Generality
Ciclosporin is an active ingredient with an immunosuppressive and anti-inflammatory action.
For this reason, its use is indicated in all those situations where it is necessary to reduce the patient's immune response and the inflammation generated by it.
Also known as cyclosporin A, this active ingredient is a cyclic polypeptide composed of 11 amino acids. Currently available ciclosporin-based medicines come in soft capsule form for oral use, concentrate for solution for infusion and eye drops . Depending on the medicinal product to be used, dispensing can take place upon presentation of a non-repeatable medical prescription or a limited prescription (medicines that can be sold to the public only on prescription from hospitals or specialists).
Examples of Specialties Medicines containing Cyclosporine
- Ciqorin®
- Ikervis®
- Sandimmun®
- Sandimmun Neoral®
Therapeutic indications
When is Cyclosporine Use Indicated?
Cyclosporine administered orally is indicated in the following cases:
- After an organ transplant, bone marrow or after a stem cell transplant to prevent rejection (in adults and children);
- Treatment of autoimmune diseases, such as:
- Atopic dermatitis, eczema or psoriasis (adults only);
- Endogenous uveitis (adults only);
- Nephrotic syndrome (adults and children);
- Severe rheumatoid arthritis (adults only).
Cyclosporine administered by intravenous infusion is also indicated in the prevention of rejection phenomena after different types of transplants.
Cyclosporine in the form of eye drops, on the other hand, is indicated in the treatment of severe keratitis and in the treatment of dry eye syndrome that does not improve with conventional therapies.
Did you know that ...
Ciclosporin is also included in the composition of various veterinary medicines used for:
- Treatment of chronic manifestations of atopic dermatitis in dogs;
- Symptomatic treatment of chronic allergic dermatitis in cats;
- Treatment of idiopathic dry keratoconjunctivitis and chronic superficial keratitis.
Warnings
Warnings and Precautions for the use of Cyclosporine
Before starting and during treatment with cyclosporine orally or parenterally, you must inform your doctor if you are in one or more of the following conditions:
- You are suffering from infections of any kind, or you have symptoms that could indicate an infection not yet diagnosed (for example, fever, sore throat, cough, etc.);
- You suffer from kidney and / or liver disorders and disorders;
- It manifests or suffers from hypertension;
- You suffer from hypomagnesemia or hyperkalemia;
- One is suffering from gout;
- You are suffering from some form of cancer;
- You suffer from epilepsy;
- Vaccinations must be carried out;
- You are pregnant or breast-feeding.
Before starting therapy with cyclosporine eye drops, however, it is necessary to inform the doctor if:
- He suffered from eye infections sustained by Herpes virus;
- You are being treated with drugs to treat glaucoma;
- You are taking corticosteroid drugs.
However, as a precautionary measure, before taking cyclosporine-based medicines, it is always advisable to inform the doctor of your health conditions, informing them of the possible presence of any type of disorder or illness, even if not present in the above reported bulleted lists.
Please note
Due to the suppressive action on the immune system, the intake of ciclosporin increases the risk of developing cancer, particularly of the skin and the lymphoid system. For this reason, it is advisable to limit exposure to UV rays as much as possible, taking care to use adequate protective filters (high protection sunscreens) and wearing appropriate protective clothing .
Finally, it is recalled that the use of cyclosporine both orally and parenterally as well as through the eye can lead to the appearance of side effects that can alter the ability to drive vehicles and / or use machinery ; therefore, these activities should be avoided during treatment with the active ingredient in question.
Pharmacological Interactions
Interactions between Cyclosporine and Other Drugs
Because of the pharmacological interactions that can occur, before starting treatment with cyclosporine orally or parenterally, you must inform your doctor if you are taking, or have recently taken, drugs such as:
- Drugs capable of increasing the levels of potassium in the blood (for example, potassium-sparing diuretics, drugs containing potassium, etc.);
- Methotrexate;
- Digoxin;
- Nifedipine;
- Drugs that can cause nephrotoxicity;
- Drugs that can increase cyclosporine blood levels, such as:
- Antibiotics and antifungals;
- antihypertensive;
- Oral contraceptives;
- Metoclopramide;
- Medicines for the treatment of gout;
- HIV treatment drugs;
- Anti-cancer drugs;
- Etc.
- Drugs that can reduce cyclosporin blood levels, such as:
- Anticonvulsants and barbiturates;
- Drugs for the treatment of tuberculosis;
- Bosentan (active ingredient used in the treatment of pulmonary hypertension);
- Products based on St. John's wort (or St. John's wort, a plant with known antidepressant properties);
- Etc.
Please note
During oral and parenteral therapy with ciclosporin it is necessary to avoid the intake of grapefruit, its derivatives or products containing it, as they could interfere with the therapeutic activity of the active ingredient.
Instead, before taking cyclosporine in the form of eye drops, you need to tell your doctor if you are taking other corticosteroid based eye drops .
In any case, before starting cyclosporine therapy - either by mouth or topically - it is necessary to tell the doctor if you are taking, or if you have recently been, drugs or products of any kind, including medicines without a medical prescription (SOP), over-the-counter drugs (OTC), herbal and phytotherapeutic products and homeopathic products.
Side effects
Side effects caused by the intake of cyclosporine
Ciclosporin can cause several side effects although not all patients manifest them or manifest them in the same way. In fact, each person reacts subjectively to the administration - oral, parenteral or ocular - of ciclosporin, showing side effects that are different in type and / or intensity, or not at all.
Cyclosporine by oral and parenteral route
The following are some of the major side effects induced by the administration of oral and parenteral ciclosporin.
Blood disorders
Treatment with ciclosporin may cause:
- Leukopenia;
- Thrombocytopenia;
- Anemia;
- Microangiopathic hemolytic anemia;
- Thrombocytopenic thrombotic purpura.
Nervous system disorders
Cyclosporine therapy can give rise to:
- Headache;
- Tremors;
- paresthesia;
- Convulsions;
- encephalopathies;
- Insomnia;
- Confusion;
- Ataxia;
- Paresis;
- Vision disorders;
- Coma;
- Motor polyneuropathy.
Skin and subcutaneous tissue disorders
Cyclosporine intake can cause:
- Acne;
- Hypertrichosis and hirsutism;
- Skin eruptions.
Gastrointestinal disorders
Treatment with ciclosporin may promote the appearance of:
- Nausea and vomit;
- Abdominal pain;
- Diarrhea;
- Peptic ulcer;
- Pancreatitis.
Other side effects
Other side effects that could occur during ciclosporin therapy consist of:
- Allergic reactions, even serious, in sensitive individuals;
- Reactions at the site of administration in case of intravenous infusion;
- Fever and fatigue;
- Hot flashes;
- Hypertension;
- Liver and / or renal dysfunction;
- Hepatotoxicity and / or nephrotoxicity;
- Hyperlipidemia;
- Hyperglycemia;
- hyperkalemia;
- hypomagnesemia;
- Anorexia;
- Menstrual disorders;
- Gynecomastia;
- Muscle aches and / or cramps;
- Muscle weakness;
- Body weight gain.
Cyclosporine for Via Oculare
Among the most common side effects that can occur during the administration of cyclosporine based eye drops, we recall:
- Allergic reactions, even serious, in sensitive individuals;
- Pain at the administration site;
- Irritation;
- Increased lacrimation;
- Blurred vision;
- Ocular hyperemia;
- Erythema and edema of the eyelid;
- Bacterial keratitis;
- Herpes zoster ophthalmic.
Overdose
If you are taking excessive doses of cyclosporine, you must immediately inform the doctor or go to the nearest emergency room, taking care to bring the packaging of the medicine taken with you. Antidotes are not known and the treatment is symptomatic and supportive . However, prompt induction of vomiting and gastric lavage may prove useful.
Action mechanism
How does Cyclosporine work?
Ciclosporin is a cyclic polypeptide with immunomodulatory, immunosuppressive and even anti-inflammatory properties .
The mechanisms of action by which cyclosporine is able to carry out the aforementioned activities are the following:
- Inhibition of cell-mediated immune responses that include:
- The production of antibodies dependent on T lymphocytes;
- Transplantation reaction to host (GVHD);
- Allogeneic transplant immunity.
- Blockade of quiescent lymphocytes in the G0 or G1 phase of the cell cycle.
- Inhibition of interleukin 2 release and release of lymphokines by activated T cells.
Use and Posology
How to take Cyclosporine
Ciclosporin is available in different pharmaceutical formulations suitable for oral administration (soft capsules), parenteral administration (concentrate for solution for intravenous infusion) and ocular administration (eye drops).
The soft capsules must be swallowed whole with the help of a little water; the concentrate for solution for infusion must be previously diluted and then administered by slow intravenous infusion by specialized personnel ; the eye drops, of course, must be instilled directly into the affected eye .
The ciclosporin dosage (dose and duration of treatment) must be established by the doctor on an individual basis for each patient. However, below are some of the dosages usually used in therapy.
Oral cyclosporine
When ciclosporin is administered orally, the dose to be taken varies depending on why it is necessary to use the active ingredient:
- Prevention of rejection in case of organ transplantation, stem cells or bone marrow: daily dose between 2 mg and 15 mg of cyclosporine per kilogram of body weight.
- Nephrotic syndrome :
- Adults : daily dose between 2.5 mg and 5 mg of ciclosporin per kilogram of body weight;
- Children : daily dose between 2.5 mg and 6 mg of cyclosporine per kilogram of body weight.
- Endogenous uveitis : daily dose between 5 mg and 7 mg of cyclosporine per kilogram of body weight.
- Psoriasis and atopic dermatitis : daily dose between 2.5 mg and 5 mg of ciclosporin per kilogram of body weight.
- Severe rheumatoid arthritis : daily dose between 3 mg and 5 mg of ciclosporin per kilogram of body weight.
Daily doses of oral cyclosporine should be divided into two doses . Furthermore, recruitment should take place at the same time every day .
Intravenous cyclosporine
The amount of cyclosporine usually used intravenously is between 3 mg and 5 mg per kilogram of body weight, to be administered in two divided doses .
Cyclosporine via the eye
As for cyclosporine in the form of eye drops, the usual recommended dose is one drop in each affected eye, once a day, in the evening before bedtime for night rest.
Please note
If you wear contact lenses, they must be removed before instilling cyclosporine eye drops. The lenses can then be worn again the following morning.
Pregnancy and breastfeeding
Can cyclosporine be taken in pregnancy and during breastfeeding?
The use of ciclosporin - administered by any route - is generally not recommended during pregnancy (in vivo experiments, but not confirmed in humans, have shown an increased risk of malformations in the fetus), both during breastfeeding. breast (the active ingredient is excreted in breast milk).
Therefore, if the need arises to undertake a treatment based on ciclosporin, pregnant women and breastfeeding mothers must necessarily inform the doctor of their status.
Contraindications
When Cyclosporine should not be used
The use of ciclosporin through any route of administration is contraindicated in case of known hypersensitivity to ciclosporin itself and / or to one or more of the excipients contained within the medicinal product to be used.
The use of cyclosporine via both oral and parenteral (intravenous infusion) is also contraindicated in the following cases:
- If you are already on medication with:
- Dabigatran (active ingredient with anticoagulant activity belonging to the group of direct thrombin inhibitors);
- Bosentan (active ingredient used in the treatment of pulmonary hypertension);
- Aliskiren (active ingredient with antihypertensive action, belongs to the group of direct renin inhibitors).
- If you are taking products based on St. John's wort (or St. John's wort, a plant with known antidepressant properties).
Finally, the use of cyclosporin in the form of eye drops is contraindicated in the presence of eye infections .
Please note
For more in-depth information on indications, warnings and precautions, interactions, side effects, use during pregnancy and during lactation and contra-indications of cyclosporine, it is advisable to consult your doctor and carefully read the package insert of the medicinal product from it prescribed and that you will have to use.
