Orion Pharma Ireland is pleased to announce the addition of Bufomix Easyhaler 80/4.5mcg to its current portfolio. It is now available with the complete range of strengths and license indication of the original brand.
Bufomix Easyhaler is a fixed-dose budesonide/formoterol combination inhaler, indicated for the treatment of asthma and chronic obstructive pulmonary disease.

Three strengths are now available;
– New: 80/4.5mcg (for adults, adolescents and children 6 years and older)
– 160/4.5mcg (for adults and adolescents 12 years and older)
– 320/9mcg (for adults and adolescents 12 years and older)

Bufomix Easyhaler has two treatment approaches:
– Maintenance therapy: Taken as regular maintenance treatment with a separate rapid-acting bronchodilator as rescue.
– Maintenance & Reliever therapy (for adults only): Bufomix Easyhaler 80/4.5mcg and 160/4.5mcg can be taken as regular maintenance treatment and as needed in response to symptoms.

For further information, please contact Orion Pharma (Ireland) Ltd. at (01) 4687500.

Tara Sweeney

Company: Guna S.p.a.

Legal category: Food supplement.

Active ingredients: Iron Fumarate in ionic ferrous form with a bioavailability of 30-35% (i.e. 5mg. of iron per sachet) 14mg, L-ascorbic acid (vitamin C) 30mg, copper citrate 0.36mg, baobab (Adansonia digitata L.) fruit pulp 650mg.

Description: Orodispersible granules in sachets.

Presentation: 28, €22.00.

Indications: Iron deficiency. Promotes production of haemoglobin and red blood cell formation. Optimal in cases of pregnancy, post-partum period, breastfeeding, intestinal disorders that compromise iron absorption (especially celiac disease) and increased physiological (heavy menstrual bleeding) or pathological (gastro-duodenal ulcers, gastritis and other gastrointestinal disorders) blood loss.

Pharmacology: Iron is a haematinic essential for satisfactory erythropoiesis during haemoglobin synthesis. Ascorbic acid promotes hematopoiesis, increases iron absorption for up to 30%. Copper promotes action of the enzymes involved in iron metabolism.  The Baobab fruit pulp with naturally high content of vitamins, minerals and trace elements helps to increase iron retention. Additionally the Baobab fruit pulp has natural analgesic and anti-inflammatory properties, promotes intestinal eubiosis and counteracts diarrhoea.

Dosage: Adult: Dissolve contents of one sachet directly in the mouth, without water. 1-2 sachets daily (see product brochure).

Special precautions: Excessive consumption may produce laxative effects. Should not be used as a substitute for a varied diet and a healthy lifestyle. Contains sorbitol, sucralose.

Drug interactions: None studied.

Adverse drug reactions: Does not induce side effects in the gastrointestinal system.

Full prescribing information and references available from Biomedico. Telephone: 085 2054460.  E-mail: sales@biomedico.ie

Tara Sweeney

The Health Products Regulatory Authority (HPRA) would like to remind healthcare professionals of the need for vigilance when prescribing, dispensing and/or counselling patients in relation to methotrexate.

Oral methotrexate* is indicated in the treatment of active rheumatoid arthritis, adult psoriasis and in a number of oncological indications, with differing dosage regimens for the respective indications (Summary of Product Characteristics (SmPCs) available on www.hpra.ie).

For rheumatology and dermatology indications, methotrexate should be administered as a once weekly dose only. Patients and/or carers should be informed of the risks associated with an overdose and of the importance of adhering to once weekly dosing. For these indications, it is also suggested that the day of intake should be specified on the prescription and dispensing label.

Medication errors resulting in inadvertent overdose due to daily intake of a weekly dose have been reported in Ireland and elsewhere. These reports have included cases of serious adverse reactions, some of which resulted in a fatal outcome, particularly due to the haematological toxicity of methotrexate, but also as a result of pulmonary toxicity.  Reports of medication errors have occurred in a range of areas, including prescribing and administration errors (mainly for hospitalised patients), to errors in self-administration (by patients at home, either inadvertently, or by misunderstanding the medication schedule). The HPRA would like to remind healthcare professionals of the need for vigilance when prescribing, dispensing, administering and counselling patients and/or carers in relation to methotrexate, particularly following initiation of treatment, a change in the dose, or in circumstances where therapy is re-started.

The HPRA previously highlighted the risk of inadvertent overdose due to medication errors associated with methotrexate and the recommendations to reduce this risk (HPRA Drug Safety Newsletter Edition 47) following an EU review of this issue completed in 2012.  The product information (SmPC and Package Leaflet (PL)) was updated at that time to emphasise the need for adherence to once weekly dosing and to strengthen existing warnings regarding the risk of overdose.  The Pharmaceutical Society of Ireland (PSI) also updated and re-issued its guidance to support safe dispensing of methotrexate around that time. A reminder of these recommendations was  highlighted in the 71st Edition of the HPRA Drug Safety Newsletter published in December 2015 and in the MIMS Compendium circulated in January 2016.

Advice to Healthcare Professionals

• Cases of overdose, sometimes fatal, due to erroneous daily  instead of weekly intake of methotrexate have been reported.
• Methotrexate, for dermatology and rheumatology indications, should be taken as a single once weekly dose.
• Healthcare professionals should ensure that the patient and/or their carer understand the prescribed therapy, including the dose and frequency, with any treatment changes highlighted. Great care should be taken to give and repeat clear instructions on dosage.
• Patients and/or carers should be encouraged to read the PL provided with their methotrexate and to discuss any concerns with a relevant healthcare professional.
• Patients and/or carers should be informed of the potential risks of serious adverse reactions in the case of overdose and of the signs and symptoms of toxicity.
• Any adverse reactions suspected to be related to a medication error with methotrexate should be notified to the HPRA in the usual way.

Key Message

• Methotrexate for oral use for rheumatology and dermatology indications should be taken once a week only.
• Patients and/or carers should be informed of the risk of overdose due to erroneous daily intake of the weekly dose and should be advised to contact a healthcare professional promptly, if they consider an error in dosing has occurred.

*Further details on methotrexate products are available on  www.hpra.ie

Caroline McDermott

The outcome of the Europe-wide review of valproate-containing medicines was communicated to healthcare professionals in December 2014 via the HPRA Drug Safety Newsletter (Edition 65) and a Direct Healthcare Professional Communication (DHPC) circulated by the Marketing Authorisation Holder (MAH) following approval by the HPRA. This review recommended strengthening of restrictions for use of valproate and further characterising the risk of birth defects and developmental disorders in the product information (Summary of Product Characteristics (SmPC) and Package Leaflet (PL)). In May 2015, educational materials were made available by the MAH (following HPRA approval) as part of the risk minimisation measures developed to inform healthcare professionals and patients about the risks associated with use of valproate by females of child-bearing potential and during pregnancy.

These educational materials have now been updated and enhanced to further support awareness and to facilitate discussion of the risks between healthcare professionals and patients. The additional educational materials include the following:

Booklet for Healthcare Professionals

• This booklet provides up to date information about  the risk of neurodevelopmental disorders in children of women who have taken valproate during pregnancy, in addition to the known risk of congenital malformations in exposed babies.
• It also provides points to consider and steps to take when deciding to treat women of child-bearing potential with valproate.
• The booklet should be used in conjunction with the patient guide and checklist, as well as the complete Summary of Product Characteristics (SmPC).

Valproate Patient Guide

• This booklet includes information for all females taking any medicine containing valproate.
• Healthcare professionals should ensure that female patients treated with valproate are provided with the valproate patient guide and that they understand the information it contains. If a patient is a young girl, the guide should be explained to her parent/carer.

Valproate Patient Card

• Pharmacists are requested to distribute a valproate patient card whenever a valproate-containing medicine is dispensed to a female of child-bearing age, unless she confirms that she already has one.
• The pharmacist should encourage the patient to read the patient guide and card together, to understand the information provided and enter her name and date on the card to indicate she has read and understood the information.

• Checklist for Prescribers
• If a prescribing doctor concludes it is necessary to treat, or to continue treating a woman of child-bearing age with a valproate-containing medicine, then the checklist should be used to ensure that all necessary information has been provided to the patient and/or carer and that they fully understand it.

These updated materials have been recently distributed to doctors and pharmacists by the MAH with an accompanying DHPC. The educational materials are also available from the HPRA website (www.hpra.ie).

Advice to Healthcare Professionals

• Valproate should not be prescribed to female children, female adolescents, women of child-bearing potential or pregnant women unless other treatments are ineffective or not tolerated.
• Children exposed in utero to valproate are at a high risk of serious developmental disorders (in up to 30-40% of cases) and/or congenital malformations (in approximately 10% of cases).
• Valproate treatment should only be commenced and supervised by a doctor experienced in managing epilepsy or bipolar disorder.
• Before initiating treatment, the balance of the benefits of treatment with valproate must be weighed against the risks. This should also be considered at routine treatment reviews, when a female reaches puberty and when a woman plans a pregnancy or becomes pregnant. The prescribing doctor should consult the booklet for healthcare professionals.
• All female patients must be informed of and understand the risks associated with valproate during pregnancy and the steps to take if pregnancy occurs or is planned. The valproate patient guide and patient card should be provided to all female patients of child-bearing age and discussed with them to ensure full understanding of the associated risks.
• The prescribing doctor should also use the checklist available to ensure that all necessary information has been provided to the patient and/or carer.
• Further updates will be made to the outer packaging for all valproate-containing products to include a warning forwomen on the risk of adverse pregnancy outcomes.
• All suspected adverse reactions associated with valproate-containing medicines should be reported to the HPRA via the usual methods (www.hpra.ie).

Key Message

• Valproate-containing medicines should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women, unless other treatments are ineffective or not tolerated, due to the risk of serious developmental disorders and/or congenital malformations.
• To further improve awareness of the risks associated with use of valproate-containing medicines in females of child-bearing potential and in pregnancy, updated educational materials and patient alert cards are available and should be used by healthcare professionals to support appropriate and safe prescribing/dispensing of valproate-containing medicines, and by patients/carers to increase their knowledge of these risks.

Further details on valproate-containing medicines are available at www.hpra.ie

Caroline McDermott

Treatment of storage and voiding symptoms associated with benign prostatic hyperplasia

Astellas wish to announce that Vesomni^TM, a fixed-dose combination (FDC) tablet containing the active ingredients solifenacin (antimuscarinic) plus tamsulosin (alpha-blocker), is now available in Ireland. It is indicated for the treatment of moderate to severe storage symptoms (urgency, increased micturition frequency) and voiding symptoms associated with benign prostatic hyperplasia (BPH) in men who are not adequately responding to treatment with monotherapy.¹

Lower urinary tract symptoms (LUTS) associated with BPH are common in men and can include storage symptoms (frequency, urgency, nocturia) and/or voiding symptoms (e.g. hesitancy, intermittency).^2,3 Storage and voiding symptoms are attributed to the bladder and prostate, respectively. In the EpiLUTS study, which included 14,139 men aged ≥40 years, of the 71% who reported at least one LUTS, 49% of these men reported both storage and voiding symptoms (see Figure 1). Storage symptoms are the most bothersome to the patient⁴ and can have a significant impact on quality of life (QoL).⁵

Alpha-blockers are currently first-line treatment for voiding symptoms in men with LUTS but often do not adequately relieve storage symptoms.³ Storage symptoms are generally undertreated in men due to a perceived increased risk of acute urinary retention (AUR) with antimuscarinics.⁶ Clinical trials with antimuscarinic plus alpha-blocker combinations suggest that the risk of AUR is low in men with LUTS.⁷ Current European Association of Urology guidelines suggest that antimuscarinics can be used in combination with an alpha-blocker when symptom relief is insufficient with either agent alone.³

Solifenacin and tamsulosin have independent and complementary mechanisms of action in the treatment of LUTS associated with BPH, with storage symptoms.¹ Solifenacin inhibits detrusor muscle contractions in the bladder, resulting in predominantly storage symptom relief.⁸ Tamsulosin relaxes smooth muscle in the prostate and bladder neck, giving predominantly voiding symptom relief.⁹

Combination therapy with solifenacin and the oral controlled absorption system (OCAS) formulation of tamsulosin has been evaluated in several clinical studies for the treatment of storage and voiding LUTS.^10-13 Results from the phase 2 SATURN study showed that solifenacin plus tamsulosin OCAS offered significant storage and QoL benefits over tamsulosin OCAS alone in a subpopulation of men with moderate to severe storage symptoms and voiding symptoms.¹¹

Vesomni received marketing authorisation based on the outcomes of the NEPTUNE study, which investigated the efficacy and safety of FDC treatment of solifenacin plus tamsulosin OCAS in men with moderate to severe storage symptoms and voiding symptoms. Efficacy and safety during long-term therapy were evaluated in the follow-up NEPTUNE II extension study.

NEPTUNE study

The efficacy and safety of FDC therapy with solifenacin plus tamsulosin OCAS was established in the randomised, double-blind, parallel-group, placebo-controlled, phase 3 NEPTUNE study. The trial enrolled men aged ≥45 years with storage and voiding LUTS, defined as total International Prostate Symptom Score (IPSS) ≥ 13, maximum urinary flow rate 4.0-12.0 ml/s, two or more urgency episodes per 24 h, and eight or more micturitions per 24h. Patients (n=1334) were randomised (1:1:1:1) to double-blind treatment with placebo, tamsulosin OCAS alone, or two different doses of FDC therapy with solifenacin plus tamsulosin OCAS over a 12 week period.

The two primary efficacy endpoints were change from baseline to end of treatment in total IPSS and Total Urgency and Frequency Score (TUFS). TUFS is a measure capturing the two important storage symptoms, urgency and frequency, in a single parameter. Secondary efficacy endpoints were change from baseline to end of treatment in IPSS storage and voiding subscores, micturition diary variables, and QoL parameters.¹²

Vesomni significantly improved storage symptoms and quality of life vs tamsulosin monotherapy

Vesomni was superior to placebo (-7.0 vs -5.4; p<0.001) and non-inferior to tamsulosin OCAS alone for reductions in total IPSS (-7.0 vs -6.2; p=0.001) (see Figure 2). It showed superiority to placebo (-8.1 vs -4.4; p<0.001) and tamsulosin OCAS alone for reductions in TUFS (-8.1 vs -6.7; p<0.05) (see Figure 3).

Compared with placebo and tamsulosin OCAS alone, Vesomni significantly improved IPSS storage subscores, micturition frequency, and mean voided volume per micturition. Significant improvements were also observed in IPSS voiding subscores, urgency, and nocturia for Vesomni compared with placebo. Furthermore, patients reported significant improvements with Vesomni in QoL parameters compared with placebo, and with the exception of the symptom bother score, compared with tamsulosin OCAS alone.¹²

NEPTUNE II study

Patients who completed the 12 week, double-blind NEPTUNE study could continue to the 40 week, open-label, flexible-dosing, phase 3 NEPTUNE II extension study. In all, 1066 patients completed NEPTUNE and continued in NEPTUNE II. Patients could switch between two different doses of FDC therapy with solifenacin plus tamsulosin OCAS in NEPTUNE II.

Efficacy and safety data from patients taking part in both NEPTUNE and NEPTUNE II were combined for both FDCs for up to a total of 52 weeks. Total FDC therapy was up to 40 weeks for patients receiving placebo or tamsulosin OCAS alone in NEPTUNE, and up to 52 weeks for those receiving either FDC in NEPTUNE. Primary and secondary efficacy end points were similar to those in NEPTUNE, and were assessed from baseline (week 0, NEPTUNE) to end of treatment (up to 52 weeks later, NEPTUNE II).

Reductions in both mean total IPSS and TUFS observed in the NEPTUNE study with FDC treatment were maintained throughout NEPTUNE II. Mean total IPSS was reduced by 9.0 points, and mean TUFS was reduced by 10.1 points, from baseline to end of treatment, equivalent to reductions of 48.1% and 37.1%, respectively.

Clinically relevant improvements were also observed for secondary efficacy end points, including mean IPSS storage and voiding subscores, mean number of micturitions, urgency episodes, incontinence episodes per 24 h, mean voided volume per micturition, and QoL parameters.¹³

Two different doses of solifenacin plus tamsulosin OCAS (6mg/0.4mg and 9mg/0.4mg) were evaluated in NEPTUNE and NEPTUNE II. The 6mg/0.4mg dose was chosen for marketing authorisation because the higher dose of solifenacin did not demonstrate additional benefit to the 6mg/0.4mg dose.^12,13

Safety profile

Of the patients receiving therapy in NEPTUNE II, 499 (46.8%) experienced treatment-emergent adverse events while on FDC therapy in NEPTUNE or NEPTUNE II; the majority were mild to moderate in severity. The most common were dry mouth (12.4%), constipation (5.2%), and dyspepsia (2.7%). Of all patients who received FDC therapy during NEPTUNE and/or NEPTUNE II, including those who did not continue into NEPTUNE II, 13 of 1208 (1.1%) had urinary retention, and 8 of these 13 (0.7%) developed AUR.¹³

Conclusions

In men with moderate to severe storage symptoms and voiding symptoms, treatment with Vesomni significantly improved bladder symptoms and QoL compared with tamsulosin monotherapy, and demonstrated significant improvements in bladder and prostate symptoms and QoL versus placebo. ¹² Long-term therapy was efficacious and well tolerated, with a low incidence of AUR. ¹³

References: 1.Vesomni SPC (revised June 2015). 2.Abrams P et al. Neurourol Urodyn 2002; 21: 167-78. 3. European Association of Urology Guidelines. Available at https://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#5 Accessed 29th July 2016. 4.Sexton C et al. BJU Int 2009;103(Suppl 3): 12–23. 5.Milsom I et al. BJU Int 2001; 87(9): 760-766. 6.Helfand B et al. Eur Urol 2010;57: 586–91. 7.Kaplan S et al. Int J Clin Pract 2011;65: 487–507. 8.Vesitirim SPC (revised June 2015). 9.Omnexel SPC (revised June 2016). 10.Kaplan S et al. Eur Urol 2013;63:158–65. 11.Van Kerrebroeck P et al. Eur Urol 2013;64:398–407. 12.Van Kerrebroeck P et al. Eur Urol 2013;64:1003–12. 13.Drake M et al. Eur Urol 2015;67:262-270.

VSO16018IE

Full prescribing information and references available from Astellas Pharma Co Ltd. Telephone: (01) 467 1555.

MIMS Ireland Copyright®

Written by Caroline McDermott PhD, Editor, MIMS Ireland

Sponsored by Astellas Pharma Co Ltd.

Caroline McDermott

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-Improvements in the treatment of rheumatoid arthritis (RA) over the last few decades means that disease remission is now a realistic goal for many patients.

-Standardised assessment of disease activity in RA can facilitate treating to target, which has been shown to improve disease outcomes.

-The American College of Rheumatology (ACR) evaluated the 63 currently available RA disease activity measurement tools in order to determine which disease activity measures reliably distinguish between different levels of disease activity in RA and are feasible to implement in clinical practice.

-These disease activity measurement tools were progressively filtered down to the following 6 ACR-recommended measures:

• Clinical Disease Activity Index (CDAI),
• Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein) (DAS28 [ESR or CRP]),
• Patient Activity Scale (PAS),
• PAS-II,
• Routine Assessment of Patient Index Data with 3 measures (RAPID-3), and
• Simplified Disease Activity Index (SDAI).

-These measures were chosen because they are accurate reflections of disease activity; are sensitive to change; discriminate well between low, moderate, and high disease activity states; have remission criteria; and are feasible to perform in clinical settings.

-Some of these measures are purely patient reported (PAS, PAS-II, and RAPID- 3), some add provider assessment (CDAI), and some add provider assessment and laboratory acute-phase reactants (SDAI and DAS28).

-Key features of each measure are summarised in the ACR recommendations to allow those treating patients with RA to select the one best suited to their clinical practice.

-Utilisation of these validated RA disease activity measures in clinical practice will aid adherence to the ACR guidelines for the treatment of RA and provide the necessary tools for treating to target.

*Measures are not shown in order of preference. Abbreviations: PAS, Patient Activity Scale; RAPID-3, Routine Assessment of Patient Index Data with 3 measures; CDAI, Clinical Disease Activity Index; DAS28, Disease Activity Score with 28-joint counts; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; SDAI, Simplified Disease Activity Index; RA, rheumatoid arthritis; HAQ, Health Assessment Questionnaire; VAS, visual analog scale; Pt Global VAS, patient global assessment of disease activity VAS; Lab, laboratory value required; N/A, not applicable; MDHAQ  Multidimensional HAQ; 28TJC, 28 tender joint count; 28SJC, 28 swollen joint count; Pr Global VAS, provider global assessment of disease activity VAS; admin., administration.

Reference: 1. Anderson J et al. Rheumatoid Arthritis Disease Activity Measures: American College of Rheumatology Recommendations for Use in Clinical Practice. Arthritis Care & Research May 2012; 64(5): 640–647.

MIMS Ireland Copyright®

Caroline McDermott

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• Chronic pain has been defined by the International Association for the Study of Pain (IASP) as “pain without apparent biological value that has persisted beyond the normal tissue healing time (usually taken to be three months)”.¹
• According to the European Pain Federation EFIC, “Pain is a major healthcare problem in Europe. Although acute pain may reasonably be considered a symptom of disease or injury, chronic and recurrent pain is a specific healthcare problem, a disease in its own right”.²
• Chronic pain can be nociceptive, neuropathic or a mixture of both. Nociceptive pain is associated with injury or damage to body tissues. Neuropathic pain is caused by damage to or malfunction of the nerves or nervous system.
• Back pain (55%) is the most common cause of chronic pain, followed by joint pain (46%) and neck pain (34%). Other common causes include headache, arthritis, migraine, fibromyalgia, neuropathic, surgery/medical procedures, visceral pain, diabetes, cancer, and post-herpetic neuralgia.
• Chronic pain is reported in 13% of adults in Ireland. On average, people are forced to wait 2.6 years from first seeking help to reaching diagnosis, and 1.4 years until their pain is adequately managed. However, 35% of people report that their pain is still not adequately managed.
• Chronic pain can cause significant physical and psychological suffering and is associated with serious co-morbidities and psychological disorders (e.g. anxiety, depression). Data from the Pain Proposal survey across Europe show that 27% of people with chronic pain feel socially isolated and lonely because of their pain, with 50% worrying about the effect of their chronic pain on their relationships, and 29% worrying about losing their job. Uncontrolled pain can affect the ability to work productively, think or function normally, to exercise or even sleep.³

Management of Chronic Pain

The World Health Organisation (WHO) analgesic ladder was developed and validated only for the treatment of cancer pain, but is also widely used to guide basic treatment of acute and chronic pain. Commencement of appropriate pharmaceutical treatment requires careful assessment and diagnosis of chronic pain. Regular, scheduled re-assessment of pain relief and side-effects is required for successful management of patients.^4,5

WHO Three Step Analgesic Ladder

Click on image to enlarge

The WHO recommends a progressive, stepwise use of analgesics depending on the level of pain – mild, mild to moderate, or moderate to severe pain.

SIGN 2013 Guidelines on Chronic Pain⁵

• The Scottish Intercollegiate Guidelines Network (SIGN) published recommendations in 2013 based on current evidence for best practice in the assessment and management of adults with chronic non-malignant pain in non-specialist settings.
• These guidelines recommend that a concise history, examination and biopsychosocial assessment, identifying pain type (neuropathic/nociceptive/mixed), severity, functional impact and context should be conducted in all patients with chronic pain, to inform selection of treatment options most likely to be effective.

Non-opioid analgesics

• Chronic non-specific low back pain – may be treated with NSAIDs (caution is advised with regards to cardiovascular and gastrointestinal risk).
• Hip or knee osteoarthritis – may be treated with paracetamol (1-4g daily) alone or in combination with NSAIDs.
• Chronic pain from musculoskeletal conditions – may be treated with topical NSAIDs, especially those patients who cannot tolerate oral NSAIDs.
• Peripheral neuropathic pain – may be treated with topical capsaicin patches (8%) when first-line pharmacologics are ineffective or not tolerated.
• Post-herpetic neuralgia – may be treated with topical lidocaine if first-line pharmacologics are ineffective.

Opioids

• There are a number of different classifications for opioids, but for the purposes of this guideline they are divided into weak opioids (e.g. codeine, tramadol) and strong opioids (e.g. morphine, hydromorphone, oxycodone, fentanyl, buprenorphine, methadone). ^a,b
• Chronic low back pain or osteoarthritis – treatment with strong opioids is an option. Continue only if there is ongoing pain relief, with regular review.
• Advise patients prescribed opioids of common side-effects such as nausea and constipation. ^a,b
• Assess all patients on strong opioids regularly for changes in pain relief, side-effects and quality of life. Consider gradual reduction to the lowest effective dose.
• Both effectiveness and side-effects vary between opioids; therefore, it may be necessary to trial more than one opioid sequentially.
• Consider opioid rotation for chronic pain that is likely to respond to opioids, if there are problems with efficacy or side-effects.
• At re-assessment of patients using strong opioids, check for signs of abuse and addiction. Assess pre-existing risk factors for developing opioid misuse.
• Seek specialist referral or advice if there are concerns about rapid-dose escalation with continued unacceptable pain relief, or if >180 mg/day morphine equivalent dose is required.

Anti-epileptics

• Neuropathic pain – may be treated with gabapentin (titrated up to at least 1,200mg daily).
• Neuropathic pain – pregabalin (titrated up to at least 300mg daily) is recommended if other first- and second line-pharmacologics have failed.
• Flexible dosing may improve tolerability. Failure to respond after an appropriate dose for several weeks should result in trial of a different compound.
• Neuropathic pain – consider carbamazepine. Advise patients of potential risks of adverse events.

Antidepressants

• Review patients with chronic pain conditions using antidepressants regularly. Assess for ongoing need and ensure benefits outweigh risks.
• Tricyclic antidepressants (TCAs) should not be used for managing chronic low back pain.
• Alternative TCAs may be tried to reduce side-effect profile.
• Diabetic neuropathic pain – may be treated with duloxetine (60mg/day) if other first- or second-line pharmacologics have failed.
• Optimised antidepressant therapy may be used in patients with chronic pain with moderate depression.
• Depression is a common co-morbidity with chronic pain. Monitor and treat patients for depression as necessary.

Combination therapies

• Neuropathic pain – combination therapies may be used.
• In patients with neuropathic pain who do not respond to gabapentin or pregabalin alone, and who are unable to tolerate other combinations, consideration should be given to the addition of an opioid such as morphine or oxycodone (taking into account the risks and benefits of opioid use).

^a Tapentadol is a strong analgesic with mu opioid receptor agonism and noradrenaline reuptake inhibition. As it does not rely solely on opioid binding for analgesic effect, the result is an opioid sparing effect and reduced incidence of some of the typical opioid-induced side-effects, compared to equianalgesic doses of classical opioids. ^6,7 May have a role in neuropathic pain.⁵

^b An oxycodone/naloxone combination product is available which provides systemically available oxycodone to effectively control pain, while the naloxone component blocks mu opioid receptor activation locally in the gut, thereby counteracting opioid-induced constipation.^8,9

Prescribers should refer to the relevant sections of MIMS Ireland and Summary of Product Characteristics for individual products for full details of licensing.

References: 1.Merskey H et al. International Association for the Study of Pain. Available at http://www.iasp-pain.org/files/Content/ContentFolders/Publications2/FreeBooks/Classification-of-Chronic-Pain.pdf. Accessed 17th August 2016. 2.EFIC. Declaration on pain as a major health problem, a disease in its own right. Available at: http://www.iasp-pain.org/files/Content/ContentFolders/GlobalYearAgainstPain2/20042005RighttoPainRelief/painasadisease.pdf. Accessed 17th August. 3.Pain Proposal: Improving the current and future management of chronic pain. A European Consensus Report. 2010. Available at http://www.efic.org/userfiles/file/pain_proposal.pdf. Accessed 17th August 2016. 4.WHO Analgesic Ladder. Available at http://www.who.int/cancer/palliative/painladder/en/. Accessed 17th August. 5.SIGN guidelines 2013. Management of chronic pain. Available at http://www.sign.ac.uk/pdf/SIGN136.pdf. Accessed 17th August 2016. 6.Sánchez Del Águila et al. Clin Ther. 2015; 37(1): 94-113. 7.Hartrick and Rozek. CNS Drugs 2011; 25(5):359-370. 8.Vondrackova D et al. J Pain. 2008;9:114–54. 9.Lowenstein O et al. Expert Opin Pharmacother. 2009;10:531–43. MIMS Ireland Copyright®

Caroline McDermott

Company: Recordati Ireland Ltd.

Legal category: Prescription. GMS pending. Sport permitted.

Active ingredient: Alprostadil 3mg/g.

Description: White cream in AccuDose single dose container.

Presentation: 100mg-4, €40.00 (PTW).

Indication: Treatment of erectile dysfunction (ED).

Pharmacology: Alprostadil is chemically identical to prostaglandin E1, the actions of which include vasodilatation of blood vessels in the erectile tissues of the corpora cavernosa and increase in cavernosal artery blood flow, causing penile rigidity.

Dosage: Adult: Apply the contents of 1 Accudose container (300mcg) to the tip of penis within 5 to 30 minutes prior to intercourse. Maximum once per 24 hour period and 2-3 times per week. Children: Under 18 years, not recommended.

Contraindications: Hypersensitivity to alprostadil or any of the ingredients. Orthostatic hypotension, myocardial infarction, syncope. Predisposition to priapism (sickle cell anaemia or trait, thrombocythemia, polycythemia, multiple myeloma, leukaemia) or at increased risk of priapism (prone to venous thrombosis, hyperviscosity syndrome). Abnormal penile anatomy (e.g. severe hypospadias), anatomical deformation of the penis (e.g. curvature), urethritis, balanitis. Men for whom sexual activity is inadvisable (unstable cardiovascular or cerebrovascular conditions). Pregnancy, lactation. Use condom barrier during sex.

Special precautions: Exclude treatable causes of ED before initiation. Avoid intraurethral exposure. Advise patients to seek immediate medical assistance if erection lasts >4 hours. Symptomatic hypotension and syncope may occur. No data: History of neurological disease or spinal injury, hepatic/renal impairment, repeated long-term intraurethral exposure, use of non-latex-based condoms, penile implants. Driving/using machines (within 1-2 hours).

Drug interactions: Do not use PDE5 inhibitors. Possible effects may be seen with antihypertensive and vasoactive drugs (especially elderly), smooth muscle relaxants (papaverine), alpha blockers (e.g. intracavernosal phentolamine, thymoxamine), sympathomimetics, decongestants, appetite suppressants, anticoagulants, platelet aggregation inhibitors; drug interactions unlikely; no interaction studies performed.

Adverse drug reactions: Rash, urethral pain, penile burning, penile pain, penile erythema, penile oedema, penile tingling, penile throbbing, penile numbness, genital pain, genital discomfort, genital erythema, genital pruritis, increased erection, balantitis.

Full prescribing information and references available from Recordati Ireland Ltd. Telephone: 1800 303 351.
E-mail: medinfo@recordati.co.uk

Tara Boland

Company: Consilient Health Ltd.

Legal category: Prescription. Sport permitted.

Active ingredients: Levonorgestrel/ ethinylestradiol 100/20mcg.

Description: Pink, cylindrical, biconvex, film coated tablet.

Presentation: 3 x 21, €7.50 (PTW).

Indication: Oral contraception.

Pharmacology: Ethinylestradiol/levonorgestrel inhibits ovulation and changes the cervical mucus.

Dosage: Adult: 1 daily for 21 days starting on 1st day of menstruation, then 7 tablet-free days.

Contraindications: Hypersensitivity to the active substances or to any of the excipients. Presence/risk of venous thromboembolism (VTE) or arterial thromboembolism (ATE), presence/history of severe hepatic disease as long as liver function values not normal, liver tumours (or history), history of migraine with focal neurological symptoms. Pregnancy, lactation.

Special precautions: Risk of VTE, ATE. Hypertriglyceridaemia (or family history; risk of pancreatitis). Suspend treatment if a sustained hypertension develops; may resume if normotensive values achieved with antihypertensive therapy. Acute or chronic hepatic impairment, suspend treatment until liver function tests normal. Liver tumours reported rarely; consider if severe upper abdomen pain, hepatomegaly, or intraabdominal haemorrhage signs occur. May occur or deteriorate: Jaundice and/or pruritus related to cholestasis (discontinue upon recurrence if occurred during pregnancy or sex steroid use); gallstones; porphyria; systemic lupus erythematosus; haemolytic uraemic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis-related hearing loss; (hereditary) angioedema. Worsening of endogenous depression, epilepsy, Crohn’s disease and of ulcerative colitis reported. Avoid sun/UV if tendancy to chloasma. Diabetes. Exclude malignancy/pregnancy if bleeding irregularities persist or occur after previously regular cycles. Contains lactose.

Drug interactions: Add a barrier method during and for 7 days after administration of antibiotics or for 28 days after administration of hepatic microsomal enzyme inducers, rifampicin or griseofulvin. Ciclosporin, lamotrigine. Troleandomycin. HIV protease and non-nucleoside reverse transcriptase inhibitors. Drugs increasing GI motility.

Adverse drug reactions: Depressed mood, altered mood, headache, dizziness, gastrointestinal upset, breast pain, breast tenderness, increased weight.

Full prescribing information and references available from Consilient Health Ltd. Telephone: (01) 2057760.

Tara Boland

Company: A. Menarini Pharmaceuticals Ireland Ltd.

Legal category: Prescription. GMS. Sport permitted.

Active ingredients: Acetylsalicylic acid/atorvastatin/ramipril 100/20/2.5mg, 100/20/5mg, 100/20/10mg.

Description: Hard capsules.

Presentation: 100/20/2.5mg-28, €8.37; 100/20/5mg-28, €9.87; 100/20/10mg-28, €12.97.

Indication: Secondary prevention of cardiovascular (CV) accidents as substitution therapy in adults adequately controlled with the monocomponents given concomitantly at equivalent therapeutic doses.

Pharmacology: Acetylsalicylic acid irreversibly inhibits platelet aggregation due to cyclooxygenase acetylation. This irreversibly inhibits synthesis of thromboxane A2 (a platelet aggregation promoting and vasoconstricting prostaglandin) in the platelets. Acetylsalicylic acid also inhibits the synthesis of prostacyclin (a platelet aggregation inhibiting prostaglandin but with vasodilatory effects) in vascular endothelial cells but this effect is temporary. Atorvastatin lowers plasma cholesterol and lipoprotein serum concentrations by inhibiting HMG-CoA reductase and subsequently cholesterol biosynthesis in the liver and increases the number of hepatic low-density lipoprotein (LDL) receptors on the cell surface for enhanced uptake and catabolism of LDL. Atorvastatin has been shown to reduce concentrations of total-cholesterol (total-C), LDL-C, apolipoprotein B and triglycerides; reductions in total-C, LDL-C, and apolipoprotein B have been proven to reduce risk for CV events and CV mortality. Ramipril is a prodrug to the active metabolite ramiprilat, which inhibits the angiotensin-converting enzyme (ACE). This enzyme catalyses the conversion of angiotensin I to the active vasoconstrictor substance angiotensin II, as well as the breakdown of the active vasodilator bradykinin. Reduced angiotensin II formation and inhibition of bradykinin breakdown lead to vasodilatation.

Dosage: Adult: One capsule daily, preferably after a meal. Initiate under close medical supervision. Target maintenance dose of ramipril is 10mg once daily. Swallow whole with liquid. Renal impairment: Creatinine clearance (cc) ≥60ml/min, 10mg ramipril (maximum); cc 30-60ml/min, 5mg ramipril (maximum). Hepatic impairment: 2.5mg ramipril (maximum). Elderly: Initiate with caution. Children: Under 18 years, contraindicated.

Contraindications: Hypersensitivity to the active substances or to any of the excipients. History of asthma attacks or other allergic reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Active, or history of recurrent peptic ulcer and/or gastrointestinal (GI) haemorrhage, other kinds of bleeding. Haemophilia and other bleeding disorders. Severe renal/hepatic impairment. Haemodialysis. Severe heart failure. Nasal polyps. Active liver disease or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal (ULN). History of angioedema. Extracorporeal treatments leading to contact of blood with negatively charged surfaces. Renal artery stenosis. Hypotensive or haemodynamically unstable states. Tartrazine, soya or peanut allergy. Pregnancy, lactation. Inadequate contraception.

Special precautions: If dual blockade of the renin-angiotensin-aldosterone system (RAAS) is considered absolutely necessary, use only under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure (BP). Caution in patients with: Known allergies, bronchial asthma, hay fever, swollen nasal mucous membranes, or other chronic respiratory diseases; history of gastric or enteric ulcers, or of GI bleeding; renal/hepatic impairment; particular risk of hypotension (strongly activated RAAS, heart failure (HF) post-MI, risk of cardiac or cerebral ischemia, monitor BP in case of acute hypotension); deterioration of CV circulation; risk of elevated levels of uric acid; high alcohol intake and/or history of liver disease. Higher rate of angioedema and less effective in black patients. Perform liver function tests if signs of liver injury develop, periodically if hepatic effects occur, or before start of treatment and periodically thereafter in hepatic impairment. Suspend a few days prior to major surgery. Renal impairment (especially with congestive heart failure or after renal transplant). Risk of development of hyperkalaemia; monitor serum potassium regularly. May cause myalgia, myositis, and myopathy that may progress to rhabdomyolysis. Do not initiate if CK levels >5 x ULN at baseline. Discontinue if CK levels >10 x ULN occur, or if rhabdomyolysis is suspected. Advise patients to promptly report muscle pain, cramps, or weakness; discontinue if CK levels >5 x ULN. Consider discontinuation if muscular symptoms severe and cause daily discomfort, even if CK levels ≤5 x ULN. Discontinue if interstitial lung disease occurs. Monitor patients at risk of diabetes. Discontinue if angioedema occurs (initiate emergency treatment promptly). Intestinal angioedema reported. Anaphylactic reactions during desensitisation (consider treatment suspension). Monitor white blood cells for neutropenia/agranulocytosis and more regularly at start of treatment, renal impairment, concomitant collagen disease and other drugs that can change the blood picture. Non-productive, persistent cough. Contains lactose.

Drug interactions: Contraindicated: Aliskiren (diabetes, renal impairment), methotrexate (≥15mg/week), tipranavir, ritonavir, ciclosporin, telaprevir. Not recommended: Angiotensin-receptor blockers (especially diabetic nephropathy), aliskiren, lithium, grapefruit juice. Avoid: Potent CYP3A4 inhibitors, CYP3A4 inducers, transport protein inhibitors, gemfibrozil/fibric acid derivatives. Caution: Colchine, potassium salts, heparin, potassium-retaining diuretics and other plasma potassium increasing active substances, antihypertensives and other agents that may decrease BP, vasopressor sympathomimetics and other substances, allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other substances that may change the blood cell count. Moderate CYP3A4 inhibitors, niacin, ezetimibe, colestipol, fusidic acid, digoxin, oral contraceptives, warfarin, antiplatelets, NSAIDs, antirheumatics, systemic glucocorticoids, diuretics, alcohol, selective serotonin re-uptake inhibitors, uricosuric agents, anticoagulants, thrombolytics, antidiabetics (including insulin), methotrexate, valproic acid, antacids, vancomycin, interferon a, barbiturates, zidovudine, phenytoin, laboratory tests. Monitor as appropriate.

Adverse drug reactions: GI disorders, non-productive tickling cough, bronchitis, sinusitis, dyspnoea, headache, dizziness, rash (maculopapular), increased blood potassium, myalgia, muscle spasms, pain (chest, pharyngolaryngeal, extremity, back), fatigue, hypotension, decreased orthostatic BP, syncope, epistaxis, nasopharyngitis, allergic reactions, hyperglycaemia, joint swelling, arthralgia, abnormal liver function test, increased blood creatine kinase, paroxysmal bronchospasm, rhinitis, nasal congestion.

Full prescribing information and references available from A. Menarini Pharmaceuticals Ireland Ltd. Telephone: (01) 284 6744. E-mail: ireland@menarini.ie

Tara Boland

Company: Scope Ophthalmics Ltd.

Legal category: Prescription. OTC. GMS. Sport pending.

Active ingredients: Sodium hyaluronate 0.1% w/v, dexpanthenol 2% w/v.

Description: Preservative-free, sterile eye drops.

Presentation: 7.5ml, €6.06 (PTW); €7.13 (trade price).

Indication: To aid the natural healing of a damaged surface of the eye due to surgical procedures or dry eyes.

Pharmacology: Sodium hyaluronate forms an even and long lasting lubricating film on the surface of the eye without impairing vision. Dexpanthenol belongs to the group of B vitamins and assists regeneration of the corneal and conjunctival epithelia.

Dosage: Adult/Child: Instill 1 drop into conjunctival sac of each eye 3 times daily or as required.

Contraindications: Hypersensitivity to any of the ingredients.

Special precautions: Consult ophthalmologist if used more than 10 times daily, or if complaints persist.

Drug interactions: Apply at least 30 minutes after other eye drops. Administer eye ointments after Hylo-Care.

Full prescribing information and references available from Scope Ophthalmics Ltd. Telephone: 1800 816 005.
E-mail: info@scopeophthalmics.com

Tara Boland

Company: Servier Laboratories (Ireland) Ltd.

Legal category: Prescription. GMS. Sport permitted.

Active ingredient: Perindopril arginine 5mg, 10mg.

Description: White, round orodispersible tabs.

Presentation: 5mg-30, €4.80; 10mg-30, €7.83.

Indications: Both strengths: Treatment of hypertension. Stable coronary artery disease (CAD) – reduction of risk of cardiac events in patients with history of myocardial infarction (MI) and/or revascularisation. 5mg only: Treatment of symptomatic heart failure (HF).

Pharmacology: Perindopril inhibits the angiotensin converting enzyme (ACE) leading to reduced aldosterone secretion, increased plasma renin activity and increased activity of circulating and local kallikrein-kinin systems (and thus also activation of the prostaglandin system).

Dosage: Adult: Hypertension: Initially, 5mg once daily in morning before a meal. Strongly activated renin-angiotensin-aldosterone system (RAAS): Initially, 2.5mg once daily; may increase to 10mg after 1 month. Discontinue diuretic 2-3 days beforehand. If not possible, initiate with 2.5mg. Symptomatic HF: Initially 2.5mg in the morning before a meal (under medical supervision). If tolerated, increase to 5mg after 2 weeks. Severe HF: Initiate under careful supervision. CAD: Initially 5mg once daily in the morning before a meal for two weeks; if well tolerated increase to 10mg once daily. Renal impairment: Cc ≥60ml/min, 5mg per day; 30ml/min< cc <60ml/min, 2.5mg per day; 15ml/min< cc <30ml/min, 2.5mg every other day; cc <15ml/min, 2.5mg on day of dialysis. Elderly: Hypertension: Initially, 2.5mg once daily; increase to 5mg after one month, then 10mg if necessary. Symptomatic HF: As per adults. CAD: Initially 2.5mg once daily for one week; then 5mg once daily the next week; may then be increased up to 10mg once daily. Only increase dose if previous lower dose is well tolerated. Children: Under 18 years, not recommended.

Contraindications: Hypersensitivity to the active ingredients or to any of the excipients. History of angioedema. Pregnancy, lactation.

Special precautions: If dual blockade of the RAAS is considered absolutely necessary, use only under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure (BP). Assess risk/benefit if any unstable angina pectoris episode occurs during 1st month of treatment. Closely monitor initiation and dose adjustment in patients at higher risk of symptomatic hypotension (volume/salt-depletion, severe renin-dependent hypertension, severe degrees of HF), or with ischaemic heart or cerebrovascular disease in whom an excessive fall in BP could result in MI or cerebrovascular accident. Discontinue if angioedema (administer emergency therapy if tongue, glottis or larynx involved) or jaundice or marked elevations of hepatic enzymes occur. Intestinal angioedema reported rarely. May be less effective in black people. Non-productive, persistent cough reported. Risk of development of hyperkalemia; monitor serum potassium regularly. Caution: Mitral valve stenosis and obstruction in outflow of left ventricle (aortic stenosis, hypertrophic cardiomyopathy). Renal impairment; monitor potassium and creatinine routinely. Renal artery stenosis; start treatment under close medical supervision with low doses and careful dose titration. Recent kidney transplantation (no experience). Anaphylaxis reported in dialysis with high flux membranes, during LDL apheresis with dextran sulphate, or during desensitisation treatment. Neutropenia/agranulocytosis, thrombocytopenia and anaemia reported;  use with extreme caution in collagen vascular disease (especially if pre-existing renal impairment). Monitor white blood cell counts periodically and advise  patients to report any sign of infection (e.g. sore throat, fever). Discontinue one day prior to major surgery. Diabetes (monitor glycaemia levels closely). Driving/using machines. Contains lactose, aspartame.

Drug interactions: Contraindicated: Aliskiren (diabetes, renal impairment). Not recommended: Angiotensin II receptor blockers (especially in diabetic nephropathy), aliskiren, lithium, potassium sparing drugs, potassium supplements or potassium-containing salt substitutes, estramustine. Caution: Other drugs associated with increases in serum potassium (e.g. heparin), immunosuppressant therapy, allopurinol, procainamide, antidiabetics, non-steroidal anti-inflammatory drugs (especially in elderly or renal impairment), antihypertensives, vasodilators, other drugs with BP-reducing potential, tricyclic antidepressants, antipsychotics, anaesthetics, sympathomimetics, baclofen, non-potassium-sparing diuretics, gliptins, injectable gold.

Adverse drug reactions: Headache, dizziness, vertigo, paraesthesia, visual impairment, tinnitus, hypotension, cough, dyspnoea, gastrointestinal disorders, rash, pruritus, muscle cramps, fatigue.

Full prescribing information and references available from Servier Laboratories (Ireland) Ltd. Telephone: (01) 663 8110.

Tara Boland

Company: Servier Laboratories (Ireland) Ltd.

Legal category: Prescription. GMS. Sport prohibited in specific sports.

Active ingredients: Bisoprolol fumarate/ perindopril arginine 5/5mg, 5/10mg, 10/5mg, 10/10mg.

Description: Pink beige, oblong, oblong, round or oblong, bilayer film-coated tablets marked with company logo on one side and strength on reverse, respectively. 5/5mg and 5/10mg tablets are scored.

Presentation: 5/5mg-30, €7.13; 5/10mg-30, €10.16; 10/5mg-30, €7.13; 10/10mg-30, €10.16.

Indications: All strengths: As substitution therapy for treatment of hypertension and/or stable coronary artery disease (with a history of myocardial infarction (MI) and/or revascularisation) in patients adequately controlled with bisoprolol and perindopril given concurrently at the same dose level. 5/5mg and 10/5mg only: For stable chronic heart failure (HF) with reduced systolic left ventricular function in patients adequately controlled with bisoprolol and perindopril given concurrently at the same dose level.

Pharmacology: Bisoprolol is a highly beta1-selective-adrenoreceptor blocking agent, lacking intrinsic sympathomimetic and relevant membrane stabilising activity. It is generally not expected to influence airway resistance and beta2-mediated metabolic effects. Perindopril inhibits the angiotensin converting enzyme (ACE) leading to reduced aldosterone secretion, increased plasma renin activity and increased activity of circulating and local kallikrein-kinin systems (and thus also activation of the prostaglandin system).

Dosage: Adult: Titration of individual components recommended. One tablet (or half tablet) daily in the morning before a meal. Patients should be stabilised at the same dose for at least 4 weeks. Renal impairment: Creatinine clearance (Cc) ≥60ml/min, one tablet of 5/5mg or 10/5mg or half tablet of 5/10mg; 30ml/min< cc <60ml/min, one half tablet of 5/5mg only. Elderly: As per adults. Children: Not recommended.

Contraindications: Hypersensitivity to the active substances, or to any of the excipients. Acute HF or during episodes of HF decompensation requiring IV inotropic therapy, cardiogenic shock, second or third degree AV block (without pacemaker), sick sinus syndrome, sinoatrial block, symptomatic bradycardia, symptomatic hypotension, severe bronchial asthma, severe chronic obstructive pulmonary disease, severe peripheral arterial occlusive disease, severe Raynaud’s syndrome, untreated phaeochromocytoma, metabolic acidosis, history of angioedema. Pregnancy, lactation.

Special precautions: If dual blockade of the renin-angiotensin-aldosterone system (RAAS) is considered absolutely necessary, use only under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure (BP). Closely monitor initiation and dose adjustment in patients at higher risk of symptomatic hypotension (volume/salt-depletion, severe renin-dependent hypertension, severe degrees of HF), or with ischaemic heart or cerebrovascular disease in whom an excessive fall in BP could result in MI or cerebrovascular accident. Discontinue if angioedema (administer emergency therapy if tongue, glottis or larynx involved) or jaundice or marked elevations of hepatic enzymes occur. Intestinal angioedema reported rarely. May be less effective in black people. Non-productive, persistent cough reported. Risk of development of hyperkalemia; monitor serum potassium regularly. Downtitrate using individual components if symptomatic bradycardia occurs. Caution: First degree AV block, mitral valve stenosis and obstruction in outflow of left ventricle (aortic stenosis, hypertrophic cardiomyopathy), diabetics with large fluctuations in blood glucose, strict fasting. Prinzmetal’s angina. Renal impairment; monitor potassium and creatinine routinely. Renal artery stenosis; start treatment under close medical supervision with low doses and careful dose titration. Recent kidney transplantation (no experience). Anaphylaxis reported in dialysis with high flux membranes, during LDL apheresis with dextran sulphate, or during desensitisation treatment. Neutropenia/agranulocytosis, thrombocytopenia and anaemia reported;  use with extreme caution in collagen vascular disease (especially if pre-existing renal impairment). Monitor white blood cell counts periodically and advise  patients to report any sign of infection (e.g. sore throat, fever). Bronchial asthma or other chronic obstructive lung diseases. Aggravation of peripheral arterial occlusive disease may occur. Discontinue one day prior to major surgery. Psoriasis (or with a history of). Thyreotoxicosis may be masked. No therapeutic experience  treatment of HF in patients with: Insulin dependent diabetes mellitus (type I), severe renal/hepatic impairment, restrictive cardiomyopathy, congenital heart disease, haemodynamically significant organic valvular disease, MI within the last 3 months. Discontinue gradually over 2 weeks. Driving/using machines (especially at start of treatment or change of therapy, in conjunction with alcohol).

Drug interactions: Contraindicated: Aliskiren (diabetes, renal impairment). Not recommended: Angiotensin II receptor blockers (especially in diabetic nephropathy), aliskiren, lithium, potassium sparing drugs, potassium supplements or potassium-containing salt substitutes, calcium antagonists (verapamil or diltiazem type), class I antiarrhythmics, centrally acting antihypertensives, estramustine. Caution: Other drugs associated with increases in serum potassium (e.g. heparin), immunosuppressant therapy, allopurinol, procainamide, antidiabetics, non-steroidal anti-inflammatory drugs (especially in elderly or renal impairment), antihypertensives, vasodilators, other drugs with BP-reducing potential, tricyclic antidepressants, antipsychotics, anaesthetics, sympathomimetics, calcium antagonists (dihydropyridine type), class III antiarrhythmics, parasympathomimetics, topical beta-blockers, digitalis glycosides, baclofen, non-potassium-sparing diuretics. Mefloquine, monoamine oxidase inhibitors (except MAO-B inhibitors), gliptins, injectable gold.

Adverse drug reactions: Headache, dizziness, vertigo, dysgeusia, paraesthesia, visual impairment, tinnitus, bradycardia, HF worsening, hypotension, coldness or numbness in extremities, cough, dyspnoea, gastrointestinal disorders, rash, pruritus, muscle cramps, fatigue.

Full prescribing information and references available from Servier Laboratories (Ireland) Ltd. Telephone: (01) 663 8110.

Tara Boland

Implanon NXT 68mg is a radiopaque, non-biodegradable progestogen only flexible implant for subdermal use (containing the active substance etonogestrel), which is authorised in Ireland since 2010 for contraception. It is strongly recommended that Implanon NXT should only be inserted and removed by healthcare professionals (HCPs) who have completed training in the use of the applicator and techniques for insertion and removal, and, where appropriate, that supervision be requested prior to inserting or removing the implant.

There have been reports of migration of the implant within the arm from the insertion site, which may be related to deep insertion or external forces (e.g. manipulation or contact sports). There have also been rare post-marketing reports of etonogestrel implants (non-radiopaque and radiopaque) located within the vessels of the arm and the pulmonary artery, which may be related to deep insertions or intravascular insertions. Following a review of relevant data from global sources, the product information (Summary of Product Characteristics (SmPC) and Package Leaflet (PL)) for Implanon NXT has been updated to highlight this risk and to inform healthcare providers and patients about the potential consequences and possible actions to take should intravascular migration occur, as well as providing updated instructions for insertion in order to further minimise this risk.

Advice to Healthcare Professionals

• An implant should only be inserted subdermally and by a healthcare professional that has been appropriately trained.
• Insertion, localisation and removal should closely adhere to the detailed guidance and recommendations described in the SmPC.
• Immediately after insertion, the presence of the implant should be verified by palpation.
• The patient should be advised that if the implant cannot be palpated immediately after insertion, or at any time, she should be advised to return to the healthcare professional who inserted the implant immediately.
• If the implant cannot be found in the arm after comprehensive localisation attempts, consideration should be given to applying imaging techniques to the chest.
• In cases where the implant has migrated to the pulmonary artery, endovascular or surgical procedures may be needed for removal.
• As part of the risk minimisation activities to support safe and effective use of Implanon NXT, the Marketing Authorisation Holder (MAH) has updated their Clinical Training Programme providing a framework to offer practical and consistent guidance and training on Implanon NXT insertion, localisation and removal to all interested healthcare professionals. The MAH has also been requested to bring this information to the attention of healthcare professionals who have already participated in training programmes.
• A Direct Healthcare Professional Communication (DHPC) was circulated by the MAH to relevant healthcare professionals in May 2016 to highlight these updates.

Key Message

• There have been rare reports of Implanon NXT implants reaching the lung via the pulmonary artery.
• An implant that cannot be palpated at its insertion site in the arm should be located as soon as possible and removed at the earliest opportunity.
• The product information (SmPC and PL) for Implanon NXT has been updated to reflect this information and a DHPC was circulated to healthcare professionals in May 2016.
• The MAH is currently updating their Clinical Training Programme for healthcare professionals. Healthcare professionals who have previously been trained will have the option to re-train.
• Further details on Implanon NXT are available at  www.hpra.ie

Caroline McDermott

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Updated September 2016

Overview of NICE Guidelines 2015 on Management of Menopause

MIMS Ireland Copyright®

Caroline McDermott

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The NICE guidelines advise adopting an individualised approach at all stages of diagnosis, investigation and management of menopause in women.

INFORMATION AND ADVICE

– Give information to patients on the following:

• the stages of menopause
• common symptoms and diagnosis – vasomotor (e.g. hot flushes and sweats), musculoskeletal (e.g. joint and muscle pain), effects on mood (e.g. low mood), urogenital symptoms (e.g. vaginal dryness), sexual difficulties (e.g. low sexual desire)
• lifestyle changes and interventions that may help general health and wellbeing
• benefits and risks of treatments – hormonal (e.g. hormone replacement therapy), non-hormonal (e.g. clonidine), non-pharmaceutical (e.g. cognitive behavioural therapy [CBT])
• long-term health implications of menopause
• contraception

– Give information in different ways to help encourage patients to discuss their symptoms and needs.

– Offer patients who are likely to go through menopause as a result of medical or surgical treatment support and information about menopause and fertility before they have their treatment, and referral to a menopause specialist.

MANAGING SHORT-TERM SYMPTOMS

Vasomotor symptoms

– Offer patients HRT after discussing the short-term (up to 5 years) and longer-term benefits and risks:

• oestrogen and progestogen to women with a uterus
• oestrogen alone to women without a uterus.

– Do not routinely offer selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) or clonidine as first-line treatment for vasomotor symptoms alone.

Psychological symptoms

– Consider HRT to ease low mood, or CBT to ease low mood or anxiety.

– There is no clear evidence that SSRIs or SNRIs ease low mood in menopausal women who have not been diagnosed with depression.

Urogenital atrophy

– Offer patients vaginal oestrogen (including those on systemic HRT) and continue treatment for as long as needed to relieve symptoms.

– If vaginal oestrogen is not effective, consider increasing dose, after seeking advice from a specialist.

– Consider vaginal oestrogen if systemic HRT is contraindicated, after seeking advice from a specialist.

– Explain to patients that symptoms often come back when treatment is stopped, that adverse effects from vaginal oestrogen are very rare, and that they should report unscheduled vaginal bleeding.

– Advise patients with vaginal dryness that moisturisers and lubricants can be used alone or with vaginal oestrogen.

– Do not offer routine monitoring of endometrial thickness during treatment for urogenital atrophy.

REVIEW AND REFERRAL

– Remind patients of the need to keep up-to-date with national health screening.

– Review treatment at 3 months and annually thereafter unless earlier review is clinically indicated (e.g. treatment ineffectiveness, side-effects or adverse events).

– Refer patients to a specialist if symptoms do not improve or they have ongoing troublesome side-effects.

– Consider referral to a specialist if there are contraindications to HRT or uncertainty about the most suitable treatment.

STARTING AND STOPPING HRT

Explain to patients with a uterus that unscheduled vaginal bleeding is a common side-effect of HRT within the first 3 months of treatment but should be reported promptly if it occurs after 3 months.

Explain to patients that gradually reducing HRT may limit recurrence of symptoms in the short term, and that gradually reducing or immediately stopping HRT makes no difference to symptoms in the longer term.

WOMEN WITH, OR AT HIGH RISK OF, BREAST CANCER

– Refer to NICE guidelines on early and locally advanced breast cancer and NICE guidelines on familial breast cancer for advice on the treatment of menopausal symptoms in women with breast cancer or at high risk of breast cancer.

– Offer patients information on all available treatment options, information that the SSRIs paroxetine and fluoxetine should not be used in patients with breast cancer who are taking tamoxifen, and referral to a menopause specialist.

LONG-TERM BENEFITS AND RISKS OF HRT

Venous thromboembolism

– Explain to patients that:

• the risk of venous thromboembolism (VTE) is increased by oral HRT compared with baseline population risk
• the risk of VTE associated with HRT is greater for oral than transdermal preparations
• the risk of VTE associated with transdermal HRT at standard therapeutic doses is no greater than baseline population risk.

– Consider transdermal rather than oral HRT for patients at increased risk of VTE (e.g. BMI >30kg/m²).

– Consider referring patients at high risk of VTE (e.g. a strong family history of VTE or a hereditary thrombophilia) to a haematologist before considering HRT.

Cardiovascular disease

– Explain to patients that HRT:

• does not increase cardiovascular disease (CVD) risk when started in women aged under 60 years
• does not affect the risk of dying from CVD.

– Cardiovascular risk factors are not a contraindication to HRT if they are optimally managed.

– Explain to patients that:

• the baseline risk of coronary heart disease and stroke for women around menopausal age varies from one woman to another according to the presence of cardiovascular risk factors
• HRT with oestrogen alone is associated with no, or reduced, risk of coronary heart disease
• HRT with oestrogen and progestogen is associated with little or no increase in the risk of coronary heart disease – an estimated 5 more cases (RCT estimate)^a of coronary artery disease per 1000 current HRT users over 7.5 years for oestrogen plus progestogen versus baseline population risk of 26.3 cases per 1000 women over 7.5 years; see guidelines for other estimates
• taking oral (but not transdermal) oestrogen is associated with a small increase in the risk of stroke – an estimated 3 more stroke cases (observational estimate)^b for oestrogen alone and an estimated 6 more stroke cases (RCT estimate)^a for oestrogen plus progestogen per 1000 current HRT users over 7.5 years versus baseline population risk of 11.3 cases per 1000 women over 7.5 years; see guidelines for other estimates
• the baseline population risk of stroke in women aged under 60 years is very low.

Type 2 diabetes

– Explain to patients that HRT (oral or transdermal) is not associated with an increased risk of developing type 2 diabetes.

– Explain to patients with type 2 diabetes that HRT is generally not associated with an adverse effect on blood glucose control.

– Take comorbidities into account when considering HRT in patients with type 2 diabetes and seek specialist advice if needed.

Breast cancer

– Explain to patients around the age of natural menopause that :

• the baseline risk of breast cancer around menopausal age varies from one woman to another according to the presence of underlying risk factors
• HRT with oestrogen alone is associated with little or no change in the risk of breast cancer
• HRT with oestrogen and progestogen can be associated with an increase in the risk of breast cancer – an estimated 5 more cases (RCT estimate)^a to 17 more cases (observational estimate)^b per 1000 current HRT users for oestrogen plus progestogen over 7.5 years versus baseline population risk of 22.48 cases per 1000 women over 7.5 years; see guidelines for other estimates
• any increase in the risk of breast cancer is related to treatment duration and reduces after stopping HRT.

Osteoporosis

– Give patients advice on bone health and discuss these issues at review appointments.

– Explain to patients that:

• the baseline population risk of fragility fracture for women around menopausal age is low and varies from one woman to another
• their risk of fragility fracture is decreased while taking HRT – an estimated 16 fewer cases (observational estimate)^a to 23 fewer cases (RCT estimate)^b of osteoporosis per 1000 current HRT users versus baseline population risk of 69 cases per 1000 women over 3.43 years; see guidelines for other estimates
• this benefit is maintained during treatment but decreases once treatment stops, and may continue for longer in women who take HRT for longer.

a: Randomised controlled trial (RCT) estimates.

b: Observational estimates are based on cohort studies with several thousand women.

Reference: 1. [adapted] NICE guideline [NG23] Menopause: diagnosis and management. Published November 2015. Available at www.nice.org.uk/guidance/ng23?unlid=4799121020169841645. Last accessed 19th September 2016.

Options for Hormone Replacement Therapy

MIMS Ireland Copyright®

Caroline McDermott

Company: MSD Ireland (Human Health) Ltd.

Legal category: Prescription. Hospital only. Sport permitted.

Active ingredients: Ceftolozane/tazobactam 1g/500mg.

Description: Powder for concentrate for solution for infusion.

Presentation: 10 vials, price on request.

Indications: Treatment of complicated intra‑abdominal infections (in combination with metronidazole when anaerobic pathogens are suspected), acute pyelonephritis, and complicated urinary tract infections (UTIs).

Pharmacology: Ceftolozane belongs to the cephalosporin class of antimicrobials, and exerts bactericidal activity through binding to important penicillin-binding proteins, resulting in inhibition of bacterial cell‑wall synthesis and subsequent cell death. Tazobactam is a beta‑lactam structurally related to penicillins. It is an inhibitor of many Molecular Class A beta-lactamases.

Dosage: Adult: 1g/500mg every 8 hours by intravenous (IV) infusion over 1 hour. Duration 4 – 14 days in intra-abdominal infection, 7 days in Urinary Tract Infection and pyelonephritis. Renal impairment: Creatinine clearance (cc) 30-50ml/min, 500/250mg every 8 hours; cc 15-29ml/min, 250/125mg every 8 hours; End stage renal disease on haemodialysis, loading dose of 500/250mg followed 8 hours later by 100/50mg every 8 hours. All doses administered by IV infusion over 1 hour. Elderly: As per adults. Children: Under 18 years, not recommended.

Contraindications: Hypersensitivity to the active substances or to any of the excipients. Hypersensitivity to any cephalosporin. Severe hypersensitivity to other beta‑lactams. Lactation.

Special precautions: Caution: Hypersensitivity to penicillins or other beta-lactams. Discontinue if severe allergic reaction occurs. Renal impairment. No data: Immunocompromised patients, severe neutropenia. May occur: Clostridium difficile‑associated diarrhoea (consider discontinuation), super infection, decline in renal function, positive Coombs test. Pregnancy (assess risk/benefit). Driving/using machines. Contains sodium.

Drug interactions: Inhibitors of OAT1 or OAT3.

Adverse drug reactions: Thrombocytosis, hypokalaemia, insomnia, anxiety, headache, dizziness, hypotension, gastrointestinal disorders, rash, pyrexia, infusion site reactions, increased alanine aminotransferase, increased aspartate aminotransferase.

Full prescribing information and references available from MSD Ireland (Human Health) Ltd. Telephone: (01) 299 8700.

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Company: Boehringer Ingelheim Ltd.

Legal category: Pharmacy only. Sport permitted.

Active ingredient: Ambroxol hydrochloride 20mg (lozenges), 17.86mg/ml (spray).

Description: Round, white, mint or lemon lozenges. Oromucosal spray.

Presentation: Lozenges: 18, €3.99. Spray: 20ml, €5.74.

Indications: Lysopadol mint: Pain relief of mild to moderate symptoms of acute sore throat. Spray and lysopadol lemon: Pain relief in acute sore throat.

Pharmacology: Ambroxol hydrochloride exerts a local anaesthetic effect which is likely to result from its sodium channel blocking properties. It also exerts an anti-inflammatory effect.

Dosage: Adult: 1 dose: 1 lozenge (sucked) or 4 actuations (into back of throat). Maximum 6 doses per day for 3 days. Children: Over 12 years, as per adults. Under 12 years, not recommended.

Contraindications: Hypersensitivity to the active substance or to any of the excipients. Pregnancy, lactation.

Special precautions: Not for oral ulcers. Seek medical advice: If signs of progressive skin rash occur (discontinue immediately), if symptoms worsen or persist after 3 days, before use in patients with renal impairment or severe hepatopathy. Dyspnoea may occur. Lysopadol lemon (also contains sucrose) and lysopadol mint (also contains lactose) contain sorbitol. Spray contains ethanol, propylene glycol.

Drug interactions: None reported.

Adverse drug reactions: Dysgeusia, oral and pharyngeal hypoaesthesia, nausea.

Full information and references available from Boehringer Ingelheim Ltd. Telephone: (01) 295 9620.
E-mail: medinfo.bra@boehringer-ingelheim.com

The post Lysopadol appeared first on Irish Medical Times.

Company: Pharmacosmos UK Ltd.

Legal category: Prescription. Sport permitted.

Active ingredient: Iron (as iron(III) isomaltoside 1000) 50mg/ml.

Description: Solution for injection.

Presentation: 25 x 2ml, €735.29.

Indication: Treatment of iron deficiency in patients with chronic kidney disease on dialysis, when oral iron preparations are ineffective or cannot be used.

Pharmacology: Iron isomaltoside is a haematinic. The strongly bound complex comprising iron and isomaltoside 1000 enables a controlled and slow release of bioavailable iron to iron-binding proteins with little risk of free iron. Reticuloendothelial system cells rapidly take up iron isomaltoside 1000, remove circulating iron from the plasma and split the complex into its components. The released iron is immediately bound to the available protein moieties to form hemosiderin, ferritin or transferrin. This iron, which is subject to physiological control, replenishes haemoglobin and depleted iron stores.

Dosage: Adult: Up to 200mg (based on response, see SPC) by intravenous bolus injection or directly into venous limb of dialyser; maximum 1000mg weekly. Elderly: As per adults. Children: Under 18 years, not recommended.

Contraindications: Hypersensitivity to the active substance, or any of its excipients. Known serious hypersensitivity to other parenteral iron products. Non-iron deficiency anaemia (eg. haemolytic anaemia). Iron overload or disturbances in utilisation of iron (eg. haemochromatosis, haemosiderosis). Decompensated liver cirrhosis and hepatitis.

Special precautions: Risk of anaphylaxis; facilities for full resuscitation must be available; monitor patient during and for 30 minutes after each administration. Ongoing bacteraemia (do not use). Caution: Acute or chronic infection, known allergies, history of severe asthma or eczema, immune or inflammatory conditions (eg. systemic lupus erythematosus, rheumatoid arthritis). Hypotensive episodes may occur if IV injection too rapid. Pregnancy (2nd or 3rd trimester), lactation. Contains sodium.

Drug interactions: Caution: Oral iron, do not start earlier than 5 days after last injection.

Adverse drug reactions: None common.

Full prescribing information and references available from Pharmacosmos UK Ltd. Telephone: +44 1844 269007.
E-mail: support@pharmacosmos.ie

The post Diafer ▼ appeared first on Irish Medical Times.

Company: Rowex Ltd.

Legal category: Prescription. GMS reimbursable. Sport permitted.

Active ingredients: Alendronic acid (as alendronate sodium trihydrate)/ colecalciferol 70mg/5600 IU.

Description: White, oval tablet marked 714.

Presentation: 4, €7.49.

Indications: Treatment of postmenopausal osteoporosis in women at risk of vitamin D insufficiency not receiving vitamin D supplementation. Reduces the risk of vertebral and hip fractures.

Pharmacology: Alendronate sodium is a bisphosphonate that inhibits osteoclastic bone resorption. Vitamin D3 is an essential dietary nutrient (in the absence of adequate sunlight exposure). The active calcium-mobilizing hormone 1,25-dihydroxyvitamin D3 increases intestinal absorption of both calcium and phosphate as well as regulating serum calcium, renal calcium and phosphate excretion, bone formation and bone resorption.

Dosage: Adult: One tablet once weekly. Consider supplementation with calcium or additional vitamin D. Swallow whole. Take at least 30 minutes before first food, drink, or drug of the day with plain water only and do not lie down for at least 30 minutes. Elderly: As per adults. Children: Under 18 years, not recommended.

Contraindications: Hypersensitivity to the active substances or to any of the excipients. Abnormalities of the oesophagus and other factors which delay oesophageal emptying (such as stricture or achalasia). Inability to stand or sit upright for at least 30 minutes. Hypocalcaemia. Pregnancy, lactation.

Special precautions: Not recommended: Creatinine clearance less than 35ml/min. Caution: Active upper gastrointestinal (GI) problems (such as dysphagia, oesophageal disease, gastritis, duodenitis, ulcers), recent history of major GI disease (such as peptic ulcer), active GI bleeding, surgery of the upper GI tract other than pyloroplasty. Re-evaluate periodically based on the benefit/risk ratio, especially after 5 or more years of use. Barrett’s oesophagus (assess benefit/risk). Reported: Osteonecrosis of the jaw (consider dental examination prior to therapy in patients at risk, avoid invasive dental procedures); oesophagitis, oesophageal ulcers, oesophageal erosions; bone, joint and/or muscle pain; atypical subtrochanteric and diaphyseal femoral fractures (consider discontinuation pending evaluation). Discontinue if dysphagia, pain on swallowing, retrosternal pain, new or worsening heartburn develops. Reported rarely, gastric and duodenal ulcers (severe). Correct hypocalcaemia and other disorders affecting mineral metabolism (such as vitamin D deficiency and hypoparathyroidism) before starting treatment; monitor serum calcium and symptoms of hypocalcaemia during treatment. Symptomatic hypocalcaemia reported rarely (occasionally severe). Ear symptoms (consider osteonecrosis of the external auditory canal). Patients should report any thigh, hip or groin pain; evaluate for incomplete femur fracture. Monitor urine and serum calcium in patients with disease associated with unregulated overproduction of calcitriol (e.g. leukaemia, lymphoma, sarcoidosis). Patients with malabsorption may not adequately absorb vitamin D3. Contains sucrose. Driving/using machines.

Drug interactions: Caution: Non steroidal anti-inflammatory drugs. Olestra, mineral oils, orlistat, bile acid sequestrants (e.g. cholestyramine, colestipol), anticonvulsants, cimetidine, thiazides, glucocorticoids.

Adverse drug reactions: Headache, dizziness, vertigo, GI disorders, alopecia, pruritus, musculoskeletal (bone, muscle or joint) pain, joint swelling, asthenia, peripheral oedema.

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

The post Alendronate/Colecalciferol Rowex appeared first on Irish Medical Times.