737
until the surgical wound is fully healed; after minor surgery References. Multiple sclerosis. Alemtuzumab has been licensed in the et al. it may be restarted when the wound is fully healed. 1. Hale G, Alemtuzumab (Campath-1H) for treatment of lymphoid EU for the treatment of multiple sclerosis (p. 996.3). How malignancies in the age of nonmyeloablative conditioning? Bone Marrow Severe hypertension, including cases of hypertensive Transplant 2002; 30: 797-804. ever, an FDA committee has raised concerns about its crisis, has been reported. Blood pressure should be AJ. Drugs 63: 2. Frampton JE, Wagstaff Alemtuzumab. 2003; 1229-43. adverse effects such as auto-immune cytopenias and auto monitored every 2 weeks and antihypertensive therapy 3. Keating M, et al. Management guidelines for use of alemtuzumab in B· immune thyroid disease which can be fatal and may out Clin Lymphoma 4: started when necessary. Aflibercept may need to be cell chronic lymphocytic leukemia. 2004; 220-7. weigh its benefits. For further information on the adverse 4. Fader! S, et al. The evolving role of alemtuzumab in management of withheld and the dose reduced after severe or recurrent patients with CLL. Leukemia 2005; 19: 2147-52. effects of alemtuzumab, see under Adverse Effects, Treat hypertension is under control; it should be stopped in 5. Morris PJ, Russell NK. Alemtuzumab (Campath- lH): a systematic ment, and Precautions, below. patients with hypertensive crisis or hypertensive encephalo review in organ transplantation. Transplantation 2006; 81: 1361-7. lt has been proposed that the secondary progressive 6. pathy. Patients should also be monitored for proteinuria Magliocca JF, Knechtle SJ. The evolving role of alemtuzumab phase of the disease might be due to post-inflammatory (Campath·1H) for immunosuppressive therapy in organ transplanta during aflibercept therapy, which may need to be withheld tion. Transpl Int 2006; 19: 705-14. neurodegeneration and that immunotherapy would or the dose reduced; it should be stopped in those who 7. Ravandi F, O'Brien S. Alemtuzumab in CLL and other lymphoid influence long-term disability only if given early in the develop nephrotic syndrome or thrombotic microangio neoplasms. Cancer Invest 2006; 24: 718-2 5. disease course. A phase 2 randomised study assigned 8. in pathy. Boyd K, Dearden CE. Alemtuzumab the treatment of chronic treatment-naive patients with early, relapsing-remitting lymphocytic lymphoma. Expert Rev Anh"cancer Ther 2008; 8: 525-33. A complete blood count with differential count should be 9. Robak T. Alemtuzumab for B-cel\ chronic lymphocytic leukemia. Expert multiple sclerosis to either alemtuzumab or interferon beta. made before each dose of intravenous aflibercept; treatment Rev Anticancer Ther 2008; 8: 1033-51. Alemtuzumab (at a dose of either 12 mg daily or 24 mg should be delayed if the neutrophil count is below 10. Ciancio G, Burke GW. Alemtuzumab (Campath·lH) in kidney daily) was given by intravenous infusion on 5 consecutive Am Transplant 2008; 8: 1500 cells/mm3 transplantation. 1 15-20. days during the first month, and on 3 consecutive days at 11. Dhesi S, et al. Alemtuzumab and liver transplantation: a review. Curr Opin Organ Transplant 2009; 14: 245-9. months 12 and 24; interferon beta-1a at a dose of Pharmacokinetics 12. Gribben JG, Hallek M. Rediscovering alemtuzumab: current and 44 micrograms was given subcutaneously 3 times weekly emerging therapeutic roles. Br J Haemato/ 2009; 144: 818-3 1. after dose escalation. All patients received intravenous O etal. Systemic absorption occurs after intravitreal administration 13. sterburg A, Management guidelines for the use of alemtuzumab methylprednisolone at the time of infusion. There were no in chronic lymphocytic leukemia. Leukemia 2009; 23: 1980-8. of aflibercept; peak plasma concentrations are low and occur significant differences between the groups receiving either within 3 days, and free plasma-aflibercept concentrations dose of alemtuzumab on any outcome measure or adverse are undetectable 2 weeks following administration. The Administration. Subcutaneous use of alemtuzumab has event. However, 6 cases of immune thrombocytopenic terminal half -life of free aflibercept in plasma is about 6 days been investigated as a means of reducing adverse infusion purpura occurred with alemtuzumab treatment, including following intravenous administration of doses of 2 to reactions associated with intravenous dosage. Studies have one fatality, prompting suspension of therapy with 4mg/kg. found it to be safe and effective.1•2 Similar blood concen alemtuzumab. Nonetheless, compared with interferon trations are achieved to those after intravenous use, beta, alemtuzumab significantly improved mean disability although accumulation in the blood took longer to scores and reduced the rate of relapse; efficacy was achieve with subcutaneous use, and higher cumulative maintained over 36 months, even though some 70% of (details are given in Volume B) ProprietaryPreparations doses were required.' A dose of 30 mg subcutaneously alemtuzumab-treated patients were not given the planned Single-ingredient Preparations.Fr.: Eylea; Jp n: Eylea; Neth.: Zal three times weekly has been widely used; given for 4 to third cycle due to safety concerns. Alemtuzumab also trap; Switz.: Eylea; Zaltrap; UK: Eylea; Zaltrap; USA: Eylea; Zal 12 weeks it has been shown to be as effective and safe as increased brain volume on magnetic resonance imaging, trap. intravenous alemtuzumab in patients with fludarabine whereas brain atrophy advanced among patients receiving refractory disease, and it has been suggested that the con interferon beta. The authors of the study noted that, while venience of subcutaneous injection, which can be given alemtuzumab appears to be more effective than interferon on an outpatient basis, makes it the preferred route for beta when given in the earliest stages of multiple sclerosis, (BAN, r/NN) Alemtuzumab this indication 4 Although treatment has normally been there is a dilemma as to whether to expose young adults 1\temtutsumabi; A!emtuzurriilbum; Campath:1; Campath· started with lower doses and gradually increased (e.g. with little disability to the potentially serious adverse effects 3mg on day l, 10mg on day 30mg on day 3, and then of alemtuzumab. 1 1 _:Ah�M'!y3yMa6. · . 2, lmmur1oglobullnN; G_1 monoclonal CAMPATH·JH 30 mg three times weekly), use with the higher dose from Extended follow-up of patients in this study group, for up yl-.Chain ah!ihuman antigen CD52), disulfidE! the outset has been investigated. 5 Prolonged treatment to 5 years from the start of therapy, found that alemtuzumab remained significantly more effective than ratrn onqclonal CAMPATH·lH light,chair\, dirnei.\10th 1:\pman with subcutaneous low-dose alemtuzumab ( 10 mg three : . times weekly for 18 weeks) has also been tried and was interferon beta-la.2 The superiority of alemtuzumab CAS -- 216503-SJ-0. reported to be as effective as intravenous infusion in compared with interferon beta-la was further confirmed -- Lin>:co4. in a phase 3 study of previously untreated patients with ATC patients with chronic lymphocytic leukaemia and a poor prognosis. 6 early, relapsing-remitting multiple sclerosis' and also in ATC Vet� 3A l89Dfi42V. 1. Montillo M, et al. Safety and efficacy of subcutaneous Campath-lH for those with at least one relapse after disease-modifying NOTE.UN!/ -The name FluCam has been used for a regimen of treating residual disease with chronic lymphocytic leukemia responding therapy with either interferon beta or glatiramer.4 Haematologica 2002; 87: 695-700. alemtuzumab with fludarabine. Distinguish from Flucam, to fludarabine. I. Coles AJ, et al. CAMMS223 Trial Investigators. Alemtuzumab vs. 2. Lundin J, et at. Phase II trial of subcutaneous anti-CD52 monoclonal N Eng/ Med 359: which is a proprietary name for ampiroxicam (p. 21.1). interferon beta- 1a in early multiple sclerosis. 1 2008; antibody alemtuzumab (Campath-lH) as first-line treatment for patients 1786-1801. Blood 2002; 100: with B-cell chronic lymphocytic leukemia (B·CLL) . 2. Coles AJ, et a!. Alemtuzumab more effective than interferon fi -la at 5· 768-73. year follow-up of CAMMS223 clinical trial. Neurology 2012; 78: 1069- Uses and Administration 3. Hale G, et al. Blood concentrations of alemtuzumab and antiglobulin 78. Alemtuzumab is a humanised derivative of campath-IG, a responses in patients with chronic lymphocytic leukemia following 3. Cohen JA, et al. Alcmtu:z.umab versus interferon beta I a as first-line intravenous or subcutaneous routes of administration. Blood 2004; 104: rat monoclonal antibody to the CD52 antigen found on treatment for patients with relapsing-remitting multiple sclerosis: a 948-5 5. randomised controlled phase 3 trial. Lancet 2012; 380: 1819-28. lymphocytes. It is used in the treatment of B-ee!! chronic 4. Stilgenbauer S, et al. Subcutaneous alemtuzumab in fludarabine 4. Coles AJ, et al. Alemtuzumab for patients with relapsing multiple lymphocytic leukaemia (p. 693.3) and is also licensed in the refractory chronic lymphocytic leukemia: clinical results and prognostic sclerosis after disease-modifying therapy: a randomised controlled phase EU (under the trade name of Lemtrada) for use in relapsing marker analyses from the CLL2H study of the German Chronic 3 trial. Lancet 2012; 380: 1829-39. Clin Oncol 2009; 27: Lymphocytic Leukemia Study Group. 1 3994-400 1. remitting multiple sclerosis (below). 5. Karlsson C, et al. Phase II study of subcutaneous alemtuzumab without For the treatment of chronic lymphocytic leukaemia dose escalation in patients with advanced-stage, relapsed chronic the dose of alemtuzumab must be increased gradually to lymphocytic leukaemia. Br J Haematol 2009; 144: 78�85. Adverse Effects, Treatment, and Precautions avoid infusion-related reactions (see Adverse Effects, 6. Cortelczzi A, et al. A pilot study of low-dose subcutaneous alemtuzumab For general discussions, see Antineoplastics, p. 726.1, therapy for patients with hemotherapy-refractory [sic] chronic below). Alemtuzumab should be diluted in 100mL sodium lymphocytic leukemia. Haematologica 2005; 90: 410-12. p. 730.2, and p. 732.2. chloride 0.9% or glucose 5%. The initial dose is 3mg daily, Alemtuzumab commonly causes bone marrow depres given as an intravenous infusion over 2 hours (it may be sion, which may be severe and prolonged; fatalities have increased up to 8 hours in some patients, see Adverse Administration in subsequent cycles. The dose of alemtu occurred. Auto-immune anaemia and auto-immune Effects, below). This dose should be repeated daily until it is zumab may be modified from the usual intravenous main thrombocytopenia and haemolytic anaemia have been tolerated; the dose should then be increased to 10mg daily. tenance dose (see Uses and Administration, above) for reported less commonly; however, fatalities have been When this dose is tolerated, the maintenance dose of 30 mg neutropenia and thrombocytopenia in those being treated reported. Single doses greater than 30 mg, or cumulative can be started; this dose escalation usually takes 3 to 7 days. for chronic lymphocytic leukaemia as follows: weekly doses greater than 90 mg should not be used, The maintenance dose of 30 mg is given three times weekly In patients with higher baseline values whose absolute because of the increased incidence of pancytopenia. on alternate days. The total duration of therapy, including neutrophil count (AN C) falls to < 250 cells/mm3 and/or Complete blood and platelet counts should be measured dose escalation, is 12 weeks. Doses should be modified whose platelet count falls to S25 000 cells/mm3: weekly during alemtuzumab therapy, and more frequently according to haematological toxidty (see Administration in • for first occurrence: withhold alemtuzumab. Resume at if anaemia, neutropenia, or thrombocytopenia occur. Subsequent Cycles, below). 30mg when ANC ""500 cells/mm3 and platelet count Treatment should be interrupted if severe myelosuppression For the treatment of multiple sclerosis alemtuzumab ""'50000 cells/mm3 or evidence of haematological toxicity are seen and stopped has been given by intravenous infusion over 4 hours for 2 • for second occurrence: withhold alemtuzumab. Resume permanently if auto-immune anaemia or auto-immune treatment courses, as follows: at 10 mg when ANC ""' 500 cells/mm3 and platelet count thrombocytopenia develops. Lymphopenia may be pro • initial treatment course: 12 mg daily for 5 consecutive ""'50 000 cells/mm3 found with alemtuzumab therapy, and opportunistic days, to a total dose of 60 mg • for third occurrence: stop alemtuzumab infections are common, and occasionally life-threatening. • second treatment course given 12 months after the initial In patients who are started on alemtuzumab with a baseline Antimicrobial prophylaxis is recommended from the start of course: 12 mg daily for 3 consecutive days, to a total dose ANC already S 250 cells/mm3 and/or a baseline platelet therapy until after completion; if serious infection occurs, of 36mg count S25 000 cells/mm3, and who have a 2:50% decrease treatment should be interrupted. Recovery of lymphocyte Missed doses within a treatment course should not be given from baseline: counts may take 6 months or longer after stopping on the same day as a scheduled dose. Patients should be pre • for first occurrence: withhold alemtuzumab. Resume at treatment. treated with a corticosteroid on each of the first 3 days of 30 mg upon return to baseline value Alemtuzumab commonly causes an acute cytokine any course. Oral prophylaxis with 200 mg twice daily of • for second occurrence: withhold alemtuzumab. Resume release syndrome. The reaction usually includes rigors, aciclovir (or similar) for herpes infection should also be at l 0 mg upon return to baseline value fever, nausea and vomiting, hypotension, rash, urticaria, started on the first day of each course and continued for a • for third occurrence: stop alemtuzumab pruritus, shortness of breath, headache, and diarrhoea. minimum of l month following treatment. If alemtuzumab is withheld, and the time to recovery is 2: 7 Rarer, more serious reactions may include bronchospasm, Alemtuzumab is under investigation for induction days, then alemtuzumab should be restarted at the usual syncope, pulmonary infiltrates, acute respiratory distress therapy in transplantation (see Organ and Tissue initial dose and increased gradually (see Uses and syndrome, respiratory arrest, myocardial infarction, and Transplantation, p. 1936.2, et seq). Administration, above). cardiac arrest. Cardiac adverse effects have been fatal in
The symbol t denotes a preparation no longer actively marketed 738 Antineoplastics
some instances. These infusion-related reactions are most 4. Kurie JM, et a!. Treatment of former smokers with 9�ds�retinoic acid common at the start of therapy: the dose must be increased Interactions reverses loss of retinoic add receptor-beta expression in the bronchial epithelium: results from a randomized placebo-controlled trial. J Natl gradually when beginning treatment, or if it is interrupted There are no formal interaction studies with alemtuzumab; Cancer Inst 2003; 95: 206-14. for 7 days or more. Pre-medication with an oral or however, it is recommended that it should not be given 5. Aboulafia DM. et a/. 9�cis�Retinoic acid capsules in the treatment of intravenous corticosteroid, oral antihistamine, and analge within 3 weeks of other chemotherapy drugs, and that AIDS�related Kaposi sarcoma: results of a phase 2 multicenter clinical Arch Dermatol 2003; sic should also be used, particularly before the first dose, and patients should not receive live viral vaccines for at least 12 trial. 139: 178-86. 6. Ruzicka T, et al. Oral alitretinoin (9�cis-retinoic add) therapy for chronic months after receiving alemtuzumab. with dose increases. If acute infusion reactions persist, the hand dermatitis in patients refractory to standard therapy: results of a infusion time may be extended to 8 hours from the time of randomized. double-blind, placebo�controlled, multicenter trial. Arch reconstitution. Dermatol 2004; 140: 1453-9. Pharmacokinetics et al. Other adverse effects include fatigue, anorexia, asthenia, 7. Ruzicka T, Efficacy and safety of oral alitretinoin (9�ds retinoic In patients with B-ee!! chronic lymphocytic leukaemia, add) in patients with severe chronic hand eczema refractory to topical malaise, arthralgia, myalgia, bone pain, back pain, chest corticosteroids: results of a randomized, double�blind, placebo� pain, hypertension, cyanosis, and bradycardia or tachy distribution of alemtuzumab is mainly to the extracellular controlled, multicentre trial. Br J Dermato/ 2008; 158: 808-17. cardia. Localised oedema, stomatitis, mucositis, and abdo fluid and plasma. Over 12 weeks, clearance has been found 8. Garnock�Jones KP, Perry CM. Alitretinoin: in severe chronic hand Drugs minal pain have been reported, as have dizziness, to decrease with repeated dosing, with consequent . eczema. 2009; 69: 162 5-34. accumulation in plasma, and the rate of elimination to 9. NICE. Alitretinoin for the treatment of severe chronic hand eczema paraesthesia, tremor, and taste loss. Confusion, insomnia (technology appraisal guidance 177, issued AugUst 2009). Available at: or somnolence, depression, or anxiety may occur. Electro approach zero-order kinetics. The half-life is reported to be 8 http://www .nice.org. uk/nicemedia/live/12219/4522 5/4522 5.pdf lyte disturbances include hyponatraemia and hypocalc hours after a first dose of 30 mg, and 6 days after the last (accessed 28/06110) aemia. Coughing, haemoptysis, sinusitis, bronchitis, and 30 mg dose. Steady-state concentrations are reached after pharyngitis have been reported. about 6 weeks of therapy. Adverse Effects Alemtuzumab is contra-indicated for patients with active References. Oral doses of alitretinoin may produce similar adverse et al. systemic infection, or underlying immunodeficiency. l. Rebello P, Pharmacokinetics of CAMPATH-IH in BMT patients. effects to those of isotretinoin (see p. 1707.2). Decreases in Cytotherapy 2001; 3: 261-7. concentrations of thyroid stimulating hormone and free T 2. Mould DR, et al. Population pharmacokinetics�pharmacodynamics of 4 Auto-immune disorders. Aside from auto-immune cyto alemtuzumab (CampatbRTM) in patients with chronic lymphocytic are also often reported with alitretinoin, as are increases in penias, alemtuzumab has been associated with the devel leukaemia and its link to treatment response. Br J Clin Pharmacal 2007; platelets and increases in blood concentrations of creatine opment of auto-immune thyroid disease in 20 to 30% of 64: 278-91. phosphokinase. Ankylosing spondylitis is uncommon. 3. Elter T, et al. Pharmacokinetics of alemtuzumab and the relevance in patients, occurring months to years after treatment.1 Anti clinical practice. Leuk Lymphoma 2008; 49: 2256-62. Local skin toxicity may occur on topical application of glomerular basement membrane disease has also been alitretinoin, in particular erythema and oedema, and in reported after alemtuzumab, 2 as has Guillain-Barre some patients this may be dose-lintiting. Pain, paraesthesia, syndrome.' It has been commented' that B-cell recovery ���P.�.��.!��-��---········································································· rashes, pruritus, exfoliative dermatitis, and other skin tends to precede T-cell recovery after alemtuzumab treat ProprielaryPreparations (details are given in Volume B) disorders may also occur locally. Lymphadenopathy, ment, and that the auto-immune diseases seen after ther phlebitis, cellulitis, and bacterial infections have been Arg.: Campath; Austral.: Mab apy are mainly antibody-mediated, and respond to B-ee!! Single-ingredient Preparations. Campath; MabCampatht; MabCampatht; reported. Alitretinoin may have a weak photosensitising Austria: Bel· g.: Braz. : depletion. Campatht; Canad.: MabCampath; cz.: MabCampatht; Denm.: effect, and patients should minimise exposure of treated 1. Jones JL, et al. IL-21 drives secondary autoimmunity in patients with MabCampatht; Fr.: MabCampatht; Ger.: MabCampatht; Gr.: areas to sunlight or other ultraviolet light during therapy. multiple sclerosis, following therapeutic lymphocyte depletion with MabCampatht; Hong Kong: MabCampath; Hung.: MabCam alemtuzumab (Campath�lH). J Clin Invest 2009; ll9: 2052-6 1. 2. Clatworthy MR, etal. Anti�glomerular basement membrane disease after patht; Ind1»1.:MabCampath; Irl. : MabCampatht; Israel: Mab Precautions alemtuzumab. N Engl J Med 2008; 359: 768-9. Campatht; Ital.: MabCampatht; Malaysia: MabCampath; Mex.: When alitretinoin is given orally, the precautions desctibed 3. Abbi KKS, et al. Guillain�Barre syndrome after use of alemtuzumab MabCampath; Neth.: MabCampatht; Norw.: MabCampatht; (Campath) in a patient with T�cell prolymphocytic leukemia: a case NZ: MabCampath; Pol.: MabCampatht; Port.: MabCampatht; under isotretinoin (see p. 1709.2) including report and review of the literature. Leuk Res 2010; 34: e154-el56. Rus.: Campath (1<3MllllC); S.Afr.: MabCampath; Singapore: contra-indication of use in pregnancy and during breast MabCampath; Spain: MabCampatht; Swed.: MabCampatht; feeding, should be adopted. Although absorption does not Effects on the lungs. Diffuse alveolar haemorrhage has Switz. : MabCampatht; Thai.: MabCampath; Turk.: MabCam seem to occur to any great extent with topical use licensed been reported after a single dose of alemtuzumab was path; UK: MabCampatht; Ukr. : MabKampat (Ma6KaMrraT); product information also contra-indicates such use in used during renal transplantation in a patient with X USA: Campath. pregnancy and in breast-feeding mothers. Oral alitretinoin linked Alport syndrome (an inherited disorder involving is further contra-indicated in patients with severe renal damage to the kidneys, haematuria, and hearing loss) 1 impairment and uncontrolled hypothyroidism. Topical A. treatment with alitretinoin should not be used on lesions in 1. Sachdeva Matuschak GM. Diffuse alveolar hemorrhage following Alitretinoin IBAN. usAN, riNNi alemtuzumab. Chest 2008; 133: 1476-8. dose proximity to other skin disorders.
Infection. Reactivation of hepatitis B,1 hepatitis C, 2 and Interactions CMV3 has been reported with the use of alemtuzumab. The interactions described under isotretinoin (see p. 1710.1) Patients who have been pretreated with purine analogues also apply to oral alitretinoin. Alitretinoin is metabolised by or those with advanced disease and not responding to the hepatic cytochrome P450 isoenzyme system, particu alemtuzumab therapy appear to be at highest risk for larly CYP3A4. Use with CYP3A4 inhibitors such as infectious complications. Recommendations for screening ketoconazole increases the plasma concentration of and prophylaxis4 and guidelines' and reviews' concerning alitretinoin and dose reduction may be required. Use of management have been published. Six infection-related products containing diethyltoluamide is not recommended deaths have been reported' after previously untreated during topical alitretinoin therapy, as animal studies indicate patients with B-ee!! chronic lymphocytic leukaemia were an increase in diethyltoluamide toxicity with concurrent treated with fludarabine and rituximab, followed by alem use. tuzumab. These deaths may have resulted from a pro longed period of immunosuppression due to the sequen Uses and Administration Pharmacokinetics cing of these drugs without sufficient recovery time. In Alitretinoin is a retinoid related to isotretinoin (p. 1706.2). It After oral doses alitretinoin is variably absorbed from the the EU, alemtuzumab is licensed for use in patients for is given orally for severe chronic hand eczema (p. 1684. 1) whom fludarabine combination chemotherapy is not gastrointestinal tract. When alitretinoin is taken with food, that is unresponsive to treatment with potent topical absorption becomes less variable and the systemic exposure appropriate. corticosteroids. Patients with mainly hyperkeratotic eczema is enhanced by a factor of 4. Alitretinoin is highly bound to 1. lannitto E, et al. Hepatitis B virus reactivation and alemtuzumab therapy. are more likely to respond to treatment with alitretinoin. It Bur J Haematol 2005; 74: 254-8. plasma proteins. It undergoes metabolism by oxidation in is also used topically, in the management of cutaneous 2. Anoop P, et al. Severe liver dysfunction from hepatitis C virus the liver by the cytochrome P450 isoenzyme system into the reactivation following alemtuzum.ab treatment for chronic lymphocytic lesions in patients with AIDS-related Kaposi's sarcoma major metabolite 4-oxo-alitretinoin. Alitretinoin and its Br J Haematol 2010; leukaemia. 148: 484-6. (p. 718.1). metabolites are excreted mainly in the urine, with about 3. Laurenti L, et al. Cytomegalovirus reactivation during alemtuzumab The recommended starting dose of oral alitretinoin in therapy for chronic lymphocytic leukemia: incidence and treatment 30% excreted in the faeces. The elimination half-life of adults is 30 mg once daily, with reduction to 10 mg once with oral gandclovir. Haematologica 2004; 89: 1248-52. unchanged alitrerinoin is about 2 to 0 hours. Alitretinoin et al. daily if adverse effects occur. The usual dose range is from 10 4. Thursky KA, Spectrum of infection, risk and recommendations for and 4-oxo-alitrerinoin do not accumu:lateI in the body. prophylaxis and screening among patients with lymphoproliferative to 30 mg once daily, taken with meals. Treatment may be Systemic absorption of topical alitretinoin is not disorders treated with alemtuzumab. Br J Haematol 2006; 132: 3-12. continued for 12 to 24 weeks depending on response. In the 5. O'Brien SM, et al. Updated guidelines on the management of considered to be extensive. event of relapse, further treatment courses may be cytomegalovirus reactivation in patients with chronic lymphocytic leukemia treated with alemtuzumab. Clin Lymphoma Myeloma 2006; 7: considered. 125-30. Topical treatment with a 0.1% alitretinoin gel is applied ���P.�.��!��-��---········································································· 6. Elter T, et al. Management of infections in patients with chronic directly to the lesions twice daily, increasing to up to 4 times Proprietary Preparations (details are given in Volume B) Ann Hematol lymphocytic leukemia treated with alemtuzumab. 2009; daily if tolerated. Doses should be increased at intervals of at 88: 121-32. Single-ingredient Preparations. Arg. : Panretin; Austria: Panretio; 7. Bayer, UK; Genzyme, UK. hnportant safety information: six infection� least 2 weeks. If local toxicity occurs, application frequency Toctino; Canad.: Toctino; Cz. : Panretin; Denm.: Toctino; Fin.: related deaths reported after treatment with MabCampath(alemtuzu� should reduced, or treatment temporarily stopped, until Toctino; Fr.: Panretin; Toctino; Ger.: Panretin; Toctino; Gr.: mab) following Fludarabine+Rituximab induction in patients with B� the symptomsbe subside. EU licensed product information Panretin; Irl.: Panretin; Israel: Toctino; Neth.: Panretin; Tocti Cell Chronic Lymphocytic Leukemia (CLL) (issued 1 1th February 2008) . states that if no response is seen after 12 weeks, therapy no; Norw. : Toctino; Pol. : Panretin; Port. : Panretin; Spain: Pan Available at: http://www.mhra.gov.uk/home/idcplg?IdcService=GET_ FILE&dDocName=CONO 141 04&Revisi onSelectionMethod=Latest should be stopped; however, US licensed product retin; Switz.: Toctino; UK: Toctino; USA: Panretin. (accessed 12/05/08) information states that some patients have required over 14 weeks to respond. Treatment may be continued as long Porphyria. The Drug Database for Acute Porphyria, com as the patient responds. Altretamine (BAN, USAN. r/NN) piled by the Norwegian Porphyria Centre (NAPOS) and References. the Porphyria Centre Sweden, classifies alemtuzumab as 1. Cheer SM, Foster RH. Alitretinoin. Am J Clin Dermatol 2000; 1: 307-14. not porphyrinogenic; it may be used as a drug of first 2. Bodsworth NJ, et al. Phase III vehicle�controlled, multi-centered study of topical alitretinoin gel 0.1% in cutaneous AIDS-related Kaposi's choice and no precautions are needed.1 sarcoma. Am J Clin Dermatol 2001; 2.: 77-87. I. The Drug Database for Acute Porphyria. Available at: http://www. 3. Miles SA, et al. Antitumor activity of oral 9-cis-retinoic add in HN� drugs�porphyria.org (accessed 29/09/ll) associated Kaposi's sarcoma. AIDS 2002; 16: 421-9.
All cross-references refer to entries in Volume A