1

ADRsTypes, Reporting, Evaluation,

Monitoring, Preventing & Management

Dr.C.SUHAS REDDY

Dr.C.SUHAS REDDY 2

Definition

• 'A response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological function'.

Dr.C.SUHAS REDDY 3

BASED ON INCIDENCE Classification

• VERY COMMON• COMMON• UNCOMMON• RARE• VERY RARE

Dr.C.SUHAS REDDY 4

• VERY COMMON ADR- incidence >10% (1 in 10 ppl)• Ex- drowsiness associated with carbamazepine

• COMMON ADR- incidence is 1-10 to 1-100• Ex-fluid retention with carbamazepine

Dr.C.SUHAS REDDY 5

• UNCOMMON ADR- incidence 0.1-1.0 % (1-1000 to 1-100)• Ex- diarrhea associated with carbamazepine

• RARE ADR- incidence 0.01-0.1 % (1-10000 to 1-1000)• Ex- depression associated with carbamazepine

• VERY RARE- incidence <0.01% (1-10000)• EX-arrhythmia associated with carbamazepine

Dr.C.SUHAS REDDY 6

BASED ON SEVERITY / INTENSITY Classification

• MILD (minor)• MODERATE• SEVERE (major)

Dr.C.SUHAS REDDY 7

• MILD (minor)- does not required any therapy / may not notice

• MODERATE – required change in drug therapy• SEVER (major) – capable of damaging any organ / life

threatening, hospitalization, disability (significant, persistent or permanent, congenital anomaly, required intervention to prevent permanent impairment or damage

Dr.C.SUHAS REDDY 8

TRADITIONALLY Classification

• TYPE-A (Augmented)• TYPE-B (Bizarre)• TYPE-C (continuous)• TYPE-D (delayed)• TYPE-E (End of Dose)• TYPE-F (Failure of therapy)

Dr.C.SUHAS REDDY 9

TYPE-A (Augmented)

• Commonest (up to 70%) – Dose dependent, severity increases with dose.

• Preventable in most part by slow introduction of low dosages. • Predictable by the pharmacological mechanisms, • e.g., hypotension by beta-blockers, • hypoglycaemia caused by insulins or oral hypoglycaemics,• NSAID induced gastric ulcers.

Dr.C.SUHAS REDDY 10

TYPE-B (Bizarre)

• Rare, idiosyncratic, genetically determined, unpredictable, mechanisms are unknown, serious, can be fatal; unrelated to the dose,

• e.g. ,hepatitis caused by halothane, • aplastic anaemia caused by chloramphenicol, • neuroleptic malignant syndrome caused by some

anaesthetics and antipsychotics.

Dr.C.SUHAS REDDY 11

TYPE-C (continuous)

• Occurs as a result of continuous drug use. • May be irreversible, unexpected, unpredictable,• e.g., tardive dyskinesias by antipsychotics,• dementia by anticholinergic medications.

Dr.C.SUHAS REDDY 12

TYPE-D (delayed)

• Delayed occurrence of ADRs, even after the cessation of treatment.

• e.g., corneal opacities after thioridazine, • ophthalmopathy after chloroquine.

Dr.C.SUHAS REDDY 13

TYPE-E (End of Dose)

• Withdrawal reactions. Occurs typically with the depressant drugs.

• e.g., hypertension and restlessness in opiate abstainer, • seizures on alcohol or benzodiazepines withdrawal; • first dose hypotension caused by alpha-blockers (Prazosin)

or ACE inhibitors.

Dr.C.SUHAS REDDY 14

TYPE-F (Failure of therapy)

• Results from the ineffective treatment (previously excluded from analysis according to WHO definition),

• e.g., accelerated hypertension because of inefficient control.

Dr.C.SUHAS REDDY 15

Dr.C.SUHAS REDDY 16

How to recognize ADRs• Ensure, medicine received & actually taken by the patient at the dose advised• Verify the onset of suspected ADR is after taking the drug• Determine the time interval between drug taken – onset of event• Evaluate the suspected ADR after discontinuing the drug / reduced dose,

monitor status.• Analyse the alternate cause (other than the drug)• Use relevant literature & experienced physician opinion & information PV

ceneter• Report the ADR

Dr.C.SUHAS REDDY 17

• WHAT TO REPORT ?• WHO SHOULD REPORT• WHEN TO REPORT• HOW TO REPORT• WHERE TO REPORT

Dr.C.SUHAS REDDY 18

?

Dr.C.SUHAS REDDY 19

WHAT TO REPORT ?• Any undesirable adverse event suspected to be associated with use

of drug.• Include - All ADRs as a result of prescription and non-prescription • All ADRs – irrespective of the used (acc with PI provided by

company)• Unexpected reactions - regardless of their nature or severity • ADRs-in special field – drug abuse, drug use – pregnancy / lactation• ADRs occurring from overdose or medication error

Dr.C.SUHAS REDDY 20

Information required for ADR case reporting

• Patient information-

- patient identifier- age at time of event or date of birth- gender- weight

Dr.C.SUHAS REDDY 21

• Adverse event or product problem--description of event or problem- date of event- date of this report- relevant tests/laboratory data (if available)- other relevant patient information/history- outcomes attributed to adverse even

Dr.C.SUHAS REDDY 22

Suspected medication (s)

- name (INN and brand name)- dose, frequency & route used- therapy date- diagnosis for use- event abated after use stopped or dose reduced

- batch number- expiration date- event reappeared after reintroduction of the treatment- concomitant medical products and therapy dates

Dr.C.SUHAS REDDY 23

• Reporter-• - name, address and telephone number

- speciality and occupation

Dr.C.SUHAS REDDY 24

WHO SHOULD REPORT

• doctors, dentists, pharmacists, nurses, assistant medical officers,

clinical officers, pharmaceutical technicians, pharmaceutical assistants, traditional medicine practitioners and others health care providers.

Dr.C.SUHAS REDDY 25

WHEN TO REPORT

• Any suspected ADR should be reported as soon as possible.

• Delay in reporting will make reporting inaccurate and unreliable.

• If possible, report while the patient is still in the health facility this gives a chance to reporter to clear any ambiguity by re-questioning or examining the patient

Dr.C.SUHAS REDDY 26

HOW TO REPORT • CDSCO suspected ADR Reporting Form

Dr.C.SUHAS REDDY 27

Dr.C.SUHAS REDDY 28

WHERE TO REPORT• Please return the completed form to the nearest Adverse

drug reaction Monitoring Centre (AMC) or to National Coordinating Centre

• A list of nationwide AMCs is available at:• http://cdsco.nic.in/pharmacovigilance.htm

Dr.C.SUHAS REDDY 29

Flow of

Reporting

Dr.C.SUHAS REDDY 30

What happens to the submitted information:

• Information provided in this form is handled in strict confidence. • The causality assessment is carried out at (AMCs) by using

WHO-UMC.• The analyzed forms are forwarded to the National Coordinating

Centre through the ADR database. • Finally the data is analyzed and forwarded to the Global

Pharmacovigilance Database managed by WHO Uppsala Monitoring Center in Sweden.

Dr.C.SUHAS REDDY 31

• The reports are periodically reviewed by the National Coordinating Centre (PvPI). The information generated on the basis of these reports helps in continuous assessment of the benefit-risk ratio of medicines.

• The information is submitted to the Steering Committee of PvPI constituted by the Ministry of Health and Family Welfare. The Committee is entrusted with the responsibility to review the data and suggest any interventions that may be required.

Dr.C.SUHAS REDDY 32

Types of Reporting

• INTERNAL REPORTING• SPONTANEOUS REPORTING• VOLUNTARY REPORTING

Dr.C.SUHAS REDDY 33

MONITORING OF ADR

• WHO-UMC• NARANJO’S CAUSALITY ASSESSMENT• HARTWIG SACLE- ADR severity assessment scale

Dr.C.SUHAS REDDY 34

ADR severity assessment scale

Dr.C.SUHAS REDDY 35

PREVENTION OF ADR

• Anticipation by patient monitoringEx- anemia- due to deficiency of G6PD, check the condition• Anticipation of dosage reeducationEx- impaired renal / liver function – dosage should reduce• Monitoring the serum levels(drug)Ex- theophylline, aminoglycosides

Dr.C.SUHAS REDDY 36

• Monitoring of pharmacological activity (extensive of P’cology activity)

Ex-diuretics- to promote salt & water loss , but causes electrolyte depletion & dehydration. So therapeutic end point not exceeded.

Dr.C.SUHAS REDDY 37

• Minimizing of non-preventable- Idiosyncratic / hypersensitivity not preventable.

• Can be done by carful observation / monitoring of patientEx- patient with meningitis – should be with penicillin (even if pt is allergic).Chemotherapy – nausea

Dr.C.SUHAS REDDY 38

Management of the adverse reaction

• Confirmation of the ADRs: indicate what assisted in confirming the suspected adverse reactions. For example:

• i. Drug reactions confirmed by disappearance of the reaction after stopping administration of the drug or reducing the doses.

• ii. Recovery on withdrawal of suspected drug(s) if no other drug is withdrawn and no therapy given.

• iii. Recovery follows treatment of the reaction in addition to withdrawal of drug.

Dr.C.SUHAS REDDY 39

• 2. Mention the criteria for regarding the reaction as serious

• 3. Mention any treatment given to the patient after experiencing the ADRs.

• 4. Outcome: indicate the outcome of the adverse reaction by marking X in the appropriate box with dates in case of fatal outcome.

Dr.C.SUHAS REDDY 40

REFERENCE

• CLINICAL PHARMACY TEXT BOOK - G.PARTHASARATHI • CLINICAL PHARMACY TEXT BOOK - RAVI KUMAR• WHO website• Adverse drug reaction-causality assessment-ijrpc 2011,

1(3).