This presentation is about a skincare drug methotrexate

1. Methotrexate

2. Objectives:
 Overview of the drug
 Pharmacology
 Indications in dermatology
 Dosage
 Adverse effects
 Contraindications
 Monitoring

3. Introduction:
 Synthetic DMARD that interferes with:
 Cell growth
 Slows production of new cells
 Reduces inflammation
 Used as:
 Chemotherapeutic
 Immunosuppressive
 Anti-inflammatory

4. Introduction:
 Toxic Folic acid analogue
 Formula: C20H22N8O5

6. Common Brand Names:
 Cytotrexate 2.5 mg

7. History:
 Formarly known as Amethopterin
 Used in 1958 by Edmundson & Guy in treatment
of Psoriasis
 Berlin suggest intermittent dosage schedule in
1963
 Weinstein and Frost introducd weekly dosage
schedule in 1971

8. Administration,Absorption
and distribution:
 Administered orally, I/V, I/M or S/C
 Intrathecal in some chemotherapeutic regimens
 Triphasic reduction in plasma level
 distribution
 renal excretion
 termination

9. Mechanism of action:
 DNA synthesis effects:
 Inhibit Dihydrofolate reductase which converts
dihydrofolate to tetrahydrofolate
 Tetrahydrofolate is essential for DNA synthesis
 DNA Replication effects:
 Inhibit thymidylate synthase
 Decrease dTMP sythesis

10. Continued:
 Anti-inflammatory effects:
 Inhibits AICART enzyme and increase adenosine
concentration
 Inhibits MTHFR and decrease methionine
concentration
 T-cell effects:
 Inhibit T cells activation
 Suppression of intracellular adhesion molecules

11. Mechanism of action:

13. Pharmacokinetics
 Bioavailability : 60%
 Protein Binding : 35-50%
 Carrier protein: RFC1
 Metabolism: Hepatic and intracellular
 Half Life : 6-8 Hrs
 Excretion : Urine (8-100%),bile (small amount)

14. Dermatological Indications:
 Severe Psoriasis
 Immunobullous disorders
 Pemphigus
 Bullous pemphigoid
 Cicatricial pemphigoid

15. Continued:
 Connective tissue disorders:
 Dermatomyositis
 Lupus erythromatosus
 Scleroderma
 Vasculitides
 Neutrophilic dermatosis
 Pyoderma gangrenosum
 Sweet syndrome

16. Continued:
 Inflammatory disorders
 Atopic eczema
 Sarcoidosis
 Cutaneous crohn disease
 Chronic idiopathic urticaria
 Proliferative disorders
 Mycosis fungoides
 Sezary syndrome
 Pityriasis lichenoides
 Petyriasis rubra pilaris

17. Contraindications:
Absolute:
 Pregnancy
 Lactation
 Hypersensitivity
Relative:
 Diabetes Mellitus
 Obesity
 Blood dyscrasias
 Alcohol intake
 Hepatic and renal impairment
 Immunodefeciency and latent infection

18. Dosage and preparations:
 0.2-0.4 mg/kg
 Varies from 2.5 to 25mg
 Should not exceed 25mg weekly
 Oral:
 2.5 mg
 10 mg
 Injectable: ( I.M, I.V, S.C)
 5 mg
 50 mg
 500mg
 Accumulation dose: 1.5 gm

19. Adverse effects:
 Systemic:
 Myelotoxicity
 Hepatotoxicity
 GI toxicity
 Nephrotoxicity
 Reproductive toxicity
 Pulmonery toxicity
 Malignancy

20. Continued:
 Cutaneous:
 Aphthous stomatitis
 Alopecia
 Hyperpigmentation
 Phototoxicity
 Toxic epidermal necrolysis
 Ulceration in psoriatic plaques
 Acral erythema
 Vasculitis

21. Drug-drug interactions:

22. Folate supplementation
Folic acid:
 Competes with MTX for DHFR
 Reduce bone marrow,GI tract and liver adverse effects
 5 mg once weekly on day following MTX
Folinic acid:
 Also known as leucovorin
 Used in MTX toxicity
 Bypass step catalyzed by DHFR and competes with MTX for
RFC1 intracellular transportation
 Rescue bone marrow and GI cells
 5 mg three doses at 12 hrs interval after 24 hrs of MTX weekly
dose if folic acid is not improving GI symptoms,liver
abnormalities or macrocytosis

23. Pretreatment screening:
Patient information leaflet
Risk counselling
 Infection
 Bone marrow suppression
 Skin malignancy
Contraception
Sun protection measures
Blood tests
 CBC
 U/E
 LFTs
 Hep B/C Serology

24. Continued:
 Vaccinations
 Pneumococcal
 Influenza
 Hep B
 Vericella zoster virus
 Pregnancy test
 CXR

25. Monitoring:
 Close monitoring in elderly and renal patients
 Blood tests: CBC,LFTs and creatinine
 Weekly for 1 month
 2 weekly for 2 months
 Monthly for 3 months
 3 months afterwards
 Symptoms of bone marrow supresssion
 Avoidence of drugs which interact with MTX
 Serum liver fibrosis markers
 Procollagen-III aminoterminal propeptide,hyaluronic
acid,tissue inhibitor of matrix metalloproteinase-1

26. Take home message:
 MTX is a human teratogen and abortificient-avoid
pregnancy
 Requires regular blood tests monitoring
 Used for a veriety of dermatological diseases