THERAPY
Betaseron / Extavia
Coverage
Protocols
Before Initiation of Therapy :
General
- Negative pregnancy test and counsel with regards to contraception
- CBC, liver enzymes, bilirubin, TSH,
- HBsAg, anti-HBc, anti-HBs, Hepatits C, HIV, VZV serology
- Vaccination status verified and updated if necessary
- Pneumococcus and Haemophilus influenza type B vaccines
Schedule for Dose Titration
- Schedule for Dose Titration
- Days 7, 9, 11: 0.125 mg (4 MIU) 0.5 mL
- Days 13, 15, 17: 0.1875 mg (6 MIU) 0.75 mL
- Days ≥ 19 0.250 mg (8 MIU) 1.0 mL
The titration period may be adjusted if any significant adverse reaction occurs.
In the secondary-progressive MS study, patients initiated treatment with half the dose (4 MIU SC
every other day) for a period of 2 weeks prior to escalating to the recommended dose of
8 MIU (SC every other day).
Monitoring During Therapy :
- CBC,Liver enzymes Q1month X6 then Q4 months
- TSH Q6 months
- Nabs any time after 12 months
Discontinue Therapy :
- ALT>5X ULN or jaundice
- Nabs (+)
- Recurrent injection site reaction or necrosis
- Severe thrombocytopenia especially in setting of fever and encephalopathy (R/O TTP)
- Severe leukopenia or pancytopenia
- Depression or suicidal ideation
- Unexplained cardiomyopathy with /out congestive heart failure
- Pregnancy
- Seizure
Studies
Product Monograph
Specific Concerns
Storage :
Should be stored in a refrigerator . Extremes in temperature and exposure to ligth should be avoided
Patient Selection :
Should be used with caution in patients with prior seizure disorder, liver disease, ongoing depression or concomitantly with other potentially liver toxic therapies
Adverse Events :
- Most frequent adverse event is flu like symptoms (76%) and injections site reactions (85%) . The former tends to diminish in severity and frequency with time (10% after 3 years ).
- Decreased peripheral blood counts in all cell lines, including very rare pancytopenia and thrombocytopenia have been reported from post-marketing experience
- Elevated liver enzymes from hepatic injury or hepatitis including hepatic failure have been reported
- Can lead to autoimmune disorders such as drug induced SLE, autoimmune hepatitis, hyper or hypothyroidism, thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome. These events can may occur after several weeks to several years after starting treatment with interferon beta.
- Anaphylaxis has been reported as a rare complication. Other allergic reactions have included dyspnea, orolingual edema, skin rash and urticaria
- Pancreatitis has been observed with BETASERON use, often associated with
hypertriglyceridemia - Cases of nephrotic syndrome with different underlying nephropathies including collapsing focal
segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranoproliferative
glomerulonephritis (MPGN) have been reported during treatment with interferon-beta products. - Rare cases of secondary systemic capillary leak sydrome (Clarkson syndrome) has been reported with interferon beta administration to patients with underlying monoclonal gammopathy
Injection Site Reactions :
Injection site reaction will occur in 85% of patients. Injection site necrosis (5%) tend to occur early within the first 2-3 months of initiating therapy and rarrely extends to subcutanous fat or fascia.
Neutralizing Antibodies :
Serum neutralizing antibodies (Nabs) were reported to develop in 23 to 41% of patients. Nabs tend to occur by the end of the first year of treatment. Over the subsequent 5 year observation period, approximately 50% of these patients will revert to being Nabs negative. Nabs however have been shown, during the period of Nab positivity to impact clinical efficacy and MRI measures.
Long Term Study (BENEFIT CIS 11 yrs FU Study) :
59% of the original 468 patients were recruited. At year 11, 67% were on a DMT and more specifically only 30% were on Betaseron. No significant difference was found between early and late treatment groups with regards to EDSS, SPMS conversion rate and MRI outcomes.
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