adverse drug reactions - katalyst hls

Adverse Drug Reactions

Pharmacovigilance05/02/23

Katalyst Healthcares & Life Sciences

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Risk - Benefit EvaluationBenefit/Risk Ratio

• Exposure to personal risk is recognized as a normal aspect of everyday life.

• We accept a certain level of risk in our lives as necessary to achieve certain benefits.

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Any harmful effect caused by administration of a drug at a normal dosage during normal use

Adverse Drug Reaction (ADR) =

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Type-A: Augmented pharmacologic effects - dose dependent and predictable (e.g. hypoglycaemia with insulin, bleeding after anticoagulants, drowsiness after opioids)

They are common but often not severe, they are usually caused by too high dosage or alered pharmacokinetics (genetic factors, age, reduced renal or hepatal elimination)

most often with drugs that have a steep dose-response curve and/or a low therapeutic index

Type-B: Bizarre effects (or idiosyncratic) - dose independent and unpredictable are relatively rare and may occur with very low doses (e.g. drug allergy – skin rashes – anaphylaxis, blood dyscrasias)

Types of Adverse Drug Reactions (A-B-C-D-E):

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Type-C: Chronic effects after chronic administration (e.g. analgesic nephropathy after some analgesics or tardive dyskinesia after antipsychotics)

Type-D: Delayed effects (e.g. teratogenic effects – thalidomide , cancerogenic effects – stilbestrol during pregnancy > vaginal carcinoma in daughters 20+years later)

Type-E: End-of-treatment effects(e.g. withdrawal effects opioids, antiepileptics, anxiolytics, rebound phenomenon- hypnotics)

Types of Adverse Drug Reactions (A-B-C-D-E):

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Examples of Adverse Effects associated with Specific Medications

Bleeding in GIT NSAIDs

Thrombosis hormonal contraceptives

Ototoxicity, nephrotoxicity aminoglycoside antibiotics

Parkinsonism 1st generation (typical) antipsychotics

Aplastic anaemia chloramphenicol

Agranulocytosis clozapine (atypical antipsychotic)

Hair loss anticancer drugs

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Pharmacovigilance

collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of drugs

Major goal of pharmacovigilance is to detect a signal on an unknown serious adverse drug reaction as soon as possible

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• Pharmaceutical companies are required by law in all countries to report ADRs during clinical trials, testing new drugs on people before they are made generally available.

• Because these pre-registration clinical trials involve only several thousand patients at most, less-common ADRs are often unknown when a drug enters the market.

Limits of Detecting rare ADRs before Drug Registration/Marketing

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Post-Marketing Surveillance

Pharmacovigilance after Drug Registration/Marketing

Major sources of information on ADRs:

1.Spontaneous reporting of suspected ADRs by healthcare

professionals.

2.Reporting of ADRs by pharmaceutical companies

(marketing authorisation holders).

3.ADRs reported in medical journals.

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Spontaneous reporting of suspected ADRs

by healthcare professionals

to their national pharmacovigilance center (or to the manufacturer)

is indispensable in data-generating system of pharmacovigilance

Spontaneous Reporting

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Spontaneous reporting of ADRs by physicians is legally obligatory in many countries

Origin of spontaneous reporting of ADRs by physicians:

Yellow Card Scheme founded in the UK in 1964 – forms to fill in, sent by post or electronically to the UK pharmacoviligance center

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• ADRs that have caused death or a serious illness.• Any ADR, however minor, if associated with a new

medicine or one that is under continued monitoring (highlighted in the British National Formulary (BNF) with a ▼ black triangle).

• Any ADR, however minor, if associated with a child (under 18 years of age) or in pregnancy.

Yellow Card Scheme

The sort of ADRs that should be reported are:

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The American Food and Drug Administration:

• Death• Life-threatening• Hospitalization (initial or prolonged)• Disability - significant, persistent, or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities or quality of life.• Congenital anomaly• Requires intervention to prevent permanent impairment or damage

The sort of ADRs that should be reported are:

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* marketing authorisation holders

Pharmaceutical companies* continually monitor and assess ADRs in their medicines and are expected to report of them to authorisation agencies and/or to certain pharmacovigilance centers

Periodic Safety Update Reports (PSURs)

PSUR is an update report, at defined time points after authorization, of the worldwide safety experience of a medicinal product. The PSUR is to be submitted to the authorisation agency (e.g. to the European Medicines Agency) by a marketing authorisation holder. PSUR provides succinct summary information together with a critical evaluation of the benefit/risk balance of the product in the light of new or changing post-authorisation information. This evaluation should ascertain whether further investigations need to be carried out and whether changes should be made to the marketing authorisation (e.g. to the product information). 05/02/23


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International collaboration in the field of Pharmacovigilance:

Spontaneous reports of suspected ADRs are sent from national pharmacovigilance centers (n ≈100)

to the Uppsala Monitoring Centre

where they are processed, evaluated and entered into the WHO International Database

This may lead to the detection of a signal – an alert about a possible hazard communicated to members countries.

WHO International Drug Monitoring Programm

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European Medicines Agency (EMA)

EudraVigilance - the system of collecting all suspected serious ADRs

Pharmacovigilance in EU:

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Post-marketing surveillance is overseen by the

Food and Drug Administration (FDA),

which operates a system called MedWatch,

to which doctors or the general public can voluntarily report adverse reactions to drugs

Pharmacovigilance in USA:

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e.g. Bulletin of European Medicines Agency (EMA):

PhVWP monthly report on safety concerns, guidelines andgeneral matters

SPC (/Summary of Product Characteristics: frequency

Solid sources of information on ADRs

Solid Drug Databases e.g. Micromedex, UpToDate, BNF, AISLP etc

ADRs in general:

ADRs recently reported:

PhVWP = The CHMP Pharmacovigilance Working PartyCHMP = Committee for Medicinal Products for Human Use

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• Very common (>10%) >= 1/10

• Common (frequent) (1-10%) > = 1/100 and < 1/10

• Uncommon (infrequent) (0,1 - 1 %) >= 1/1000 and < 1/100

• Rare (0,001-0,1%) >= 1/10000 and < 1/1000

• Very rare (< 0,001 %) < 1/10000

Frequency of Adverse Drug Reactions

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PsychiatricVery common 1/10 Sleep disorders including abnormal dreams and insomniaCommon 1/100; <1/10 NervousnessNervous system disordersVery Common 1/10 Headache, dizziness Common 1/100;<1/10 TremorCardiac DisordersCommon 1/100;<1/10: PalpitationsUncommon 1/1000; <1/100 TachycardiaRespiratory, Thoracic and Mediastinal DisordersCommon 1/100; <1/10 Dyspnoea, pharyngitis, coughGastrointestinal DisordersVery Common 1/10 Nausea, vomitingCommon 1/100;<1/10 Dyspepsia, abdominal pain upper, diarrhoea, dry mouth, constipationSkin and Subcutaneous Tissue DisordersCommon 1/100; <1/10 Sweating increasedVery rare <1/10000 Dermatitis allergic, dermatitis contact,photosensitivityMusculoskeletal and Connective Tissue DisordersCommon 1/100; <1/10 Arthralgia, myalgia

Example: Frequency of ADRs in NicotineTransdermal Patches (from SPC):

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Summary – „a message to take home“:

Spontaneous reporting of suspected ADRs

by healthcare professionals

to their national pharmacovigilance center (or to the manufacturer)

is essential in Pharmacovigilance

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Thank YouThank You&&

QuestionsQuestions

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Contact:Katalyst Healthcare’s & Life SciencesSouth Plainfield, NJ, USA 07080.E-Mail: [email protected]

mailto:[email protected]

adverse drug reactions - katalyst hls

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