Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

TACROLIMUS

NFPA

PRODUCT USE

Immunosuppressive macrolide. It reduces peptidyl- prolyl isomerase activity by binding to
the immunophilin FKBP- 12 (FK506 binding protein) creating a new complex. This FKBP12-
FK506 complex interacts with and inhibits calcineurin thus inhibiting both T- lymphocyte
signal transduction and IL- 2 transcription. Also used to suppress the inflammation
associated with ulcerative colitis, a form of inflammatory bowel disease. In the treatment
of eczema, particularly atopic. Suppresses inflammation in a manner similar to steroids
without causing steroid- like effects (atrophy) Has similar immunosuppressive properties
to cyclosporin, but is much more potent in equal volumes. Also like cyclosporin it has a
wide range of adverse interactions, including that with grapefruit which increases plasma-
tacrolimus concentration. Several of the newer class of antifungals, especially of the
azole class (fluconazole, posaconazole) also increase drug levels by competing for
degradative enzymes. Immunosuppression with tacrolimus was associated with a significantly
lower rate of acute rejection compared with cyclosporin- based immunosuppression (30.7% vs
46.4%)

SYNONYMS

C44-H69-N-O12, C44-H69-N-O12, "3S-[3R*[E(1S*, 3S*, 4S*)]", ", 4S*, 5R*, 8S*, 9E, 12R*,
14R*, 15S*, 16R*, 18S*, 19S*, 26aR*]]", "-5, 6, 8, 11, 12, 13, 14, 15, 16, 17, 18, 19, 24,
25, 26, 26a", "-hexadecahydro-5, 19-dihydroxy", "-hexadecahydro-5, 19-dihydroxy", -3-[2-
(4-hydroxy-3-methoxycyclohexyl), -3-[2-(4-hydroxy-3-methoxycyclohexyl), "-1-
methylethenyl]-14, 16-dimethoxy", "-1-methylethenyl]-14, 16-dimethoxy", "-4, 10, 12, 18-
tetramethyl-8-(2-propenyl)", "-4, 10, 12, 18-tetramethyl-8-(2-propenyl)", "-15, 19-epoxy-
3H-pyrido[2, 1-c] [1, 4] oxaazacyclotricosine-1, 7, 20, 21(4H, 23H)", "-15, 19-epoxy-3H-
pyrido[2, 1-c] [1, 4] oxaazacyclotricosine-1, 7, 20, 21(4H, 23H)", "-tetrone,
monohydrate", (-)-FK506, "FR 900506", Fujimycin, "L 679934", "FK 506", Prograf, Protopic,
Tsukubaenolide, "immunosuppressive macrolide"

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

EMERGENCY OVERVIEW

RISK

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  Accidental ingestion of the material may be harmful; animal experiments indicate that ingestion of less than 150 gram may be fatal or may produce serious damage to the health of the individual.  At sufficiently high doses the material may be nephrotoxic(i.e. poisonous to the kidney).  Macrolides comprise a large group of antibiotics derived from Streptomyces spp. having in common a macrocyclic lactone ring to which one or more sugars are attached. They are all weak bases. The most common side effect produced by the family of macrolide antibiotics is gastrointestinal discomfort. Supra-infections may occur although these are rare. Several macrolides produced allergic sensitization but, again, these are rare. Symptoms include watery eyes, shortness of breath, nasal congestion, choking, coughing and wheezing. Allergic skin reactions have also occurred. Exposure to at least one member of the family, erythromycin, at high concentrations, has produced reversible deafness (ototoxicity). Systemic reactions including fever, rash, and lymph-node pain or swelling have been produced by the avermectin group. Ivermectin has produced ataxia (incoordination), lethargy, bradypnea (slowed breathing), vomiting, mydriasis (dilated pupils), sedation, tremors and death in animals. The avermectin group (anthelmintics, insecticides and acaricides) mediate the transmission of gamma-butyric acid (GABA), an inhibitory neurotransmitter, in mammals thus causing paralysis. Hepatotoxic effects with transient disturbances and jaundice have resulted from the use of oleandomycin. Transient alterations in heart rate/ rhythm have also been produced by several members of the family (notably tilmicosin). Heart muscle degeneration, characterized by small areas of cell death have also been reported in animals exposed to tilmicosin. Cross-resistance is often observed between the macrolide, lincosamide and streptogramin group of antibiotics.  

EYE

  Although the material is not thought to be an irritant, direct contact with the eye may cause transient discomfort characterized by tearing or conjunctival redness (as with windburn). Slight abrasive damage may also result. The material may produce foreign body irritation in certain individuals.  

SKIN

  The material is not thought to produce adverse health effects or skin irritation following contact (as classified using animal models). Nevertheless, good hygiene practice requires that exposure be kept to a minimum and that suitable gloves be used in an occupational setting.  Entry into the blood-stream, through, for example, cuts, abrasions or lesions, may produce systemic injury with harmful effects. Examine the skin prior to the use of the material and ensure that any external damage is suitably protected.  

INHALED

  The material is not thought to produce respiratory irritation (as classified using animal models). Nevertheless inhalation of dusts, or fume, especially for prolonged periods, may produce respiratory discomfort and occasionally, distress.  Inhalation of vapors or aerosols (mists, fumes), generated by the material during the course of normal handling, may be damaging to the health of the individual.  

CHRONIC HEALTH EFFECTS

  There has been some concern that this material can cause cancer or mutations but there is not enough data to make an assessment.  Long term exposure to high dust concentrations may cause changes in lung function i.e. pneumoconiosis; caused by particles less than 0.5 micron penetrating and remaining in the lung. Prime symptom is breathlessness; lung shadows show on X-ray.  · CAUTION: May produce immunosuppression in individuals occupationally exposed to the material.  Exposure to immunosuppressives may aggravate infectious diseases.  Chronic exposure to therapeutic doses of compounds which produce immunosuppression has been associated with development of lymphomas (occasionally malignant) and mammary tumours. These may be secondary effects induced by activation of endogenous retroviruses.  Increased incidences of neoplasms, in mice and humans, have been reported after long-term immunosuppression by azathioprine and cyclosporin. Cyclosporin has been classified as a human carcinogen, by IARC, based on development of lymphomas after repeated and prolonged exposures to therapeutic doses.