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Osetljivosti. Direktna vizualizacija epiglotisa, posebno kod odraslih, je neophodna kako bi se isklju~io epiglotitis. Kod dece kod koje se sumnja na epiglotitis, Rtg vrata mo`e biti najsigurniji prvi korak. Na kraju, treba u~initi procenu kardiovaskularnog stanja kako bi se otkrili i se na bol u grlu i bol pri gutanju, posetio tri lekara bez rezultata; ~etvrti lekar je obavio Rtg snimanje mekih tkiva aj stranog tela Ve ; ina pacijenata koja se javi zbog ose ; aja stranog tela u grlu to ~ini kratko nakon jela, obi~no ribe ili pileta. esto su u stanju da poka`u nivo i stranu gde ose ; aju strano telo i na taj na~in informi i, o i, ~vr i objekti obi~no pro kroz farinks i smeste se u krikofaringeus, gornju tre ; inu ezofagusa ili gastroezofagealni sfinkter. Glavni simptom faringealnog stranog tela je bol za vreme gutanja, ali abrazije erozije ; farinksa mogu dati sli~ne simptome. Me|utim, bol od faringealnih abrazija se tokom vremena smanjuje, dok se kod stranog tela pogor aj stranog tela vi i da proguta smotuljak vate namo~en u barijum. Pozicija smotuljka ; e ozna~iti polo`aj stranog tela i potvrditi dijagnozu. Strategija odstranjenja stranog tela se diskutuje kasnije u ovom poglavlju. FARINGITIS Kako je striktno definisan, faringitis je inflamacija farinksa uzrokovana infektivnim ili neinfektivnim agensima, koja dovodi do subjektivnog ose ; aja "bolnog grla". e va`nosti za urgentnog lekara da odredi glavni poreme ; aj kako bi se izbegle ozbiljne komplikacije. Ogromna ve ; ina faringitisa nastaje zbog virusne ili bakterijske infekcije, ali postoje druga bolesna stanja kod kojih je faringitis glavni simptom, te je va`no biti sposoban da se prepoznaju njihove raznovrsne manifestacije i da se bude sposoban da se diferenciraju me|usobno na bazi fizikalnog pregleda i ili laboratorijskih testova. Streptokokne infekcije "Strep skra ; enica od streptokok - prim. prev. ; grlo" je verovatno najvi e zloupotrebljavana dijagnoza i nepotrebno le~ena bolest u dana njoj medicini. Mnogi klini~ari su pogre nog mi ljenja da su svi pacijenti sa faringitisom i pozitivnim brisom na grupu A -hemoliti~kog streptokoka u velikoj opasnosti.
Combination therapy involves the use of pegylated interferon injections, once a week, and daily ribavirin capsules. A potentially serious side effect of ribavirin is anaemia caused by haemolysis destruction of red blood cells and resultant release of haemoglobin ; . Doctors will therefore monitor a person's blood counts very closely, especially in the first few weeks. Also, ribavirin has been shown to cause birth defects in animal studies. Combination therapy, therefore, is not available to women who are pregnant and or breastfeeding, or to anyone both women and men ; who do not use adequate contraception during, and for up to six months after, treatment.
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Percentage increases suggesting the absolute fall is part of the generalized lymphopaenia associated with therapy[70]. Three large multicentre studies have been presented comparing pegylated interferon with ribavirin to standard interferon ribavirin. Two ACTG A5071 and APRICOT ; have utilised pegylated interferon alpha 2a Pegasys ; , and the third, RIBAVAC, utilised pegylated interferon alpha 2b Viraferon peg ; [51-53]. Due to differences in the patient populations recruited to these studies it is not possible to make a comparison between the two forms of pegylated interferon. 5.4.2.1. APRICOT study [51] The APRICOT study randomised individuals to interferon alpha 2a 3 miu , 3 times a week plus ribavirin 800mg daily n 285 ; pegylated interferon alpha 2a plus ribavirin placebo n 286 ; or pegylated interferon alpha 2 plus ribavirin 800mg daily n 289 ; . Individuals were treated for 48 weeks and followed for a further 24 weekspost thaerapy. Results were reported as end of treatment ET ; and as sustained response SR ; defined as hepatitis C PCR-negative 24 weeks post cessation of therapy. The results of this study showed the SR to be superior in the pegylated interferon with ribavirin treated arm. 12% of the standard interferon arm, 20% of the pegylated interferon + placebo arm and 40% in the pegylated interferon + ribavirin arm achieved SR. Response rates were greater in all arms for individuals with genotype 2 or 3. For those treated with pegylated interferon and ribavirin response rates for genotype 1 were 38% ET and 29% SR and in genotype 2 or 3 and 62% SR. This study also showed that a poor early 12 week ; virological response defined as failure to achieve a HCV RNA less than 50 iu, or less than a 2 log drop in HCV RNA was highly predictable of lack of treatment response. In individuals failing to achieve these responses at 12 weeks treatment should be stopped unless the aim is to achieve histological improvement rather than HCV eradication. 5.4.2.2 . ACTG A5071 [53] ACTG A5071 randomised individuals to receive either pegylated interferon alpha 2a weekly with ribavirin at an escalating dose from 600mg to 1, 000mg per day depending on toleration or interferon alpha 2 alpha 6 mega units three times a week for 12 weeks, reducing to 3 mega units 3 times a week for a further 36 weeks with the same escalating dosage of ribavirin. Individuals were treated for 48 weeks in total with 24 weeks of follow up. The end of treatment response rate was greater in the pegylated interferon arm 41% vs 12% ; as was the sustained response 27% vs 12% ; . Individuls with genotype non-1 had a greater chance of both end of treatment response 80% vs 29% ; and sustained virological response 73% vs 14% ; 5.4.2.3. RIBAVIC [52] The RIBAVIC study compared pegylated interferon alpha 2b 1.5 g kg week ; plus ribavirin 800mg per day with standard interferon 3 million units three times per week plus ribavirin 800mg per day. The results of this study are difficult to interpret due to a very high drop out rate. SR was achieved in 27% of the pegylated interferon arm and 19% of the 10.
SNF-report No. 20 05 Besides the weaknesses in the establishment of law, there are still many gaps to be filled, concerning fishery investment, security and administration. Fishery investment should include both governmental financial support and private funds and credit. It involves the investment in fishing and its management as well as the research and the introduction of fishery technology. In this regard, much is yet to be done, and our governmental financial support makes up less than 2% of world's total. In 2000, Chinese governmental support to fishery was below the European lever of 1977, approximately equal to 1 6 that of United States, much lower than that of Japan.
| What is RibavirinIn the published literature regarding efficacy. Reported outcomes have been inconsistent, and they have not been proven in large, well-designed studies to increase pregnancy rates compared to AI. Superovulation with intrauterine insemination involves the intentional development and ovulation of multiple follicles. Indications for artificial insemination: pharmacologic treatment alone has not been successful unexplained infertility abnormal cervical mucus donor insemination presence of antisperm antibodies low sperm counts with normal motility and requip.
FIGURE 4. Effect of ribavirin on BALB cJ macrophage TNF- production induced by MHV-3. One million macrophages from BALB cJ mice were stimulated with MHV-3 at a MOI of 2.5. TNF levels in the supernatants were measured by ELISA after incubation for 8 h. Data are presented as mean SD for three separate experiments done in duplicate. * represents p 0.01 compared with macrophages MHV-3.
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Not include , 031, 290 from the exercise of previously granted stock options. In addition, directors are reimbursed for expenses incurred as part of their service as directors. An increase in directors' remuneration was approved at the annual shareholders meeting held on May 4, 2006. In addition, the remuneration of the Company's statutory independent directors was recently increased, with their current remuneration equal to the remuneration of the other directors who are not chairpersons of any committee, excluding the chairman and the vice chairman. The compensation amount includes the remuneration for Mr. Eli Hurvitz, Chairman of the Board, and Dr. Phillip Frost, Vice Chairman of the Board, as approved by Teva shareholders at the special meeting held on October 5, 2006, and effective as of July 3, 2006. Accordingly, in 2006, Mr. Hurvitz and Dr. Frost received a pro-rated share of 0, 000 and 5, 000 per annum plus VAT, respectively. None of the non-employee directors have agreements with Teva that provide for benefits upon termination of service. Teva has adopted a number of stock option or stock incentive programs covering either ordinary shares or ADRs. Following the approval of Teva's 2005 Omnibus Long-Term Share Incentive Plan by Teva's shareholders in July 2005, the compensation committee authorized, in December 2005, the granting of options to purchase an aggregate of 1, 014, 799 ordinary shares or ADRs to Teva's executive officers, at an average exercise price of .64 per share or ADR and an average expiration date in 2012, as well as 260, 067 restricted share unit awards. In addition, the compensation committee authorized, in November and December 2006, the granting of options to purchase an aggregate of 4, 066, 463 ordinary shares or ADRs to Teva's executive officers, at an average price of .57 per share or ADR and an average expiration date in 2013, as well as 441, 333 restricted share unit awards. As of December 31, 2006, options for an aggregate of approximately 42.7 million shares, with an average exercise price of .56 per share, were outstanding under Teva's stock option and incentive programs, with options for an aggregate of approximately 35.6 million shares available for future grant. For further information regarding outstanding Teva options, see Note 9 to the Notes to Consolidated Financial Statements. Board Practices Teva's board of directors is comprised of 15 persons, of whom 11 have been determined to be independent within the meaning of applicable Nasdaq regulations. The Board includes two independent directors mandated under Israeli law and subject to additional criteria to help ensure their independence. See "--Statutory Independent Directors Financial Experts" below. The terms of the directors are set forth in the table above. All directors are entitled to review and retain copies of Teva's documentation and examine Teva's assets, as required to perform their duties as directors and to receive assistance, in special cases, from outside experts at the expense of Teva subject to approval by the Board or by court ; . Board Practices and Procedures. Teva's Board members are generally elected for terms of three years. Teva believes that this system of multi-year terms allows Teva's directors to acquire and provide Teva with the benefit of a high level of expertise with respect to its complex business. Teva also provides an orientation and continuing education program for board members which includes the provision of materials, meetings with key management and visits to company facilities. Board Meetings. Meetings of the board of directors are generally held every 4-6 weeks throughout the year, with additional special meetings scheduled when required. The Board held 19 meetings in 2006, five of which took place in Teva's various European facilities. The average attendance rate at board meetings held during 2006 was 84%. Executive Sessions of the Board. The independent members of the Board met in executive session without management or non-independent directors' participation ; one time during 2006. They will continue to meet in executive session on a regular basis. Prof. Meir Heth serves as Chairman of the executive sessions of the Board. 76 and ropinirole, for example, ribavirin exposure.
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Nephrol Dial Transplant 1997 ; 12: patients: evidence for environmental transmission. Nephrol Dial Transplant 1995; 10: 240246 Dussol B, Chicheportiche C, Cantaloube JF et al. Detection of hepatitis C infection by polymerase chain reaction among hemodialysis patients. J Kidney Dis 1993; 22: 574580 Mondelli MU, Smedile V, Piazza V et al. Abnormal alanine aminotransferase activity reflects exposure to hepatitis C virus in haemodialysis patients. Nephrol Dial Transplant 1991; 6: 480483 Mondelli MU, Cristina G, Piazza V, Cerino A, Villa G, Salvadeo A. High prevalence of antibodies to hepatitis C virus in hemodialysis units using a second generation assay. Nephron 1992; 61: 350351 Silini E, Bono F, Cerino A, Piazza V, Solcia E, Mondelli MU. Virological features of hepatitis C infection in hemodialysis patients. J Clin Microbiol 1993; 31: 29132917 Belloni G, Balduzzi C, Vitali F, Garavelli G, Ferrari L. Prevalenza dell'infezione da virus C tra 46260 assistiti in medicina generale: studio epidemiologico in provincia di Pavia. Boll Soc Med Chir Pavia 1996; 110: 203208 Albano A, Pianetti A, Biffi MR et al. Prevalence of anti-HCV in subjects of various age groups. Eur J Epidemiol 1992; 8 2 ; : 309311 Fabrizi F, Marcelli D, Bacchini G, Guarnori I, Erba G, Locatelli F. Antibodies to hepatitis C virus HCV ; in chronic renal failure CRF ; patients on conservative therapy: prevalence, risk factors and relationship to liver disease. Nephrol Dial Transplant 1994; 9: 780784 Vagelli G, Calabrese G, Guaschino R, Gonella M. Effect of HCV + isolation on HCV infection incidence in a dialysis unit. Nephrol Dial Transplant 1992; 7: 1070 Druwe PM, Michielsen PP, Ramon AM, De Broe ME. Hepatitis C and nephrology. Nephrol Dial Transplant 1994; 9: 230237 Fabrizi F, Lunghi G, Guarnori I et al. Incidence of seroconversion for hepatitis C virus in chronic haemodialysis patients: a prospective study. Nephrol Dial Transplant 1994; 9: 16111615 Aucella F, Valente GL, Di Tullio M et al. Efficacia delle misure universali nella prevenzione dell'infezione nosocomiale da HCV in emodialisi: risultati di uno studio prospettico. Giorn It Nefrol 1995; 12: 373379 Gilli P, Soffritti S, De Paoli Vitali E, Bedani PL. Prevention of hepatitis C virus in dialysis units. Nephron 1995; 70: 301306.
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IN WITNESS WHEREOF, the Parties hereto through their fully authorized representatives have agreed to this Settlement Agreement, the attachments hereto, Rider A to this Settlement Agreement, and the settlement embodied herein and therein, on the date first above herein written. STATE LAW SS PLAIN11rrS By: tep ER , LO DANNENBER BEMPORAJ ; & SELIN ER, P .C. The Gateway, 11th Floor One North Lexington Avenue White Plains, NY 10601 Tel: 914 ; 997-0500 Fax : 914 ; 997-0035 AVENTIS PHARMACEUTICALS INC . By: Joseph Rebein. Esq . SHOOK, HARDY & BACON L .L.P. One Kansas City Place 1200 Main Street Kansas City, MO 64105-2118 Tel: 816 ; 4746550 Fax : 816 ; 421-4066 Counselfor Defendant Aventis Pharmaceuticalt Inc and tretinoin.
Bottom Line Health interviewed Michael Samuels, MD, an instructor at San Francisco State Institute of Holistic Medicine. He has a private practice specializing in guided imagery in Bolinas, California, and is the author of six alternative healing books, including most recently, Healing with the Mind's Eye Wiley.
Infergen is being studied in ongoing clinical trials to evaluate its potential for daily use with ribavirin and retrovir.
Table 9 * Clinical Adverse Events Occurring in 2% of Patients Treated with ZETIA and at an Incidence Greater than Placebo, Regardless of Causality Body System Organ Class Adverse Event Body as a whole general disorders Fatigue Gastro-intestinal system disorders Abdominal pain Diarrhea Infection and infestations Infection viral Pharyngitis Sinusitis Musculo-skeletal system disorders Arthralgia Back pain Respiratory system disorders Coughing Placebo % ; n 795 1.8 2.8 ZETIA 10 mg % ; n 1691 2.2 3.0.
At the present time there is a medication treatment strategy that is FDA approved for the treatment of the Hepati~is C infection: Pegylated Interferon and Ribavirin combination treatment. Patients are treated for 24-48 weeks and are followed for 24 weeks post-treatment. The goal of treatment is to achieve sustained virologic clearance. Response to treatment is defined as undetectable-- HCV RNA and normalization of ALT at 24 weeks posttreatment. It is important to note that there is no data regarding whether Pegylated Interferon treatment will prevent transmission of HCV infection to others. Additionally, it is not known if treatment with Pegylated Interferon will cure Hepatitis C or prevent cirrhosis, liver failure, or liver cancer that may be the result of infection with the Hepatitis C virus. Approximately 10-14% of patients discontinued treatment due to side effects. It is recommended that patients receiving Pegylated Interferon, alone or in combination with Ribavirin, be discontinued from treatment if HCV viral levels remain high after six months of treatment and rifater.
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2. To demonstrate left ventricular tolerance of resistance exercise left ventricular stroke work index was assessed because it integrates preload, diastolic pulmonary artery pressur ; , afterload mean arterial pressure ; , and contractility stroke volume ; . 3. During resistance exercise at 80% MVC load, stroke work index increased by 23%. Again, the amount of increase was relatively greater than that measured during exercise at 60% load. These results indicate enhanced left ventricular function during dynamic resistance exercise. In the study of Karlsdottir et al. echocardiograph measurements were performed in CHF patients NYHA class II III; mean ejection fraction 355% ; while they were exercising at two-footed leg press, shoulder press and biceps curl sets of 10 repetitions each; contraction intensity 60-70% of 1RM ; .5 Also, echocardiographic measurements were performed during a 12-min steady state cycle ergometry at intensity of 90% of ventilatory threshold. For comparison, clinical stable coronary patients with mild left ventricular dysfunction 568% ; and healthy subjects underwent the same procedure. They found: 1. In CHF patients asked to do cycling exercises, left ventricular ejection fraction increased from 35% to 42% but remained unchanged when they did leg press, shoulder press and biceps curl exercises between 38% and 35% ; . 2. Ejection fraction responses indicated no deterioration of left ventricular function during the course of resistance exercise. Besides the clear differences in the absolute value of ejection fraction with lower values in CHF compared to coronary patients and healthy subjects ; , there were similar responses within the three groups to different types of exercise and between groups to the same exercise. In contrast to resistance exercise using sustained muscle contraction, the results indicate that the rhythmic sequence of submaximal muscle contractions taking place during dynamic resistance exercises actually help to reduce systemic vascular resistance; seem to help maintain venous return and peripheral muscle blood flow; and keep left ventricular afterload within tolerable limits. This may be why dynamic resistance exercise is well tolerated by patients with clinically stable CHF. Intervention studies and resistance training Ten studies on resistance exercise training have been reported6-15 Table 1 ; involving 242 patients with CHF mean age 60 yr; mean left ventricular ejection Clin Invest Med Vol 29, no 3, June 2006 167 and rifampin.
Interleukin 6, interleukin 12, and interferon gamma. Proc Natl Acad Sci U S A 93, 2879-83. Koltover, I., Salditt, T., Radler, J. O. and Safinya, C. R. 1998 ; . An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery. Science 281, 78-81. Kotsopoulou, E., Kim, V. N., Kingsman, A. J., Kingsman, S. M. and Mitrophanous, K. A. 2000 ; . A Rev- independent human immunodeficiency virus type 1 HIV1 ; -based vector that exploits a codon-optimized HIV-1 gag-pol gene. J Virol 74, 4839-52. Krieg, A. M., Love-Homan, L., Yi, A. K. and Harty, J. T. 1998a ; . CpG DNA induces sustained IL-12 expression in vivo and resistance to Listeria monocytogenes challenge. J Immunol 161, 2428-34. Krieg, A. M., Wu, T., Weeratna, R., Efler, S. M., Love-Homan, L., Yang, L., Yi, A. K., Short, D. and Davis, H. L. 1998b ; . Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs. Proc Natl Acad Sci U S A 95, 12631-6. Krieg, A. M., Yi, A. K., Matson, S., Waldschmidt, T. J., Bishop, G. A., Teasdale, R., Koretzky, G. A. and Klinman, D. M. 1995 ; . CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374, 546-9. Krieg, A. M., Yi, A. K., Schorr, J. and Davis, H. L. 1998c ; . The role of CpG dinucleotides in DNA vaccines. Trends Microbiol 6, 23-7, because hepatitis c interferon ribavirin.
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The guanosine analogue ribavirin was tested for antiviral activity in two neural cell lines, human oligodendrocytes and rat glia, against Borna disease virus BDV ; strains V and He 80. Ribavirin treatment resulted in lower levels of virus and viral transcripts within 12 h. Addition of guanosine but not adenosine resulted in a profound reduction of the ribavirin effect. Ribavirin appears to be an effective antiviral agent for treatment of BDV infection in vitro. A likely mechanism for its activity is reduction of the intracellular GTP pool, resulting in inhibition of transcription and capping of BDV mRNAs. Borna disease virus BDV ; is a nonsegmented negativestrand RNA virus that transcribes and replicates in the nucleus of infected cells 4, 7 ; and employs a number of strategies to direct expression of its genome including RNA splicing, overlap of transcription units and transcriptional signals, readthrough of transcription initiation sites, and differential use of translational initiation codons reviewed in reference 39 ; . In concert, these result in noncytolytic replication and persistence and may contribute to BDVs neurotropism. Although BDV is classically associated with meningoencephalitis of horses and sheep in central Europe, more recent data 3, 5, 26, ; indicate that the host range of BDV probably extends to most warmblooded animals and suggest that the geographic distribution includes Asia and North America as well as greater Europe 14, 21, 26, ; . The spectrum of clinical disease due to BDV infection ranges from subtle impairment of learning and memory to progressive, immune-mediated, frequently fatal meningoencephalitis 1, 9, 33, ; . Asymptomatic infection has also been described 14, 21, 32, ; . Recognition of BDV's broad host range and predilection to target higher integrative circuits of the brain and the observation that disturbances in infected animals are reminiscent of some aspects of human neuropsychiatric diseases led to the proposal that BDV might be implicated in their pathogenesis. Although there is consensus that humans are likely to be susceptible to BDV infection, the epidemiology and clinical consequences of human infection remain controversial reviewed in reference 18 ; . Amantadine has been reported to be effective in vivo and in vitro against one strain of BDV. Bode and coworkers 2 ; described clearance of strain Hu-HI from cultured oligodendrocytes and from peripheral blood mononuclear cells of a patient with bipolar disorder. However, an antiviral effect of amantadine was not confirmed with other BDV isolates in studies of infected cultured cells, rodents, or horses 6, 11, 13, ; . In an effort to identify antiviral agents for BDV, we tested an encoded panel of 10 nucleoside analogues Table 1 ; for activity against the two best-characterized laboratory strains of BDV, strains V and He 80, in two neural cell lines, OL human oligodendrocytes ; and C6 rat glia ; . Strain V was originally isolated from naturally infected horse brain in 1929 48 ; , and strain He 80 was originally isolated from naturally infected horse brain in 1980 19 ; . Both viruses were later passaged in rabbits, rats, and a variety of cultured cells. Each of the compounds was initially tested with uninfected cells to establish a toxicity threshold defined as growth arrest Table 1 ; . Thereafter, efficacy against BDV was tested by using 10-fold dilutions of drug beginning at the toxicity threshold. One compound of the 10 examined, ribavirin, significantly reduced viral load at concentrations of 2 to 200 M. No effect was seen with the other compounds, including 2 , 3 -dideoxyinosine ddI ; Table 1 ; . To further characterize the antiviral effect of ribavirin, OL cells persistently infected with strain V Fig. 1A and C ; and C6 cells persistently infected with strain He 80 Fig. 1B and D ; were treated for up to 13 days with 20 M ribavirin or ddI negative control ; . At 3, 6, 9, and 12 days OL cells ; or 4, 7, 10, and 13 days C6 cells ; the numbers of host cells were determined and infectious virus and total cellular RNA were isolated from cells treated with ribavirin, ddI, or vehicle dimethyl sulfoxide without antiviral drug ; . Virus was titered by focus immunoassay using fetal rat glial cells and antiserum against viral nucleo- and phosphoproteins P ; 35 ; . mRNA originating from the second transcription unit encoding the BDV P was quantitated by Northern hybridization 24 ; and PhosphorIm.
And water before feeding your child. Prior to each feeding, the tube must be checked for patency being free to move ; of fluids through the tube and the gastric contents measured checking for residual ; the Doctor will tell you the level he feels is appropriate for your child but as a rule under 150cc's is acceptable, if over that amount, withhold the feeding until the level goes down, you must be certain to reinstall the withdrawn gastric stomach fluid ; contents, to prevent loss of nutrients and electrolytes, and to check the markings cm ; on the tube to be sure it has not moved. Formula should be given at room temperature too hot or cold could make your child uncomfortable ; , unused formula or blenderized foods should be refrigerated and warmed to room temperature before feeding at the next time, but never heat the solution as this could increase the growth of bacteria. Your child should be fed in an upright position at least 30 degrees ; and remain there for 30-60 minutes following the feeding to minimize the possibility of aspiration and its complications and roxithromycin.
Ribavirin 1-4-D-ribofuranosyl-lH-1, 2, 4-triazole-3-carboxamide ; eliminates foot-and-mouth disease virus from persistently infected cell cultures. The latter are 10-fold more sensitive to ribavirin than lytically infected cells. In treated cells no viral RNA or proteins could be detected by dot-blot hybridization to cDNA probes, virus and RNA infectivity assays, or immunofluorescence. A potential application of the drug for the treatment of animals carrying the virus is suggested.
There has been no experience with overdosage in human clinical trials. Single doses higher than 500 mg m2 have not been tested in controlled studies. 5.2 Fludarabine Phosphate 5.21 Other Names Fludara, fludarabine, 2-fluoro-adenine arabinoside-5-phosphate, 2-fluoro-ARA AMP, FAMP, NSC#312887. 5.22 Classification Purine antimetabolite. 5.23 Mode of Action Fludarabine is rapidly phosphorylated in vivo to 2-fluoro-ARA-A, incorporated into cells and converted to the active triphosphate form, which inhibits DNA polymerase and ribonucleotide reductase, thus inhibiting DNA synthesis. Fludarabine is also incorporated into DNA. 5.24 Storage and Stability Unreconstituted vials should be stored in the refrigerator. At a concentration of 25 mg mL and following dilution in normal saline or 5% dextrose to a concentration of 1 mg mL the drug is chemically stable for at least 16 days at room temperature under normal laboratory light. Solutions of 0.04 mg mI in 5% dextrose or normal saline in glass bottles or PVC bags are chemically stable for at least 48 hours at room and refrigerated temperatures. 5.25 Preparation Fludarabine, 50 mg vial, is reconstituted with 2 ml of sterile water, resulting in a 25 mg mi solution. The desired dose is further diluted to concentrations of 0.04 - 1 mg mi in normal saline or 5% dextrose 100- 125 ml ; . 5.26 Administration Usually administered by IV infusion over 30 minutes or longer. 5.27 Incompatibilities No information available. 5.28 Availability Fludarabine, 50 mg vial, is commercially available. 5.29 Side Effects 5.291 Hematologic: Leukopenia, primarily lymphopenia and granulocytopenia, and thrombocytopenia, dose-related; may be cumulative, dose-limiting; anemia. 5.292 Derrnatologic: Alopecia uncommon, mild rash rare dermatitis rare ; . 5.293 Gastrointestinal: Nausea and vomiting are relatively uncommon and preventable with standard antiemetic drugs; anorexia; stomatitis rare with conventional doses rare; diarrhea, constipation, abdominal cramps. Hepatic: Increased SGOT, mild and transient and reboxetine and ribavirin, for example, ribavirin dosage.
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