Tacforius: Uses, Dosage & Side Effects
A calcineurin inhibitor immunosuppressant used to prevent organ rejection after kidney or liver transplantation, available as prolonged-release capsules for convenient once-daily dosing
Tacforius (tacrolimus) is a potent immunosuppressive medicine belonging to the calcineurin inhibitor class. It is used to prevent organ rejection (graft rejection) in adult patients who have received a kidney or liver transplant. Tacforius works by suppressing the activity of T-cells, a type of white blood cell responsible for recognizing and attacking the transplanted organ. The prolonged-release formulation allows for once-daily dosing, which may improve adherence compared to twice-daily immediate-release tacrolimus products. Tacforius requires a prescription and must be initiated and supervised by a physician experienced in transplant medicine. Regular blood level monitoring is mandatory to ensure the drug remains within its narrow therapeutic window.
Quick Facts: Tacforius
Key Takeaways
- Tacforius (tacrolimus prolonged-release) is a calcineurin inhibitor immunosuppressant taken once daily to prevent organ rejection after kidney or liver transplantation; it works by blocking T-cell activation through inhibition of the calcineurin-NFAT signaling pathway.
- Therapeutic drug monitoring (TDM) of tacrolimus trough blood levels is mandatory throughout treatment, as the drug has a narrow therapeutic index – levels that are too low risk rejection, while levels that are too high risk serious toxicity including nephrotoxicity and neurotoxicity.
- Tacforius must not be substituted with other tacrolimus formulations (immediate-release capsules or granules) on a milligram-for-milligram basis without medical supervision, because the bioavailability and pharmacokinetic profiles differ significantly between formulations.
- Common side effects include tremor, headache, kidney impairment, hyperglycemia (new-onset diabetes after transplantation), hypertension, diarrhea, and insomnia; serious risks include opportunistic infections, lymphoproliferative disorders, and thrombotic microangiopathy.
- Numerous drug interactions exist, particularly with CYP3A4 inhibitors (e.g., ketoconazole, voriconazole) that increase tacrolimus levels and CYP3A4 inducers (e.g., rifampicin, St John’s Wort) that decrease them; ciclosporin must never be used concurrently with tacrolimus.
What Is Tacforius and What Is It Used For?
Tacforius contains the active substance tacrolimus (as monohydrate), a macrolide lactone originally isolated from the soil bacterium Streptomyces tsukubaensis. Tacrolimus is one of the most widely used immunosuppressive agents in solid organ transplantation worldwide and is included on the World Health Organization (WHO) Model List of Essential Medicines. The Tacforius brand, manufactured by Teva, offers tacrolimus in a prolonged-release (extended-release) hard capsule formulation that permits convenient once-daily oral administration.
The mechanism of action of tacrolimus centers on the inhibition of calcineurin, a calcium- and calmodulin-dependent serine/threonine phosphatase that plays a pivotal role in T-cell signal transduction. Upon entering the T-cell, tacrolimus binds with high affinity to the intracellular immunophilin FK-binding protein 12 (FKBP-12). The resulting tacrolimus-FKBP-12 complex then binds to and inhibits calcineurin. Under normal circumstances, calcineurin dephosphorylates the nuclear factor of activated T-cells (NFAT), enabling its translocation into the nucleus where it drives the transcription of interleukin-2 (IL-2) and other pro-inflammatory cytokines essential for T-cell proliferation and the adaptive immune response. By blocking calcineurin, tacrolimus effectively prevents NFAT activation, suppresses IL-2 production, and halts the cascade of T-cell-mediated immune responses that would lead to transplant rejection.
In addition to its effects on T-cells, tacrolimus has been shown to inhibit the release of other cytokines including interleukin-3 (IL-3), interleukin-4 (IL-4), tumor necrosis factor alpha (TNF-alpha), and interferon-gamma (IFN-gamma). It also suppresses the expression of the IL-2 receptor on T-cells, further reducing the immune system’s ability to mount a rejection response. This broad immunosuppressive profile makes tacrolimus a cornerstone of modern transplant immunosuppressive regimens, typically used in combination with corticosteroids and an antiproliferative agent such as mycophenolate mofetil or mycophenolic acid.
Tacforius is indicated for the following uses in adult patients:
- Prevention of kidney transplant rejection: Tacforius is used as part of a multi-drug immunosuppressive regimen to prevent the body from rejecting a transplanted kidney. It is initiated at the time of transplantation and continued long-term, often for the lifetime of the functioning graft. Kidney transplantation is the treatment of choice for end-stage renal disease, and effective immunosuppression is critical for graft and patient survival.
- Prevention of liver transplant rejection: Tacforius is similarly used to prevent rejection of a transplanted liver. Liver transplantation is performed for patients with end-stage liver disease or acute liver failure, and tacrolimus-based immunosuppression has been a standard of care in liver transplantation for decades, with large clinical trials demonstrating superior graft survival compared to ciclosporin-based regimens.
- Rescue therapy (rejection treatment): Tacforius may be used as rescue therapy in patients who are experiencing transplant rejection despite treatment with other immunosuppressive agents. In this setting, tacrolimus may replace a failing immunosuppressive regimen or be added to intensify immunosuppression, with the goal of reversing the rejection episode and preserving organ function.
The prolonged-release formulation of tacrolimus in Tacforius provides a modified pharmacokinetic profile compared to immediate-release tacrolimus products such as Prograf. The extended-release technology results in a slower absorption rate, a lower and later peak concentration (Cmax), and a more sustained drug exposure over the 24-hour dosing interval. This pharmacokinetic profile supports once-daily dosing, which has been associated with improved medication adherence in transplant recipients – a critical factor given that even small gaps in immunosuppressive therapy can precipitate acute rejection episodes and graft loss.
Tacforius is designed for once-daily oral administration, taken preferably in the morning on an empty stomach. Studies have shown that simplifying immunosuppressive regimens from twice-daily to once-daily dosing can improve patient adherence by up to 15–20%. In transplant medicine, non-adherence to immunosuppressive therapy is one of the leading preventable causes of late graft loss, making the convenience of once-daily dosing clinically significant. However, it is essential that Tacforius is not interchanged with immediate-release tacrolimus formulations without close medical supervision, as the bioavailability and blood level profiles differ.
What Should You Know Before Taking Tacforius?
Contraindications
Tacforius must not be used in certain situations. Understanding these contraindications is essential before starting treatment.
- Hypersensitivity: Do not take Tacforius if you are allergic to tacrolimus, to other macrolide compounds (such as sirolimus or macrolide antibiotics like erythromycin), or to any of the other ingredients in the capsules, including lactose, hypromellose, ethylcellulose, magnesium stearate, or the capsule shell components.
- Concurrent use with ciclosporin: Tacrolimus must never be used together with ciclosporin (another calcineurin inhibitor). The combination produces additive and potentially synergistic nephrotoxicity and immunosuppression without clinical benefit. If switching from ciclosporin to tacrolimus, a washout period of at least 24 hours after the last ciclosporin dose is required, with monitoring of ciclosporin blood levels to confirm clearance before initiating tacrolimus.
Warnings and Precautions
Tacrolimus has been associated with the development of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS). These are potentially life-threatening conditions characterized by low platelet count, microangiopathic haemolytic anaemia (fragmented red blood cells on blood smear), and organ damage – particularly of the kidneys and brain. Symptoms may include unusual bruising, petechiae, fatigue, jaundice, decreased urine output, confusion, and seizures. If TMA is suspected, tacrolimus should be discontinued promptly and aggressive supportive treatment initiated. Contact your transplant team immediately if you develop unexplained bruising, bleeding, or dark-colored urine.
Before and during treatment with Tacforius, discuss the following with your transplant team:
- QT prolongation: Tacrolimus may prolong the QT interval on the electrocardiogram, which can predispose to potentially fatal cardiac arrhythmias including torsades de pointes. Particular caution is advised in patients with congenital long QT syndrome, pre-existing heart disease, electrolyte disturbances (especially low potassium or magnesium), or those taking other QT-prolonging medications. Regular ECG monitoring may be recommended.
- Nephrotoxicity: Tacrolimus is inherently nephrotoxic. It can cause acute and chronic kidney damage, including tubular damage, arteriolar hyalinosis, and thrombotic microangiopathy. Kidney function must be monitored regularly with serum creatinine, estimated GFR, and urine analysis. Dose adjustments are often necessary to balance immunosuppression with preservation of kidney function.
- Neurotoxicity: Neurological side effects ranging from mild (tremor, headache) to severe (seizures, encephalopathy, posterior reversible encephalopathy syndrome [PRES]) may occur. PRES is characterized by headache, altered consciousness, visual disturbances, and seizures, often with characteristic findings on brain MRI. If PRES is suspected, blood pressure should be controlled and tacrolimus reduced or discontinued.
- New-onset diabetes after transplantation (NODAT): Tacrolimus has a well-documented diabetogenic effect. It can impair insulin secretion from pancreatic beta cells and increase insulin resistance, leading to hyperglycemia and, in some patients, new-onset diabetes mellitus requiring treatment with oral hypoglycemics or insulin. Blood glucose should be monitored regularly, particularly in the early post-transplant period.
- Sun exposure and skin cancer: Immunosuppressed patients have a significantly increased risk of developing skin malignancies, particularly squamous cell carcinoma and basal cell carcinoma. You should minimize sun exposure, wear protective clothing, and use high-SPF sunscreen. Avoid tanning beds. Regular dermatological screening is recommended.
- Lymphoproliferative disorders: Long-term immunosuppression with tacrolimus increases the risk of post-transplant lymphoproliferative disorder (PTLD), a potentially life-threatening condition related to Epstein-Barr virus (EBV) infection. The risk is highest in EBV-seronegative patients and during the first year after transplantation.
- Herbal medicines – St John’s Wort: St John’s Wort (Hypericum perforatum) and other herbal remedies must be strictly avoided during tacrolimus therapy. St John’s Wort is a potent inducer of CYP3A4 and P-glycoprotein and can dramatically reduce tacrolimus blood levels, leading to subtherapeutic immunosuppression and acute graft rejection. Always consult your transplant team before taking any herbal products or dietary supplements.
- Handling precautions: Tacforius capsules should be swallowed whole with liquid (preferably water) immediately after removal from the blister. They should not be crushed, chewed, or opened. The capsule contents should not come into contact with skin or mucous membranes; if accidental contact occurs, the area should be washed with soap and water.
- Pediatric use: Tacforius prolonged-release capsules are not recommended for children and adolescents under 18 years of age due to insufficient data on safety and efficacy in this population. Other tacrolimus formulations may be used in pediatric transplant patients under specialist guidance.
Pregnancy and Breastfeeding
Tacrolimus crosses the placental barrier and is found in fetal blood. Data from pregnant transplant recipients indicate that tacrolimus use during pregnancy is associated with an increased risk of premature delivery (approximately 50% of exposed pregnancies), low birth weight, and neonatal complications including transient kidney impairment, hyperkalemia (high potassium levels), and metabolic disturbances in the newborn. There have also been reports of an increased incidence of preeclampsia and gestational diabetes in mothers taking tacrolimus.
However, discontinuing immunosuppressive therapy during pregnancy risks acute transplant rejection, which poses a greater threat to both mother and fetus. Therefore, pregnancy in transplant recipients must be carefully planned with the transplant team. Tacrolimus is generally considered one of the safer immunosuppressive options during pregnancy (compared to mycophenolate mofetil, which is contraindicated in pregnancy), but close monitoring of drug levels, kidney function, blood pressure, and fetal development is mandatory. Tacrolimus blood levels tend to fluctuate during pregnancy due to physiological changes in blood volume, protein binding, and metabolism.
Tacrolimus is excreted in human breast milk. Although the amounts detected in breast milk are generally low, a risk to the nursing infant cannot be excluded. The decision on whether to breastfeed during tacrolimus therapy should be made in consultation with your transplant team, weighing the benefits of breastfeeding against the potential risks to the infant.
Driving and Operating Machinery
Tacrolimus may cause neurological side effects such as tremor, dizziness, headache, blurred vision, and impaired consciousness. These effects may impair your ability to drive or operate machinery safely. If you experience any of these symptoms, do not drive, cycle, or operate machinery until the symptoms have resolved. Discuss with your transplant team if you have concerns about your ability to drive safely.
Important Information About Ingredients
Tacforius capsules contain lactose (as lactose monohydrate). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
The 5 mg capsule shell contains Ponceau 4R (E124), a red azo dye that may cause allergic reactions in susceptible individuals, including those with aspirin sensitivity. The 0.5 mg and 1 mg capsule shells contain iron oxide yellow (E172), and the 3 mg capsule shell contains iron oxide red (E172). All capsules contain titanium dioxide (E171). Patients with known hypersensitivity to any of these colorants should inform their transplant team.
How Does Tacforius Interact with Other Drugs?
Tacrolimus is extensively metabolized by the cytochrome P450 enzyme CYP3A4 (and to a lesser extent CYP3A5) in the liver and intestinal wall. It is also a substrate of the efflux transporter P-glycoprotein (P-gp). Consequently, any drug, food, or herbal product that inhibits or induces CYP3A4 or P-gp can significantly alter tacrolimus blood concentrations. Because tacrolimus has a narrow therapeutic index, even modest changes in blood levels can lead to either toxicity (if levels are too high) or graft rejection (if levels are too low). Therapeutic drug monitoring and dose adjustments are essential whenever interacting medications are started, stopped, or have their doses changed.
Major Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Ciclosporin | Additive/synergistic nephrotoxicity and immunosuppression; prolongs ciclosporin half-life | Absolute contraindication – never combine; washout period required when switching |
| Ketoconazole, Voriconazole, Itraconazole (azole antifungals) | Strong CYP3A4 inhibition; dramatically increases tacrolimus blood levels (up to 5–10 fold with voriconazole) | Dose reduction of tacrolimus usually required (often 50–80%); frequent blood level monitoring mandatory |
| Erythromycin, Clarithromycin (macrolide antibiotics) | CYP3A4 inhibition; increases tacrolimus levels; erythromycin may increase levels 2–4 fold | Use with caution; consider azithromycin as alternative (minimal CYP3A4 interaction); monitor levels closely |
| Rifampicin (rifampin) | Potent CYP3A4 inducer; can reduce tacrolimus levels by 60–90%, risking graft rejection | Avoid combination if possible; if essential, major dose increase and daily level monitoring required |
| Phenytoin, Carbamazepine, Phenobarbital (anticonvulsants) | CYP3A4 induction; significantly reduces tacrolimus blood levels | Dose increase required; consider non-inducing alternatives (levetiracetam, gabapentin); monitor levels |
| St John’s Wort (Hypericum perforatum) | Potent CYP3A4 and P-gp inducer; can cause precipitous drop in tacrolimus levels | Strictly contraindicated – multiple reports of acute rejection and graft loss |
| HIV protease inhibitors (ritonavir, nelfinavir, saquinavir) | Strong CYP3A4 inhibition; may increase tacrolimus levels dramatically (up to 10–100 fold with ritonavir) | Massive dose reduction required (often to 0.5–1 mg per week); specialist pharmacist involvement essential |
Minor Interactions
| Interacting Drug / Substance | Effect | Clinical Significance |
|---|---|---|
| Grapefruit / grapefruit juice | Inhibits intestinal CYP3A4; increases tacrolimus absorption and blood levels | Must be avoided throughout treatment; can cause unpredictable level spikes |
| Oral contraceptives | Possible reduced efficacy of hormonal contraception; tacrolimus levels may also be affected | Use additional barrier methods; discuss family planning with transplant team |
| NSAIDs (ibuprofen, diclofenac, naproxen) | Additive nephrotoxicity; may worsen tacrolimus-induced kidney damage | Avoid if possible; paracetamol preferred for pain relief; monitor kidney function if used |
| Potassium supplements / potassium-sparing diuretics | Tacrolimus reduces potassium excretion; additive hyperkalemia risk | Monitor serum potassium regularly; avoid unless clinically necessary |
| Statins (atorvastatin, simvastatin, rosuvastatin) | Tacrolimus may increase statin exposure; increased risk of myopathy/rhabdomyolysis | Use lower statin doses; monitor for muscle symptoms (pain, weakness); pravastatin may be preferred |
| Metoclopramide | Increases gastric motility and tacrolimus absorption; may raise blood levels | Monitor tacrolimus levels if metoclopramide is started or stopped |
| Antacids (aluminium/magnesium hydroxide) | May alter tacrolimus absorption, though clinical significance is variable | Separate administration by at least 2 hours; monitor blood levels |
| Corticosteroids (prednisolone, methylprednisolone) | High-dose corticosteroids may induce CYP3A4 and lower tacrolimus levels; dose reductions may raise levels | Monitor tacrolimus levels during steroid dose changes; commonly co-prescribed in transplant regimens |
Grapefruit and grapefruit juice must be completely avoided while taking Tacforius. Grapefruit contains furanocoumarins that irreversibly inhibit CYP3A4 in the intestinal wall, significantly increasing the absorption of tacrolimus and leading to higher blood levels. Even a single glass of grapefruit juice can raise tacrolimus levels unpredictably, increasing the risk of nephrotoxicity and other serious side effects. The effect can persist for up to 72 hours after grapefruit consumption. Seville (bitter) oranges and pomelos should also be avoided as they contain similar compounds.
What Is the Correct Dosage of Tacforius?
Tacforius is always prescribed and managed by a physician experienced in transplant immunosuppressive therapy. The dose is individualized for each patient based on body weight, the type of transplant, the time since transplantation, concomitant immunosuppressive agents, clinical response (rejection status and organ function), tolerability (side effects), and most critically, tacrolimus trough blood concentrations. Tacforius should be taken orally once daily, in the morning, on an empty stomach (at least 1 hour before or 2–3 hours after a meal), swallowed whole with liquid (preferably water).
Adults – Kidney Transplant
Kidney Transplant – Rejection Prevention
Starting dose: 0.20–0.30 mg/kg/day, taken as a single oral dose in the morning
Timing: Tacforius should be initiated within 24 hours of transplantation
Target trough levels: Typically 10–20 ng/mL in the early post-transplant period (first 3 months), then gradually tapered to 5–15 ng/mL during maintenance therapy, depending on the immunological risk profile and institutional protocol
Duration: Lifelong (as long as the transplant is functioning)
The dose is adjusted based on regular blood level monitoring. Trough levels are measured immediately before the next dose (C0). Most transplant centers aim for specific target ranges that balance adequate immunosuppression against the risk of toxicity.
Kidney Transplant – Rejection Rescue Therapy
Dose: 0.20–0.30 mg/kg/day, taken as a single oral dose
Note: When Tacforius is used to replace another calcineurin inhibitor (ciclosporin), an appropriate washout period is required. A delay of at least 24 hours after the last ciclosporin dose is recommended, with confirmation that ciclosporin blood levels have fallen to an acceptable level before starting tacrolimus.
Target trough levels: Generally targeted at the higher end of the therapeutic range during active rejection treatment
Adults – Liver Transplant
Liver Transplant – Rejection Prevention
Starting dose: 0.10–0.20 mg/kg/day, taken as a single oral dose in the morning
Timing: Tacforius should be initiated approximately 12–18 hours after the transplant operation, as soon as the patient can take oral medication. If oral administration is not feasible immediately, intravenous tacrolimus may be used initially and then switched to Tacforius once the patient is able to swallow.
Target trough levels: Typically 5–20 ng/mL in the early post-transplant period, then individualized during maintenance; liver transplant patients generally require lower tacrolimus doses than kidney transplant patients to achieve similar blood levels
Duration: Lifelong (as long as the transplant is functioning)
Children and Adolescents
Tacforius prolonged-release capsules are not recommended for use in children and adolescents under 18 years of age. There are insufficient clinical data on the use of Tacforius in the pediatric population. Other tacrolimus formulations (e.g., immediate-release capsules or oral suspension/granules) that have been studied in children should be used under the guidance of a pediatric transplant specialist.
Missed Dose
If you forget to take your Tacforius capsule in the morning, take it as soon as you remember on the same day. Do not take a double dose to make up for the missed one. If it is almost time for your next scheduled dose (the following morning), skip the missed dose and resume your normal dosing schedule. Missing doses of tacrolimus can increase the risk of transplant rejection. If you frequently forget to take your medication, discuss strategies with your transplant team, such as setting a daily alarm or using a pill organizer. Record any missed doses and report them at your next clinic visit.
Overdose
If you accidentally take more Tacforius than prescribed, contact your transplant team, the nearest hospital emergency department, or the national poisons information service immediately. Symptoms of tacrolimus overdose may include tremor, headache, nausea, vomiting, kidney failure, neurological disturbances (including seizures and coma), ECG abnormalities (QT prolongation), and infections. There is no specific antidote for tacrolimus overdose. Treatment is supportive and symptomatic. Due to its high molecular weight, poor water solubility, and extensive binding to red blood cells and plasma proteins, tacrolimus is not expected to be significantly removed by dialysis. Activated charcoal may be considered if ingestion occurred recently. Gastric lavage may be appropriate within 1–2 hours of a large overdose.
Therapeutic drug monitoring (TDM) is a mandatory component of tacrolimus therapy and is one of the most important tools your transplant team uses to optimize your treatment. Tacrolimus trough levels (C0) are measured from a blood sample taken just before your morning dose. Target trough levels vary depending on the type of transplant, time since transplantation, concomitant immunosuppression, and individual patient factors. In the early post-transplant period, blood levels are typically checked 2–3 times per week and can be reduced to monthly or less frequent measurements once stable levels are achieved during long-term maintenance. Always take your blood sample before your morning dose and inform your transplant team if you accidentally took your dose before the blood test.
What Are the Side Effects of Tacforius?
Like all immunosuppressive medicines, Tacforius can cause side effects, although not everyone gets them. Many side effects are dose-dependent and may improve when tacrolimus blood levels are reduced. Your transplant team will carefully balance the dose to minimize side effects while maintaining adequate immunosuppression to protect your transplant.
Very Common
May affect more than 1 in 10 people
- Diabetes mellitus / hyperglycemia (new-onset diabetes after transplantation, NODAT)
- Insomnia (difficulty sleeping)
- Tremor (shaking, especially of the hands)
- Headache
- Hypertension (high blood pressure)
- Diarrhea
- Nausea
- Abnormal liver function tests
- Renal impairment / increased serum creatinine (kidney problems)
Common
May affect up to 1 in 10 people
- Blood count changes (anemia, leukopenia, thrombocytopenia, leukocytosis)
- Electrolyte disturbances (hypomagnesemia, hypophosphatemia, hyperkalemia, hypokalemia, hypercalcemia, hyponatremia, hyperuricemia)
- Metabolic acidosis, hyperlipidemia
- Anxiety, confusion, disorientation, depression, mood changes, nightmares
- Seizures (convulsions)
- Peripheral neuropathy (numbness, tingling in hands/feet)
- Dizziness, impaired writing
- Visual disturbances (blurred vision, photophobia)
- Tinnitus (ringing in the ears)
- Tachycardia (fast heartbeat), palpitations
- Hemorrhagic events (bleeding, nosebleeds)
- Venous thromboembolism
- Dyspnea (shortness of breath), cough, pharyngitis
- Gastrointestinal symptoms: vomiting, abdominal pain, constipation, flatulence, bloating, diarrhea, gastritis, mouth ulcers
- Skin problems: rash, pruritus (itching), alopecia (hair loss), acne, excessive sweating
- Musculoskeletal pain: arthralgia (joint pain), muscle cramps, back pain, limb pain
- Urinary tract infections, oliguria (decreased urine output)
- Infections (bacterial, viral, fungal)
- Fever, edema (swelling), fatigue, abnormal wound healing
Uncommon
May affect up to 1 in 100 people
- Coagulation disorders, pancytopenia
- Dehydration, hypoproteinemia
- Coma, encephalopathy, cerebrovascular events (stroke)
- Speech disorders, paralysis, amnesia
- Cataracts
- Cardiac arrest, cardiac failure, cardiomyopathy
- Arrhythmias (including ventricular arrhythmias and atrial fibrillation)
- Deep vein thrombosis, pulmonary embolism
- Pancreatitis
- Bile duct disorders, hepatitis
- Renal failure (acute kidney injury)
- Hemolytic uremic syndrome (HUS)
Rare
May affect up to 1 in 1,000 people
- Thrombotic thrombocytopenic purpura (TTP)
- Toxic epidermal necrolysis (TEN)
- Stevens-Johnson syndrome (SJS)
- Blindness (usually reversible with dose reduction)
- Pericardial effusion
- Acute respiratory distress syndrome (ARDS)
- QT prolongation on ECG
- Torsades de pointes
Not Known
Frequency cannot be estimated from available data
- Posterior reversible encephalopathy syndrome (PRES) – headache, confusion, visual loss, seizures
- Optic neuropathy
- Pure red cell aplasia (severe reduction in red blood cell production)
- Agranulocytosis (severe drop in white blood cells)
- Hemolytic anemia
- Febrile neutropenia
Because Tacforius suppresses the immune system, you are at increased risk of developing serious infections, including opportunistic infections caused by organisms that rarely affect people with normal immune function. These include cytomegalovirus (CMV) reactivation, BK polyomavirus nephropathy (which can cause transplant kidney damage and graft loss), Pneumocystis jirovecii pneumonia (PCP), invasive fungal infections (Aspergillus, Candida), and in rare cases, progressive multifocal leukoencephalopathy (PML) caused by JC virus. Prophylactic medications against CMV and PCP are typically prescribed during the initial months after transplantation. Report any signs of infection (fever, chills, persistent cough, unusual fatigue, painful urination, skin lesions) to your transplant team immediately.
How Should You Store Tacforius?
Tacforius capsules should be stored in their original blister packaging within the aluminum overpouch to protect them from light and moisture. The storage temperature should not exceed 25°C (77°F). Once the aluminum overpouch has been opened, the capsules should be used within 1 year. Do not remove capsules from the blister until immediately before taking them.
Do not use Tacforius after the expiry date stated on the carton and blister. The expiry date refers to the last day of that month. Keep this medicine out of the sight and reach of children. Do not dispose of any medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures help to protect the environment and prevent accidental ingestion.
What Does Tacforius Contain?
Active Ingredient
- Tacforius 0.5 mg: Each prolonged-release hard capsule contains 0.5 mg of tacrolimus (as monohydrate)
- Tacforius 1 mg: Each prolonged-release hard capsule contains 1 mg of tacrolimus (as monohydrate)
- Tacforius 3 mg: Each prolonged-release hard capsule contains 3 mg of tacrolimus (as monohydrate)
- Tacforius 5 mg: Each prolonged-release hard capsule contains 5 mg of tacrolimus (as monohydrate)
Inactive Ingredients (Excipients)
Capsule contents:
- Hypromellose
- Ethylcellulose
- Lactose monohydrate
- Magnesium stearate
Capsule shell:
- Titanium dioxide (E171)
- Iron oxide yellow (E172) – 0.5 mg and 1 mg capsules
- Iron oxide red (E172) – 3 mg capsule
- Ponceau 4R (E124) – 5 mg capsule
- Gelatin
Printing ink: Shellac, propylene glycol, black iron oxide (E172), potassium hydroxide.
Capsule Appearance
- 0.5 mg capsule: Light yellow cap and body, printed with “TR” and “0.5 mg” in black ink. Contains white to off-white prolonged-release pellets.
- 1 mg capsule: White cap and light yellow body, printed with “TR” and “1 mg” in black ink. Contains white to off-white prolonged-release pellets.
- 3 mg capsule: Orange cap and white body, printed with “TR” and “3 mg” in black ink. Contains white to off-white prolonged-release pellets.
- 5 mg capsule: Greyish-red cap and white body, printed with “TR” and “5 mg” in black ink. Contains white to off-white prolonged-release pellets.
Manufacturer
Tacforius is manufactured by Teva Pharma B.V. and marketed by Teva. The marketing authorisation holder is Teva B.V., Swensweg 5, 2031 GA Haarlem, Netherlands.
Frequently Asked Questions About Tacforius
Tacforius (tacrolimus prolonged-release capsules) is an immunosuppressant used to prevent organ rejection after kidney or liver transplantation in adult patients. It suppresses the immune system to prevent it from attacking the transplanted organ. It can also be used as rescue therapy when previous immunosuppressive treatment has not adequately controlled rejection. Tacforius is taken once daily as part of a multi-drug immunosuppressive regimen, typically in combination with corticosteroids and an antiproliferative agent such as mycophenolate.
Both Tacforius and Prograf contain the same active substance, tacrolimus, but they differ in their formulation and dosing frequency. Prograf is an immediate-release formulation taken twice daily (morning and evening), while Tacforius is a prolonged-release formulation designed for once-daily dosing (in the morning). The two formulations have different bioavailability profiles, meaning they are not interchangeable on a milligram-for-milligram basis. Switching between formulations must always be done under the supervision of a transplant specialist with careful blood level monitoring before and after the switch.
No, grapefruit and grapefruit juice must be completely avoided during treatment with Tacforius. Grapefruit contains compounds (furanocoumarins) that inhibit the CYP3A4 enzyme in the intestinal wall, which is responsible for breaking down tacrolimus during absorption. Consuming grapefruit can significantly increase tacrolimus blood levels, leading to an increased risk of serious side effects including kidney damage. The inhibitory effect can last for up to 72 hours after ingestion. Seville oranges and pomelos should also be avoided. Always consult your transplant team if you are unsure about any food interactions.
Blood test frequency depends on the time since your transplant and the stability of your tacrolimus levels. In the first weeks after transplantation, blood tests (including tacrolimus trough levels, kidney function, liver function, blood glucose, electrolytes, and blood counts) are typically performed 2–3 times per week. As your condition stabilizes, testing may be reduced to weekly, then every 2 weeks, then monthly, and eventually every 2–3 months during long-term maintenance. Your transplant team will determine the appropriate monitoring schedule based on your individual situation. Additional blood tests are performed whenever you start or stop interacting medications, experience illness, or have signs of rejection or toxicity.
If you miss a dose of Tacforius, take it as soon as you remember on the same day. Do not take a double dose to make up for the missed one. If it is almost time for your next scheduled dose the following morning, skip the missed dose and continue with your normal schedule. Missing doses of immunosuppressive medication can increase your risk of organ rejection, so it is important to develop a consistent routine. Consider using daily alarms, smartphone reminders, or a weekly pill organizer to help you remember. Inform your transplant team about any missed doses at your next visit.
Pregnancy is possible during tacrolimus therapy, and many successful pregnancies have been reported in transplant recipients taking tacrolimus. However, pregnancy must be carefully planned with your transplant team. Tacrolimus crosses the placenta and is associated with risks including premature delivery, low birth weight, and transient neonatal kidney problems. Despite these risks, tacrolimus is generally considered one of the safer immunosuppressive medications for use during pregnancy, especially compared to mycophenolate mofetil (which is contraindicated). Your transplant team will adjust your tacrolimus dose during pregnancy based on frequent blood level monitoring, as tacrolimus pharmacokinetics change during pregnancy. Close monitoring of both maternal and fetal health is essential throughout.
References
- European Medicines Agency (EMA). Tacforius (tacrolimus) – Summary of Product Characteristics. Last updated 2025. Available from: EMA EPAR.
- U.S. Food and Drug Administration (FDA). Tacrolimus (Prograf) Prescribing Information. Revised 2024. Available from: FDA Drug Label.
- Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients. Am J Transplant. 2024;24(S2):S1–S120.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List. Geneva: WHO; 2023.
- Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation. Clin Pharmacokinet. 2004;43(10):623–653. doi:10.2165/00003088-200443100-00001.
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