Refeeding Syndrome

In my 2-week attachment at the surgical ward, I came across quite a few Total Parenteral Nutrittion (TPN) cases. The calories required by patient is calculated based on 20 kcal/kg then titrate up by 5 kcal/kg. The reason for this is to prevent refeeding syndrome.


Refeeding syndrome is the potentially fatal shift in fluids and electrolytes that may occur in malnourished patients receiving artificial feeding (enterally or parenterally). It was first described inFar East prisoners of ward in WWII. Eating again after prolonged period of starvation seemed to precipitate cardiac failure.

Prolonged Fasting
Muscles & other tissues: decrease use of ketone bodies, use fatty acids as main energy source

Increase in blood levels of ketone bodies stimulate the brain to use ketone bodies (instead of glucose) as its main energy source

Liver decreases rate of gluconeogenesis, thus preserving muscle protein

Several intracellular minerals become severely depleted during the period of prolonged starvation. However, serum concentrations of these minerals (including phosphate) may remain normal because they are mainly in the intracellular compartment.

Refeeding
Sudden shift from fat to carbohydrate metabolism occurs and secretion of insulin increases

Insulin stimulates glycogen, fat & protein synthesis, which require minerals such as phosphate (Po4) & Magnesium (Mg) and cofactors such as thiamine.

Insulin stimulates the absorption of K into the cells through Na-K-ATPase symporter, which also transports glucose into the cells.

Mg and PO4 are also taken up into the cells, water follows by osmosis.

These result in a decrease in the serum levels of PO4, Mg, K, all of which are already depleted.

This phenomenon usually occurs within 4 days of starting to feed again.


How can refeeding syndrome be prevented?
Identify patients with high risk of developing refeeding syndrome, and the management that follows suit is illustrated in the figure below.

Patients with high risk of developing refeeding syndrome-
1. Patients with 1 or more of the following:

• BMI <16>
• Unintentional weight loss > 15% in the past 3-6 months
• Little or no nutritional intake for > 10 days
• Low levels of K, Mg, or PO4 before feeding

2. Patients with 2 or more of the following:

• BMI > 18 kg/m2
• Unintentional weight loss > 10% in the past 3-6 months
• Little or no nutritional intake for > 5 days
  
• History of alcohol misuse or drugs, including insulin, antacids, chemotherapy or diuretics

The NICE guidelines recommend that refeeding should start at a maximum of 0.021 MJ/kg/day (10 kcal/kg/day), with cardiac monitoring due to the risk of cardiac arrhythmias.



References
1. Hearing SD. Refeeding syndrome is underdiagnosed and undertreated, but treatable. BMJ 2004; 328 (7445): 908-909. Available from: URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC390152/

2. Mehanna HS, Moledina J and Travis J. Refeeding syndrome: what it is, and how to prevent adn treat it. BMJ 2008; 336: 1495-1498. Available from: URL: http://www.bmj.com/cgi/content/full/336/7659/1495

Antibiotics Use in MRSA

An ICU patient was undergoing continuous veno-venous haemodiafiltration and had line-related bacteraemia. She has MRSA currently and was put on IV linezolid. IV Vancomycin was deemed not suitable as patient was on it for 2 months (previous admission) and showed no clinical response. Interestingly, blood culture showed sensitivity to vancomycin, rifampicin, fusidic acid, and clindamycin.


The issue raised by one pharmacist was, is linezolid a substitute for vancomycin (when patient does not response to it) in bacteraemia? She pointed out that while linezolid is efficacious when vancomycin fails in pneumonia, linezolid is not indicated for bacteraemia.


The most appropriate (antibiotic) treatment [can include removal of source, i.e. the line] is beyond the scope of this post as we did not follow up the case personally and thus do not have a full picture of her condition. However, the ICU case presentation prompted me to read up on antibiotics use in MRSA and I would like to share the findings here.


Community-acquired MRSA (CA-MRSA)- acquired by persons who have not been recently (within the past year) hospitalised or had a medical procedure (e.g. dialysis, surgery, catheters)

Hospital-acquired MRSA (HA-MRSA)-acquired by persons who have had frequent or recent contact with hospitals or healthcare facilities (e.g. nursing homes, dialysis centres) withint the previous year, have recently undergone an invasive medical precodure, or are immunocompromised.

A very good comparison between CA-MRSA and HA-MRSA (in the aspects of areas affected, modes of transmission, treatment & management, prevention) is available at a glance HERE.

Some other points of interest:
The treatment of choice for cutaneous abscesses caused by S aureus, irrespective of antibiotic susceptibility, is incision and drainage.


Vancomycin: still considered the first-line treatment for hospitalised patients with invasive S. aureus infection.

Microbiologic treatment failure may occur with vancomycin even if there is no increase in the minimal inhibitory concentration (MIC) on susceptibility testing. S. aureus isolates with low-level (so-called intermediate) resistance to vancomycin (MIC, >2 µg per milliliter) as well as those with high-level resistance (MIC, >16 µg per milliliter) have been described. <--Perhaps an explanation to patient's lack of response to vancomycin?

Also, nephrotoxicity is associated with high doses needed to attain the recommended vancomycin trough concentrations of 15—20 μg/mL.


Linezolid is FDA-approved for the treatment of complicated skin infections and hospital-acquired pneumonia due to MRSA in adults.

However, linezolid is expensive and has the potential for substantial toxicity, including myelosuppression, peripheral neuropathy, optic neuritis, and lactic acidosis.

Parenteral linezolid lacks bactericidal activity, which some experts believe is important in treating intravascular infection, a common feature of invasive disease. One of the selling points by the drug company is that linezolid is also available in oral form [Tab linezolid 600 mg is available in the blue book] so patient can be converted to the oral form upon discharge. However, this situation is more applicable in overseas (discharged while disease is almost resolved as they have healthcare system which includes home visits); in the government hospitals here, patients will be managed in the hospital until they are fully recovered.


Rifampicin or fusidic acid could be used as adjunctively with another active drug or together; neither agent should be used alone because resistance is likely to emerge during single-drug therapy.

Watch out for potential drug-drug interactions in patient on this regimen as rifampicin is a potent inducer of drug-metabolizing enzymes.


Tigecycline, a parenteral glycylcycline–minocycline derivative, was also recently approved by the Food and Drug Administration (FDA) for the treatment of skin and soft-tissue infections caused by MRSA.

A fixed combination of the streptogramins quinupristin and dalfopristin was licensed by the FDA for the treatment of skin and soft-tissue infections caused by MRSA. Its use has been limited by the potential for drug–drug interactions and by side effects (including arthralgias, myalgias, and gastrointestinal toxic effects).


References:

1. Deleo FR et al. Community associated methicillin-resistant Staphylococcus aureus. The Lancet, 2010 March 5. Available from: URL: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2961999-1/fulltext?_eventId=login
2. Daum RS. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. New Engl J med 2007; 357: 380-390. Available on: URL: http://content.nejm.org/cgi/content/full/357/4/380
3. Strategies for Clinical Management of MRSA in the Community: Summary of an Experts’ Meeting Convened by the Centers for Disease Control and Prevention.2006 March. Available from: URL: http://www.cdc.gov/ncidod/dhqp/pdf/ar/CAMRSA_ExpMtgStrategies.pdf

MPS 43rd AGM & Seminar

First of all, we would like to wish you all a very Happy Chinese New Year! May we soar to greater heights in the year of the Tiger =)

The Malaysian Pharmaceutical Society (MPS) is having its 43rd Annual General Meeting & Seminar with the theme 'Transcending Pharmacy to Greater Heights':

Date: 19/3/10 (Fri)-21/4/10(Sun)
Venue: Berjaya Times Square Hotel, K.L.

For session 1 & 5, it is FREE for MPS members.
More information on seminar registration fees & registration procedure HERE


Here are the programmes at a glance:
19/3/10 (Fri)
Session 1: Extra Optional Programme
Lecture 1: Hypertension & Antihypertensives: How low can you go? How high can you give?
Lecture 2: Role of enoxaparin in surgical thromboprophylaxis
Lecture 3: Treating schizophrenia in the government setting-cost vs. outcomes
Lecture 4: Ideal basal insulin


20/3/10 (Sat)
Session 2: Updates in Paediatric Pharmacy (1)
Lecture 5: Roles of pharmacists in paediatric unit
Lecture 6: Common paediatric problems in Malaysia
Lecture 7: Special symposium
Lecture 8: Safe prescribing in children
Lecture 9: Pharmacists involvement in neonatal ICU
Lecture 10: Special symposium

Session 3: 43rd MPS Annual General Meeting
-Election of the new Council Members

7.30 p.m.-11.00 p.m.: Annual Dinner


21/3/10 (Sun)
Session 4: Updates in Paediatric Pharmacy (2)
Lecture 11: Pharmacist involvement in paediatric oncology
Lecture 12: Clinical pharmacokinetic monitoring in paediatric
Lecture 13: Special symposium
Lecture 14: Special symposium
Lectuer 15: Pharmacist involvement in paediatric asthma
Lecture 16: Treatment of common skin problems in paediatric
Lecture 17: Special symposium


Sesssion 5: Building Community Pharmacy Practices
Lecture 18: Community pharmacy-where we are heading
Lecture 19: Sponsored symposium
Lecture 20: Pharmacy-oriented services in the community
Lecture 21: Staying competitive through networking

Zolendronic acid, annual bisphosphate

Zoledronic acid is indicated for the treatment of hypercalcemia of malignancy, bone lesions associated with multiple myeloma and bone metastases from solid tumors, osteoporosis in postmenopausal women, and Paget's disease of bone.

Osteoporosis

In a 3-year, randomized, double-blind, placebo-controlled study of postmenopausal women with evidence of osteoporosis (n=7765), annual intravenous infusions of zoledronic acid were superior to placebo in reducing the risk of vertebral, hip, and other types of fractures.(Black et al, 2007)

A single-intravenous dose of zoledronic acid was noninferior to once daily oral risedronate for the prevention and treatment of glucocorticoid-induced osteoporosis in the multicenter, randomized, double-blind, double-dummy Health Outcomes and Reduced Incidence with Zoledronic acid Once yearly (HORIZON) trial (n=833). (Reid et al, 2009).

Paget Disease

Zoledronic acid, administered as a single intravenous infusion, produced a quicker, more complete and sustained responses in Paget's disease (osteitis deformans) compared to daily oral treatment with risedronate.(Reid et al, 2005).

Malignancy (vs Pamidronate)

Direct comparisons with pamidronate in patients with hypercalcemia of malignancy have shown greater response rates and extended relapse times with zoledronic acid in clinical trials (Major et al, 2001). However, direct comparisons with other bisphosphonates, including alendronate and ibandronate are needed to determine if zoledronic acid offers any significant advantages in either clinical efficacy or safety.

An expert panel from the American Society of Clinical Oncology recommends intravenous pamidronate or intravenous zoledronic acid as a supportive benefit to multiple myeloma patients. The panel also recommends initiating these agents for patients with pain due to osteolytic disease and as adjunctive treatment for patients receiving radiation therapy, analgesics, or surgical intervention to stabilize fractures or impending fractures (Berenson et al, 2002).

Intravenous zoledronic acid and pamidronate were similarly efficacious when used to treat osteolytic and mixed-bone metastases arising from advanced breast cancer (stage IV, with at least 1 metastatic lesion) or multiple myeloma(Rosen et al, 2001).

Zoledronic acid induced higher rates of response compared with pamidronate when used to treat hypercalcemia of malignancy . Fever, anemia, nausea, constipation, and dyspnea were the adverse events most commonly reported, occurring at similar frequencies among patients receiving either zoledronic acid or pamidronate (Major et al, 2001).

Monitoring Parameters:

• biochemical markers of bone formation/resorption
• radiologic evidence of fracture
• serum calcium (albumin-adjusted)
• standard hypercalcemia-related metabolic parameters
• oral examination by the prescriber prior to treatment; a dental examination in patients at risk for osteonecrosis of the jaw (cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene, pre-existing dental disease or infection, anemia, coagulopathy)
• periodic dental exam for signs of osteonecrosis of the jaw
• hemoglobin and hematocrit
• signs and symptoms of incapacitating bone, joint, and/or muscle pain (common as it will appear within few days post infusion)
• urine albumin; every 3 to 6 months
• cardiac function esp to watch out any atrial fibrillation
• monitoring serum creatinine, it is not advisable to initial in patient with CrCl <35ml/min

References:

Black DM, Delmas PD, Eastell R, et al: Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007; 356(18):1809-1822.

Reid DM, Devogelaer JP, Saag K, et al: Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet 2009; 373(9671):1253-1263.

Reid IR, Miller P, Lyles K, et al: Comparison of a single infusion of Zoledronic Acid with Risedronate for Paget's disease. N Engl J Med 2005; 353(9):898-908.

Major P, Lortholary A, Hon J, et al: Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001; 19(2):558-567

Berenson JR, Hillner BE, Kyle RA, et al: American society of clinical oncology clinical practice guidelines: the role of bisphophonates in multiple myeloma. J Clin Oncol 2002; 20:3719-3736.

Rosen LS, Gordon D, Kaminski M, et al: Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind comparative trial. Cancer J 2001; 7(5):377-387.

Telmisartan, a 2nd-generation of ARB

Telmisartan vs Valsartan

An 8-week course of once-daily TELMISARTAN 80 mg produced greater decreases in diastolic blood pressure during the last 6 hours of 24-hour ambulatory blood pressure monitoring than did once daily valsartan 80 mg (-7.5 millimeters mercury (mmHg) versus -5.2 mmHg, respectively; p less than 0.01), with both drugs showing good tolerability, according to a randomized, open-label, blinded primary end-point trial (n=426).

Littlejohn T, Mroczek W, Marbury T, et al: A prospective, randomized open-label trial comparing telmisartan 80 mg with valsartan 80 mg in patients with mild to moderate hypertension using ambulatory blood pressure monitoring. Can J Cardiol 2000; 16(9):1123-1132.

Telmisartan vs Ramipril

No significant differences were found in the rates of major cardiovascular events between treatment with telmisartan, ramipril, or the combination of the two in patients with coronary, peripheral, or cerebrovascular disease, or with high-risk diabetic patients with evidence of end-organ damage in the randomized, controlled, non-inferiority ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) study, although combination-therapy treatment led to a higher risk of adverse events.

More patients discontinued treatment in the ramipril group vs the telmisartan group due to cough (4.2% vs 1.1%, p less than 0.001) and angioedema (0.3% vs 0.1%, p=0.01) while more patients discontinued treatment in the telmisartan group vs the ramipril group due to hypotensive symptoms (2.7% vs 1.7%, p less than 0.001). In the combination-therapy group, more patients discontinued treatment compared to the ramipril group due to hypotensive symptoms (4.8% vs 1.7%, p less than 0.001), syncope (0.3% vs 0.2%, p=0.03), diarrhea (0.5% vs 0.1%, p less than 0.001), and renal impairment (1.1% vs 0.7%, p less than 0.001)

Yusuf S, Teo KK, Pogue J, et al: Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358(15):1547-1559.

Comparison of Statin : Chemistry/Functional, Pharmacokinetic, Pharmacodynamic, Cost Effectiveness Differences

As a special offer to whoever viewing this blog, a summary of comparison of statin, from the perspective of chemistry/functional, pharmacokinetics, pharmacodynamic and cost effectivenss, an updated version, is available upon your request to :

1. bpharmer05@gmail.com

OR

2. dmcancw@yahoo.com, direct to me, Mai. I will then send to you after receiving your email.

European Medicines Agency Recommends Suspension of Sibutramine

Updated 29/1/10:
In view of the results from SCOUT study [more information below] conducted by Abbott for its product Reductil, the Drug Control Authority of Malaysia will instruct all Sibutramine product registration holders to circulate a 'Dear Healthcare Professional' letter to all prescribers in Malaysia regarding the new information as well as adding the description of the SCOUT study in the product insert to further strengthen its safety information.


Comment by the Malaysian Pharmaceutical Society:
The NST did their round in some pharmacies and highlighted that pharamcies are not doing their job in alerting clients on the potential adverse reactions. There is no excuse to this as pharmacists are the custodian of medicines and they should be counselling patients/customers with the latest information. The counselling should not be limited to just on medicine, but also on lifestyle.

In addition, the newspaper also highlighted that Sibutramine was easily available with no prescvription required. In fact, Sibutramine is a Group B item and pharmacists should only dispense it with prescription.

The news in NST HERE


Ed's note:
As pharmacists, we should always uphold our profession with integrity and ensure that our practice is according to the law. It is bad apples like those highlighted in the news that further hinder our championing of dispensing separation rights.



LONDON -- January 22, 2010 -- The European Medicines Agency has finalised a safety review of medicines containing sibutramine (Reductil, Reduxade, and Zelium). The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that the risks of these medicines are greater than their benefits and recommended the suspension of marketing authorisations for these medicines across the European Union.

Physicians should no longer prescribe, and pharmacists should no longer dispense the medicine. Patients currently taking sibutramine should make an appointment with their doctor at the next convenient time to discuss alternative measures to lose weight.

The review was initiated because data from the Sibutramine Cardiovascular Outcome Trial (SCOUT) showed an increased risk of serious, non-fatal cardiovascular events, such as stroke or myocardial infarctions (MI), with sibutramine compared with placebo.

The SCOUT trial, in which nearly 10,000 patients were enrolled for up to 6 years, was designed to determine the impact of weight loss with sibutramine on cardiovascular problems in a large group of overweight and obese individuals with known or high risk for cardiovascular disease.

The CHMP noted that the use of sibutramine was not in accordance with the prescribing information for most of the patients enrolled in the SCOUT study, as sibutramine is contraindicated in patients with known cardiovascular disease. The treatment duration in the study was also longer than normally recommended. However, because obese and overweight patients are likely to have a higher risk of cardiovascular events, the Committee was of the opinion that the data from SCOUT are relevant for the use of the medicine in clinical practice.

The Committee also noted that the data from available studies showed that the weight loss achieved with sibutramine is modest and may not be maintained after stopping. The CHMP was therefore of the opinion that the benefit of sibutramine as a weight-loss aid do not outweigh the cardiovascular risks.

The Committee's recommendation for the suspension of the marketing authorisations has now been forwarded to the European Commission for the adoption of a decision.

SOURCE: European Medicines Agency

Adapted from http://www.docguide.com/news/content.nsf/news/852576140048867A852576B3004A348B

(accessed online 24 Jan 2010)