Paclitaxel - administration of paclitaxel in combination with trastuzumab resulted in
1.5 increase in trastuzumab serum levels

Breast cancer

Most common adverse reactions-
anemia, diarrhea, dyspnea, fatigue, fever, headache, increased cough, infections,
infusion  reactions, myalgia, nausea, neutropenia, rash and vomiting.

Adverse reactions requiring discontination-
CHF, pulmonary toxicity, severe infusion reactions, and significant decline in left ventricular
cardiac function.

Cardiovascular -   cardiac arrhythmias  2%  cardiac failure congestive 2%
                               ejection fraction decreased  3%   hypertension  3%
                               palpitations  2%

CNS -                     asthenia   4%    dizziness  3%    headache 9% 

Dermatologic -      nail disorders  2%   pruritus  2%  rash  3%

GI -                         constipation 2%   diarrhea  6%    nausea   5%  vomiting  3%

Musculoskeletal -  arthalgia  7%    back pain  4%   bone pain 2%   muscle pain 2%
                                myalgia   3%

Respiratory -        cough   4%  dyspnea  2%   influenza  3% nasopharyngitis  7%
                               rhinitis  2%    sinusitis  2%  upper respiratory infection  3%

Miscellaneous-      chills 4%         edema peripheral 4%  pyrexia  5%
                                 urinary tract infection 2%

Special precautions/Warnings-

Cardiovascular effects- trantuzumab can cause left ventricular cardiac dysfunction,
arrhthmias, hypetension, disabling cardiac failure , cardiomyopathyb and cardiac death

Evaluate left ventricular function in all patients to and during treatment with trastuzumab.
Discontinue trastuzumab treatment inn patients receiving adjuvant therapy and strongly
consider discontinuation of trastuzumab treatment in patients with metastatic breast cancer

Discontinue transtuzumab for infusion reaction manifesting anaphylaxis, angioedema,
interstitial pneumonitis or acute respiratory distress syndrome

Pulmonary toxicity - trastuzumab use can result in serious and fatal pulmonary toxicity.
Pulmonary toxicity include dyspnea, interstitial pneumonitis, pulmonary infiltrates,
pulmonary insufficiency , acute respiratory distress etc.

Pregnancy - if trastuzumab is used during pregnancy or if a women becomes pregnant
while on treatment, appraise her of the potential hazard to the fetus.

Lactation- Decide whether to discontinue breast feeding or the drug taking  into account the the elimination half-life of trastuzumab and importance of the drug to the mother.

Children- safety and eficacy of trastuzumab in pediatric patients have not been established

Elderly- risk of cardiac dysfunction increased in elderly patients as compared with younger
patients

Monitoring-  conduct through cardiac assessment including history , physical examination,
and determination of LVEF by echocardiogram, multiple gated acqusition scan.

Indication-

Breast cancer

Dosage-

Do not administer as an intravenous IV push or bolus

Adjuvant breast cancer treatment- administer according to one of the following following
doses and schedule for a total of 52 weeks of trastuzumab therapy

During and following paclitaxel , docetaxel or docetaxel/carboplatin -
initial dose is 4mg/kg as an IV infusion over 90 minutes, and then 2mg/kg as an
IV infusion over 30 minutes weekly during chemotherapy for the first 12 weeks
( paclitaxel or docetaxel ) or 18 weeks ( docetaxel/carboplastin )

One week following the last weekly dose of trastumuzab , administer trastuzumab
6mg/kg as an IV infusion over 90 minutes

Metastatic breast  cancer-  administer trastuzumab alone or in combination with paclitaxel
at an initial dose of 4mg/kg as a 90 minute IV infusion followed by subsequent weekly
doses of 2m/kg as a 30 minute IV  infusion until disease progression

Dose modification- decrease the rate of infusion for mild  to moderate infusion reactions.
Discontinue transtuzumab for severe or life threatening infusion reactions.

1. Advice patients to inform their doctor immediately if they notice, new onset or worsening
   shortness of breath ,cough, swelling of ankles/ legs, swelling of the face, palpitations,
    weight gain of more than 5 pounds in 24  hours, dizziness or loss of consciousness.

2. Advice women with reproductive potential to use contraceptive methods during
  treatment and for a minimum period of  6 months following trastuzumab

Pregnancy -
If trastuzumab is used during pregnancy or if a women becomes pregnant
while on treatment, appraise her of the potential hazard to the fetus.

Lactation-
Decide whether to discontinue breast feeding or the drug taking  into account the
the elimination half-life of trastuzumab and importance of the drug to the mother.

Children-                                                                                                                          Safety and eficacy of trastuzumab in pediatric patients have not been established

Elderly-
Risk of cardiac dysfunction increased in elderly patients as compared with younger
patients