guaifenesin brand name(s) mucinex
topotecan

| Common                                                                                                                                                                                                                                                                  | Serious            |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------|
| Orthostatic hypotension Electrolyte imbalance (2-4%) Hyperuricemia  Constipation (2%) Diarrhea (2%) Indigestion (2%) Nausea (2%) Muscle cramp Dizziness (3%) Fatigue Headache (7%) Insomnia (1%) Nervous feeling (1%) Excessive urination (7%) Cough (2%) Rhinitis (3%) | Ototoxicity (rare) |  
- Patient should avoid activities requiring mental alertness or coordination until drug effects are realized.  
- Advise patient to rise slowly from a lying/sitting position, as this drug may cause orthostatic hypotension.  
- This drug may cause headache and excessive urination. - Instruct patient to report signs/symptoms of ototoxicity (tinnitus, hearing loss).  
| Tranylcypromine                                                                                                                                              |                                                                                                                                                                                         |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Common                                                                                                                                                       | Serious                                                                                                                                                                                 |
| Edema Orthostatic hypotension Weight gain Constipation Diarrhea Loss of appetite Nausea Xerostomia Asthenia Dizziness Headache Insomnia Somnolence Impotence | Hypertensive crisis Agranulocytosis (rare) Anemia (rare) Leucopenia (rare) Thrombocytopenia (rare) Hepatitis (rare) Worsening depression (rare) Suicidal thoughts (rare) Suicide (rare) |  
- Patient should avoid activities requiring mental alertness or coordination until drug effects are realized, as drug may cause dizziness or somnolence.  
- Instruct patient to rise slowly from a sitting/supine position, as drug may cause orthostatic hypotension.  
- This drug may cause edema, weight gain, anticholinergic effects, diarrhea, anorexia, nausea, asthenia, headache, insomnia, agitation, anxiety, manic behavior, or impotence.  
- Advise patient that full symptomatic improvement may not be seen for up to 3 weeks.  
- Instruct patient to report worsening depression, suicidal ideation, or unusual changes in behavior, especially at initiation of therapy or with dose changes. Children and adolescents are at higher risk for these effects during the first few months of therapy.  
- Advise patient against sudden discontinuation of drug.  
- Advise patient there are multiple significant drug-drug interactions for this drug. Consult healthcare professional prior to new drug use (including over-the-counter and herbal drugs).  
- Patient should not drink alcohol while taking this drug. - Tell patient to limit amount of caffeine during therapy. - Patient should avoid eating foods high in tyramine while taking this drug, as this may cause extremely high blood pressure. High tyramine foods include dried or very ripe fruits, liver, sausage, and other meats, and aged or fermented foods/drinks such as wine, cheese or pickles.  
| Risks and side effects related to trastuzumab include those which are: Likely Less Likely                                                                                                                                                                                                                                                                                                                    | Rare but serious                                                                                                                                                                                                                                                                                 |                                                                                                       |                                                                                                                                                                                                                                                                                         |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Diarrhea                                                                                                                                                                                                                                                                                         |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| The following reactions are  more common with the first  dose of tratuzumab but could  occur with any infusion of the  drug  - Nausea and vomiting - Headache - Rash during the infusion - Fever and chills including  shaking chills.  - Feeling short of breath - Pain in the abdomen, the  back or at the tumor site - A feeling of tiredness or  weakness - A decrease or an increase in  blood pressure | -                                                                                                                                                                                                                                                                                                | Damage to the heart muscle  which may make you tired,  weak, feel short of breath,  and retain fluid* |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | A feeling of tiredness                                                                                                                                                                                                                                                                           |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Muscle and joint aches and  pains                                                                                                                                                                                                                                                                |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Bone, chest and nerve pain                                                                                                                                                                                                                                                                       |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Numbness and tingling in  the fingers and toes                                                                                                                                                                                                                                                   |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Fluid retention and buildup in the tissues usually of  the lower legs leading to an  increase in weight                                                                                                                                                                                                                                                                                                  |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Inflammation of the  sinuses, the throat and nose  which could lead to pain or  pressure, runny nose or  change in your voice                                                                                                                                                                    |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Infections including  bladder or kidney  infections and skin  infections                                                                                                                                                                                                                         |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Wheezing and/or shortness  of breath                                                                                                                                                                                                                                                             |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Rash, hives or itchiness                                                                                                                                                                                                                                                                         |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Acne                                                                                                                                                                                                                                                                                             |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Rash with skin sores                                                                                                                                                                                                                                                                             |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Fast or irregular heart beat  during the infusion                                                                                                                                                                                                                                                |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Mouth Sores with  inflammation and pain                                                                                                                                                                                                                                                          | -                                                                                                     | Allergic reactions during the  infusion that can be severe and  life-threatening and may lead to  difficulty in breathing, a drop in  blood pressure, irregular heart  beat, a sudden stopping of the  heart (cardiac arrest), fluid in the  lungs or damage to the lungs and  shock.** |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Fewer white blood cells, red  blood cells and platelets in the  blood  o a low number of white blood  cells can make it easier to get  infections  o a low number of red blood  cells can make you feel tired  and weak o a low number of platelets  causes you to bruise and  bleed more easily |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Severe allergic reaction which can  be life threatening with rapid  build-up of fluid under the skin, in  the lining of the intestine and  possibly in the throat or swelling  of the tongue which could make it  difficult to breath.                                                           |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| -                                                                                                                                                                                                                                                                                                                                                                                                            | Sudden, temporary feeling of  chest tightness, wheezing or  coughing making it difficult to  breath which can occur during or                                                                                                                                                                    |                                                                                                       |                                                                                                                                                                                                                                                                                         |
| 7/19/05                                                                                                                                                                                                                                                                                                                                                                                                      |                                                                                                                                                                                                                                                                                                  |                                                                                                       |                                                                                                                                                                                                                                                                                         |
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guaifenesin brand name(s) mucinex
trastuzumab

| shortly after the infusion   |                                                                                                                                                                                                               |
|------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| -                            | Inflammation and scarring of the  lungs that can lead to fluid in the  lungs and affect your ability to  breath and the levels of oxygen in  your blood.                                                      |
| -                            | Damage to the heart which can  lead to inflammation of the heart  muscle and a build-up of fluid  around the heart which may be  painful and affect the ability of  the heart to work normally                |
| -                            | Damage to the kidneys that causes  protein to be lost from the blood  by leaking from the kidneys into  the urine and causing swelling  usually in the legs and ankles  from fluid build-up in body  tissues. |
| -                            | Loss of desire to eat                                                                                                                                                                                         |
| -                            | Dizziness or fainting                                                                                                                                                                                         |
| -                            | Cough                                                                                                                                                                                                         |
| -                            | Depression                                                                                                                                                                                                    |
| -                            | Difficulty sleeping                                                                                                                                                                                           |
| -                            | Elevation in the blood of  certain enzymes found in  the liver                                                                                                                                                |
| -                            | Fever with a low white  blood cell count which  could indicate infection  and may require  hospitalization and  treatment with antibiotics                                                                    |  
* Trastuzumab rarely causes decreases in heart function when administered by itself.  
When Trastuzumab is given alone, these changes in heart function are usually reversible. When Trastuzumab is given in combination with chemotherapy drugs called anthracyclines (for example doxorubicin) or cyclophosphamide, there is a much greater risk of heart damage, though this complication is still uncommon. Such damage can result in a rapid heart beat, decreased pumping strength of the heart, and accumulation of fluid in the lungs which may rarely interfere with breathing.  
**Some patients may have a severe of life-threatening reaction during or after treatment with Trastuzumab. These reactions can involve a drop in blood pressure and shortness of breath, and have resulted in death in several patients. These severe reactions may be more common in patients who already have breathing difficulties or lung disease. If you develop any clear discomfort during or after a treatment with Trastuzumab, you should contact your physician immediately or go to the nearest Emergency Care facility.  
| Common                                                                                                                                                  | Serious                                                                                                                                                                                                                                    |              |
|---------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------|
| Sweating symptom Weight change Constipation Diarrhea Loss of appetite Nausea Vomiting Xerostomia Dizziness Headache Insomnia Lethargy Memory impairment | Cardiac diysrhythmia (rare) Hypertension (rare) Hypotension (rare) Hemolytic anemia (rare) Leukocytosis (rare) Methemoglobinemia (rare) Seizure (rare) Worsening depression (rare) Suicidal thoughts (rare) Suicide (rare) Priapism (rare) |              |
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guaifenesin brand name(s) mucinex
valproic acid

Risks and side effects related to the valproic acid include those which are: Likely:
- nausea
- vomiting
- abdominal pain - diarrhea
- headache
- sleepiness
- tremor
- loss of strength and energy
- dizziness
- hair loss
- rash
- dry skin
- itching of the skin
- numbness and tingling of your hands and/or feet
- short-term weakness of your hands and/or feet Less Likely:
- loss of appetite - heartburns - flu-like syndromes
- double vision
- blurred vision
- unsteadiness
- unsteady eye movement
- sleeplessness - loss of memory
- Patient should avoid driving and other activities requiring mental alertness or coordination until drug effects are realized, as this medicine may cause dizziness or somnolence.  
- This drug may cause sweating, weight change, anticholinergic effects, diarrhea, anorexia, nausea, vomiting, headache, insomnia, lethargy, and memory impairment.  
- Advise patient that symptomatic improvement may not be seen for 2 to 4 weeks.  
- Instruct patient to report worsening depression, suicidal ideation, or unusual changes in behavior, especially at initiation of therapy or with dose changes. Children and adolescents are at higher risk for these effects during the first few months of therapy.  
- Patient should take with food or milk.  
- Advise patient against sudden discontinuation of drug. - Patient should not drink alcohol while taking this drug.  
- moodiness
- anxiety or nervousness
- ringing in the ear
- pneumonia
- weight gain or loss
- abnormal thyroid function - low platelet count, which may cause easy bruising or bleeding
- abnormal blood clotting which can lead to excessive bleeding during and after surgery Rare but can be serious:
- sores in the mouth or on the tongue
- hyperactivity
- confusion
- coma
- severe reactions involving skin, mouth, and eyes, including blisters
- redness, swelling, and/or peeling of your skin, resulting in pain and infection
- eye pain and irritation
- low white and/or red blood cell count
- abnormal effects on unborn babies (see "Risks of Pregnancy", below)
- severe to life-threatening inflammation of the pancreas and liver
- hearing loss
- abnormal sodium level in the blood
- fast and/or irregular heart beats, high blood pressure
- peeing frequently, vaginal yeast infection - inflammation of the kidney
- irregularities in your periods, including complete stoppage of your periods
- gum bleeding or swelling, infection around your teeth
- abnormal change in the bone marrow leading to chronic transfusions, and possibly leading to a pre-leukemia condition called myelodysplastic syndrome.  
- abnormal clotting tests and possibly increased risk of bleeding
guaifenesin brand name(s) mucinex
vandetanib adverse effects serious

- **Cardiovascular:** Heart failure (0.9%), Prolonged QT interval (all Grades, 14%; Grade 34, 8%)
- **Dermatologic:** Stevens-Johnson syndrome - **Gastrointestinal:** Pancreatitis (0.4%) - **Hematologic:** Hemorrhage, Decreased platelet count (9%), Neutropenia (10%) - **Immunologic:** Sepsis - **Neurologic:** Ischemic stroke (1.3%), Reversible posterior leukoencephalopathy syndrome
- **Respiratory:** Aspiration pneumonia, Interstitial lung disease, Respiratory arrest, Respiratory failure  
- **Cardiovascular:** Hypertension (all Grades, 33%; Grade 3-4, 5%)
- **Dermatologic:** Acne (all Grades, 35%; Grade 3-4, 1%), Rash (all Grades, 53%; Grade 34, 5%), Dry Skin (15%), Photosensitivity (13%), Pruritis (11%)
- **Endocrine metabolic:** Decreased calcium level (all Grades, 57%; Grade 3-4, 6%),
Decreased glucose level (24%), Hypomagnesemia (7%), Decreased weight (10%)
- **Gastrointestinal:** Abdominal pain (all Grades, 21%; Grade 3-4, 3%), Colitis, Diarrhea, Loss of appetite (all Grades, 21%; Grade 3-4, 4%), Nausea (all Grades, 33%; Grade 3-4, 1%)
- **Hepatic:** ALT/SGPT level raised (all Grades, 51%; Grade 3-4, 2%)
- **Neurologic:** Headache (all Grades, 26%; Grade 3-4, 1%), Asthenia (15%)
- **Opthalmic:** Blurred vision (9%)
- **Psychiatirc:** Depression (10%)
- **Renal:** Proteinuria (10%), Serum creatinine raised (16%) - **Respiratory:** Cough (11%),Nasopharyngitis (11%)
- **Other:** Fatigue (all Grades, 24%; Grade 3-4, 6%)  
| Common                                                   | Serious                                                   |
|----------------------------------------------------------|-----------------------------------------------------------|
| Edema Hypotension Constipation Nausea Dizziness Headache | Angina (rare) Myocardial infarction (rare) Syncope (rare) |  
- Patient should avoid activities requiring mental alertness or coordination until drug effects are realized, as this medicine may cause dizziness and light-headedness.  
- This drug may cause edema, constipation, nausea, and headache. - Patient should watch for signs/symptoms of hypotension with initial dosing and dose changes.  
- Advise patient against sudden discontinuation of drug, as this may precipitate hypertensive rebound/crisis.  
- Patient should not drink alcohol while taking this drug.
guaifenesin brand name(s) mucinex
vinblastine

| Risks and side effects related to Vinblastine include those which are: Likely Less Likely   | Rare but serious                                                                                                                                                                                                                                                                                    |              |                                                                                         |
|---------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------|-----------------------------------------------------------------------------------------|
| -                                                                                           | Hair loss                                                                                                                                                                                                                                                                                           |              |                                                                                         |
| -                                                                                           | Fewer white blood  cells, red blood cells  and platelets in the  blood  o a low number of  red blood cells can  make you feel tired  and weak o a low number of  white blood cells  can make it easier  to get infections o a low number of  platelets causes you  to bruise and bleed  more easily | -            | Constipation                                                                            |
| -                                                                                           | Diarrhea                                                                                                                                                                                                                                                                                            |              |                                                                                         |
| -                                                                                           | Nausea and /or vomiting                                                                                                                                                                                                                                                                             |              |                                                                                         |
| -                                                                                           | Loss of Appetite                                                                                                                                                                                                                                                                                    |              |                                                                                         |
| -                                                                                           | Reversible nerve problem that may  affect the way you walk or the  feelings in your fingers or toes  (Numbness and tingling) or may  make you feel weak                                                                                                                                             |              |                                                                                         |
| -                                                                                           | A hoarse voice                                                                                                                                                                                                                                                                                      |              |                                                                                         |
| -                                                                                           | Mouth sores                                                                                                                                                                                                                                                                                         |              |                                                                                         |
| -                                                                                           | Depression                                                                                                                                                                                                                                                                                          |              |                                                                                         |
| -                                                                                           | Jaw pain                                                                                                                                                                                                                                                                                            |              |                                                                                         |
| -                                                                                           | Bone pain                                                                                                                                                                                                                                                                                           |              |                                                                                         |
| -                                                                                           | Headache                                                                                                                                                                                                                                                                                            |              |                                                                                         |
| -                                                                                           | A feeling or tiredness or not well                                                                                                                                                                                                                                                                  |              |                                                                                         |
| -                                                                                           | Rash and a tendency to burn more  easily in the sun (very rarely  reported)                                                                                                                                                                                                                         |              |                                                                                         |
| -                                                                                           | Inflammation and discomfort in the  vein through which the medicine was  given                                                                                                                                                                                                                      |              |                                                                                         |
| -                                                                                           | A sore throat                                                                                                                                                                                                                                                                                       |              |                                                                                         |
| -                                                                                           | Pain and bloating in your abdomen                                                                                                                                                                                                                                                                   |              |                                                                                         |
| -                                                                                           | Drooping eyelids                                                                                                                                                                                                                                                                                    |              |                                                                                         |
| -                                                                                           | Double vision                                                                                                                                                                                                                                                                                       |              |                                                                                         |
| -                                                                                           | Rapid, jerky movements of the eye  which are not under your control and  can alter your vision                                                                                                                                                                                                      |              |                                                                                         |
| -                                                                                           | Difficulty with urination or increase  desire to urinate                                                                                                                                                                                                                                            |              |                                                                                         |
| -                                                                                           | Abnormal hormone function which  may lower the level of salt in the  blood                                                                                                                                                                                                                          |              |                                                                                         |
| -                                                                                           | Damage to the ear causing hearing  loss which maybe temporary or  permanent, balance problems  (dizziness) and ringing in the ears                                                                                                                                                                  |              |                                                                                         |
| -                                                                                           | Absence or decrease in the number of  sperm and/or damage to the testis  which may be temporary or  permanent which may decrease the  ability to have children in the future                                                                                                                        |              |                                                                                         |
| -                                                                                           | Absence of menstrual cycles  (periods) and damage to the ovaries  that may decrease the ability to have                                                                                                                                                                                             | -            | Complete stoppage of your  intestinal activity which can  result in intestinal blockage |
| -                                                                                           | If the drug leaks out of the  vein when being administered  it will cause damage to nearby  tissue                                                                                                                                                                                                  |              |                                                                                         |
| -                                                                                           | The rapid death of large  numbers of tumor cells which  can cause the uric acid in the  blood to rise quickly and this  could lead to damage to the  kidneys.                                                                                                                                       |              |                                                                                         |
| -                                                                                           | Seizures                                                                                                                                                                                                                                                                                            |              |                                                                                         |
| -                                                                                           | A sudden onset of shortness  of breath which may be  accompanied by wheezing  and/or coughing and a feeling  of tightness in the chest                                                                                                                                                              |              |                                                                                         |
| -                                                                                           | Fluid build up in the lungs                                                                                                                                                                                                                                                                         |              |                                                                                         |
| -                                                                                           | A heart attack or an abnormal  heart rhythm                                                                                                                                                                                                                                                         |              |                                                                                         |
| -                                                                                           | Bleeding from the  gastrointestinal tract including  from a stomach ulcer, the  colon or the rectum                                                                                                                                                                                                 |              |                                                                                         |
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| Issued 12 June 2013                                                                         |                                                                                                                                                                                                                                                                                                     |              |                                                                                         |  
| children in the future   |                                                                                                                                                             |
|--------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------|
| -                        | Temporary inflammation of the liver  leading to an elevation in the blood of  certain enzymes found in the liver                                            |
| -                        | High blood pressure                                                                                                                                         |
| -                        | Blanching (whiteness) of the fingers  or toes when they are exposed to cold  or when you are under stress, that  may make them feel cold or throb and  ache |
guaifenesin brand name(s) mucinex
vinorelbine

| Vinorelbine                                                                                                                              | Rare But Serious                                                                                                                                                                                                |              |           |          |     |
|------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------|-----------|----------|-----|
| Happens to less than 3 patients  out of every 100                                                                                        |                                                                                                                                                                                                                 |              |           |          |     |
| -                                                                                                                                        | Injection                                                                                                                                                                                                       | site         | reactions |          |     |
| including                                                                                                                                | redness,                                                                                                                                                                                                        | pain         |           |          |     |
| and vein discoloration                                                                                                                   |                                                                                                                                                                                                                 |              |           |          |     |
| -                                                                                                                                        | Nausea                                                                                                                                                                                                          |              |           |          |     |
| -                                                                                                                                        | Vomiting                                                                                                                                                                                                        |              |           |          |     |
| -                                                                                                                                        | A drop in white blood cells  and red blood cells in the  blood o a low number of red  blood cells can make  you feel tired and  weak o a low number of white  blood cells can make it  easier to get infections |              |           |          |     |
| -                                                                                                                                        | Tiredness                                                                                                                                                                                                       |              |           |          |     |
| -                                                                                                                                        | Constipation                                                                                                                                                                                                    |              |           |          |     |
| -                                                                                                                                        | Increased                                                                                                                                                                                                       | liver        | enzyme    |          |     |
| levels                                                                                                                                   | Likely                                                                                                                                                                                                          |              |           |          |     |
| Happens to 10-30 patients out of  every 100                                                                                              | Less Likely                                                                                                                                                                                                     |              |           |          |     |
| Happens to 3-10 patients out of  every 100                                                                                               |                                                                                                                                                                                                                 |              |           |          |     |
| -                                                                                                                                        | Diarrhea                                                                                                                                                                                                        |              |           |          |     |
| -                                                                                                                                        | Hair loss                                                                                                                                                                                                       |              |           |          |     |
| -                                                                                                                                        | Fever                                                                                                                                                                                                           |              |           |          |     |
| -                                                                                                                                        | A drop in platelets in the  blood o a low number of platelets  causes you to bruise and  bleed more easily                                                                                                      |              |           |          |     |
| -                                                                                                                                        | Muscle weakness                                                                                                                                                                                                 |              |           |          |     |
| -                                                                                                                                        | Inflammation                                                                                                                                                                                                    | of           | the       | vein     |     |
| through which the drug was  given                                                                                                        |                                                                                                                                                                                                                 |              |           |          |     |
| -                                                                                                                                        | Decreased appetite                                                                                                                                                                                              |              |           |          |     |
| -                                                                                                                                        | Reversible                                                                                                                                                                                                      | nerve        | problem   |          |     |
| that may affect the way you  walk or the feelings in your  fingers or toes, the likelihood  of which increases with the  number of doses |                                                                                                                                                                                                                 |              |           |          |     |
| -                                                                                                                                        | Pain in your abdomen                                                                                                                                                                                            |              |           |          |     |
| -                                                                                                                                        | Mouth sores                                                                                                                                                                                                     |              |           |          |     |
| -                                                                                                                                        | Rash                                                                                                                                                                                                            |              |           |          |     |
| -                                                                                                                                        | Increased                                                                                                                                                                                                       | bilirubin    | which     |          |     |
| may                                                                                                                                      | result                                                                                                                                                                                                          | in           | a         | yellow   |     |
| appearance                                                                                                                               |                                                                                                                                                                                                                 |              |           |          |     |
| -                                                                                                                                        | Increased                                                                                                                                                                                                       | or           | decreased |          |     |
| blood pressure                                                                                                                           |                                                                                                                                                                                                                 |              |           |          |     |
| -                                                                                                                                        | Muscle aches                                                                                                                                                                                                    |              |           |          |     |
| -                                                                                                                                        | Redness and peeling skin on  the palms and soles                                                                                                                                                                |              |           |          |     |
| -                                                                                                                                        | Hearing loss                                                                                                                                                                                                    |              |           |          |     |
| -                                                                                                                                        | Headache                                                                                                                                                                                                        |              |           |          |     |
| -                                                                                                                                        | Jaw pain                                                                                                                                                                                                        |              |           |          |     |
| -                                                                                                                                        | Bleeding of the bladder                                                                                                                                                                                         |              |           |          |     |
| -                                                                                                                                        | A                                                                                                                                                                                                               | return       | of        | redness  | and |
| inflammation                                                                                                                             | at                                                                                                                                                                                                              | a            | site      | of       |     |
| previous radiation therapy                                                                                                               | -                                                                                                                                                                                                               | Severe       | allergic  | reaction |     |
| which                                                                                                                                    | can                                                                                                                                                                                                             | be           | life      |          |     |
| threatening with shortness  of breath, low blood  pressure, rapid heart rate,  chills and fever                                          |                                                                                                                                                                                                                 |              |           |          |     |
| -                                                                                                                                        | Complete stoppage of your  intestinal activity which can  result in intestinal blockage  and damage                                                                                                             |              |           |          |     |
| -                                                                                                                                        | Fluid buildup in the lungs                                                                                                                                                                                      |              |           |          |     |
| -                                                                                                                                        | Difficult                                                                                                                                                                                                       | breathing    | or        |          |     |
| shortness of breath                                                                                                                      |                                                                                                                                                                                                                 |              |           |          |     |
| -                                                                                                                                        | Chest pain or heart attack                                                                                                                                                                                      |              |           |          |     |
| -                                                                                                                                        | If the drug leaks out of the  vein when being  administered it may cause  damage to nearby tissue                                                                                                               |              |           |          |     |
| -                                                                                                                                        | Liver damage                                                                                                                                                                                                    |              |           |          |     |
| -                                                                                                                                        | Inflammation                                                                                                                                                                                                    | of           | the       |          |     |
| pancreas                                                                                                                                 |                                                                                                                                                                                                                 |              |           |          |     |
| -                                                                                                                                        | Clots in veins such as the  ones in the legs or lungs                                                                                                                                                           |              |           |          |     |
| -                                                                                                                                        | Severe shortness of breath  and respiratory failure due  to injured lungs that can be  fatal                                                                                                                    |              |           |          |     |
| Version 2.0 Final                                                                                                                        | Page 262 of 268                                                                                                                                                                                                 | Confidential |           |          |     |
| Issued 12 June 2013                                                                                                                      |                                                                                                                                                                                                                 |              |           |          |     |
guaifenesin brand name(s) mucinex
vorinostat

Risks and side effects related to the vorinostat include those which are:
Likely
- Low Blood Counts: decreased red blood cells that carry oxygen in the body
(anemia), decrease in a type of white blood cell called neutrophils, decreased total numbers of white blood cells (infection fighting cells) which may increase your risk of infection, decrease in the type of blood cells called platelets that help to clot blood.  
- fatigue
- weight loss
- loss of appetite - diarrhea
- nausea
- vomiting
- high blood level of creatinine, a substance normally eliminated by the kidneys into the urine
- high level of sugar in the blood
guaifenesin brand name(s) mucinex
less likely

- Low Blood Counts: decreased number of a type of white blood cell called lymphocytes
- changes in heart rhythm - abnormal levels of blood protein in a blood test to check blood clotting ability
- fever - chills - hair loss
- constipation
- dehydration
- dry mouth
- heartburn
- taste alteration
- fever with dangerously low white blood cell count - infection
- swelling of the limbs such as the arms or legs
- low levels of a blood protein called albumin
- abnormal liver or bone enzyme level - abnormal liver enzyme level
- abnormal level of bilirubin in the blood. Bilirubin is a bile pigment found in the liver.  
- decreased blood calcium level
- increased blood magnesium level
- decreased blood phosphate level
- decreased blood potassium level
- decreased blood sodium level
- muscle spasms
- muscle weakness
- dizziness
- Condition of the nervous system that causes numbness, tingling, burning.  
- pain in the abdomen or belly - headache
- cough
- shortness of breath
- formation or presence of a blood clot inside a blood vessel.  
Rare but serious
- death of the skin tissue called tissue necrosis
guaifenesin brand name(s) mucinex
zolendronic acid

| Likely                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     |                  |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------|
| Happens to 10- 30 patients out  of every 100                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     | Less Likely                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | Rare But Serious |
| Happens to 3-10 patients out of every 100                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        | Happens to less than 3 patients  out of every 100                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   |                  |
| - Fatigue  (tiredness)  - Flu-like  symptoms  including  fever, chills,  and joint and  muscle aches,  which are  generally seen  after the first  infusion  - Low levels of  calcium in the  blood which  may cause  muscle cramps - Anorexia (loss  of appetite)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               | -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   | Headaches        |
| - Insomnia  - Anxiety  - Stomach irritation - Bone, back, muscle, and joint pain - Tachycardia (rapid heart rate) - Abnormal kidney function tests - Diarrhea  - Tingling in the fingers and toes - Nausea, vomiting, constipation, and /or  abdominal pain - Low red blood cell counts which may  cause tiredness, shortness of breath or  fatigue  - Allergic reactions, which include itching,  flushing, rash, and shortness of breath - Low levels of potassium, magnesium,  and/or phosphate in the blood. In almost all  cases, you would not experience symptoms  from these effects. If these levels fall to  extremely low levels, possible side effects  could include muscle twitching, muscle  weakness, and abnormal heart rhythm. - A reaction at the injection site, which  might include pain, redness, tenderness,  swelling, and/or bruising. | - Kidney failure - Severe allergic reactions - Permanent damage to the jawbone  that may be painful and might  require surgery to remove the  damaged area. There is more  information about this below.*  This might be more likely to  happen in patients who have  certain dental procedures. If you  see a dentist, you should inform  them that you are receiving  zoledronic acid. - Serious eye problems. If you  suspect you are having an eye side  effect after receiving the study  drug, you should call the study  doctor.  - Chest pain - Red puffy eyes (conjunctivitis) - Low platelets (increased risk for  bleeding) - Low white blood count (increased  risk of infection)  - Low blood pressure |                  |
| *A condition called osteonecrosis of the jaw (ONJ) has been seen in patients taking zoledronic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     |                  |  
*A condition called osteonecrosis of the jaw (ONJ) has been seen in patients taking zoledronic acid or other bisphosphonates. This happens in less than 1% of patients. ONJ can show up as a non-healing wound in the gum tissue covering the jaw bone, or roof of the mouth, that exposes the bone. The wound can be painful, can worsen over time and often involves an infection in the area with ONJ. This means a portion of the jawbone becomes permanently damaged, may be painful, and may require dental treatment or removal of the damaged area. Little is known about how the wound develops. Based on available evidence, a causal relationship between ONJ and bisphosphonates, including zoledronic acid, has not been established. Most of the patients who got ONJ had cancer and were receiving repeated monthly doses of bisphosphonates and most were also receiving chemotherapy and corticosteroids. Other risk factors for ONJ include radiotherapy and concurrent medical conditions (for example, anemia, a defect in the blood clotting mechanism, infection and pre-existing oral disease). In most cases, the patient also had surgery in the mouth or a tooth removed. ONJ has been much less frequently reported in noncancer patients taking bisphosphonates. For patients requiring oral surgery, there are no data available to suggest whether stopping bisphosphonate treatment reduces the risk of ONJ. In patients who develop ONJ, surgery at the affected area may make the condition worse. If you think you have this condition see your Study Doctor and dentist immediately.  
| Tissue                                                      | Tissue Sub Detail   |
|-------------------------------------------------------------|---------------------|
| Brain                                                       | Amygdala            |
| Esophagus Brain                                             | Corpus Callosum     |
| Large  Intestine                                            | Cecum               |
| Small  Intestine                                            | Jejunum             |
| Prostate  Gland Tonsil Salivary Gland                       | Submandibular Gland |
| Brain                                                       | Amygdala            |
| Nipple Lymph Node Testis Prostate  Gland Corpus Uteri Brain | Temporal Lobe L     |
| Brain                                                       | Accumbens           |
| Skeletal  Muscle                                            | Quadriceps Femoris  |
| Brain                                                       | Accumbens           |
| Brain                                                       | Putamen             |
| Brain                                                       | Entorhinal Cortex   |
| Brain                                                       | Putamen             |
| Adrenal  Gland Corpus Uteri                                 | Myometrium          |
| Corpus Uteri                                                | Myometrium          |
| Liver Uterus                                                | Endometrium         |
| Uterus                                                      | Endometrium         |
| Brain                                                       | Substantia Nigra    |
| Heart Brain                                                 | Hippocampus         |
| Kidney                                                      | Medulla             |
| Corpus Uteri                                                | Endometrium         |
| Skin Bronchus Brain                                         | Frontal Lobe NOS    |
| Brain                                                       | Hippocampus         |
| Corpus uteri                                                | Myometrium          |
| Skin                                                        |                     |  
Page 266  
| Spleen Small  Intestine   | Ileum                      |
|---------------------------|----------------------------|
| Brain                     | Brain, Subthalamic Nucleus |
| Brain                     | Thalamus                   |
| Brain                     | Accumbens                  |
| Brain                     | Occipital Cortex           |
| Gland                     | Pituitary Gland            |  
  
The total number of drugs that can be selected by the OncInsights service is 327.  The diagram
represents the total number of drugs which can be selected by each method.  Because one or more drugs can be selected by one or more methods the sum of drugs listed in the figure will not equal the unique drug count.