How do you answer the student? Do you answer at all? Is he right or wrong or in need of some mentoring?

** This was an actual case.**

Although case reports of prolonged QTc intervals have been published regarding risperidone, this SHOULD be reported through the hospital's ADR process. (FYI -this could have been caused by risperidone alone or because of concomitant use with paroxetine, a potent CYP 450 inhibitor) Generally, any reaction or suspected adverse and/or unintended reaction to a drug (oral, injectable, etc) should be reported, esp if the reaction caused hospitalization, prolonged a hospital stay, required other treatment (surgery, resuscitation, etc), or required treatment with another drug. Treatment failures, although unintended, are NOT considered reportable ADRs.

Causes of ADRs can be many, including but not limited to, an interaction between the suspect drug and another drug (ex. azole antifungal and a HMG CoA reductase inhibitor), interaction of the suspect drug with the patient's disease state (a beta blocker in a patient with reactive airway disease or severe CHF), an extension of the drug's pharmacological activity (respiratory depression from an opioid or excessive hypoglycemia from a sulfonylurea), an allergy, etc.

There is a JCAHO requirement to report and review ADRs within the hospital. JCAHO standard TX.3.9 says "Medication effects on patients are continually monitored." This includes continuous monitoring of medication effects and reporting of adverse drug reactions.

For those of you old enough or in the medicine business for a while can appreciate the following. How did we find out about these agents/ADRS? A lot of them were through ADR reporting through the respective hospitals, manufacturers, and finally the FDA. Many were actually pulled from the market. Other just had black box warnings added to their prescribing information, new/different warnings/precautions/contraindications. Some examples are:

Zomepirac [Zomax®] - an NSAID pulled from the market?

Selacryn ® - an antihypertensive that causes serious liver toxicity?

Terfenadine [Seldane®] and astemizole [Hismanal®] - non-sedating antihistamines that caused prolonged QTc intervals, alone and in combination with other drugs, and even cases of torsades de pointes?

ACEI cough - how did we figure out that the annoying dry cough was caused by the patient's ACE inhibitor?

Oraflex ® - a NSAID that caused liver and kidney toxicity?

Trovafloxacin [Trovan®] - a superspectrum fluoroquinolone caused serious liver toxicity?

Troglitazone [Rezulin®] - a thiazolidinedione that caused serious liver toxicity, some requiring transplant?

Dexfenfluramine [Redux®] - an appetite suppressant suspected of causing heart valve abnormalities and primary pulmonary hypertension?

Phenformin [DBI-TD®] - pulled from the market for causing lactic acidosis?

And the list goes on ........

How to report ADRs here at WHMC? A number of ways can be used. A couple of examples are:

1) call 292-DRUG (2-3784)

2) call the clinical pharmacy office (292-6291)

3) call any pharmacy

4) complete a ADR report form/card (WHMC Form 3468). IMPORTANT POINT - ANYONE (physician, nurse, tech, student, housekeeper, etc) can report an ADR. All we need is the patient's name, last 4 of the SSN, suspect medication(s), and adverse reaction. Our pharmacy staff will further evaluated all ADR reports. The local P&T committee reviews all reported ADRs and decides whether to forward to the manufacturer and/or the FDA.

If you're not sure whether a reaction or condition is the result of an ADR, the following nomogram or scoring sheet may help you determine the answer. The Naranjo nomogram has been widely used to help health care professionals more accurate determine if a condition is drug induced or not. All you do is answer the 10 questions, determine an appropriate score for all 10 questions, and total the scores. The total score will helps you determine whether the drug is 1) likely or probably caused the reaction, 2) possibly caused the reaction, or 3) unlikely to have caused the reaction.

Table 1. Naranjo Adverse Drug Reactions Probability Scale

Question    Yes    No    Don't know    Score

1. Are there previous conclusive reports on this reaction?    + 1    0   0       

2. Did the adverse event appear after the suspected drug was administered?   + 2      - 1      0   

3. Did the adverse reaction improve when the drug was improve when the drug was discontinued or a specific antagonist was administered?      + 1      0    0       

4. Did the adverse reaction reappear when the drug was readministered?    + 2    - 1     0     

5. Are there alternative causes (other than the drug) that could on their own have caused the reaction?    - 1    + 2    0       

6. Did the reaction reappear when a placebo was given?    - 1    + 1    0

7. Was the drug detected in the blood (or other fluids) in concentrations known to be toxic?    + 1    0    0       

8. Was the reaction more severe when the dose was increased, or less severe when the dose was decreased?    + 1    0    0       

9. Did the patient have a similar reaction to the same or similar drugs in any previous exposure?    + 1    0    0       

10. Was the adverse event confirmed by any objective evidence?    + 1    0    0     

TOTAL SCORE*       

*Score of > 9 = definite ADR, 5-8 = probable ADR, 1-4 = possible ADR, 0 = doubtful ADR

REFERENCES:

Naranjo CA, Busto J, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239-45.

Hartwig S et al. Am J Hosp Pharm 1991;48:2611.