Azathioprine

Name: Azathioprine indications and doage in dermatology| Dermatology Games
Published: 2020-09-14T13:18:20+00:00

Dermatology Games

4 years ago

Indications

Off-label dermatologic uses
- Immunobullous dermatoses.
  - Bullous pemphigoid.
  - Pemphigus vulgaris.
  - Cicatricial pemphigoid.
- Vasculitis
  - Leukocytoclastic vasculitis.
  - Wegener’s granulomatosis.
  - Polyarteritis nodosa.
- Neutrophilic dermatoses
  - Behçet’s syndrome.
  - Pyoderma gangrenosum.
- Autoimmune connective tissue diseases
  - Systemic lupus erythematosus.
  - Discoid lupus erythematosus.
  - Dermatomyositis.
  - Polymyositis.
  - Relapsing polychondritis.
- Dermatitis and papulosquamous dermatoses
  - Contact dermatitis.
  - Atopic dermatitis.
  - Lichen planus (oral and cutaneous).
  - Psoriasis.
- Photodermatoses.
  - Chronic actinic dermatitis.
  - Persistent light reaction.
  - Polymorphous light eruption.
Other dermatoses
- Sarcoidosis (especially pulmonary features).
- Erythema multiforme (persistent).
- Chronic graft-versus-host disease.

According to TMPT assay :
- TPMT < 5 U = no treatment with azathioprine.
- TPMT between 5–13.7 U = up to 0.5 mg/kg daily.
- TPMT between 13.7–19 U = up to 1.5 mg/kg/day.
- TPMT > 19 = up to 2.5 mg/kg/day.

The active metabolites of azathioprine (6‐thioguanine nucleotides(6‐TGNs)) are similar to the endogenous purines >> Incorporation into DNA and RNA >> inhibit purine metabolism and cell division>> antiproliferative, anti‐inﬂammatory and immunosuppressant properties.

Clinical evaluation:
- Discuss the risk/benefit profile and adverse effects with each patient.
- Discuss alternative treatments and the requirement of multiple blood tests.
- Discuss sun avoidance and birth control/abstinence if women of child bearing potential.
- History of prior use of alkylating agents or current use of allopurinol or febuxostat.
- Careful physical exam with focus on skin and lymphoreticular system should be done.
Lab
- Pregnancy test.
- CBC.
- Renal function tests.
- Liver function tests.
- Hepatitis B and C screen.
- Urine analysis.
- Tuberculin skin test ( depending on clinical situation).
Special tests
- TPMT assay.

Clinical
- Annual complete physical examination (exclude Scc – lymphoma).
Lab (biweekly for the first 2 months, every 2–3 months thereafter).
- CBC.
- ALT – AST.

Malignancies.
- Cutaneous SCC.
- Lymphomas.
Myelosuppression (correlates with low  TPMT activity).
- Neutropenia.
- Agranulocytosis and pancytopenia (rare).
Infections
- Human papilloma virus, herpes simplex, scabies.
- True opportunistic infections uncommon with azathioprine for dermatologic indications.
Teratogenicity
- Various congenital malformations.
Hypersensitivity syndrome
- Cutaneous : morbilliform rash, purpura, erythema multiforme, urticaria, angioedema, erythema nodosum.
Gastrointestinal
- Gastritis.
- Pancreatitis.
Hepatic
- Transaminase elevations.
- Severe hepatocellular toxicity (rare).

Absolute
- Hypersensitivity to azathioprine.
- Patients with low TPMT enzyme activity.
Relative
- Pregnancy.
- Active serious infection.
- Allopurinol use – can prescribe azathioprine cautiously with signifcantly reduced dose.
- Prior use of alkylating agents (theoretically increased malignancy risk.

Allopurinol: increased risk of pancytopenia (if using concurrently, lower azathioprine dose by 75%).
Captopril: may increase risk of anemia and leukopenia.
Warfarin : may need an increased dose of warfarin.
Pancuronium: may need an increased dose of this for adequate paralysis.
Co-trimoxazole: increased risk of hematologic toxicity.
Rifampicin: decreases azathioprine effcacy, also hepatotoxic.
Clozapine: increased risk of agranulocytosis.

Pregnancy category D.
- It can be used if the benefits outweigh the risks.
Breast-feeding :
- In patients who have been taking 200 mg daily, low or undetectable amounts have been found in breast milk and newborn serum.
- To reduce the dose recieved by the breastfed infants, it is recommended to avoid breastfeeding for 4 hours after the last given dose.
- Some authors recommend to ask for CBC and liver function tests to monitor such infants.

Stop using azathioprine if signifcantly reduced blood counts occur (WBC <3500–4000/mm3, hemoglobin <10 g/dL,platelets <100 000/mm3)\n.
Caution is advised when administering live vaccine to immunosuppressed patients.
Concomitant use of co-trimoxazole and penicillamine should be avoided.
Azathioprine is not recommended in breastfeeding women.

Despite the rapid absorption, metabolism and excretion of AZA, its active metabolites only slowly accumulate in tissues, and thus the therapeutic immunosuppressive effects of AZA may take 6–12 weeks to develop.