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PHARMACOVIGILANCE CASE

PRESENTATION

Dr. Pranesh PawaskarFirst Year ResidentDept. of PharmacologyL.T.M.M.C. Sion, Mumbai 400022Date : 06/01/2017

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Prednisolone induced vaso - occlusive crisis

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case• Male

• 12 Years

• K/C/O Sickle Cell Anaemia + Thalassaemia

Major.

• Chief Complaints – 4 Episodes Of Convulsion

- Severe Pain In Lower Limbs

&

- Altered Consciousness

-

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Course of reactionPatient is a k/c/o sickle cell anaemia +

thalassemia major since childhood (family history +ve)

.

.Requires periodic blood transfusion

.

.Patient got admitted with

• Excruciating pain in lower limbs (L>R) (since 2/12/16),

• 4 episodes of Convulsions (4/12/16),• Altered Consciousness

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Course of reactionOn 4/12/16

Admitted to Sion hospital Under Dr.MVM in Ward 37

.

.Patient has chronic bone pain but was

exaggerated since one monthOn 6/11/16

For which he was started with T. Prednisolone @ 2 mg/kg/dayPt was continuously taking

T. Prednisolone 60 mg in two divided doses daily

( tapered to 30mg/kg on 4/12/16, 15mg/kg on 12/12/16 and 10mg/kg on 19/12/16 )

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Course of reaction

Treatment at Sion Hospital –

• i.v. fluids. (N.S. with 5% Dextrose).

• Cap. Hydroxyurea 400 mg.

• Inj. Paracetamol 500 mg SOS.

• Inj. Pantoprazole 40mg O.D.

• Inj. Ondansetron 8 mg B.D.

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Investigations• MRI lower limbs –

• s/o Ischaemic changes Left > right.

• MRI Brain –

• S/o Normal vasculature.

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Seriousness of reaction

• Reaction was SERIOUS as it Required

Hospitalisation of patient.

• Patient Recovered And Discharged on 20/12/16

• Diagnosis- Steroid Induced Vaso-occlusive

Crisis.

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Causality assessment

• According to Naranjo Scale score is 4

POSSIBLE

BECAUSE -1) Reasonable time-event relationship.2) De-challenge response positive.

POSSIBLE

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VASO – OCCLUSIVE CRISIS

• The Vaso-occlusive Crisis is caused by

sickle-shaped red blood cells that obstruct

capillaries and restrict blood flow to an

organ.

• Resulting in Ischaemia, Pain, Necrosis, and

often Organ Damage.

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SICKLE CELL DISEASE• Inherited blood disorder.

• Inheritation of 2

abnormal copies of Hb

gene one from each

parent.

• Caused by a mutation in

the beta-globin gene that

changes the sixth amino

acid from glutamic acid

to valine.

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SICKLE CELL DISEASE• It results in an abnormal

haemoglobin found in red

blood cells.

• This leads to a rigid,

sickle-like shape under

certain circumstances.

• Problems in sickle cell

disease typically begin

around 5 to 6 months of

age.

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SICKLE CELL DISEASE• A number of health problems may develop,

such as attacks of pain ("Sickle-cell

Crisis"), Anaemia, Bacterial Infections,

And Stroke.

• Long term pain may develop as people get

older.

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CAUSES OF VASO-OCCLUSIVE CRISIS

• Infections• Severe dehydration• Exposure to very high or very low temperatures, or rapid change in temperature.• High altitudes, where oxygen levels are low• Drugs

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PREDNISOLONE

• Prednisolone is a Steroid Medication used to

treat certain types of Allergies, Inflammatory

Conditions, Autoimmune Disorders

• Some of these conditions include

Adrenocortical Insufficiency, High Blood

Calcium, Rheumatoid Arthritis, Dermatitis, Eye

Inflammation, Asthma, And Multiple Sclerosis

• It is use by oral,intravenous injection, as a

skin cream, and as eye drops.

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PHARMACOLOGY

• Absorption duration – 18 -36

hr

• Protein bound 65-91 %

• Vd = 0.22 – 0.7 L/kg

• Extensively metabolised in

liver

• Half – Life = 3 hr

• Excretion = Urine

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USES

ADULT

• Rheumatoid Arthritis

• Multiple Sclerosis

• Acute Exacerbation of

COPD

• Bells Palsy

PAEDIATRIC

• Inflammation

• Acute Asthmatic

Exacerbation

• Nephrotic Syndrome

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ADVERSE EFFECTS

• Acne

• Adrenal Suppression

• Diabetes Mellitus

• Menstrual Irregularity

• Myopathy

• Neuritis

• Peptic ulcer

• Osteoporosis

• Psychosis

• Weight Gain

• Seizures

• Vertigo

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INTERACTIONS

• Mifepristone

• Live Vaccines

• Ketoconazole, Cimetidine

• Erythromycin, Carbamazepine, Rifampin

• Aceclofenac, Aspirin, Ibuprofen

• Heparin, Liraglutide

• Serolimus, Tacrolimus

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MECHANISM BEHIND VASO-OCCLUSIVE CRISIS

• The potential mechanism(s) involved in systemic

steroid-induced vaso-occlusion is unclear.

• Bone marrow infarction and likely associated

Fat Embolism may have contributed to the

adverse events.

• There is a well-documented association of

corticosteroid therapy and Bone Marrow

Necrosis.

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Mechanism Behind Vaso-occlusive Crisis

• Additionally, we speculate that Steroid-induced

Leucocytosis could be another potential factor.

• High WBC counts in steady state have been linked

to worse clinical course, and Polymorphonuclear

Leukocytes appear to play an active role in vaso

-occlusive crises.

• Granulocytes or Stimulating Agents have been

associated with the apparent triggering of

sickle-related crises and multiorgan failure in

isolated case reports.

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MECHANISM BEHIND VASO-OCCLUSIVE CRISIS

1. A patient with Hemoglobin-S/C Disease who

developed fatal sickle cell crisis after

receiving Granulocyte Colony Stimulating Factor

was also on daily Dexamethasone.

2. Severe complications were observed in ten of

the 16 patients (62%). Eight patients

experienced severe vaso-occlusive events (VOE)

within the 2 months following the initiation of

steroid treatment. Frequency of painful crises

(2X),severe pain episode, Acute Chest Syndrome,

stroke,& Renal infarction.

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Management of vaso-occlusive crisis

• For Milder Crisis, manage on Nonsteroidal

Anti-inflammatory Drugs (Diclofenac or

Naproxen.)

• For more Severe Crises, most patients require

inpatient management for Intravenous Opioids;

Patient-controlled Analgesia Devices are

commonly used in this setting.

• Vaso-occlusive crisis involving organs such as

the Penis or Lungs are considered an emergency

and treated with Red-blood Cell Transfusions.

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MANAGEMENT OF VASO-OCCLUSIVE CRISIS

• Painful Crises are treated with Hydration,

Analgesics, & Blood Transfusion; Pain

management requires Opioid Administration at

regular intervals.

• Vigorous hydration.

• Bone pain may respond as well to Ketorolac

(30–60 mg initial dose, then 15–30 mg every

6–8 h).

• Morphine (0.1–0.15 mg/kg every 3–4 h) should

be used to control severe pain

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MANAGEMENT OF VASO-OCCLUSIVE CRISIS

• Many crises can be managed at home with oral

hydration and oral analgesia.

• Most crises resolve in 1–7 days.

• Use of blood transfusion should be reserved

for extreme cases, transfusions do not

shorten the duration of the crisis.

• The most significant advance in the therapy

of sickle cell anaemia has been the

introduction of Hydroxyurea as a mainstay of

therapy for patients with severe symptoms.

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MANAGEMENT OF VASO-OCCLUSIVE CRISIS

• Hydroxyurea (10–30 mg/kg per day) increases

fetal haemoglobin.

• Exert beneficial affects on RBC Hydration,

Vascular Wall Adherence, and Suppression of the

granulocyte and Reticulocyte count.

• Maintain a white cell count between 5000 and

8000/L.

• White Cells And Reticulocytes may play a major

role in the pathogenesis of sickle cell crises,

their suppression may be an important benefit of

hydroxyurea therapy.

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CONCLUSION

• The present case emphasizes the poor tolerance

of steroids in SCD patients

• Review of literature suggest that systemic

corticosteroids play an important role in the

development of severe adverse events in some

patients with SCD.

• With better understanding of risk factors,

prevalence and pathophysiology of these

events, systemic corticosteroids should be

used with caution in this population.

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CONCLUSION

• Prompt Red-cell Transfusion or Exchange

Transfusion along with aggressive clinical

management can improve the clinical outcome

in severe cases.

• Red blood cell transfusions given with

corticosteroid therapy in SCD patients may

attenuate the risk of such complications.

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