Ribavirin dosing

Jen J, Laughlin M, Chung C, Heft S, Affrime MB, Gupta SK, Glue P, Hajian G (2002) Ribavirin dosing in chronic hepatitis C application of population pharmacokinetic-pharmacodynamic models, Clin Pharmacol Ther 72 349-361... 

It is recommended that a patient whose hemoglobin level falls below 10 g/dL have his/her ribavirin dose reduced to 600 mg daily (1 x 200 mg capsule AM, 2 X 200 mg capsules PM) for adults and 7.5 mg/kg/day (divided dose AM and PM) for pediatric patients. Permanently discontinue ribavirin therapy in patients whose hemoglobin level falls below 8.5 g/dL. 

History of cardiovascular disease with hemoglobin decreases by >2 g/dL during any 4-week period Decrease ribavirin dose to 600 mg s.c. q.d. If the hemoglobin remains <12 g/dL after 4 weeks on the rednced dose, discontinue ribavirin therapy... 

Ribavirin is not incorporated into the DNA or RNA of either mammalian or viral systems. It has been shown (123), however, that a high dosage of ribavirin given over a prolonged period to Rhesus monkeys results in anemia of red blood cells. This effect is dose related and reversible upon cessation of treatment. Guanosine partially reverses the antiviral effect of ribavirin against certain vimses. 

Pegylated IFN-a-ribavirin combination therapy can be improved by increasing the dose of pegylated IFN-a and/or ribavirin in selected patients and by tailoring the length of treatment to the virological response. 

HCV infection is rarefy diagnosed in the acute phase, as most acutely infected individuals are asymptomatic. Between 50% and 90% of patients develop chronic infection, however, and this warrants early therapy. After occupational exposure with a known date, treatment should not be started before the acute episode characterized by alanine aminotransferase elevation, but it should always be started within 24 weeks after the onset of symptoms. The optimal treatment schedule for acute hepatitis C is controversial. Pegylated IFN-a monotherapy at the standard dose for 24 weeks yielded SVR rates close to 100% in symptomatic patients referred to tertiary care centers (De Rosa et al. 2006 Jaeckel et al. 2001 Santantonio et al. 2005 Wiegand et al. 2006). Shorter therapy may be envisaged (Calleri et al. 2007). Combination with ribavirin is recommended if a first course of pegylated IFN-a monotherapy fails to eradicate the infection. Viral elimination appears to be independent of the HCV genotype and the HCV RNA level (Calleri et al. 2007 De Rosa et al. 2006 Jaeckel et al. 2001). 

IFN-co (Intarcia Therapeutics, Emeryville, California) has been reported to be well tolerated and safe, in patients infected with various HCV genotypes, at doses of 15-120pg three times weekly for 12 weeks, with dose-dependent virological and biochemical responses (Plauth et al. 2002). At a dose of 25 pg daily, IFN-co induced a 2-log HCV RNA dechne at week 12 in two-thirds of 74 patients infected with HCV genotype 1 (Gorbakov et al. 2005). In a recent trial, SVR was achieved in 6% and 36% of patients receiving the same dose of IFN-O) without and with ribavirin, respectively (Novozhenov et al. 2007). A new trial of IFN-m, delivered continuously by an implantable device, will start soon. 

In nonresponders to IFN-a-ribavirin, the antiviral effect of boceprevir appeared to be strictly additive to that of pegylated IFN-a2b (Sarrazin et al. 2007). In an ongoing phase II chnical trial, higher doses of boceprevir are being administered to treatment-naive patients, in combination with pegylated IFN-a and ribavirin. 

Lindahl K, Stable L, Bruchfeld A, Schvarcz R (2005) High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C. Hepatology 41 275-279... 

Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J (2004) Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 351(15) 1521-1531 Lindahl K, Stable L, Bruchfeld A, Schvarcz R (2005) High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C. Hepatology 41(2) 275-279... 

Adherence to therapy is another important factor in increasing and maintaining SVR. Patients who were adherent with interferon and ribavirin therapy (taking more than 80% of doses for more than 80% of the treatment duration) had an SVR of 52% whereas those who were not compliant had an SVR of 44% 42... 

Ribavirin causes a dose-related hemolytic anemia. Once treatment has been initiated, the hemoglobin concentration may... 

The current standard of treatment for chronic HCV infection is a combination of once-weekly PEG-IFN and a daily oral dose of ribavirin. Sustained virologic response rates are 54% to 56%. Therapy is optimized based on genotype, patient weight, and response to therapy. Recommended treatment regimens for HCV infection are given in Table 25-8 and Fig. 25-3. 

Fig. 1.2 a Microtiter plate illustrating dose response activity of an extract of the red alga Gigartina skottsbergii (A4) as weU as unrelated and ineffective extract in well F2. b Plaque reduction assay depicting a marked reduction of virus replication in cells treated with extract A4 (50 p-g/mL) compared with No Drug or the unrelated ineffective extract F2. The effect of A4 is similar to that of the control drug ribavirin... 

Fig. 1.4 Hemagglutination assay results from the active fraction of the red alga Gigartina skottsbergii. a Red blood cells (RBCs) hemagglutinate in the presence of influenza virus top row) and with extract A4 -t- virus or extract A4 alone. The bottom two rows present the back titration of the virus used in this experiment, b In contrast to the other anti-influenza drugs (ribavirin, amantadine, rimantadine, and zanamivir) that do not induce hemagglutination of human as well as chicken RBCs, extract A4 does it in a dose-dependent manner...

Concentration response data are analyzed by a nonlinear regression logistic dose response model. Each of the crude extracts are fractionated into 10-15 subfractions. For each crude extract and the associated subfractions, ICsos and IC90S are determined as outlined above. All crude and subfractions of a particular marine organism are assayed simultaneously (within one assay) and include ribavirin as reference drugs using only A/WY/03/2003 virus. 

Tablets The daily dose of ribavirin tablets is 800 to 1200 mg administered orally in 2 divided doses with food.

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