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)

Volunteer to Promote the Role of Pharmacist

Dear fellow pharmacists,

Here is an opportunity for us to promote our role as pharmacists to the public while networking with people from other fields (as well as catching up with each other ^^)!!

Edited on 22/1/09: This event has been postponed until further notice by the Malaysian Professional Centre. myPharmacists will keep you all posted on the new date =)

The Malaysian Professional Centre (or BIM – Balai Ikhthisas Malaysia) is organising an event called “PROFESSIONALS CONNECT”.

Date: 6/2/10 (Sat)-7/2/10(Sun)
Time: 9 a.m.-7 p.m.
Venue: Malaysian Tourism Centre, Jalan Ampang

The event will feature:

• Public forum on current topics and emerging issues
• Exhibition by professinoal bodies with free advice and consultancy services, sales of books and publications

There will also be a carnival to raise funds for charity (Food Fest, Sale Bazaar) in support of Mercy Malaysia.

MPS shall be taking up booth to be part of the campaign for the public to know the pharmacist better. Volunteers are required to take charge of the booth. It will be on a 5-hour shift as follows:

6/2/10: Shift 6A: 9 a.m.-2 p.m./ Shift 6B: 2 p.m.-7 p.m.

7/2/10: Shift 7A: 9 a.m.-2 p.m./ Shift 7B: 2 p.m.-7 p.m.

Please email in your prefer scheduled (subject list as: PC - your name / Shift XX ) and also provide your place of work and contact to MPS.

If you are not yet a MPS member, what are you waiting for? JOIN now at http://202.144.202.76/new_mps/cfm/membership_application_form.cfm!!

It is with power in an organization that we can exert influence and change =)

If you are a PRP, click on 'Postgraduate' (Application fee: RM45).

New Drugs in MOH Formulary

According to the pekeliling in Dec 2009 by Bahagian Perkhidmatan farmasi, there are some additions to the MOH Formulary.

[Drug name][Category][Indication]

Introduction of New Drug

Inj Cetrorelix 0.25 mg (A*)-Prevention of premature ovulation in pt undergoing a controlled ovarian stimulation, followed by oocyte pick-up and assisted reproductive technique.

Inj Ganirelix 0.25 mg/0.5 mL (A*)- Prevention of premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for assisted reproduction technique.

Inj Carbetoin 100 mcg/mL (A*)- Prevention of uterine atony and postpartum haemorrhage following elective caesarean section uner epidural or spinal anaesthesia.

Cap Dabigatran etexilate 75 mg (A*)- Prevention of venous thromboembolic events in patients who have undergone total knee replacement or total hip replacement surgery.

Cap Dabigatran etexilate 110 mg (A*)- Patients at risk for bleeding, recent bipsy or major trauma, spinal & epidural anaesthesia, lumbar puncture, pregnancy & lactation, children.

Cap Rifampicin 150 mg (B)- Initial phase (2 months) of tuberculosis

Tab Isoniazid 75 mg (B)- Initial phase (2 months) of tuberculosis

Tab Pyrazinamide 400 mg(B)- Initial phase (2 months) of tuberculosis

Tab Paliperidone 3 mg/6 mg/9 mg [extended release] (A)- Second or third line treatment of schizophrenia.

Human Papillomavirus (Types 6, 11, 16, 18) vaccine injection [Gardasil] (A)- For the prevention of cervical cancer due to papilloma virus. To be used as part of the public health programme only.

Human Papillomavirus (Types 16, 18) vaccine injection [Cervarix] (A)- For the prevention of cervical cancer due to papilloma virus. To be used as part of the public health programme only.

Tab Sodium dichloroisocyanurate 2.5 g/5 mg (C)-Low and medium level disinfectant

Addition of Formulation

Typhoid vaccine capsule (B)- Active immunisation against typhoid fever in adult and child 6 years of age or older.

Fentanyl 12 mcg/hr transdermal patch (A*)- As a second line drug in the management of chronic severe cancer pain not responding to non-narcotic analgesic. Not to be use in opioid naïve patients. The use is to be restricted to pain specialists, palliative medicine specialists and oncologists.

Menotrophin 75 IU injection (Follicle Stimulating Hormone 75 IU and Luteinizing Hormone 75 IU) (A*)

Menotrophin, Highly Purified 75 IU injection (Follicle Stimulating Hormone 75 IU and Luteinizing Hormone 75 IU) (A*)-

Treatment of infertility where clomifene has failed or stimulation of follicle growth as part of an assisted reproductive technology.

Addition of Indication

Salmeterol 50 mcg and fluticasone propionate 500 mcg inhalation [Seretide] (A)

Old indication- Regular treatment of reversible obstructive airways disease including asthma

New indication-

· Regular treatment of reversible obstructive airways disease including asthma

· COPD including chronic bronchitis and emphysema

Tab Leflunomide 10 mg/20 mg/100 mg (A*)

Old indication- Persistent active rheumatoid arthritis

New indication-

· Persistent active rheumatoid arthritis

· Active psoriatic arthritis