[INTRODUCTION] Reporting & Evaluating ADRs

Adverse Drug Reactions (ADR)

[REPORTING AND EVALUATING ADR]

These are noxious, unintended reaction to drug in doses used in prophylaxis, diagnosis, and treatment.

● Based on pharmacologic activity

● Dose-dependent

● Predictable

[ADR CATEGORY]

Key features of AUGMENTED ADR:

Augmented

[ADR CATEGORY]

● Based on pharmacologic activity

● Dose-dependent

● Predictable

● Abnormal reactions

● Unpredictable

● Non-dose dependent

[ADR CATEGORY]

Key features of BIZARRE ADR:

Bizarre

[ADR CATEGORY]

● Abnormal reactions

● Unpredictable

● Non-dose dependent

● Dependence

● Tolerance

● Addiction

[ADR CATEGORY]

Key features of CONTINUOUS ADR:

Continuous

[ADR CATEGORY]

● Dependence

● Tolerance

● Addiction

● Carcinogenicity

● Teratogenicity

[ADR CATEGORY]

Key features of DELAYED ADR:

Delayed

[ADR CATEGORY]

● Carcinogenicity

● Teratogenicity

● Withdrawal effects

● Rebound symptoms

● Gradual tapering of the drug

[ADR CATEGORY]

Key features of END OF USE ADR:

End of Use

[ADR CATEGORY]

● Withdrawal effects

● Rebound symptoms

● Gradual tapering of the drug

● Resistance

● Drug interactions

● Poor adherence

[ADR CATEGORY]

Key features of FAILURE OF THERAPY ADR:

Failure of Therapy

[ADR CATEGORY]

● Resistance

● Drug interactions

● Poor adherence

The pharmacist should facilitate:

● Analysis of each reported ADR

● Identification of drugs and patients at high risk for being involved in ADRs

● Development of policies and procedures for the ADR monitoring program

● Description of the responsibilities and interactions of pharmacists, physicians, nurses, risk managers, and other health professionals in the ADR program

● Use of the ADR program for educational purposes

● Development, maintenance, and evaluation of ADR records within the organization

● Organizational dissemination and use of information obtained through the ADR program

● Reporting of serious ADRs to the FDA or the manufacturer (or both)

[REPORTING AND EVALUATING ADR]

ASHP Guidelines on ADR Monitoring and Reporting:

● Pediatrics

● Geriatrics

● Pregnant

[REPORTING AND EVALUATING ADR]

Special populations include:

● Underdeveloped organs

● ADRs associated with UDP-glucuronosyltransferase deficiency (e.g., gray baby syndrome and kernicterus)

[REPORTING AND EVALUATING ADR]

Special considerations in PEDIATRICS:

Chloramphenicol

[REPORTING AND EVALUATING ADR]

Gray Baby Syndrome is caused by:

Sulfonamides

[REPORTING AND EVALUATING ADR]

Kernicterus is caused by:

● Comorbidity

● Polypharmacy

● Less functional organs

[REPORTING AND EVALUATING ADR]

Special considerations in GERIATRICS:

Teratogenic agents

[REPORTING AND EVALUATING ADR]

Special considerations in PREGNANCY:

Pregnancy Category A

[FDA PREGNANCY CATEGORY]

● No study in animals

●Adequate well controlled studies in pregnant women have not shown an increased risk of fetal abnormalities to the fetus in any trimester of pregnancy.

Pregnancy Category A

[FDA PREGNANCY CATEGORY]

● Levothyroxine

● Folic acid

● Liothyronine

● Levothyroxine

● Folic acid

● Liothyronine

[FDA PREGNANCY CATEGORY]

Drugs under Pregnancy Category A:

Pregnancy Category B

[FDA PREGNANCY CATEGORY]

●Animal studies have revealed NO evidence of harm to the fetus.

●NO adequate and well controlled studies in pregnant women or animal studies have shown an ADVERSE EFFECT

● Adequate and well controlled studies to pregnant women have FAILED to demonstrate a RISK to the fetus in any trimester.

Pregnancy Category B

[FDA PREGNANCY CATEGORY]

● Metformin

● Hydrochlorothiazide (HCTZ)

● Amoxicillin

● Pantoprazole

● Cyclobenzaprine

● Metformin

● Hydrochlorothiazide (HCTZ)

● Amoxicillin

● Pantoprazole

● Cyclobenzaprine

[FDA PREGNANCY CATEGORY]

Drugs under Pregnancy Category B:

Pregnancy Category C

[FDA PREGNANCY CATEGORY]

● Animal studies have shown an adverse effect.

● There are no adequate and well controlled studies in pregnant women.

Pregnancy Category C

[FDA PREGNANCY CATEGORY]

● Tramadol

● Gabapentin

● Amlodipine

● Trazodone

● Tramadol

● Gabapentin

● Amlodipine

● Trazodone

[FDA PREGNANCY CATEGORY]

Drugs under Pregnancy Category C:

Methyldopa ( + hydralazine, labetalol, nifedipine)

[FDA PREGNANCY CATEGORY]

Antihypertensives safe in pregnancy:

Pregnancy Category D

[FDA PREGNANCY CATEGORY]

● Adequate well controlled or observational studies in pregnant women have demonstrated a risk to the fetus.

● However, benefits may overweigh the potential risk.

Pregnancy Category D

[FDA PREGNANCY CATEGORY]

● Lisinopril

● Alprazolam

● Losartan

● Clonazepam

● Lorazepam

Pregnancy Category X

[FDA PREGNANCY CATEGORY]

Adequate well controlled or observational studies in pregnant women have demonstrated positive evidence of fetal abnormalities or risks.

Pregnancy Category X

[FDA PREGNANCY CATEGORY]

● Isotretinoin

● Warfarin

● Valproic acid

● Methotrexate

● Thalidomide

● Statins

● Isotretinoin

● Warfarin

● Valproic acid

● Methotrexate

● Thalidomide

● Statins

[FDA PREGNANCY CATEGORY]

Drugs under Pregnancy Category X:

Augmented

[ADR CATEGORY]

CLASSIFY:

● OHA → hypoglycemia

● Diazepam → sedation

● Loop diuretics → hypokalemia

● Anticoagulants → bleeding

● Antihistamines → sedation

● Narcotics → constipation

● Paracetamol overdose → hepatotoxicity

● OHA → hypoglycemia

● Diazepam → sedation

● Loop diuretics → hypokalemia

● Anticoagulants → bleeding

● Antihistamines → sedation

● Narcotics → constipation

● Paracetamol overdose → hepatotoxicity

[ADR CATEGORY]

Drugs under AUGMENTED ADRs:

Bizarre

[ADR CATEGORY]

CLASSIFY:

Idiosyncracy

● Antipsychotic agents → malignant hyperthermia

● Vancomycin → Redman's syndrome

● Sulfonamides, Phenytoin, Carbamazepine → Stevens-Johnson Syndrome (SJS)

● Antimalarials, Sulfonamides → hemolytic anemia

Bizarre

[ADR CATEGORY]

CLASSIFY:

Type I (Immediate or Anaphylactic Immune Response)

● Anaphylaxis from penicillins

● Hay fever

● Asthma triggered by NSAIDs or aspirin (ASA)

● Urticaria (hives)

Bizarre

[ADR CATEGORY]

CLASSIFY:

Type II (Cytotoxic Reactions)

● Methyldopa → hemolytic anemia

● Chloramphenicol → aplastic anemia

● Aspirin/Ibuprofen → ITP (immune thrombocytopenic purpura)

● Blood transfusion reactions

Bizarre

[ADR CATEGORY]

CLASSIFY:

Type III (Immune Complex)

● Serum sickness

● Hydralazine, Isoniazid, Procainamide, Pyrazinamide → drug-induced Systemic Lupus Erythematosus (SLE)

Bizarre

[ADR CATEGORY]

CLASSIFY:

Type IV (Delayed, Cell-mediated)

● Tuberculin Skin Test → Intradermal route of administration

● Poison Ivy (urushiol) → Contact dermatitis

● Tissue/Organ Rejection

Idiosyncracy

● Antipsychotic agents → malignant hyperthermia

● Vancomycin → Redman's syndrome

● Sulfonamides, Phenytoin, Carbamazepine → Stevens-Johnson Syndrome (SJS)

● Antimalarials, Sulfonamides → hemolytic anemia

Type I (Immediate or Anaphylactic Immune Response)

● Anaphylaxis from penicillins

● Hay fever

● Asthma triggered by NSAIDs or aspirin (ASA)

● Urticaria (hives)

Type II (Cytotoxic Reactions)

● Methyldopa → hemolytic anemia

● Chloramphenicol → aplastic anemia

● Aspirin/Ibuprofen → ITP (immune thrombocytopenic purpura)

● Blood transfusion reactions

Type III (Immune Complex)

● Serum sickness

● Hydralazine, Isoniazid, Procainamide, Pyrazinamide → drug-induced Systemic Lupus Erythematosus (SLE)

Type IV (Delayed, Cell-mediated)

● Tuberculin Skin Test → Intradermal route of administration

● Poison Ivy (urushiol) → Contact dermatitis

● Tissue/Organ Rejection

[ADR CATEGORY]

Drugs under BIZARRE ADRs:

Continuous

[ADR CATEGORY]

CLASSIFY:

Addiction:

● Marijuana

● Opiates

Dependence:

● Benzodiazepines

● Caffeine

● Steroids

Tolerance:

● Nicotine

Addiction:

● Marijuana

● Opiates

Dependence:

● Benzodiazepines

● Caffeine

● Steroids

Tolerance:

● Nicotine

[ADR CATEGORY]

Drugs under CONTINUOUS ADR:

Delayed

[ADR CATEGORY]

CLASSIFY:

Carcinogenicity:

● Antineoplastic agents

● Aromatic hydrocarbons (benzene)

● Heterocyclic amines

● Aflatoxins

● Nitrosamines

Teratogenicity

Carcinogenicity:

● Antineoplastic agents

● Aromatic hydrocarbons (benzene)

● Heterocyclic amines

● Aflatoxins

● Nitrosamines

Teratogenicity

[ADR CATEGORY]

Drugs under DELAYED ADR:

End of Use

[ADR CATEGORY]

CLASSIFY:

● Opiate withdrawal

● Clonidine → rebound hypertension

● Steroids → adrenal insufficiency (Addison's disease)

● Oxymetazoline → rhinitis medicamentosa (rebound congestion)

● Opiate withdrawal

● Clonidine → rebound hypertension

● Steroids → adrenal insufficiency (Addison's disease)

● Oxymetazoline → rhinitis medicamentosa (rebound congestion)

[ADR CATEGORY]

Drugs under END OF USE ADR:

Failure of Therapy

[ADR CATEGORY]

CLASSIFY:

Therapeutic failure due to the following:

● Lack of efficacy

● Poor patient compliance

● Counterfeit drugs

● Drug interactions

● Antimicrobial resistance

● Inappropriate use/wrong route of administration

● Manufacturing errors/toxic excipients

● Expired drugs