Adverse drug reaction of chemotherapy

1. GROUPMEMBER
• Preceptor: Pharm. Raji Abdulfatai
• Supervisors: Pharm. Bulus Emmanuel
Pharm. Samira Umar
• Members: Pharm. Ugwu Martins
Pharm. Ezema Jude C.

2. OUTLINE
• INTRODUCTION
• EPIDEMIOLOGY
• COMMON CAUSES ADR
• FACTORS AFFECTING ADR
• CHEMOTHERAPY INDUCED NAUSEAAND VOMITTING
• MUCOSCITIS
• ALOPECIA
• ROLE OF PHARMACISTS IN ADR OF CHEMOTHRAPY
• CONCLUSION
• REFERENCE

3. INTRODUCTION
• Cancer refers to cells that grows rapidly out of control
and invade other cells due to accumulation of defects or
mutation in their DNA.
• Chemotherapy is a type of cancer treatment that uses one
or more anti-cancer drugs as part of a standardized
chemotherapy regimen.

4. • WHO defines ADR as ‘Any response to a drug which is
noxious and unintended and which occurs at doses used
in man for prophylaxis, diagnosis or therapy of disease or
for the modification of physiological function.

5. Why does chemotherapy bring
about Reactions ?

6. Intro. Cnt’d…
• They therefore induce various forms of ADRs,
such as suppression of the bone marrow, hair
loss, nausea and vomiting, mucositis,
neutropenia, anaemia hepatotoxicity and
nephrotoxicity.
• Also, patients on chemotherapy will be on multi-
drug treatments making them at risk to ADRs.

7. EPIDEMIOLOGY
Adverse drug reactions (ADRs), which account for
6.5%-10.9% of hospital admissions and fatality
rates of 0.15-2.9%, are a substantial cause of
morbidity and mortality. They also place an
additional financial burden on patients, their
caregivers, and the healthcare systems that treat
them.

8. COMMON CAUSES OFADRS
• Failure to maintain correct dosage regimen
• overdosing (accidental)
• Allergies to chemical component
• Consuming alcohol when on drugs
• Drug interactions

9. FACTORSAFFECTINGADR
• Drug- related factors
• Dose
• Duration
• Inherent toxicity of the
agent
• Pharmacokinetic
properties
• Pharmacodynamic
properties
• Patient-related factors
• Age
• Sex
• Genetic influence
• Compliance with dosing
regimen
• Previous adverse drug
reactions
• total number of
medication

10. CHEMOTHERAPYINDUCED NAUSEAANDVOMITING (CNIV)
• CINV are the two of the most feared ADR of
cancer treatment
• Up to 80% of patients undergoing chemotherapy
experience N/V

11. TYPES OF CINV
Three distinct types of CINV have been defined: acute,
delayed and anticipatory n/v.
1. Acute N/V
• Most commonly begins within one to two hours of
chemotherapy
• Usually peaks in the first four to six hours

12. Types of CINV
2. Delayed N/V
• Occurs more than 24 hours after chemotherapy
• It is best characterized following treatment with
high dose Cisplatin.

13. TYPES OF CINV
3. Anticipatory N/V
• Occurrs prior to treatment as a conditioned
response in patients who have developed
significant nausea and vomiting during previous
cycles of chemotherapy
• Infants and young children usually do not
experience anticipatory n/v

14. PATHOPHYSIOLOGY

15. RISK FACTORS OF CINV
• Age >3yrs
• Sex: females are more predisposed than males
• Past history of CINV
• Past history of motion sickness
• Emetogenic potential of the chemotherapy
• Administration schedule of chemotherapy

16. POTENTIALCOMPLICATIONS OF CINV
• Discomfort
• Delay of treatment
• Interference with Qol
• Dehydration
• Metabolic disturbances
• Anorexia and weight loss
• Physical debilitation from
malnutrition
• Straining of abdominal
muscles
• Increased intracranial
pressure
• Aspiration

17. Management of CINV
Drug category Example MOA Dose
5-HT3 recertor
antagonist
Ondanosteron Selective 5-HT3
receptor
antagonist
24mg(3 8mg tablets)
PO B4 admin of highly
ematogenic CT agent
without regard to
food
Neurokinin-1
receptor antagonist
Aprepitant Selective human
subst. P/NK1 RA
One capsule (40mg)
orally 1hr before CT
Glucocorticoids Dexamethasone Unknown 20mg orally 30min
before chemo
Dopamine receptor
antagonist
metoclopramide Potent D2
receptor
aantagonist
1-2mg IV 30 min
before chemotherapy

18. MUCOSITIS
• Mucositis is a general term referring to inflammation
of any mucosal membranes, including the oral cavity.
• Oral Mucositis traditionally has been attributed to the
direct effects of cytotoxic drugs or radiation on
epithelial stem cells.

19. ORAL MUCOSITIS
• The incidence of oral mucositis varies based on type of
chemotherapy, dose and schedule.
• Radiation therapy directed at mucosa increases the risk,
and incidence varies depending on the dose, field, and
whether chemotherapy is used concurrently..

20. RISK FACTORS
• Age
• History of smoking
• Poor oral hygiene
• Previous history of oral lessions

21. ORAL MUCOSITIS CONT’D…
The following classes of chemotherapy agents are
associated with mucositis.
A. Antimetabolites; increased risk noted with 5FU ,6-
macaptopurine and methotrexate.
B. Antitumour antibiotics; doxorubucin
C. Alkylating agents: Increased risk noted with high
dose cyclophosphamide.
d. Biologic agents particularly IL-2 and IFN.

22. ORAL MUCOSITIS CONT’D…
• The signs and symptoms of mucositis include
• Changes in taste and ability to swallow.
• Hoarseness or decreased voice strength
• Pain
• Changes in the color of the oral mucosa (e.g pallor,
erythema of varying degrees, white patches,
discolored lesions or ulcers).
• Changes in oral moisture (e,g. amount of saliva,
quality of secretions).
• Edema of oral mucosa and tongue.
• Mucosal Ulcerations.

24. MANAGEMENT OF MUCOSITIS
• Oral debridement (eg, brushing, toothettes); mucolytic
agents, such as Alkalol, help dislodge dried secretions.
• Oral decontamination, including antibacterial and
antifungal rinses.
• Topical and systemic pain management.

25. MANAGEMENT OF MUCOSITIS
• Prophylaxis, such as ice-chip cryotherapy.
• Nutritional support, Patients with severe oral
mucositis may require total parenteral nutrition
• Photobiomodulation therapy (low-level laser
therapy).

27. PHOTOBIOMODULATION THERAPY

28. ALOPECIA
• Alopecia is a transient and usually (although not
always) reversible consequence of systemic cancer
therapy that can be psychologically and socially
devastating.
• It is most prominent on the scalp, eyebrows and
eyelashes (madarosis), as well as axillary and pubic
hair.

29. ALOPECIA
• Some chemotherapy agents may cause prolonged
or permanent alopecia, most notably docetaxel
given at doses of 75 mg or higher per cycle, and
less commonly paclitaxel.
• Other agents with high risks are
cyclophosphamide, doxorubicin and etopside.

30. VARYING DEGREES OFALOPECIA

31. RISK FACTORS
• Drug related factors
• route
• dose
• schedule of drug administration.
• Patient’s factors include
• poor drug metabolism
• Prior exposure to scalp irradiation
• Older age
• Use of prior chemotherapy

32. TREATMENT
• Pharmacotherapy
• 2% topical Minoxidil 12 hourly.
• 0.03% topical bimatoprost once daily.
• Non pharmacological approach
• Scalp cooling: is the application of cold to the scalp
using a device cap that is pre-cooled in a freezer or
exchanges coolant with reservoir .(Dignicap and
Paxman scalp hypothermia system.

33. SCALP COOLING

34. ADDITIONAL INFORMATION
• UA is a 60 year old woman being managed for left
invasive ductal carcinoma , she has had two cycles of
chemotherapy and was admitted to the FMW in FMC
Keffi on account of generalized body weakness,
dizziness ,anorexia , difficulty in swallowing, fever,
and passage of non bloody mucoid stool about 5
times.
• Vital signs: PR 108bpm, BP 124/80mmHg, PCV
24%(35-44.9%), Neutrophils 45%(54-62%),
lymphocytes 42%(20-40%).
• ASSESSMENT: Neutropenic sepsis and Anaemia

35. DRUGS DOSE
Pre-medication Iv Dexamethasone 4 mg stat
Iv Chlorpheniramine 4mg stat
Iv Ondansetrone 4mg stat
IV Rabeprazole 40 mg stat
Chemotherapy IV Epirubicin 170mg once in 3 weeks
IV Cyclophosphamide 1000 mg once in 3 weeks
IV 5FU 100 mg once in 3 weeks
Past medication History

36. Plan
Drugs Dose duration
01 Inj Ceftriazone 1g bd x 5/7
02 IV Metronidazole 500mg tds x 5/7
03 Inj Paracetamol 600 mg tds x 3/7
04 IV Normal saline 500ml 8 hrly
05 Tabs Ferrous Sulphate 200 mg bd 1/52
06 Tabs Vitamin C 200 mg tds x 2/52
Blood transfusion with 2 units of whole blood under
furosemide cover 20mg pre and post.

37. PHARMACISTROLEIN ADVERSEDRUGREACTION
OF CHEMOTHERAPY
• Pharmacists perform daily evaluations of medication
profiles to ensure each drug is dosed appropriately.
• Pharmacists education about expected adverse effects
of chemotherapy.
• Pharmacist should document all reported ADR and
follow to ensure resolution.
• Finally, pharmacists work closely with a patient’s
oncologist in order to achieve the best possible
outcome. And being able to manage a patient’s
supportive care plan, which often focuses on pain,
neuropathy, nausea, or vomiting

38. CONCLUSION
• Adverse effects are common in patients receiving
chemotherapy.
• Nausea and vomiting are common in patients with
cancer receiving cancer therapy and decrease quality
of life.
• Mucositis can cause pain and prevent sufficient oral
intake, leading to undernutrition and weight loss.
• chemotherapy agents may cause prolonged or
permanent alopecia,
• ADR can be prevented and treated through
administration of pre and post medications .

39. REFERENCE
• Anekha Antony, Juno J Joel, Jayaram Shetty,Neethu
Fathima Umar, Identification and analysis of adverse
drug reactions associated with cancer chemotherapy in
hospitalized patients, International Journal of
Pharmacy and Pharmaceutical Sciences2016, 8(7).
• Luanpitpong S, Rojanasakul Y. Chemotherapy induced
Alopecia. Available from: http://intechopen.com •
• Sonis S, Elting L, Keefe D, Peterson D, Schubert M,
Hauer-Jensen M et al. Perspectives on cancer therapy-
induced mucosal injury. Cancer. 2004;100(S9):1995-
2025. •

40. REFERENCE
• Shrestha S, Shakya R, Shrestha S, Shakya S. Adverse
drug reaction due to cancer chemotherapy and its
financial burden in different hospitals of Nepal. Int J
Pharmacovigilance 2017;2:1-7.
• Kumar S, Badrudeen B, Singh SP, Mohammad IK. A
prospective study of adverse drug reactions due to
platinum analogs – Chemotherapy in a tertiary care
hospital. Asian J Pharm Clin Res 2018;11:215-8.
• Angiji A. Adverse Drug Reactions related to Mortality
and Morbidity: Drug-Drug Interactions and Overdoses
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