Posology : מינונים

4.2 Posology and method of administration
IMPORTANT: Intron A Interferon alfa-2b, recombinant for Injection dosing regimens are different for each of the following indications described in this section of the product information sheet.
Treatment must be initiated by a physician experienced in the management of the disease.

Multidose presentations must be for individual patient use only.

The pen is designed to deliver its contents of 18 million IU in doses ranging from 1.5 to 6 million IU.
The pen will deliver a maximum of 12 doses of 1.5 million IU over a period not to exceed 27 days.

If adverse events develop during the course of treatment with Intron A for any indication, modify the dose or discontinue therapy temporarily until the adverse events abate. If persistent or recurrent intolerance develops following adequate dose adjustment, or disease progresses, discontinue treatment with Intron A. At the discretion of the physician, the patient may self-administer the dose for maintenance dose regimens administered subcutaneously.

Chronic hepatitis B
The recommended dose is in the range 5 to 10 million IU administered subcutaneously three times a week (every other day) for a period of 4 to 6 months.

The administered dose should be reduced by 50 % in case of occurrence of haematological disorders (white blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3). Treatment should be discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe thrombocytopaenia (< 70,000/mm3).

For all patients, if no improvement on serum HBV-DNA is observed after 3 to 4 months of treatment (at the maximum tolerated dose), discontinue Intron A therapy.

Chronic hepatitis C
Intron A is administered subcutaneously at a dose of 3 million IU three times a week (every other day) to adult patients, whether administered as monotherapy or in combination with ribavirin.
(See ribavirin capsules SPC for dose of ribavirin capsules and dose modification guidelines for combination therapy).

Relapse patients
Intron A is given in combination with ribavirin. Based on the results of clinical trials, in which data are available for 6 months of treatment, it is recommended that patients be treated with Intron A in combination with ribavirin for 6 months.

Naïve patients
The efficacy of Intron A is enhanced when given in combination with ribavirin. Intron A should be given alone mainly in case of intolerance or contraindication to ribavirin.

- Intron A in combination with ribavirin
Based on the results of clinical trials, in which data are available for 12 months of treatment, it is recommended that patients be treated with Intron A in combination with ribavirin for at least 6 months.

Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and high pre-treatment viral load.

Other negative prognostic factors (age > 40 years, male gender, bridging fibrosis) should be taken into account in order to extend therapy to 12 months.

During clinical trials, patients who failed to show a virologic response after 6 months of treatment (HCV-RNA below lower limit of detection) did not become sustained virologic responders (HCV-RNA below lower limit of detection six months after withdrawal of treatment).

- Intron A alone
The optimal duration of therapy with Intron A alone is not yet fully established, but a therapy of between 12 and 18 months is advised.

It is recommended that patients be treated with Intron A alone for at least 3 to 4 months, at which point HCV-RNA status should be determined. Treatment should be continued in patients who exhibit negative HCV-RNA.

Hairy cell leukaemia
The recommended dose is 2 million IU/m2 administered subcutaneously three times a week (every other day) for both splenectomised and non-splenectomised patients. For most patients with hairy cell leukaemia, normalisation of one or more haematological variables occurs within one to two months of Intron A treatment. Improvement in all three haematological variables (granulocyte count, platelet count and haemoglobin level) may require six months or more. This regimen must be maintained unless the disease progresses rapidly or severe intolerance is manifested.

Chronic myelogenous leukaemia
The recommended dose of Intron A is 4 to 5 million IU/m2 administered daily subcutaneously. Some patients have been shown to benefit from Intron A 5 million IU/m2 administered daily subcutaneously in association with cytarabine (Ara-C) 20 mg/m2 administered daily subcutaneously for 10 days per month (up to a maximum daily dose of 40 mg). When the white blood cell count is controlled, administer the maximum tolerated dose of Intron A (4 to 5 million IU/m2 daily) to maintain haematological remission.
Intron A treatment must be discontinued after 8 to 12 weeks of treatment if at least a partial haematological remission or a clinically meaningful cytoreduction has not been achieved.

Non-Hodgkin's lymphoma (follicular lymphoma)
Adjunctively with chemotherapy, interferon alfa-2b may be administered subcutaneously, at a dose of 5 million IU three times a week (every other day) for a duration of 18 months. CHOP-like regimens are advised, but clinical experience is available only with CHVP (combination of cyclophosphamide, doxorubicin, teniposide and prednisolone).

Malignant melanoma
As induction therapy, interferon alfa-2b is administered intravenously at a dose of 20 million IU/m2 daily for five days a week for a four-week period; the calculated interferon alfa-2b dose is added to sodium chloride 9 mg/ml (0.9 %) solution for injection and administered as a 20-minute infusion (see section 6.6). As maintenance treatment, the recommended dose is 10 million IU/m2 administered subcutaneously three days a week (every other day) for 48 weeks.

If severe adverse events develop during interferon alfa-2b treatment, particularly if granulocytes decrease to < 500/mm3 or alanine aminotransferase/aspartate aminotransferase (ALT/AST) rises to > 5 x upper limit of normal, discontinue treatment temporarily until the adverse event abates.
Interferon alfa-2b treatment is to be restarted at 50 % of the previous dose. If intolerance persists after dose adjustment or if granulocytes decrease to < 250/mm3 or ALT/AST rises to > 10 x upper limit of normal, discontinue interferon alfa-2b therapy.

Although the optimal (minimum) dose for full clinical benefit is unknown, patients must be treated at the recommended dose, with dose reduction for toxicity as described.

AIDS-related Kaposi's sarcoma
The optimal dosage is not yet known. Efficacy has been demonstrated at a daily dose of 10 million IU administered subcutaneously. The minimum effective dose is not established. The maximum tolerated daily dose of Intron A is 20 million IU.

If severe adverse reactions develop, the dosage should be modified (50% reduction) or therapy discontinued temporarily until adverse reactions abate.
When disease stabilization or treatment response occurs, treatment should continue until there is no further evidence of tumour or until discontinuation is required by evidence of a severe opportunistic infection or adverse effect. INTRON A therapy has been administered in an outpatient regimen.

Metastatic renal cell carcinoma
As monotherapy: Optimal dose and schedule have not been determined. INTRON A has been administered subcutaneously at doses ranging from 3 to 30 million IU/m 2 either three times a week, five days per week, or daily. The highest response rates were achieved when INTRON A was administered subcutaneously at doses of 3 to 10 million IU/m2 three times a week.
In combination with other therapeutic agents, such as interleukin-2: Optimal dose has not been determined. INTRON A has been administered subcutaneously at doses ranging from 3 to 20 million IU/m2 in combination with interleukin-2. In the trials reporting the highest overall response rates, INTRON A was administered subcutaneously at a dose of 6 million IU/m2 three times a week; dose was adjusted as needed during treatment.