GASTROENTEROLOGY IN FOCUS
Year : 2001 | Volume
: 7 | Issue : 1 | Page : 42--43
Bandar Al Knawy
Bandar Al Knawy
|How to cite this article:|
Al Knawy B. Ribavirin.Saudi J Gastroenterol 2001;7:42-43
|How to cite this URL:|
Al Knawy B. Ribavirin. Saudi J Gastroenterol [serial online] 2001 [cited 2020 Aug 5 ];7:42-43
Available from: http://www.saudijgastro.com/text.asp?2001/7/1/42/33415
Ribavirin (1-b-D-ribofuranosy1-1, 2,4-traizole-3 carboxamide) is a synthetic nucleoside analogue with a structure similar to that of guanosine. Ribavirin has been recognized as a broad-spectrum antiviral agent for many years, with documented activity against a variety of RNA and DNA viruses. However the potency of this activity for most viruses is small and has not resulted in widespread clinical applications, except for its use in aerosolized form for the treatment of respiratory syncytial virus. The addition of ribavirin to interferon (IFN) regimens has improved the response rate for patients with chronic hepatitis C. For the treatment of hepatitis C infection in patients weighting 75kg or less, the usual dosage of oral ribavirin is 400mg every morning and 600mg every evening (1000mg daily) in combination with IFN alfa-2b in a dosage of three million units given three times weekly by subcutaneous injection. For the treatment of hepatitis C infection patients weighing more than 75kg, the usual dosage of oral ribavirin is 600mg every morning and evening (1200g daily) in combination with IFN in a dosage of three million units given three times weekly by subcutaneous injection.
Therapeutic Benefits: Ribavirin alone
In contrast To IFN, ribavirin is an attractive antiviral agent because it can be administered orally, and hemolysis is its only major toxicity. Patients treated with ribavirin achieved normal alanine aminotransferase (ALT) activity in 35% compared with none in the controls, which relapsed immediately after treatment cessation. Serum hepatitis C virus (HIV) RNA levels did not change during or after therapy. Whereas, minimal improvement in necroinflammatory activity was seen in hepatic histology at the end of therapy. Given the lack of virological response and sustained biochemical response, ribavirin as a single agent has a limited role; therefore it is not recommended for the treatment of patients with chronic hepatitis C, as monotherapy.
Therapeutic Benefits: Ribavirin and IFN Combination
Monotherapy with IFN results in normalization of the serum ALT, loss of detectable serum HCV, RNA and histologic improvement in approximately 40% of patients. However, regardless of the duration of initial therapy, most patients relapsed within the first few months after the drug is stopped and only 15% of patients have sustained virological response. Retreatment of IFN relapses with the combination of IFN and oral ribavirin for six months results in endof-treatment loss of detectable HCV RNA and normalization of the ALT level in over 80% of patients. Furthermore, combination treatment with IFN and ribavirin has been shown to increase sustained response rates to 40% in patients who have never been treated with IFN. Histologic treatment occurs in nearly two thirds of patients retreated with combination therapy and is most pronounced in those who lose serum HCV RNA.
Adverse effects of ribavirin
The dose limiting toxicity of ribavirin is a reversible normochromic, normocytic, hemolytic anemia. While the mechanism by which this agent includes hemolysis is not yet defined. Ribavirin is known to accumulate to a much greater degree (60-to-70- fold) in nonnucleated cells (i.e., erythrocytes) than in nucleated cells. Moreover, the reduced erythrocyte half-life may in part be due to the adverse effects of ribavirin on oxidative respiration. Despite the mechanism(s) mediating the anemia, hemoglobin levels decline from baseline within the first 2-4 weeks following initiation of recombinant IFN ribavirin combination therapy, with a mean maximum decrease of about 2.9 to 3.1 g/dL.
Dose of ribavirin for patients with pre-exiting stable cardiovascular disease should be permanently reduced in patients who experience a decrease in hemoglobin of 2g/dL or greater during any fourweek period. Patients with hemoglobin less than 12g/dL after receiving the reduced dosages for four weeks should be closely monitored with regular blood testing and their therapy may be discontinued. Patients without heart disease whose hemoglobin falls below 10g/dL the dosage of oral ribavirin should be reduced. Therapy with ribavirin should be discontinued in any patient with a hemoglobin concentration less than 8.5g/L.
Due to the universal cellular distribution of es nucleoside transporter, ribavirin accumulates in all cell types, including erythrocytes, ova and spermatozoa. Because of ribavirin teratogenic liability, contraceptive cover is mandated for both males and females during and after ribavirin therapy. The extensive accumulation of ribavirin nucleotides and their slow dephosphorylation constitute to the long half-life following multiple dosing (approximately 300 hours). To prevent potential teratogenic effects, it is estimated that six months (approximately 15 half-lives) is required to ensure a complete washout following cessation of therapy.
Ribavirin is teratogenic and absolutely contraindicated during pregnancy.
The management of chronic viral hepatitis C is evolving rapidly. It was the addition of the oral antiviral agent ribavirin to alpha IFN therapy that marked a key advance in the therapy of chronic hepatitis C. Combination therapy with ribavirin and alfa interferon compared with alfa interferon monotherapy has been shown to significantly enhance sustained virologic response rates in relapsed and naive patients with chronic hepatitis C.
|1||DiBisceglie, AM, Foreword: Advances in the Treatment of Chronic Hepatitis C. Seminars in Liver Disease, 1999, Vol. 19, Suppl. 1:1-2.|
|2||Glue P. The Clinical Pharmacology of Ribavirin. Seminars in Liver Disease, 1999, Vol. 19, Suppl. 1:17-24.|
|3||Gutfreund KS, Bain CG. Chronic Viral Hepatitis C: Management Update. CMAJ. 2000; 162:827-33.|