DOSAGE AND ADMINISTRATION
(See CLINICAL PHARMACOLOGY: Special Populations; see WARNINGS.)
Ribavirin/INTRON A Combination Therapy
Adults
The recommended dose of ribavirin capsules in patients 18 years of age and older depends on the patient’s body weight. The recommended dose of ribavirin is provided in TABLE 6.
The recommended duration of treatment for patients previously untreated with interferon is 24 to 48 weeks. The duration of treatment should be individualized to the patient depending on baseline disease characteristics, response to therapy, and tolerability of the regimen. (See Description of Clinical Studies and ADVERSE REACTIONS). After 24 weeks of treatment, virologic response should be assessed. Treatment discontinuation should be considered in any patient who has not achieved an HCV RNA below the limit of detection of the assay by 24 weeks. There are no safety and efficacy data on treatment for longer than 48 weeks in the previously untreated patient population.
In patients who relapse following non-pegylated interferon mono-therapy, the recommended duration of treatment is 24 weeks. There are no safety and efficacy data on treatment for longer than 24 weeks in the relapse patient population.
TABLE 6. Recommended Dosing for Patients 18 years of age and older | Body Weight | Ribavirin Capsules |
|
≤75 kg
|
2 x 200 mg capsules AM,
3 x 200 mg capsules PM
daily p.o. |
|
>75 kg
|
3 x 200 mg capsules AM,
3 x 200 mg capsules PM
daily p.o. |
Ribavirin may be administered without regard to food, but should be administered in a consistent manner with respect to food intake. (See CLINICAL PHARMACOLOGY).
Dose Modifications
(See TABLE 7.)
If severe adverse reactions or laboratory abnormalities develop during combination ribavirin/INTRON A therapy the dose should be modified, or discontinued if appropriate, until the adverse reactions abate. If intolerance persists after dose adjustment, ribavirin/INTRON A therapy should be discontinued.
Ribavirin should not be used in patients with creatinine clearance <50 mL/min. Subjects with impaired renal function and/or those over the age of 50 should be carefully monitored with respect to development of anemia. (See WARNINGS and CLINICAL PHARMACOLOGY: Special Populations).
Ribavirin should be administered with caution to patients with pre-existing cardiac disease. Patients should be assessed before commencement of therapy and should be appropriately monitored during therapy. If there is any deterioration of cardiovascular status, therapy should be stopped. (See WARNINGS).
For patients with a history of stable cardiovascular disease, a permanent dose reduction is required if the hemoglobin decreases by ≥2 g/dL during any 4-week period. In addition, for these cardiac history patients, if the hemoglobin remains <12 g/dL after 4 weeks on a reduced dose, the patient should discontinue combination ribavirin/INTRON A therapy.
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. A patient whose hemoglobin level falls below 8.5 g/dL should be permanently discontinued from ribavirin therapy. (See WARNINGS).
TABLE 7. Guidelines for Dose Modifications and Discontinuation for Anemia |
Dose Reduction
Ribavirin –
600 mg daily adults |
Permanent
Discontinuation of
Ribavirin Treatment |
| Hemoglobin | | |
| No Cardiac History | < 10 g/dL | < 8.5 g/dL |
|
Cardiac History Patients
|
≥2 g/dL decrease
during any 4-week
period during treatment |
< 12 g/dL after
4 weeks dose
reduction |
DOSAGE AND ADMINISTRATION
INTRON A Injection should be administered subcutaneously and ribavirin capsules should be administered orally. Ribavirin capsules may be administered without regard to food, but should be administered in a consistent manner. (See CLINICAL PHARMACOLOGY.)
Adults
The recommended dose of ribavirin capsules in patients 18 years of age and older depends on the patient’s body weight. The recommended doses of ribavirin capsules and INTRON A for adults are given in TABLE 6.
The recommended duration of treatment for patients previously untreated with interferon is 24 to 48 weeks. The duration of treatment should be individualized to the patient depending on baseline disease characteristics, response to therapy, and tolerability of the regimen (see Description of Clinical Studies and ADVERSE REACTIONS). After 24 weeks of treatment virologic response should be assessed. Treatment discontinuation should be considered in any patient who has not achieved an HCV-RNA below the limit of detection of the assay by 24 weeks. There are no safety and efficacy data on treatment for longer than 48 weeks in the previously untreated patient population.
In patients who relapse following interferon therapy, the recommended duration of treatment is 24 weeks. There are no safety and efficacy data on treatment for longer than 24 weeks in the relapse patient population.
TABLE 6. Recommended Adult Dosing | Body Weight | Ribavirin Capsules | INTRON A Injection |
|
≤75 kg
|
2 x 200 mg capsules AM,
3 x 200 mg capsules PM
daily p.o. |
3 million
IU 3 times weekly s.c.
|
|
>75 kg
|
3 x 200 mg capsules AM,
3 x 200 mg capsules PM
daily p.o. |
3 million
IU 3 times weekly s.c.
|
Under no circumstances should ribavirin capsules be opened, crushed or broken (see CONTRAINDICATIONS and WARNINGS).
Dose Modifications
(See TABLE 7.)
In clinical trials, approximately 26% of patients required modification of their dose of ribavirin capsules, INTRON A Injection, or both agents. If severe adverse reactions or laboratory abnormalities develop during combination ribavirin capsules/INTRON A therapy the dose should be modified, or discontinued if appropriate, until the adverse reactions abate. If intolerance persists after dose adjustment, ribavirin capsules/INTRON A therapy should be discontinued.
Ribavirin capsules/INTRON A therapy should be administered with caution to patients with preexisting cardiac disease. Patients should be assessed before commencement of therapy and should be appropriately monitored during therapy. If there is any deterioration of cardiovascular status, therapy should be stopped. (See WARNINGS.)
For patients with a history of stable cardiovascular disease, a permanent dose reduction is required if the hemoglobin decreases by ≥2 g/dL during any 4-week period. In addition, for these cardiac history patients, if the hemoglobin remains <12 g/dL after 4 weeks on a reduced dose, the patient should discontinue combination ribavirin capsules/INTRON A therapy.
It is recommended that a patient whose hemoglobin level falls below 10 g/dL have his/her ribavirin capsules dose reduced to 600 mg daily (1 x 200 mg capsule AM, 2 x 200 mg capsules PM). A patient whose hemoglobin level falls below 8.5 g/dL should be permanently discontinued from ribavirin capsules/INTRON A therapy. (See WARNINGS.)
It is recommended that a patient who experiences moderate depression (persistent low mood, loss of interest, poor self image, and/or hopelessness) have his/her INTRON A dose temporarily reduced and/or be considered for medical therapy. A patient experiencing severe depression or suicidal ideation/attempt should be discontinued from ribavirin capsules/INTRON A therapy and followed closely with appropriate medical management. (See WARNINGS.)
TABLE 7. Guidelines for Dose Modifications |
Dose Reduction
Ribavirin capsules –
Adults 600 mg daily
INTRON A – Adults
1.5 million IU TIW |
Permanent
Discontinuation
of Treatment
Ribavirin capsules
and INTRON A |
|
Hemoglobin
|
<10 g/dL
(Ribavirin capsules) |
<8.5 g/dL
|
|
Cardiac History
Patients Only
|
≥2 g/dL decrease
during any 4-week
period during treatment
(Ribavirin capsules/
INTRON A) |
< 12 g/dL after
4 weeks of dose
reduction
|
| White blood count | <1.5 x 109/L (INTRON A) | <1.0 X 109/L |
| Neutrophil count | <0.75 x 109/L (INTRON A) | <0.5 X 109/L |
|
Platelet count
|
Adults: <50 x 109/L
(INTRON A) |
Adults: <25 x 109/L
|
Administration of INTRON A Injection
At the discretion of the physician, the patient may self-administer the INTRON A. [See illustrated Appendix to Medication Guide on ribavirin capsules for instructions.]
The Intron A Injection is supplied as a clear and colorless solution. The appropriate INTRON A dose should be withdrawn from the vial or set on the multidose pen and injected subcutaneously. The INTRON A Injection supplied with the B-D Safety Lok™ syringes contain a plastic sleeve to be pulled over the needle after use. The syringe locks with an audible click when the green stripe on the safety sleeve covers the red stripe on the needle. After administration of INTRON A Injection, it is essential to follow the procedure for proper disposal of syringes and needles. [See Appendix to Medication Guide on ribavirin capsules for detailed instructions.]
| Vial/Pen Label Strength | Fill Volume | Concentration |
| 3 million IU vial | 0.5 mL | 3 million IU/0.5 mL |
| 18 million IU multidose vial
| 3.8 mL | 3 million IU/0.5 mL |
| 18 million IU multidose pen
| 1.5 mL | 3 million IU/0.2 mL |
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. INTRON A Injection may be administered using either sterilized glass or plastic disposable syringes.
Stability
INTRON A Injection provided in vials is stable at 35°C (95°F) for up to 7 days and at 30°C (86°F) for up to 14 days. INTRON A Injection provided in a multidose pen is stable at 30°C (86°F) for up to 2 days. The solution is clear and colorless.
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