CellSept - Instructions For Use, Price, 250 Mg, Tablets 500 Mg, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

SellSept

CellSept: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. Drug interactions
12. 12. Analogs
13. 13. Terms and conditions of storage
14. 14. Terms of dispensing from pharmacies
15. 15. Reviews
16. 16. Price in pharmacies

Latin name: CellCept

ATX code: L04AA06

Active ingredient: mycophenolate mofetil (Mycophenolate mofetil)

Manufacturer: Rosh S.p. A. (Roche, S. p. A.) (Italy); Roche Farma SA (Spain); F. Hoffmann-La Roche Ltd. (F. Hoffmann-La Roche, Ltd.) (Switzerland)

Description and photo update: 2019-09-07

CellSept is a selective immunosuppressive drug used after organ transplantation (kidney, liver, heart).

Release form and composition

CellSept dosage form:

• film-coated tablets: lavender, engraved with “CellCept 500” on one side, “Roche” on the other (in a cardboard box, 5 blisters of 10 tablets);
• capsules: with a brown body and a blue lid, size No. 1, hard gelatinous, opaque; with black lettering on the case "Roche", on the lid - "CellCept 250"; the capsules contain a granular fine powder, partially crumpled, from almost white to white (in a cardboard box, 10 blisters of 10 capsules).

Each pack also contains instructions for the use of CellSept.

Composition of 1 tablet:

• active ingredient: mycophenolate mofetil - 500 mg;
• auxiliary components: microcrystalline cellulose - 244 mg; croscarmellose sodium - 32.5 mg; magnesium stearate - 12.2 mg; povidone K90 - 24.4 mg;
• shell: Opadry Lavender Y-5-10272-A (hypromellose, hyprolose, titanium dioxide, macrogol 400, red iron oxide dye, indigo carmine dye) - 24 mg.

Composition of 1 capsule:

• active ingredient: mycophenolate mofetil - 250 mg;
• auxiliary components: croscarmellose sodium - 11.9 mg; magnesium stearate - 4.5 mg; povidone K90 - 5.95 mg; pregelatinized corn starch - 29.76 mg;
• capsule body: titanium dioxide, red iron oxide dye, yellow iron oxide dye, gelatin;
• capsule cap: titanium dioxide, indigo carmine dye, gelatin;
• ink: shellac, potassium hydroxide, black iron oxide dye.

Pharmacological properties

Pharmacodynamics

The active substance of CellSepta - MMF (mycophenolate mofetil), is a 2-morpholinoethyl ester of IFC (mycophenolic acid). It is a potent, selective, noncompetitive and reversible inhibitor of IMPDH (inosine monophosphate dehydrogenase) that inhibits the biosynthesis of guanosine nucleotides. The mechanism by which the enzymatic activity of IMPDH is suppressed is probably related to the fact that structurally IFC mimics not only the cofactor nicotinamide dinucleotide phosphate, but also the catalyzing water molecule. This becomes an obstacle to the oxidation of IMP (inosine monophosphate) into xanthose-5-monophosphate, which is the most important stage in the biosynthesis of guanosine nucleotides.

IFC has a more pronounced cytostatic effect on lymphocytes than on other cells, since the proliferation of B and T lymphocytes largely depends on the synthesis of purines, while cells of other types can switch to bypass metabolic pathways.

In order to prevent rejection after organ transplantation (kidney, liver and heart), therapy of refractory rejection of a transplanted kidney MMF is prescribed in combination with muromonab-CD3, antithymocyte globulin, corticosteroids and cyclosporine.

In the case of kidney transplantation, when MMF is combined with cyclosporine and corticosteroids, the incidence of treatment failure in the first six months after transplantation and histologically proven rejection during treatment decreases; when used in a daily dose of 2000 mg, the cumulative incidence of graft death and mortality in 12 months after kidney transplantation decreases, but when used in a daily dose of 3000 mg, there is an increase in the frequency of premature withdrawal from the study for any reason.

MMF surpasses azathioprine in the frequency of histologically proven rejection, mortality, and repeated transplantations in heart transplants.

MMF therapy in combination with cyclosporine and corticosteroids is more effective than azathioprine. This prevents acute rejection and provides a similar survival rate to azathioprine in primary liver transplant patients.

Against the background of the use of MMF, the incidence of graft death or deaths decreases six months after the start of treatment by 45% (p = 0.062) in patients who underwent kidney transplantation with cell-mediated acute transplant rejection refractory to treatment.

In doses that are 2–3 times higher than the therapeutic ones in the case of kidney transplantation and 1.3–2 times higher than those in patients after heart transplantation, MMF did not have a carcinogenic effect and did not affect the fertility of male rats. At doses that have strong cytotoxic properties, in two tests (as determined by thymidine kinase in mouse lymphoma cells and in mouse micronucleoli), MMF can potentially lead to chromosomal instability.

In animal studies, oral intake of CellCept at a dose that is 0.5 times higher in terms of systemic exposure to the daily dose of 2000 mg after kidney transplant and approximately 0.3 times higher in terms of systemic exposure to the clinical daily dose of 3000 mg recommended after heart transplant. led to malformations (including anophthalmia, hydrocephalus and agnathy) in the first generation of offspring without toxic effects on fertility and mother, as well as on the reproductive performance of subsequent generations.

As a result of studies of teratogenicity in animals, it was found that rats who received the drug at a dose of approximately 0.5 times higher than 3000 mg per day in systemic exposure were observed fetal resorption and congenital malformations (including anophthalmia, hydrocephalus and agnathy), in the offspring of rabbits malformations of the kidneys, cardiovascular system, ectopia of the heart and kidneys, umbilical and diaphragmatic hernias were identified, while signs of toxic effects on the mother were not registered.

In toxicological studies of MMF in animals, the main lesions were localized in the lymphoid and hematopoietic organs and developed at a level of systemic exposure to CellCept, which is equivalent or lower than the clinical effect of the dose of 2000 mg per day recommended for patients after kidney transplantation. The nonclinical toxicity profile of MMF is consistent with adverse events reported in human clinical trials, resulting in safety data that are more relevant to the patient population.

Pharmacokinetics

The pharmacokinetic characteristics of MMF were studied in patients who underwent kidney, liver and heart transplants. In general, the pharmacokinetic profile of MMF is not different in heart and kidney transplant patients. During the early post-transplant period, in liver transplant patients receiving 1500 mg of MMF, the IFC concentrations were the same as in patients after kidney transplantation receiving 1000 mg of MMF.

After oral administration, MMF is rapidly and fully absorbed, while the substance undergoes complete first-pass metabolism of MMF with the formation of IFC (active metabolite). When CellSept is taken orally, the bioavailability of MMF, in accordance with the _IFC AUC (area under the concentration-time curve), averages 94% of the value of this indicator when administered intravenously. In cases where MMF is administered orally, its plasma concentration is not determined.

During the early post-transplant period (up to 40 days after a kidney, liver or heart transplant), the average _IFC AUC values are approximately 30% lower, and the C _max (maximum concentration of the substance) is approximately 40% lower than that observed in the late post-transplant period (within 3-6 months after transplantation).

The degree of absorption of MMF (_IFC AUC) when used 2 times a day, 1500 mg in patients after kidney transplantation, food intake has no effect. However, when taken with food, the C _{max of the} IFC is reduced by 40%.

As a rule, approximately 6-12 hours after taking CellCept, a secondary increase in the plasma concentration of IFC is noted, this is an indication that there is a hepatic-intestinal recirculation of the drug. With simultaneous therapy with cholestyramine, the _IFC AUC decreases by approximately 40%, which indicates an interruption of the hepatic-intestinal circulation.

IFC in clinically significant concentrations binds to plasma albumin at 97%.

IFC metabolism occurs mainly under the influence of glucuronyl transferase, with the formation of pharmacologically inactive phenolic MPKG (IFC glucuronide). Later, in the course of hepatic-intestinal recirculation, MPKG is transformed into free MPK.

93% of the received dose of radioactively labeled MMF after oral administration is excreted in the urine, 6% of the dose is excreted in the feces. Approximately 87% of the administered dose is excreted as MPCG in the urine. Up to 1% of the dose is excreted in the form of IFC in the urine.

Clinically detectable concentrations of IFC and MPKG are not removed by hemodialysis. In the case of higher concentrations of MPCG (from 100 μg / ml), some of the concentration can be removed. Bile acid sequestrants such as colestyramine, interrupting hepatic-intestinal recirculation, lower the _IFC AUC.

When conducting a bioequivalence study of two dosage forms of the drug release, it was found that 4 CellSept 250 mg capsules are equivalent to 2 CellSept 500 mg tablets.

In a study with single dose of MMF on the background of severe chronic renal failure (in patients with glomerular filtration rate <25 mL / min / 1.73 m ²) AUC value _IFC was at 28-75% higher than in patients having less severe lesions kidney, and healthy volunteers. In patients with severe renal insufficiency, the AUC of _MPKG after taking a single dose is 3-6 times higher, which is consistent with the known data on the excretion of MPKG by the kidneys.

Studies on repeated administration of MMF against the background of severe chronic renal failure have not been conducted.

The mean AUC _0-12 for IFC in patients with delayed renal graft function after transplantation is comparable to the value in patients in whom there was no delay in graft function after transplantation, and the mean plasma AUC _0-12 for IFCG was 2–3 times more.

In volunteers with alcoholic cirrhosis of the liver, after ingestion of MMF, changes in the pharmacokinetic parameters of IFC and IFC were not detected. In this regard, it was found that damage to the liver parenchyma is not a contraindication for the appointment of MMF. There is an assumption that the influence of hepatic pathology on this process is determined by a specific disease. In patients with liver disease with a predominance of biliary tract lesions (in particular with primary biliary cirrhosis), the effect may be different.

Children who have had a kidney transplant, after oral administration of MMF 2 times a day at a dose of 600 mg / m ² (maximum - up to 1000 mg 2 times a day) AUC IFC is comparable to that in adult kidney transplant recipients who receive MMF 2 times a day at a dose of 1000 mg both during the early and late post-transplant period. Between age groups, the AUC value for IFC was the same in the early and late transplantation period.

Pharmacokinetic parameters of CellCept in elderly and senile patients (from 65 years) have not been studied.

Indications for use

CellSept is prescribed in combination with cyclosporine and corticosteroids in the following cases:

• acute organ rejection (prevention), organ rejection in patients after allogeneic kidney transplant, refractory to therapy (treatment);
• acute organ rejection (prevention) and use to improve graft survival and patient survival after allogeneic heart transplant;
• acute organ rejection in patients after allogeneic liver transplantation (prevention).

Contraindications

Absolute:

• lactation period;
• individual intolerance to mycophenolate mofetil, mycophenolic acid and other components of the drug.

Relative (CellSept is prescribed under medical supervision):

• exacerbation of diseases of the gastrointestinal tract;
• pregnancy.

CellSept, instructions for use: method and dosage

CellSept capsules and tablets are taken orally.

Adults

For the prevention of kidney transplant rejection, CellCept is prescribed 2 times a day, 1000 mg. In clinical studies, it was found that the use of the drug in a single dose of 1500 mg is also safe and effective, however, the benefits in terms of effectiveness in this group of patients have not been established. The overall safety profile in patients receiving 2000 mg of CellCept per day is better than with therapy at a daily dose of 3000 mg.

For the prevention of liver and heart transplant rejection, as well as for the treatment of the first / refractory kidney transplant rejection, CellCept is prescribed 2 times a day, 1500 mg.

The first dose of CellCept after a kidney, liver or heart transplant should be taken as soon as possible.

Against the background of neutropenia (in patients with an absolute number of neutrophils <1300 in 1 μl of blood), therapy should be interrupted or the dose of CellCept should be reduced. Careful monitoring of the patient's condition is required.

In patients with severe chronic renal failure (with a glomerular filtration rate less than 25 ml / min / 1.73 m ²) outside the immediate post-transplant period or after treatment for acute / refractory rejection, a daily dose of CellCept exceeding 2000 mg should be avoided. There are no data on patients with severe renal impairment who have undergone liver or heart transplants.

Children

There are no data on the safety and efficacy of CellCept in the prevention of heart or liver transplantation and in the treatment of first / refractory renal transplant rejection.

The recommended dosage regimen of CellCept after kidney transplantation for patients over 12 years old (depending on body surface area):

• 1.25-1.50 m ²: 2 times a day, 750 mg;
• from 1.5 m ²: 2 times a day, 1000 mg.

Side effects

Due to the underlying disease and the combined use of CellCept with many other drugs, the profile of adverse reactions associated with immunosuppressive therapy is often difficult to establish.

According to clinical studies, the main side effects associated with the use of CellCept along with corticosteroids and cyclosporine for the prevention of renal, hepatic or cardiac transplant rejection are sepsis, diarrhea, vomiting and leukopenia. There is also evidence of an increase in the frequency of opportunistic infections.

In the treatment of refractory renal rejection, the safety profile of MMF is similar to that when used for the prevention of renal rejection using CellCept in a daily dose of 3000 mg. The predominant side effects that occurred in patients receiving MMF more often than in patients receiving intravenous corticosteroids were leukopenia and diarrhea, followed by abdominal pain, vomiting, nausea, anemia, and sepsis.

Lymphomas or lymphoproliferative diseases developed in 0.4-1% of patients who underwent a kidney, liver or heart transplant and were observed for at least 1 year, receiving MMF (in a daily dose of 2000 or 3000 mg) in combination with other immunosuppressants. The occurrence of skin carcinoma (except melanoma) was noted in 1.6–4.2% of cases, malignant neoplasms of other types - in 0.7–2.1% of cases.

Data on the safety of CellCept use over three years in patients after heart or kidney transplantation, in comparison with annual rates, did not reveal any unexpected changes in the incidence of malignant neoplasms. After liver transplantation, patients were monitored for one to three years.

The incidence of lymphomas in the treatment of refractory renal rejection was 3.9% with a mean follow-up of up to 42 months.

The likelihood of opportunistic infections is increased in all post-transplant patients and increases as the degree of immunosuppression increases. When MMF was prescribed (in a daily dose of 2000 or 3000 mg) in combination with other immunosuppressants in patients who were observed for one year after transplantation of a kidney (in a daily dose of 2000 mg), liver and heart, the most common infections were mucosal candidiasis and skin, CMV syndrome / CMV viremia (in 13.5% of cases) and herpes simplex virus infection.

The incidence of adverse reactions and their type with oral administration of CellSept 2 times a day at a dose of 600 mg in children from 3 months to 18 years did not practically differ from those in adult patients who took 1000 mg 2 times a day. However, side effects such as anemia, leukopenia, diarrhea, sepsis, infections, were more common (≥ 10%) in children, especially under 6 years of age.

In patients over 65 years of age, during combined immunosuppressive treatment, including MMF, the risk of certain infections (including tissue invasive forms of manifest WVD infection), as well as, probably, pulmonary edema and gastrointestinal bleeding is higher than in patients with more young age.

Adverse reactions reported in patients after kidney transplantation with the use of MMF simultaneously with corticosteroids and cyclosporine (often - ≥ 10%; infrequently - 3-10%):

• genitourinary system: often - renal tubular necrosis, hematuria, urinary tract infections; infrequently - impotence, albuminuria, pyelonephritis, dysuria, hydronephrosis, frequent urination;
• lymphatic system: often - thrombocytopenia, anemia (including hypochromic), leukopenia, leukocytosis; infrequently - polycythemia, ecchymosis;
• metabolism: infrequently - weight gain, dehydration, respiratory / metabolic acidosis, hypervolemia;
• cardiovascular system: often - increased blood pressure; infrequently - vasodilation, atrial fibrillation, thrombosis, tachycardia, angina pectoris, lowering blood pressure, orthostatic hypotension;
• digestive system: often - constipation, dyspepsia, diarrhea, vomiting, nausea, oral candidiasis; infrequently - candidiasis of the gastrointestinal tract, gingivitis, esophagitis, gingival hyperplasia, stomatitis, intestinal obstruction, hepatitis, anorexia, gastroenteritis, flatulence, gastrointestinal bleeding;
• respiratory organs: often - pneumonia, increased cough, pharyngitis, shortness of breath, bronchitis; infrequently - pleural effusion, rhinitis, pulmonary edema, sinusitis, asthma;
• skin and its appendages often: - herpes simplex, acne; infrequently - herpes zoster, fungal dermatitis, rash, skin hypertrophy (including actinic keratosis), skin ulcers, excessive sweating, hirsutism, skin cancer, itching, hair loss, benign skin growths;
• the nervous system often - insomnia, dizziness, tremors; infrequently - paresthesia, anxiety, hypertonicity, depression, drowsiness;
• musculoskeletal system: infrequently - leg cramps, pain in muscles and joints, muscle weakness;
• endocrine system: infrequently - disease of the parathyroid glands (increased levels of parathyroid hormone), diabetes mellitus;
• sense organs: infrequently - cataracts, amblyopia, conjunctivitis;
• laboratory parameters: often - hyperkalemia, hyperglycemia, hypophosphatemia, hypokalemia, hypercholesterolemia; infrequently - an increase in the activity of alkaline phosphatase (alkaline phosphatase), an increase in the activity of enzymes, including gamma-glutamyl transpeptidase, LDH (lactate dehydrogenase), AST (aspartate aminotransferase) and ALT (alanine aminotransferase) in the blood serum, increased serum creatininemia, hypocalipinemia, hyperocaleuricemia hypoglycemia, hypercalcemia;
• the body as a whole: often - peripheral sepsis, edema, infections, fever, asthenia, headache, pain (in the chest, abdomen, lower back); infrequently - cysts (including hydrocele and lymphocele), pain in the pelvis, flu-like syndrome, facial swelling, bleeding, hernia, malaise, bloating.

Adverse reactions reported in patients after liver transplantation when using MMF simultaneously with corticosteroids and cyclosporine:

• genitourinary system: often - oliguria, impaired renal function, urinary tract infections; infrequently - scrotal edema, acute renal failure, hematuria, dysuria, renal failure, urinary incontinence, frequent urination;
• lymphatic system: often - thrombocytopenia, anemia (including hypochromic), leukopenia, leukocytosis; infrequently - an increase in prothrombin time, ecchymosis, pancytopenia;
• metabolism: often - impaired wound healing; infrequently - hypoxia, hypervolemia, hypovolemia, weight loss, weight gain, metabolic / respiratory acidosis, dehydration;
• cardiovascular system: often - tachycardia, increase or decrease in blood pressure; infrequently - atrial fibrillation, arterial thrombosis, syncope, arrhythmias, vasodilation, bradycardia;
• respiratory organs: often - pleural effusion, atelectasis, sinusitis, increased cough, shortness of breath, pneumonia, pharyngitis; infrequently - rhinitis, respiratory tract candidiasis, epistaxis, asthma, bronchitis, hyperventilation, pulmonary edema, pneumothorax;
• digestive system: often - oral candidiasis, dyspepsia, hepatitis, flatulence, vomiting and nausea, constipation, anorexia, cholestatic jaundice, cholangitis, diarrhea; infrequently - dysphagia, esophagitis, gastritis, intestinal obstruction, gastrointestinal bleeding, jaundice, ulceration of the oral mucosa, melena, gastric ulcer, rectal lesions, xerostomia;
• skin and its appendages: often - itching, rash, excessive sweating; infrequently - herpes zoster, vesicular-bullous rash, benign skin neoplasms, skin ulcers, hirsutism, acne, fungal dermatitis, herpes simplex, hemorrhages;
• nervous system: often - tremor, paresthesia, confusion, anxiety, dizziness, depression, insomnia; infrequently - psychosis, neuropathy, psychomotor agitation, convulsions, memory loss, delirium, drowsiness, hypertonicity, hypesthesia;
• sense organs: infrequently - conjunctivitis, visual impairment, amblyopia, deafness;
• musculoskeletal system: infrequently - pain in muscles and joints, muscle weakness, leg cramps, osteoporosis;
• endocrine system: infrequently - diabetes mellitus;
• laboratory parameters: often - increased residual nitrogen, hyperbilirubinemia, increased creatinine, hyperkalemia, hyperglycemia, hypocalcemia, hypokalemia, hypoproteinemia, hypoglycemia, hypophosphatemia, hypomagnesemia; infrequently - increased ALP activity, increased serum enzyme activity (AST and ALT) in the blood, hyponatremia, hypercholesterolemia, hyperphosphatemia, hyperlipidemia;
• the body as a whole: often - peripheral edema, asthenia, ascites, fever, bloating, sepsis, peritonitis, hernia, chills, headache, infections, pain (in the lower back, abdomen, chest); infrequently - inflammation of the subcutaneous tissue, abscess, cysts (including hydrocele and lymphocele), neck pain, flu-like syndrome, malaise, bleeding.

Adverse reactions reported in patients after heart transplant when using MMF simultaneously with corticosteroids and cyclosporine:

• genitourinary system: often - oliguria, impaired renal function, urinary tract infections; infrequently - frequent urination, nocturia, dysuria, impotence, hematuria, renal failure, urinary retention / incontinence;
• the lymphatic system often - leukopenia, leukocytosis, ecchymosis, thrombocytopenia, anemia (including hypochromic); infrequently - petechiae, an increase in thromboplastin and prothrombin time;
• metabolism: often - hypervolemia, metabolic / respiratory acidosis, weight gain; infrequently - alkalosis, gout, dehydration, impaired wound healing, hypovolemia, weight loss, hypoxia, thirst, respiratory acidosis;
• cardiovascular system: often - pericardial effusion, bradycardia, arrhythmia, heart failure, increase / decrease in blood pressure; infrequently - angina pectoris, arrhythmias (ventricular and supraventricular extrasystoles, atrial fibrillation and atrial flutter, ventricular and supraventricular tachycardias), increased venous pressure, vasospasm, cardiac arrest, fainting, orthostatic hypotension, congestive heart failure, pulmonary;
• respiratory organs: often - pneumonia, sinusitis, rhinitis, pleural effusion, increased cough, asthma, shortness of breath, pharyngitis; infrequently - hiccups, pneumothorax, voice changes, increased sputum production, pulmonary edema, apnea, bronchitis, atelectasis, epistaxis, hemoptysis, neoplasms;
• digestive system: often - flatulence, vomiting, nausea, oral candidiasis, constipation, diarrhea, dyspepsia; infrequently - gingival hyperplasia, melena, jaundice, esophagitis, stomatitis, dysphagia, anorexia, gingivitis, gastroenteritis;
• nervous system: often - hypertonicity, tremor, drowsiness, psychomotor agitation, confusion, anxiety, depression, paresthesia, dizziness, insomnia; infrequently - emotional lability, vertigo, memory loss, neuropathy, convulsions, hallucinations;
• skin and its appendages: often - shingles, acne, rash, herpes simplex; infrequently - fungal dermatitis, benign skin neoplasms, itching, skin ulcers, excessive sweating, hemorrhages, hypertrophy and skin cancer;
• sense organs: often - amblyopia; infrequently - pain in the ear, tinnitus, bleeding in the eye, visual impairment, deafness, conjunctivitis;
• musculoskeletal system: often - muscle pain, leg cramps, muscle weakness; infrequently - joint pain;
• endocrine system: infrequently - Cushing's syndrome, diabetes mellitus, hypothyroidism;
• laboratory indicators: often - hypercholesterolemia, hyperlipidemia, hyperkalemia, hypokalemia, hyperuricemia, hyponatremia, hypomagnesemia, hyperglycemia, increased creatinine, hyperbilirubinemia, increased residual nitrogen, increased activity of enzymes (AST, LDH, ALT) in serum; infrequently - increased ALP activity, hypoproteinemia, hypocalcemia, hypoglycemia, hypochloremia, hypophosphatemia;
• the body as a whole: often - sepsis, peripheral edema, asthenia, chills, fever, headache, infections, pain (in the lower back, abdomen, chest); infrequently - malaise, inflammation of the subcutaneous tissue, bleeding, cysts (including hydrocele and lymphocele), pallor of the skin, swelling of the face, neck pain, flu-like syndrome, hernia, bloating, pain in the pelvis;

The safety profile of MMF in the prevention of renal transplant rejection in the case of using the drug in a daily dose of 2000 mg was slightly better than in a dose of 3000 mg.

Adverse reactions registered during the post-marketing use of CellSepta:

• digestive system: isolated cases of intestinal villi atrophy, colitis (in some cases of cytomegalovirus genesis), pancreatitis;
• immune system: isolated cases of severe, life-threatening infections (infective endocarditis, meningitis), an increase in the frequency of certain infections such as atypical mycobacterial infections and tuberculosis.

Some patients have had cases of PML (progressive multifocal leukoencephalopathy), sometimes fatal. These cases have reported additional risk factors for PML, which include impaired immunity and immunosuppressive therapy.

When used in combination with other immunosuppressive drugs, there have been cases of the development of PCA (partial red cell aplasia).

In patients who took MMF during pregnancy simultaneously with other immunosuppressants, cases of fetal anomalies (including ear malformations) have been reported.

Other side effects observed with the post-registration use of CellCept do not differ from the disorders that have been registered in the course of clinical trials.

Overdose

Information about an overdose of CellSept was obtained during clinical trials and during post-marketing use. In most cases, no side effects were reported. Adverse events that developed during overdose coincided with the established safety profile of the drug.

Expected symptoms: immunosuppression (and, as a consequence, increased sensitivity to infections), bone marrow suppression.

Therapy: with the development of neutropenia, a decrease in the dose of CellSept or complete withdrawal of the drug is indicated.

It is impossible to remove IFC from the body by hemodialysis. However, at high plasma concentrations of MPKG (> 100 μg / ml), small amounts of it are still excreted.

Drugs that bind bile acids can contribute to the elimination of IFC from the body (by increasing its excretion).

special instructions

During the period of use of CellCept, as a combined immunosuppression in general, there is an increased risk of lymphomas and other malignant neoplasms, especially the skin. This risk is probably associated not with the use of the drug as such, but with the duration and intensity of immunosuppression.

As with all patients at high risk of skin cancer, it is imperative to limit UV and sun exposure by wearing closed clothing. You should also use sunscreen with a high protective factor value.

Any sign of infection, bleeding, bleeding, or other symptoms of bone marrow suppression should be reported to your doctor immediately.

Against the background of excessive suppression of the immune system, an increase in sensitivity to infections, including opportunistic ones, sepsis, and other fatal infections, is possible.

Patients taking CellCept have had cases of PML, sometimes with fatal outcome. As a rule, this happened in the presence of additional risk factors for PML, including immunosuppressive therapy and deterioration of the immune state. In the presence of neurological symptoms, patients with immunosuppression should undergo differential diagnosis of PML. It was recommended to consult a neurologist.

Cases of PACA have been reported in patients who took CellCept in combination with other immunosuppressive drugs. The mechanism of PACA development while taking the drug, as well as other immunosuppressants and their combinations, has not been determined. Sometimes PCAA after discontinuation of the drug or reduction of its dose was reversible. However, in patients who have undergone a transplant, a decrease in immunosuppression may pose a threat to the transplant.

Vaccination during MMF therapy may be less effective. Live attenuated vaccines should be avoided. Influenza vaccination can be given according to national guidelines.

The use of MMF may be accompanied by disorders of the gastrointestinal tract (in the form of ulceration of the mucous membrane, gastrointestinal bleeding, perforation); caution should be exercised when prescribing CellSept to patients with exacerbations of diseases of the digestive tract.

MMF is an inhibitor of IMPDG, therefore, theoretically, it should not be prescribed to patients with a rare genetically determined hereditary deficiency of hypoxanthine guanine phosphoribosyltransferase (Kelly-Sigmiller and Lesch-Nyhan syndromes).

The simultaneous use of CellCept and azathioprine is not recommended. Both drugs lead to bone marrow suppression, and their combined use has not been studied.

Caution is required with the combined use of MMF and drugs that affect the hepatic-intestinal circulation, since they can reduce the effectiveness of CellCept.

Patients with severe chronic renal impairment should avoid prescribing doses greater than 1000 mg 2 times a day.

There is no need to adjust the dose in patients with delayed renal graft function, but they should be closely monitored. There are no data on patients who have undergone liver or heart transplants and have severe renal failure.

The risk of adverse events in elderly patients may exceed that in younger patients.

During the period of CellSept therapy, it is necessary to determine the expanded blood formula weekly during the first month, during the second and third months of therapy - 2 times a month, and further during the first year - once a month. The development of neutropenia can be associated with both the use of MMF and with the use of other drugs, with viral infections, or a combination of these reasons. In case of neutropenia (with an absolute number of neutrophils less than 1300 in 1 μl), the dose of CellSept is reduced or the drug is completely canceled. The condition of these patients should be carefully monitored.

In an experiment on rabbits and rats, MMF exhibited a teratogenic effect; therefore, the tablets should not be broken and the integrity of the capsules should not be broken. Avoid inhalation of the powder contained in the capsules, or direct contact with mucous membranes or skin. If this happens, rinse the area thoroughly with soap and water, and your eyes with just water.

Influence on the ability to drive vehicles and complex mechanisms

Patients during the period of taking CellCept should take into account the likelihood of developing dizziness and other adverse reactions that may affect the ability to drive vehicles.

Application during pregnancy and lactation

• pregnancy: the appointment of CellSept to pregnant women is possible only in cases where the benefits of therapy are higher than the possible harm;
• lactation period: the use of the drug is contraindicated.

CellCept, according to the FDA classification - US Food and Drug Administration, belongs to category D.

When using the drug in the first trimester of pregnancy, there is an increased risk of spontaneous miscarriage, while the likelihood of congenital malformations increases, including anomalies of the kidneys, heart and esophagus, cleft lip, cleft palate, anomalies in the development of the distal extremities and external ear.

In case of pregnancy planning, CellCept should not be used as long as other drugs with immunosuppressive action are effective. When planning / starting a pregnancy, a woman should take into account the existing potential harm to the fetus.

You should not start taking MMF until confirmation of the absence of pregnancy using the method of urine analysis or serum with a sensitivity of at least 25 mIU / ml (no later than 1 week before you start taking CellSept). Before starting the use of MMF, during therapy and for 6 weeks after the end of treatment, it is imperative to use reliable methods of contraception, even if the woman has a history of infertility (except for cases of hysterectomy). If a woman cannot abstain from sexual intercourse, she should use two reliable methods of contraception at the same time, since during the therapy with CellSept, when taking oral contraceptives, it is potentially possible to reduce the level of hormones.

MMF in rats is excreted in milk. It is not known whether the substance is excreted in human milk. Due to the fact that many drugs are excreted in human milk, as well as the possibility of developing serious side effects on MMF in infants, the choice between taking CellCept or continuing breastfeeding is made taking into account the importance of therapy for the mother.

Pediatric use

The safety profile of CellCept in the prevention of heart or liver transplantation and the treatment of first / refractory renal transplant rejection in pediatric patients has not been studied.

After kidney transplantation, CellCept can be administered to children over 12 years of age.

Drug interactions

• acyclovir: against the background of renal failure, the plasma concentration of both drugs increases, which may be associated with competition with respect to tubular secretion and lead to a further increase in the concentration of both drugs;
• antacids containing aluminum and magnesium hydroxide: the absorption of MMF is reduced;
• cholestyramine: there is a significant decrease in _IFC AUC, therefore, combined use requires caution;
• cyclosporin A: MMF does not affect its pharmacokinetics; with simultaneous use, the effect of MMF decreases by 30-50% in comparison with patients who receive MMF in combination with sirolimus;
• ganciclovir: when prescribing these drugs in patients with renal failure, careful monitoring of their condition is required;
• oral contraceptives: in addition to these, other methods of contraception must be used;
• trimethoprim / sulfamethoxazole, metronidazole, norfloxacin: when IFC is administered with one of the antibacterial drugs, bioavailability does not change; after a single use of CellSept simultaneously with norfloxacin and metronidazole, there is a 30% decrease in AUC _{0–48 of} IFC;
• tacrolimus: its AUC in patients with stable hepatic transplant after repeated administration of MMF 2 times a day at a dose of 1500 mg increases by approximately 20%;
• rifampicin: after dose adjustment, there is a 70% decrease in the effect of IFC (AUC _0-12) in patients after single-stage lung and heart transplantation; in case of combined administration, it is recommended to control the effect of IFC and adjust the CellCept dose in order to maintain the clinical effect;
• ciprofloxacin and amoxicillin in combination with clavulanic acid: on the days immediately after oral administration of amoxicillin or ciprofloxacin simultaneously with clavulanic acid in patients after kidney transplantation, a significant decrease in _{Cmin of} IFC is observed. With continued treatment, this effect decreases, and after discontinuation of therapy disappears. The clinical significance is unknown because the change in C _min may not adequately reflect the change in the total exposure to IFC;
• probenecid (tubular secretion blockers): the concentration of MPKG increases;
• sevelamer: AUC _0–12 and C _max IFC decreases by 25 and 30%, respectively. Sevelamer and other phosphate binders, which do not include calcium, should be used 2 hours after taking CellSept, which will reduce their effect on IFC absorption;
• live vaccines: during CellSept therapy, they should not be administered; the formation of antibodies in response to other vaccines may be reduced.

Analogs

CellSept's analogues are Mayfortic, Maysept, Mycophenolate sodium, Mycophenolate-Teva, Mycophenolic acid, Sodium mycophenolate, MMF 500, FELOMIKA, Supresta.

Terms and conditions of storage

Store in a place protected from light and moisture at temperatures up to 30 ° C in its original packaging. Keep out of the reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about CellSepte

Reviews of CellSepte are mostly positive. On specialized forums, the question of where the drug can be purchased cheaper is most often discussed, since it has a fairly high cost. Usually they indicate that the therapy is well tolerated, the development of side effects is rarely reported.

SellSept price in pharmacies

The price for CellCept depends on the form of release. The approximate cost may be:

• CellSept capsules 250 mg (100 pcs. in a package) - 3100 rubles,
• Coated tablets CellSept 500 mg (50 pieces per pack) - 2961 rubles.

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!