ADVERSE DRUG REACTIONS AND SERIOUS ADVERSE EVENTS Dr. Manjunath.G.N SSMC Tumkur
Definition Any
occurrence or worsening of an undesirable or unintended sign, symptom (including an abnormal laboratory finding), or disease temporally associated with the use of a medicinal product/procedure, whether or not related to the medicinal product/procedure.
Types Dose
related (Predictable – type A) Non dose related (Unpredictable – type B) Long term effects Delayed effects
Severity
Grade 1, Mild: Transient or mild discomfort; no limitation in activity; 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 and hospitalization possible Grade 4, Life-Threatening: Extreme limitation in activity, significant assistance required; significant medical intervention/therapy required; hospitalization or hospice care probable
Incidence Hospital
in-patients – 10-20% Deaths in hospital in-patients - 0.24-2.9% Hospital admissions – 0.3-5%
Classification of ADR
Dose related 1.Pharmaceutical variation 2.Pharmacokinetic variation a) b) c) d)
Pharmacogenetic variation Hepatic disease Renal disease Cardiac disease
3.Pharmacodynamic variation a) b)
Hepatic disease Altered fluid and electrolyte imbalance
Contd.
Non dose related a) b)
Immunological reaction Pharmacogenetic variation
Long term effects a) b) c)
Adaptive changes Rebound phenomena Other long term effects
Contd.
Delayed effects a) b)
Carcinogenesis Effects connected with reproduction Impaired infertility b) Teratogenesis c) Drugs in breast milk a)
Various ADR Side
effects Secondary effects Toxic effects Intolerance – quantitative
- qualitative 1. Idiosyncracy 2. Hypersensitivity Photosensitization
Contd. Drug
withdrawal reaction Drug dependence Teratogenecity Carcinogenecity/mutagenecity Iatrogenecity
Manifestations of ADR Haemopoietic
toxicity Hepatotoxicty- direct immunological Nephrotoxicity Ocular toxicity Ototoxicity
Contd. Behavioural
toxicity Electrolyte imbalance Endocrine disturbance Skin toxicity Unmasking and exacerbation of disease Acute withdrawal reaction
Contd. Carcinogenesis Teratogenesis Alteration
of taste Drug dependance
Types of ADR Type
Type of effect
Features
examples
A
Augmented
Common, predictable, low mortality
Bradycardia–β-blockers
B
Bizarre
Uncommon, unpredictable, high morbidity & high mortality
Anaphylaxis - Penicillin
C
Chronic
Dose related & time related
Dyskinesia - Levodopa
D
Delayed
Time Related
Teratogenesis
E
End of use
Withdrawal of chronic therapy abruptly
Corticosteroids
F
Failure
Unexpected failure of therapy
Oral contraceptive failure Rifampin
What is a Serious Adverse Event? A
serious adverse event or reaction is defined as any adverse event that suggests a significant contraindication to ongoing therapy
Criteria 1.Death Report if the patient's death is suspected as being a direct outcome of the adverse event. 2.Life-Threatening Report if the patient was at substantial risk of dying at the time of the adverse event or it is suspected that the use or continued use of the product would result in the patient's death. Examples: Pacemaker failure; gastrointestinal hemorrhage; bone marrow suppression; infusion pump failure which permits uncontrolled free flow resulting in excessive drug dosing.
3.Hospitalization (initial or prolonged) Report if admission to the hospital or prolongation of a hospital stay results because of the adverse event. Examples: Anaphylaxis;or bleeding causing or prolonging hospitalization. 4.Disability Report if the adverse event resulted in a significant, persistent, or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities or quality of life. Examples: Cerebrovascular accident due to drug-induced hypercoagulability; toxicity; peripheral neuropathy.
6. Requires Congenital Anomaly Report if there are suspicions that exposure to a medical product prior to conception or during pregnancy resulted in an adverse outcome in the child. Examples: Vaginal cancer in female offspring from diethylstilbestrol during pregnancy; malformation in the offspring caused by thalidomide. 7. Intervention to Prevent Permanent Impairment or Damage Report if you suspect that the use of a medical product may result in a condition which required medical or surgical intervention to preclude permanent impairment or damage to a patient. Examples: Acetaminophen overdose-induced hepatotoxicity requiring treatment with acetylcysteine to prevent permanent damage; breakage of a screw requiring replacement of hardware to prevent malunion of a fractured long bone.
Schedule Y requirement Unsuspected
adverse event is communicated from 1.Sponsor to regulatory authorities within 14 days 2. Investigator to sponsor within 24 hours 3. Investigator to ethics committee within 7 days
Serious Adverse Event Reporting
Within 24 hours of the event, complete a serious adverse event form Fax supporting documentation – – – – –
Narrative summary Discharge summary (if applicable) Laboratory tests, consultation and biopsy reports, and/or any other reports Any additional information related to the event All information contained in the form should be supported by source documentation
External SAEs - outside the site
Is the event serious?
Internal SAEs Is the event serious?
Thank you
Dr.Manjunath