Several new high-strength insulin products have been approved for use throughout the EU since 2013*. High-strength insulin products contain a concentration of insulin which exceeds the standard 100 units/ml (e.g. they may contain 200 units/ml or 300 units/ml) and provides for a better dissolution profile over the duration of action, helping to meet an increasing need for higher doses while reducing the number and volume of injections. However, there are important differences in the way that high-strength insulin products are used compared with existing standard-strength insulin formulations. There is therefore a risk of medication error and accidental mix-up. Information and recommendations for use can be found in the product information (Summary of Product Characteristics (SmPC) and Package Leaflets (PLs)) for the individual insulin preparations.

The packaging and pre-filled syringes or pre-filled pens for high-strength insulins have been designed to mitigate the risk of medication error and mix-ups, with devices calibrated to ensure the correct dose of insulin is delivered. It is essential that insulins are not extracted from these devices for delivery by an insulin syringe. In addition, educational materials are available for the various high-strength insulin products which provide information on dosing, dose adjustment, and the need for dose conversion when switching between standard and high-strength products (if necessary), interchangability and monitoring as appropriate to the individual product.

Healthcare professionals and patients therefore need to understand the insulin strength of these products and how to use them correctly in order to minimise the risk of medication errors such as administering the wrong insulin dose. Prescribers should specify the strength in the prescription and ensure it is differentiated from the dose, for any products where both strengths are available. When dispensing products where there are two strengths available, pharmacists should confirm the strength and liaise with patients to reinforce advice as necessary. Patients should be reminded that the dose is in units on the pen and no calculations need to be made. Patients should also be advised to carefully check the units on the pen and use them to dial up their dose in units, seeking assistance if needed.

The European Medicines Agency (EMA) has published guidance on prevention of medication errors with high-strength insulins which provides further important information and guidance on the safe and effective use of these medicines. This was recommended as part of the risk minimisation strategy for high-strength and fixed-combination insulin products which is also available on the EMA website.

Electronic versions of educational materials approved by the HPRA for specific medicinal products on the Irish market are available on the HPRA website under Educational Materials on the HPRA homepage (www.hpra.ie). Hard copy versions of these materials are available directly from the marketing authorisation holder of the specific product.

Key Message

• Healthcare professionals and patients should be aware of the availability of high-strength insulin products coming onto the Irish market and that some product ranges may include both standard-strength and high-strength insulin preparations.
• Prior to starting treatment with any of these products or when switching from a standard-strength insulin to a high-strength insulin, prescribers should consult the product information (SmPC and PL) and any educational materials provided with these medicinal products.
• Healthcare professionals should ensure that patients and/or carers read and understand the PL and any patient educational material provided with the product and receive appropriate training on the correct use of the product prior to use.
• Any reports of suspected adverse reactions associated with use of these products should be notified to the HPRA in the usual way.

*High-Strength insulin products include Tresiba, Humalog, and Toujeo. Further details on these products are available on www.hpra.ie and www.ema.europa.eu

The post High-Strength Insulin Preparations appeared first on Irish Medical Times.

The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) advised that healthcare professionals and patients be informed of product information (Summary of Product Characteristics (SmPC) and Package Leaflet (PL)) changes in relation to the immunosuppressive effect of fingolimod and to reiterate some important recommendations for use.

Fingolimod is a sphingosine-1-phosphate receptor modulator, metabolised by sphingosine kinase to the active metabolite fingolimod-phosphate. It is indicated as single disease modifying therapy in adult patients with highly active relapsing remitting multiple sclerosis despite a full and adequate course of treatment with at least one disease-modifying therapy. It has been approved in the US since September 2010 and for use across the EU since March 2011.

Due to its potent immunosuppressive effects, patients are at risk of serious adverse reactions and healthcare professionals are advised as follows:

Advice to Healthcare Professionals

Basal Cell Carcinoma (BCC)

• Cases of BCC have been reported in patients receiving fingolimod from both the clinical trial setting and post-marketing surveillance.
• Healthcare professionals and patients should be aware that vigilance for skin lesions is warranted.
• Medical evaluation of the skin is recommended at initiation, after at least one year and then at least yearly taking into consideration clinical judgement.
• Patients should be referred to a dermatologist if suspicious lesions are detected.
• Patients with active malignancies (including BCC) should not be treated with fingolimod.

Opportunistic Infections

The immunosuppressive effects of fingolimod may increase the risk of CNS infections including opportunistic infections such as viral (e.g. herpes simplex virus, varicella zoster virus), fungal infections (e.g. cryptococcal meningitis) or bacterial infections (e.g. atypical mycobacterium). Prescribers are therefore reminded that:

• Initiation of treatment with fingolimod should be delayed in patients with severe active infection until the infection is completely resolved;
• The benefit-risk balance of using fingolimod should be considered for each individual patient prior to initiation of treatment and also prior to re-initiation of treatment;
• Suspension of treatment should be considered if a patient develops a serious infection;
• Following discontinuation of treatment, fingolimod may take up to two months to be eliminated from the body and healthcare professionals and patients should be alert for symptoms of infection during this period.

Lymphoma

• Cases of lymphoma have been reported in patients treated with fingolimod.

Progressive Multifocal Leukoencephalopathy (PML)

• PML is an opportunistic infection which may be fatal or result in severe disability and cases of PML have been reported in association with fingolimod;
• Before initiating treatment with fingolimod, a baseline MRI should be available (usually within 3 months as a reference).
• During routine MRI scans, healthcare professionals should pay attention to PML suggestive lesions;
• Patients and carers should be informed of the early symptoms suggestive of PML (e.g. change in behaviour/mood, memory lapses, speech difficulties) and recommended to seek immediate medical attention if any of these symptoms are experienced;
• If PML is suspected, treatment with fingolimod should be suspended until PML has been excluded.
• PML only occurs in the presence of a JCV infection. If JCV testing is undertaken however, it should be considered that the influence of lymphopenia on the accuracy of the anti-JCV antibody test has not been studied in fingolimod treated patients. Therefore a negative JCV antibody test does not preclude the possibility of subsequent JCV infection.

Complete Blood Count (CBC) Monitoring

• A recent (i.e. within the last six months or after discontinuation of prior therapy) complete blood count (CBC) should be available to healthcare professionals prior to initiating treatment with fingolimod to ensure that immune effects of previous therapy have resolved.
• Assessment of CBC is also recommended periodically during treatment i.e. three months after starting treatment and at least annually thereafter. CBC should also be measured in case of signs of infection.

Key Message

• In patients receiving fingolimod, medical evaluation of the skin before treatment initiation and during treatment is recommended due to a risk of BCC.
• Healthcare professionals/carers should be alert to the risk of PML and should inform patients/carers of early symptoms suggestive of PML recommending they seek medical advice if any experienced. During routine MRI scans, healthcare professionals should pay close attention to lesions suggestive of PML.
• Treatment with fingolimod should not be initiated in patients with severe active infection and suspension of treatment should be considered if a patient develops a serious infection.
• A CBC should be available prior to initiating treatment and regular CBC is recommended (i.e. 3 months after commencing treatment and at least annually thereafter).
• This information was highlighted in the HPRA’s Drug Safety Newsletter (74th edition) and a Direct Healthcare Professional Communication (DHPC) was circulated to relevant healthcare professionals by the marketing authorisation holder in January 2016. Both documents are available from the HPRA website (www.hpra.ie).
• The product information for fingolimod (SmPC and PL) has been updated with this information.

*Further details on Gilenya are available on www.hpra.ie and www.ema.europa.eu

The post Fingolimod (Gilenya) – Risks related to immunosuppressive effects appeared first on Irish Medical Times.

Download PDF

Table 1. Antihyperglycaemic Therapy in Type 2 Diabetes – List of agents available in Ireland

*combination containing metformin and another active ingredient. The above table was prepared from data available in October 2016. Prescribers should refer to section 6.4 of MIMS Ireland and SPCs of each product for full up-to-date details of licensing. MIMS Ireland Copyright®

Focus on Type 2 Diabetes – ICGP Guidelines 2016

The post Antihyperglycaemic Therapy in Type 2 Diabetes – List of agents available in Ireland appeared first on Irish Medical Times.

The ICGP’s ‘Practical Guide to Integrated Type 2 Diabetes Care’, launched in 2016, advocates an integrated care pathway with the joint involvement of all levels of care (primary, secondary and tertiary levels), in order to optimise the outcomes in patients with diabetes. This means that both primary and secondary care centres assume joint responsibility for patients.

According to the ICGP guidelines, patients with uncomplicated type 2 diabetes will be managed by primary care only. If patients develop complications, then they should be referred to secondary care for specialist opinion in diabetes, and will have their care shared between primary and secondary care. Certain patients will have their diabetes managed in secondary care only. (Please refer to full ICGP guidelines for more information).

The guidelines note that organisations such as the American Diabetes Association (ADA), the International Diabetes Federation (IDF) and the UK’s National Institute for Health and Care Excellence (NICE) recommend metformin as an option for first-line or combination therapy. NICE also recommends metformin both for those who are overweight (BMI>25.0kg/m²) and not overweight as the first-line glucose-lowering therapy where blood glucose is inadequately controlled using lifestyle interventions alone. If the HbA_1c target is not achieved quickly with metformin, there are six drug choices including a second oral agent (sulphonylurea, thiazolidinedioine, DPP-4 inhibitor, or SGLT2 inhibitor), a GLP-1 receptor agonist, or basal insulin. The higher the HbA_1c, the more likely insulin will be required.

The ICGP guidelines emphasise that early detection and prompt intervention are essential in the management of complications, and stress the importance of systematic screening for complications as part of integrated care. The guidelines outline a range of measures to prevent or delay the development of micro- and macrovascular complications of diabetes, covering lifestyle interventions, glucose control, hypertension, lipid management and statins, anti-platelet therapy, foot care, eye care, and renal disease.¹

Blood Glucose Lowering Therapy in Type 2 Diabetes Patients Not Achieving Glycaemic Targets¹

Targets and monitoring

• HbA_1c ≤ 53mmol/mol (≤7.0%) is appropriate for the majority of patients and has been shown to reduce diabetes related complications
• Targets should be set in consultation with the patient and taking their individual circumstances into consideration
• More stringent HbA_1c goals such as <48mmol/mol (<6.5%) may be considered for selected individuals if this can be achieved without significant hypoglycemia or other adverse effects
• Less stringent HbA_1c targets such as <58mmol/mol (<8%) may be appropriate for some individuals, with particular consideration for older or frail patients with type 2 diabetes
• Monitor HbA_1c level every four months and adjust treatment as appropriate if target not achieved

Figure 1. Antihyperglycaemic Treatment Recommendations in Patients with Healthy Weight (BMI between 18.5 – 25kg/m²)¹

Insulin initiation is usually carried out in a Diabetes Day Centre; however insulin initiation in General Practice is considered feasible once the practice has established its integrated diabetes service, including education of the Practice Nurses and GPs and the availability of the Community Diabetes Nurse Specialists¹

Figure 2. Antihyperglycaemic Treatment Recommendations in Overweight Patients (BMI between 25 – 30kg/m²)¹

Figure 3. Antihyperglycaemic Treatment Recommendations in Obese Patients (BMI >30kg/m²)¹

Blood Pressure Management in Patients with Type 2 Diabetes¹

Targets and monitoring

• Hypertension should be treated aggressively. Low salt diet, reduced alcohol intake, exercise and weight loss should be instituted where appropriate but should not delay commencement of drug therapy
• Targets should be set in consultation with the patient and taking their individual circumstances into consideration. Target blood pressure (BP) for patients with type 2 diabetes should be systolic ≤140 mm/Hg / diastolic 80 mmHg and stricter (below 130/80 mmHg) if there is kidney, eye or cerebrovascular damage. Higher or lower systolic BP targets may be appropriate depending on patient characteristics and response to therapy
• When type 2 diabetes is diagnosed in an adult already on antihypertensive drug treatment, the BP control and medications used should be reviewed. Changes in therapy should only be made if there is poor control or if current drug treatment is not appropriate due to microvascular complications or metabolic problems
• BP should be measured annually and at every routine practice visit if it is above target level. Repeat BP measurements within one month if BP >150/90 mmHg; within 2 months if BP >140/80 mmHg; or within 2 months if BP >130/80 mmHg (and there is kidney, eye or cerebrovascular damage)

Figure 4. Blood Pressure Treatment Recommendations in Patients with Type 2 Diabetes¹

Reference: 1. Harkins, V. A Practical Guide to Integrated Type 2 Diabetes Care. Irish College of General Practitioners. Published January 2016.

MIMS Ireland Copyright®

Table 1. Antihyperglycaemic Therapy in Type 2 Diabetes – List of agents available in Ireland

The post Focus on Type 2 Diabetes – ICGP Guidelines 2016 appeared first on Irish Medical Times.

A once weekly, buffered alendronate solution for the treatment of osteoporosis

Clonmel Healthcare Ltd is pleased to announce that Binosto (alendronic acid 70mg, once weekly effervescent tablets) is now available in Ireland. It is indicated for the treatment of postmenopausal osteoporosis, and reduces the risk of vertebral and hip fractures.¹ Binosto is the first and only buffered alendronate oral solution designed to help minimise gastric tolerability issues.

Osteoporotic fractures impose a huge social and economic cost in Ireland, approximately €402 million per annum is spent to treat all falls and fractures which occur in senior citizens with osteoporosis in Ireland. In addition to healthcare costs, vertebral fractures can cause back pain, loss of height, deformity, depression and low esteem. If current trends continue it is estimated that costs will be:

• €922 – 1077 million by 2020
• €1587 – 2043 million by 2030²

NICE guidelines recommend alendronate as a first-line treatment option for the primary prevention of fragility fractures in postmenopausal women who have osteoporosis.³ Alendronate is the most commonly prescribed drug worldwide for osteoporosis.⁴ It has proven efficacy to reduce the risk of vertebral and hip fractures.⁵ However, patient compliance is a major problem with alendronate. The majority of patients (59.9%) discontinue bisphosphonate treatment within one year.⁶

Alendronate may cause dyspepsia, dysphagia, oesophageal ulcers and oesophagitis, particularly if not taken according to dosing instructions.^7,8 Dysphagia and swallowing difficulties are common especially among elderly people, and the perceived potential for upper gastrointestinal (GI) side-effects is an obstacle to good long-term adherence.⁴

The implications of non-adherence to bisphosphonate therapy are significant, with a 46% greater fracture risk in patients with poor compliance versus compliant patients.⁹ Hip fractures are an enormous cost to the healthcare system, with hospital treatment of hip fracture averaging €20,166* per patient over 2 years.¹⁰ Patients who discontinue bisphosphonate therapy within the first 6 months have the same fracture risk as those who did not receive treatment.⁷ Compliance of at least 80% is necessary for full anti-fracture efficacy with alendronate, and increasing compliance with prescription refills is associated with progressively lower fracture rates in patients.⁴

*£16,302 converted to € 08/04/2016

In the daily clinical setting, where patients are not often offered frequent follow-up visits and regular reminders on how to take the medication, GI side-effects are the most common reason for alendronate discontinuation.^4,5 Proton pump inhibitors, potent acid-suppressive medications commonly used for management of acid-related diseases such as gastroesophageal reflux disease, can increase the risk of fracture.¹¹

Alendronate tablets can contribute to gastric tolerability issues in a number of ways:

• Early tablet disintegration in the oesophagus
• Slow transit time
• Acid reflux^7,8

In an effort to increase compliance and decrease upper GI irritation, soluble formulations of alendronate have been developed.^4,7,12 Adherence to oral osteoporosis therapy in patients treated with soluble alendronate is significantly higher compared with those receiving alendronate tablets.¹³ Soluble alendronate is bioequivalent to alendronate tablets.¹²

Binosto, an effervescent, buffered alendronate solution with high acid neutralising capacity, was designed to achieve two characteristics: (a) to minimise particulate alendronate from contacting the mucosa, and (b) to prevent strong stomach acidity being present with alendronate in the stomach, diminishing damage potential in cases of oesophageal reflux. Mucosal exposure to alendronate at a pH less than 3 is irritating to gastro-oesophageal tissue.⁸

Study design

A clinical study was designed to evaluate the gastric environment differences between Binosto and a standard alendronate tablet formulation. This was a single-centre, open-label, randomised, two-way crossover study in 12 healthy female volunteers. Study objectives were to assess the gastric emptying times and gastric pH after dosing of Binosto and standard alendronate tablets, and to evaluate potential dosing advantages of Binosto when compared to standard alendronate tablets. Gastric pH was monitored by nasogastric probes, and gastric emptying was determined by scintigraphic imaging of the radiolabelled formulations.⁸

To assess gastric transit, the primary variables were gastric emptying t_50% (time after dosing to 50% gastric emptying) and gastric emptying t_90% (time after dosing to 90% gastric emptying). To assess gastric pH, the primary variables were pH at t_50% and pH at t_90%. Secondary variables were time for gastric contents’ pH to go below pH 3 after dosing and pH at 30 minutes (min.) after dosing.⁸

Results

Mean gastric pH at t_50% was significantly higher in Binosto vs standard alendronate tablet treated subjects (3.5 +/- SD 1.2 vs pH 1.9 +/- SD 0.5 respectively, p=0.008). At t_90%, mean pH values were comparable (1.8 +/- SD 0.8 vs pH 1.3 +/- SD 0.3 respectively, p=0.155). Mean time to cross the pH 3 threshold post-dose was also significantly higher in Binosto vs standard alendronate tablet treated subjects (56.0 min +/- SD 56.0 vs 3.9 min +/- SD 3.0 respectively, p=0.014). Results for standard alendronate tablet treated subjects (n = 2) with t_50% greater than 30 min. indicated that acidic alendronate was present in their stomachs at 30 min.; however, all Binosto subjects in this subgroup maintained an elevated pH at 30 min. There was no statistically significant or physiologically relevant differences in gastric emptying times. Both dosage formulations were well tolerated and completely reached the stomach without oesophageal adhesion.⁸

Conclusions

Binosto was delivered to the stomach completely with no retention of dosage form in the oesophagus which mitigates the potential for pill oesophagitis. Gastric pH after dosing with Binosto was generally established and maintained to levels above pH 3 until gastric emptying or when food would normally be ingested. This minimises the risk of exposing the oesophagus (in case of reflux) and stomach to acidified alendronate. Taken according to dosing instructions, the standard alendronate tablet entered the stomach directly with no oesophageal adhesion; however, improper administration can result in tablets lodging in the oesophagus. Gastric pH was found to be strongly acidic after dosing with the standard alendronate tablet, a recognised risk factor for oesophageal irritancy with alendronate treatment.⁸

Binosto offers the potential of enhanced gastric tolerability and improved compliance and persistence with treatment compared with alendronate tablets, and the potential to decrease the fracture risk in osteoporotic patients.⁷

References: 1. Binosto SPC (revised September 2015). 2. Irish Society of Osteoporosis Guidelines 2012. Available at http://www.irishosteoporosis.ie/images/uploads/IOS%20Guidelines%20Sept%202012(1).pdf. 3. NICE Technology Appraisal Guidance [TA160]. Published October 2008. Available at https://www.nice.org.uk/guidance/ta160?unlid=9383636202016224913 4. Brandi M and Black D. Clinical Cases Miner Bone Metab 2013;120(3):187-190. 5. Black DM et al. J Clin Endocrinol Metab 2000; 85(11):4118-4124. 6. Modi A et al. J Manag Care Spec Pharm 2015;21(6):499-506. 7. Invernizzi M et al. Aging Clin Exp Res 2015;27:107-113. 8. Hodges LA et al. Int Journal of Pharmaceutics 2012;432:57-62. 9. Imaz I et al. Osteoporosis Int 2010;21:1943-1951. 10. Available at http://www.iofbonehealth.org/news/prevention-costly-hip-fractures-should-be-priority-uk. 11. Yu EW et al. Am J Med 2011;124(6):519-526. 12. Acotto CG et al. Calcif Tissue Int 2012;91:325-334. 13. Coaccioli S et al. Clin Cases Miner Bone Metab 2014; 11(2): 123-125.

Date prepared: October 2016

2016/ADV/BIN/086

Full prescribing information and references available from Clonmel Healthcare Ltd. Telephone: (052) 617 7777.

Written by Caroline McDermott PhD, Editor, MIMS Ireland

Sponsored by Clonmel Healthcare Ltd.

The post Binosto (alendronic acid 70mg) appeared first on Irish Medical Times.

Direct-Acting Antivirals (Daklinza, Exviera, Harvoni, Olysio, Sovaldi, Victrelis, Viekirax, Zepatier and Epclusa)* are used to treat chronic hepatitis C virus (HCV) infection. These medicines reduce the amount of HCV in the body by preventing HCV from multiplying, and in most cases, they cure HCV.

A signal of a potential drug interaction leading to a reduced international normalised ratio (INR) has recently been identified with co-administration of Direct-Acting Antivirals and vitamin K antagonists. The case reports on which the signal was based were reviewed by the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC). The PRAC has recommended that the product information of Direct-Acting Antivirals should be updated to include a recommendation for close monitoring of INR in patients treated with vitamin K antagonists, as liver function may change during treatment with Direct-Acting Antivirals. Pharmacokinetic studies with warfarin have been performed for Olysio, Viekirax and Exviera. While no change in the pharmacokinetics of warfarin is expected, close monitoring of INR is recommended with all vitamin K antagonists. This is due to liver function changes during treatment with Direct-Acting Antivirals.

Advice to Healthcare Professionals

As liver function may change during treatment with Direct-Acting Antivirals, it is recommended that INR is closely monitored in patients concurrently treated with vitamin K antagonists.

Key Message

• Liver function changes during treatment with Direct-Acting Antivirals may lead to a reduced INR in patients concurrently treated with warfarin and other vitamin K antagonists.
• Healthcare professionals should be alert to this potential interaction and closely monitor INR in these patients.
•  The product information (Summary of Product Characteristics (SmPC) and Package Leaflet (PL)) for these products will be updated shortly.

*Daklinza (daclatasvir), Exviera (dasabuvir), Harvoni (sofosbuvir/ledipasvir), Olysio (simeprevir), Sovaldi (sofosbuvir), Victrelis (boceprevir) and Viekirax (ombitasvir/paritaprevir/ritonavir). Further details are available on www.hpra.ie and  www.ema.europa.eu

The post Direct-Acting Antivirals for Hepatitis C: Advice on interaction potential with warfarin and other vitamin K antagonists leading to a reduced international normalised ratio (INR) appeared first on Irish Medical Times.

Maintenance bronchodilator treatment to relieve symptoms in adults with COPD

Spiolto Respimat is a fixed dose combination inhalation solution containing a long acting muscarinic receptor antagonist, tiotropium and a long acting beta₂-adrenergic agonist, olodaterol (LAMA/LABA) which is delivered via the Respimat soft mist inhaler device.

Muscarinic receptors are more prominent in the central airways while beta₂ adrenoceptors have a higher expression level in the peripheral airways. Therefore the combination of a LAMA and a LABA should provide optimal bronchodilatation in all regions of the lungs.

Spiolto is indicated as a maintenance bronchodilator treatment to relieve symptoms in adults with chronic obstructive pulmonary disease (COPD). The recommended dose is tiotropium/olodaterol 5/5mcg given as two puffs once daily, at the same time of the day.¹

Respimat is a soft mist inhaler device designed for more effective drug delivery to the lungs. It produces a low velocity, long-lasting aerosol cloud, with a higher fine particle fraction than most other inhalers.^2,3 It has a lower throat deposition and higher whole lung deposition than other commercially available devices.^4,5

The majority of patients with COPD are already suffering from moderate airflow limitation at diagnosis,⁶ when initiation of maintenance therapy is recommended.⁷ Decreasing lung function causes breathlessness and leads to a downward spiral of reduced physical activity, worsening symptoms and further inactivity.⁸ Decreasing exercise capacity reduces quality of life and increases the risk of disability and death.⁹

Patients with moderate COPD have a steeper decline in lung function than those with more severe disease.¹⁰ Pharmacotherapeutic intervention in patients with moderate COPD has been associated with significant improvements in health status, and reductions in exacerbations and rate of decline of lung function, compared with placebo.^11,12

Spiolto received marketing authorisation based on data from the TOviTO clinical trial programme (>15,000 patients), including the pivotal TONADO trials. This programme was designed to evaluate the effect of Spiolto on many of the important clinical outcomes of COPD (e.g. lung function, quality of life, breathlessness, physical activity, ability to exercise, exacerbations).

Studies design

TONADO 1 and TONADO 2 were two 52 week, replicate, randomised, double-blind, active-controlled, parallel-group, multicentre, phase III trials (total n = 5162) in which the efficacy and safety of the tiotropium/olodaterol 5/5mcg combination were compared with the individual components, tiotropium 5mcg or olodaterol 5mcg. All study drugs were administered once-daily in the morning via the Respimat inhaler. Patients received inhaled corticosteroids, rescue medication (salbutamol/albuterol), oral steroids or theophylline preparations as required during treatment.¹³

The three primary efficacy end points were assessed after 24 weeks of treatment: Forced expiratory volume in 1 second (FEV₁) area under the curve from 0 to 3 hours (AUC_0–3) response, trough FEV₁ response, and St George’s Respiratory Questionnaire (SGRQ) total score. A key secondary efficacy end point was Mahler Transition Dyspnoea Index (TDI) focal score at 24 weeks.

Main inclusion criteria for the studies: Patients aged ≥40 years with a history of moderate to very severe COPD (GOLD stages 2–4); post-bronchodilator FEV₁ <80% of predicted normal; post-bronchodilator FEV₁/forced vital capacity (FVC) <70%; current or ex-smokers with a smoking history of >10 pack–years.¹³

Spiolto provided significant improvements in lung function, quality of life and breathlessness

Significant improvements in FEV₁ AUC_0-3 and trough FEV₁ responses (i.e. change from baseline) after 24 weeks (lung function primary end points) were observed in patients treated with the tiotropium/olodaterol combination compared to those treated with tiotropium or olodaterol alone in the individual studies and the combined analysis (p≤0.0001 for all comparisons).

The combination treatment showed a 110ml or 128ml improvement in FEV₁ AUC_0-3 response vs tiotropium or olodaterol alone, respectively, and a 60ml or 85ml improvement in trough FEV₁ response vs tiotropium or olodaterol alone, respectively, in the combined analysis (see figure 1).

Pre-specified combined analysis of SGRQ total score after 24 weeks from both studies (quality of life primary end point) showed significant improvements for the combination treatment compared to tiotropium or olodaterol alone (decrease from baseline of 6.8 units vs 5.6 units [p<0.05] or vs 5.1 units [p<0.01], respectively) (see figure 2). More patients treated with the combination had a clinically meaningful improvement in SGRQ total score (defined as a decrease of at least 4 units from baseline) compared to tiotropium or olodaterol alone (57.5% vs 48.7% [p=0.0001] or vs 44.8% [p<0.0001], respectively) in the combined analysis.

Pooled analysis of Mahler TDI focal score at 24 weeks from both studies (breathlessness secondary end point) revealed significant improvements for the combination treatment compared to tiotropium or olodaterol alone (increase from baseline of 1.98 units vs 1.63 units [p<0.05] or vs 1.56 units [p<0.005], respectively) (see figure 3).

The incidence of adverse events was comparable across all treatment groups, with the majority being mild to moderate in severity. The majority of treatment-emergent adverse events with an incidence of >3% were respiratory events, in particular COPD exacerbations and infections.¹³

Spiolto improved lung function profile over 24 h

The findings of the TONADO trials are complemented and supported by a randomised, double-blind, 6-week phase III trial (n=219) which showed significant improvements in FEV₁AUC from 0 to 24 hours with the tiotropium/olodaterol combination compared with tiotropium or olodaterol alone (treatment difference of 110ml or 115ml [p<0.0001 for both comparisons], respectively).¹⁴

Conclusions

Spiolto provided significant improvements in lung function, quality of life and breathlessness over tiotropium or olodaterol alone in patients with moderate to very severe COPD, with a comparable safety profile.

References: 1. Spiolto Respimat SPC (revised March 2016). 2. Anderson P et al. Int J COPD 2006;1(3):251–259. 3. Dalby R, Spallek M, Voshaar T. Int J Pharm 2004;283:1–9. 4. Ciciliani A, Wachtel H, Langguth P. Respiratory Drug Delivery 2014;2:453–456. 5. Ciciliani A et al. Respiratory Drug Delivery Europe 2015;2:357-362. 6. Mapel DW et al. Int J COPD 2011; 6: 573–581. 7. NICE Clinical guideline [CG101]. Available at: https://www.nice.org.uk/guidance/cg101. Last accessed November 2016. 8. Reardon JZ et al. Am J Med 2006; 119 (10 Suppl 1): 32-7. 9. Casaburi R. Am Thorac Soc 2011; 8(4):334-7.  10. Tantucci C, Modina D. Int J Chron Obstruct Pulmon Dis 2012; 7:95-9. 11. Decramer M et al. Lancet. 2009;374(9696):1171–1178. 12. Jenkins CR et al. Respir Res. 2009;10:59. 13. Buhl R et al. Eur Respir J 2015; 45(4):969-79. 14. Beeh KM et al. Pulm Pharmacol Ther 2015;32:53–59. MIMS Ireland Copyright^®

Written by Caroline McDermott PhD, Editor, MIMS Ireland

Initiated, funded and reviewed by Boehringer Ingelheim Ltd.

The post Spiolto Respimat (tiotropium/olodaterol) appeared first on Irish Medical Times.

Company: Eli Lilly and Co (Ireland) Ltd.

Legal category: Prescription. High tech reimbursable. Sport permitted.

Active ingredient: Ixekizumab 80mg/ml.

Description: Solution for injection in pre-filled syringe or pen.

Presentation: 1 syringe; 1 or 2 pens. Price available on request.

Indication: Treatment of moderate to severe plaque psoriasis in candidates for systemic therapy.

Pharmacology: Ixekizumab is an IgG4 monoclonal antibody that binds with high affinity and specificity to interleukin 17A. Elevated concentrations of IL‑17A have been implicated in the pathogenesis of psoriasis by promoting keratinocyte proliferation and activation. Neutralisation of IL‑17A by ixekizumab inhibits these actions.

Dosage: Adult: Administer by subcutaneous injection. Consider discontinuation if no response after 16 to 20 weeks. Avoid skin areas that show psoriasis. 160mg at Week 0, followed by 80mg at Weeks 2, 4, 6, 8, 10, and 12. Maintenance, 80mg every 4 weeks. Elderly: As per adults. 75 years and older, limited data. Children: Under 18 years, not recommended.

Contraindications: Hypersensitivity to the active substance or to any of the excipients. Clinically important active infections.  Pregnancy. Women should use contraception and not breast feed (assess risk/benefits) during treatment and ≤10 weeks after.

Special precautions: Caution: Inflammatory bowel disease, chronic infection (closely monitor if develops; suspend if serious or if no response to standard therapy). Latent tuberculosis (TB), consider anti-TB therapy prior to initiation. Discontinue immediately if hypersensitivity reactions occur.

Drug interactions: Not recommended: Live vaccines. CYP450 substrates with a narrow therapeutic index.

Adverse drug reactions: Upper respiratory tract infection, tinea infection, oropharyngeal pain, nausea, injection site reactions.

Full prescribing information and references available from Eli Lilly and Co (Ireland) Ltd. Telephone: (01) 664 0446. E-mail: ukmedinfo@lilly.com

The post Taltz ▼ appeared first on Irish Medical Times.

Company: Santen UK Limited.

Legal category: Prescription. GMS reimbursable. Sport permitted.

Active ingredient: Ciclosporin 1mg/ml.

Description: Eye drops.

Presentation: 30 x 0.3ml single-dose containers, €86.50.

Indications: Treatment of severe keratitis in patients with dry eye disease not improved by tear substitutes.

Pharmacology: Ciclosporin is a cyclic polypeptide immunomodulator with immunosuppressant properties and an anti-inflammatory effect. Following ocular administration, ciclosporin is passively absorbed into T-lymphocyte infiltrates in the cornea and conjunctiva and inactivates calcineurin phosphatase. Ciclosporin-induced inactivation of calcineurin inhibits the dephosphorylation of the transcription factor NF-AT and prevents NF-AT translocation into the nucleus, thus blocking the release of pro-inflammatory cytokines such as IL-2.

Dosage: Adult: Must be initiated by an ophthalmologist or HCP qualified in ophthalmology. One drop to affected eye(s) once daily at bedtime (maximum). Review at least every 6 months. Elderly: As per adults. Children: Under 18 years, no relevant use.

Contraindications: Hypersensitivity to the active substance or to any of the excipients. Active or suspected ocular or peri-ocular infection. Pregnancy, lactation; assess risk/benefit.

Special precautions: Remove contact lenses before instillation (may reinsert at wake-up time); carefully monitor patients with severe keratitis. Caution: Glaucoma (especially with beta-blockers), history of ocular herpes. May affect immune system. Driving/usingmachines (ensure clear vision). Contains cetalkonium chloride.

Drug interactions: Administer other ophthalmic products at least 15 minutes apart with Ikervis last. Corticosteroids.

Adverse drug reactions: Instillation site pain, instillation site irritation, instillation site erythema, instillation site lacrimation, eyelid erythema, eyelid oedema, increased lacrimation, ocular hyperaemia, blurred vision, conjunctival hyperaemia, eye irritation, eye pain.

Full prescribing information and references available from Santen. Telephone: (01) 695 0008. E-mail: medinfo@santen.co.uk

The post Ikervis appeared first on Irish Medical Times.

Company: Rowex Ltd.

Legal category: Prescription. GMS reimbursable. Sport permitted.

Active ingredient: Desogestrel 75mcg.

Description: Round, plain, white film-coated tablets.

Presentation: 3 x 28, €6.92.

Indications: Contraception.

Pharmacology: The progestogen desogestrel inhibits ovulation and increases viscosity of cervical mucus.

Dosage: Adult: One tablet taken daily at the same time every day with first tablet taken on first day of menstrual bleeding. Start new blister directly the day after previous one. Children: Under 18 years, not recommended.

Contraindications: Hypersensitivity to the active ingredient or to any of the excipients. Active venous thromboembolic disorder, severe hepatic disease (or history) as long as liver function values not normal, sex-steroid sensitive malignancies, undiagnosed vaginal bleeding.

Special precautions: Withdraw immediately if pregnancy occurs during use. Assess risk/benefit if presence/ appearance/ aggravation of: Breast cancer, liver cancer, liver function disturbances. Caution: History of thrombo-embolic disorders, diabetes. Discontinue if: Thrombosis, long-term immobilisation due to surgery or illness, sustained hypertension. Avoid sun/UV if tendency to chloasma. Bleeding disturbances may occur; consider another contraceptive method if very frequent and irregular. Consider ectopic pregnancy if amenorrhoea or abdominal pain occurs. Contains lactose, soya-bean oil.

Drug interactions: Microsomal enzyme-inducing drugs, use a barrier method during and for 28 days after administration. Medicinal charcoal.

Adverse drug reactions: Mood changes, decreased libido, headache, nausea, acne, breast pain, irregular menstruation, amenorrhoea, increased weight.

Full prescribing information and references available from Rowex Ltd. Telephone: 1800 304400. Fax: (027) 50417. E-mail: rowex@rowa-pharma.ie

The post Desogestrel Rowex appeared first on Irish Medical Times.

Please check back here again early in the new year for more information on our new website which will feature a searchable online database of medicines listed in our publication

The post New MIMS Ireland website coming soon appeared first on Irish Medical Times.

The World Anti-Doping Agency (WADA) has issued a new Prohibited List of Substances and Methods which will come into effect from 1 January 2017.

The WADA List Expert Group reviews the List annually and considers submissions from stakeholders, advancements in science and medical research, information on doping practices etc. A substance or method is added to the List if it meets two of three criteria: it is performance-enhancing, poses a danger to athletes’ health or its use is against the spirit of sport.

Changes of note include the following:

In section 3 Beta-2-agonists: The dosing limit of salbutamol has been further refined to clarify that the full 24-hour dose should not be administered at one time.  Inhaled salbutamol is permitted to a maximum of 1,600µg over 24 hours, not to exceed 800µg every 12 hours.

In section 3 Beta-2-agonists: The maximum dose of salmeterol has now been stated as 200µg over 24 hours.

Monitoring Programme: To detect patterns of use, the following have been added to the 2017 Monitoring Programme – the opioid codeine has been added to the programme under in-competition narcotics while the concurrent use of multiple beta-2-agonists has been added to the monitoring programme both in- and out-of-competition.

Commenting on the publication of the 2017 WADA List, Dr Una May, Director of Participation and Ethics in Sport Ireland said “It is important that anyone with a role in supporting athletes needs to ensure that they keep themselves up to date at all times in relation to Anti-Doping. MIMS is an essential part of Sport Ireland’s Anti-Doping Prevention and Information programme and provides the necessary information for medical personnel regarding WADA’s Prohibited List.”

The updates to the 2017 List will be reflected in the Sport Ireland Athlete’s wallet cards, MIMS Ireland, the Eirpharm.com Drugs in Sport Database and the Medication Checker App which allows users to access the live Eirpharm Drugs in Sport Database.

More information is available from Sport Ireland at (01) 8608818,  fax: (01) 8608860, website: www.sportireland.ie/Anti-Doping, www.eirpharm.com and National Governing Bodies of Sport.

The post World Anti-Doping Agency announces changes to its Prohibited List for 2017 appeared first on Irish Medical Times.

Company: MSD Ireland (Human Health) Ltd.

Legal category: Prescription. GMS reimbursable. Sport permitted.

Active ingredients: Elbasvir/grazoprevir 50/100mg.

Description: Beige, oval film‑coated tablet marked 770.

Presentation: 28, price on request.

Indication: Treatment of chronic hepatitis C in patients with genotypes 1a, 1b and 4.

Pharmacology: Elbasvir (HCV NS5A inhibitor) and grazoprevir (HCV NS3/4A inhibitor) combine two direct-acting antiviral agents which provide distinct mechanisms of action and non-overlapping resistance profiles to target HCV at multiple steps in the viral lifecycle. HCV NS5A, is essential for viral RNA replication and virion assembly. The HCV NS3/4A protease is necessary for the proteolytic cleavage of the HCV encoded polyprotein and is essential for viral replication.

Dosage: Adult: Swallow whole once daily. Genotype 1a, Zepatier for 12 weeks (consider Zepatier for 16 weeks plus ribavirin in patients with baseline HCV RNA level >800,000 IU/ml and/or presence of specific NS5A polymorphisms causing ≥5-fold reduction in elbasvir activity); genotype 1b, Zepatier for 12 weeks; genotype 4, Zepatier for 12 weeks (consider Zepatier for 16 weeks plus ribavirin in patients with baseline HCV RNA level >800,000 IU/ml). If vomiting occurs within 4 hours, take additional tablet. Elderly: As per adults. Children: Under 18 years, not recommended.

Contraindications: Hypersensitivity to the active substances or to any of the excipients. Moderate or severe hepatic impairment. Lactation.

Special precautions: Not recommended: HCV genotypes 2, 3, 5 and 6. Perform hepatic testing prior to therapy, at week 8, and as clinically indicated (with additional testing at week 12 for patients receiving 16 weeks of therapy). Seek immediate medical advice if onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice or discoloured faeces occur. Consider discontinuation if ALT levels >10 X ULN. Discontinue if ALT elevation accompanied by signs of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or international normalised ratio. Safety and efficacy not established: Liver transplant recipients, HCV/HBV co‑infected patients. Retreatment (including drugs of same class), efficacy not established. Pregnancy (assess risk/ benefit). Male patients and female partners of male patients taking ribavirin must use effective form of contraception; see ribavirin SPC. Patients requiring ribavirin (see ribavirin SPC prior to initiation). Driving/using machines (fatigue reported). Contains lactose, sodium.

Drug interactions: Contraindicated: Organic anion transporting polypeptide 1B (OATP1B) inhibitors, CYP3A or P-gp inducers, St. John’s wort, bosentan, efavirenz, etravirine, elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate (fixed-dose combination), modafinil, some anticonvulsants/ protease inhibitors/ immunosuppressants. Not recommended: Strong CYP3A inhibitors, some antifungals/ antimycobacterials. P-gp inhibitors (minimal effect), BCRP substrates, BSEP, tacrolimus, some anticoagulants. Atorvastatin, fluvastatin, lovastatin, simvastatin daily doses >20mg; rosuvastatin daily doses >10mg. Laboratory abnormalities.

Adverse drug reactions: Decreased appetite, insomnia, anxiety, depression, headache, dizziness, gastrointestinal disorders, pruritus, alopecia, arthralgia, myalgia, fatigue, irritability.

Full prescribing information and references available from MSD Ireland (Human Health) Ltd. Telephone: (01) 2998700.

The post Zepatier ▼ appeared first on Irish Medical Times.

Company: Rowex Ltd.

Legal category: Prescription. GMS reimbursable. Sport permitted.

Active ingredient: Pramipexole (as dihydrochloride monohydrate) 1.05mg, 2.1mg.

Description: White, cylindrical, biconvex prolonged-release tablets marked 105 or 210, respectively.

Presentation: 1.05mg-30, €39.63; 2.1mg-30, €69.93.

Indications: Treatment of signs and symptoms of idiopathic Parkinson’s disease, alone or in combination with levodopa.

Pharmacology: Pramipexole is a dopamine agonist that binds with high selectivity and specificity to the D2 subfamily of dopamine receptors of which it has a preferential affinity to D3 receptors, and has full intrinsic activity. It alleviates parkinsonian motor deficits by stimulation of dopamine receptors in the striatum. It inhibits dopamine synthesis, release, and turnover.

Dosage: Adult: Swallow whole at same time each day. Week 1, 0.26mg base (0.375mg salt) daily, may increase daily dose every 5-7 days if tolerated; Week 2, 0.52mg base (0.75mg salt); Week 3, 1.05mg base (1.5mg salt). May further increase daily dose by 0.52mg base (0.75mg salt) at weekly intervals (maximum 3.15mg base (4.5mg salt) per day). May switch from pramipexole immediate-release tablets to prolonged-release tablets overnight, at same daily dose and adjust depending on therapeutic response. When co-prescribed, reduce dose of levodopa while titrating pramipexole. Renal impairment: See SPC. Children: Under 18 years, not recommended.

Contraindications: Hypersensitivity to the active substance or to any of the excipients. Pregnancy (unless clearly necessary), lactation.

Special precautions: Inform patients that somnolence/sudden sleep onset (reduce dose/ discontinue) and hallucinations may occur. Dyskinesia may occur during initial titration (reduce dose). Monitor for impulse control disorders, mania and delirium (reduce dose/ discontinue). Patients with psychotic disorders (assess risk/benefit). Regular ophthalmologic monitoring recommended or if vision abnormalities occur. Severe cardiovascular disorders (monitor blood pressure). Renal impairment. Neuroleptic malignant syndrome reported with abrupt withdrawal (see SPC). Hepatic impairment, no data. Driving/using machines.

Drug interactions: Avoid: Antipsychotics. Caution: Alcohol, sedating drugs. Levodopa, other anti-parkinsonian drugs. Inhibitors/competitors of active renal elimination pathway (reduce pramipexole dose).

Adverse drug reactions: Abnormal dreams, insomnia, dizziness, headache, somnolence, gastrointestinal disorders, fatigue, behavioural symptoms of impulse control disorders and compulsions, confusion, hallucinations, dyskinesia, amnesia, visual disturbances, hypotension, peripheral oedema, weight loss.

Full prescribing information and references available from Rowex Ltd. Telephone: 1800 304400. Fax: (027) 50417. E-mail: rowex@rowa-pharma.ie

The post Prapexin appeared first on Irish Medical Times.

Company: Dermal Laboratories Ltd.

Legal category: OTC. Sport permitted.

Therapeutic ingredients: Isopropyl myristate/ liquid paraffin 15%/15% w/w.

Description: Emollient gel.

Presentation: 100g, €3.42.

Indications: Management of dry or chapped skin conditions (e.g. eczema, psoriasis, ichthyosis).

Pharmacology: Isopropyl myristate and liquid paraffin are oily ingredients that help rehydrate and soften dry skin while being relatively non-greasy. They form an occlusive barrier within the skin surface, which reduces drying from evaporation of water that diffuses from underlying layers, thus restoring normal protective skin function. The excipient glycerol is a humectant which also helps retain moisture.

Dosage: Adult: Apply over and around affected areas as often as necessary, even when skin appears normal. Elderly: As per adults. Children: As per adults.

Contraindications: Hypersensitivity to the therapeutic ingredients or to any of the excipients.

Special precautions: Do not rub skin vigorously. Avoid oral ingestion (treat symptomatically if diarrhoea occurs, do not induce vomiting). Discontinue if local skin reactions occur (rare). Contains glycerol, carbomer, sorbitan laurate, trolamine, phenoxyethanol.

Drug interactions: None (if using other topical treatments, allow sufficient time for previous application to soak in before administration).

Adverse drug reactions: None common.

Full prescribing information and references available from Dermal Laboratories Ltd. E-mail: info@dermal.co.uk

The post Doublebase appeared first on Irish Medical Times.

Company: Teva Pharmaceuticals Ireland.

Legal category: Prescription. GMS reimburseable. Sport permitted.

Active ingredient: Tiotropium (as bromide) 10mcg per delivered dose.

Description: Hard capsule containing inhalation powder for use with Zonda device.

Presentation: 30 + Zonda inhaler, €28.93.

Indications: Maintenance bronchodilator treatment to relieve symptoms of chronic obstructive pulmonary disease (COPD).

Pharmacology: Tiotropium, an anticholinergic, is a long-acting, specific muscarinic receptor antagonist which competitively and reversibly binds to M3 receptors in bronchial smooth musculature, antagonising the cholinergic (bronchoconstrictive) effects of acetylcholine, resulting in bronchial smooth muscle relaxation.

Dosage: Adult: Inhale one capsule once daily with Zonda inhaler at same time each day (maximum). Elderly: As per adults. Children: Under 18 years, not recommended.

Contraindications: Hypersensitivity to the active ingredient or to any of the excipients.

Special precautions: Not for use in acute episodes of bronchospasm. Immediate hypersensitivity reactions may occur after administration. Discontinue immediately if paradoxical bronchospasm occurs. Caution: Narrow-angle glaucoma, prostatic hyperplasia, bladder-neck obstruction, recent myocardial infarction <6 months, unstable or life-threatening cardiac arrhythmia requiring intervention or a change in drug therapy in the past year, hospitalisation for heart failure during previous year. May be associated with dental caries with long term use. Moderate-severe renal impairment (assess risk/benefit). Discontinue and seek immediate specialist advice if eye symptoms develop. Driving/using machines (dizziness, blurred vision). Pregnancy (avoid), lactation (assess risk/benefit).Contains lactose.

Drug interactions: Not recommended: Other anticholinergics.

Adverse drug reactions: Dry mouth.

Full prescribing information and references available from Teva Pharmaceuticals Ireland. Telephone: 1800 201700.

The post Braltus appeared first on Irish Medical Times.

Company: Raisio.

Legal category: OTC.

Composition: Plant stanol ester 0.5g per piece.

Description: Lemon & lime soft chews (food supplement).

Presentation: 45, €9.67.

Indications: Helps to lower cholesterol.

Dosage: Adult: 1.5-3g (3-6 pieces) maximum per day taken with a meal. Children: Under 5 years, contraindicated. Keep out of reach of small children.

Contraindications: Pregnancy, lactation.

Special precautions: Should not be considered as a substitute for a varied, balanced diet and lifestyle. Contains xylitol, glycerol, trisodium citrate, malic acid. Packaging contains rapeseed oil.

Drug interactions: Seek medical advice if taking cholesterol lowering drugs.

Adverse drug reactions: None.

Full prescribing information and references available from AM Brands. Telephone: (0044) 2892 605 621. Fax: (0044) 2892 604 738.

E-mail: info@am-brands.co.uk

The post Benecol appeared first on Irish Medical Times.

Company: Rowex Ltd.

Legal category: Prescription. Hi tech reimbursable. Sport permitted.

Active ingredient: Imatinib (as mesilate) 100mg, 400mg.

Description: Very dark yellow to brownish orange, round or ovaloid, biconvex film-coated tablets marked with NVR or 400 on one side and SA or SL on either side of score line on reverse, respectively.

Presentation: 100mg-60, €470.86; 400mg-30, €941.72.

Indications: Newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) when bone marrow transplantation not considered as first line treatment. Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis. Newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy. Adults only: Relapsed or refractory Ph+ ALL as monotherapy; myelodysplastic/ myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements; advanced hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL) with FIP1L1-PDGFRa rearrangement; unresectable dermatofibrosarcoma protuberans (DFSP) and recurrent and/or metastatic DFSP when not eligible for surgery.

Pharmacology: Imatinib is a small molecule protein-tyrosine kinase inhibitor that potently inhibits the activity of the Bcr-Abl tyrosine kinase (TK), as well as several receptor TKs: Kit, the receptor for stem cell factor (SCF) coded for by the c-Kit protooncogene, the discoidin domain receptors (DDR1 and DDR2), the colony stimulating factor receptor (CSF-1R) and the platelet-derived growth factor receptors alpha and beta (PDGFR-alpha and PDGFR-beta). It also inhibits cellular events mediated by activation of these receptor kinases.

Dosage: Adult: Take with meal and large glass of water, if unable to swallow may disperse in glass of still water or apple juice. CML: Chronic phase, 400mg once daily; accelerated phase or blast crisis, 600mg once daily. May consider increasing dose to up to 800mg/day (maximum) as 400mg twice daily (morning and evening) in certain circumstances (see SPC). Ph+ ALL (supervise): 600mg once daily until disease progression. MDS/MPD: 400mg once daily. HES/CEL: 100mg once daily, may increase to 400mg if tolerated and response insufficient. Continue as long as patient benefits. DFSP: 800mg/day. Dose adjustments: See SPC. Hepatic impairment: 400mg daily, reduce if not tolerated. Renal impairment, dialysis (caution): Initially 400mg daily, increase/reduce if tolerated/not tolerated, respectively. Elderly: As per adults. Children: CML: Chronic or advanced phase, 340mg/m2 once daily dose or split (morning and evening); may consider increasing dose to 570mg/m2 daily in certain circumstances (see SPC); maximum 800mg total dose. Under 2 years, no experience. Ph+ ALL: 340mg/m2 (maximum 600mg total dose). Under 1 year, no experience. MDS/MPD, DFSP, HES/CEL: Under 18 years, not recommended.

Contraindications: Hypersensitivity to the active substance or to any of the excipients. Pregnancy (unless clearly necessary), lactation.

Special precautions: Evaluate renal function (closely monitor during therapy) prior to initiation, correct clinically significant dehydration and high uric acid levels prior to initiation, assess risk/benefit of HES/CEL patients prior to initiation. Hepatitis B reactivation may occur (consult expert if positive for serology prior to initiation or if HBV infection occurs during treatment); closely monitor carriers during therapy and for several months following discontinuation. Caution: Severe renal impairment, cardiac dysfunction. Cardiac disease (monitor for cardiac failure). Monitor liver enzymes (especially in patients with hepatic impairment, also monitor peripheral blood counts). Severe fluid retention (weigh patients regularly). Thyroidectomy patients undergoing levothyroxine replacement (closely monitor thyroid-stimulating hormone levels). Monitor for gastrointestinal (GI) haemorrhage (consider discontinuation). Closely monitor growth in children. Perform complete blood counts regularly. Cytopenias may occur in CML patients; may need to suspend or reduce dose. Driving/using machines (caution).

Drug interactions: Avoid: Strong CYP3A4 inducers, coumarin derivatives (use low-molecular-weight or standard heparin instead). Caution: CYP3A4 substrates, inducers, and inhibitors, paracetamol (with high dose Imatinib), CYP2D6 substrates with a narrow therapeutic window, levothyroxine, L-asparaginase.

Adverse drug reactions: Neutropenia (including febrile), thrombocytopenia, anaemia, pancytopenia, anorexia, insomnia, headache, dizziness, paraesthesia, taste disturbance, hypoaesthesia, fluid retention, oedema (including eyelid, face, periorbital), increased lacrimation, conjunctival haemorrhage, conjunctivitis, dry eye, blurred vision, flushing, haemorrhage, dyspnoea, epistaxis, cough, GI disorders, increased hepatic enzymes, dermatitis/ eczema/ rash, pruritus, dry skin, erythema, alopecia, night sweats, photosensitivity reaction, muscle spasm and cramps, pain (bone, musculoskeletal including myalgia), arthralgia, joint swelling, fatigue, weakness, pyrexia, anasarca, chills, rigors, increased/ decreased weight.

Full prescribing information and references available from Rowex Ltd. Telephone: 1800 304400. Fax: (027) 50417. E-mail: rowex@rowa-pharma.ie

The post Imatinib Rowex appeared first on Irish Medical Times.

Apremilast is a selective immunosuppressant medicine indicated for use alone or in combination with disease modifying antirheumatic drugs (DMARDs) for the treatment of active psoriatic arthritis in adult patients who have had an inadequate response, or who have been intolerant to DMARD therapy previously. It is also indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who failed to respond to, or who have a contraindication to, or are intolerant to other systematic therapy including cyclosporine, methotrexate and ultraviolet-A light (PUVA).

It is important to note that suicidal behaviour-related events and depression are considered to occur more commonly in patients with psoriasis and psoriatic arthritis than in the general population. However, following a recent, thorough regulatory review of this issue, evidence from clinical trials and post-marketing experience suggests a causal association between suicidal ideation and behaviour with the use of apremilast.

Advice to Healthcare Professionals

• Suicidal ideation and behaviour have been reported from clinical trials and post-marketing experience (with or without a history of depression) with a frequency of uncommon (≥1/1000 to ≤1/100), while cases of completed suicide were reported during the post-marketing period in patients taking apremilast.
• The balance of benefits and risks of treatment with apremilast should be carefully considered in patients with a history of psychiatric symptoms or patients taking medicines which are likely to cause psychiatric symptoms.
• Treatment with apremilast should be discontinued in patients who present with new or  worsening psychiatric symptoms, or if suicidal ideation/suicidal behaviour is identified.
• Patients and carers should be informed of these risks and advised to contact the prescriber if any changes in mood or behaviour occur or in the case of any signs of suicidal ideation.
• The product information (Summary of Product Characteristics (SmPC) and Package Leaflet (PL)) for apremilast will be updated shortly.

Key message

• Following a regulatory review, evidence from clinical trials along with post-marketing experience suggests a causal association between suicidal ideation and behaviour with the use of apremilast.
• It is therefore recommended that the risks and benefits of commencing or continuing treatment with apremilast should be carefully assessed in patients with previous or existing psychiatric symptoms or if concomitant treatment with other medicinal products that are known to cause psychiatric effects.
• Patients and carers should be fully informed of these risks and advised to contact their doctor if symptoms emerge.
• All suspected adverse reactions associated with apremilast should be reported to the HPRA via the various reporting methods available (www.hpra.ie)

Further information on apremilast is available from www.hpra.ie and www.ema.europa.eu

The post Otezla (apremilast) – Important advice regarding suicidal ideation and behaviour appeared first on Irish Medical Times.

The World Anti-Doping Code, published by the World Anti-Doping Agency (WADA), harmonises anti-doping regulations across all sports and in all countries. The Prohibited List of Substances and Methods is one of the International Standards that are mandatory for all signatories of the Code. The List is a list of substances and methods which are prohibited in sport. Some of these substances are contained in medicinal products marketed in Ireland. However, in recognition of the fact that some prohibited substances may be necessary for legitimate medical treatment, the Code permits athletes and their physicians to apply for a Therapeutic Use Exemption (TUE).

Sport Ireland Therapeutic Use Exemption (TUE) Policy

If a medication is prohibited and requires a TUE, athletes should first seek to use an alternative permitted treatment. If there is no permitted alternative athletes should adhere to the Sport Ireland TUE Policy which states that athletes on the Sport Ireland Registered Testing Pool must apply for a TUE before using the substance (a Pre-Test TUE); athletes not on the Registered Testing Pool may take the substance, and if required, apply for a Post-Test TUE, but should ensure that a medical file* for use of the medication is in place. Athletes who compete at an International Level or who are on their International Federation Registered Testing Pool should check and comply with the TUE requirements of their International Federation.

*Medical file: See Glossary of MIMS Ireland.

Athletes should be advised to declare the use of all medications and supplements taken in the 14 days prior to the drug test on the doping control form (regardless if they have completed and submitted a TUE).

Full details, TUE Application Form and guidelines on the TUE Policy are available at www.sportireland.ie/Anti-Doping/Athlete-Zone/Therapeutic-Use-Exemptions-/

Summary of the WADA 2017 Prohibited List

Substances and Methods Prohibited In- and Out-of-Competition

Prohibited Substances

S0 Non-Approved Substances: Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development or discontinued, designer drugs, substances approved for veterinary use only) is prohibited.

S1 Anabolic Agents are prohibited. Examples include danazol, testosterone, stanozolol, tibolone and selective androgen receptor modulators (SARMs).

S2 Peptide Hormones, Growth Factors and Related Substances and Mimetics:

The following substances, including other substances with similar chemical structure or similar biological effect(s) and their respective releasing factors are prohibited:

1    Erythropoietin-Receptor agonists;

1.1  Eythropoiesis-Stimulating Agents (ESAs) [e.g. erythropoietin (EPO), darbepoietin (dEPO) CERA, peginesatide];

1.2  Non-erythropoietic EPO-Receptor agonists;

2   Hypoxia-inducible factor (HIF) stabilisers, e.g. cobalt and molidustat; and HIF activators, e.g. argon and xenon; Vitamin B12 is not prohibited;

3    Chorionic Gonadotrophin (CG) and Luteinizing Hormone (LH) and their     releasing factors, e.g. buserelin, gonadorelin, leuprorelin and triptorelin, are prohibited in men-only;

4  Corticotrophins and their releasing factors;

5   Growth Hormone (GH) and its releasing factors including Growth Hormone Releasing Hormone (GHRH) and its analogues, e.g. sermorelin; Growth Hormone Secretagogues (GHS), e.g. ghrelin and ghrelin mimetics and GH-Releasing Peptides (GHRPs).

Additional prohibited growth factors:

Fibroblast Growth Factors (FGFs); Hepatocyte Growth Factor (HGF); Insulin-like Growth Factor-1 (IGF-1) and its analogues; Mechano Growth Factors (MGFs); Platelet-Derived Growth Factor (PDGF); Vascular-Endothelial Growth Factor (VEGF) and any other growth factor affecting muscle, tendon or ligament protein synthesis/degradation, vascularisation, energy utilisation, regenerative capacity or fibre type switching.

S3 All Beta-2 Agonists are prohibited except:

• Inhaled salbutamol (up to a maximum dose of 1600µg over 24 hours, not to exceed 800µg every 12 hours);
• Inhaled formoterol (up to a maximum delivered dose of 54µg over 24 hours);
• Inhaled salmeterol (up to a maximum dose of 200µg over 24 hours).

To use any other inhaled beta-2 agonist, including terbutaline, indacaterol, vilanterol, olodaterol, formoterol (at delivered doses >54µg over 24 hours), salmeterol (at doses >200µg over 24 hours) and salbutamol (at doses >1600µg over 24 hours, not to exceed 800µg every 12 hours; such as by nebuliser), an athlete must adhere to the TUE Policy paying particular attention to the requirements of a medical file*. Formoterol is declared in terms of the delivered dose e.g. a Turbohaler device labelled as containing 6µg of formoterol delivers 4.5µg. Check the specific delivered dose of the device when calculating formoterol doses.

S4 Hormones and Metabolic Modulators such as aromatase inhibitors (e.g. exemestane, formestane, letrozole), selective oestrogen receptor modulators (SERMS, e.g. raloxifene, tamoxifen, toremifene), other anti-oestrogenic substances (e.g. clomiphene, fulvestrant), myostatin modifying agents and metabolic modulators including insulins and insulin mimetics and trimetazidine are prohibited.

S5 Diuretics and Masking Agents: Diuretics (including substances with a similar chemical or biological effect), desmopressin, probenecid, plasma expanders (e.g. oral and IV glycerol, IV administration of albumin, dextran, hydroxyethyl starch and mannitol, etc.), vaptans (e.g. tolvaptan) are prohibited. Note: Drosperinone, ophthalmic use of carbonic anhydrase inhibitors (e.g.  dorzolamine, brinzolamide) and local administration of felypressin in dental anaesthesia are permitted. Glycerol is prohibited as a plasma expander which requires the ingestion of quantities far beyond that which are commonly found in foodstuffs and toiletries.

The detection in an Athlete’s Sample at all times or In-Competition, as applicable, of any quantity of the following substances subject to threshold limits: formoterol, salbutamol, cathine, ephedrine, methylephedrine and pseudoephedrine, in conjunction with a diuretic or masking agent, will be considered as an Adverse Analytical Finding unless the Athlete has an approved TUE for that substance in addition to the one granted for the diuretic or masking agent.

Prohibited Methods

M1 Manipulation of blood and blood components by (1) the administration or reintroduction of any quantity of autologous, allogenic (homologous) or heterologous blood or red blood cell products of any origin into the circulatory system, (2) the use of products that enhance the uptake, transport or delivery of oxygen e.g. modified haemoglobins, or (3) any form of intravascular manipulation of the blood or blood components by physical or chemical means is prohibited. Supplemental oxygen, by inhalation, is not prohibited.

M2 Chemical or physical manipulation such as tampering or attempting to tamper to alter the integrity and validity of a sample such as urine substitution and/or adulteration (e.g. use of proteases) is prohibited.

IV infusions and/or injections of more than 50ml per 6 hour period are prohibited and require a TUE except for those legitimately received in the course of hospital admissions, surgical procedures or clinical investigations. Emergency infusions will require a retroactive TUE.

M3 Gene doping.

Substances and Methods Prohibited In-Competition

Prohibited Substances

S6 Stimulants including their related substances and their optical isomers are prohibited. Examples include amfetamine, lisdexamfetamine, modafinil and pseudoephedrine at urinary concentrations >150µg/ml.

Pseudoephedrine is found in many over the counter medicines available in pharmacies including many multi-ingredient products used as cough and cold remedies, hayfever and decongestant treatments. Athletes should stop taking any pseudoephedrine containing products at least 24 hours before competition. For therapeutic applications during the in-competition period, athletes should consider the use of alternative permitted medications after prior consultation with their doctor or pharmacist, or apply for a TUE for the use of pseudoephedrine for therapeutic purpose(s).

Local administration (e.g. nasal, ophthalmologic) of adrenaline or co-administration with local anaesthetic agents  or the topical/ophthalmic administration of imidazole derivatives such as xylometazoline are not prohibited.

S7 Narcotics: Prohibited narcotics include buprenorphine, dextromoramide, fentanyl and its derivatives, hydromorphone, methadone, morphine, nicomorphine, oxycodone, pethidine.

Note: Codeine, dextromethorphan, dihydrocodeine, pholcodine and tramadol are permitted.

S8 Cannabinoids (natural and synthetic) and Cannabimimetics are prohibited.

S9 Glucocorticoids are prohibited and require a TUE when administered by oral, rectal, intravenous or intramuscular routes. Glucocorticoids administered by all other routes do not require a TUE.

Substances Prohibited in Specific Sports

P1 Alcohol: Prohibited in-competition in certain sports including automobile (FIA) and archery (WA).

P2 Beta-Blockers: Prohibited in-competition in certain sports such as automobile (FIA), golf (IGF) and darts (WDF). Prohibited both in- and out- of competition in Archery (WA) and Shooting (ISSF, IPC).

WADA 2017 MONITORING PROGRAMME

In order to detect patterns of misuse in sport, the following are included in the 2017 Monitoring Programme:

1. Stimulants: In-Competition only: Bupropion, caffeine, nicotine, phenylephrine, phenylpropanolamine, pipradrol, synephrine;
2. Narcotics: In-Competition only: Mitragynine; tramadol and codeine;
3. Glucocorticosteroids: In-competition (by routes of administration other than oral, intravenous, intramuscular or rectal) and Out-of-Competition (all routes of administration);
4. Telmisartan: In- and Out-of-Competition;
5. Beta-2-agonists: In- and Out-of-Competition (any combination of beta-2-agonists).

This summary is deliberately concise and is intended to be used as a guide only. For an authoritative reference source consult the complete World Anti-Doping Code, The 2017 Prohibited List and the International Standard for TUE (ISTUE) which are available from Sport Ireland or www.wada-ama.org. WADA have undertaken to update the Prohibited List regularly. All information correct at time of going to press.

Only those products with a marketing authorisation or CE mark can be classified. Products should only be used in accordance with their marketing authorisation.

Classification: See list of Sport symbols in the Glossary of MIMS Ireland.

Compiled by Eirpharm.com on behalf of Sport Ireland for MIMS Ireland. More information is available from Sport Ireland (telephone: (01) 8608818; fax: (01) 8608860; website: www.sportireland.ie/anti-doping), www.eirpharm.com and National Governing Bodies of Sport.

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