Tacrolimus (Capsules) Instructions for Use

Instructions
Dosage forms

ATC Code

L04AD02 (Tacrolimus)

Active Substance

Tacrolimus (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Immunosuppressive drug

Pharmacotherapeutic Group

Immunosuppressive agent – calcineurin inhibitor

Pharmacological Action

Immunosuppressant. At the molecular level, the effects and intracellular accumulation of tacrolimus are due to binding to a cytosolic protein (FKBP 12). The FKBP 12 – Tacrolimus complex specifically and competitively inhibits calcineurin, providing calcium-dependent blockade of T-cell signal transduction pathways and preventing the transcription of a discrete set of lymphokine genes.

In in vitro and in vivo experiments, Tacrolimus significantly reduced the formation of cytotoxic lymphocytes, which play a key role in transplant rejection. Tacrolimus suppresses the formation of lymphokines (interleukin-2, interleukin-3, γ-interferon), T-cell activation, interleukin-2 receptor expression, and T-helper-dependent B-cell proliferation.

Pharmacokinetics

The absorption of tacrolimus is variable (variability of absorption in adult patients is 6-43%). The bioavailability of tacrolimus averages 20-25%. Bioavailability, as well as the rate and extent of tacrolimus absorption, are reduced when taken simultaneously with food. The nature of bile secretion does not affect the absorption of the drug. The distribution of tacrolimus in the human body after intravenous administration is biphasic. In the systemic circulation, Tacrolimus is well bound to erythrocytes. The ratio of tacrolimus concentrations in whole blood and plasma is about 20:1. A significant proportion of plasma tacrolimus (> 98.8%) is bound to plasma proteins (serum albumin, α₁-acid glycoprotein).

Tacrolimus is widely distributed in the body. The V_d at steady state, based on plasma concentrations, is about 1300 L (in healthy people). The same indicator, calculated from whole blood, averages 47.6 L.

Tacrolimus has low clearance. In healthy people, the mean total clearance, calculated from whole blood concentrations, is 2.25 L/h. In adult patients after liver, kidney, and heart transplantation, clearance values were 4.1 L/h, 6.7 L/h, and 3.9 L/h, respectively. Low hematocrit and hypoproteinemia contribute to an increase in the unbound fraction of tacrolimus, accelerating the clearance of tacrolimus. Corticosteroids used in transplantation may also increase the intensity of metabolism and accelerate the clearance of tacrolimus.

The T_1/2 of tacrolimus is long and variable. In healthy people, the mean T_1/2 in whole blood is approximately 43 hours.

Tacrolimus is actively metabolized in the liver, mainly by the CYP3A4 isoenzyme. Tacrolimus metabolism occurs intensively in the intestinal wall. Several metabolites of tacrolimus have been identified. The pharmacological activity of tacrolimus is practically independent of metabolites.

Indications

Prevention and treatment of allograft rejection of the liver, kidney in adult patients. Treatment of allograft rejection resistant to standard regimens of immunosuppressive therapy in adult patients.

ICD codes

Open the list of ICD codes

ICD-10 code	Indication
T86.1	Failure and rejection of kidney transplant
T86.4	Failure and rejection of liver transplant
T86.9	Failure and rejection of transplanted organ and tissue, unspecified

ICD-11 code	Indication
NE84	Dysfunction (failure) or rejection of transplanted organs and tissues

Dosage Regimen

The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen.

Determine the initial oral dose individually based on transplanted organ and patient status. Administer the first dose no earlier than 6 hours after liver transplantation and within 24 hours after kidney transplantation.

Take capsules consistently, either always with food or always on an empty stomach, as food decreases bioavailability. Take twice daily, approximately every 12 hours.

For liver transplantation, the initial oral dose is 0.10-0.20 mg/kg/day in two divided doses. For kidney transplantation, the initial oral dose is 0.20 mg/kg/day in two divided doses.

Adjust subsequent doses based on frequent therapeutic drug monitoring of whole blood trough concentrations. Titrate to achieve and maintain target therapeutic ranges to prevent graft rejection while minimizing toxicity.

Monitor blood concentrations especially carefully when initiating or discontinuing concomitant drugs known to interact with Tacrolimus. Adjust dose promptly in response to significant concentration changes, clinical evidence of toxicity, or rejection.

For patients with hepatic impairment, use lower initial doses due to reduced metabolism and clearance. Monitor blood concentrations closely in patients with renal impairment, as dose adjustment may be necessary.

Adverse Reactions

From the cardiovascular system very common – myocardial ischemia, tachycardia, arterial hypertension, bleeding, thromboembolic and ischemic complications, peripheral circulation disorders, arterial hypotension; uncommon – ventricular arrhythmias and cardiac arrest, heart failure, cardiomyopathies, ventricular hypertrophy, supraventricular arrhythmias, palpitations, abnormal ECG parameters, heart rhythm disorders, heart rate and pulse, myocardial infarction, deep vein thrombosis of the extremities, shock; rare – pericardial effusion; very rare – echocardiogram abnormalities.

From the hematopoietic system common – anemia, leukopenia, thrombocytopenia, leukocytosis; uncommon – pancytopenia, neutropenia; rare – thrombotic thrombocytopenic purpura.

From the blood coagulation system uncommon – coagulopathies, deviations in coagulogram parameters, rare – hypoprothrombinemia.

From the nervous system very common – tremor, headache, insomnia; common – epileptiform seizures, consciousness disorders, paresthesia and dysesthesia, peripheral neuropathies, dizziness, writing impairment, anxiety, confusion and disorientation, depression, depressed mood, emotional disorders, nightmares, hallucinations, mental disorders; uncommon – coma, CNS hemorrhages and cerebrovascular disorders, paralysis and paresis, encephalopathy, speech and articulation disorders, amnesia, psychotic disorders; rare – increased muscle tone; very rare – myasthenia.

From the organ of vision: common – blurred vision, photophobia, eye diseases; uncommon – cataract; rare – blindness.

From the organ of hearing: common – tinnitus (ringing in the ears); uncommon – hearing loss; rare – neurosensory deafness; very rare – hearing disorders.

From the respiratory system common – dyspnea, pulmonary parenchymal disorders, pleural effusion, pharyngitis, cough, nasal congestion, rhinitis; uncommon – respiratory failure, airway disorders, asthma; rare – acute respiratory distress syndrome.

From the digestive system very common – diarrhea, nausea; common – inflammatory diseases of the gastrointestinal tract, gastrointestinal ulcers and perforations, gastrointestinal bleeding, stomatitis and ulceration of the oral mucosa, ascites, vomiting, gastrointestinal and abdominal pain, dyspepsia, constipation, flatulence, feelings of bloating and fullness in the abdomen, loose stools, symptoms of gastrointestinal disorders; uncommon – paralytic intestinal obstruction (paralytic ileus), peritonitis, acute and chronic pancreatitis, increased blood amylase levels, gastroesophageal reflux disease, impaired gastric evacuation function; rare – subileus, pancreatic pseudocysts.

From the liver: common – increased levels of liver enzymes, liver function disorders, cholestasis and jaundice, liver cell damage and hepatitis, cholangitis; rare – hepatic artery thrombosis, obliterating endophlebitis of the hepatic veins; very rare – liver failure, bile duct stenosis.

From the urinary system: very common – renal function impairment; common – renal failure, acute renal failure, oliguria, acute tubular necrosis, toxic nephropathy, urinary syndrome, bladder and urethra disorders; uncommon – anuria, hemolytic uremic syndrome; very rare – nephropathy, hemorrhagic cystitis.

Dermatological reactions: common – itching, rash, alopecia, acne, hyperhidrosis; uncommon – dermatitis, photosensitivity; rare – toxic epidermal necrolysis (Lyell’s syndrome); very rare – Stevens-Johnson syndrome.

From the musculoskeletal system: common – arthralgia, muscle cramps, limb pain, back pain; uncommon – joint disorders.

From the endocrine system very common – hyperglycemia, diabetes mellitus; rare – hirsutism.

From metabolism very common – hyperkalemia; common – hypomagnesemia, hypophosphatemia, hypokalemia, hypocalcemia, hyponatremia, hypervolemia, hyperuricemia, decreased appetite, anorexia, metabolic acidosis, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, electrolyte disorders; uncommon – dehydration, hypoproteinemia, hyperphosphatemia, hypoglycemia.

Infections and infestations: during therapy with tacrolimus, as with other immunosuppressants, the risk of local and generalized infectious diseases (viral, bacterial, fungal, protozoal) increases. The course of previously diagnosed infectious diseases may worsen; cases of BK virus-associated nephropathy, as well as progressive multifocal leukoencephalopathy.

Injuries, poisonings, procedural complications: common – primary graft dysfunction.

Benign, malignant and unidentified neoplasms: patients receiving immunosuppressive therapy have a higher risk of malignant tumors. With the use of tacrolimus, the occurrence of both benign and malignant neoplasms has been noted, including Epstein-Barr virus-associated lymphoproliferative diseases and skin cancer.

From the reproductive system uncommon – dysmenorrhea and uterine bleeding. A negative effect of tacrolimus on male fertility, expressed in a decrease in the number and motility of spermatozoa, has been established in rats.

Allergic reactions: allergic and anaphylactic reactions have been observed in patients taking Tacrolimus.

From the body as a whole: common – asthenia, febrile conditions, edema, pain and discomfort, increased blood alkaline phosphatase levels, weight gain, body temperature perception disorders; uncommon – multiple organ failure, flu-like syndrome, ambient temperature perception disorders, feeling of chest tightness, feeling of anxiety, malaise, increased blood LDH activity, weight loss; rare – thirst, loss of balance (falls), feeling of stiffness in the chest, difficulty moving; very rare – increase in adipose tissue mass.

Contraindications

Pregnancy; lactation (breastfeeding) period; hypersensitivity to tacrolimus.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and during lactation (breastfeeding).

Special Precautions

In the initial post-transplantation period, regular monitoring of the following parameters should be carried out: blood pressure, ECG, neurological status and vision condition, fasting blood glucose level, electrolyte concentrations (especially potassium), liver and kidney function indicators, hematological parameters, coagulogram, proteinemia level. If clinically significant changes are present, correction of immunosuppressive therapy is necessary.

During the use of tacrolimus, the prescription of herbal preparations containing St. John’s wort (Hypericum perforatum), as well as other herbal remedies that may cause a decrease (change) in the concentration of tacrolimus in the blood and have an adverse effect on the clinical effect of tacrolimus, should be avoided.

In diarrhea, the concentration of tacrolimus in the blood can change significantly; if diarrhea occurs, careful monitoring of tacrolimus blood concentrations is necessary.

Simultaneous use of cyclosporine and tacrolimus should be avoided, and caution should be exercised when treating with tacrolimus in patients who have previously received cyclosporine.

Effect on ability to drive vehicles and mechanisms

Tacrolimus may cause visual and neurological disorders, especially in combination with alcohol. During treatment, patients should refrain from driving vehicles and working with mechanisms.

Drug Interactions

After oral administration, Tacrolimus undergoes metabolism in the intestinal cytochrome CYP3A4 system. Simultaneous administration of drugs or herbal medicines with established inhibitory or inducing effects on CYP3A4 may respectively increase or decrease tacrolimus blood concentrations.

Based on clinical experience, it has been established that the following drugs can significantly increase the concentration of tacrolimus in the blood: antifungal agents (ketoconazole, fluconazole, itraconazole, voriconazole), macrolide antibiotics (erythromycin), HIV protease inhibitors (ritonavir) (with this combination, a dose reduction of tacrolimus may be required). Pharmacokinetic studies have shown that the increase in tacrolimus blood concentration is primarily a consequence of an increase in the bioavailability of oral tacrolimus caused by inhibition of intestinal metabolism of tacrolimus. Suppression of hepatic metabolism of tacrolimus plays a secondary role.

A less pronounced drug interaction was observed with the simultaneous use of tacrolimus with clotrimazole, clarithromycin, josamycin, nifedipine, nicardipine, diltiazem, verapamil, danazol, ethinyl estradiol, omeprazole and nefazodone.

In vitro studies have shown that the following substances are potential inhibitors of tacrolimus metabolism: bromocriptine, cortisone, dapsone, ergotamine, gestodene, lidocaine, mephenytoin, miconazole, midazolam, nilvadipine, norethindrone, quinidine, tamoxifen, (triacetyl)oleandomycin.

It is recommended to avoid the consumption of grapefruit juice due to the possibility of increasing the level of tacrolimus in the blood.

Lansoprazole and cyclosporine may potentially inhibit CYP3A4-mediated metabolism of tacrolimus and increase its blood concentration.

Based on clinical experience, it has been established that the following drugs can significantly reduce the concentration of tacrolimus in the blood: rifampicin, phenytoin, St. John’s wort (Hypericum perforatum).

Clinically significant interaction was observed with phenobarbital.

Corticosteroids in maintenance doses usually reduce the concentration of tacrolimus in the blood. High doses of prednisolone or methylprednisolone used to treat acute rejection may increase or decrease the concentration of tacrolimus in the blood.

Carbamazepine, metamizole and isoniazid can reduce the concentration of tacrolimus in the blood.

Tacrolimus inhibits the CYP3A4 isoenzyme and, when taken simultaneously, may affect drugs metabolized by the CYP3A4 isoenzyme. The T_1/2 of cyclosporine increases when used concomitantly with tacrolimus. Synergistic/additive nephrotoxic effects may also be observed. For these reasons, simultaneous administration of cyclosporine and tacrolimus is not recommended, and caution should be exercised when prescribing tacrolimus to patients who have previously taken cyclosporine.

Tacrolimus increases the concentration of phenytoin in the blood.

Tacrolimus may reduce the clearance of hormonal contraceptives.

Experimental animal studies have shown that Tacrolimus may potentially reduce the clearance and increase the T_1/2 of phenobarbital and antipyrine.

Prokinetic agents (metoclopramide, cisapride), cimetidine, magnesium and aluminum hydroxide may increase the bioavailability of tacrolimus.

Simultaneous use of tacrolimus with drugs that have nephro- or neurotoxicity (for example, aminoglycosides, gyrase inhibitors, vancomycin, co-trimoxazole, NSAIDs, ganciclovir, acyclovir) may enhance these effects.

Enhanced nephrotoxicity was observed with the combined use of tacrolimus with amphotericin B and ibuprofen.

Tacrolimus may promote or enhance hyperkalemia (simultaneous use of potassium or potassium-sparing diuretics in high doses should be avoided).

Immunosuppressants may alter the body’s response to vaccination. Vaccination during treatment with tacrolimus may be less effective. The use of live attenuated vaccines should be avoided.

Tacrolimus actively binds to plasma proteins. Possible competitive interaction of tacrolimus with drugs that have high affinity for plasma proteins (NSAIDs, oral anticoagulants, oral hypoglycemic agents) should be taken into account.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.

Medical Disclaimer

Brand (or Active Substance), Marketing Authorisation Holder, Dosage Form

Tacrolimus [Lok-Beta Pharmaceuticals (India), Private Limited (India)]
Capsules 0.5 mg: 10, 20 or 30 pcs.

Marketing Authorization Holder

Lok-Beta Pharmaceuticals (India), Private Limited (India)

Dosage Form

Tacrolimus

Capsules 0.5 mg: 10, 20 or 30 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin No. 5, opaque, light blue; capsule contents – powder white or almost white.

	1 caps.
Tacrolimus monohydrate	0.511 mg,
Equivalent to tacrolimus content	0.5 mg

Excipients : lactose monohydrate – 79.114 mg, talc – 4.375 mg, hypromellose – 0.5 mg, croscarmellose sodium – 0.5 mg.

Capsule shell composition: gelatin – 23.2112 mg, purified water – 4.06 mg, sodium lauryl sulfate – 0.0224 mg, methylparaben – 0.224 mg, propylparaben – 0.056 mg, titanium dioxide – 0.42 mg, brilliant blue dye (E 133) – 0.0064 mg.

10 pcs. – blisters made of aluminum foil (1) – cardboard packs.
10 pcs. – blisters made of aluminum foil (2) – cardboard packs.
10 pcs. – blisters made of aluminum foil (3) – cardboard packs.
100 pcs. – polyethylene bags (1) – jars (1) – cardboard boxes (for hospitals).
100 pcs. – polyethylene bags (1) – jars (6) – cardboard boxes (for hospitals).
100 pcs. – polyethylene bags (1) – jars (12) – cardboard boxes (for hospitals).
100 pcs. – polyethylene bags (1) – jars (24) – cardboard boxes (for hospitals).
500 pcs. – polyethylene bags (1) – jars (1) – cardboard boxes (for hospitals).
500 pcs. – polyethylene bags (1) – jars (6) – cardboard boxes (for hospitals).
500 pcs. – polyethylene bags (1) – jars (12) – cardboard boxes (for hospitals).
500 pcs. – polyethylene bags (1) – jars (24) – cardboard boxes (for hospitals).

Tacrolimus [Lok-Beta Pharmaceuticals (India), Private Limited (India)]
Capsules 1 mg: 10, 20 or 30 pcs.

Marketing Authorization Holder

Lok-Beta Pharmaceuticals (India), Private Limited (India)

Dosage Form

Tacrolimus

Capsules 1 mg: 10, 20 or 30 pcs.

Dosage Form, Packaging, and Composition

Capsules are hard, opaque, gelatin, size No. 5, light greenish-blue in color; the capsule contents are a white or almost white powder.

	1 capsule
Tacrolimus monohydrate	1.022 mg,
Equivalent to tacrolimus content	1 mg

Excipients: lactose monohydrate – 77.228 mg, talc – 4.75 mg, hypromellose – 1 mg, croscarmellose sodium – 1 mg.

Composition of the gelatin capsules: gelatin – 23.3296 mg, purified water – 4.06 mg, sodium lauryl sulfate – 0.0224 mg, methylparaben – 0.224 mg, propylparaben – 0.056 mg, titanium dioxide – 0.3078 mg, brilliant blue dye (E133) – 0.0002 mg.

Tacrolimus [Lok-Beta Pharmaceuticals (India), Private Limited (India)]
Capsules 5 mg: 10, 20 or 30 pcs.

Marketing Authorization Holder

Lok-Beta Pharmaceuticals (India), Private Limited (India)

Dosage Form

Tacrolimus

Capsules 5 mg: 10, 20 or 30 pcs.

Dosage Form, Packaging, and Composition

Capsules are hard, opaque, gelatin, size No. 5, light orange in color; the capsule contents are a white or almost white powder.

	1 capsule
Tacrolimus monohydrate	5.11 mg,
Equivalent to tacrolimus content	5 mg

Excipients: lactose monohydrate – 66.14 mg, talc – 3.75 mg, hypromellose – 5 mg, croscarmellose sodium – 5 mg.

Composition of the gelatin capsules: gelatin – 23.328 mg, purified water – 4.06 mg, sodium lauryl sulfate – 0.0224 mg, methylparaben – 0.224 mg, propylparaben – 0.056 mg, titanium dioxide – 0.3078 mg, sunset yellow dye (E110) – 0.0018 mg.

Tacrolimus [Atoll LLC (Russia)]
Capsules 0.5 mg: 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 30, 35, 40, 50, 70 or 100 pcs.
Capsules 1 mg: 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 30, 35, 40, 50, 70 or 100 pcs.
Capsules 5 mg: 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 30, 35, 40, 50, 70 or 100 pcs.

Marketing Authorization Holder

Atoll LLC (Russia)

Manufactured By

Ozon, LLC (Russia)

Dosage Forms

	Tacrolimus	Capsules 0.5 mg: 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 30, 35, 40, 50, 70 or 100 pcs.
		Capsules 1 mg: 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 30, 35, 40, 50, 70 or 100 pcs.
		Capsules 5 mg: 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 30, 35, 40, 50, 70 or 100 pcs.

Dosage Form, Packaging, and Composition

Capsules are hard gelatin, size No. 2; the body is yellow with a light beige tint, the cap is yellow with a light beige tint, opaque; the capsule contents: a mixture of powder and granules, white or almost white in color; compaction of the capsule contents into lumps shaped like the capsule is allowed, easily destroyed by light pressure with a glass rod.

	1 capsule
Tacrolimus monohydrate	0.511 mg
Equivalent to tacrolimus content	0.5 mg

Excipients: lactose monohydrate (milk sugar) – 226.252 mg, croscarmellose sodium – 0.5 mg, hypromellose – 2.277 mg, magnesium stearate – 0.46 mg.

Composition of the capsule body: iron oxide yellow dye — 0.1%, titanium dioxide — 2%, gelatin – up to 100%.
Composition of the capsule cap: iron oxide yellow dye — 0.1%, titanium dioxide — 2%, gelatin – up to 100%.

1 pc. – contour cell packaging (1) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
1 pc. – contour cell packaging (2) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
1 pc. – contour cell packaging (3) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
1 pc. – contour cell packaging (4) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
1 pc. – contour cell packaging (5) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
1 pc. – contour cell packaging (10) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
7 pcs. – contour cell packaging (1) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
7 pcs. – contour cell packaging (2) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
7 pcs. – contour cell packaging (3) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
7 pcs. – contour cell packaging (4) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
7 pcs. – contour cell packaging (5) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
7 pcs. – contour cell packaging (10) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
10 pcs. – contour cell packaging (1) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
10 pcs. – contour cell packaging (3) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
10 pcs. – contour cell packaging (4) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
10 pcs. – contour cell packaging (5) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
10 pcs. – contour cell packaging (10) – bags made of combined materials based on aluminum foil (1) – cardboard packs.
10 pcs. – dark glass bottles (1) – cardboard packs.
20 pcs. – dark glass bottles (1) – cardboard packs.
30 pcs. – dark glass bottles (1) – cardboard packs.
40 pcs. – dark glass bottles (1) – cardboard packs.
50 pcs. – dark glass bottles (1) – cardboard packs.
100 pcs. – dark glass bottles (1) – cardboard packs.

Capsules are hard gelatin, size No. 2; the body is yellow, the cap is yellow, opaque; the capsule contents: a mixture of powder and granules, white or almost white in color; compaction of the capsule contents into lumps shaped like the capsule is allowed, easily destroyed by light pressure with a glass rod.

	1 capsule
Tacrolimus monohydrate	1.022 mg
Equivalent to tacrolimus content	1 mg

Excipients: lactose monohydrate (milk sugar) – 225.241 mg, croscarmellose sodium – 1 mg, hypromellose – 2.277 mg, magnesium stearate – 0.46 mg.

Composition of the capsule body: quinoline yellow dye – 0.75%, sunset yellow dye – 0.0059%, titanium dioxide – 2%, gelatin – up to 100%.
Composition of the capsule cap: quinoline yellow dye – 0.75%, sunset yellow dye – 0.0059%, titanium dioxide – 2%, gelatin – up to 100%.

Capsules are hard gelatin, size No. 2; the body is white, the cap is white, opaque; the capsule contents: a mixture of powder and granules, white or almost white in color; compaction of the capsule contents into lumps shaped like the capsule is allowed, easily destroyed by light pressure with a glass rod.

	1 capsule
Tacrolimus monohydrate	5.11 mg
Equivalent to tacrolimus content	5 mg

Excipients: lactose monohydrate (milk sugar) – 217.153 mg, croscarmellose sodium – 5 mg, hypromellose – 2.277 mg, magnesium stearate – 0.46 mg.

Composition of the capsule body: titanium dioxide – 2%, gelatin – up to 100%.
Composition of the capsule cap: titanium dioxide – 2%, gelatin – up to 100%.

Tacrolimus [Nanopharma Development, LLC (Russia)]
Capsules 0.5 mg: 10, 30, 50, 60, 80 or 100 pcs.
Capsules 1 mg: 10, 30, 50, 60, 80 or 100 pcs.
Capsules 5 mg: 10, 30, 50, 60, 80 or 100 pcs.

Marketing Authorization Holder

Nanopharma Development, LLC (Russia)

Manufactured By

Nanopharma Development, LLC (Russia)

Izvarino Pharma LLC (Russia)

Primary Packaging

NANOPHARMA DEVELOPMENT, LLC (Russia)

IZVARINO PHARMA, LLC (Russia)

Secondary Packaging

IZVARINO PHARMA, LLC (Russia)

Quality Control Release

NANOPHARMA DEVELOPMENT, LLC (Russia)

IZVARINO PHARMA, LLC (Russia)

Dosage Forms

	Tacrolimus	Capsules 0.5 mg: 10, 30, 50, 60, 80 or 100 pcs.
		Capsules 1 mg: 10, 30, 50, 60, 80 or 100 pcs.
		Capsules 5 mg: 10, 30, 50, 60, 80 or 100 pcs.

Dosage Form, Packaging, and Composition

Capsules are hard gelatin, size No. 4, the capsule body is white or almost white, opaque, the capsule cap is yellow, opaque; the capsule contents are a powder or compacted powder mass, white or white with a yellowish or brownish tint.

	1 capsule
Tacrolimus (as tacrolimus monohydrate)	0.5 mg

Excipients: lactose – 136.27 mg, tartaric acid – 0.07 mg, hypromellose – 0.05 mg, croscarmellose sodium – 1 mg, colloidal silicon dioxide – 0.7 mg, magnesium stearate – 1.4 mg.

Capsule body: titanium dioxide – 2%, gelatin – up to 100%.
Capsule cap: titanium dioxide – 1.3333%, quinoline yellow dye – 0.9197%, sunset yellow dye – 0.0044%, gelatin – up to 100%.

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (5) – cardboard packs.
10 pcs. – contour cell packaging (6) – cardboard packs.
10 pcs. – contour cell packaging (8) – cardboard packs.
10 pcs. – contour cell packaging (10) – cardboard packs.

Capsules are hard gelatin, size No. 4, the capsule body and cap are white or almost white, opaque; the capsule contents are a powder or compacted powder mass, white or white with a yellowish or brownish tint.

	1 capsule
Tacrolimus (as tacrolimus monohydrate)	1 mg

Excipients: lactose – 133.84 mg, tartaric acid – 0.14 mg, hypromellose – 0.1 mg, croscarmellose sodium – 2.8 mg, colloidal silicon dioxide – 0.7 mg, magnesium stearate – 1.4 mg.

Capsule body:titanium dioxide – 2%, gelatin – up to 100%.

Capsule cap:titanium dioxide – 2%, gelatin – up to 100%.

10 pcs. – contour cell packaging (1) – cardboard packs.

10 pcs. – contour cell packaging (3) – cardboard packs.

10 pcs. – contour cell packaging (5) – cardboard packs.

10 pcs. – contour cell packaging (6) – cardboard packs.

10 pcs. – contour cell packaging (8) – cardboard packs.

10 pcs. – contour cell packaging (10) – cardboard packs.

Capsules hard gelatin No. 4, capsule body white or almost white, opaque, capsule cap green, opaque; capsule contents – powder or compacted powder mass white or white with a yellowish or brownish tint.

	1 caps.
Tacrolimus (in the form of tacrolimus monohydrate)	5 mg

Excipients: lactose – 124.59 mg, tartaric acid – 0.7 mg, hypromellose – 0.5 mg, croscarmellose sodium – 7 mg, colloidal silicon dioxide – 0.7 mg, magnesium stearate – 1.4 mg.

Capsule body:titanium dioxide – 2%, gelatin – up to 100%.

Capsule cap:titanium dioxide – 1%, indigo carmine – 0.3%, iron oxide yellow dye – 1.7143%, gelatin – up to 100%.

10 pcs. – contour cell packaging (1) – cardboard packs.

Capsules hard gelatin, size No. 4, with a yellow body and a green cap; capsule contents – white or almost white granular powder.

	1 caps.
Tacrolimus (calculated on 100% dry substance)	1 mg

Excipients: lactose – 127.6 mg, croscarmellose sodium – 5 mg, hypromellose E5 – 5 mg, magnesium stearate – 1.4 mg.

Shell composition body – gelatin – 81.56%, methylparaben – 0.8%, propylparaben – 0.2%, sodium lauryl sulfate – 0.1%, purified water – 14.5%, brilliant blue FCF dye – 0.0015%, quinoline yellow dye – 0.09%, sunset yellow FCF dye – 0.041%, titanium dioxide – 2.7%; cap – gelatin – 81.987%, methylparaben – 0.8%, propylparaben – 0.2%, sodium lauryl sulfate – 0.1%, purified water – 14.5%, brilliant blue FCF dye – 0.052%, quinoline yellow dye – 0.068%, azorubine – 0.023%, titanium dioxide – 2.27%.

10 pcs. – contour non-cell packaging (5) – cardboard packs.

Medixlife (Author)

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