Sandimmune Neoral soft capsules 100mg, 50pcs

Composition

1 capsule contains cyclosporine 100 mg;

excipients:

D, L-α-tocopherol,

ethanol, propylene glycol,

mono -, di-and triglycerides of corn oil,

polyoxyl 40 hydrogenated castor oil.

capsule shell composition:

iron oxide black,

titanium dioxide,

glycerol 85%,

propylene glycol,

gelatin.

Pharmacological action

Sandimmun Neoral is an immunosuppressive agent, a cyclic polypeptide consisting of 11 amino acids.

Inhibits the development of cell-type reactions, including allograft immunity, delayed-type skin hypersensitivity, allergic encephalomyelitis, Freund’s adjuvant-induced arthritis, graft-versus-host disease, and T-lymphocyte-dependent antibody formation.

At the cellular level, it blocks resting lymphocytes in the G0 or G1 phases of the cell cycle and suppresses the production and secretion of cytokines triggered by the antigen (including interleukin 2, T-lymphocyte growth factor). activated T-lymphocytes.

It has a reversible effect on lymphocytes. It does not inhibit hematopoiesis and does not affect the functioning of phagocytic cells.

Indications

In combination with other immunosuppressive drugs and corticosteroids – for the prevention of rejection reactions in bone marrow, kidney, liver, heart, combined cardiopulmonary graft, lungs or pancreas transplantation. Graft-versus-host disease (prevention and treatment), graft rejection in patients previously treated with other immunosuppressants.

Autoimmune diseases, endogenous uveitis (active, vision-threatening uveitis of the middle or posterior part of the eye of non-infectious etiology, if conventional therapy does not work or leads to severe side effects), Behcet uveitis (with recurrent attacks of inflammation affecting the retina; atopic dermatitis (in severe form, in cases where systemic therapy is indicated); nephrotic syndrome (in remission, steroid-dependent and steroid-resistant form); psoriasis (severe persistent course, insufficient response to systemic treatment); rheumatoid arthritis (severe forms of active course in cases where classic slow-acting antirheumatic drugs are ineffective or their use is impossible).

Contraindications

Hypersensitivity; malignant neoplasms, precancerous skin diseases; children’s age (up to 1 year), lactation period, children’s age (for use in the treatment of psoriasis and rheumatoid arthritis).

With caution. Chickenpox (currently or recently transferred, including recent contact with the patient), Varicella zoster (risk of generalization of the process), and other viral diseases, renal and/or liver failure, hyperkalemia, arterial hypertension, infections, malabsorption syndrome.

Side effects

Many of the side effects associated with cyclosporine use are dose-dependent and reversible when the dose is reduced. The spectrum of side effects is generally the same for different indications, although the frequency and severity of side effects may vary. In transplant patients, due to the higher dose and longer duration of treatment, side effects are more common and usually more pronounced than in patients with other indications.

Cases of anaphylactoid reactions have been reported with intravenous cyclosporine use. Patients receiving immunosuppressive treatment with cyclosporine or combination therapy including cyclosporine have an increased risk of developing local and generalized infections (viral, bacterial, fungal etiology) and parasitic infestations. It is also possible to exacerbate previously existing infectious diseases. Cases of fatal infectious lesions have been reported.

Patients receiving immunosuppressive treatment with cyclosporine or combination therapy including cyclosporine have an increased risk of developing lymphomas, lymphoproliferative diseases, and malignancies, especially of the skin. The incidence of malignant neoplasms increases with increasing intensity and duration of immunosuppressive therapy.

The incidence of adverse events was assessed as follows: very common (≥1/10), common (≥1/100; Urinary system disorders: very common – impaired renal function.

From the cardiovascular system: very often – increased blood pressure.

From the central nervous system and peripheral nervous system: very often – tremor, headache; often – paresthesia; sometimes – signs of encephalopathy, such as convulsions, lethargy, disorientation, slow reactions, agitation, sleep disorders, visual disturbances, cortical blindness, coma, paresis, cerebellar ataxia; rarely – motor polyneuropathy; very rarely – edema of the optic disc (including the optic nipple), secondary to benign intracranial hypertension.

From the digestive system: often – anorexia, nausea, vomiting, abdominal pain, diarrhea, gum hyperplasia, liver dysfunction; rarely-pancreatitis.

From the side of metabolism: very often – hyperlipidemia; often-hyperuricemia, hyperkalemia, hypomagnesemia; rarely-hyperglycemia.

From the musculoskeletal system: often-muscle spasms, myalgia; rarely-muscle weakness, myopathy.

From the hematopoietic system: sometimes-anemia, thrombocytopenia; rarely-microangiopathic hemolytic anemia, hemolytic uremic syndrome.

Dermatological reactions: often-hypertrichosis; sometimes-allergic rash.

From the body as a whole: often – fatigue; sometimes – edema, weight gain.

From the endocrine system: rarely-violation of the menstrual cycle, gynecomastia.

Interaction

Increases the effect of quinidine, theophylline, sodium valproate. When treating cyclosporine, excessive intake of K+ in the body (with food, with potassium-containing drugs) should be avoided, and potassium-sparing diuretics, potassium-containing penicillins, heparin, ACE inhibitors, beta-blockers, cardiac glycosides, suxamethonium should not be prescribed.

When using cyclosporine together with other immunosuppressive drugs (azathioprine, chlorambucil, corticosteroids, cyclophosphamide, mercaptopurine), there is a risk of developing excessive immunosuppression, which can lead to increased sensitivity to infections and the development of lymphoproliferative diseases.

Increases the risk of nephrotoxicity of aminoglycosides, amphotericin B, fluoroquinolones, melphalan, colchicine, trimethoprim, NSAIDs (it is necessary to reduce the dose of both drugs).

Reduces the clearance of prednisone, treatment with high doses of prednisone may increase the concentration of cyclosporine in the blood. Allopurinol, bromocriptine, cimetidine, clarithromycin, androgens, estrogens, danazol, diltiazem, some macrolide antibiotics (including erythromycin and josamycin), doxycycline, oral contraceptives, propafenone, some BMCC (including verapamil, diltiazem, nicardipine), miconazole, fluconazole, itraconazole, ketoconazole, HIV protease inhibitors, metoclopramide, immunosuppressants, grapefruit juice may increase the concentration of cyclosporine (inhibition of the CYP3A isoenzyme), increasing the risk of hepatotoxicity and nephrotoxicity.

Inducers of P450 of the CYP3A isoenzyme (barbiturates, carbamazepine, phenytoin, metamizole sodium, benzodiazepine derivatives, aminoglutetimide, estrogen-progestogenic drugs, progesterone, isoniazid, rifampicin, nafcillin, as well as sulfadimidine and trimethoprim) accelerate cyclosporine metabolism (dose adjustment is necessary). Statins (lovastatin and simvastatin) increase the risk of rhabdomyolysis and acute renal failure. Colchicine increases the risk of developing myalgia and weakness; nifedipine increases the risk of gum hyperplasia.

NSAIDs (Indometacin, diclofenac, naproxen) they increase the risk of kidney failure and hyperkalemia. Activated charcoal, methoxalene, trioxalene, PUVA therapy (psoriasis) increase the risk of developing skin malignancies.

NSAIDs can potentially reduce glomerular filtration rate, and their addition or increase in dose should be accompanied by strict monitoring of renal function (especially at the initial stages of treatment). During cyclosporine treatment, vaccination may be less effective (use of live attenuated vaccines should be avoided).

How to take it, course of use and dosage

Sandimmun Neoral is taken orally: adults with solid organ transplantation should start treatment 12 hours before surgery at a dose of 10-15 mg / kg, divided into 2 doses.

For 1-2 weeks after surgery-daily, at the same dose, after which the dose is gradually reduced (5% / week) until the maintenance dose is reached-2-6 mg / kg / day. When prescribed in combination with corticosteroids or other immunosuppressants, lower doses are used (3-6 mg / kg / day in the initial phase of treatment). In case of bone marrow transplantation – on the day preceding the transplant, and in the transplant period, for 2 weeks, at a daily dose of 12.5-15 mg / kg, then switch to maintenance therapy at a dose of about 12.5 mg/kg / day (with impaired absorption, higher oral doses may be required or switching to intravenous use).

Maintenance treatment is continued for at least 3-6 months (preferably 6 months), after which the dose is gradually reduced so that treatment is discontinued 1 year after the transplant. Some patients develop a rejection reaction after discontinuation of treatment, in which case treatment should be resumed. For endogenous uveitis, to induce remission – in an initial daily dose of 5 mg / kg, in 1 or several doses, until the inflammation subsides and visual acuity improves.

In severe cases, the dose can be increased to 7 mg/kg/day for a limited period of time.During maintenance therapy, the dose should be slowly reduced until the lowest effective dose is reached, which should not exceed 5 mg / kg / day during remission of the disease. In nephrotic syndrome, for the induction of remission – at a daily dose of 5 mg / kg for adults and 6 mg / kg for children (in 2 doses), provided that there is no decrease in renal function (except in cases of proteinuria).

For patients with impaired renal function, the initial daily dose should not exceed 2.5 mg / kg. If cyclosporine monotherapy does not achieve the desired effect, it can be combined with small doses of corticosteroids, inside. If no positive effect is observed after 3 months of treatment, therapy should be discontinued. For maintenance treatment, the dose should be slowly reduced to the minimum effective dose.

For rheumatoid arthritis during the first 6 weeks of treatment, the daily dose is 3 mg / kg in 2 doses. In case of insufficient effect, the daily dose can be gradually increased, provided that it is satisfactorily tolerated (no more than 5 mg / kg / day). The course of treatment is up to 12 weeks. For maintenance therapy, the dose should be selected individually depending on tolerability (it can be prescribed in combination with small doses of corticosteroids and/or NSAIDs).

For psoriasis, to induce remission, the daily dose is 2.5 mg / kg in 2 divided doses. In severe cases of the disease, when a rapid effect is required, the initial daily dose may be 5 mg / kg. If it was not possible to achieve an adequate effect when used at a daily dose of 5 mg / kg for 6 weeks, the drug should be discontinued. The dose for the maintenance treatment of psoriasis should be minimally effective (should not exceed 5 mg / kg / day). For atopic dermatitis, the initial dose is 2.5 mg / kg / day.

In severe cases, the dose may be increased to 5 mg / kg / day. If a positive result is achieved, the dose should be gradually reduced until complete withdrawal.

Overdose

Symptoms: The available experience with overdoses of Sandimmun Neoral is limited. Renal dysfunction may develop, which is probably reversible if the drug is discontinued.

When taking cyclosporine orally at a dose of up to 10 g (about 150 mg / kg), in most cases, slightly pronounced clinical manifestations were observed, such as vomiting, dizziness, headache, and tachycardia. In some cases, reversible renal dysfunction of moderate degree was observed. However, in case of accidental parenteral overdose of cyclosporine in premature children in the neonatal period, the development of severe toxic complications has been reported.

Treatment: symptomatic therapy, there is no specific antidote. During the first 2 hours after ingestion, the drug can be removed from the body by vomiting or by gastric lavage. Cyclosporine is practically not eliminated during hemodialysis and hemoperfusion using activated carbon.

Special instructions

Treatment should be carried out only in specialized medical institutions.

If arterial hypertension develops, antihypertensive treatment should be initiated.

Storage conditions

Keep out of reach of children at a temperature not exceeding 25°C.

Shelf

life is 3 years.

Active ingredient

Cyclosporine

Conditions of release from pharmacies

By prescription

Dosage form

Capsules