Neoral (ciclosporin) Capsules/Liquid

What is it used for?

• Preventing organ or tissue rejection following kidney, liver, heart, lung, combined heart-lung, pancreas, bone marrow or stem cell transplants.
• Treating transplant rejection in people previously receiving other immunosuppressants.
• Prevention and treatment of graft-versus-host disease (GVHD), where the cells from transplanted bone marrow tissue attack the cells of the transplant recipient.
• A syndrome caused by kidney inflammation, characterised by a large amount of protein in the urine, swelling, weight gain and high blood pressure (nephrotic syndrome).
• Severe atopic dermatitis (eczema) for which conventional treatments are ineffective or inappropriate.
• Severe psoriasis for which conventional treatment is ineffective or inappropriate.
• Severe rheumatoid arthritis for which conventional disease-modifying antirheumatic drugs (DMARDs) are ineffective or inappropriate.
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• Sight-threatening inflammation of the middle part of the eye called the uvea (intermediary or posterior uveitis), including Behçet's uveitis.

How does it work?

• Neoral capsules and oral solution contain the active ingredient ciclosporin, which is a type of medicine called an immunosuppressant. It works by reducing the activity of the body's immune system.
• Ciclosporin reduces the activity of T and B-lymphocytes, which are white blood cells responsible for regulating and triggering immune responses. Their usual role is to provide defence against infection and foreign cells.
• Ciclosporin prevents the T-lymphocytes from producing substances called lymphokines. Lymphokines have many roles, including attracting and activating other immune cells and stimulating the production of antibodies by B-lymphocytes. By stopping the T-cells from producing lymphokines, ciclosporin prevents certain immune responses from occurring.
• If you have had an organ or bone marrow transplant, the donor cells, although matched as close as possible to yours, will not be identical to the cells in your body. As a result, your immune system will recognise that the new cells are different and try to attack and reject the transplanted tissue. Ciclosporin prevents this by suppressing the activity of the cells in your immune system that would normally attack the transplanted tissue.
• If you have had a bone marrow transplant, the new blood cells produced by the new bone marrow can attack the cells of your body in a similar way - because they recognise that your body cells are different. This is known as graft versus host disease or GVHD. Ciclosporin controls this condition by suppressing the activity of the new blood cells.
• The skin conditions psoriasis and dermatitis are also affected by the immune system. It is thought that T-cells over-react to a stimulus in these conditions, causing the scaling and inflammation of the skin. Ciclosporin can be used in severely disabling and resistant forms of these conditions to suppress the action of the T-cells and therefore improve the scaling of the skin.
• Rheumatoid arthritis, a syndrome involving the kidneys called nephrotic syndrome and a type of eye inflammation called uveitis are also treated with ciclosporin in certain cases. These conditions are thought to be caused by inappropriate activity of the immune system towards the body'’s own cells (autoimmune conditions). T-cells are involved in producing inflammation as part of their immune function. Suppressing their action can help to reduce the inflammation in the joints seen in arthritis, the inflammation in the kidneys seen in the nephrotic syndrome and the inflammation in the eyes in uveitis.

How do I take it?

• The dose of Neoral that is needed will vary from person to person depending on the condition being treated. It is important to follow the instructions given by your doctor regarding how much medicine to take and how often.
• The daily dose of Neoral is usually divided into two. These should always be taken at the same times, split evenly over the day, ideally at 12 hour intervals, eg 8am and 8pm.
• Neoral can be taken either with or without food, but you should always take it in the same way in relation to your meals.
• Neoral capsules should be swallowed whole with a drink of water.
• Neoral oral solution doses should be measured using the syringe provided with the medicine. The measured dose should be pushed out of the syringe into a glass of liquid (water or alternatively orange juice/squash or apple juice to improve the taste). Stir the mixture well with a spoon and drink at once. Neoral oral solution should never be diluted with grapefruit juice.
• The measuring syringe for Neoral oral solution must not be allowed to come into contact with the liquid in the glass that you use to dilute your dose. The measuring syringe must not be rinsed with water, alcohol or any other liquid. If it is necessary to clean it, the outside only should be wiped with a dry tissue.
• You should not eat grapefruit or drink grapefruit juice in the hour before taking your dose of Neoral capsules or Neoral oral solution, as this can increase the amount of medicine that is absorbed into the bloodstream from your gut
• If you forget to take a dose take it as soon as you remember, unless it is nearly time for your next dose. In this case leave out the missed dose and take your next dose as usual when it is due. Do not take a double dose to make up for a missed dose.
• Keep taking this medicine regularly as prescribed, until your doctor tells you stop.

Use with caution in

• Children.
• Elderly people.
• People with decreased kidney function.
• People with decreased liver function.
• People with a high level of uric acid in their blood (hyperuricaemia).
• Dermatitis patients with skin infections.
• Dermatitis and psoriasis patients with malignant (cancerous) or pre-malignant skin conditions.
• Neoral capsules and oral solution contain a small amount of alcohol, which should be taken into consideration in children, pregnant and breastfeeding women and people with liver problems, epilepsy or alcoholism.

Pregnancy and breastfeeding

• The safety of this medicine for use during pregnancy has not been established. It is not recommended for use in pregnancy unless considered essential by your doctor. Seek further medical advice from your doctor.
• This medicine passes into breast milk. As it could be harmful to a nursing infant, women who need to take this medicine should not breastfeed. Seek further medical advice from your doctor.

Side effects

Very common 

• Decreased kidney function.
• Shaking, usually of the hands (tremor).
• Headache.
• Increase in the level of fats such as cholesterol in the blood (hyperlipidaemia).
• High blood pressure (hypertension).
• Increased growth of facial and body hair (hirsutism).

Common

• Loss of appetite.
• Fever.
• Fatigue.
• Disturbances of the gut such as nausea, vomiting, diarrhoea or abdominal pain.
• Peptic ulcer.
• Swollen gums.
• Flushing.
• Acne.
• Decreased numbers of white blood cells in the blood (leucopenia). This will increase your susceptibility to infections.
• Increased blood sugar level (hyperglycaemia).
• Increased level of potassium in the blood (hyperkalaemia).
• Increased level of uric acid in the blood (hyperuricaemia), which can cause kidney problems and gout.
• Decreased level of magnesium in the blood.
• Abnormal liver function.
• Muscle cramps or aches.
• Pins and needles sensations (paraesthesia).
• Convulsions.

Uncommon

• Fluid retention (oedema).
• Weight gain.
• Allergic rashes.
• Decreased numbers of red blood cells (anaemia) or platelets (thrombocytopenia) in the blood.

Rare

• A condition involving anaemia caused by destruction of red blood cells and acute kidney failure (haemolytic uraemic syndrome).
• Problems with the nerves that control the muscles (motor polyneuropathy).
• Muscle weakness.
• Inflammation of the pancreas (pancreatitis).
• Disturbance of menstrual periods.
• Enlargement of the breasts in men.

The side effects listed above may not include all of the side effects reported by the medicine's manufacturer.

For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

The immunosuppressant tacrolimus must not be taken in combination with this medicine.

The following medicines may decrease the level of ciclosporin in the blood and could make it less effective, so if you are prescribed any of these medicines your doctor may need to increase your ciclosporin dose:

• barbiturates, eg phenobarbital, amobarbital
• bosentan
• carbamazepine
• efavirenz
• griseofulvin
• lanreotide
• modafinil
• octreotide
• oxcarbazepine
• pasireotide
• phenytoin
• primidone
• rifampicin
• sevelamer
• sulfadiazine
• sulfinpyrazone
• terbinafine
• the herbal remedy St John's wort (Hypericum perforatum).

The following medicines may reduce the absorption of ciclosporin from the gut. Ask your pharmacist for advice if you need to take any of these with ciclosporin:

• colesevelam
• colestilan
• orlistat.

The following medicines may increase the level of ciclosporin in the blood and so could increase the risk of its side effects. Your doctor may need to perform extra monitoring or lower your ciclosporin dose if you are prescribed any of these:

• acetazolamide
• allopurinol
• amiodarone
• azole antifungals such as ketoconazole, fluconazole, itraconazole, miconazole, posaconazole, voriconazole
• boceprevir
• calcium-channel blockers such as diltiazem, nicardipine, verapamil or lercanidipine 
• carvedilol
• chloramphenicol
• chloroquine
• cimetidine
• colchicine
• crizotinib
• danazol
• hydroxychloroquine
• imatinib
• macrolide-type antibiotics, eg erythromycin, clarithromycin, azithromycin
• methylprednisolone (high-dose)
• metoclopramide
• micafungin
• oral contraceptives
• propafenone
• protease inhibitors for HIV infection, eg ritonavir, amprenavir, saquinavir, indinavir
• telaprevir (ciclosporin may also increase the blood level of telaprevir)
• ursodeoxycholic acid.

Ciclosporin may increase the blood level of the following medicines. As this could increase the risk of their side effects, your doctor may need to perform extra monitoring or reduce the dose of these medicines if they are used in combination with ciclosporin:

• afatinib
• aliskiren
• ambrisentan
• caspofungin
• colchicine
• dabigatran
• darifenacin
• diclofenac
• digoxin
• doxorubicin
• epirubicin
• etoposide
• everolimus
• ezetimibe (ezetimibe may also increase the blood level of ciclosporin)
• fidaxomicin
• idarubicin
• lenalidomide
• methotrexate
• mitoxantrone
• prednisolone
• ranolazine (ranolazine may also increase the blood level of ciclosporin)
• repaglinide
• sirolimus
• ticagrelor.

If any of the following medicines are taken in combination with ciclosporin there may be an increased risk of side effects on the kidneys. If you are prescribed any of these while taking ciclosporin your doctor may want to monitor your kidney function more frequently:

• aciclovir
• aminoglycoside-type antibiotics, eg gentamicin, tobramycin
• amphotericin B
• colchicine
• co-trimoxazole
• fibrates such as fenofibrate, bezafibrate
• mannitol
• melphalan
• non-steroidal anti-inflammatory drugs (NSAIDs), eg ibuprofen, diclofenac, naproxen, sulindac
• polymixin
• quinolone-type antibiotics, eg ciprofloxacin
• sulphonamides, eg sulfamethoxazole
• trimethoprim
• vancomycin.

There is a greater risk of the level of potassium in your blood rising too high if any of the following are taken in combination with ciclosporin:

• ACE inhibitors, eg enalapril, captopril
• angiotensin II receptor antagonists, eg losartan, valsartan
• potassium-containing salt substitutes, eg Lo-Salt
• potassium salts, eg potassium citrate for treating cystitis
• potassium-sparing diuretics, eg spironolactone, amiloride, triamterene
• potassium supplements.

There may be an increased risk of side effects on the muscles, eg muscle pain, weakness or inflammation, if ciclosporin is taken in combination with statins used to lower cholesterol levels, eg atorvastatin, simvastatin, pravastatin. Ciclosporin should not be used in combination with rosuvastatin or simvastatin.

There may be an increased risk of swollen gums (a side effect called gingival hyperplasia), if this medicine is taken in combination with nifedipine.

Ciclosporin may enhance the blood sugar lowering effect of repaglinide.

Vaccines may be less effective in people taking ciclosporin. This is because ciclosporin suppresses the immune system and prevents the body forming adequate antibodies. Live vaccines should be avoided because they may cause infection. Live vaccines include the following: oral polio; rubella; measles, mumps and rubella (MMR); BCG; yellow fever and oral typhoid vaccines.

If you are taking this medicine for psoriasis or dermatitis you should not receive light treatment such as PUVA or other UV light treatment at the same time.

References:

https://echa.europa.eu/substance-information/-/substanceinfo/100.003.072

https://en.wikipedia.org/wiki/Nerol

https://pubchem.ncbi.nlm.nih.gov/compound/nerol

https://www.netdoctor.co.uk/medicines/skin-hair/a7201/neoral-ciclosporin/

https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+8262

https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/nerol