Tacrocord (Tacrolimus USP), Special warnings and precautions for use

Gafacom May 05, 2023

Tacrocord (Tacrolimus USP) Precautions for use

Tacrolimus USP, commonly known as Tacrocord, is an immunosuppressive drug used to prevent organ rejection in patients who have undergone transplant surgeries. It works by inhibiting the activity of T-cells, which play a crucial role in the body's immune response. By suppressing T-cell activity, Tacrocord reduces the risk of the transplanted organ being attacked by the patient's immune system.

Medication errors, including inadvertent, unintentional or unsupervised substitution of immediate or prolonged-release tacrolimus formulations, have been observed. This has led to serious adverse events, including graft rejection, or other side effects which could be a consequence of either under-or over-exposure to tacrolimus. Patients should be maintained on a single formulation of tacrolimus with the corresponding daily dosing regimen; alterations in formulation or regimen should only take place under the close supervision of a transplant specialist.

Tacrocord (Tacrolimus USP), Special warnings and precautions for use


Substances with potential for interaction

When substances with a potential for interaction – particularly strong inhibitors of CYP3A4 (such as telaprevir, boceprevir, ritonavir, ketoconazole, voriconazole, itraconazole, telithromycin or clarithromycin) or inducers of CYP3A4 (such as rifampicin, rifabutin) – are being combined with tacrolimus, tacrolimus blood levels should be monitored to adjust the tacrolimus dose as appropriate in order to maintain similar tacrolimus exposure.

Herbal preparations containing St. John’s wort (Hypericum perforatum) or other herbal preparations should be avoided when taking Tacrolimus Capsules USP, 0.5 mg, 1 mg and 5 mg due to the risk of interactions that lead to either a decrease in blood concentrations of tacrolimus and reduced clinical effect of tacrolimus, or an increase in blood concentrations of tacrolimus and risk of tacrolimus toxicity.

The combined administration of ciclosporin and tacrolimus should be avoided and care should be taken when administering tacrolimus to patients who have previously received ciclosporin.

High potassium intake or potassium-sparing diuretics should be avoided.

Certain combinations of tacrolimus with drugs known to have nephrotoxic or neurotoxic effects may increase the risk of these effects.

Vaccination

Immunosuppressant may affect the response to vaccination and vaccination during treatment with tacrolimus may be less effective. The use of live attenuated vaccines should be avoided.

Gastrointestinal disorders

Gastrointestinal perforation has been reported in patients treated with tacrolimus. As gastrointestinal perforation is a medically important event that may lead to a life-threatening or serious condition, adequate treatments should be considered immediately after suspected symptoms or signs occur.

Since levels of tacrolimus in blood may significantly change during diarrhoea episodes, extra monitoring of tacrolimus concentrations is recommended during episodes of diarrhoea.

Cardiac disorders

Ventricular hypertrophy or hypertrophy of the septum, reported as cardiomyopathies, have been observed on rare occasions. Most cases have been reversible, occurring primarily in children with tacrolimus blood trough concentrations much higher than the recommended maximum levels.

Other factors observed to increase the risk of these clinical conditions included pre-existing heart disease, corticosteroid usage, hypertension, renal or hepatic dysfunction, infections, fluid overload and oedema.

Lymph proliferative disorders and malignancies

Patients treated with Tacrolimus Capsules USP, 0.5 mg, 1 mg and 5 mg have been reported to develop Epstein-Barr virus (EBV)-associated lymph proliferative disorders. Patients switched to

Tacrolimus Capsules USP, 0.5 mg, 1 mg and 5 mg therapy should not receive anti-lymphocyte treatment concomitantly. Very young (< 2 years), EBV-VCA-negative children have been reported to have an increased risk of developing lymph proliferative disorders. Therefore, in this patient group, EBV-VCA serology should be ascertained before starting treatment with Tacrolimus Capsules USP, 0.5 mg, 1 mg and 5 mg. During treatment, careful monitoring with EBV-PCR is recommended. Positive EBV-PCR may persist for months and is per se not indicative of lymph proliferative disease or lymphoma.

Posterior reversible encephalopathy syndrome (PRES)

Patients treated with tacrolimus have been reported to develop posterior reversible encephalopathy syndrome (PRES). If patients taking tacrolimus present with symptoms indicating PRES such as headache, altered mental status, seizures, and visual disturbances, a radiological procedure (e.g. MRI) should be performed. If PRES is diagnosed, adequate blood pressure control and immediate discontinuation of systemic tacrolimus is advised. Most patients completely recover after appropriate measures are taken.

Opportunistic infections

Patients treated with immunosuppressant, including Tacrolimus Capsules USP, 0.5 mg, 1 mg and 5 mg are at increased risk of opportunistic infections (bacterial, fungal, viral and protozoal). Among these conditions are BK virus associated nephropathy and JC virus associated progressive multifocal leukoencephalopathy (PML). These infections are often related to a high total immunosuppressive burden and may lead to serious or fatal conditions that physicians should consider in patients with deteriorating renal function or neurological symptoms.

Pure Red Cell Aplasia

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with tacrolimus. All patients reported risk factors for PRCA such as parvovirus B19 infection, underlying disease or concomitant medications associated with PRCA.

Excipients

As Tacrolimus Capsules USP, 0.5 mg, 1 mg and 5 mg contains lactose, special care should be taken in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

The printing ink used to mark Tacrolimus Capsules USP, 0.5 mg, 1 mg and 5 mg capsules 0.5 mg and 1mg contains soya lecithin. In patients who are hypersensitive to peanut or soya, the risk and severity of hypersensitivity should be weighed against the benefit of using Tacrolimus Capsules USP, 0.5 mg, 1 mg and 5 mg.

Fertility, Pregnancy and lactation

Pregnancy: Human data show that tacrolimus is able to cross the placenta. Limited data from organ transplant recipients show no evidence of an increased risk of adverse effects on the course and outcome of pregnancy under tacrolimus treatment compared with other immunosuppressive medicinal products. However, cases of spontaneous abortion have been reported. To date, no other relevant epidemiological data are available.

Due to the need of treatment, tacrolimus can be considered in pregnant women when there is no safer alternative and when the perceived benefit justifies the potential risk to the foetus. In case of in utero exposure, monitoring of the newborn for the potential adverse effects of tacrolimus is recommended (in particular the effects on the kidneys). There is a risk for premature delivery (<37 week) as well as for hyperkalaemia in the newborn, which, however, normalizes spontaneously.

In rats and rabbits, tacrolimus caused embryofoetal toxicity at doses which demonstrated maternal toxicity.

Breast-feeding: Human data demonstrate that tacrolimus is excreted into breast milk. As detrimental effects on the newborn cannot be excluded, women should not breast-feed whilst receiving Tacrolimus Capsules USP, 0.5 mg, 1 mg and 5 mg.

Fertility: A negative effect of tacrolimus on male fertility in the form of reduced sperm counts and motility was observed in rats.

Effects on ability to drive and use machines

Tacrolimus may cause visual and neurological disturbances. This effect may be enhanced if

Tacrolimus Capsules USP, 0.5 mg, 1 mg and 5 mg is administered in association with alcohol.

Overdose

Experience with overdosage is limited. Several cases of accidental overdosage have been reported; symptoms have included tremor, headache, nausea and vomiting, infections, urticaria, lethargy, increased blood urea nitrogen and elevated serum creatinine concentrations, and increase in alanine aminotransferase levels.

No specific antidote to Tacrolimus Capsules USP, 0.5 mg, 1 mg and 5 mg therapy is available. If overdosage occurs, general supportive measures and symptomatic treatment should be conducted.

Based on its high molecular weight, poor aqueous solubility, and extensive erythrocyte and plasma protein binding, it is anticipated that tacrolimus will not be dialyzable. In isolated patients with very high plasma levels, hemofiltration or -diafiltration have been effective in reducing toxic concentrations. In cases of oral intoxication, gastric lavage and/or the use of adsorbents (such as activated charcoal) may be helpful, if used shortly after intake.

Key words

  • Tacrocord use
  • Tacrocord indications
  • Tacrocord dosage
  • Tacrocord side effects
  • Tacrocord for transplant
  • Tacrocord for kidney transplant
  • Tacrocord warnings
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