790 Antineoplastics Viessia; Vinilex; Neth.: Navelbine; Norw.: Navelbine; NZ: Navelbine; long as there is no evidence of progressive disease or unaccepta- Philipp.: Navelbine; Vinotel; Pol.: Navelbine; Navirel; Port.: Navelbine; ble toxicity. Vinorel; Rus.: Maverex (Маверекс); Navelbine (Навельбин); S.Afr.: Navel- bine; Singapore: Navelbine; Spain: Navelbine; Swed.: Navelbine; Switz.: Vorinostat is also under investigation for the treatment of multi- O Navelbine; Thai.: Navelbine; Vinelbine; Turk.: Navelbine; UK: Navelbine; ple myeloma and mesothelioma. H CO USA: Navelbine. 3 ◊ References. CH3 OO 1. O’Connor OA. Clinical experience with intravenous and oral formulations of the novel histone deacetylase inhibitor suberoy- H Vorinostat (USAN, rINN) lanilide hydroxamic acid in patients with advanced hematologic O malignancies. J Clin Oncol 2006; 24: 166–73. SAHA; Suberoylanilide Hydroxamic Acid; Vorinostatum. N-Hy- 2. Krug LM, et al. Potential role of histone deacetylase inhibitors O droxy-N′-phenyl octanediamide. in mesothelioma: clinical experience with suberoylanilide hy- H droxamic acid. Clin Lung Cancer 2006; 7: 257–61. OH O Вориностат 3. Richon VM. Cancer biology: mechanism of antitumour action of CH3 C H N O = 264.3. vorinostat (suberoylanilide hydroxamic acid), a novel histone 14 20 2 3 OH H CAS — 149647-78-9. deacetylase inhibitor. Br J Cancer 2006; 95 (suppl): S2–S6. O 4. O’Connor OA. Clinical experience with the novel histone OH deacetylase inhibitor vorinostat (suberoylanilide hydroxamic ac- O H id) in patients with relapsed lymphoma. Br J Cancer 2006; 95 H (suppl): S7–S12. HN O N 5. Duvic M, Zhang C. Clinical and laboratory experience of vori- CH3 O nostat (suberoylanilide hydroxamic acid) in the treatment of cu- taneous T-cell lymphoma. Br J Cancer 2006; 95 (suppl): S13–S19. Description. Zinostatin is an antineoplastic antibiotic obtained HN 6. Anonymous. Vorinostat (Zolinza) for cutaneous T-Cell lympho- from Streptomyces carzinostaticus. ma. Med Lett Drugs Ther 2007; 49: 23–4. OH Preparations Pharmacopoeias. Jpn includes zinostatin stimalamer. Proprietary Preparations (details are given in Part 3) Profile Adverse Effects, Treatment, and Precautions USA: Zolinza. Zinostatin is an antibiotic with antineoplastic activity and has For general discussions see Antineoplastics, p.635, p.639, and p.641. been used in the treatment of malignant neoplasms. The most common adverse effects of vorinostat are gastrointes- Zinostatin stimalamer (SMANCS), a conjugate of zinostatin Vorozole (BAN, USAN, rINN) ⊗ tinal disturbances, fatigue, chills, dry mouth and taste disorders. with a styrene-maleic acid polymer, is used for the treatment of Thrombocytopenia and anaemia also occur commonly, and are R-83842; Vorozol; Vorozolum. (+)-6-[4-Chloro-α-(1,2,4-triazol- liver cancer. dose-related; dose reductions may be necessary and in some in- 1-yl)benzyl]-1-methyl-1H-benzotriazole. stances, therapy may need to be stopped. Pulmonary embolism Ворозол has occurred. Other adverse effects include muscle spasms, alo- C16H13ClN6 = 324.8. pecia, dizziness, peripheral oedema, headache, pruritus, cough, CAS — 129731-10-8. Zorubicin Hydrochloride (USAN, rINNM) upper respiratory-tract infection, and pyrexia. Hypokalaemia and ATC — L02BG05. hyperglycaemia have been reported, as has prolongation of the ATC Vet — QL02BG05. Hidrocloruro de zorubicina; NSC-164011; RP-22050 (zoru- QT interval. Blood cell counts, electrolytes, glucose, and serum bicin); Zorubicine, Chlorhydrate de; Zorubicini Hydrochloridum. creatinine should be monitored every 2 weeks during the first 2 Benzoic acid (2S-cis)-{1-[4-(3-amino-2,3,6-trideoxy-α-L-lyxo-hex- months of therapy and monthly thereafter. Baseline and periodic Cl opyranosyloxy)-1,2,3,4,6,11-hexahydro-2,5,12-trihydroxy-7-meth- ECG monitoring should be performed. oxy-6,11-dioxonaphthacen-2-yl]ethylidene}hydrazide hydro- Interactions chloride. Severe thrombocytopenia and gastrointestinal bleeding have Зорубицина Гидрохлорид been reported when vorinostat has been given with other histone N deacetylase inhibitors such as valproic acid; platelet counts C34H35N3O10,HCl = 682.1. should be monitored every 2 weeks for the first 2 months of ther- N N CAS — 54083-22-6 (zorubicin); 36508-71-1 (zorubicin apy. Vorinostat may prolong prothrombin time and affect the hydrochloride). H C INR in patients receiving coumarin anticoagulants. 3 ATC — L01DB05. N Pharmacokinetics ATC Vet — QL01DB05. After an oral dose of vorinostat with a high-fat meal, mean time N to maximum plasma concentration was about 4 hours; this was N reduced to 1.5 hours after fasting. Aside from this decrease in the rate of absorption, a high-fat meal also increased the extent of Profile NH2 absorption. While these results were stated not to be clinically Vorozole is a selective nonsteroidal inhibitor of the aromatase HO significant, licensed product information recommends that vori- (oestrogen synthetase) system. It has been investigated in the nostat be taken with food. Plasma protein binding is about 71%. treatment of breast cancer. CH3 H C O OOHO O Vorinostat is metabolised by glucuronidation and hydrolysis fol- ◊ References. 3 lowed by oxidation; metabolites are pharmacologically inactive. H 1. Goss PE, et al. Randomized phase III trial comparing the new N N Less than 1% of a dose is recovered in the urine as unchanged potent and selective third-generation aromatase inhibitor voro- drug. The mean terminal half-life is about 2 hours for vorinostat. zole with megestrol acetate in postmenopausal advanced breast ◊ References. cancer patients. J Clin Oncol 1999; 17: 52–63. O 2. Harper-Wynne CL, et al. Comparison of the systemic and intra- H3C HO 1. Rubin EH, et al. A study to determine the effects of food and tumoral effects of tamoxifen and the aromatase inhibitor voro- OH O multiple dosing on the pharmacokinetics of vorinostat given zole in postmenopausal patients with primary breast cancer. J orally to patients with advanced cancer. Clin Cancer Res 2006; Clin Oncol 2002; 20: 1026–35. 12: 7039–45. (zorubicin) Uses and Administration Vorinostat is a histone deacetylase inhibitor used for the treat- Zinostatin (USAN, rINN) Profile ment of cutaneous T-cell lymphoma (see Non-Hodgkin’s Lym- Zorubicin is an anthracycline antibiotic with antineoplastic ac- Neocarzinostatin; NSC-69856; NSC-157365; Zinostatina; Zi- phomas, p.656). The recommended dose is 400 mg orally, given tions similar to those of doxorubicin (see p.712). It has been used nostatine; Zinostatinum. once daily with food. This may be reduced to 300 mg once daily, as the hydrochloride in the treatment of acute leukaemias. with a further reduction to 300 mg once daily for 5 consecutive Зиностатин days of each week, if needed. Treatment may be continued as CAS — 9014-02-2. 792 Antiparkinsonian Drugs rhoea. There appear to be no important differences in the agement (but see below). However, there is evidence that 18. Katzenschlager R, et al. Anticholinergics for symptomatic man- agement of Parkinson’s disease. Available in The Cochrane Da- efficacy of antimuscarinics for Parkinson’s disease but some patients may benefit from modified-release formula- tabase of Systematic Reviews; Issue 3. Chichester: John Wiley; some patients may tolerate one drug better than another. tions of levodopa with a peripheral dopa-decarboxylase or 2002 (accessed 16/02/06). Those commonly used for Parkinson’s disease include COMT inhibitor. As levodopa competes with amino acids 19. Deane KHO, et al. Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson’s disease. Avail- benzatropine, orphenadrine, procyclidine, and trihexy- for uptake into the brain, attempts to lessen fluctuations in able in The Cochrane Database of Systematic Reviews; Issue 4. phenidyl. dopamine brain concentrations have included taking levo- Chichester: John Wiley; 2004 (accessed 16/02/06). 20. Schapira AHV, Olanow CW. Neuroprotection in Parkinson dis- • Amantadine is a weak dopamine agonist with some an- dopa on an empty stomach and also delaying most of a day’s protein consumption until the evening. Addition of ease: mysteries, myths, and misconceptions. JAMA 2004; 291: timuscarinic activity although its activity as an antago- 358–64. entacapone, rasagiline, selegiline, or a dopamine agonist nist of N-methyl-D-aspartate may also have a beneficial 21. Samii A, et al. Parkinson’s disease. Lancet 2004; 363: 1783–93. 22. Thanvi BR, Lo TCN. Long term motor complications of levo- effect in Parkinson’s disease. It has mild antiparkinsoni- may also help to reduce ‘on-off’ phenomena. If fluctua- tions remain a problem subcutaneous apomorphine is of- dopa: clinical features, mechanisms, and management strate- an effects compared with levodopa but is relatively free gies. Postgrad Med J 2004; 80: 452–8. from adverse effects. It can improve bradykinesia as ten effective. In some countries a gel formulation of levo- 23. Stocchi F, Olanow CW. Continuous dopaminergic stimulation in early and advanced Parkinson’s disease. Neurology 2004; 62 well as tremor and rigidity but only a small proportion dopa with carbidopa is available for continuous infusion by an ambulatory pump into the duodenum when other (suppl 1): S56–S63. of patients derive much benefit. It is used similarly to 24. Barone P, et al. Treatment of nocturnal disturbances and exces- antimuscarinics in early disease when symptoms are available combination therapy has not been satisfactory. sive daytime sleepiness in Parkinson’s disease. Neurology 2004; Other complications of treatment