Pharmacovigilance of monkeypox and its treatment

1. PRACTICE SCHOOL
MAHAVIR INSTITUTE
OF PHARMACY,
NASIK.

2. COURSE STRUCTURE AND CONTENTS FOR
PRACTICE SCHOOL (BP706PS)
B. PHARMACY FINAL YEAR (SEMVII)
DOMAIN -18
PHARMACOVIGILANCE

3. A REVIEW ARTICLE BY :
MAHAKALE AACHAL SANJAY
FINAL YEAR B.PHARMACY
(1952811823024)
GUIDED BY:
PROF. SONIYA SATAPUTE

4. ABSTRACT
“PHARMACOVIGILANCE IS DEFINED BY WORLD HEALTH ORGANISATION
AS SCIENCE AND ACTIVITIES RELATING TO DETECTION, ASSESSMENT,
UNDERSTANDING AND PREVENTION OF ADVERSE EFFECT OR ANY
OTHER DRUG RELATED PROBLEM”. PHARMACOVIGILANCE IS
REQUIRED THROUGH ENTIRE LIFE CYCLE OF DRUG, FROM
DEVELOPMENT TO MONITORING OF DRUG. SURVEILLANCE,
OPERATION AND SYSTEM ARE MAIN SUB-SPECIALISM. AIM OF
PHARMACOVIGILANCE IS TO IMPROVE PATIENT HEALTH CARE AND
SAFETY IN RELATION TO MEDICATION. CLICAL RESEARCH HAS 3
PHASES OF CLINICAL TRIALS.
PHARMACOVIGILANCE PROGRAMME IN INDIA IS COORDINATED BY
DEPARTEMENT OF PHARMACOLOGY AT AIIMS AS NATIONAL
CORDINATING CENTRE(NCC).UNDER SUPERVISION OF STEERING
COMMITTEE.

5. INTRODUCTION TO PHARMACOVIGILANCE
• PHARMACOVIGILANCE IS REQUIRED THROUGH THE ENTIRE LIFE CYCLE OF A
DRUG – STARTING AT THE PRECLINICAL DEVELOPMENT STAGE AND GOING
RIGHT THROUGH TO CONTINUED MONITORING OF DRUGS ONCE THEY HIT THE
MARKET.
• PHARMACOVIGILANCE INCLUDES COLLECTING, ANALYZING, MONITORING, AND
PREVENTING ADVERSE EFFECTS IN NEW DRUGS AND THERAPIES.
• IT ALSO INVOLVE IDENTIFICATION OF NEW SAFETY INFORMATION AND
ASSESSMENT OF THE RISK BENEFIT BALANCE OF MEDICINE.

6. CONCEPT OF PHARMACOVIGILANCE
• DEFINITION
• PHARMACOVIGILANCE IS THE SCIENCE AND ACTIVITIES RELATING TO
THE DETECTION, ASSESSMENT, UNDERSTANDING AND PREVENTION OF
ADVERSE EFFECTS OR ANY OTHER MEDICINE/VACCINE RELATED
PROBLEM.
• AIM OF PHRMACOVIGILANCE:
• 1. IMPROVE PATIENT CARE AND SAFETY IN RELATION TO THE USE OF
MEDICINES AND ALL MEDICAL AND PARAMEDICAL INTERVENTIONS.
• 2. RESEARCH THE EFFICACY OF DRUG AND BY MONITORING THE
ADVERSE EFFECTS OF DRUGS RIGHT FROM THE LAB
TO THE PHARMACY AND THEN ON FOR MANY YEARS.
• 3.IMPROVE PUBLIC HEALTH AND SAFETY IN RELATION TO THE USE OF
MEDICINES.

7. CLINICAL TRAILS:
• CLINICAL TRIALS ARE A TYPE OF RESEARCH THAT STUDIES NEW TESTS AND
TREATMENTS AND EVALUATES THEIR EFFECTS ON HUMAN HEALTH OUTCOMES.
PEOPLE VOLUNTEER TO TAKE PART IN CLINICAL TRIALS TO TEST MEDICAL
INTERVENTIONS INCLUDING DRUGS, CELLS AND OTHER BIOLOGICAL
PRODUCTS, SURGICAL PROCEDURES, RADIOLOGICAL PROCEDURES, DEVICES,
BEHAVIOURAL TREATMENTS AND PREVENTIVE CARE.
• CLINICAL TRIALS ARE CAREFULLY DESIGNED, REVIEWED AND COMPLETED, AND
NEED TO BE APPROVED BEFORE THEY CAN START. PEOPLE OF ALL AGES CAN
TAKE PART IN CLINICAL TRIALS, INCLUDING CHILDREN.

8. • THERE ARE 4 PHASES OF BIOMEDICAL CLINICAL TRIALS:
• PHASE I STUDIES USUALLY TEST NEW DRUGS FOR THE FIRST TIME IN A SMALL
GROUP OF PEOPLE TO EVALUATE A SAFE DOSAGE RANGE AND IDENTIFY SIDE
EFFECTS.(15-30 PATIENTS)
• PHASE II STUDIES TEST TREATMENTS THAT HAVE BEEN FOUND TO BE SAFE IN
PHASE I BUT NOW NEED A LARGER GROUP OF HUMAN SUBJECTS TO MONITOR
FOR ANY ADVERSE EFFECTS.(FEWER THAN 100)
• PHASE III STUDIES ARE CONDUCTED ON LARGER POPULATIONS AND IN
DIFFERENT REGIONS AND COUNTRIES, AND ARE OFTEN THE STEP RIGHT
BEFORE A NEW TREATMENT IS APPROVED.(100-1000S OF PATIENT)
• PHASE IV STUDIES TAKE PLACE AFTER COUNTRY APPROVAL AND THERE IS A
NEED FOR FURTHER TESTING IN A WIDE POPULATION OVER A LONGER
TIMEFRAME.

10. 1. FUNCTIONS OF (DCGI) DRUG CONTROLLER GENERAL OF INDIA:
(1) TO PREPARE AND MAINTAIN THE NATIONAL REFERENCE STANDARD FOR
DRUGS
(2) REGULATE MEDICAL AND PHARMACEUTICAL DEVICES IN THE COUNTRY
(3) TO ENSURE THAT THE PROVISIONS OF THE DRUGS AND COSMETICS ACT ARE
ENFORCED UNIFORMLY IN THE COUNTRY.
(4) TO TRAIN DRUG ANALYSTS DEPUTED BY STATE DRUG CONTROL
LABORATORIES AND OTHER INSTITUTIONS
(5) TO SURVEY AND ANALYZE SAMPLES OF COSMETICS AND DRUGS RECEIVED
FROM CDSCO
(6) TO FUNCTION AS THE APPELLATE AUTHORITY IF ANY DISPUTE ARISES
REGARDING THE QUALITY OF THE DRUGS

11. 2. FUNCTIONS OF CDSCO-
(1)APPROVAL OF NEW DRUGS AND CLINICAL TRIALS
(2)IMPORT REGISTRATION AND LISCENCING
(3)LICENSE APPROVING OF BLOOD BANKS, LPVS,VACCINES, R-DNA PRODUCTS &
SOME MEDICAL DEVICES
(4)AMENDMENT TO D & C ACT AND RULES
(5)BANNING OF DRUGS AND COSMETICS
(6)GRANRT OF TEST LICENSE , PERSONAL LICENSE , NOCS FOR EXPORT
(7)TESTING OF NEW DRUG

12. TYPE OF REGULATORY APPLICATION:
• INVESTIGATIONAL NEW DRUG:
• AN INVESTIGATIONAL NEW DRUG APPLICATION (IND) IS A REQUEST FOR
AUTHORIZATION SUBMITTED BY A SPONSOR TO THE FDA SO THE
SPONSOR CAN CONDUCT CLINICAL TRIALS FOR UNAPPROVED DRUGS.
THE PURPOSE OF AN IND APPLICATION IS TO ALLOW SPONSORS TO
START CONDUCTING CLINICAL TRIALS ON HUMANS, AND APPROVAL TO
SHIP THE DRUGS ACROSS STATE LINES IN ORDER TO CONDUCT THESE
TRIALS.
• NEW DRUG APPLICATION:
• THE NEW DRUG APPLICATION (NDA) IS THE VEHICLE THROUGH WHICH
DRUG SPONSORS FORMALLY PROPOSE THAT THE FDA APPROVE A NEW
PHARMACEUTICAL FOR SALE AND MARKETING IN THE UNITED STATES.

13. ABBREVIATED NEW DRUG APPLICATION:
• AN ABBREVIATED NEW DRUG APPLICATION (ANDA) CONTAINS DATA
WHICH IS SUBMITTED TO FDA FOR THE REVIEW AND POTENTIAL
APPROVAL OF A GENERIC DRUG PRODUCT. ONCE APPROVED, AN
APPLICANT MAY MANUFACTURE AND MARKET THE GENERIC DRUG
PRODUCT TO PROVIDE A SAFE, EFFECTIVE, LOWER COST
ALTERNATIVE TO THE BRAND-NAME DRUG IT REFERENCES.

14. GOOD CLINICAL PRACTICES:
OBJECTIVE AND SCOPE OF “ICH-GOOD CLINICAL PRACTICE”
• THE OBJECTIVE OF THIS ICH GCP GUIDELINE IS TO PROVIDE A UNIFIED
STANDARD FOR THE EUROPEAN UNION (EU), JAPAN AND THE UNITED STATES
TO FACILITATE THE MUTUAL ACCEPTANCE OF CLINICAL DATA BY THE
REGULATORY AUTHORITIES IN THESE JURISDICTIONS.
• SCOPE-
• GOOD CLINICAL LABORATORY PRACTICES SHOULD BE USED BY ALL
LABORATORIES WHERE TESTS ARE DONE ON BIOLOGICAL SPECIMEN FOR
DIAGNOSIS, PATIENT CARE, DISEASE CONTROL AND RESEARCH SUCH AS:
• MICROBIOLOGY & SEROLOGY
• HEMATOLOGY & BLOOD BANKING
• MOLECULAR BIOLOGY AND MOLECULAR PATHOLOGY
• CLINICAL PATHOLOGY

15. CONCEPT OF PHARMACOVIGILANCE
• DEFINITION
• PHARMACOVIGILANCE IS THE SCIENCE AND ACTIVITIES RELATING TO THE
DETECTION, ASSESSMENT, UNDERSTANDING AND PREVENTION OF ADVERSE
EFFECTS OR ANY OTHER MEDICINE/VACCINE RELATED PROBLEM.
• OBJECTIVE-
• IMPROVEMENT OF PATIENT CARE AND SAFETY IN RELATION TO THE USE OF
MEDICINES.
• THE MAIN OBJECTIVES OF PHARMACOVIGILANCE INVOLVE EXHIBITING THE
EFFICACY OF DRUGS BY MONITORING THEIR ADVERSE EFFECT PROFILE FOR
MANY YEARS FROM THE LAB TO THE PHARMACY; TRACKING ANY DRASTIC
EFFECTS OF DRUGS BY MONITORING THEIR ADVERSE EFFECT PROFILE FOR
MANY YEARS FROM THE LAB TO THE PHARMACY TRACKING ANY DRASTIC
EFFECT OF DRUGS IMPROVING PUBLIC HEALTH AND SAFETY IN RELATION TO
THE USE OF MEDICINE ENCOURAGING THE SAFE, RATIONAL AND COST-
EFFECTIVE USE OF DRUGS.

16. COMPONENT OF PHARMACOVIGILANCE:

17. PHARMOCOVIGILANCE PROGRAM IN
INDIA
THE PROGRAMME IS COORDINATED BY THE DEPARTMENT OF PHARMACOLOGY AT AIIMS AS
A NATIONAL COORDINATING CENTRE (NCC). THE CENTRE WILL OPERATE UNDER THE
SUPERVISION OF A STEERING COMMITTEE.
• GOLE AND OBJECTIVE
• 1.GOLE- TO ENSURE THAT THE BENEFITS OF USE OF MEDICINE OUTWEIGHS THE RISKS
AND THUS SAFEGUARD THE HEALTH OF THE INDIAN POPULATION.
• 2.OBJECTIVE-
• TO MONITOR ADVERSE DRUG REACTIONS (ADRS) IN INDIAN POPULATION
• TO CREATE AWARENESS AMONGST HEALTH CARE PROFESSIONALS ABOUT THE
IMPORTANCE OF ADR REPORTING IN INDIA TO MONITOR BENEFIT-RISK PROFILE OF
MEDICINES
• TO MONITOR BENEFIT-RISK PROFILE OF MEDICINES

18. LIST OF NATIONAL ADVERSE DRUG
REACTION MONITORING CENTRE AND THEIR
FUNCTION

19. FUNCTIONS OF NATIONAL ADR CENTRE:
Data Retrieval
Storage
Time
Consumption
Documentation
Analyst
Unawareness

20. INTERNATIONAL CONFERENCE ON HARMONIZATION (ICH)
E2E GUIDELINE
• ELEMENTS OF CLINICAL & NON-CLINICAL SAFETY SPECIFICATION:
• SAFETY SPECIFICATION CAN INCLUDE:
Identified
RISK
Important
potential
risk
Important
Missing
Informatio
n

21. • 1. NON- CLINICAL
• TOXICITY (INCLUDING REPEAT-DOSE TOXICITY,
REPRODUCTIVE/DEVELOPMENTAL TOXICITY, NEPHROTOXICITY.
• DRUG INTERACTIONS;
• OTHER TOXICITY-RELATED INFORMATION
• 2.CLINICAL-
• ADVERSE DRUG REACTION
• LIMITATIONS OF THE SAFETY DATABASE (E.G., RELATED TO THE SIZE OF
THE STUDY POPULATION)
• ANY NEW OR DIFFERENT SAFETY ISSUES IDENTIFIED;
• ANY REGULATORY ACTIONS RELATED TO SAFETY

22. EVALUATION OF DRUG-DRUG & DRUG-
FOOD INTERACTION
DRUG –DRUG
INTERACTION

23. DRUG – FOOD INTERACTION
DRUG
FOO
D
ACTION
FOR
DRUG
ACTIO
N FOR
DRUG
ADVERSE
EFFECT

24. DESIGN AND CONDUCT OF OBSERVATION
STUDIES
• THERE ARE THREE TYPE OF OBSERVATION STUDIES, SUCH AS
CONTROLLED, NATURALISTIC, AND PARTICIPANT STUDIES.
• AN OBSERVATION STUDY IS A FORM OF QUALITATIVE RESEARCH
IN WHICH THE RESEARCHER OBSERVES PARTICIPANTS
BEHAVIOUR.
• THE SECOND EDITION OF DESIGN OF OBSERVATIONAL STUDIES
IS BOTH AN INTRODUCTION TO STASTICAL INFERENCE IN
OBSERVATIONAL STUDIES AND A DETAILED DISCUSSION OF THE
PRINCIPLE THAT GUIDE THE DESIGN OF OBSERVATIONAL
STUDIES.

25. SELECTION OF DRUG CLASS:
• SELECTED CLASS OF DRUG:
• ANTIVIRAL CLASS
• DRUG NAME IS TICOVIRIMAT
• ANTIVIRAL DRUG =
• ANTIVIRAL DRUGS ARE A CLASS OF MEDICATION USED FOR TREATING VIRAL
INFECTIONS. MOST ANTIVIRALS TARGET SPECIFIC VIRUSES, WHILE A BROAD-
SPECTRUM ANTIVIRAL IS EFFECTIVE AGAINST A WIDE RANGE OF VIRUSES

26. TICOVIRIMAT
• TECOVIRIMAT (ALSO KNOWN AS TPOXX OR ST-246) IS THE FIRST ANTIVIRAL
INDICATED FOR THE TREATMENT OF SMALLPOX IN ADULTS AND PEDIATRIC
PATIENTS WEIGHING AT LEAST 3 KG AND IS CONSIDERED THE TREATMENT OF
CHOICE.
• TECOVIRIMAT WORKS BY INHIBITING THE VIRAL ENVELOPE PROTEIN VP37,
WHICH BLOCKS THE FINAL STEPS IN VIRAL MATURATION AND RELEASE FROM
THE INFECTED CELL, THUS INHIBITING THE SPREAD OF THE VIRUS WITHIN AN
INFECTED HOST.

27. PROFILING OF DRUG CLASS:
• MECHANISM OF ACTION:

28. PHARMACOLOGY:
• ANTIVIRAL AGENT; TARGETS AND INHIBITS THE ACTIVITY OF THE
ORTHOPOXVIRUS VP37 PROTEIN (ENCODED BY AND HIGHLY CONSERVED IN
ALL MEMBERS OF THE ORTHOPOXVIRUS GENUS) AND BLOCKS ITS
INTERACTION WITH CELLULAR RAB9 GTPASE AND TIP47, WHICH PREVENTS
THE FORMATION OF EGRESS-COMPETENT ENVELOPED VIRIONS NECESSARY
FOR CELL-TO-CELL AND LONG-RANGE DISSEMINATION OF VIRUS.
• ABSORPTION
• PEAK PLASMA TIME: 4-6 HR
• PEAK PLASMA CONCENTRATION: 2106 NG/ML
• MINIMUM PLASMA CONCENTRATION: 587 NG/ML

29. • DISTRIBUTION:
• PROTEIN BOUND: 77-82%
• METABOLISM
• METABOLIC PATHWAYS INCLUDE HYDROLYSIS
• ELIMINATION
• HALF-LIFE: 20 HR
• CLEARANCE: 31 L/HR
• ADVERSE REACTION
• NAUSEA
• ABDOMINAL PAIN
• VOMITING
• GASTROINTESTINAL: DRY MOUTH, CHAPPED LIPS, DYSPEPSIA, ERUCTATION
• NERVOUS SYSTEM: MIGRAINE, DISTURBANCE IN ATTENTION, DYSGEUSIA,
PARESTHESIA

30. DRUG INTERACTION:
• MIDAZOLAM: TICOVIRIMAT MAY DECREASE THE SERUM
CONCENTRATION OF MIDAZOLAM.
• RIPAGLINIDE: TICOVIRIMAT MAY INCREASE THE SERUM
CONCENTRATION OF RIPAGLINIDE.
INDICATIONS:
• ANTIVIRAL INFECTION CAUSING SMOLLPOX.

31. INDICATIONS OF ADVERSE REACTION OF
TICOVIRIMAT:
•MILD UPSET STOMACH, DRY MOUTH, DECREASED
CONCENTRATION AND DYSPHORIA.
•MILD NAUSEA AND FEVER, MODERATE DIARRHEA, SEVERE
HEADACHE.
•MILD PALPABLE PURPURA.
•MILD NAUSEA, FEVER AND CHILLS.
•MILD FACIAL REDNESS, FACIAL SWELLING AND PRURITUS

33. HOSPITAL VISIT:
• DELHI’S FIRST MONKEYPOX CASE: INDIA’S TALLY AT 4
• DELHI HAS REPORTED THE FIRST CASE OF MONKEYPOX IN A 34-YEAR-OLD MAN
WITH NO TRAVEL HISTORY.
• THE PATIENT IS PRESENTLY RECOVERING AT THE DESIGNATED ISOLATION
CENTRE AT LOK NAYAK HOSPITAL (LNJP).THE CLOSE COATACTS OF THE CASE
HAVE BEEN IDENTIFIED ARE UNDER QUARANTINE AS PER MOHFW GUIDELINE,
THE GOVERNMENT SAID.
• THE PATIENT, A RESIDENT OF WEST DELHI, WAS ADMITTED TO THE HOSPITAL
AROUND THREE DAYS AGO HE SHOWED SYMPTOMS OF MONKEYPOX.
• HIS SAMPLE WERE SENT TO THE NATIONAL INSTITUTE OF VIROLOGY (NIV) PUNE
ON SATURDAY WHICH CAME OUT POSITIVE, SOURCES WERE QUOTED AS
SAYING BY NEWS AGENCY PTI.
• THE MAN HAD REPORTEDLY ATTENDED A STAG PARTY RECENTLY IN MANALI IN
HIMACHAL PRADESH.

34. CONCLUSION
PHRAMCOVIGILANCE IS ONLY WAY TO ENSURE SAFETY OF DRUG
THROUGHOUT THE LIFE CYCLE OF DRUG. THE KNOWLEDGE AND
INFORMATION AVAILABLE REGARDING SAFETY OF ANY DRUG IS VERY
MUCH IMPORTANT TO TAKE APPROPRIATE DECISION BY DRUG
REGULATORS TO SAFE GUARD PUBLIC HEALTH. DCGI REGULATE
MEDICAL AND PHARMACEUTICAL DEVICES IN COUNTRY. CDSCO APPROVE
THE NEW DRUG AND CLINICAL TRAIL.
TICOVIRIMAT IS USED FOR MONKEYPOX . IT IS ANTIVIRAL AGENT.
TICOVIRIMAT WORK BY INHIBITING THE VIRAL ENVELOP PROTEIN VP37,
WHICH BLOCKS THE FINAL STEPS IN VIRAL MATURATION AND RELEASE
FROM THE INFECTED CELL, THUS INHIBITING THE SPREAD OF THE VIRUS
WITHIN AN INFECTED HOST.

35. THANK YOU………