Anticoagulants/ aniplatelet agents -
weigh the potential benefts of medications that interfere with platelet function and/or
anticoagulation against the potential increased risk  of bleeding and hemorhage

Non- Hodgins lymphoma ( NHL )

Most serious adverse reactions -
prolonged cytopenia, and sequelae of cytopeniaa, which inclued infections ( sepsis )
and hemorrhage in thrombocytopenic patients, allergic reactions ( bronchospasm and
angioededma ) secondary leukemia and myelodyplasia

Most common adverse reactions-
neytropenia, thrombocytopenia, and anemia.

Less common but severe -
pneumonia,  pleural effusion, dehydration

Cardiovascular -  hypotension   6%    vasodilation 4%

CNS -    dizziness  4%     headache 13%    somnolence 3%

Dermatologic -   rash  15%   pruritus  8%    sweating 7%

GI-             abdominal pain   13%    anorexia   13%    constipation 5%  diarrhea   10%
                dyspepsia   5%       nausea  34%           vomiting  13%

Metabolic -      peripheral edema   8%                 weight loss 5%

Musculoskeletal -   arthalgia   8%   myalgia  12%

Respiratory-          increased cough 20%   dyspnea 10%   pneumonia 5% 
                               pharyngitis 10%             rhinitis   8%

Miscellaneous -  asthenia    44%    back pain  7%    chest pain 6%   chills  16%
                             fever   35%           hypothyroidism  6%   infection 19%
                             neck pain   5%    pain  17%

Known hypersensitivity to murine proteins or any component of the therapeutic regimen

Special Precations/Warnings-

Hypersenstivity reactions- serious hypersenstivity reactions including some with fatal outcome have been reported.
Make medications for the treament of hypersenstivity reactions eg antihistamines, corticosteroids epinephrine available for immediate use in the event of an allergic reactions during the therapy.

Renal function impairment - 1 131 I-tostitumomab and I131 are excreted primarily in the kidneys.
Impaired renal function may decrase the rate of excretion of the radiolabeled iodine and
 increase patient exposure to the radioative component of the therapeutic regimen

Pregnancy - instruct patients to use effective contraceptive measures during treatment and
for 12 months following administration of the therapeutic regimen

Lactation- substitute formula feeding before starting treatment. Advice women to discontinue breast feeding.

Children- safety and efficacy of the therapeutic regimen in children have not been established

Elderly - because of limited experience  greater sensitivity of some older individuals cannot
be ruled out.

Monitoring- obtain complete blood cell and differential and platelet count prior to and at least weekly following administering of the therapeutic regimen

Continue weekly monitoring of blood counts for a minimum period of 10 weeks or if persistant until severe cytopenia have completely resolved.

Monitor  thyroid-stimulating hormone TSH levels before treatment and annully therafter.

Measure creatinine levels immediately prior to administratin of the therapeutic regimen.

Assess pregnancy potential prior to adminstration in women with child bearing potential  

Indication-

Non- Hodgins lymphoma ( NHL )

Dosage-
therapeutic regimen is  intended  as  a single course of treatment of patients with CD20
antigen expressing , relapsed or refractory, low grade ,folicular or transformed  NHL
inculding patients with rutuximab -refractory NHL

Premedication- acetaminophen 650mg orally and diohenhydramine 50mg orally 30 minutes
prior to administration of tositumomab in the dosimetric and therapeutic steps.

1. Inform patients that they will have a radioactive material in their body for several days upon release from the hospital or clinic.

2. After discharge provide patients with oral and written instructions for minimising exposure
of family members ,friends and general public. Give patients a copy of written instructions
for use asa reference for the recommended precautionary actions

3. Assess the pregnancy status of women of childbearing potential and advice them of
the potential risks to the fetus. Instruct women of the resultant harmful effects to the infant
if these instructions are not followed.

4. Advice patients of the potential risk of toxic efects on the male and female glands
following the therapetic  regimen, and instruct patients to use effective contraceptive
measures during treatment and for 12 months following administration of the therapeutic
regimen

5. Inform patients of the risk of cytopenia and symptoms associated with cytopenia and
the need for frequent monitoring  for upto 12 weeks after treatment and that the potential
for persistent cytopenia beyond 12 weeks.

6. Inform patients that certain antineoplastic agents used in the treatment of malignancy
including this therapeutic regimen have been associated with the development of MDS
secondary leukemia and solid tumors 

7. Because of the lack of controlled clinical studies and high  background incidence in
the heavily pretreated patient population, the relative risk of development of MDS/acute
leukemia and solid tumors caused by the therapeutic regimen cannot be determined

8. Inform patients of the possibility of developing a HAMA immune response  and that
HAMA may affect the results of the vitro and vivo diagnostic tests, as well as results
of therapies that rely on murine antibody technology.

Pregnancy -
Instruct patients to use effective contraceptive measures during treatment and
for 12 months following administration of the therapeutic regimen

Lactation-
Substitute formula feeding before starting treatment. Advice women to discontinue
breast feeding.

Children-
Safety and efficacy of the therapeutic regimen in children have not been established

Elderly -
Because of limited experience  greater sensitivity of some older individuals cannot
be ruled out.