 mg





What Neostigmine Injection is and what it is used for



The injection contains the active ingredient neostigmine methylsulphate as a 2.5 mg in 1 ml sterile solution.




Neostigmine injection belongs to a group of medicines used to:



  • Treat abnormally tired and weak muscles (myasthenia gravis).


  • Reverse the effects of muscle relaxants.


  • Improve movement in the small intestine.


  • Reduce urine retention after surgical procedures.





Before you are given Neostigmine Injection




Please tell your doctor or pharmacist before being given your injection if:



  • You are sensitive or allergic to neostigmine.


  • You have an obstruction of the stomach or cannot urinate.


  • You are pregnant or breast feeding.


  • You are receiving certain muscle relaxants, i.e. Suxamethonium.


  • You are asthmatic.



If you are going to have an operation, please tell your doctor if you are receiving neostigmine.



This medicinal product contains approximately 3.54 mg sodium per ml. This should be taken into consideration by patients on a controlled sodium diet.





How to use Neostigmine Injection



The injection should only be administered to you by a member of the medical profession.



The amount of neostigmine you will be given depends on your condition and other factors.



You may be given another injection depending on the response to the first injection.





Possible side effects



  • You may feel or actually be sick.

  • You may produce more saliva than usual.

  • You may suffer from diarrhoea.

With higher doses of neostigmine, you may suffer from stomach cramps.



If you have any problems, please tell your doctor.





Storing Neostigmine Injection



Your injection will be kept for you by your doctor or pharmacist. An expiry date can be found on the label e.g.: August 2007.





Further information



The injection is a clear colourless solution in clear glass ampoules containing 2.5 mg neostigmine methylsulphate in 1 ml. 10 ampoules are supplied in each carton.




Neostigmine Injection contains the following inactive ingredients:



Sodium Chloride



Sterile Water for Injections




Registered PL No. 1502/0023





The marketing authorization holder of this medicine is:




hameln pharmaceuticals ltd

Gloucester

UK





The medicine is manufactured by:




hameln pharmaceuticals gmbh

Langes Feld 13

31789 Hameln

Germany





Revised July 2006



43849/50/06






Neupogen Singleject Syringes






Neupogen Singleject 30 MU (0.6 mg/ml)



Neupogen Singleject 48 MU (0.96 mg/ml)



solution for injection in a pre-filled syringe


filgrastim



Read all of this leaflet carefully before you start using this medicine.


  • Keep this leaflet. You may need to read it again.

  • If you have any further questions, ask your doctor, nurse or pharmacist.

  • This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

  • If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, nurse or pharmacist.



In this leaflet:


1. What Neupogen is and what it is used for

2. Before you use Neupogen

3. How to use Neupogen

4. Possible side effects

5. How to store Neupogen

6. Further information

7. Instructions for injecting Neupogen





What Neupogen Is And What It Is Used For


Neupogen is a white blood cell growth factor (granulocyte colony stimulating factor) and belongs to a group of medicines called cytokines. Growth factors are proteins that are produced naturally in the body but they can also be made using biotechnology for use as a medicine. Neupogen works by encouraging the bone marrow to produce more white blood cells.


A reduction in the number of white blood cells (neutropenia) can occur for several reasons and makes your body less able to fight infection. Neupogen stimulates the bone marrow to produce new white cells quickly.


Neupogen can be used:


  • to increase the number of white blood cells after treatment with chemotherapy to help prevent infections;

  • to increase the number of white blood cells after a bone marrow transplant to help prevent infections;

  • before high-dose chemotherapy to make the bone marrow produce more stem cells which can be collected and given back to you after your treatment. These can be taken from you or from a donor. The stem cells will then go back into the bone marrow and produce blood cells;

  • to increase the number of white blood cells if you suffer from severe chronic neutropenia to help prevent infections;

  • in patients with advanced HIV infection which will help reduce the risk of infections.



Before You Use Neupogen



Do not use Neupogen


  • if you are allergic (hypersensitive) to filgrastim or any of the other ingredients of Neupogen.

  • if you have Kostman’s Syndrome (severe condition acquired at birth), your doctor will discuss with you whether or not you should take Neupogen.



Take special care with Neupogen


Please tell your doctor before starting treatment:


  • if you have sickle cell anaemia, as Neupogen may cause sickle cell crisis;

  • if you have an allergy to natural rubber (latex). The needle cover on the syringe is made from a type of natural rubber and may cause severe allergic reactions;

  • if you have osteoporosis (bone disease).

If you are a stem cell donor, you must be aged between 16 and 60 years.



Take special care with other products that stimulate white blood cells.


Neupogen is one of a group of products that stimulate the production of white blood cells. Your healthcare professional should always record the exact product you are using.




Using other medicines


Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription as they may affect the way Neupogen works.




Pregnancy and breast feeding


Neupogen has not been tested in pregnant women. It is important to tell your doctor if you are pregnant, think you may be pregnant or plan to get pregnant, as the doctor may decide that you should not use this medicine. Neupogen could affect your ability to become pregnant or stay pregnant.


You must not use this medicine if you are breast feeding.


Ask your doctor or pharmacist for advice before taking any medicine.




Driving and using machines


Neupogen should not affect your ability to drive and use machines. However, it is advisable to wait and see how you feel after taking Neupogen and before driving or operating machinery.




Important information about some of the ingredients of Neupogen


Neupogen contains less than 1 mmol (23 mg) sodium per 0.6 mg/ml or 0.96 mg/ml dose, i.e. essentially sodium free.


Neupogen contains sorbitol (E420), if you have been told by your doctor that you have a reaction to some sugars, contact your doctor before taking this medicinal product.





How To Use Neupogen


Always use Neupogen exactly as your doctor has told you. You should check with your doctor, nurse or pharmacist if you are not sure.



How is Neupogen given and how much should I take?


Neupogen is usually given as a daily injection into the tissue just under the skin (known as a subcutaneous injection). It can also be given as a daily slow injection into the vein (known as an intravenous infusion). The usual dose varies depending on your illness and weight. Your doctor will tell you how much Neupogen you should take.


You, or people caring for you, can be taught how to give subcutaneous injections so that you can continue your treatment at home. However, you should not attempt this unless you have been properly trained first.




How long will I have to take Neupogen?


You will need to take Neupogen until your white blood cell count is normal. Regular blood tests will be taken to monitor the number of white blood cells in your body. Your doctor will tell you how long you will need to take Neupogen.




Neupogen and children


Neupogen is used to treat children who are receiving chemotherapy or who suffer from severe low white blood cell count (neutropenia). The dosing in children is the same as for adults.




If you use more Neupogen than you should


Do not increase the dose your doctor has given you. If you think you have injected more than you should, contact your doctor as soon as possible.




If you forget to use Neupogen


If you have missed an injection, or injected too little, contact your doctor as soon as possible. Do not take a double dose to make up for any missed doses.



If you have any further questions on the use of this product, ask your doctor, nurse or pharmacist.




Possible Side Effects



Please tell your doctor immediately during treatment:


  • if you experience an allergic reaction including weakness, drop in blood pressure, difficulty breathing, swelling of the face (anaphylaxis), skin rash, itchy rash (urticaria), swelling of the face lips, mouth, tongue or throat (angioedema) and shortness of breath (dyspnoea);

  • if you experience a cough, fever and difficulty breathing (dyspnoea) as this can be a sign of Adult Respiratory Distress Syndrome (ARDS);

  • if you get left upper belly (abdominal) pain or pain at the tip of your shoulder, as there may be a problem with your spleen.

Like all medicines, Neupogen can cause side effects, although not everybody gets them.



Very common side effects (seen in more than 1 in 10 people who take Neupogen):



in cancer patients


  • nausea and vomiting

  • pain in your bones (musculoskeletal pain), which can be helped by taking standard pain relief medicines (analgesics)

  • changes in blood chemistry


in normal stem cell donors


  • headache

  • increase in white blood cells (leukocytosis), decrease of platelets which reduces the bloods ability to clot (thrombocytopenia)

  • pain in your bones (musculoskeletal pain), which can be treated with standard pain relief tablets


in severe chronic neutropenia patients


  • low red blood cell count (anaemia), enlargement of the spleen (splenomegaly)

  • changes in blood chemistry

  • pain in your bones (musculoskeletal pain)

  • nose bleeds (epistaxis)


in HIV patients


  • pain in your bones (musculoskeletal)


Common side effects (seen in more than 1 in 100 people taking Neupogen):



in cancer patients


  • tiredness (fatigue), generalised weakness

  • headache

  • constipation, anorexia, diarrhoea, soreness and swelling of the digestive tract lining which runs from the mouth to the anus (mucositis)

  • chest pain, pain in your bones (musculoskeletal pain)

  • cough, sore throat

  • unusual hair loss or thinning (alopecia), skin rash


in normal stem cell donors


  • changes in blood chemistry


in severe chronic neutropenia patients


  • headache

  • diarrhoea

  • decrease of platelets which reduces the bloods ability to clot (thrombocytopenia)

  • enlargement of the liver (hepatomegaly)

  • disease which causes bones to become less dense, making them weaker, more brittle and likely to break (osteoporosis)

  • unusual hair loss or thinning (alopecia), injection site pain, rash


in HIV patients


  • enlargement of the spleen (splenomegaly)


Uncommon side effects (seen in more than 1 in 1000 people taking Neupogen):



in cancer patients


  • unspecified pain


in normal stem cell donors


  • changes in blood chemistry

  • enlargement of the spleen (splenomegaly)


in severe chronic neutropenia patients


  • enlargement of the spleen (splenomegaly)

  • blood in the urine (haematuria)

  • excess protein in the urine (proteinuria)


Rare side effects (seen in more than 1 in 10,000 people taking Neupogen):



in cancer patients


  • problems with your blood vessels (vascular disorders)


Very rare side effects (seen in less than 1 in 10,000 people taking Neupogen):



in cancer patients


  • pain when passing urine (dysuria)


Frequency unknown



in cancer patients


  • inflammation of the blood vessels in the skin (cutaneous vasculitis)

  • plum-coloured, raised, painful sores on the limbs and sometimes the face and neck with a fever (Sweet’s syndrome)

  • worsening of rheumatoid arthritis

  • a cough, fever and difficulty breathing (dyspnoea)

  • problems with your lungs (pulmonary) including serious lung infection (interstitial pneumonia), swelling and/or fluid in the lungs (pulmonary oedema)

  • pain and swelling of the joints, similar to gout (pseudogout)


in normal stem cell donors


  • cough, fever and difficulty breathing or coughing up blood.

Some changes may occur in your blood, but these will be detected by routine blood tests.



If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, nurse or pharmacist.




How To Store Neupogen


Keep out of the reach and sight of children.


Store in a refrigerator (2°C – 8°C).


Accidental freezing will not harm Neupogen.


Do not use Neupogen after the expiry date which is stated on the syringe label and carton after EXP.


The expiry date refers to the last day of that month.


Do not use Neupogen if you notice discolouration, cloudiness or particles, it should be a clear, colourless liquid.


Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.




Further Information



What Neupogen contains


  • The active substance is filgrastim 30 million units (0.6 mg/ml) or 48 million units (0.96 mg/ml).

  • The other ingredients are sodium acetate, sorbitol (E420), polysorbate 80, water for injections.



What Neupogen looks like and contents of the pack


Neupogen is a clear colourless solution for injection (injection) /concentrate for solution for infusion (sterile concentrate) in a pre-filled syringe.


Neupogen is available in packs of one or five pre-filled syringes. Not all pack sizes may be marketed.




Marketing Authorisation Holder and Manufacturer



Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

The Netherlands



This medicine is marketed in the European Economic Area under the name Neupogen, except in Cyprus, Greece and Italy where it is called Granulokine.




This leaflet was last approved in July 2010.


Detailed information on this medicine can be found on the following web sites:


  • For UK residents, the Medicines and Healthcare products Regulatory Agency (MHRA) www.mhra.gov.uk.


Instructions For Injecting Neupogen


This section contains information on how to give an injection of Neupogen.



Important: do not try to give yourself an injection unless you have received training from your doctor or nurse.


Neupogen is injected into the tissue just under the skin. This is known as a subcutaneous injection.



Equipment that you need


To give yourself a subcutaneous injection you will need:


  • a new pre-filled syringe of Neupogen; and

  • alcohol wipes or similar.



What do I do before I give myself a subcutaneous injection of Neupogen?


1. Remove the syringe from the refrigerator. Leave the syringe at room temperature for approximately 30 minutes or hold the pre-filled syringe gently in your hand for a few minutes. This will make the injection more comfortable. Do not warm Neupogen in any other way (for example, do not warm it in a microwave or in hot water).

2. Do not shake the pre-filled syringe.

3. Do not remove the needle cover until you are ready to inject.

4. Check the expiry date on the pre-filled syringe label (EXP). Do not use it if the date has passed the last day of the month shown.

5. Check the appearance of Neupogen. It must be a clear and colourless liquid. If there is discolouration, cloudiness or particles in it, you must not use it.

7. Wash your hands thoroughly.

8. Find a comfortable, well-lit, clean surface and put all the equipment you need within reach.




How do I prepare my Neupogen injection?


Before you inject Neupogen you must do the following:


1. To avoid bending the needle, gently pull the cover from the needle without twisting as shown in pictures 1 and 2.

2. Do not touch the needle or push the plunger.

3. You may notice a small air bubble in the pre-filled syringe. You do not have to remove the air bubble before injecting. Injecting the solution with the air bubble is harmless.

4. You can now use the pre-filled syringe.





Where do I give my injection?



The best places to inject are the top of your thighs and the abdomen. If someone else is injecting you, they can also use the back of your arms.


You may change the injection site if you notice the area is red or sore.




How do I give my injection?


1. Disinfect your skin by using an alcohol wipe and pinch (without squeezing) the skin between your thumb and forefinger.

2. Put the needle fully into the skin as shown by your nurse or doctor.

3. Pull slightly on the plunger to check that a blood vessel has not been punctured. If you see blood in the syringe, pull the needle out and re-insert it in another place.

4. Push the plunger with a slow constant pressure, always keeping your skin pinched, until the syringe is empty.

5. Remove the needle and let go of your skin.

6. If you notice a spot of blood you may gently dab it away with a cotton ball or tissue. Do not rub the injection site. If needed, you may cover the injection site with a plaster.

7. Only use each syringe for one injection. Do not use any Neupogen that may be left in the syringe.



Remember: if you have any problems, please do not be afraid to ask your doctor or nurse for help and advice.




Disposing of used syringes


  • Do not put the cover back on used needles, as you may accidentally prick yourself.

  • Keep used syringes out of the reach and sight of children.

  • Syringes should not be thrown out in the household rubbish. Your pharmacist will know how to dispose of used syringes or syringes no longer needed.




Local representative of the marketing authorisation holder:



United Kingdom



Amgen Limited

240 Cambridge Science Park

Cambridge

CB4 0WD

United Kingdom

Tel:01223 420305


Neupogen is available on the Royal National Institute of the Blind (RNIB) Medicines Information Line who can provide this leaflet in a number of physical formats including large/clear print, Braille and audio CD.


You can also listen to this leaflet when you call the Medicines Information Line.


The RNIB Medicines Information Line is free to use and available 24 hours a day, 7 days a week. Please call them on
0800 198 5000.






Nevanac 1mg / ml eye drops, suspension





1. Name Of The Medicinal Product



NEVANAC 1 mg/ml eye drops, suspension


2. Qualitative And Quantitative Composition



1 ml of suspension contains 1 mg nepafenac.



Excipients: benzalkonium chloride 0.05 mg.



For a full list of excipients, see section 6.1.



3. Pharmaceutical Form



Eye drops, suspension (eye drops)



Light yellow to dark yellow uniform suspension, pH 7.4 (approximately).



4. Clinical Particulars



4.1 Therapeutic Indications



Prevention and treatment of postoperative pain and inflammation associated with cataract surgery (see section 5.1).



4.2 Posology And Method Of Administration



Use in adults, including the elderly



The dose is one drop of NEVANAC in the conjunctival sac of the affected eye(s) 3 times daily beginning 1 day prior to cataract surgery, continued on the day of surgery and for the first 2 weeks of the postoperative period. Treatment can be extended to the first 3 weeks of the postoperative period, as directed by the clinician. An additional drop should be administered 30



Paediatric patients



NEVANAC is not recommended for use in children below 18 years due to a lack of data on safety and efficacy.



Use in hepatic and renal impairment



NEVANAC has not been studied in patients with hepatic disease or renal impairment. Nepafenac is eliminated primarily through biotransformation and the systemic exposure is very low following topical ocular administration. No dose adjustment is warranted in these patients.



Method of administration



For ocular use.



Instruct patients to shake the bottle well before use.



If more than one topical ophthalmic medicinal product is being used, the medicines must be administered at least 5 minutes apart.



To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip of the bottle. Instruct patients to keep the bottle tightly closed when not in use.



4.3 Contraindications



Hypersensitivity to the active substance, to any of the excipients, or to other nonsteroidal anti



Like other NSAIDs, NEVANAC is also contraindicated in patients in whom attacks of asthma, urticaria, or acute rhinitis are precipitated by acetylsalicylic acid or other NSAIDs.



4.4 Special Warnings And Precautions For Use



Do not inject. Instruct patients not to swallow NEVANAC.



Instruct patients to avoid sunlight during treatment with NEVANAC.



Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of NEVANAC and should be monitored closely for corneal health.



Topical NSAIDs may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems.



Post-marketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid arthritis or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse reactions which may become sight threatening. Topical NSAIDs should be used with caution in these patients. Prolonged use of topical NSAIDs may increase patient risk for occurrence and severity of corneal adverse reactions.



There have been reports that ophthalmic NSAIDs may cause increased bleeding of ocular tissues (including hyphaemas) in conjunction with ocular surgery. Use NEVANAC with caution in patients with known bleeding tendencies or who are receiving other medicinal products which may prolong bleeding time.



There are no data on the concomitant use of prostaglandin analogues and NEVANAC. Considering their mechanisms of action, the concomitant use of these medicinal products is not recommended.



NEVANAC contains benzalkonium chloride which may cause irritation and is known to discolour soft contact lenses. Additionally, contact lens wear is not recommended during the postoperative period following cataract surgery. Therefore, patients should be advised not to wear contact lenses during treatment with NEVANAC.



Benzalkonium chloride, which is commonly used as a preservative in ophthalmic products, has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Since NEVANAC contains benzalkonium chloride, close monitoring is required with frequent or prolonged use.



An acute ocular infection may be masked by the topical use of anti-inflammatory medicines. NSAIDs do not have any antimicrobial properties. In case of ocular infection, their use with anti-infectives should be undertaken with care.



Cross-sensitivity



There is a potential for cross-sensitivity of nepafenac to acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs.



4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction



In vitro studies have demonstrated a very low potential for interaction with other medicinal products and protein binding interactions (see section 5.2).



4.6 Pregnancy And Lactation



Pregnancy



There are no adequate data from the use of nepafenac in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Since the systemic exposure in non



Lactation



It is unknown whether nepafenac is excreted in human milk. Animal studies have shown excretion of nepafenac in the milk of rats. However, no effects on the suckling child are anticipated since the systemic exposure of the breastfeeding woman to nepafenac is negligible. NEVANAC can be used during lactation.



4.7 Effects On Ability To Drive And Use Machines



As with any eye drops, temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machinery.



4.8 Undesirable Effects



In clinical studies involving over 800 patients receiving NEVANAC eye drops, approximately 5% of patients experienced adverse reactions. These events led to discontinuation in 0.5% of patients, which was less than placebo-treated patients (1.3%) in these same studies. No serious adverse events related to NEVANAC were reported in these studies.



The following undesirable effects were assessed to be treatment-related and are classified according to the following convention: very common (



Nervous system disorders



Common: headache



Eye disorders



Common: punctate keratitis, eye pain, blurred vision, eye pruritus, dry eye, foreign body sensation in eyes, eyelid margin crusting



Uncommon: iritis, keratitis, corneal deposits, choroidal effusion, eye discharge, photophobia, eye irritation, allergic conjunctivitis, ocular discomfort, eyelid disorder, increased lacrimation, conjunctival hyperaemia



Gastrointestinal disorders



Uncommon: nausea, dry mouth



Skin and subcutaneous tissue disorders



Uncommon: cutis laxa (dermatochalasis)



Immune system disorders



Uncommon: hypersensitivity



Adverse reactions identified from post



Eye disorders: ulcerative keratitis, corneal epithelium defect/disorder, corneal abrasion, anterior chamber inflammation, impaired healing (cornea), reduced visual acuity, corneal scar, corneal opacity



Patients with evidence of corneal epithelial breakdown should immediately discontinue use of NEVANAC and should be monitored closely for corneal health (see section 4.4).



Post-marketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid arthritis or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse reactions which may become sight threatening.



4.9 Overdose



There is no experience of overdose with ocular use. The application of more than one drop per eye is unlikely to lead to unwanted side



5. Pharmacological Properties



5.1 Pharmacodynamic Properties



Pharmacotherapeutic group: Antiinflammatory agents, non-steroids, ATC code: S01BC10



Mechanism of action



Nepafenac is a non-steroidal anti-inflammatory and analgesic prodrug. After topical ocular dosing, nepafenac penetrates the cornea and is converted by ocular tissue hydrolases to amfenac, a nonsteroidal anti-inflammatory drug. Amfenac inhibits the action of prostaglandin H synthase (cyclooxygenase), an enzyme required for prostaglandin production.



Secondary Pharmacology



In rabbits, nepafenac has been shown to inhibit blood-retinal-barrier breakdown, concomitant with suppression of PGE2 synthesis. Ex vivo, a single topical ocular dose of nepafenac was shown to inhibit prostaglandin synthesis in the iris/ciliary body (85%



Pharmacodynamic effects



The majority of hydrolytic conversion is in the retina/choroid followed by the iris/ciliary body and cornea, consistent with the degree of vascularised tissue.



Results from clinical studies indicate that NEVANAC eye drops have no significant effect on intraocular pressure.



Clinical Effects



Three pivotal studies were conducted to assess the efficacy and safety of NEVANAC dosed 3 times daily as compared to placebo and/or ketorolac trometamol in the prevention and treatment of postoperative pain and inflammation in patients undergoing cataract surgery. In these studies, study medication was initiated the day prior to surgery, continued on the day of surgery and for up to 2



In two double-masked, randomised placebo-controlled studies, patients treated with NEVANAC had significantly less inflammation (aqueous cells and flare) from the early postoperative period through the end of treatment than those treated with placebo.



In one double-masked, randomised, placebo-and active-controlled study, patients treated with NEVANAC had significantly less inflammation than those treated with placebo. Additionally, NEVANAC was non-inferior to ketorolac 5 mg/ml in reducing inflammation and ocular pain, and was slightly more comfortable upon instillation.



A significantly higher percentage of patients in the NEVANAC group reported no ocular pain following cataract surgery compared to those in the placebo group.



5.2 Pharmacokinetic Properties



Absorption



Following three-times-daily dosing of NEVANAC eye drops in both eyes, low but quantifiable plasma concentrations of nepafenac and amfenac were observed in the majority of subjects 2 and 3 hours post-dose, respectively. The mean steady-state plasma Cmax for nepafenac and for amfenac were 0.310 ± 0.104 ng/ml and 0.422 ± 0.121 ng/ml, respectively, following ocular administration.



Distribution



Amfenac has a high affinity toward serum albumin proteins. In vitro, the percent bound to rat albumin, human albumin and human serum was 98.4%, 95.4% and 99.1%, respectively.



Studies in rats have shown that radioactive labelled active substance-related materials distribute widely in the body following single and multiple oral doses of 14C



Metabolism



Nepafenac undergoes relatively rapid bioactivation to amfenac via intraocular hydrolases. Subsequently, amfenac undergoes extensive metabolism to more polar metabolites involving hydroxylation of the aromatic ring leading to glucuronide conjugate formation. Radiochromatographic analyses before and after βmax.



Interactions with other medicinal products: Neither nepafenac nor amfenac inhibit any of the major human cytochrome P450 (CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4) metabolic activities in vitro at concentrations up to 300 ng/ml. Therefore, interactions involving CYP-mediated metabolism of concomitantly administered medicinal products are unlikely. Interactions mediated by protein binding are also unlikely.



Excretion/Elimination



After oral administration of 14C-nepafenac to healthy volunteers, urinary excretion was found to be the major route of radioactive excretions, accounting for approximately 85% while faecal excretion represented approximately 6% of the dose. Nepafenac and amfenac were not quantifiable in the urine.



Following a single dose of NEVANAC in 25 cataract surgery patients, aqueous humour concentrations were measured at 15, 30, 45 and 60 minutes post-dose. The maximum mean aqueous humour concentrations were observed at the 1 hour time-point (nepafenac 177 ng/ml, amfenac 44.8 ng/ml). These findings indicate rapid corneal penetration.



5.3 Preclinical Safety Data



Non-clinical data reveal no special hazard for humans based upon conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.



Nepafenac has not been evaluated in long-term carcinogenicity studies.



In reproduction studies performed with nepafenac in rats, maternally toxic doses



6. Pharmaceutical Particulars



6.1 List Of Excipients



Mannitol (E421)



Carbomer



Sodium chloride



Tyloxapol



Disodium edetate



Benzalkonium chloride



Sodium hydroxide and/or hydrochloric acid (for pH adjustment)



Purified water



6.2 Incompatibilities



Not applicable.



6.3 Shelf Life



2 years.



Discard 4 weeks after first opening.



6.4 Special Precautions For Storage



Do not store above 30˚C.



6.5 Nature And Contents Of Container



5 ml round low density polyethylene bottle with a dispensing plug and white polypropylene screw cap containing 5 ml suspension.



Carton containing 1 bottle.



6.6 Special Precautions For Disposal And Other Handling



No special requirements.



7. Marketing Authorisation Holder



Alcon Laboratories (UK) Ltd.



Boundary Way



Hemel Hempstead



Herts HP2 7UD



United Kingdom



8. Marketing Authorisation Number(S)



EU/1/07/433/001



9. Date Of First Authorisation/Renewal Of The Authorisation



10. Date Of Revision Of The Text




Navelbine 10 mg / ml concentrate for solution for infusion






NAVELBINE 10 mg/ml



concentrate for solution for infusion


Vinorelbine (as tartrate)



Read all of this leaflet carefully before you start using this medicine.


  • Keep this leaflet. You may need to read it again.

  • If you have further questions, please ask your doctor or your pharmacist.

  • If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.



In this leaflet:


  • 1. What Navelbine is and what it is used for

  • 2. Before you use Navelbine

  • 3. How to use Navelbine

  • 4. Possible side effects

  • 5. How to store Navelbine

  • 6. Further information




What Navelbine is and what it is used for


Navelbine belongs to a family of medicines used to treat cancer called the vinca-alkaloid family.



Navelbine is used to treat:


  • Non-small cell lung cancer

  • Advanced breast cancer that has not responded to other medicines.

It is not recommended for use by children under 18 years old.





Before you use Navelbine



Do not use Navelbine


  • If you are allergic (hypersensitive) to the active substance (vinorelbine), or to any of the related family of cancer drugs called the vinca alkaloids

  • If you are pregnant or think that you might be pregnant

  • If you are breast feeding

  • If you have a low white blood cell (neutrophil) count or a severe infection

  • If you have a low platelet count (thrombocytopenia)

  • If you have a low blood platelet count (thrombocytopenia)

  • If you plan to receive a yellow fever vaccination or have just received one.



Take special care with Navelbine


Please inform your doctor if:


  • you have a history of heart attack or severe chest pain

  • you have problems with your liver or you have received radiotherapy where the treatment field included the liver

  • you have signs or symptoms of infection (such as fever, chills, joint pain)

  • you take or have recently taken any other medicines including medicines obtained without prescription.

  • you plan to have a vaccination or have just had one

Before and during your treatment with Navelbine, blood cell counts are performed to check that it is safe for you to receive treatment. If the results of this analysis are not satisfactory, your treatment may be delayed and further checks made until these values return to normal.




Using with other medicines


Please inform your doctor or pharmacist if you are taking, or have recently taken, any other medicines including medicines obtained without prescription.


Your doctor should take special attention if you are taking the following medicines:


  • medicines used to thin your blood (anticoagulants)

  • an anti-epileptic medicine called phenytoin

  • antifungal medicines such as itraconazole and ketaconazole,

  • an anti-cancer medicine called mitomycin C

  • medicines that impair your immune system such as ciclosporin and tacrolimus.

Live attenuated vaccines (e.g. Measles vaccine, Mumps vaccine, Rubella vaccine…) and yellow fever vaccines are not recommended with Navelbine as they may increase the risk of life-threatening vaccine disease.


If you are given Navelbine as well as medicines that affect your bone marrow it may make some of the side effects worse.




Using Navelbine with food and drink


There are no known interactions with food and drink when using Navelbine. However, you should check with your doctor if taking alcohol is advisable for you.




Male fertility


Men being treated with Navelbine are advised not to father a child during treatment and for up to 3 months after the end of the treatment.


The effects of anti-cancer drugs on the unborn child are not fully known. Navelbine is one of the anti-cancer drugs which are known to have adverse effects in pregnant animals.




Women of child-bearing potential


Women of child-bearing potential must use effective contraception (birth control) during treatment and for up to 3 months after the end of the treatment.




Pregnancy


  • Do not take Navelbine if you are pregnant or think that you might be pregnant.

  • If you have to start treatment with Navelbine and are pregnant or if pregnancy occurs during your treatment with Navelbine, you must immediately contact your doctor for advice.



Breast-feeding


  • Do not take Navelbine if you are breast feeding.

  • Breast-feeding must be discontinued if treatment with Navelbine is necessary.



Driving and using machines


No studies on the effects on the ability to drive and use machines have been performed. However, some of the possible side effects of Navelbine could affect your ability to drive or perform skilled tasks: see section 4; Possible side effects below for details. Therefore, it is recommended that you should not drive if you feel unwell or if your doctor has advised you not to drive.





How to use Navelbine


Navelbine should be prescribed by a qualified doctor who is experienced in the use of cancer treatments.


Navelbine is used in patients over 18 years old. It is not recommended for use by children under 18 years old.



Dosage


Before and during treatment with Navelbine your doctor will check your blood cell count. The results of your blood test will decide when you receive your treatment. The dose will depend on your height and weight and your general condition. Your doctor will calculate your body surface area and will determine the dose you should receive.




Frequency of administration.


Normally Navelbine is scheduled once a week. The frequency will be determined by your doctor who will take into account any other medicines you are being given.




Duration of treatment.


The duration of your treatment is decided by your doctor.




Method and route of administration


  • Navelbine must be diluted before administration

  • Navelbine must only be administered into a vein. It will be given by an infusion into one of your veins. It will take between 5 to 10 minutes.

  • After administration the vein will be rinsed thoroughly with a sterile solution.



If you use more Navelbine than you should


Your dose of Navelbine is carefully monitored and checked by your doctor and pharmacist. However, although you will have received the correct amount of chemotherapy your body may sometimes react giving severe symptoms. Some of these symptoms may develop as signs of an infection (such as fever, chills, joint pain). You may also become severely constipated. You must immediately contact your doctor if any of these severe symptoms occur.




If you stop using Navelbine


Your doctor will decide when you should stop your treatment. However, if you want to stop your treatment earlier, you should discuss other options with your doctor.



If you have any further questions on the use of this medicine, ask your doctor or pharmacist.




Possible side effects


Like all medicines, Navelbine can cause side effects, although not everybody gets them.


While taking Navelbine, if you develop any of the following symptoms you should contact your doctor immediately:


  • signs of a major infection such as cough, fever and chills,

  • severe constipation with abdominal pain when your bowels have not been open for several days,

  • severe dizziness, light-headedness when you stand up,

  • severe chest pain which is not normal for you,

  • signs of allergy such as itching, shortness of breath.

Below is a list of side effects that have occurred in some people following treatment with Navelbine. This list is classified according to the decreasing frequency of side effects occurrence.








Very common side effects


(can occur in more than 1 in 10 patients treated)



• Feeling sick (nausea), vomiting

If this becomes uncontrollable, immediately contact your doctor. These side effects may be controlled with standard anti-sickness therapy.



• A fall in white blood cells which makes you more vulnerable to infection. This can commonly cause bacterial, viral or fungal infections in your body (respiratory, urinary, gastro-intestinal systems and possibly others).

If your temperature reaches 38°C or higher, immediately contact your doctor.



• A fall in red blood cells (anaemia) which can make the skin pale and cause weakness or breathlessness

If this symptom becomes severe, immediately contact your doctor for treatment.



• Loss of some reflex reactions, occasionally difference in the perception of touch.

• Weakness of the lower extremities

If these symptoms become severe, immediately contact your doctor for treatment.



• Inflammation or sores in the mouth or throat (stomatitis)

• Constipation. If you have abdominal pain or if you do not have a bowel movement for several days
Immediately contact your doctor if you experience any of these side effects.



• Abnormal liver test

Your doctor should check your liver function when you are receiving chemotherapy.



• Hair loss (alopecia)

• Reactions at the site where Navelbine was administered such as redness (erythema), burning pain, vein discolouration, inflammation of the veins (local phlebitis)

Ask your doctor for advice if these symptoms persist. These are possible symptoms when receiving chemotherapy.

Common side effects

(can occur in less than 1 in 10 patients treated)



• Tiredness, fever, pain at different sites in your body such as chest pain and pain where the tumour is

If the symptoms persist or if your temperature reaches 38°C or higher, ask your doctor for advice. These symptoms are expected when receiving chemotherapy.



• A fall in platelets which increases the risk of bleeding or bruising (thrombocytopenia).

• Diarrhoea, joint pain (arthralgia), jaw pain, muscle pain (myalgia)

If these symptoms become severe, immediately contact your doctor.

Uncommon side effects

(can occur in less than 1 in 100 patients treated)

Effects on your blood:

• Severe signs of a major infection such as cough, fever, chills and blood infection.
Immediately contact your doctor if you experience any of these side effects.

Effects on your heart and blood vessels:

• Reduced blood pressure (hypotension with symptoms such as dizziness or feeling faint)

• Raised blood pressure (hypertension) with symptom such as a headache.

• A sudden feeling of heat and skin redness of the face and neck (flushing)

• Feeling cold in the hands and feet (peripheral coldness)
Immediately contact your doctor if you experience any of these side effects.

Effects on your respiratory system:

• Difficulty in breathing or wheezing (dyspnoea and bronchospasm)
Immediately contact your doctor if you experience any of these side effects.

Effects on your nervous system:

• Severe difficulties with your body movements and sense of touch (severe paresthesias)
Immediately contact your doctor if you experience any of these side effects.

Rare side effects

(can occur in less than 1 in 1,000 patients treated)

Effects on your blood:

• Severe hyponatremia which is when there are low blood levels of sodium in your blood (which can cause symptoms of tiredness, confusion, muscle twitching and coma)
Immediately contact your doctor if you experience any of these side effects.

Effects on your heart and blood vessels

• Severe chest pain, heart attack (ischaemic heart disease, angina pectoris, myocardial infarction)

• Severe drop in blood pressure causing dizziness, fainting (severe hypotension, collapse).
Immediately contact your doctor if you experience any of these side effects.

Effects on your respiratory system:

• If you are receiving another cancer drug called mitomycin C, you may experience breathing difficulties (interstitial pneumopathies).
Immediately contact your doctor if you experience any of these side effects.

Effects on your gastrointestinal system:

• Severe constipation with abdominal pain when your bowels have not been open for several days (paralytic ileus)

• Severe abdominal and back pain (pancreatitis)
Immediately contact your doctor if you experience any of these side effects.

Allergic reaction effects

• Skin rashes on your body such as rashes and eruptions (generalised cutaneous reactions)

• Ulcer at the injection site where the Navelbine was given (local necrosis).
Immediately contact your doctor if you experience any of these side effects.

Very rare side effects

(can occur in less than 1 in 10,000 patients treated)



• Irregular heartbeats (tachycardia, palpitation, and heart rhythm disorders)

• Life threatening infections in your body such as severe fever, chest infections and infections at other sites in your body (septicaemia)
Immediately contact your doctor if you experience any of these side effects.



Other side effects have been reported:


  • Generalised allergic reactions. These are serious reactions which can cause severe difficulty in breathing, dizziness, rash affecting your whole body, swelling of the eyelids, face lips, throat (anaphylactic shock, anaphylaxis, anaphylactoid type reactions).

  • Low sodium level due to an overproduction of a hormone causing fluide retention and resulting in weakness, tiredness or confusion (Syndrome of Inappropriate Antidiuretic Hormone secretion SIADH)

  • Loss of appetite (anorexia).


Do not be alarmed by this list. If you suffer from any of these side effects or if you have any other unusual symptom or feelings, you should contact your doctor as soon as possible.



If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.




How to store Navelbine


Keep out of the reach and sight of children.


Do not use Navelbine after the expiry date which is stated on the vial and box (after Exp). The expiry date refers to the last day of that month.


Navelbine will be diluted and stored by hospital staff.




Further Information



What Navelbine contains


  • The active substance is Vinorelbine (as tartrate). Each 1 ml of solution contains 10 mg of vinorelbine as vinorelbine tartrate.

  • The other ingredient is water for injection.



What Navelbine looks like and contents of the pack


Navelbine is a clear colourless to pale yellow solution


This medicinal product is a concentrate for solution for infusion, in glass vials of 1, 4 or 5 ml.


Navelbine is available as:


Box of 10 vials of 1ml,


Box of 10 vials of 4 ml,


Box of 10 vials of 5 ml.


Not all pack sizes may be marketed.




Marketing Authorisation Holder



PIERRE FABRE Ltd

Hyde Abbey House

23 Hyde Street

Winchester

Hampshire

SO23 7DR

UNITED KINGDOM




Manufacturer



Pierre Fabre Médicament Production

Avenue du Bearn - BP 9097

F-64320 - Pau Idron - Bizanos

FRANCE




Other formats:


To listen to or request a copy of this leaflet in Braille, large print or audio please call, free of charge:


0800 198 5000 (UK Only): Please be ready to give the following information:




Product Name : Reference Number



NAVELBINE 10mg/ml concentrate for solution for infusion : 00603/0028



This is a service provided by the Royal National Institute of the Blind.




This leaflet was last approved in July 2009







Neo-Naclex K tablets





1. Name Of The Medicinal Product



Neo-Naclex-K 2.5mg/630mg Tablets


2. Qualitative And Quantitative Composition



Each tablet contains 2.5mg Bendroflumethiazide in the white layer and 630mg Potassium chloride in the pink layer, providing 330mg elemental potassium (8.4 mEq).



3. Pharmaceutical Form



Film coated, two-layered white and pink tablet.



4. Clinical Particulars



4.1 Therapeutic Indications



Essential hypertension



The mechanism whereby the thiazides exert their antihypertensive effect has not been clearly established. In non-oedematous patients there may be little noticeable diuretic effect. Neo-Naclex-K may be used as the sole anti-hypertensive agent, or as an adjunct to other anti-hypertensive drugs whose action may be enhanced.



Oedema.



Neo-Naclex-K inhibits the renal tubular absorption of salt and water by its action at the beginning of the distal convoluted tubule. Sodium and chloride ions are excreted in equivalent proportions. Because potassium excretion is promoted, metabolic alkalosis may occur secondary to hypokalaemia. There is no important effect upon carbonic anhydrase. Neo-Naclex-K causes a steady diuresis lasting about 12 hours. It is indicated in the treatment of oedema associated with conditions such as congestive heart failure, nephritic syndrome and cirrhosis of the liver.



4.2 Posology And Method Of Administration



Neo-Naclex-K tablets should be swallowed whole with water.



Adults:-



When Neo-Naclex-K is added to other antihypertensive drugs, the dosage of the latter can usually be reduced as the Neo-Naclex-K takes effect.



Essential hypertension-



1 tablet once daily, alone or in conjunction with other anti-hypertensive agents.



Oedema-



2 tablets once daily in the morning usually produce the desired effect without diuresis interfering with sleep. The dose can be increased to 4 tablets, if required. During the first few days of treatment, there is usually a large increase in urinary volume, which diminishes as treatment continues.



Maintenance-



Many patients will respond adequately to a daily dose of 1 to 2 tablets on only two or three days in a week.



Elderly:



See precautions.



Children:



Neo-Naclex-K is not recommended for children.



Route of administration:



Oral.



Neo-Naclex-K tablets should be swallowed whole with water



4.3 Contraindications



Severe renal or hepatic failure. Hypersensitivity to the product or other sulphonamide-like drugs. Addisons's disease, diabetic keto-acidosis, hyperkalaemia and hypercalaemia. Neo-Naclex-K is a solid potassium- containing preparation and is therefore contraindicated in conditions of the gastrointestinal tract where strictures may form. Neo-Naclex-K should not be administered concurrently with lithium carbonate.



4.4 Special Warnings And Precautions For Use



When treatment is prolonged and intensive, potassium depletion can develop insidiously. Periodic serum electrolyte determinations should be done. Neo-Naclex-K tablets usually provide sufficient potassium to maintain the serum concentration in hypertension, but it is sometimes advisable to give potassium chloride in addition to that contained in Neo-Naclex- K. If the patient is vomiting, has diarrhoea, or is suffering from an acute febrile or chronic illness (especially cirrhosis of the liver or heart failure), supplementary potassium may be particularly important. Additional potassium chloride to prevent hypokalaemia and the danger of arrhythmias, and other ECG changes is strongly recommended if patients receiving digitalis require prolonged treatment. Hypocalaemia may increase toxicity of glycosides and antagonise the effects of anti-arrhythmic drugs. In concurrent therapy with carbenoxolone or corticosteroids, additional potassium supplements are recommended. Patients at risk of myocardial infarction, and patients admitted for cardiac surgery also needpotassium supplements.



Potassium depletion may cause polyuria, malaise, muscle weakness or cramp, decreased tendon reflexes, anorexia, dizziness, nausea or vomiting, also increased sensitivity to digitalis may increase and signs of overdosage appear.



Prolonged potassium depletion may induce chronic pyelonephritis. Renal function should be monitored. Neo-Naclex-K and additional potassium supplements must not be given in renal insufficiency complicated by hyperkalaemia.



In addition, in prolonged therapy it is necessary to test for glycosuria and investigate polyuria. In renal insufficiency, renal function should be monitored. The possibility of magnesium depletion should also be considered.



In cirrhosis of the liver, thiazides may participate hepatic encephalopathy



Thiazides may aggravate existing diabetes mellitus and causes symptoms in patients with latent disease. Neo-Naclex-K may impair control of diabetes in patients receiving sulphonylureas. Thiazides should be used with caution in systemic lupus erythematosus. Serum uric acid levels may be raised, with or without gout, in some patients. Thiazides may cause or aggravate hyperlipidaemia; pancreatitis may occur. The elderly are sensitive to the effects of thiazides on blood pressure and electrolyte. Administration of supplementary potassium is particularly important in the elderly. Patients with prostatic hypertrophy may develop acute urinary retention.



4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction



Diabetes mellitus: Thiazides may impair control in diabetics receiving sulphonylureas.



Lithium toxicity:-the renal clearance of lithium carbonate is reduced: concomitant use is contraindicated.



Anaesthesia: - The hypotensive effect of Halothane is increased by thiazides.



Sensitivity to Tubocurarine is increased in hypokalaemia. Plasma potassium should be monitored prior to its use in patients treated with thiazides. The action of lidocaine is antagonised by hypokalaemia.



Antagonism and hypokalaemia: Carbenoxolone, indomethacin, phenylbutazone and corticosteroids may both antagonise the hypotensive effect of thiazides and increase potassium loss. Monitoring and potassium supplements are recommended.



Hypotension: Enhanced hypotensive effects may follow the concomitant use of thiazides and barbiturates, alcohol, other antihypertensives, (e.g. beta blocking agents, ACE inhibitors, calcium antagonists), MAOI's or narcotics.



Cardiac Toxicity(increased QT Interval): Due to disopyramide, flecainide, sotalol, atomoxetine, pimozide and sertindole is increased if hypokalemia occurs.



Hypersensitivity: Use of Allopurinal and a thiazide in patients with renal dysfunction should be avoided; severe hypersensitivity vasculitis has been reported.



Cardiac glycosides: Hypokalaemia may increase the toxicity of glycosides and antagonize the effects of anti-arrhythmic drugs.



Potassium imbalance: - Caution is required in the use of Neo-Naclex-K with any drug or disease state which has a potential for producing potassium imbalance.



Vitamin B12: Potassium chloride, as in Neo-Naclex-K, may reduce absorption of oral Vitamin B12.



4.6 Pregnancy And Lactation



Pregnancy:



Diuretics are best avoided in the management of oedema of pregnancy or hypertension of pregnancy, as their use may be associated with hypovolaemia, increased blood viscosity and reduced placental perfusion. There is inadequate evidence of safety in human pregnancy, there are reports of foetal and neonatal bone depression, thrombocytopoenia, electrolyte imbalance, hypoglycaemia and jaundice.



Expectant mothers who receive thiazide diuretics may be at increased risk from acute haemorrhagic pancreatitis. In parturition, thiazides may cause uterine inertia and delay the onset of labour.



Thiazides are only indicated in pregnancy if oedema complicates a pathological lesion and, even then, after assessing risk versus benefit including the undesirability of administering drugs in the first trimester.



Lactation:



As thiazides diuretics are secreted in mother's milk, breast feeding should be avoided.



4.7 Effects On Ability To Drive And Use Machines



When driving vehicles or operating machines it should be taken into account that dizziness may occur.



4.8 Undesirable Effects



If abdominal pain, distension, nausea, vomiting or gastro-intestinal bleeding occur during the administration of tablets containing potassium salts, they should be discontinued immediately. Small bowel lesions are usually associated with enteric coated tablets and are less likely to occur with Neo- Naclex-K. The following have been reported: Disturbance of electrolyte, acid-base balance, lipids, glucose and uric acid levels; thirst, polyuria, weakness, dizziness, muscle cramps and reversible impotence: nausea, vomiting, mild anorexia, gastric irritation, diarrhoea or constipation; rashes, skin reactions, purpura and blood dyscrasias including thrombocytopoenia, hypocalciuria, precipitation of gout, pancreatitis, hepatic encephalopathy and postural hypotension.



4.9 Overdose



CNS depression (e.g. drowsiness, lethargy and coma) may occur without cardiovascular or respiratory depression. Hypovolaemia, hyperkalaemia, and mild hypoglycaemia are likely to be present.



In the case of recent ingestion, gastric lavage should be carried out; activated charcoal may help reduce absorption.



Treatment should be symptomatic, directed at fluid and electrolyte replacement. Severe hyperkalaemia following overdose with potassium-containing thiazide combinations is rare. Lethargy, confusion, muscle weakness, paralysis, arrhythmia or cardiac arrest may occur. Measurement of plasma potassium, ECG monitoring and correction of any abnormalities are required. Other treatment depends on plasma potassium concentration. When this is less than 6.5mEq/l, fluid replacement with oral calcium polystyrene sulphonate is recommended. For levels of 6.5mEq/l, or greater, urgent treatment is required with intravenous insulin, glucose, sodium bicarbonate and/or calcium gluconate, oral calcium polystyrene sulphonate and possibility haemodialysis.



5. Pharmacological Properties



5.1 Pharmacodynamic Properties



Neo-Naclex-K contains Bendroflumethiazide, a thiazide diuretic. Thiazide diuretics inhibit sodium and chloride reabsorption in the renal tubules and produce a corresponding increase in potassium excretion.. The mechanism whereby the thiazides exert their antihypertensive effect has not been clearly established.



Neo-Naclex-K also contains potassium chloride as a potassium supplement to offset the potassium-losing effect of Bendroflumethiazide.



5.2 Pharmacokinetic Properties



Not supplied.



5.3 Preclinical Safety Data



No further data of relevance.



6. Pharmaceutical Particulars



6.1 List Of Excipients


















White layer




Pink layer




Lactose




Cellulose acetate phthalate




Maize starch




Ethylcellulose 100




Silicon dioxide




Indigo Carmine E132




Magnesium stearate




Carmoisine E122




Methanol




Polyethylene glycol 6000




Methylene Chloride




Purified water



Film coat



Hydroxypropylmethylcellulose



Ethylcellulose 50



Acetylated monoglyceride



Propylene glycol



Polysorbate 80



Methylene Chloride



Isopropyl alcohol



6.2 Incompatibilities



None



6.3 Shelf Life



24 months



6.4 Special Precautions For Storage



Securitainer:



Store below 30C and protect from light and moisture.



Blister:



Store below 25C and protect from light and moisture.



6.5 Nature And Contents Of Container



Tamper-evident, polypropylene container with low-density polyethylene lid, containing 30,100, 250 and 500 Neo-Naclex-K tablets.



PVC/PVdC blisters with aluminium foil backing containing 28, 56,112 tablets.



6.6 Special Precautions For Disposal And Other Handling



None



7. Marketing Authorisation Holder



Goldshield Group Limited



NLA Tower



Croydon



Surrey CR0 OXT



8. Marketing Authorisation Number(S)



10972/0001



9. Date Of First Authorisation/Renewal Of The Authorisation



12 January 1993



10. Date Of Revision Of The Text



11 May 2010