Pharmacotherapy of Anaemia

By Nidhi MaheshwariDepartment of PharmacologyMIMER Medical CollegeTalegaon-Dabhade

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Sideroblastic

anaemia of chronic disease

Sickle cell

Megaloblastic

Iron Deficiency

Hemolytic

Thalasemia

Aplastic

IRON DEFICIENCY ANAEMIA

Preparations: ORAL (Preferred) / PARENTERAL

Ferrous sulphate (Fersolate): (200 mg tab = 60 mg elemental iron)• Most commonly used• LESS EXPENSIVE• Metallic taste

Ferric Hydroxy Polymaltose (100% iron content)• Better absorbed• Less bowel upset• EXPENSIVE

Ferrous gluconate, Ferrous fumarate, Ferrous succinate, carbonyl iron, Iron polysaccharide complex

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Commonly available oral combinations:

Autrin: Ferrous fumarate +B12 +Folic Acid Dumasules: Ferrous fumarate+ Vit B12+Folic acid+Vit B1+Niacinamide+Vit C+Vit B6 Polyron, Biofer, Polyfer: Ferric hydroxy polymaltose + Folic Acid Hbfast: Carbonyl iron + Folic Acid

TYPE DOSE

(mg)

Elemental Iron Content (mg)

SULPHATE(desiccated)

200 TDS 195

GLUCONATE 300 TDS 108

FUMARATE 200 TDS 198

SUCCINATE 300 OD 105

POINTS TO REMEMBER…

Do not use irrational hematinic combinations (shotgun preparations)

Consider ELEMENTAL iron content

Sustained release preparation: Irrational

Liquid preparations: Put on the back of the tongue and swallow

Empty stomach: better absorption but more side effects

Escalate the dose

Treatment continued: 3-5 months after attaining normal Hb: (Stores)

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METALLIC taste Teeth discoloration GI disturbances: Epigastric pain, nausea, vomiting, Black stools

Constipation (astringent action), diarrhea (reflect irritant action)

↑ Absorption: Vit C, meat, acidic pH (Fe+++ Fe ++)

↓ Absorption: Alkalies, antacids, phytates (maize, wheat), phosphates (egg yolk), tetracyclines, captopril, milk, calcium

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ADRs - Oral Iron

Factors affecting absorption

Indications for Parenteral Iron : Oral iron intolerance Severe malabsorption syndrome: Sprue, IBD Colostomy Severe deficiency with chronic bleeding With erythropoetin: in advanced kidney disease

Dose requirement: Iron req.(mg)=4.4 x body weight (kg) x Hb deficit (g/dl)

Response to oral or parental route is similar (about 0.7-1 gm% rise in Hb/wk)

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Available preparations for IM use:

IRON DEXTRAN (imferon, dexferrum) Old , HMW complex Can be given iv 25% added in calculated dose 100mg in 2 ml vial IM: Z-technique – deeply in gluteal region to avoid staining Sensitivity test is done before iv/im

Others Iron sorbitol-citric acid complex : not favoured now Iron sucrose and sodium ferric gluconate.

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Available preparations for IV use

FERROUS SUCROSE(uniferon, microfer)

New HMW complex Not im / sc as alkaline Do not give oral iron concurrently or till 5 days 100mg iv in 5 min max: 200 mg Once a day/week Low hypersensitivity reactions Preferred in pregnants

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FERRIC CARBOXY MALTOSE (ENCICARB)

New, Safest Never IM 100 mg/ml iv or

1000mg/100ml saline for infusion( not with glucose) for 15 min Mildest side effects Not used in children(<14 yrs): no safety data available Causes rapid ↑ in Hb

Others: HMW iron dextran (imferon) LMW iron dextran (casmofer) Iron saccharate, Ferric gluconate

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Adverse Drug Effects

IM Route:

Local toxicity pain permanent discoloration local inflammation and regional lymphadenopathy

Systemic toxicity Fever, headache, joint pains, flushing, tachycardia, chest pain, lymph node

enlargement

I V Route Same as IM but v rare

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IRON TOXICITY

ACUTE IRON POISONING

Common in children: (≥1 gm: Toxic)

Abdominal pain, vomiting, haematemesis, diarrhea,

acidosis, dehydration, cyanosis, convulsions, shock,

cardiovascular collapse

Death within 12-48 hrs (Metabolic acidosis: damage liver and/or brain)

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Treatment

Desferrioxamine: Iron chelator, a specific antidote, reduces mortality significantly

0.5-1 gm (50mg/kg) IM: repeat 4-12 hrly

10-15mg/kg/hr (max:75mg/kg) IV: if shock present

DTPA / Calcium Edetate

Vomiting, Gastric lavage with Sodium Bicarbonate

Diazepam in case of convulsions

Milk and egg yolk orally

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THALASSEMIA

Multiple blood transfusions can result in iron overload (CHRONIC IRON OVERLOAD) Desferrioxamine High affinity for Fe 3+

1 gm chelates 85 mg elemental iron

0.5-1mg/kg or 500 mg BD IM daily injection

With blood transfusion in thalassemia: 2gm desferrioxamine at 15mg/kg/hr by separate iv line slowly

Inexpensive and safer in long term

s/e: diarrhoea, hypotension, skin rashes, hearing loss, flushing,

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Desferasirox: not in use Deferiprone Oral Preferred in thalassemia: compliance is good Less affinity for Zn and Cu Better tolerated: Only GI upset

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MEGALOBLASTIC ANAEMIA

VIT B12

Hydroxocobalamine: 500,1000 µg/ml (im)

Cyanocobalamine: 100 µg/ml (im/sc): usually IM

Oral formulations: given for maintenance.

Hydroxocobalamine Slow absorption highly protein bound Slow excretion Long acting

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Dose : 500-1000µg IM daily on alternate day for 2 WEEKS followed by ONCE a month

Add folic acid and iron: reinstitution of brisk haemopoiesis unmask deficiency of

these factors

In neurological deficits

Maintenanace dose: every 1-2 weeks for 6 months before switching to monthly injections

Methylcobalamine : 1000-1500/µg/day orally

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FOLIC ACID

2-5mg/day (folvite) : orally with vitamin B12

Absorption: jejunum

For DNA synthesis, folic acid and Vit B12 both are required

Don’t give folate alone in megaloblastic anameia as only folic acid improves anaemia but worsens neurological deficit (Succinyl Co A from methyl malonyl CoA requires Vit B12)

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PROPHYLAXIS

3-10 µg/day Vit B12 orally in those at risk of developing deficiency

100 mg IRON and 500 μg FOLIC ACID is given for 100 days in pregnancy

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ANAEMIA OF CHRONIC DISEASE

Recombinant DNA erythropoietin

Available in 2000,4000,10000 IU in 1 ml prefilled syringes

Epoetin alpha T1/2 :4-13 hrs in renal failure patients, not cleared by dialysis Given IV thrice a week

Darbepoetin alpha Once a week, longer T1/2

Epoetin beta once in 2-4 weeks, iv or sc

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In patients treated with an Erythropoietin

Increase in reticulocyte count is seen in 10 days

Increase in hematocrit and Hb level is seen in 2-6 weeks

ADR: Allergic reactions, Pure red cell aplasia, hypertension, headache, nausea

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SICKLE CELL ANAEMIA

Antibiotics: Penicillin (initial 5 yrs): to prevent childhood illness

Malaria Chemoprophylaxis

Pneumococcal vaccination

Analgesics: NSAIDs and OPIOIDS

Blood transfusion

Hydroxyurea: Increases Hb F level, which interferes with the polymerization of HbS

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SICKLE CELL ANAEMIA

Drugs precipitating hemolysis:

Sulphonamaide, Dapsone Nitrofurantoin, Nalidixic acid, Flouroquinlones Primaquine, Quinine, Proguanil Salicylates, Methylene blue, Chloramphenicol

For prophylaxis: Folic acid may be given

G6PD patients are more prone.

In SIDEROBLASTIC ANAEMIA : Pyridoxine ( Vit B6) may be given

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REFERENCES

Sharma and Sharma Tripathi Katzung Harrison book of Medicine Internet

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THANK YOUJul 23, 2017

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