Note:  The following toxicity table is a DRAFT and designed to provide
general guidance on parameters for monitoring safety in clinical
trials.  This toxicity table is not comprehensive and should not be
applied directly to all trials.  

 

When selecting a toxicity table, the following are some of the items
that must be taken into consideration:

 

-   The population being studied

    -   Does the clinical trial evaluate healthy subjects, subjects with
        a particular disease or condition? 

-   The stage of test article development

    -   Is the clinical trial a Phase I (is it for the fisrt time in
        human subjects?) , II, III or IV?

-   The type of test article 

    -   Does the clinical trial evaluate a drug, device, vaccine
        or other biologic agent? 

-   The prior human and preclinical experience with the test article

    -   Are there any specific findings that require adjustment of the
        toxicity table? 

    -   Has it been approved for this indication in adult population?

 

Single site clinical trials evaluating healthy subjects should conform
to the laboratory normal values at the single site. Multi-center
clinical trials should reconcile among their laboratory normal values
when evaluating a healthy volunteer population.

 

Please confer with the DMID protocol team and DMID\'s Office of Clinical
Research Affairs when selecting or developing a toxicity table for a
DMID-sponsored trial.

**[ABBREVIATIONS]{.underline}:** Abbreviations utilized in the Table:

> ULN = Upper Limit of Normal LLN = Lower Limit of Normal
>
> R~x~ = Therapy Req = Required
>
> Mod = Moderate IV = Intravenous
>
> ADL = Activities of Daily Living Dec = Decreased

**[ESTIMATING SEVERITY GRADE]{.underline}**

For abnormalities NOT found elsewhere in the Toxicity Tables use the
scale below to estimate grade of severity:

**GRADE 1 Mild** Transient or mild discomfort

(\< 48 hours); no medical intervention/therapy required

**GRADE 2 Moderate** Mild to moderate limitation in activity - some
assistance may be needed; no or minimal medical intervention/therapy
required

**GRADE 3 Severe** Marked limitation in activity, some assistance
usually required; medical intervention/therapy required,
hospitalizations possible

**GRADE 4 Life-threatening** Extreme limitation in activity, significant
assistance required; significant medical intervention/therapy required,
hospitalization or hospice care probable

**GRADE 5 Death**

**[SERIOUS OR LIFE-THREATENING AEs]{.underline}**

ANY clinical event deemed by the clinician to be serious or
life-threatening should be considered a grade 4 event. Clinical events
considered to be serious or life-threatening include, but are not
limited to: seizures, coma, tetany, diabetic ketoacidosis, disseminated
intravascular coagulation, diffuse petechiae, paralysis, acute
psychosis, severe depression.

# COMMENTS REGARDING THE USE OF THESE TABLES

**•** Standardized and commonly used toxicity tables (Division of AIDS,
NCI's Common Toxicity Criteria (CTC), and World Health Organization
(WHO)) have been adapted for use by the Division of Microbiology and
Infectious Diseases (DMID) and modified to better meet the needs of
participants in DMID trials.

**•** For parameters not included in the following Toxicity Tables,
sites should refer to the "Guide For Estimating Severity Grade" located
above.

• Criteria are generally grouped by body system.

• Some protocols may have additional protocol specific grading criteria,
which will supercede the use of these tables for specified criteria.

## ![](media/image1.wmf)(Selected Values for children less than or equal 

## to 3 months of age -- does not apply for preterm infants) 

For all parameters not listed on this table, please refer

to the DMID Toxicity Table for children \> 3 months of age.

+-------------+-------------+-------------+-------------+-------------+
| **H         |             |             |             |             |
| EMATOLOGY** |             |             |             |             |
+-------------+-------------+-------------+-------------+-------------+
|             | **GRADE 1** | **GRADE 2** | **GRADE 3** | **GRADE 4** |
+-------------+-------------+-------------+-------------+-------------+
| Hemoglobin  |             |             |             |             |
+-------------+-------------+-------------+-------------+-------------+
| 1-7 days    | 13.0-14.0   | 12.0-12.9   | \<12 gm/dL  | Cardiac     |
| old         | gm/dL       | gm/dL       |             | Failure\    |
|             |             |             |             | secondary   |
|             |             |             |             | to Anemia   |
+-------------+-------------+-------------+-------------+-------------+
| 8-21 days   | 12.0-13.0   | 10.0-11.9   | \<10.0      | Cardiac     |
| old         | gm/dL       | gm/dL       | gm/dL       | Failure\    |
|             |             |             |             | secondary   |
|             |             |             |             | to Anemia   |
+-------------+-------------+-------------+-------------+-------------+
| 22-35 days  | 9.5-10.5    | 8.0-9.4     | \<8.0 gm/dL | Cardiac     |
| old         | gm/dL       | gm/dL       |             | Failure\    |
|             |             |             |             | secondary   |
|             |             |             |             | to Anemia   |
+-------------+-------------+-------------+-------------+-------------+
| 36-60 days  | 8.5-9.4     | 7.0-8.4     | \<7.0 gm/dL | Cardiac     |
| old         | gm/dL       | gm/dL       |             | Failure\    |
|             |             |             |             | secondary   |
|             |             |             |             | to Anemia   |
+-------------+-------------+-------------+-------------+-------------+
| 61-90 days  | 9.0-9.9     | 7.0-8.9     | \<7.0 gm/dL | Cardiac     |
| old         | gm/dL       | gm/dL       |             | Failure\    |
|             |             |             |             | secondary   |
|             |             |             |             | to Anemia   |
+-------------+-------------+-------------+-------------+-------------+
| Abs         |             |             |             |             |
| Neutrophil  |             |             |             |             |
| Ct          |             |             |             |             |
+-------------+-------------+-------------+-------------+-------------+
| 1 day old   | 5000        | 3000        | 1500        | \           |
|             | -7000/mm^3^ | -4999/mm^3^ | -2999/mm^3^ | <1500/mm^3^ |
+-------------+-------------+-------------+-------------+-------------+
| 2-6 days    | 1750        | 1250        | 750         | \<750/mm^3^ |
| old         | -2500/mm^3^ | -1749/mm^3^ | -1249/mm^3^ |             |
+-------------+-------------+-------------+-------------+-------------+
| 7-60 days   | 1200        | 900         | 50          | \<500/mm^3^ |
| old         | -1800/mm^3^ | -1199/mm^3^ | 0-899/mm^3^ |             |
+-------------+-------------+-------------+-------------+-------------+
| 61-90 days  | 750         | 40          | 25          | \<250/mm^3^ |
| old         | -1200/mm^3^ | 0-749/mm^3^ | 0-399/mm^3^ |             |
+-------------+-------------+-------------+-------------+-------------+
| ### Bi      |             |             |             |             |
| lirubin (Fr |             |             |             |             |
| actionated  |             |             |             |             |
| bilirubin t |             |             |             |             |
| est must be |             |             |             |             |
|  preformed  |             |             |             |             |
| when total  |             |             |             |             |
| bilirubin i |             |             |             |             |
| s elevated) |             |             |             |             |
+-------------+-------------+-------------+-------------+-------------+
| \<7 days    | .           | 20-25mg/dL  | 26-30 mg/dL | \>30 mg/dL  |
| old         |             |             |             |             |
+-------------+-------------+-------------+-------------+-------------+
| 7-60 days   | 1.1-1.9xN   | 2.0-2.9Xn   | 3.0-7.5xN   | \>7.5xN     |
| old         |             |             |             |             |
+-------------+-------------+-------------+-------------+-------------+
| 61-90 days  | 1.1-1.9xN   | 2.0-2.9xN   | 3.0-7.5xN   | \>7.5xN     |
| old         |             |             |             |             |
+-------------+-------------+-------------+-------------+-------------+

##  ![](media/image2.wmf)(Selected Values for children less than or equal 

## ![](media/image3.wmf)to 3 months of age) 

+-----------+-----------+--------------+----------------+-------------+
| # HEMA    |           |              |                |             |
| TOLOGY (c |           |              |                |             |
| ontinued) |           |              |                |             |
+-----------+-----------+--------------+----------------+-------------+
|           | **GRADE   | **GRADE 2**  | **GRADE 3**    | **GRADE 4** |
|           | 1**       |              |                |             |
+-----------+-----------+--------------+----------------+-------------+
| C         |           |              |                |             |
| reatinine |           |              |                |             |
+-----------+-----------+--------------+----------------+-------------+
| \<7 days  | 1.0-1.7   | 1.8-2.4      | 2.5-3.0 mg/dL  | \>3.0 mg/dL |
| old       | mg/dL     | mg/dL        |                |             |
+-----------+-----------+--------------+----------------+-------------+
| 7-60 days | 0.5-0.9   | 1.0-1.4      | 1.5-2.0 mg/dL  | \>2.0 mg/dL |
| old       | mg/dL     | mg/dL        |                |             |
+-----------+-----------+--------------+----------------+-------------+
| 61-90     | 0.6-0.8   | 0.9-1.1      | 1.2-1.5 mg/dL  | \>1.5 mg/dL |
| days old  | mg/dL     | mg/dL        |                |             |
+-----------+-----------+--------------+----------------+-------------+
| Cr        |           |              |                |             |
| Clearance |           |              |                |             |
+-----------+-----------+--------------+----------------+-------------+
| \<7 days  | 35-40     | 30-34 ml/min | 25-29 ml/min   | \<25 ml/min |
| old       | ml/min    |              |                |             |
+-----------+-----------+--------------+----------------+-------------+
| 7-60 days | 45-50     | 40-44 ml/min | 35-39 ml/min   | \<35 ml/min |
| old       | ml/min    |              |                |             |
+-----------+-----------+--------------+----------------+-------------+
| 61-90     | 60-75     | 50-59 ml/min | 35-49 ml/min   | \<35 ml/min |
| days old  | ml/min    |              |                |             |
+-----------+-----------+--------------+----------------+-------------+
| ### Hyp   |           |              |                |             |
| ocalcemia |           |              |                |             |
+-----------+-----------+--------------+----------------+-------------+
| \<7 days  | 6.5--6.9  | 6.0-6.4      | 5.5-5.9 mEq/L  | \<5.5 mEq/L |
| old       | mEq/L     | mEq/L        |                |             |
+-----------+-----------+--------------+----------------+-------------+
| 7-60 days | 7.6-8.0   | 7.0-7.5      | 6.0-6.9 mEq/L  | \<6.0 mEq/L |
| old       | mEq/L     | mEq/L        |                |             |
+-----------+-----------+--------------+----------------+-------------+
| 61-90     | 7.8-8.4   | 7.0-7.7      | 6.0-6.9 mEq/L  | \<6.0 mEq/L |
| days old  | mEq/L     | mEq/L        |                |             |
+-----------+-----------+--------------+----------------+-------------+
| Hype      |           |              |                |             |
| rcalcemia |           |              |                |             |
+-----------+-----------+--------------+----------------+-------------+
| \<7 days  | 12.0-12.4 | 12.5-12.9    | 13.0-13.5      | \>13.5      |
| old       | mEq/L     | mEq/L        | mEq/L          | mEq/L       |
+-----------+-----------+--------------+----------------+-------------+
| 7-60 days | 10.5-11.2 | 11.3-11.9    | 12.0-13.0      | \>13.0      |
| old       | mEq/L     | mEq/L        | mEq/L          | mEq/L       |
+-----------+-----------+--------------+----------------+-------------+
| 61-90     | 10.5-11.2 | 11.3-11.9    | 12.0-13.0      | \>13.0      |
| days old  | mEq/L     | mEq/L        | mEq/L          | mEq/L       |
+-----------+-----------+--------------+----------------+-------------+

##  (Greater than 3 months of age)

+-------------+-------------+-------------+-------------+--------------+
| # LOCA      |             |             |             |              |
| L REACTIONS |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
|             | **GRADE 1** | **GRADE 2** | **GRADE 3** | **GRADE 4**  |
+-------------+-------------+-------------+-------------+--------------+
| Induration  | \< 10mm     | 10-25 mm    | 26-50mm     | \>50mm       |
+-------------+-------------+-------------+-------------+--------------+
| Erythema    | \< 10mm     | 10-25 mm    | 26-50mm     | \>50mm       |
+-------------+-------------+-------------+-------------+--------------+
| Edema       | \< 10mm     | 10-25 mm    | 26-50mm     | \>50mm       |
+-------------+-------------+-------------+-------------+--------------+
| Rash at     | \< 10mm     | 10-25 mm    | 26-50mm     | \>50mm       |
| Injection   |             |             |             |              |
| Site        |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| Pruritus    | Slight      | Moderate    | Itching at  | Itching over |
|             | itching at  | itching at  | injection   | entire body  |
|             | injection   | injection   | extremity   |              |
|             | site        | extremity   | and other   |              |
|             |             |             | sites       |              |
+-------------+-------------+-------------+-------------+--------------+

+-------------+-------------+-------------+-------------+--------------+
| **H         |             |             |             |              |
| EMATOLOGY** |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| #           | **GRADE 1** | **GRADE 2** | **GRADE 3** | **GRADE 4**  |
+-------------+-------------+-------------+-------------+--------------+
| Hemoglobin  | 9.0-9.9     | 7.0-8.9     | \<7.0 gm/dL | Cardiac      |
| for         | gm/dL       | gm/dL       |             | Failure\     |
| children    |             |             |             | secondary to |
| greater     |             |             |             | anemia       |
| than        |             |             |             |              |
|             |             |             |             |              |
| months and  |             |             |             |              |
| less than 2 |             |             |             |              |
| years of    |             |             |             |              |
| age         |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| Hemoglobin  | 10-10.9     | 7.0-9.9     | \<7.0 gm/dL | Cardiac      |
| for         | gm/dL       | gm/dL       |             | Failure\     |
| children    |             |             |             | secondary to |
| greater     |             |             |             | anemia       |
| that 2      |             |             |             |              |
| years of    |             |             |             |              |
| age         |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| Absolute    | 750         | 40          | 25          | \<250/mm^3^  |
| Neutrophil  | -1200/mm^3^ | 0-749/mm^3^ | 0-399/mm^3^ |              |
| Count       |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| Platelets   | \-          | 50,000-7    | 25,000-4    | \<           |
|             | \-\-\-\-\-- | 5,000/mm^3^ | 9,999/mm^3^ | 25,000/mm^3^ |
+-------------+-------------+-------------+-------------+--------------+
| Prothrombin | 1.1-1.2 x   | 1.3 -1.5 x  | 1.6 -3.0 x  | \>3.0 x ULN  |
| Time (PT)   | ULN         | ULN         | ULN         |              |
+-------------+-------------+-------------+-------------+--------------+
| Partial     | 1.1-1.6 x   | 1.7-2.3 x   | 2.4 -3.0 x  | \>3.0 x ULN  |
| Thr         | ULN         | ULN         | ULN         |              |
| omboplastin |             |             |             |              |
| Time (PTT)  |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+

##  (Greater than 3 months of age) 

<table>
<colgroup>
<col style="width: 12%" />
<col style="width: 6%" />
<col style="width: 1%" />
<col style="width: 16%" />
<col style="width: 1%" />
<col style="width: 16%" />
<col style="width: 1%" />
<col style="width: 16%" />
<col style="width: 2%" />
<col style="width: 23%" />
</colgroup>
<tbody>
<tr class="odd">
<td colspan="10"><strong>GASTROINTESTINAL</strong></td>
</tr>
<tr class="even">
<td colspan="2"><h1 id="section-1"></h1></td>
<td colspan="2"><strong>GRADE 1</strong></td>
<td colspan="2"><strong>GRADE 2</strong></td>
<td colspan="2"><strong>GRADE 3</strong></td>
<td colspan="2"><strong>GRADE 4</strong></td>
</tr>
<tr class="odd">
<td colspan="2">Bilirubin (when accompanied by any increase in other
liver function test)</td>
<td colspan="2">1.1 - &lt;1.25 x ULN</td>
<td colspan="2">1.25 - &lt;1.5 x ULN</td>
<td colspan="2">1.5 – 1.75 x ULN</td>
<td colspan="2">&gt; 1.75 x ULN</td>
</tr>
<tr class="even">
<td colspan="2">Bilirubin (when other liver function are in the normal
range)</td>
<td colspan="2">1.1 - &lt;1.5 x ULN</td>
<td colspan="2">1.5 - &lt;2.0 x ULN</td>
<td colspan="2">2.0 – 3.0 x ULN</td>
<td colspan="2">&gt; 3.0 x ULN</td>
</tr>
<tr class="odd">
<td colspan="2">AST (SGOT)</td>
<td colspan="2">1.1 - &lt;2.0 x ULN</td>
<td colspan="2">2.0 – &lt;3.0 x ULN</td>
<td colspan="2">3.0 – 8.0 x ULN</td>
<td colspan="2">&gt; 8 x ULN</td>
</tr>
<tr class="even">
<td colspan="2">ALT (SGPT)</td>
<td colspan="2">1.1 - &lt;2.0 x ULN</td>
<td colspan="2">2.0 – &lt;3.0 x ULN</td>
<td colspan="2">3.0 – 8.0 x ULN</td>
<td colspan="2">&gt; 8 x ULN</td>
</tr>
<tr class="odd">
<td colspan="2">GGT</td>
<td colspan="2">1.1 - &lt;2.0 x ULN</td>
<td colspan="2">2.0 – &lt;3.0 x ULN</td>
<td colspan="2">3.0 – 8.0 x ULN</td>
<td colspan="2">&gt; 8 x ULN</td>
</tr>
<tr class="even">
<td colspan="2">Pancreatic Amylase</td>
<td colspan="2">1.1-1.4 x ULN</td>
<td colspan="2">1.5-1.9 x ULN</td>
<td colspan="2">2.0-3.0 x ULN</td>
<td colspan="2">&gt;3.0 x ULN</td>
</tr>
<tr class="odd">
<td colspan="2">Uric Acid</td>
<td colspan="2">7.5-9.9mg/dL</td>
<td colspan="2">10-12.4 mg/dL</td>
<td colspan="2">12.5-15.0 mg/dL</td>
<td colspan="2">&gt;15.0 mg/dL</td>
</tr>
<tr class="even">
<td>CPK</td>
<td colspan="9">See Neuromuscular Toxicity</td>
</tr>
<tr class="odd">
<td colspan="3">Appetite</td>
<td colspan="2">-----------------</td>
<td colspan="2">Decreased appetite</td>
<td colspan="2">Appetite very decreased, no solid food taken</td>
<td>No solid or liquid taken</td>
</tr>
<tr class="even">
<td colspan="3">Abdominal Pain</td>
<td colspan="2">Mild</td>
<td colspan="2">Moderate-<br />
No Treatment Needed</td>
<td colspan="2">Moderate-<br />
Treatment Needed</td>
<td>Severe-<br />
Hospitalized for treatment</td>
</tr>
<tr class="odd">
<td colspan="3">Diarrhea</td>
<td colspan="2">Slight change in consistency and/or frequency of
stools</td>
<td colspan="2">Liquid stools</td>
<td colspan="2">Liquid stools greater that 4x the amount or number
normal for this child</td>
<td>Liquid stools greater than 8x the amount or number normal for this
child</td>
</tr>
</tbody>
</table>

##  (Greater than 3 months of age) 

+-------------+-------------+-------------+-------------+--------------+
| **GASTR     |             |             |             |              |
| OINTESTINAL |             |             |             |              |
| (c          |             |             |             |              |
| ontinued)** |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| #  {        | **GRADE 1** | **GRADE 2** | **GRADE 3** | **GRADE 4**  |
| #section-2} |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| C           | Slight      | Hard, dry   | Abdominal   | Distention   |
| onstipation | change in   | stools with | pain        | and Vomiting |
|             | the         | a change in |             |              |
|             | consistenc  | frequency   |             |              |
|             | y/frequency |             |             |              |
|             | of stool    |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| Nausea      | Mild        | Moderate-\  | Sev         | Unable to    |
|             |             | Decreased   | ere-Little\ | ingest food\ |
|             |             | oral intake | oral intake | or fluid for |
|             |             |             |             | more than 24 |
|             |             |             |             | hours        |
+-------------+-------------+-------------+-------------+--------------+
| Vomiting    | 1           | 2-3         | 4-6         | Greater than |
|             | episode/day | episodes    | episodes    | 6 episodes   |
|             |             |             | per day     | per day or   |
|             |             | per day     |             | Intractable  |
|             |             |             |             | Vomiting     |
+-------------+-------------+-------------+-------------+--------------+

##  (Greater than 3 months of age) 

+-------------+-------------+-------------+-------------+--------------+
| **ELE       |             |             |             |              |
| CTROLYTES** |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
|             | **GRADE 1** | **GRADE 2** | **GRADE 3** | **GRADE 4**  |
+-------------+-------------+-------------+-------------+--------------+
| CREATININE  |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| 3 Months -2 | 0.6-0.8 x   | 0.9-1.1 x   | 1.2-1.5 x   | \>1.5 x ULN  |
| Years of    | ULN         | ULN         | ULN         |              |
| age         |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| 2 Years- 12 | 0.7-1.0 x   | 1.1-1.6 x   | 1.7-2.0 x   | \>2.0 x ULN  |
| Years of    | ULN         | ULN         | ULN         |              |
| age         |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| Greater     | 1.0-1.7 x   | 1.8-2.4 x   | 2.5-3.5 x   | \>3.5 x ULN  |
| than        | ULN         | ULN         | ULN         |              |
|             |             |             |             |              |
| 12 Years of |             |             |             |              |
| age         |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+

##  (Greater than 3 months of age) 

+-------------+-------------+-------------+-------------+--------------+
| **ELE       |             |             |             |              |
| CTROLYTES** |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| #  {        | **GRADE 1** | **GRADE 2** | **GRADE 3** | **GRADE 4**  |
| #section-3} |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| Hy          |             | \<145-149   | 150-155     | \>155 mEq/L  |
| pernatremia |             | mEq/L       | mEq/L       | or abnormal  |
|             |             |             |             | sodium AND   |
|             |             |             |             | mental       |
|             |             |             |             | status       |
|             |             |             |             | changes      |
+-------------+-------------+-------------+-------------+--------------+
| H           |             | 130-135     | 129-124     | \<124 mEq/L  |
| yponatremia |             | mEq/L       | mEq/L       | or abnormal  |
|             |             |             |             | sodium AND   |
|             |             |             |             | mental       |
|             |             |             |             | status       |
|             |             |             |             | changes      |
+-------------+-------------+-------------+-------------+--------------+
| H           | 5.0-5.9     | 6.0-6.4     | 6.5-7.0     | \>7.0 mEq/L  |
| yperkalemia | mEq/L       | mEq/L       | mEq/L       | or abnormal  |
|             |             |             |             | potassium    |
|             |             |             |             | AND cardiac  |
|             |             |             |             | arrhythamia  |
+-------------+-------------+-------------+-------------+--------------+
| Hypokalemia | 3.0-3-5     | 2.5-2.9     | 2.0-2.4     | \<2.0 mEq/L  |
|             | mEq/L       | mEq/L       | mEq/L       | or abnormal  |
|             |             |             |             | potassium    |
|             |             |             |             | AND cardiac  |
|             |             |             |             | arrhythmia   |
+-------------+-------------+-------------+-------------+--------------+
| Hy          | 10.         | 11.3-11.9   | 12.0-12.9   | \>13.0 mg/dL |
| percalcemia | 5-11.2mg/dL | mg/dL       | mg/dL       |              |
+-------------+-------------+-------------+-------------+--------------+
| H           | 7.8-8.4     | 7.0-7.7     | 6.0-6.9     | \<6.0 mg/dL  |
| ypocalcemia | mg/dL       | mg/dL       | mg/dL       |              |
+-------------+-------------+-------------+-------------+--------------+
| Hyp         | 1.2-1.4     | 0.9-1.1     | 0.6-0.8     | \<0.6 mEq/L  |
| omagnesemia | mEq/L       | mEq/L       | mEq/L       | or abnormal  |
|             |             |             |             | magnesium    |
|             |             |             |             | AND cardiac  |
|             |             |             |             | arrhythmia   |
+-------------+-------------+-------------+-------------+--------------+
| H           | 55-65 mg/dL | 40-54 mg/dL | 30-39 mg/dL | \<30 mg/dL   |
| ypoglycemia |             |             |             | or abnormal  |
|             |             |             |             | glucose AND  |
|             |             |             |             | mental       |
|             |             |             |             | status       |
|             |             |             |             | changes      |
+-------------+-------------+-------------+-------------+--------------+
| Hy          | 116-159     | 160-249     | 250-400     | \>400 mg/dL  |
| perglycemia | mg/dL       | mg/dL       | mg/dL       | or           |
|             |             |             |             | ketoacidosis |
+-------------+-------------+-------------+-------------+--------------+
| Proteinuria | Tr-1+       | 2+          | 3+          | 4+           |
|             |             |             |             |              |
|             | or          | or          | or          | or           |
|             |             |             |             |              |
|             | \<150       | 150-499     | 500-1000    | Nephrotic    |
|             | mg/day      | mg/day      | mg/day      | syndrome     |
|             |             |             |             | \>1000       |
|             |             |             |             | mg/day       |
+-------------+-------------+-------------+-------------+--------------+
| Hematuria   | Microscopic | Microscopic |             | Gross        |
|             | \<25        | \>25        |             | hematuria    |
|             | cells/hpf   | cells/hpf   |             |              |
+-------------+-------------+-------------+-------------+--------------+

##  (Greater than 3 months of age)

+-------------+-------------+-------------+-------------+--------------+
| # CENTRA    |             |             |             |              |
| L NERVOUS S |             |             |             |              |
| YSTEM (CNS) |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| #####  {    | **GRADE 1** | **GRADE 2** | **GRADE 3** | **GRADE 4**  |
| #section-4} |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| Generalized |             |             | Dizziness   | Hypotonic,   |
| CNS         |             |             |             | hy           |
| Symptoms    |             |             |             | poresponsive |
|             |             |             |             | episodes;    |
|             |             |             |             |              |
|             |             |             |             | Seizures;    |
|             |             |             |             | Apnea/       |
|             |             |             |             | Bradycardia; |
|             |             |             |             |              |
|             |             |             |             | Inconsolable |
|             |             |             |             | crying \> 3  |
|             |             |             |             | hrs;         |
+-------------+-------------+-------------+-------------+--------------+
| Headache    | Mild        | Moderate,   | Moderate to | Intractable  |
|             |             | Responds to | Severe,\    |              |
|             |             | n           | Responds to |              |
|             |             | on-narcotic | narcotic    |              |
|             |             | analgesia   | analgesia   |              |
+-------------+-------------+-------------+-------------+--------------+
| Level of    |             | Slightly    | Very        | Inconsolable |
| Activity    |             | irritable   | irritable   | OR Obtunded  |
|             |             | OR slightly | OR          |              |
|             |             | subdued     |             |              |
|             |             |             | Lethargic   |              |
+-------------+-------------+-------------+-------------+--------------+
| Visual      |             | Blurriness, | More than 1 | Decrease in  |
|             |             | diplopia,   | episode of  | visual       |
|             |             | or          | Grade 2     | acuity,      |
|             |             | horizontal  | symptoms    | visual field |
|             |             | nystagmus   | per week,   | deficit, or  |
|             |             | of \< 1     | or an       | oculogyric   |
|             |             | hour        | episode of  | crisis       |
|             |             | duration,   | Grade 2     |              |
|             |             | with        | symptoms    |              |
|             |             | spontaneous | lasting     |              |
|             |             | resolution  | more than   |              |
|             |             |             |             |              |
|             |             |             | 1 hour with |              |
|             |             |             | spontaneous |              |
|             |             |             | resolution  |              |
|             |             |             | by 4 hours  |              |
|             |             |             | or vertical |              |
|             |             |             | nystagmus   |              |
+-------------+-------------+-------------+-------------+--------------+
| Myelopathy  |             | None        | None        | Myelop       |
|             |             |             |             | athic/spinal |
|             |             |             |             | cord         |
|             |             |             |             | symptoms,    |
|             |             |             |             | such as:     |
|             |             |             |             | pyramidal    |
|             |             |             |             | tract        |
|             |             |             |             | weakness and |
|             |             |             |             | di           |
|             |             |             |             | sinhibition, |
|             |             |             |             | sensory      |
|             |             |             |             | level, loss  |
|             |             |             |             | of           |
|             |             |             |             | pro          |
|             |             |             |             | prioception, |
|             |             |             |             | b            |
|             |             |             |             | ladder/bowel |
|             |             |             |             | dysfunction  |
+-------------+-------------+-------------+-------------+--------------+

##  (Greater than 3 months of age)

+-------------+-------------+-------------+-------------+--------------+
| *           |             |             |             |              |
| *PERIPHERAL |             |             |             |              |
| NERVOUS     |             |             |             |              |
| SYSTEM**    |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
| # PARAMETER | **GRADE 1** | **GRADE 2** | **GRADE 3** | **GRADE 4**  |
+-------------+-------------+-------------+-------------+--------------+
| Neuropathy/ |             | Mild        | Persistent  | Onset of     |
|             |             | transient   | or          | significant  |
| Lower Motor |             |             | progressive | weakness,    |
| Neuropathy  |             | Paresthesia | pa          | decrease or  |
|             |             | only        | resthesias, | loss of      |
|             |             |             | burning     | DTRs,        |
|             |             |             | sensation   | sensory loss |
|             |             |             | in feet, or | in           |
|             |             |             | mild        | \"stocking   |
|             |             |             | d           | glove\"      |
|             |             |             | ysesthesia; | d            |
|             |             |             | no          | istribution, |
|             |             |             | weakness;   | radicular    |
|             |             |             | mild to     | sensory      |
|             |             |             | moderate    | loss,        |
|             |             |             | deep tendon | multiple     |
|             |             |             | reflex      | cranial      |
|             |             |             | changes; no | nerve        |
|             |             |             | sensory     | involvement; |
|             |             |             | loss        | bladder or   |
|             |             |             |             | bowel        |
|             |             |             |             | dysfunction, |
|             |             |             |             | fas          |
|             |             |             |             | ciculations, |
|             |             |             |             | respiratory  |
|             |             |             |             | e            |
|             |             |             |             | mbarrassment |
|             |             |             |             | from chest   |
|             |             |             |             | wall         |
|             |             |             |             | weakness.    |
+-------------+-------------+-------------+-------------+--------------+
| Myopathy or | Normal or   | Mild        | Proximal    | Onset of     |
| Ne          | mild        | proximal    | muscle      | mya          |
| uromuscular |             | weakness    | weakness    | sthenia-like |
| Junction    | (\<2 x ULN) | and/or      | and/or      | symptoms     |
| Impairment  | CPK         | atrophy not | atrophy     | (fatigable   |
|             | elevation   | affecting   | affecting   | weakness     |
|             |             | gross motor | motor       | with         |
|             |             | function.   | function    | external,    |
|             |             | Mild        | +/- CPK     | variable     |
|             |             | myalgias,   | elevation;  | oph          |
|             |             | +/- mild    | or severe   | thalmoplegia |
|             |             | CPK         | myalgias    | and/or       |
|             |             | elevation   | with CPK    | ptosis), or  |
|             |             | (\<2 x ULN) | \>2 x ULN;  | n            |
|             |             |             |             | euromuscular |
|             |             |             |             | junction     |
|             |             |             |             | blockade     |
|             |             |             |             | (acute       |
|             |             |             |             | paralysis)   |
|             |             |             |             | symptoms     |
+-------------+-------------+-------------+-------------+--------------+

##  (Greater than 3 months of age) 

+-------------+-------------+-------------+-------------+--------------+
| # OTHER     |             |             |             |              |
+-------------+-------------+-------------+-------------+--------------+
|             | **GRADE 1** | **GRADE 2** | **GRADE 3** | **GRADE 4**  |
+-------------+-------------+-------------+-------------+--------------+
| Allergy     | Pruritus    | Pruritic    | Mild        | Severe       |
|             | without     | Rash        | Urticaria   | Urticaria\   |
|             | Rash        |             |             | Anaphylaxis, |
|             |             |             |             | Angioedema   |
+-------------+-------------+-------------+-------------+--------------+
| Drug Fever  | .           | 38.5-40C    | Greater     | Sustained    |
| (Rectal)    |             |             | than 40.0C  | Fever:\      |
|             |             | 101.3 --    |             | Equal or     |
|             |             | 104.0F      | Greater     | greater than |
|             |             |             | than 104.0F | 40C (104.0F) |
|             |             |             |             | for longer   |
|             |             |             |             | than 5 days  |
+-------------+-------------+-------------+-------------+--------------+
| Cutaneous   | Localized   | Diffuse     | Generalized | Ste          |
|             | rash        | ma          | urticaria   | vens-Johnson |
|             |             | culopapular |             | Syndrome or  |
|             |             |             |             | Erythema     |
|             |             | Rash        |             | multiforme   |
+-------------+-------------+-------------+-------------+--------------+
| Stomatitis  | Mild        | Painful,    | Painful:    | Painful:     |
|             | discomfort  | difficulty  | unable to   | unable to    |
|             |             | swallowing, | swallow     | swallow      |
|             |             | but able to | solids      | liquids;     |
|             |             | eat and     |             | requires IV  |
|             |             | drink       |             | fluids       |
+-------------+-------------+-------------+-------------+--------------+
| Clinical    | No therapy; | May require | Requires    | Requires     |
| symptoms    | monitor     | minimal     | medical     | active       |
| *not        | condition   | i           | care and    | medical      |
| otherwise   |             | ntervention | possible    | i            |
| specified*  |             | and         | hosp        | ntervention, |
| in this     |             | monitoring  | italization | hosp         |
| table       |             |             |             | italization, |
|             |             |             |             | or hospice   |
|             |             |             |             | care         |
+-------------+-------------+-------------+-------------+--------------+
| Laboratory  | Abnormal,   | S           | S           | Life         |
| values *not | but         | ufficiently | ufficiently | -threatening |
| otherwise   | requiring   | abnormal to | severe to   | severity;    |
| specified*  | no          | require     | require     | Requires     |
| in this     | immediate   | evaluation  | evaluation  | immediate    |
| table       | in          | as to       | and         | evaluation,  |
|             | tervention; | causality   | treatment,  | treatment,   |
|             | follow      | and perhaps | including   | and usually  |
|             |             | mild        | at least    | hosp         |
|             |             | therapeutic | temporary   | italization; |
|             |             | in          | suspension  | Study drug   |
|             |             | tervention, | of study    | must be      |
|             |             | but not of  | drug        | stopped      |
|             |             | sufficient  |             | immediately  |
|             |             | severity to |             | and should   |
|             |             | warrant     |             | not be       |
|             |             | immediate   |             | restarted    |
|             |             | changes in  |             | until the    |
|             |             | study drug  |             | abnormality  |
|             |             |             |             | is clearly   |
|             |             |             |             | felt to be   |
|             |             |             |             | caused by    |
|             |             |             |             | some other   |
|             |             |             |             | mechanism    |
|             |             |             |             | that study   |
|             |             |             |             | drug         |
+-------------+-------------+-------------+-------------+--------------+