Dr Sharon Rees @reesprescribe
Day 1: In the same class as ciclosporin A (superior to), #tacrolimus was found in Japan ©1984 from soil bacterium strep. tsukubaensis; the name is a combination of tsuku, macrolide and immunosuppressant. The first use was as an anti-rejection drug post-transplant, then later was formulated as a topical application for dermatological use.
Dr Sharon Rees @reesprescribe
Day 2: #tacrolimus is taken orally once daily for prevention of graft rejection or iv infusion for up to 1-week post-transplant pre-oral therapy; dose varies per organ/licensed neonatal, child, adult. Topical is licensed for atopic eczema; also an alternative to topical steroids eg use on the face. 0.03 or 0.1% ointment (short-term or intermittent long-term). Licensed from age 2 for atopic eczema only, but 0.03% if <16; Off-license adult-use includes 2nd line psoriasis face/flexures/genitals. Can use with emollients, but leave 2 hr window.
Dr Sharon Rees @reesprescribe
Day 3: #tacrolimus has moderate oral bioavailability, best fasted. Despite high RBC and protein binding, distribution is high. Liver CYP3A4 breakdown and bile/faecal elimination. T½ ~43 hr, but half-life is reduced post-transplant. Narrow therapeutic index with high variation in kinetics; systemic use needs therapeutic monitoring.
Dr Sharon Rees @reesprescribe
Day 4: Enzyme calcineurin's role is calcium-related signalling in nerve and T cells. In T cells, it joins protein FKBP-12 to activate the transcription family NFAT, which leads to an immune response/cytokine production. #tacrolimus binds to FKBP-12 blocking calcineurin function and hence impairs T cell activation.
Dr Sharon Rees @reesprescribe
Day 5: #tacrolimus ADEs; Common oral/iv include alopecia, cough, depression, gastrointestinal and renal disorders, vomiting. Signs of toxicity incl nephrotoxicity, infection, hyperkalaemia, nausea/vomiting, and tremor (NOT exhaustive). Topical ADEs; local burning/itching/infection. Alcohol intolerance (typically skin flushing) is ‘common’ via inhibition acetaldehyde dehydrogenase leading to build up in skin; can occur after course completion. An ‘uncommon’ effect is lymphadenopathy with topical use and frequency unknown for malignancy.
Dr Sharon Rees @reesprescribe
Day 6: #tacrolimus drug-drug interactions: three issues with systemic use:
- Increased nephrotoxicity eg NSAID
- Hyperkalaemia eg ACEi
- #tacrolimus levels eg reduces primidone and increases ritonavir. Avoid grapefruit juice as inhibits breakdown. Topical use: alcohol risk of flushing and skin reaction.
Dr Sharon Rees @reesprescribe
Day 7: There are many off-license topical uses for #tacrolimus, including seborrheic dermatitis, vitiligo, lichen planus, pityriasis alba.
Earn Your CPD Certificate
With the help of Prescribing and Therapeutics Training Ltd and the Journal of Prescribing Practice, you can earn your 1-hour CPD certificate
In addition to the tweets, read the BNF treatment summaries on eczema and the monograph on tacrolimus. Another useful source is the Summary of Product Characteristics for tacrolimus. These are listed below. Please submit the answers to reesprescribe@gmail.com as a numbered list with TRUE/FALSE or the correct A,B,C,D option. If you achieve 8 or more out of ten on the questions, a CPD certicate will be emailed to you.
- Tacrolimus was originally used as a drug to prevent organ rejection TRUE or FALSE?
- Tacrolimus is usually used long-term for atopic eczema TRUE or FALSE?
- Which is TRUE?
- Tacrolimus is similar, but not as potent as ciclosporin A
- Systemic tacrolimus has minimal monitoring requirements
- Tacrolimus inhibits calcineurin, which is needed to activate T cells
- Tacrolimus is more nephrotoxic than ciclosporin A
- Tacrolimus has a narrow therapeutic index TRUE or FALSE?
- Which is FALSE?
- Tacrolimus cures the underlying dermatological condition
- Tacrolimus has many off license uses in dermatology
- Topical tacrolimus can encourage local infections
- Tacrolimus cannot be used topically for those under 2 years old
- Tacrolimus does not cause skin atrophy, which is useful for facial use TRUE or FALSE?
- Which of the following does NOT indicate tacrolimus toxicity?
- Nephrotoxicity
- Anaphylactoid reaction
- Hyperkalaemia
- Tremor
- Grapefruit should be avoided because it weakens the drug's activity TRUE or FALSE?
- Alcohol taken when using topical tacrolimus can cause hepatic failure TRUE or FALSE?
- You can use emollients in tandem with topical tacrolimus TRUE or FALSE?
Further reading on #tacrolimus
- Eczema: https://bnf.nice.org.uk/treatment-summary/eczema.html
- Tacrolimus: https://bnf.nice.org.uk/drug/tacrolimus.html
- Prograf 0.5 mg Hard Capsules: https://www.medicines.org.uk/emc/product/6720/smpc#gref
- Protopic 0.1% ointmen: https://www.medicines.org.uk/emc/product/1608/smpc#gref