Thalidomide (Rheumatology / Dermatology)

VERBATIM US §2.3 Recommended Dosage for Erythema Nodosum Leprosum: 'The recommended dose of THALOMID for an episode of cutaneous ENL is 100 to 300 mg/day once daily orally with water, preferably at bedtime and at least 1 hour after the evening meal. Initiate dosing for patients weighing less than 50 kilograms at the low end of the dose range. Consider dosing in the higher dosage range for patients with a severe cutaneous ENL reaction, or in those who have previously required higher doses to control the reaction (possibly up to 400 mg/day) once daily at bedtime or in divided doses with water, at least 1 hour after meals. Consider concomitant use of corticosteroids in patients with moderate to severe neuritis associated with a severe ENL reaction. Steroid usage can be tapered and discontinued when the neuritis has ameliorated. Continue dosing with THALOMID until signs and symptoms of active reaction have subsided, usually a period of at least 2 weeks. Patients may then be tapered off medication in 50 mg decrements every 2 to 4 weeks. Patients who have a documented history of requiring prolonged maintenance treatment to prevent the recurrence of cutaneous ENL or who flare during tapering should be maintained on the minimum dose necessary to control the reaction. Tapering off medication should be attempted every 3 to 6 months, in decrements of 50 mg every 2 to 4 weeks.' NOTE the sub-50 kg rule is a BAND rule, not a per-kilogram calculation. WHAT THE UK SPC DOSES INSTEAD — DO NOT CARRY IT ACROSS: the fetched eMC SPC ('Myrin 100 mg coated tablets') is a first-line MULTIPLE MYELOMA licence. §4.2, verbatim: 'The recommended dose of thalidomide is 200 mg orally per day... A maximum number of 12 cycles of 6 weeks (42 days) should be used', given 'in combination with melphalan and prednisone' with thalidomide 'dosed once daily at bedtime on Days 1 to 42 of each 42-day cycle'; starting dose falls to '100 mg daily' for patients aged over 75 ('For patients > 75 years of age, the thalidomide recommended starting dose is 100 mg per day'). Those are myeloma figures for a myeloma combination and are not a rheumatology/dermatology dose. The US label gives the same myeloma regimen (§2.2: 'The recommended dose of THALOMID in combination with dexamethasone is 200 mg once daily (in 28-day treatment cycles)'). TABLET STRENGTH: the UK product is 100 mg coated tablets and §4.2 warns 'Myrin is only available as 100 mg coated tablets. Thus, it is not possible to administer Myrin to patients that require less than a full 100 mg dose. If an alternate dose is required, other thalidomide products offering such an option should be used.' US capsules come as 50 mg, 100 mg, 150 mg and 200 mg, so the 100–300 mg range and the 50 mg tapering decrements above assume a product with a 50 mg strength. MISSED DOSE (UK §4.2, verbatim): 'If less than 12 hours have elapsed since missing a dose, the patient can take the dose. If more than 12 hours have elapsed since missing a dose at the normal time, the patient should not take the dose, but take the next dose at the normal time on the following day.' HANDLING (UK §4.2): 'If powder from thalidomide makes contact with the skin, the skin should be washed immediately and thoroughly with soap and water.' PRESCRIBING GATE (UK §4.2, verbatim): 'Treatment must be initiated and monitored under the supervision of physicians with expertise in managing immunomodulatory or chemotherapeutic agents and a full understanding of the risks of thalidomide therapy and monitoring requirements.' A pregnancy prevention programme is mandatory for all male and female patients (UK §4.4); in the US, 'THALOMID must only be administered in compliance with all of the terms outlined in the THALOMID REMS program' (§2.1). DOSE MODIFICATION for thalidomide-related neuropathy (UK §4.2 Table 2, quoted for the myeloma licence but the graded scheme is the only one fetched): Grade 1 — continue and monitor, consider reducing dose if symptoms worsen; Grade 2 — 'Reduce dose or interrupt treatment and continue to monitor the patient with clinical and neurological examination. If no improvement or continued worsening of the neuropathy, discontinue treatment'; Grade 3 and Grade 4 — 'Discontinue treatment.' Thalidomide 'interruption or discontinuation should be considered for Grade 2-3 skin rash' and must be discontinued permanently for angioedema, anaphylactic reaction, Grade 4 rash, exfoliative or bullous rash, or suspected SJS, TEN or DRESS.