Dosing and Administration of P-trovite I.V Injection

Composition:-

Ampoule 1 each 5ml contains:

Thiamine HCl BP (Vit B1) 250mg

Pyridoxine HCl (Vit B6) 50mg

Riboflavine (Vit B2) 4mg

Ampoule 2 each 5ml contains:

Dexpanthenol 5mg

Dextrose (anhydrous) BP 1000mg

Nicotinamide BP 160mg

Ascorbic Acid as Sodium Salt 500mg

Dosing:

Adults:-

• For Acute Conditions: 1 pair IV Ampoules BD for 2-3 days followed by 1 pair IV Ampoules daily for 5-7days
• For Less Serious cases: 1 pair IV Ampoules OD for 3-7 days

Pediatrics:-

• Children <6years old: One tenth to one quarter adult dose
• Children 6 – 14 years: One third to two third adult dose
• 14 years and above: Dosing as adults

Administration:

• P-trovite is suitable for intravenous administration. 
• The content of each pair of ampoules (No 1 and No 2) should be mixed prior to injection. 
• Although compatible with commonly used intravenous solution it is recommended that P-trovite is diluted with 50ml to 100ml of either normal saline or 5% glucose solution 
• Given over a period of 30 minutes by slow injection. 

References:

1. P-trovite IV Injection Product Leaflet
2. Pabrinex Intravenous Package Leaflet
3. MyBlueBook

Clozapine induced Hypersalivation

• Many antipsychotics can cause hypersalivation, but it affects around 30% of patients taking clozapine (reported range 10-80%) (1,2,3). 
• It usually develops early in treatment, is often more prominent at night, and may reduce compliance (1,2,3,4).  
• The exact mechanism of clozapine-induced hypersalivation is unknown (2,3,5).  

Management

• If clozapine dose reduction (in appropriate patients) has not alleviated symptoms and an alternative antipsychotic is not an option, various pharmacological interventions have been used to manage hypersalivation (see Table 1 for treatment options). 
• Non-pharmacological strategies (e.g. sugarless chewing gum) have been recommended first-line but they are often ineffective (2,6,7).  
• A Cochrane Review to determine the clinical effects of pharmacological interventions (including traditional Chinese medicines) for clozapine-induced hypersalivation identified 15 trials. The authors concluded that “There are currently insufficient data to confidently inform clinical practice” 

Intervention Summary

• There is very limited comparative efficacy data to support the choice of one treatment for clozapine-induced hypersalivation over another.  In practice the potential risks and benefits of each option should be considered on an individual basis.   Some options have specific risks:
• Some agents may have additive hypotensive effects with clozapine (e.g. amitriptyline, terazosin, clonidine, lofexidine). Blood pressure should be monitored in these patients.
• Some may cause drowsiness (e.g. hyoscine, benzatropine, amitriptyline).
• Some may cause psychiatric side effects (e.g. depression with clonidine, agitation with trihexyphenidyl).
• Antimuscarinic agents will have additive side effects with clozapine. Cognitive function may also be impaired. Pirenzepine, glycopyrronium and ipratropium are believed to have little CNS penetration. Peripherally, anticholinergics can impair the gag reflex, compromising swallowing and increasing the risk of aspiration (23).
• Amitriptyline with clozapine may increase the risk of convulsions.
• Amisulpride with clozapine may cause hyperprolactinaemia.

Intervention Dosing and Outcomes:

Intervention	Report Descriptions [ref]	Dose of Intervention	Outcome and notes when used in clozapine patients
Antimuscarinics
Amitriptyline oral	(a) Case reports (n=4) [9] (b) Case report [10]	(a) 75-100mg per day. (b) 25mg at night.	Marked improvement.
			Beware additive side effects (e.g. fits, hypotension) [10,11].
Atropine eye drops 1% sublingually	(a) Case report [12] (b) Case reports (n=3) [6] (c) Case report [13]	(a) 1-2 drops in the morning. (b) 1 drop at night (plus top-up overnight dose of 1 drop in water prn (n=1)). (c) 2 drops bd.	(a) Resolution. (b) “Immediate relief”. (c) Resolution.
			Fast relief [6] but may not be sustained [14]; dropper can be hard to use with risk of accidental overdose [14]. Beware additive anticholinergic side effects [13] and bitter taste [15].
Hyoscine hydrobromide patch/oral	(a) Case reports (n=4) [15] (b) Case report [23] (c) Anecdotal [3,4]	(a) Patch (dose not given). (b) Patch 1.5mg every 72hrs. (c) 300 microgram tablet nocte increased to tds if necessary, sucked & swallowed.	(a) Improvement, including pts failing other treatments. (b) Persistent improvement. (c) Widely used in practice (e.g. KwellsÒ). Beware cognitive impairment, drowsiness.
Trihexyphenidyl (benzhexol) hydrochloride oral	(a) Non-comparative study (n=14) for 15 days [30] (b) Case report with 3 month follow-up [31]	(a) 5mg nocte, gradually increasing to maximum of 15mg nocte. (b) 6mg per day in divided doses.	(a) 11 pts improved; 3 pts did not. (b) Marked reduction in nocturnal hypersalivation and disappearance of daytime hypersalivation.
			May impair cognitive function [4].
Adrenoceptor Antagonists
Terazosin oral	Retrospective chart review (n=60) [16]	See benzatropine above.
			Beware additive hypotension [34].
Miscellaneous
Amisulpride oral	(a) Randomised, double-blind, placebo-controlled, cross-over study (n=20). 3 wks active treatment [38] (b) Open-label crossover trial vs. moclobemide (n=53) [39] (c) Case report; patient also on pirenzepine throughout [40] (d) Case report with 3 month follow-up [41] (e) Case report	(a) Amisulpride 100mg/day titrated up to 400mg/day over 1 week. b) Amisulpride 400mg/day vs. moclobemide 300mg/day. (c) Amisulpride up to 600mg daily with clozapine dose reduction. (d) Amisulpride 50mg/day. (e) Amisulpride 50mg/day increased over 2 weeks to 150mg/day.	(a) Statistically significant improvement. Prolactin levels rose in most patients and may need monitoring. (b) At 2 weeks, 39 improved, 1 worsened and 13 unchanged. Less effective than moclobemide. (c) Enabled reduced pirenzepine dose. Hyper-salivation markedly improved. (d) Significant improvement in hypersalivation. (e)  Marked improvement in daytime hypersalivation but night-time hypersalivation still present. Constipation and tachycardia reported.

References:

1. Medicines Information (UKMi) pharmacists for NHS healthcare professionals
2. Lexicomp

Administration of Olanzapine Orodispersible tablet

Available dose: 

Zyprexa Zydis 5mg & 10mg orodispersible tablet

Administration:

• The orodispersible tablet is a rapid-dispersing preparation to be placed in the mouth or alternatively to be dispersed in water or other suitable beverage for administration.

• This orodispersible tablet may be dispersed in a full glass of water or other suitable beverage (orange juice, apple juice, milk or coffee) immediately before administration.

• Olanzapine orodispersible tablets can be dispersed in water for administration orally or via a feeding tube.

References:

Zyprexa Zydis Product Leaflet

MyBlueBook

http://www.medicinesmanagementstoke.nhs.uk/documents/Crushing_Tabs_FAQs_December_2011_FINAL.PDF

Chemical Pleurodesis

• accepted palliative therapy for patients with recurrent, symptomatic malignant pleural effusions.
• Not all chemical agents have undergone direct comparison under similar conditions
• Talc was the most effective agent (success rate of 93%). The most commonly reported adverse effects were pain and fever
• In a systematic review, talc was the chemical agent that most frequently resulted in complete success (no recurrence of pleural fluid)
• based on the more recent guidelines (BTS Pleural Disease Guideline 2010) only talc is recommended as part of the therapy

Indication

• have significant symptoms that are relieved when pleural fluid is evacuated
• evidence of complete re-expansion of the lung without evidence of bronchial obstruction or fibrotic trapped lung

Doxycycline

• success rate of up to 80–85% in carefully selected patients
• Most studies have recommended the utilization of 500 mg of doxycycline mixed with 50–100 cm3 of sterile saline
• narcotic analgesic and/or conscious sedation is often recommended as pain is the most common complication

Administration

• If is receiving corticosteroid therapy, the drug should be stopped or the dose reduced if possible because of concerns of decreased efficacy of pleurodesis
• Most commonly, pleurodesis is performed via a standard tube thoracostomy
• intravenous narcotic analgesics and/or sedation are often recommended because of the pain associated with many sclerosing agents
• sclerosing agent of choice is then added to the chest tube, typically in a solution of 50–100 cm3 of sterile saline
• chest tube is then clamped for 1 h, without rotation of the patient being required. 
• The chest tube is then subsequently reconnected to 20 cm H2O suction. It is then recommended that suction be applied to the chest tube until the 24-h output from the chest tube is less than 150 cm3

References:

1. www.uptodate.com
2. https://www.brit-thoracic.org.uk/document-library/clinical-information/pleural-disease/pleural-disease-guidelines-2010/pleural-disease-guideline-quick-reference-guide/
3. https://www.thoracic.org/statements/resources/pleural-disease/1987

Comparison between Heparin, LMWH, Fondaparinux

• Anticoagulants are medications that are commonly called "blood thinners". 
• These medications do not actually thin the blood, but rather helps to prevent new blood clots from forming.

References:

1. Lexicomp
2. http://universityhealthsystem.com/files/10-Heparin

Phenytoin Compatibility

• Phenytoin has a pH in the range of 10 - 12.3. It will only stay in solution when the pH is considerably alkaline (about 10 - 12). 
• The mixing of phenytoin sodium injection with other drugs is not recommended

Compatible diluents	Incompatible diluent
0.9% sodium chloride Lactated Ringer's injections	Dextrose containing solutions as it provokes significant precipitation of phenytoin sodium injection via interruption of the cosolvent effect of propylene glycol. crystals were observed in all dextrose solutions after dilution. factors other than pH and cosolvent concentration may affect phenytoin stability in dextrose solutions.

Administration

• increased risk of adverse cardiovascular reactions associated with rapid administration, IV should not exceed 50 mg per minute in adults. 
• In pediatric patients, the drug should be administered at a rate not exceeding 1-3 mg/kg/min or 50 mg per minute, whichever is slower
• As non-emergency therapy, Phenytoin Sodium Injection should be administered more slowly as either a loading dose or by intermittent infusion. 
• Because of the risks of cardiac and local toxicity associated with IV phenytoin, oral phenytoin should be used whenever possible
• Because of the risk of local toxicity, IV Phenytoin Sodium Injection should be administered directly into a large peripheral or central vein through a large-gauge catheter. 
• Patency of the IV catheter should be tested with a flush of sterile saline. 
• Each injection of parenteral Phenytoin Sodium Injection should then be followed by a flush of sterile saline through the same catheter to avoid local venous irritation due to the alkalinity of the solution

Storage:

• Store at 20°-25°C, excursions permitted to 15°-30°C
• The diluted infusion mixture (Phenytoin Sodium Injection plus normal saline) should not be refrigerated. 
• If the undiluted parenteral Phenytoin Sodium Injection is refrigerated or frozen, a precipitate might form: this will dissolve again after the solution is allowed to stand at room temperature. 
• The product is still suitable for use. A faint yellow coloration may develop, however this has no effect on the potency of the solution.

References:

1. http://www.drugs.com/pro/phenytoin-sodium.html
2. https://www.medicines.org.uk/emc/medicine/27054
3. http://www.ncbi.nlm.nih.gov/pubmed/22223379

Management of Hyperthyroidism

Availability:

Tab Carbimazole 5mg

Tab Propylthiouracil 50mg

*Methimazole and Carbimazole are interchangeable (10mg Carbimazole = 6mg Methimazole)

Thionamides:

• Thionamide compounds inhibit thyroid hormone synthesis. 
• They are actively transported into the thyroid gland where they inhibit both the organification of iodine to tyrosine residues in thyroglobulin and the coupling of iodotyrosines

Methimazole (MMI)  

• MMI is usually preferred over PTU because it reverses hyperthyroidism more quickly and has fewer side effects.
• MMI requires an average of six weeks to lower T4 levels to normal and is often given before radioactive iodine treatment.
• MMI can be taken once per day.
• MMI is less likely than PTU to be associated with failure of radioiodine therapy when thionamides are given to normalize thyroid function before radioiodine treatment

Propylthiouracil (PTU) 

• PTU does not reverse hyperthyroidism as rapidly as MMI and it has more side effects.
• Because of its potential for liver damage, it is used only when MMI or carbimazole are not appropriate.
• PTU must be taken two to three times per the day.
• indications for PTU:
• - In pregnant women during their first trimester
• - In patients with life-threatening thyrotoxicosis or thyroid storm (because of PTU's ability to inhibit peripheral conversion of T4 to T3)
• - In patients with adverse reactions to MMI (other than agranulocytosis) who are not candidates for radioiodine or surgery

Antithyroid drugs during pregnancy 

• PTU used to be the drug of choice during pregnancy because it causes less severe birth defects than methimazole.
• But experts now recommend that PTU be given during the first trimester only. This is because there have been rare cases of liver damage in people taking PTU. 
• After the first trimester, women should switch to methimazole for the rest of the pregnancy.
• For women who are nursing, methimazole is probably a better choice than PTU (to avoid liver side effects).

Dosing	Carbimazole	PTU
Initial	Mild: 15mg  Moderate: 30-40mg  Severe: 60mg  [in divided doses (TDS)]	initially 300mg/day  400mg/day in severe HyperT occasionally can go up to 600-900mg/day [in 3 divided doses]
Maintenance	5-15 mg OD	100 – 150mg/day
Monitoring	Wide variation in sensitivity Recommended monthly for the first year, thereafter 3-6 monthly interval continued for approximately 12–18 months, then tapered or discontinued if the TSH is normal	Clinical improvement in 1-3 months Dosage reduction maybe needed to prevent HypoT Discontinuation considered after 12-18 months Monitored 2 monthly for 6 months thereafter till remission
Assessment	serum free T4 should be obtained about 4 weeks after initiation and dose adjusted accordingly. Serum T3 also may be monitored, since the estimated serum free T4 levels may normalize with persistent elevation of serum T3. Appropriate monitoring intervals are every 4–8 weeks until euthyroid levels are achieved with the minimal dose Once the patient is euthyroid, biochemical testing and clinical evaluation can be undertaken at intervals of 2–3 months. serum free T4 and TSH are required before treatment and at intervals after starting the treatment. Serum TSH may remain suppressed for several months after starting therapy and is therefore not a good parameter to monitor therapy early in the course

Beta Blockers

• beta-blocker should be started (assuming there are no contraindications to its use) in most patients as soon as the diagnosis of hyperthyroidism is made, even before determining the cause of the hyperthyroidism. 
• Beta-adrenergic blockade should be given to elderly patients with symptomatic thyrotoxicosis and to other thyrotoxic patients with resting heart rates in excess of 90 bpm or coexistent cardiovascular disease.
• leads to a decrease in heart rate, systolic blood pressure, muscle weakness, and tremor, as well as improvement in the degree of irritability, emotional lability, and exercise intolerance
• They should be continued until resolution of hyperthyroidism.
• relative/absolute contraindication - asthma or chronic obstructive pulmonary disease, severe peripheral vascular disease, Raynaud phenomenon, bradycardia, second or third degree heart block, and hypoglycemia-prone diabetics in whom the early warning symptoms of hypoglycemia may be masked
• Patients with relative contraindications to beta blockade may better tolerate beta1-selective drugs such as atenolol or metoprolol

References:

1. My Blue Book
2. Lexicomp
3. Medscape
4. http://www.uptodate.com
5. https://www.aace.com/files/hyper-guidelines-2011.pdf

What is Ocular Gyric Crisis(OGC) and the use of Procyclidine

Oculogyric crisis is an acute dystonic reaction of the ocular muscles characterized by bilateral dystonic elevation of visual gaze lasting from seconds to hours. This reaction is most commonly explained as an adverse reaction to drugs such as antiemetics, antipsychotics, antidepressants, antiepileptics, and antimalarials.

Initial symptoms include restlessness, agitation, malaise, or a fixed stare followed by the more characteristically described maximal upward deviation of the eyes in the sustained fashion. The eyes may also converge, deviate upward and laterally, or deviate downward. The most frequently reported associated findings are backwards and lateral flexion of the neck, widely opened mouth, tongue protrusion, and ocular pain. A wave of exhaustion follows some episodes. The abrupt termination of the psychiatric symptoms at the conclusion of the crisis is most striking.

Causes or triggering factors in OGC include: neuroleptics, amantadine, benzodiazepines, carbamazepine, chloroquine, cisplatin, diazoxide, influenza vaccine, levodopa, lithium, metoclopramide, nifedipine, pemoline,  phencyclidine, reserpine, tricyclics, postencephalitic Parkinson's, Tourette's syndrome, multiple sclerosis, neurosyphilis, head trauma, bilateral thalamic infarction, lesions of the fourth ventricle, cystic glioma of the 3^rd ventricle, herpes encephalitis, and juvenile Parkinson's

Treatment in the acute phase involves reassurance and treatment with Cogentin (IV or MI)  and/or Benadryl (diphenhydramine) and/or Diazepam or lorazepam. Maintenance therapy with oral forms of the above medications or amantadine  are indicated in more chronic recurrent cases. According to a journal published, procyclidine 5-10mg stat can be given for acute dystonic reaction. From Bluebook, Procyclidine can be given 5 – 10mg stat as a single dose, may repeat after 20mins if needed. (Max:20mg/day)

References:

http://www.biomedcentral.com/content/pdf/1757-1626-2-186.pdf

http://www.cmdg.org/Movement_/drug/Oculogyric_Crisis/oculogyric_crisis.htm

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964159/

MyBlueBook

Calcium Gluconate dosing for hypocalcemia in Pediatrics

Calcium Gluconate 10% / 10ml

1ml = 8.9 mg of calcium

1g of Calcium gluconate salt = 93mg of elemental calcium

1ml = 0.22 mmol

1) Dosing:

• For hypocalcemia (dose depends on clinical condition and serum calcium level)

Intravenous: 

Frankshaan	0.5 ml/kg  (10% calcium gluconate) (Max: 20 ml)                                       or 4.45 mg/kg (in elemental calcium) (Max: 178 mg)
Drugs.com	4.65 mg/kg to 11.6 mg/kg (dosing in elemental calcium)
BNF for Children	For Fast correction 0.5 ml/kg  (10% calcium gluconate) (Max: 20 ml) via slow infusion over 5-10 mins For Maintenance 4.5 ml/kg over 24 hrs

2) Administration:

• Oral

Administer with plenty of fluids with or following meals. The 10% calcium gluconate injection may be administered orally in young pediatrics.

• IV

It is usually administered slowly; not exceeding 200mg/min except in emergency situations through a small needle into a large vein in order to avoid too rapid increase in the serum calcium and extravasation. It is recommended that Calcium Gluconate injection be diluted with either 0.9%NaCl, 5% Glucose in Water, Lactate Ringers Injection or 5% glucose in 0.9%NaCl when intended to be administered as an IV infusion.

References:

1. http://www.drugs.com/dosage/calcium-gluconate.html
2. Frankshaan 16th Edition 2014
3. Lexicomp
4. BNF For Children 2014

Interaction: Shiitake Mushroom and Warfarin

Product

• preparation is called Lentinus edodes mycelium extract (LEM). 
• LEM is rich in polysaccharides and lignans

Rationale

• Taken both as vegetable and also exist in the form of supplementation
• is used for boosting the immune system, loweringbloodcholesterol levels, treating prostate cancer, and as an anti-aging agent.
•  Lentinan, derived from shiitake (Lentinus edodes), has been injected as an adjunct treatment for cancer and HIV infection, although currently high quality human scientific evidence is lacking for many proposed indications

Vitamin K Content

• Most mushroom (shiitake, white, Portabella, etc) has very small amount to no vitamin K
• Thus it does not cause reduction in INR

Blood Thinning Properties

• Several products containing mushroom extracts have not established any relationship with warfarin
• In a laboratory study, essential oil from shiitake inhibited platelet aggregation and therefore may increase the risk of bleeding 
•  Lentinan, the polysaccharide derivative of shiitake, may cause mildly abnormal blood cell counts (thrombocytopenia)
• Lentinus edodes has been shown to inhibit cyclooxygenase activity in laboratory study 
• Mushroom polysaccharides, especially beta-glucans such as lentinan from Lentinus edodes, may interfere with the way the liver breaks down certain drugs (through the suppression of CYP1As) (minor pathway in warfarin metabolism)

Recommendation

• Moderate intake vegetable should not cause much fluctuations in INR
• However, if taken in the form of supplementation consistently, may consider to review patient after a short period to assess changes in INR (expeced to increase slightly)

References

1. http://www.shopnaturesoasis.com/ns/DisplayMonograph.asp?storeID=0E75F5E3C2DF416C896EF03680134ECB&DocID=bottomline-shiitake
2. http://www.rxlist.com/maitake_mushroom-page3/supplements.htm
3. http://www.healthaliciousness.com/articles/low-vitamin-k-foods-for-a-coumadin-warfarin-diet.php
4. http://www.researchgate.net/profile/Prakash_Bisen/publication/44619902_Lentinus_edodes_a_macrofungus_with_pharmacological_activities/links/09e414ff4f0ceb5e9d000000.

Iron deficiency in CKD

• Iron deficiency arising from multiple factors directly or indirectly related to kidney dysfunction.
• Dietary intake of iron inadequate due to poor appetite or advice to consume a low-protein diet, 
• Possibly exacerbated by chronic iron loss from repeated intestinal bleeding resulting from CKD-related abnormal platelet function. 
• The chronic inflammatory status of many CKD patients induces increased hepcidin synthesis, which in turn inhibits uptake of dietary iron by enterocytes and export of iron from enterocytes, macrophages, and storage cells. 
• These effects restrict the availability of iron for hemoglobin synthesis and other functions. 
• In patients undergoing hemodialysis, regular blood loss compounds these problems, but even in nondialysis CKD (ND-CKD), iron is estimated to affect over half of all adults with CKD Stage 3 or 4.
• Prevalent in CKD patients receiving treatment with an erythropoiesis-stimulating agent (ESA) due to the marked increase in the demand for iron, and is a major cause of nonresponsiveness to ESA therapy with associated negative implications for anemia correction and healthcare costs

Target

• a minimum serum ferritin level above 100 ng/ mL 
• a minimum transferrin saturation (TSAT) greater than 20% in ESA-treated CKD patients

References:
http://www.ncbi.nlm.nih.gov/pubmed/23314137

Lugol’s Solution in Thyroid Storm

Contains 100 mg potassium iodide and 50 mg iodine; provided 8 mg iodide/drop, 20 drops per ml
Mechanism of Action:

• Lowering circulating (thyroid Hormone) TH’s levels is achieved either preventing TH’s synthesis or blocking TH’s release. 
• Both propylthiouracil (PTU) and methimazole (MMI) inhibit the synthesis of new TH interfering with the iodide oxidation and organification process. The effect is delayed in 3-4 days. 
• Inorganic iodine preparations block the TH’s release by inhibiting thyroglobulin protheolysis (Wolff-Chaikof effect).
•  The iodine therapy must be administered after successful inhibition of new TH’s synthesis is achieved (2-3 h after PTU or MMI administration) since the use of iodine alone would lead to enhance intraglandular TH’s stores and possible worsening of the thyrotoxic crisis (escape phenomenon)

Dose

• 4-8 drops every 6-8 hours; begin administration ≥1 hour following the initial dose of either propylthiouracil or methimazole OR
• 0.3 mL of strong iodine solution (Lugol's solution) 3 times daily (range, 0.1 to 0.9 mL daily) OR
• 10-20 drops 8 hourly (Sarawak Handbook of Medical Emergencies) OR
• In the UK, many experts prescribe 1 ml of Lugol's solution orally every 6 hours.

Recommendation

• Most guides are consistent with the lower drops of Lugol’s Solution (up to 10 drops). The higher amount (20 drops) Is seen in the management of thyroid storm in pregnant patient. 
• None of the guidelines recommended any duration  of action. 
• Iodides can be discontinued after initial improvement

References:

1. http://www.drugs.com/ppa/iodine.html
2. https://www.medicines.org.uk/emc/medicine/25154
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475282/
4. http://www.europeanreview.org/wp/wp-content/uploads/158
5. http://www.womenshealthsection.com/content/obsmd/obsm015.php3

Maximum dose of Neurobion

Content:
Thiamine 100mg , Pyridoxine 200mg, Cyanocobalamin 200mcg
Recommended dose:

• 1 tablet 3 times daily
• No information on maximum dose
• Maximum dosing based on individual components

Thiamine 

• usual dose of thiamine is 5-30 mg daily in either a single dose or divided doses for one month.
• The typical dose for severe deficiency can be up to 300 mg per day

Pyridoxine 

• 20-50mg TDS (B6 deficiency)
• 100-400 g daily in divided doses (sideroblastic anaemia)
• Long term use in doses above 200mg has been associated with neuropathy

Cyanocobalamin

• Bioavailability is approximately 25%
• Adults: 50-6000 mcg/ day

References:
MOH Drug Formulary
https://ods.od.nih.gov/factsheets/Thiamin-HealthProfessional/

http://www.drugs.com/dosage/thiamine.html

http://www.drugs.com/dosage/pyridoxine.html

http://www.drugs.com/ppa/cyanocobalamin-vitamin-b12.html

Iron Dose Calculation & Administration

Tab Ferrous Fumarate 200mg (elemental iron 66mg) 
Absorption : 10-30% (iron deficient), 5-15% (non-iron deficient)
Ferric Hexacyanoferrate Citrate, FAC (80mg elemental iron/5ml)
Oral Therapy

• The usual recommended dose in adults is 100–200 mg of elemental iron daily, in 2 to 3 divided doses.
• Lower doses may be as effective and better tolerated.
• After therapeutic doses of oral iron, reticulocytosis should occur within 72 hours, and Hb levels should rise by about 20 g/L every 3 weeks. 
• Oral iron should be continued for 3 months after anaemia has been corrected to replenish stores.
• Inadequate response to oral iron therapy can be due to a number of factors with more than one often being involved

Intravenous therapy
IV Iron Sucrose 100mg/5ml (20mg elemental iron /ml)
Calculating total body iron deficit 

• The patient’s total body iron deficit (cumulative amount of iron required to replete body iron stores) is NOT the same as the allowable iron dose per infusion which is DIFFERENT for each product.

Ganzoni formula: 
Total body iron deficit/cumulative iron dose (mg) = body weight (kg) x (target Hb – actual Hb in g/L) x 0.24* + iron depot (mg)**
*The factor 0.24= 0.0034 x 0.07 x 1,000:
*(factor is 2.4 if Hb level is measured in g/dL)
For this calculation the iron content of haemoglobin = 0.34%, blood volume = 7% of the bodyweight, and 1,000 is the conversion from g to mg
**Iron depot:
<35kg : iron depot = 15mg/kg body weight
>35kg : iron depot = 500mg

• For example a 70 kg female with Hb 80 g/L has an iron deficit of: 70 x (150 – 80) x 0.24 + 500 = 1676 mg

Administration
Infusion

• Venofer must be diluted only in sterile 0.9% m/V sodium chloride solution: 

1. 100 mg iron (5 ml Venofer) in maximum 100 ml sterile 0.9% m/V sodium chloride solution 
2. For stability reasons, dilutions to lower Venofer concentrations are not permissible. 

• As infusion, maximum tolerated single dose per day given not more than once per week: 

1. Patients above 70 kg: 500 mg iron (25 ml Venofer) in at least 3 ½ hours 
2. Patients of 70 kg and below: 7 mg iron / kg body weight in at least 3 ½ hours 

• Dilution must take place immediately prior to infusion the solution should be administered

1. 100 mg iron ( 5 ml Venofer) in at least 15 minutes 
2. 200 mg iron (10 ml Venofer) in at least 30 minutes 3 
3. 300 mg iron (15 ml Venofer) in at least 1 ½ hours
4.  400 mg iron (20 ml Venofer) in at least 2 ½ hours 

Intravenous injection:

1. Venofer can be administered undiluted by slow intravenous injection as follows: 

• 100 mg iron (5 ml Venofer) in at least 5 minutes 
• 200 mg iron (10 ml Venofer) in at least 10 minutes. 

Injection into dialyser: 

• Venofer may be administered during a haemodialysis session directly into the venous limb of the dialyser under the same conditions as for intravenous injection

References:

1. http://www.blood.gov.au/system/files/documents/iron-product-choice-dose-calc-adult
2. http://www.medsafe.govt.nz/profs/datasheet/v/venoferinf
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767254/
4. iron deficient Calculator
5. http://reference.medscape.com/calculator/iron-replacement-parenteral-dosing

Post Splenectomy Prophylaxis

When to Give

Elective Splenectomy 

• Vaccination should take place at least two weeks before the planned splenectomy. 
• Vaccination to be optimal if performed 4-6 weeks before the splenectomy but also advises that if the splenectomy needs to be performed more urgently it should not be deferred to allow this 4-6 weeks interval to be achieved  

Emergency/Unplanned Splenectomy 

• Vaccine is most effective if performed at least 14 days after surgery

Influenza Vaccination:

• An annual influenza vaccine of the appropriate type is recommended. 
• Some guidelines suggest giving influenza vaccine either pre-splenectomy (if planned) or after emergency splenectomy (or as soon as possible after a patient is identified as being hyposplenic).

Recommendations:

Antibiotic Prophylaxis

IM Benzathine Penicillin Prophylaxis

• based according to our Thalassaemia CPG, IM Benzathine Penicillin 3-4 weekly can be given as an alternative
• Although monthly administration of 1.2 MU of intramuscular benzathine penicillin is recommended as an alternative to oral penicillin V (cellulitis and rheumatic fever prophylaxis), based on management of asplenia patient, only oral antibiotics are recommended
• for those not tolerating orally, Benzylpenicillin (Penicillin G) 600mg iv bd (or clarithromycin 500mg iv bd if allergic to penicillin) can be given till patient is able to take oral antibiotics
• until the patient can take oral medication,

References:

1. http://www.surgicalcriticalcare.net/Guidelines/splenectomy_vaccines
2. http://www.racgp.org.au/download/documents/AFP/2010/June/201006jones
3. http://www.gloshospitals.nhs.uk/SharePoint1/Procedures%20and%20Guidelines/A0326
4. CPG Management of Transfusion Dependent Thalassaemia 2009

Paraquat Toxicity- update 2

A) MANAGEMENT OF MILD TO MODERATE TOXICITY 

• Following decontamination, supportive care is the mainstay of care. 
• Glucocorticoids (dexamethasone 5 mg IV every 6 hours) with cyclophosphamide (15 mg/kg) in 200 mL of D5NS over 2 hours daily for 2 days) should be administered to a patient at risk of moderate or severe pulmonary toxicity and those with symptoms consistent with moderate to severe toxicity. 

B) MANAGEMENT OF SEVERE TOXICITY 

• Following decontamination, supportive care is the mainstay of care. 
• Aggressive fluid resuscitation should aim to replace fluid losses and maintain renal blood flow in order to augment toxin elimination. 
• Glucocorticoids (dexamethasone 50 mg IV every 6 hours until PaO2 is greater than 80 mmHg then gradual taper) with cyclophosphamide (15 mg/kg in 200 mL of D5NS over 2 hours daily for 2 days) should be administered. 

C) DECONTAMINATION 
PREHOSPITAL: DERMAL EXPOSURE: 

• Remove contaminated clothing and wash thoroughly with soap and water. 

HOSPITAL: DERMAL EXPOSURE: 

• Remove contaminated clothing and wash thoroughly with soap and water. 
• Care should be taken not to abrade the skin because disruption of the stratum corneum may lead to increased toxin absorption. 

INGESTION: 

• Patients with a recent ingestion should receive nasogastric suction with a soft, small gauge tube in order to remove any liquid remaining in the stomach. 
• After gastric decontamination with an NG tube, aggressive antiemetic therapy should be provided to facilitate administration of the adsorbent agent. 
• Patients with an ingestion should be given one of the following: 
• ACTIVATED CHARCOAL: 
• ADULT: 50 to 100 g; CHILD: 1 g/kg)
• BENTONITE CLAY (7% solution): 
• ADULT: 100 to 150 g; CHILD less than 12 years of age: : 2 g/kg; or 
• FULLER'S EARTH (30% solution) 
• ADULT: 100 to 150 g; CHILD less than 12 years of age: 2 g/kg). 
• AVOID: Gastric lavage is NOT recommended because of corrosive injuries imparted by the solution itself may increase the risk of iatrogenic perforation. 
• OCULAR EXPOSURE: Copious irrigation with saline or sterile water and ophthalmology consultation. 

D) AIRWAY MANAGEMENT 

• Airway support should be considered for patients with severe CNS depression or those at risk of aspiration. 

E) ANTIDOTE 

• There is NO antidote available for paraquat toxicity. 

F) HYPOTENSION 

• Treat hypotension with isotonic fluid resuscitation until the patient is felt to be euvolemic, followed by addition of vasopressors in standard doses. 
• Cardiac dysrhythmias should be treated according to typical ACLS protocols. 

G) OXYGEN THERAPY 

• In general, oxygen therapy should be withheld until the PaO2 is below 50 mmHg, because supplemental oxygen may lead to increased production of oxygen free radicals and increased pulmonary toxicity. 
• Lung transplantation may be considered late in the course for patients with severe pulmonary injury and subsequent hypoxia after the serum paraquat concentration is zero. 

H) NAUSEA AND VOMITING

• Treatment is supportive with care to ensure replacement of gastrointestinal fluid losses. Antiemetics should be provided liberally (Ondansetron: Adult: 4 to 8 mg IV; Children: 0.15 mg/kg IV). Stress ulcer prophylaxis should be provided, since patients are likely to have corrosive injury due to the ingestion. 

I) ACUTE TUBULAR NECROSIS 

• Renal injury is due to acute tubular necrosis and is largely reversible. Adequate fluid resuscitation is key to limiting secondary renal injury. 
• Hemodialysis for oliguric renal failure is occasionally necessary as a temporizing measure until renal function improves. 

J) SEIZURES 

• Seizures should be treated with benzodiazepines. 

K) ENHANCED ELIMINATION 

• In general, NO method of enhanced elimination (ie, dialysis, hemofiltration, or hemoperfusion) has been effective at improving survival. 
• However, due to the inherent toxicity of the agent, the rapid progression of renal injury, and the lack of effective interventions, hemoperfusion, hemodialysis or hemofiltration is recommended early in the course of significant ingestions to decrease serum paraquat concentrations. 
• Hemoperfusion, if done during the first 2 hours of exposure, is the preferred method of extracorporeal elimination, if available. 

F) IMMUNOSUPPRESSIVE THERAPY 

• The combination of corticosteroids and cyclophosphamide has been shown in a randomized, controlled study to reduce mortality in severe paraquat poisoning (Lin et al, 2006). 
• The protocol used in one study was as follows (Lin et al, 2006): 
• Gastric lavage followed by administration of 1 gram/kilogram of activated charcoal in 250 milliliters of magnesium citrate in patients presenting within 24 hours of ingestion. 
• Two 8 hours courses of activated charcoal hemoperfusion within 24 hours of paraquat ingestion. 
• After hemoperfusion, administer intravenous cyclophosphamide 15 milligrams/kilogram/day in 200 ml D5NS infused over 2 hours for two consecutive days. Also administer 1 gram methylprednisolone in 200 milliliters D5NS infused over 2 hours daily for 3 consecutive days. 
• After the initial pulse therapy, administer dexamethasone 5 milligrams intravenously every 6 hours until PaO2 is 80 mmHg (11.5 kPa) or greater. 
• If PaO2 < 60 mmHg (8.64 kPa), repeat intravenous methylprednisolone 1 gram in 200 milliliters D5NS infused over 2 hours daily for 3 consecutive days. If WBC > 3000/m(3) and it has been 2 weeks since the initial pulse of cyclophosphamide, repeat intravenous infusion of cyclophosphamide 15 milligrams/kilogram in 200 milliliters D5NS infused over 2 hours as a single dose. 
• Then continue intravenous dexamethasone 5 milligrams every 6 hours until PaO2 is 80 mmHg (kPa 11.5) or greater. Then reduce dexamethasone dose gradually. 

NAC Regimen

• The New Zealand Poison Centre (TOXINZ) on the other hand suggested NAC for the treatment of paraquat poisoning as follows:
• The use of N-acetylcysteine for bipyridylium herbicide poisoning has not been proven effective.
• N-acetylcysteine is recommended following any moderate to severe exposure to bipyridylium herbicides. It is considered unlikely to alter the course of those suffering fulminant poisoning where death occurs within one week from multiple organ failure.
• Dose and Administration
• CHILD
• As yet to be determined, but likely the same as the adult regimen
• ADULT
• Loading dose:
• 150 mg/kg N-acetylcystein in 200 mL 5% dextrose in water infused IV over 15 minutes
• Continued infusion: 300 mg/kg N-acetylcysteine in 1,000 mL 5% dextrose in water infused IV over 24 hours

reference:

1. Pusat Racun Negara
2. Micromedex
3. New Zealand Poison Centre (TOXINZ)