The Canadian Agency for Drugs and Technologies in Health (CADTH) has conducted an evidence review to address the following two research questions:
 
. What is the clinical effectiveness of short-acting benzodiazepines compared to other strategies for the management of agitation in elderly patients?
. What are the guidelines for the administration of short-acting benzodiazepines for managing agitation in elderly patients?
 
The overall findings were:
 
"The NICE-SCIE guideline on support for people with dementia and their carers recommends that healthcare professionals need to: be proficient in their ability to correctly use benzodiazepines to control behaviour; be knowledgeable of the risks associated with their use (particularly in the physically ill and dehydrated); and understand their cardiovascular effects. These guidelines also underline the importance of dosage titration in patients with dementia. Once a benzodiazepine has been ...

Source: NeLM: News
http://www.nelm.nhs.uk/en/NeLM-Area/News/2010---June/30/CADTH-review-Short-acting-benzodiazepines-versus-other-strategies-for-agitation-in-elderly-patients/

Published by the British Pain Society in January 2010.

Source: NLH: Guidelines Finder - Latest Additions
http://www.library.nhs.uk/GUIDELINESFINDER/ViewResource.aspx?resID=379475&tabID=288

. Three new fentanyl products have recently become available for the relief of breakthrough pain associated with cancer. All involve novel modes of delivery for fentanyl with two providing oramucosal delivery via sublingual (Abstral®) and buccal routes (Effentora®), and one providing mucosal delivery via the intranansal route (Instanyl®).
 
. The evidence base supporting their efficacy is generally poor. Few studies have been published, most comparisons are against placebo, and methodological and protocol faults have been identified. However, they do appear to produce meaningful and relatively rapid analgesia.
 
. As with evidence of efficacy, evidence for safety is also poorly available. No important specific safety concerns were highlighted in the clinical studies except for mouth ulceration due to the buccal tablet formulation.
 
. However, each product is associated with complicated initiation, titration, and maintenance dose instructions. It ...

Source: NeLM: Drug Specific Reviews
http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Drug-Specific-Reviews/Novel-oramucosal-Abstral-Effentora-and-nasal-Instanyl-fentanyl-for-breakthrough-pain-associated-with-cancer/

In its Final Appraisal Report, the All Wales Medicines Strategy Group (AWMSG) supported the use of  Fentanyl (InstanylT) as an option for use within NHS Wales for the treatment for the management of breakthrough pain in adults already receiving maintenance opioid therapy for chronic cancer pain.
 
Fentanyl intranasal spray should only be considered as an option for the management of breakthrough cancer pain when immediate release oral opioids (e.g. morphine, oxycodone) are either inadequate or unsuitable.
 
Fentanyl intranasal spray may be suitable for shared care but should be initiated by, and remain under the supervision of, a physician experienced in the management of opioid therapy in cancer patients.

Source: NeLM: Drug Specific Reviews
http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Drug-Specific-Reviews/All-Wales-Medicines-Strategy-Group-AWMSG-issues-Final-Appraisal-Report-on-Fentanyl-Instanyl/

Sativex is a cannabis-based medicine which contains delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in an oromucosal spray.
Currently Sativex is a Schedule 1 drug (with some restrictions lifted), but this is due to be changed when it is approved by the MHRA.
The regulatory submission for Sativex for the treatment of spasticity due to MS was filed in the UK in May 2009.
Sativex has been available on a named-patient basis in the UK since December 2005.
The trial data for the 2009 licence are not yet fully published: the data that are published do not given an indication of the clinical significance of the changes in symptoms seen with Sativex treatment, compared with placeob, or how the side effect profile compares with placebo.
272 patients, classed as responders after an initial 4-week single-blind treatment phase, were randomised to treatment with either Sativex or placebo, in a 12-week double-blind phase. The mean change from pre-randomisation baseline ...

Source: NeLM: Drug Specific Reviews
http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Drug-Specific-Reviews/Sativex-for-multiple-sclerosis/

The risks to the patient posed by thromboprophylaxis therapy while receiving or discontinuing  epidural medication are reviewed, and various methods to reduce risk highlighted.

Source: NeLM: Medicines Q & A
http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Medicines-Q--A/What-are-the-Recommendations-for-PlacementRemoval-of-Epidural-Catheters-in-Patients-Receiving-Concurrent-Thromboprophylaxis/

. Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular disorder, which can be treated symptomatically with 3,4-diaminopyridine (amifampridine).
 
. The authors of a Cochrane review concluded that limited evidence from two randomised controlled trials showed that 3,4-diaminopyridine improved muscle strength scores and compound muscle action potential amplitudes in patients with LEMS. However, there are insufficient data at present to quantify this treatment effect.
 
. Until recently, oral 3,4-diaminopyridine was only available as an unlicensed formulation as 3,4-diaminopyridine base, which was used in the RCTs. A phosphate salt formulation of oral 3,4-diaminopyridine (amifampridine) has now been licensed in the UK for the symptomatic treatment of LEMS in adults.
 
. No information on dose conversion from the base to the phosphate salt preparation of 3,4-diaminopyridine is stated in the Summary of ...

Source: NeLM: Medicines Q & A
http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Medicines-Q--A/What-is-the-difference-between-amifampridine-and-34-diaminopyridine-base-for-Lambert-Eaton-myasthenic-syndrome-in-adults/

-- National Prescribing Centre (NPC) --

Source: National Prescribing Centre eCAB Week in Review
http://www.npc.co.uk/policy/resources/mixing_of_medicines.pdf

Attempting to correct haemoglobin levels to normal in patients with chronic kidney disease (CKD) using erythropoiesis-stimulating agents (ESA) increases the risk of serious cardiovascular events, according to a systematic review and meta-analysis; evidence for benefit is limited, and of poor quality.
 
 
CKD is frequently associated with anaemia due in part to reduced secretion of erythropoietin by the kidney. Initial clinical trials showed that ESA were effective in reducing the need for transfusion, and subsequent trials attempted to determine whether better outcomes were achieved with higher doses designed to bring haemoglobin levels to near normal. There has been increasing evidence that attempting to reach normal or near normal haemoglobin levels (120 to 150 gm/l) was associated with significantly higher risk of serious adverse effects compared to lower targets (100 to 120 g/l). There have been more large trials since previous meta-analyses have been ...

Source: NeLM: News
http://www.nelm.nhs.uk/en/NeLM-Area/News/2010---April/04/Systematic-review-erythropoiesis-stimulating-agents-in-CKD---higher-doses-more-harm-than-good/

Tamoxifen is a prodrug which when metabolised by cytochrome P450 2D6, generates the potent tamoxifen metabolite, endoxifen. Many studies have demonstrated that women with impaired CYP2D6 metabolism have lower endoxifen concentrations and a greater risk of breast cancer recurrence.
 
As a result, practitioners must be aware that some of the most commonly prescribed medications co-administered with tamoxifen interfere with CYP2D6 function, thereby reducing endoxifen concentrations and potentially increasing the risk of breast cancer recurrence.
 
The authors of this review have developed an evidence based guide for the use of medications that inhibit CYP2D6 in patients administered tamoxifen. Medications are grouped into moderate-to-potent inhibitors (in vivo evidence for conversion of extensive metabolizers into poor metabolizers, or in vitro evidence for potent inhibition of CYP2D6 comparable to other potent inhibitors), weak-to-moderate inhibitors ...

Source: NeLM: News
http://www.nelm.nhs.uk/en/NeLM-Area/News/2010---April/04/Guide-to-co-prescription-of-tamoxifen-and-medications-that-inhibit-CYP2D6-2/

The U.S. Food and Drug Administration (FDA) has approved ketorolac tromethamine nasal spray (Sprix) for the short-term (up to 5 days) management of acute moderate to moderately severe pain that requires analgesia at the opioid level.
 
SPRIX is a prescription only intranasal formulation of the ketorolac designed to provide ambulatory patients with a convenient, potent, and fast-acting option for acute moderate to moderately severe pain relief.
 
[Editors note: Intranasal ketorolac is currently not available in the UK.]

Source: NeLM: News
http://www.nelm.nhs.uk/en/NeLM-Area/News/2010---May/19/Horizon-scanning-FDA-approves-ketorolac-tromethamine-nasal-spray-Sprix-for-the-short-term-management-of-acute-pain-/

GW Pharmaceuticals plc and Almirall, S.A have announced that regulatory authorities in the UK and Spain have reached consensus that all issues related to the Sativex® application have been resolved, with a positive recommendation that Sativex® is approvable. The regulatory process will now enter the national phase to finalise local wording on product packaging and related documents. After this phase, national marketing approvals can be granted in each respective country (likely second quarter 2010). Sativex®, an endocannabinoid system modulator, administered through an oromucosal spray, is indicated as add-on treatment for symptom improvement in patients with spasticity due to multiple sclerosis, who have not responded adequately to other anti-spasticity medication.
 
The Sativex regulatory submission was filed in the UK and Spain under the European decentralised procedure in May 2009, with the UK acting as the Reference Member State.
 

Source: NeLM: News
http://www.nelm.nhs.uk/en/NeLM-Area/News/2010---May/20/Sativex-on-track-to-be-approved-in-UK-for-treatment-of-spasticity-due-to-multiple-sclerosis/

BioMarin Europe has announced the launch of amifampridine (Firdapse®) for the symptomatic treatment of Lambert-Eaton Myasthenic Syndrome (LEMS) in adults.
 
The basic NHS price for 100 x 10mg tablets is £2017. The recommended starting dose of amifampridine is 15mg per day, which can be increased in 5mg increments every 4 to 5 days, to a maximum of 60mg per day. No single dose should exceed 20mg. At the maximum dose of 60mg/day at £120 per day, the annual cost per patient is approximately £44,000 .Previously, this condition was treated with a different salt form which was unlicensed (3,4 Diaminopyridine) and cost £375 (ex VAT) for 336 x 20mg tablets, representing an annual cost (using 20mg tablets at maximum dose) of £1250.
 
In the UK, there are approximately 150 patients with LEMS
 

Source: NeLM: News
http://www.nelm.nhs.uk/en/NeLM-Area/News/2010---April/20/Amifampridine-Firdapse-launched-for-the-symptomatic-treatment-of-Lambert-Eaton-Myasthenic-Syndrome-LEMS/

Citalopram is effective for hot flushes with 10mg daily virtually as effective as higher doses, according to a controlled trial.
 
The authors of this trial note that the physiology of hot flushes is poorly understood, so while some SSRI have been shown to be effective treatment this cannot be assumed to be a class effect: in support, they note that not all SSRI have been shown to have similar efficacy (sertraline < fluoxetine / paroxetine). Those SSRI shown to be most effective, fluoxetine and paroxetine, interact with tamoxifen via CYP2D6 inhibition so an alternative SSRI that could be used safely with tamoxifen would be valuable in oncology. In this trial, they aimed to determine whether citalopram was effective in relief of hot flushes. Participants were postmenopausal women who reported at least 14 bothersome hot flushes per week for at least the past month. After a medication-free baseline week, they were randomised to 5 weeks treatment with 1, 2, or 3 citalopram ...

Source: NeLM: News
http://www.nelm.nhs.uk/en/NeLM-Area/News/2010---May/27/Citalopram-effective-for-hot-flushes/

The ideal prokinetic dose of erythromycin is yet to be established but is less than the maximal antibacterial dose of erythromycin.
&nbsp;
There is not a standard regimen for erythromycin when used as a prokinetic agent. With intravenous erythromycin, satisfactory outcomes have been achieved with doses of 300mg daily in divided doses, with 250mg four times a day, and with single doses of 70mg and 200mg.
&nbsp;
Oral erythromycin at prokinetic doses of 50 - 250mg four times daily have be used effectively.

Source: NeLM: Medicines Q & A
http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Medicines-Q--A/What-is-the-optimal-prokinetic-dose-of-erythromycin-in-adults/

-- National electronic Library for Medicines (NeLM) --

Source: National Prescribing Centre eCAB Week in Review
http://www.nelm.nhs.uk/en/NeLM-Area/News/2010---April/22/Review-Ziconotide-for-treatment-of-severe-chronic-pain/

Concerns were expressed at the increased volume of prescribing of low molecular weight heparins (LMWH) in primary care in Wales, and the lack of information or guidance to support prescribers.&nbsp; In July 2009 therefore, prescribing data from sample of practices across Wales was reviewed.
&nbsp;
Following a consultation, the following recommendations have been made, which are intended to establish the scenarios where provision of service can safely be undertaken in the community whilst simultaneously ensuring timely access to specialist care when needed:&nbsp;
&nbsp;
.&nbsp;LMWH treatment for four weeks or less should be prescribed and monitored by the initiating physician (any indication). .&nbsp;Where there is a need to monitor LMWH treatment by measuring the anti-Xa level, patients should be prescribed and followed up regularly by specialist services. .&nbsp;Treatment doses of LMWH prescribed for venous thromboembolism (VTE) in cancer patients are suitable for ...

Source: NeLM: News
http://www.nelm.nhs.uk/en/NeLM-Area/News/2010---March/24/Recommendations-on-prescribing-of-LMWH-including-shared-care-in-Wales/

Published by NICE in October 2008 and updated 29 January 2010.

Source: NLH: Guidelines Finder - Latest Additions
http://www.library.nhs.uk/GUIDELINESFINDER/ViewResource.aspx?resID=70584&tabID=288

Fentanyl nasal spray (Instanyl®) is licensed for breakthrough pain in adults receiving maintenance opioid therapy for chronic cancer pain. There are several other immediate release fentanyl products already on the market for this indication. Instanyl® is the first intranasal formulation available. There are two published randomised controlled trials of Instanyl®. Its use resulted in significantly superior pain reduction at 10 minutes compared to placebo, and provided analgesia around 5 minutes faster than oral transmucosal fentanyl (Actiq®).
The safety profile of Instanyl® appears comparable to that of other fentanyl containing products indicated in the treatment of breakthrough cancer pain. Typical opioid adverse reactions have been reported. The most common adverse reactions are somnolence, dizziness, headache, vertigo, flushing, throat irritation, hyperhidrosis, nausea and vomiting.
Instanyl® is currently the most expensive immediate release fentanyl preparation on the ...

Source: NeLM: Drug Specific Reviews
http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Drug-Specific-Reviews/New-Medicines-Profile-Fentanyl-nasal-spray-Instanyl/

There have been concerns as to whether pharmaceutical products containing arachis oil are appropriate for individuals with peanut allergies or that they may increase the risk of developing peanut allergy.
Although there is some evidence that exposure to refined arachis oil does not pose a risk to patients with peanut allergy, the Summary of Product Characteristics (SPCs) of products which contain arachis oil state that they should not be used by patients with an allergy to peanuts (or soya).&nbsp; The CSM have recommended that patients known to be allergic to peanuts should not use medicines containing arachis oil.
The CSM have previously advised that there is insufficient evidence to conclude that exposure to medicinal products containing arachis oil leads to sensitisation to peanut protein.

Source: NeLM: Medicines Q & A
http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Medicines-Q--A/Arachis-oil-in-medicines-what-are-the-risks-of-developing-peanut-allergy/

-- Clinical Knowledge Summaries (PRODIGY) / SCHIN --

Source: National Prescribing Centre eCAB Week in Review
http://www.cks.nhs.uk/restless_legs_syndrome

-- Department of Health (DH) --

Source: National Prescribing Centre eCAB Week in Review
http://www.dh.gov.uk/en/Healthcare/Medicinespharmacyandindustry/Prescriptions/TheNon-MedicalPrescribingProgramme/DH_110765

Published by Program in Evidence-based Care | 05 May 2009

Source: US National Guideline Clearinghouse (NGC)
http://www.guideline.gov/summary/summary.aspx?doc_id=15047&nbr=7392&ss=6&xl=999

The Committee for Medicinal Products for Human Use (CHMP) of the EMEA has recommended the adoption of the following contraindications for Bondronat® (ibandronic acid):
&nbsp;
.&nbsp;"Hypocalcaemia" - for both the 50mg tablets and the concentrate for solution for infusion .&nbsp;"Abnormalities of the oesophagus which delay oesophageal emptying such as stricture or achalasia" - for the 50mg tablets only .&nbsp;"Inability to stand or sit upright for at least 60 minutes" - for the 50mg tablets only
&nbsp;
The following contraindications have been recommended for Bonviva® and Bondenza® (both ibandronic acid tablets):
&nbsp;
.&nbsp;"Abnormalities of the oesophagus which delay oesophageal emptying such as stricture or achalasia" .&nbsp;"Inability to stand or sit upright for at least 60 minutes" (Hypocalcaemia is already listed as a contra-indication to the use of these two products)
&nbsp;
Detailed conditions for the use of these products will be described in the ...

Source: NeLM: News
http://www.nelm.nhs.uk/en/NeLM-Area/News/2010---January/11/EMEA-approves-additional-contraindications-for-ibandronic-acid-preparations-/

According to the results of this nested case control study published early online in the British Medical Journal (BMJ), the use of venlafaxine was not associated with a higher risk of sudden cardiac death or near death than fluoxetine, dosulepin, or citalopram, in patients with depression or anxiety.
&nbsp;
The authors of the study note the cardiac cautions/contra-indications with venlafaxine, and advice issued by the MHRA in 2006 (revision of previous advice) that patients at very high risk of ventricular arrhythmia or with uncontrolled hypertension should not use venlafaxine.&nbsp; They note that that there has to their knowledge been no systematic study evaluating the risk of haemodynamically significant (malignant) arrhythmias or sudden cardiac death associated with the use of venlafaxine in usual clinical practice.&nbsp;
&nbsp;
This population-based observational study was therefore conducted, using data obtained from the United Kingdom General Practice Research ...

Source: NeLM: News
http://www.nelm.nhs.uk/en/NeLM-Area/News/2010---February/08/Risk-of-sudden-cardiac-death-or-near-death-with-venlafaxine-compared-with-other-antidepressants-/

Dear Healthcare Professional,
&nbsp;
Teva UK Limited
&nbsp;
PL 10622/0102
&nbsp;
Ondansetron IV Injection 2mg/ml (2ml) and 2 mg/ml (4ml) (All supplied in Pliva livery)
&nbsp;
Teva UK Limited have informed us that they have not complied with regulatory undertakings to update the SPC or patient information leaflet contained in already distributed packs. All stock in the distribution chain is missing some safety information.
&nbsp;
We understand that it will be about four months before acceptable stock enters the supplychain. To avoid stock shortages existing stock is not being recalled.
&nbsp;
The missing information is listed in the attached annex. Please forward this to relevant physicians.
&nbsp;
For medical information enquiries and questions about the patient information leaflet or SPC, please contact Teva UK medical information on 0207 5407717
&nbsp;
Recipients of this Drug Alert are requested to bring it to the ...

Source: NeLM: MHRA Drug Alerts
http://www.nelm.nhs.uk/en/NeLM-Area/Other-Lib-Updates/Drug-Alerts/Class-4-Drug-Alert-Caution-in-use-Teva-UK-Limited---Ondansetron-IV-Injection-2mgml-2ml-and-2--mgml-4ml----PL-106220102---EL09A35---/

Revised SPC includes changes to:

Section 4.4 (Special warnings and precautions for Use) - Concomitant use with risperidone: in risperidone placebo-controlled trials in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone (7.3%; mean age 89 years, range 75-97 years) when compared to patients treated with risperidone alone (3.1%; mean age 84 years, range 70-96 years) or furosemide alone (4.1%; mean age 80 years, range 67-90 years). Concomitant use of risperidone with other diuretics (mainly thiazide diuretics used in low dose) was not associated with similar findings.
Section 4.5 (Interaction with other medicinal products and other forms of interaction) Risperidone: Caution should be exercised and the risks and benefits of the combination or co-treatment with furosemide or with other potent diuretics should be considered prior to the decision to use.

Source: NeLM: SPC Changes
http://www.nelm.nhs.uk/en/NeLM-Area/Other-Lib-Updates/SPC-Changes/Lasix-injection-20mg2mL-furosemide---Revised-SPC/

According to research published early online in the Journal of Clinical Oncology, ibandronate and pamidronate appear to exhibit a safer drug profile concerning osteonecrosis of the jaw (ONJ) complication compared to zolendronic acid. Researchers conducted a cohort study aimed at calculating the incidence of, and identifying the risk factors for osteonecrosis of the jaw (ONJ) in patients with cancer treated with intravenous zoledronate 4mg, ibandronate 6mg, and pamidronate 90mg.
&nbsp;
The study included data obtained from 1,621 patients who received 29,006 intravenous doses of bisphosphonate. Data analysed included age, sex, smoking status, underlying disease, medical and dental history, bisphosphonates (BP) type, and doses administered. The relative risks, crude and adjusted odds ratios (aORs), and cumulative hazard ratios for ONJ development were calculated.
&nbsp;
The following results were reported: .&nbsp;Crude ONJ incidence was 8.5%, 3.1%, and 4.9% in patients with ...

Source: NeLM: News
http://www.nelm.nhs.uk/en/NeLM-Area/News/2009---October/06/Cohort-study-of-risk-factors-for-bisphosphonate-related-osteonecrosis-of-the-jaw-in-cancer-patients/

This Topic Minibite covers the assessment and management of oral candidiasis, including angular cheilitis, in both immunocompetent and immunocompromised people. The target audience is healthcare professionals working within the NHS in England, and providing first contact or primary health care.

Source: NeLM: Guidelines
http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Guidelines/CKS-Topic-Minibite-Oral-candida/