|
America's online pharmacy serving your needs for no prescriptions Your right decision! Click Here ... |
Order rebetol
Rebetol
Rebetol – the antiviral drug. It is active against several RNA and DNA-containing viruses. Apply only in combination with alpha interferon or peginterferon for treatment of chronic hepatitis C (in previously treated with interferon and had a favorable response to therapy or previously untreated patients). Combination therapy rebetolom and interferon or peginterferon alfa-2 in patients with hepatitis C is more effective than monotherapy with interferon or peginterferon alfa-2.
Latin name:
REBETOL / REBETOL.
The composition and the form of:
Rebetol capsules 84, 140 or 168 pieces. in the package.
Rebetol 1 capsule contains: 200 mg of ribavirin.
Properties / Action:
Rebetol – the antiviral drug, a synthetic nucleoside analogue, active in vitro against several RNA and DNA-containing viruses.
Rebetol is used only for the combined treatment of hepatitis C. Combination therapy Rebetolom and interferon or peginterferon alfa-2 is more effective than monotherapy with interferon or peginterferon alfa-2. At the same time he Rebetol and its metabolites in physiological concentrations, no signs of inhibition of enzymes that are specific to the hepatitis C virus, and does not inhibit the replication of the hepatitis C virus in hepatitis C Rebetolom monotherapy is ineffective, there is no elimination of hepatitis C virus, or improvement in liver histology. The mechanism by which Rebetol in combination with interferon or peginterferon alfa-2 manifests its antiviral effect is unknown.
Ribavirin accumulates intracellularly and removed from the body very slowly.
Indications:
Rebetol is used only in combination with interferon or peginterferon alfa-2:
# Chronic hepatitis C patients previously treated with interferon or peginterferon alfa-2 and had positive reaction to the therapy (normalization of the activity of “liver” enzymes / ALT / by the end of treatment), which have subsequently emerged a relapse of the disease;
# Chronic hepatitis C in previously untreated patients, seropositive for hepatitis C virus, with no signs of decompensation of liver function, with increased activity of “liver” enzymes / ALT /, including in the presence of fibrosis or significant inflammation.
Dosage and administration:
Rebetol appointed interior of 800-1200 mg / day in 2 divided doses, morning and evening. Bioavailability Rebetola grew when eating high-fat diet (AUC performance and Smax increased by 70%). In order to achieve the maximum concentration of ribavirin in plasma is recommended to take Rebetol with food.
At the same time appointed by interferon or peginterferon alfa-2 in the form of subcutaneous injections (eg, interferon alpha-2b 3 times per week for 3 mln.ME or peginterferon alfa-2b at 1.5 mcg / kg 1 time a week).
Recommended doses Rebetola depending on body weight in the application of interferon alpha-2:
Body mass dose of Rebetola Number of capsules Rebetola
less than 75 kg 1000 mg 2 in the morning and 3 evening
than 75 kg 1200 mg 3 morning and 3 evening
Recommended doses Rebetola depending on body weight when used in combination with peginterferon alfa-2:
Body mass dose of Rebetola Number of capsules Rebetola
less than 65 kg 800 mg 2 in the morning and 2 evening
65-85 kg 1000 mg 2 in the morning and 3 evening
more than 85 kg 1200 mg 3 morning and 3 evening
Duration of combined treatment is not less than 6 months. Individual duration of treatment depends on the clinical course of disease, response to treatment, tolerability of treatment, and usually does not exceed 1 year. After 6 months of treatment the patient should undertake a survey to identify virological response. In his absence should decide to terminate therapy Rebetolom and interferon or peginterferon alfa-2.
In the event of serious adverse events or abnormalities in laboratory values during treatment should adjust the dose or stop receiving Rebetola to the termination of unwanted phenomena.
Modification of the dosing regime Rebetola and interferons:
Laboratory performance decline only Rebetola dose to 600 mg per day *, if: Reducing only the dose of interferon or peginterferon alfa-2 at 50% if: Closing reception Rebetola and interferon or peginterferon alfa-2, if:
Hemoglobin less than 10 g / dl – less than 8.5 g / dl
The content of hemoglobin in patients with heart disease in a stable form of hemoglobin level fell by more than 2 g / dL during any 4 weeks during treatment (continuous use of low-dose) less than 12 g / dl 4 weeks after dose reduction
The number of white blood cells – less than 1.5 * 10 ^ 9 / L or 1500/mkl less than 1 * 10 ^ 9 / L or 1000/mkl
The number of neutrophils – less than 0.75 * 10 ^ 9 / L or 750/mkl less than 0.5 * 10 ^ 9 / L or 500/mkl
The number of platelets – less than 50 * 10 ^ 9 / L or 50000/mkl less than 25 * 10 ^ 9 / L or 25000/mkl
Associated Content bilirubin – - more than 2.5 times the upper limit of normal
Contents of free bilirubin over 5 mg / dL – more than 4 mg / dL (more than 4 weeks)
Contents of creatinine – - more than 2 mg / dL
ALT / AST – - more than 2 times higher than baseline values, or more than 10 times the upper limit of normal
* Patients who reduced the dose Rebetola to 600 mg per day, should take 1 capsule in the morning and 2 capsules in the evening.
If after correction Rebetola tolerated dose therapy does not improve, treatment should be discontinued.
Application Rebetola in human liver. Rebetol is contraindicated in expressed human liver or decompensated liver cirrhosis. Pharmacokinetics of ribavirin in the appointment of a single dose Rebetola liver failure patients with mild, moderate or severe (grades A, B or C in Child-Pugh) is similar to the pharmacokinetics of ribavirin in healthy individuals.
Application Rebetola with impaired renal function. Rebetol is contraindicated in severe renal diseases, including chronic renal insufficiency with creatinine clearance (CC) of less than 50 ml per minute, or the need for dialysis. In patients with renal insufficiency Pharmacokinetics after single dose Rebetola changes (AUC and Smax increase) compared with the control (with CC more than 90 mL per minute). The concentration of ribavirin in plasma during hemodialysis did not significantly change.
Overdose:
A case of overdose, the patient with suicide attempt in one day took 10 g Rebetola inside and 39 mln.ME interferon in the form of s / c injection. The patient was in for 2 days in the department of emergency treatment, during which time there have been serious adverse events associated with overdose.
Contraindications:
# Hypersensitivity to ribavirin or other components Rebetola;
# Severe heart disease, including unstable and uncontrollable forms (there are at least 6 months prior to treatment);
# Uncontrolled thyroid disease;
# Haemoglobinopathies, including thalassemia, sickle cell anemia;
# Severe kidney disease, including chronic renal insufficiency with creatinine clearance less than 50 ml per minute or need for dialysis;
# Expressed human liver or decompensated cirrhosis;
# Severe depression, suicidal thoughts, suicide attempts, including history;
# Autoimmune diseases, including autoimmune hepatitis;
# Children and youth under 18 years;
# Pregnancy and breastfeeding.
Rebetol used with caution:
# Other heart disease;
# Severe lung disease, including chronic obstructive pulmonary disease (COPD);
# Diabetes with a tendency toward ketoacidosis;
# Clotting of blood, including thrombophlebitis, pulmonary embolism;
# Significant inhibition of hematopoietic function of bone marrow;
# Combination with highly active antiretroviral therapy (HAART) in HIV co-infection (risk of lactic acidosis).
Application of pregnancy and breastfeeding:
Rebetol is contraindicated in pregnancy. In experimental studies have shown that ribavirin has embryotoxic and teratogenic effects in animals at doses much lower than recommended for clinical use. Animals ribavirin caused changes in sperm at doses below therapeutic. Treatment should not begin until until a negative pregnancy test, which should take place immediately prior to the application Rebetola. Patients of childbearing age and their sexual partners should use effective methods of contraception during therapy Rebetolom and within 6 months after its completion. Monthly during the entire period necessary to carry out a pregnancy test. If pregnancy occurs during treatment Rebetolom or within 6 months after its completion, the patient should be warned about the significant teratogenic risk. The sick man must also use reliable methods of contraception (condoms).
It is not known whether ribavirin is allocated to breast milk. At the time of treatment Rebetolom should stop breastfeeding.
Side effects:
Side effects of therapy may be associated both with Rebetolom and interferon or peginterferon alfa-2.
Since the cardiovascular system: chest pain, tachycardia, decreased or increased blood pressure, palpitations, fainting.
The part of the hemopoietic system: hemolysis, hemolytic anemia (the main toxic effect, usually not the cause of the cessation of therapy), leukopenia, neutropenia, granulocytopenia, thrombocytopenia (usually moderately expressed) is very rare – aplastic anemia.
From the nervous system and sensory organs: headache, dizziness, weakness, malaise, tremor, paresthesia, hyperesthesia, depression, irritability, insomnia, restlessness, decreased concentration, emotional lability, nervousness, emotional arousal, aggressive behavior, confusion, disorder view, breach or hearing loss, tinnitus, defeat the lacrimal glands, conjunctivitis, rarely – suicidal thoughts and attempts.
From the digestive system: nausea, vomiting, diarrhea, abdominal pain, anorexia, constipation, dyspepsia, dry mouth, taste perversion, pancreatitis, flatulence, stomatitis, glossitis, bleeding gums.
On the part of the respiratory system and otolaryngology: bronchitis, cough, dyspnea, rhinitis, pharyngitis, sinusitis, otitis media.
From the Endocrine: hypothyroidism, thyroid-stimulating hormone content of change.
On the part of the reproductive system: hot flashes, decreased libido, irregular menstruation, amenorrhea, menorrhagia, prostatitis.
From the Musculoskeletal System: myalgia, arthralgia.
Dermatological and allergic reactions: itching, dry skin, rash, erythema, eczema, exacerbation of herpes infection, photosensitivity, alopecia, disturbance of hair rarely – urticaria, angioedema, bronchospasm, anaphylaxis, very rarely – erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Laboratory findings: sometimes – increased uric acid, indirect bilirubin (associated with hemolysis), rare – the symptoms of gout.
Other: pain at the injection site, chills, fever, flu syndrome, fatigue, thirst, sweating, weight loss, lymphadenopathy, increased tone of smooth muscles, fungal and viral infection.
Cautions and precautions:
Safety and efficacy of combination therapy studied only in the application Rebetola with interferon alfa-2b (eg, Intron A) or peginterferon alfa-2b (eg, PegIntron). Before the appointment of combination therapy should be familiar with the instructions on the application, respectively, interferon alfa-2b or peginterferon alfa-2b, attached to these drugs.
Rebetol should be used with caution in patients with heart disease, after appropriate examination and only under the supervision of a cardiologist. During clinical trials the reduction of hemoglobin to a value below 10 g / dL was observed in 14% of patients treated with Rebetol. Although Rebetol is not characterized by a direct effect on the cardiovascular system, anemia can cause increased heart failure or worsening symptoms of coronary disease. During treatment, these patients require special monitoring. In the event of any deterioration on the part of the cardiovascular system Rebetolom treatment should be discontinued.
When allergic reactions such as urticaria, angioedema, bronchospasm, or anaphylaxis, reception Rebetola should cease immediately and appoint appropriate treatment. Transient rashes do not constitute grounds for termination of treatment.
In elderly patients prior to the application Rebetola to determine the status of the kidneys, because with the age of the functionality of the kidneys may be reduced.
Before treatment Rebetolom should assess the need for histological confirmation of diagnosis. In some cases (patients infected with genotype 2 or 3) treatment can be carried out without prior biopsy of the liver.
Laboratory tests (complete blood count, wbc, platelet count, electrolytes, and serum creatinine, liver function tests) should be carried out before starting treatment Rebetolom, then at 2 and 4 weeks of treatment, and more regularly as required.
Effects on ability to drive vehicles and management mechanisms:
Patients experiencing fatigue, drowsiness or disorientation during therapy Rebetolom should refuse to perform work requiring special attention and quickness of psychomotor reactions, including from driving or control mechanisms.
Drug Interactions:
The appearance of any interaction associated with the cytochrome P450 unlikely. Ribavirin is not an inhibitor of cytochrome P450 isozymes. Studies have shown that cytochrome P450 isozymes are not involved in the metabolic conversion of ribavirin and not give grounds for believing that Rebetol can stimulate the enzymatic activity of the liver.
No pharmacokinetic interaction was observed between Rebetolom and interferon or peginterferon alfa-2b.
Bioavailability Rebetola reducing preparations containing compounds of magnesium and aluminum (Maalox, etc.) or Simethicone. Probably, this interaction is not clinically significant.
Ribavirin in vitro showed the ability to inhibit phosphorylation of zidovudine and stavudine. Combined use Rebetola with these drugs can lead to increased concentrations of HIV in the blood plasma. We recommend close monitoring of concentrations of HIV RNA in plasma from patients who underwent this combined treatment. When the level of concentration of HIV RNA in plasma using Rebetola in combination with reverse transcriptase inhibitors should be reviewed.
Ribavirin in vitro increases the content of phosphorylated metabolites of purine nucleosides, which may potentiate the risk of lactic acidosis caused by purine nucleoside analogues (didanosine, abacavir). In patients infected with both hepatitis C and HIV and receiving Rebetol and highly active antiretroviral therapy (HAART) may develop lactic acidosis. In appointing such combined therapy should exercise increased caution.
No evidence of drug interactions Rebetola with non-nucleoside reverse transcriptase inhibitors or protease inhibitors.
Possibility of drug interactions may persist up to 2 months after cessation of Rebetola in connection with the slow breeding of ribavirin.