The HPRA continues to place great emphasis on encouraging and promoting the submission of adverse reaction reports associated with the use of medicines from its stakeholders. These reports are important to highlight potential safety issues from medicines in use and ultimately assist the HPRA in monitoring the safety of medicines on the Irish market.

During 2014, we received a total of 2,884 suspected adverse reaction reports occurring in Ireland from healthcare professionals, members of the public and pharmaceutical companies, indicating a small increase in reporting figures for 2013. A breakdown of the reports by source is outlined below and it is important to note that reports submitted by pharmaceutical companies, will have first been brought to their attention by healthcare professionals, patients and consumers, prior to onward reporting to HPRA.

In keeping with experience in other European countries, reporting rates were highest for newly authorised medicines, with nearly 20% of the reports received associated with the use of medicines subject to additional monitoring requirements. The requirements for additional monitoring introduced in the context of the legislative revisions in 2012 highlighted the importance of reporting all suspected adverse reactions associated with the use of these products, identifiable by an black inverted triangle on the product information (Summary of Product Characteristics (SmPC) and Package Leaflet (PL)) and the contribution of reporters in highlighting experience with these new medicines, for which limited data may be available, is especially helpful. Reporting rates are also influenced by their ease of recognition and may be stimulated by publicity about a particular medicine or reaction. Reporting rates are also influenced by proactive and repeated requests to healthcare professionals to submit reports on certain medicines as part of on-going post marketing surveillance, as well as other promotional and data collection activities.

Breakdown of Reports by Source for 2014

Source of Suspected Adverse Reaction Reports

Pharmaceutical Company: 67%

Community Care Doctor: 7%

General Practioner: 4%

Hospital Doctor/Specialists: 4%

Hospital Pharmacist: 4%

Community Pharmacist: 4%

Nurse: 4%

Patient/Consumer: 3%

Clinical Trial reports: 2%

Other: 1%

Individual case reports are followed up by the HPRA, with feedback information provided to reporters, as appropriate. Relevant, anonymised reports (i.e. serious, suspected cases) notified directly to the HPRA by healthcare professionals or members of the public are forwarded to the appropriate marketing authorisation holders (MAHs) and the European Medicines Agency (EMA) within the agreed timeframes and formats. The HPRA also continues to provide details of reports received to the World Health Organisation (WHO) for inclusion on its international database.

There are several options in place for reporting suspected adverse reactions to the HPRA. These are as follows:

• By following the links to the online reporting options accessible for the HPRA homepage (www.hpra.ie),
• Using the downloadable report form also accessible from the HPRA website, which may be completed manually and submitted to the HPRA via ‘freepost’,
• Using the traditional ‘yellow card’ report, which also utilises a freepost system,
• By telephone to the HPRA Pharmacovigilance section (01-6764971)

Caroline McDermott

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 Incidence and Epidemiology

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in the Western world, with an incidence of about 4:100 000/year, which increases to over 30:100 000/year in people aged over 80 years. The median age at diagnosis is 72 years. There is an inherited genetic susceptibility for CLL, with a 6- to 9-fold increased risk for relatives of CLL patients.

Diagnosis and staging

CLL is characterised by peripheral blood B-cell lymphocytosis as well as lymphadenopathy, organomegaly, cytopenias, and systemic symptoms. CLL cells have a distinctive immunophenotype, and the disease has a characteristic pattern of histological infiltration in the lymph node and bone marrow.

Diagnosis of CLL is based on the following criteria:

• Presence in the peripheral blood of ≥5000 monoclonal B lymphocytes/µl. Clonality must be confirmed by flow cytometry. Flow cytometry is used to confirm the presence of CLL cells expressing CD5, CD19, CD20 and CD23, and to differentiate CLL from other lymphoproliferative disorders.
• Microscopic examination of the peripheral blood smear shows the presence of leukaemia cells that are small, mature-appearing lymphocytes with a narrow border of cytoplasm and a dense nucleus lacking discernible nucleoli, and having partially aggregated chromatin. Larger, atypical lymphocytes or prolymphocytes may be seen but must not exceed 55%.

The following are recommended before treatment:

• History, physical examination (including careful palpation of all lymph node areas, spleen and liver) and performance status
• Complete blood cell count and differential
• Serum chemistry including serum immunoglobulin and direct antiglobulin test
• Hepatitis B and C, cytomegalovirus and human immunodeficiency virus serology should be evaluated before chemo-immunotherapy or allogeneic stem-cell transplantation to avoid virus reactivation
• Fluorescence in situ hybridisation (FISH) for detection of deletion of the chromosome 17 [del (17p)] affecting tumour protein p53 expression, and in the absence of del(17p) molecular genetics for detection of TP53 gene mutation.

Table 1. Clinical Staging Systems for CLL (used to predict median survival)

Click on image to enlarge

Treatment options

The choice of treatment will depend on several factors including the stage of the disease, whether or not the patient is experiencing symptoms, the age and overall health of the patient, and the benefits versus side effects of treatment. A variety of chemotherapy regimens are used in CLL. These regimens may include nucleoside analogues, alkylating agents and biologics, often in combination (see Fig. 1 and Fig. 2 for agents used for front-line treatment of CLL and treatment of relapsed / refractory CLL, respectively).

Please refer to section 20.1 of MIMS Ireland Oncology Reference and SPCs of individual products for more information on up-to-date details of licensing.

Figure 1. Front-line Treatment of Chronic Lymphocytic Leukaemia¹

Click on image to enlarge

a Some patients may present solely with lymphadenopathy, organomegaly, and presence of infiltrating monoclonal B cells with the same immunophenotype as CLL cells, but lacking peripheral blood lymphocytosis. This disease is called small lymphocytic lymphoma (SLL). Both CLL and SLL are currently considered different manifestations of the same entity by the 4^th edition of the World Health Organisation Classification of Tumours of Haematopoietic and Lymphoid Tissues. b Early treatment with chemotherapeutic agents does not translate into a survival advantage in patients with early-stage CLL without symptomatic, active disease. c Treatment should only be initiated in patients with symptomatic, active disease. Active disease is defined by significant B symptoms, cytopaenias not caused by autoimmune phenomena and symptoms or complications from lymphadenopathy, splenomegaly or hepatomegaly, lymphocyte doubling time of <6 months (only in patients with more than 30G lymphocytes/l), as well as autoimmune anaemia and/or thrombocytopaenia poorly responsive to conventional therapy.

CLL, chronic lymphocytic leukaemia; SLL, small lymphocytic leukaemia; FCR, fludarabine, cyclophosphamide and rituximab; BR, bendamustine plus rituximab; Clb, chlorambucil; anti-CD20 antibody, such as rituximab, ofatumumab or obinutuzumab; BCR inhibitor, B-cell receptor inhibitor such as ibrutinib or idelalisib; R, rituximab; alloHSCT, allogeneic haematopoietic stem cell transplantation

Figure 2. Treatment of Relapsed or Refractory Chronic Lymphocytic Leukaemia¹

Click on image to enlarge

a Treatment at relapse should only be started in symptomatic patients – many patients with relapsed but asymptomatic CLL can be monitored with no therapy for a long period of time. b First-line treatment may be repeated if the relapse or progression occurs at least 24–36 months after chemo-immunotherapy and if no TP53 disruption. c If relapse occurs within 24–36 months after chemo-immunotherapy, or if the disease does not respond to any first-line therapy, the therapeutic regimen should be changed. Treatment options include BCL2 antagonists (alone or in combination within a clinical study); B-cell receptor inhibitors (such as ibrutinib or idelalisib); other chemo-immunotherapy combinations should only be administered in patients without TP53 disruption. Patients not responding nor progressing upon therapy with kinase inhibitors might be switched to a different kinase inhibitor or to BCL2 antagonists when available through clinical trials. Fit patients achieving 2^nd remission following 2^nd administration of an inhibitor should proceed to allogeneic HSCT.

CLL, chronic lymphocytic leukaemia; SLL, small lymphocytic leukaemia; FCR, fludarabine, cyclophosphamide and rituximab; BR, bendamustine plus rituximab; BCR inhibitor, B-cell receptor inhibitor such as ibrutinib or idelalisib; R, rituximab; alloHSCT, allogeneic haematopoietic stem cell transplantation

References:

1. Eichhorst B et al. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26 (Suppl. 5): v78–v84 [adapted].

2. Santos FP and O’Brien S. Small lymphocytic lymphoma and chronic lymphocytic leukemia: are they the same disease? Cancer J. 2012 Sep-Oct;18(5):396-403.

Caroline McDermott

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Roche is pleased to announce that Gazyvaro (obinutuzumab) is now available in Ireland for people with previously untreated chronic lymphocytic leukaemia (CLL).

Gazyvaro, in combination with chlorambucil chemotherapy, is indicated for the treatment of adult patients with previously untreated CLL who have comorbidities making them unsuitable for an intensive therapy (full-dose fludarabine based therapy).¹

CLL, which is characterised by a neoplastic accumulation of B lymphocytes, is the most common type of leukaemia in Ireland, accounting for about 40% of cases.² The majority of patients with CLL are older than 70 years of age, and many present with coexisting medical conditions.

Gazyvaro is a type II, glycoengineered, humanised monoclonal antibody designed to target CD20, a protein found on the surface of B lymphocytes. It induces direct cell death and mediates antibody-dependent cellular cytotoxicity, with a low degree of complement-dependent cytotoxicity.

Gazyvaro received European approval based on the outcomes of the CLL11 study, which investigated the benefit of obinutuzumab combined with chlorambucil as compared with that of chlorambucil alone or rituximab combined with chlorambucil, in patients with previously untreated CLL and comorbidities.³

Study design

CLL11 is a phase III, multicentre, open-label, randomised three-arm study which investigated the efficacy and safety of obinutuzumab plus chlorambucil compared to rituximab plus chlorambucil, or chlorambucil alone, in 781 patients with previously untreated CLL and coexisting medical conditions.

Patients received six 28-day cycles of either obinutuzumab (1000mg intravenous [IV] infusion, on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2 through 6) plus chlorambucil (0.5mg/kg orally, days 1 and 15 of each cycle), or rituximab (IV infusion, 375mg/m² on day 1 of cycle 1, 500mg/m² on day 1 of cycles 2 through 6) plus chlorambucil, or chlorambucil alone. In the obinutuzumab arm, in order to reduce the rate of infusion reactions, an amendment of the study protocol was implemented and the first infusion of obinutuzumab was administered over a period of 2 days.

The primary endpoint of the study was progression-free survival (PFS), as assessed by the site investigators. Secondary endpoints included response rates (RR), minimal residual disease (MRD), overall survival (OS), and adverse events.

Significant prolongation of PFS with Gazyvaro

Obinutuzumab-chlorambucil met its primary endpoint by significantly reducing the risk of disease worsening or death by 61% compared to rituximab-chlorambucil (median PFS, 26.7 vs 15.2 months; hazard ratio [HR], 0.39; p<0.001).

Figure 1. PFS with Obinutuzumab plus Chlorambucil vs Rituximab plus Chlorambucil

Click on image to enlarge

Significant benefits in RR, MRD and OS with Gazyvaro

Treatment with obinutuzumab showed higher complete response rates (20.7% vs 7%) and a ten-fold increase in the percentage of people achieving MRD negativity in blood (37.7% vs 3.3%) compared to the rituximab arm of the study. MRD negativity in bone marrow was also significantly higher after obinutuzumab-chlorambucil treatment (19.5% vs 2.6%).

Treatment with obinutuzumab-chlorambucil provided a significant benefit in OS compared with chlorambucil monotherapy (HR, 0.41; p=0.002). No significant benefit in OS was noted for obinutuzumab-chlorambucil over rituximab-chlorambucil (HR, 0.66; p=0.08), the rates of death being 8% and 12%, respectively. OS medians were not reached.

Safety profile

The most common severe adverse events (grade ≥ 3) for obinutuzumab were infusion-related reactions (IRRs), infections, thrombocytopenia and neutropenia. IRRs and neutropenia were more common with obinutuzumab-chlorambucil than with rituximab-chlorambucil, but the rates of infection did not differ significantly. The incidence and severity of IRRs decreased dramatically after the first infusion and no severe IRRs were reported beyond the first infusion.

Conclusion

This study showed that Gazyvaro plus chlorambucil chemotherapy improves the outcomes in patients with previously untreated CLL and comorbidities. Treatment with Gazyvaro plus chlorambucil resulted in longer PFS, more complete responses and higher negative testing for MRD than with rituximab plus chlorambucil, and provided an OS advantage over chlorambucil alone.³

References

1. Gazyvaro SPC (revised 21st May 2015)

2. National Cancer Registry Ireland. Accessed 28th September 2015 at http://www.ncri.ie/atlas/2129-21218-other-cancers

3. Goede V. et al. N Engl J Med 2014;370:1101-10.

Full prescribing information and references available from Roche Products (Ireland) Ltd. Telephone: (01) 4690700. IE/GA101/1015/0001

Caroline McDermott

PRESCRIBING INFORMATION

Presentation: Each capsule contains codeine phosphate hemihydrate 15mg and paracetamol 500mg. Each effervescent tablet contains codeine phosphate hemihydrate 15mg and paracetamol 500mg. Excipients in the effervescent tablets include 389mg sorbitol and 379mg sodium. Indications: Codipar Capsules and Effervescent Tablets: For the relief of mild to severe acute pain in adults. Codeine is indicated for the treatment of acute moderate pain which is not relieved by other analgesics such as paracetamol or ibuprofen alone. Dosage and Administration: For oral administration. Swallow the capsules whole with a glass of water or dissolve the tablets in a glass of water and drink immediately. Adults: Usual dosage is 2 capsules or effervescent tablets every 6 hours as needed. Codeine should be used at the lowest effective dose for the shortest period of time. Maximum daily dose should not exceed 8 capsules or 8 tablets in a day. The duration of treatment should be limited to 3 days. Elderly: Reduced dosage may be necessary. Children: Codipar capsules and tablets are not recommended below the age of 18 years. Contraindications: Hypersensitivity to either paracetamol or codeine, or any of the excipients. Moderate to severe renal or hepatic impairment. In all paediatric patients (0-18 years of age). In conditions where morphine and opioids are contraindicated e.g. those with acute asthma, obstructive airway disease, respiratory depression, acute alcoholism, head injuries, raised intracranial pressure, after biliary surgery or diarrhoea of any cause. In patients who have taken MAO inhibitors within 14 days. In patients for whom it is known they are CYP2D6 ultra-rapid metabolisers and in women during breast-feeding. Precautions and warnings: Caution in patients with inflammatory or obstructive bowel disorders or with acute abdominal conditions, increased intracranial pressure or those taking CNS depressants, the elderly, debilitated, hypothyroidism, Addison’s disease, impaired hepatic or renal function, prostatic hypertrophy and urethral stricture. Codeine is metabolised by the liver enzyme CYP2D6 into morphine. Caution is advised in patients who are CYP2D6 ultra-rapid metabolisers as there is increased risk of developing side effects of opioid toxicity even at commonly prescribed doses. Symptoms include confusion, shallow breathing, small pupils, nausea, vomiting, constipation, lack of appetite and somnolence. Risk of paracetamol overdose is greater in those with alcoholic liver disease. Other products containing paracetamol or opiate derivatives should not be taken while on Codipar. Tolerance to codeine dependence (psychological and/physical), abuse, as well as withdrawal can develop with continued use and the incidence of unwanted effects is dose related. Long term use for headache treatment can make them worse. High doses can cause respiratory depression, cough suppression or impaired mental and physical abilities. Dose should be reduced in liver and kidney disease. Immediate medical advice should be taken after overdose especially when liver disease co-exists. Patients should not drive, operate machinery or perform hazardous tasks if Codipar causes dizziness, sedation or visual disturbance. Interactions: Antihypertensive agents, diuretics, quinine, quinidine, mexilitine, CNS depressants (anxiolytics, hypnotics, antidepressants, antipsychotics, alcohol), MAOIs or tricyclic antidepressants, anticholinergics, antidiarrhoeal agents, antimuscarinic drugs, metoclopramide, domperidone, cholestyramine, cimetidine, warfarin and other coumarins (with long term use of paracetamol), enzyme-inducing antiepileptics (carbamazepine, phenytoin, and phenobarbital) as well as CYP2D6 inhibitors (quinidine, some SSRIs, some neuroleptics and ritonavir). Opioids may interfere with results of some laboratory tests and codeine may interfere with tests for gastrointestinal function. Pregnancy and lactation: Not recommended. Undesirable effects: Common: Dizziness, light-headedness, sedation, headache, nausea, vomiting, constipation, abdominal pain, dysphoria, euphoria, shortness of breath, pruritus, rash or urticaria. Codeine can cause respiratory depression in patients with respiratory problems or with pre-existing lung disorders or in overdose situations. Paracetamol may cause liver damage. Most often this is with chronic alcohol use. Paracetamol containing products may also rarely cause blood dyscrasias (including thrombocytopenia and agranulocytosis). Addiction and withdrawal are also possible and headaches can worsen with chronic use. (Please refer to the Summary of Product Characteristics for detailed information) Overdose: Over 5g ingestion of paracetamol can cause liver damage if patient has risk factors (like taking drugs that induce liver enzymes, excessive alcohol intake, glutathione depletion, eating disorders, starvation, cystic fibrosis, HIV, cachexia) or over 10g intake otherwise. Codeine overdose may produce respiratory depression and hypotension, with circulatory failure and deepening coma. Convulsions may occur from respiratory failure. Codeine overdose is potentiated with alcohol and psychotropic drugs. Legal Category: POM. Pack sizes: Codipar Capsules: 1 x 100; Codipar Effervescent Tablets: 1 x 100. Marketing Authorisation Numbers: Codipar Capsules: PA 0899/033/002; Codipar Effervescent Tablets: PA 899/33/1. PCRS reimbursed. Marketing Authorisation Holder: Amdipharm Mercury Company Limited (AMCo), 1st Floor, Capital House, 85 King William Street, London, EC4N 7BL. Date of preparation: August 2012. Date of revision: April 2015

Reference:

1. ACC Review 50. Preventing Chronic Pain:Pharmacological treatment of sprains, strains and other minor,painful injuries. ACC 6338, March 2012.
2. A Gordon Macleod, Ashford B et al. 2002. Paracetamol versus paracetamol-codeine in the treatment of post-operative dental pain: A randomized, double-blind, prospective trial. Australian Dental Journal. Volume 47, issues 3, pages 147-151.

IRE/COD/ADV/787/2015       May 2015

Caroline McDermott

The 2016 WADA (World Anti-Doping Agency) Prohibited List comes into effect on 1 January 2016.  The List designates the substances and methods which are prohibited in- and out-of-competition and which substances are banned in particular sports. In accordance with the World Anti-Doping Code, if a substance or method is found to meet two of three criteria (performance-enhancement, danger to athletes’ health or its use is against the spirit of sport), then it could be considered for placement on the List.  WADA’s List Expert Group annually reviews the List taking into consideration submissions from stakeholders, advancements in scientific and medical research, intelligence gathered from law enforcement and pharmaceutical companies, emerging trends in doping practice etc.

Changes of interest include the following:

In S2. Peptide Hormones, Growth Factors, Related Substances and Mimetics, leuprorelin replaced triptorelin as a more universal example of a chorionic gonadotrophin and luteinizing hormone-releasing factor.

Under S4. Hormone and Metabolic Modulators, insulin-mimetics were added to the List to include all insulin-receptor agonists.  In addition, meldonium, which is also known as mildronate, was added because of evidence of its use by athletes with the intention of enhancing performance.  Meldonium is marketed as a medicinal product in Russia and the Ukraine and is regarded as an inhibitor of carnitine synthesis and reported to have cardioprotective and anti-ischaemic effects.

The List now clarifies that and that the ophthalmic use of carbonic anhydrase inhibitors (S.5 Diuretics and Masking Agents) and the alpha2 adrenoceptor agonist clonidine (S.6 Stimulants) are both permitted.

Commenting on the publication of the 2016 WADA List, Dr Una May, Director of Participation and Ethics in Sport Ireland said “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 plays a vital role in providing the necessary information for medical personnel regarding WADA’s Prohibited List.”  The updates to the 2016 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.irishsportscouncil/Anti-Doping), www.eirpharm.com and National Governing Bodies of Sport.

Tara Sweeney

Company: Eli Lilly and Co (Ireland) Ltd.

Legal category: Prescription. GMS reimbursable. Sport permitted.

Active ingredient: Dulaglutide 0.75mg/0.5ml, 1.5mg/0.5ml.

Description: Solution for injection in pre-filled pens.

Presentation: 0.75mg/0.5ml-4, €103.90; 1.5mg/0.5ml-4, €103.90.

Indications: For type 2 diabetes mellitus in adults to improve glycaemic control when diet and exercise alone are inadequate; as monotherapy when metformin is inappropriate due to intolerance or contraindications, or as add-on therapy in combination with other glucose-lowering medicines including insulin.

Pharmacology: Dulaglutide is a longacting glucagonlike peptide 1 (GLP1) receptor agonist. It is resistant to degradation by DPP4. Its large size slows absorption and reduces renal clearance resulting in a soluble formulation and a prolonged halflife of 4.7 days, therefore making it suitable for once-weekly subcutaneous administration. In addition, the dulaglutide molecule prevents the Fcg receptor-dependent immune response and reduces its immunogenic potential. Dulaglutide exhibits several antihyperglycaemic actions of GLP1. In the presence of elevated glucose concentrations, it increases intracellular cyclic AMP in pancreatic beta cells leading to insulin release. It suppresses glucagon secretion which is inappropriately elevated in type 2 diabetes patients. Lower glucagon concentrations lead to decreased hepatic glucose output. Dulaglutide also slows gastric emptying.

Dosage: Adult: Administer by subcutaneous injection in abdomen, thigh or upper arm. Monotherapy: 0.75mg once weekly. Add-on therapy: 1.5mg once weekly. Can continue current metformin and/or pioglitazone dose. Consider reducing sulphonylurea (SU) or prandial insulin dose to reduce risk of hypoglycaemia. Elderly: Monotherapy: As per adults. Add-on therapy: ≥75 years, consider 0.75mg once weekly starting dose. Children: Under 18 years, not recommended.

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

Special precautions: Do not administer by intravenous or intramuscular injection. Not for type 1 diabetes or diabetic ketoacidosis. Not recommended: Severe renal impairment, end stage renal disease, severe gastrointestinal disease (including severe gastroparesis). Acute pancreatitis reported (suspend if suspected, permanently discontinue if confirmed). Congestive heart failure (limited experience). Driving/using machines (avoid hypoglycaemia with SU or prandial insulin).

Drug interactions: Caution: Oral drugs requiring rapid gastrointestinal absorption. Prolonged release drugs, sitagliptin.

Adverse drug reactions: Hypoglycaemia, gastrointestinal disorders, fatigue, sinus tachycardia, first degree atrioventricular block.

Full prescribing information and references available from Eli Lilly and Co (Ireland) Ltd. Telephone: +353 1 664 0446.
E-mail: ukmedinfo@lilly.com.

Tara Sweeney

Company: Alexion Pharma UK.

Legal category: Prescription. Hospital only. Sport pending.

Active ingredient: Eculizumab 300mg.

Description: Concentrate for solution for infusion.

Presentation: 1 vial, €4557.50.

Indications: Treatment of paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uraemic syndrome (aHUS).

Pharmacology: Eculizumab is a recombinant humanised monoclonal IgG2/4k antibody that binds to the human C5 complement protein and inhibits terminal complement activation which leads to reduction of complement-mediated intravascular haemolysis and thrombotic microangiopathy.

Dosage: Adult: Administer by 25–45 minute intravenous infusion via gravity feed, a syringe-type pump, or infusion pump. Monitor for 1 hour after infusion (slow or stop infusion if adverse events occur; two hours maximum total infusion time). PNH: Initially 600mg once weekly for 4 weeks, 900mg for 5th week; then 900mg every 14+/- 2 days. aHUS: Initially 900mg once weekly for 4 weeks, 1200mg for 5th week, then 1200mg every 14+/- 2 days. Supplemental dosing required for aHUS patients with concomitant PE/PI (plasmapheresis or plasma exchange, or fresh frozen plasma infusion): See SPC. Duration: Continue for patient’s lifetime, unless discontinuation clinically indicated. Elderly: As per adults. Limited experience. Children: Administer over 1-4 hours. ≥40kg body weight (BW): As per adults. 30 to <40kg BW, 600mg weekly x 2, 900mg at week 3, then 900mg every 2 weeks; 20 to <30kg BW, 600mg weekly x 2, 600mg at week 3, then 600mg every 2 weeks; 10 to <20kg BW, 600mg weekly x 1, 300mg at week 2, then 300mg every 2 weeks; 5 to <10kg BW, 300mg weekly x 1, 300mg at week 2; then 300mg every 3 weeks. Monitor for 1 hour after infusion (slow or stop infusion if adverse events occur; maximum total infusion time of two hours (≥12 years) and four hours (<12 years).

Contraindications: Hypersensitivity to eculizumab, murine proteins or to any of the excipients. Initiation in patients with unresolved Neisseria meningitidis infection or unvaccinated against Neisseria meningitidis (or aHUS patients who do not receive prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination). Pregnancy (assess risk/benefit). Women must use contraception and not breastfeed during and for 5 months after treatment.

Special precautions: Do not administer as intravenous push or bolus injection. Caution: Active systemic infection. Monitor PNH patients for intravascular haemolysis (including serum-lactate dehydrogenase levels [LDH] ) during treatment (may require dose adjustment) and for at least 8 weeks after discontinuation. Monitor aHUS patients for thrombotic microangiopathy during treatment (measure platelet count, serum LDH, serum creatinine; may require dose adjustment) and after discontinuation, if discontinuation is medically justified. Patients should be informed to seek immediate medical advice if signs of meningococcal infection (monitor) occur. Vaccinate children against Haemophilus influenzae and pneumococcal infections. Hepatic impairment, safety and efficacy not established. Contains sodium.

Drug interactions: Positive Coombs test.

Adverse drug reactions: Headache, meningococcal sepsis, aspergillus infection, viral infection, upper respiratory tract infection, urinary tract infection, bacterial arthritis, nasopharyngitis, bronchitis, oral herpes, thrombocytopenia, leukopenia, haemolysis, anaphylactic reaction, decreased appetite, dizziness, dysgeusia, hypotension, dyspnoea, cough, nasal congestion, pharyngolaryngeal pain, rhinorrhoea, gastrointestinal upset, rash, alopecia, pruritus, arthralgia, myalgia, muscle spasms, pain (bone, back, neck, in extremity), oedema, chest discomfort, pyrexia, chills, fatigue, influenza like illness.

Full prescribing information and references available from Alexion Pharma UK. Telephone: 1-800 936 537.
E-mail: MedicalInformation.UK@alxn.com

Tara Sweeney

Company: Janssen-Cilag Ltd.

Legal category: Prescription. Hospital. Sport permitted.

Active ingredient: Bedaquiline (as fumarate) 100mg.

Description: White, round, biconvex, uncoated tablet, marked T over 207 on one side and 100 on reverse.

Presentation: 188, price available on request.

Indications: As part of a combination regimen for pulmonary multidrug-resistant tuberculosis when other regimens cannot be used due to resistance or tolerability.

Pharmacology: Bedaquiline is a diarylquinoline. Bedaquiline specifically inhibits mycobacterial adenosine 5’-triphosphate (ATP) synthase, an essential enzyme for the generation of energy in Mycobacterium tuberculosis which leads to bactericidal effects for both replicating and non-replicating tubercle bacilli.

Dosage: Adult: Swallow whole with food. Administer by directly observed therapy. Weeks 1-2: 400mg once daily. Weeks 3-24: 200mg three times per week (at least 48 hours between doses). Consider longer duration individually under close safety surveillance. Elderly: ≥65 years, limited data. Children: <18 years, not recommended.
Contraindications: Hypersensitivity to the active substance or to any of the excipients. Pregnancy, lactation; assess risk/benefit.

Special precautions: Caution: Moderate hepatic impairment (not recommended if severe), severe renal impairment, end-stage renal disease requiring haemodialysis or peritoneal dialysis. Obtain an electrocardiogram (ECG) before initiation and at least monthly after. Correct serum potassium, calcium, and magnesium if abnormal at baseline. Follow-up electrolyte monitoring if QT prolongation occurs. Initiation not recommended (assess risk/benefit) in patients with: Heart failure; QT interval as corrected by the Fridericia method (QTcF) >450ms (confirmed by repeat ECG); history of congenital QT prolongation; hypothyroidism/ bradyarrhythmia or history; history of Torsade de Pointes, hypokalemia. Discontinue if significant ventricular arrhythmia or QTcF interval of >500ms (confirmed by repeat ECG) develops. Obtain ECG to detect QT prolongation if syncope occurs. Monitor liver enzymes at baseline, monthly, and as needed; review and discontinue regimen if AST or ALT exceeds 5 times the upper limit of normal. Mortality reported. Driving/using machines. Contains lactose.

Drug interactions: Avoid: Other hepatotoxic drugs, alcohol (especially in patients with diminished hepatic reserve), moderate or strong CYP3A4 inhibitors (used systemically for more than 14 consecutive days), systemic moderate or strong CYP3A4 inducers. Not recommended: Fluoroquinolone antibiotics with potential for significant QT prolongation (i.e. gatifloxacin, moxifloxacin, sparfloxacin), efavirenz. Caution: QTc prolonging drugs, ritonavir-boosted HIV protease inhibitors.

Adverse drug reactions: Headache, dizziness, prolonged QT, gastrointestinal upset, increased transaminases, arthralgia, myalgia.

Full prescribing information and references available from Janssen-Cilag Ltd. Telephone: +44 1 494 567 444.

Tara Sweeney

Company: Rowex Ltd.

Legal category: Prescription. Sport permitted. Linezolid: GMS pending. Linezolid Rowex: Hospital only.

Active ingredient: Linezolid: Linezolid 600mg. Linezolid Rowex: Linezolid 2mg/ml.

Description: Linezolid: White, biconvex, oval film-coated tablets marked LZ600 on one side.  Linezolid Rowex: Solution for infusion.

Presentation: Linezolid: 10, €209.98 (PTW). Linezolid Rowex: 300ml-1, €21.00.

Indications: Treatment of nosocomial pneumonia and community acquired pneumonia when known or suspected to be caused by susceptible Gram positive bacteria. Treatment of complicated skin and soft tissue infections only when known to be caused by susceptible Gram positive bacteria.

Pharmacology: Linezolid is a synthetic antibacterial agent belonging to the oxazolidinone class of antimicrobials, used against aerobic Gram positive bacteria. Linezolid selectively inhibits bacterial protein synthesis by binding to a site on the bacterial ribosome (23S of the 50S subunit) and prevents the formation of a functional 70S initiation complex which is an essential component of the translation process.

Dosage: Adult: 600mg twice daily for 10-14 days. Maximum duration: 28 days. Duration dependent on pathogen, infection site, severity, and response. Initiate in hospital under specialist supervision. Combination therapy necessary if concomitant Gram negative pathogen suspected. Elderly: As per adults. Children: Under 18 years, not recommended.

Contraindications:  Hypersensitivity to the active substance or to any of the excipients. Uncontrolled hypertension, phaeochromocytoma, carcinoid thyrotoxicosis, bipolar depression, schizoaffective disorder, acute confusional states. Lactation. Pregnancy (unless benefit outweighs risk).

Special precautions: Complete blood counts (including haemoglobin levels, platelets, and total and differentiated leucocyte counts) should be monitored weekly. Risk of myelosuppression (including anaemia, leucopenia, pancytopenia and thrombocytopenia). Pseudomembranous colitis, lactic acidosis, peripheral and optic neuropathy have been reported. History of seizures. Severe renal or hepatic insufficiency (assess risk/benefit). Driving/using machines (dizziness, visual impairment). Solution for infusion contains glucose and sodium.

Drug interactions: Contraindicated: Monoamine-oxidase inhibitors (within 2 weeks), selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), sympathomimetic agents (including adrenergic bronchodilators, pseudoephedrine, phenylpropanolamine), vasopressive agents (e.g. epinephrine, norepinephrine), dopaminergic agents (e.g. dopamine, dobutamine), pethidine, buspirone. Large amounts of tyramine-rich foods and drinks.

Adverse drug reactions: Candidiasis (including oral, vaginal), fungal infections, headache, taste perversion, gastrointestinal disorders, abnormal liver function test (increased aspartate transaminase, alanine aminotransaminase or alkaline phosphatase), increased blood urea nitrogen. Increased lactate dehydrogenase, creatine kinase, lipase, amylase or non-fasting glucose. Decreased total protein, albumin, sodium or calcium. Increased or decreased potassium or bicarbonate. Increased neutrophils or eosinophils. Decreased haemoglobin, haematocrit or red blood cell count. Increased or decreased platelet or white blood cell counts.

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

Tara Sweeney

Company: Biogen Idec (Ireland) Ltd.

Legal category: Prescription. GMS reimbursable. Sport permitted.

Active ingredient: Fampridine 10mg.

Description: Off-white, oval biconvex, film coated prolonged-release tablet marked A10.

Presentation: 56, €146.16.

Indications: For walking improvement in multiple sclerosis patients with walking disability (EDSS 4-7).

Pharmacology: Fampridine is a potassium channel blocker. Blocking potassium channels reduces the leakage of ionic current through these channels, thereby prolonging repolarization and thus enhancing action potential formation in demyelinated axons and neurological function. Presumably, by enhancing action potential formation, more impulses might be conducted in the central nervous system.

Dosage: Adult: Swallow whole. One tablet twice daily, taken 12 hours apart without food. After two weeks, evaluate using a timed walking test, e.g. the Timed 25 Foot Walk; discontinue if no improvement. Consider suspending treatment if decline observed. Elderly: As per adults. Children: 18 years and under, not recommended.

Contraindications: Hypersensitivity to fampridine or to any of the excipients. Seizure (or history). Mild, moderate or severe renal impairment. Pregnancy, lactation.

Special precautions: Monitor renal function before and during treatment (especially in elderly). Caution: Factors lowering seizure threshold (discontinue if seizure occurs), cardiovascular symptoms of rhythm and sinoatrial or atrioventricular conduction cardiac disorders. Permanently discontinue if anaphylactic or other serious allergic reaction occurs. May increase risk of falls, infection rate or impair immune response. Driving/using machines.

Drug interactions: Contraindicated: Other drugs containing fampridine (4-aminopyridine), Organic Cation Transporter 2 (OCT2) inhibitors. Caution: OCT2 substrates.

Adverse drug reactions: Urinary tract infection, insomnia, anxiety, dizziness, headache, balance disorder, paraesthesia, tremor, dyspnoea, pharyngolaryngeal pain, gastrointestinal disorders, back pain, asthenia.

Full prescribing information and references available from Biogen Idec (Ireland) Ltd. Telephone: 1800 812 719.

Fax: +44 1748 828 801. E-mail: biogenidec@professionalinformation.co.uk

Tara Sweeney

Company: Marketed by Rowex.

Legal category: Pharmacy only. Sport permitted.

Active ingredient: Brupro: Ibuprofen 200mg. Brupro Max: Ibuprofen 400mg.

Description: White, round or oblong, biconvex film coated tablets, respectively. Brupro Max: Scored on both sides.

Presentation: Brupro: 200mg-12, €1.86; 200mg-24, €3.09. Brupro Max: 400mg-12, €3.05; 400mg-24, €5.38.

Indications: Brupro: Short-term management of mild to moderate pain, fever and symptoms of colds and influenza. Brupro Max: Management of muscular pain, backache, dental pain and dysmenorrhoea.

Pharmacology: Ibuprofen is a phenylpropionic acid derivative with analgesic, anti-inflammatory and antipyretic activity. Its therapeutic effects as a nonsteroidal anti-inflammatory drug (NSAID) are thought to result from its inhibitory effect on the enzyme cyclo-oxygenase, which results in a marked reduction in prostaglandin synthesis.

Dosage: Adults: Swallow whole with a glass of water, with or after food. Initially, 400mg and subsequently if necessary 200–400mg every four hours (maximum 1200mg in 24 hours). Use lowest dose for shortest duration possible. Elderly: Initiate with lowest dose available. Renal/hepatic impairment: Assess dose individually. Children: 12 years and older: As per adults. Under 12 years: Not recommended.

Contraindications: Hypersensitivity to the active ingredient or to any of the excipients. History of gastrointestinal bleeding or perforation related to previous NSAID therapy, active (or history) recurrent peptic ulcer/haemorrhage (≥2 distinct episodes of proven ulceration or bleeding), severe heart/ hepatic/ renal failure, conditions increasing bleeding tendency. Asthma, urticaria or allergic-type reactions after taking aspirin or other NSAIDs. Pregnancy, lactation.

Special precautions: Caution: Renal, hepatic or cardiac impairment (assess renal function prior to initiation and regularly thereafter, use lowest possible dose), elderly (discontinue if no benefit or intolerance occurs), history of heart failure/ hypertension, (history of) bronchial asthma, initiation in considerably dehydrated patients, intercranial haemorrhage and bleeding diathesis, history of GI disease. GI bleeding, ulceration or perforation reported (can be fatal, discontinue if occurs); risk higher with increasing dose, history of ulcer (especially if complicated with haemorrhage or perforation); consider combination with protective agents. History of GI toxicity (report any unusual abdominal symptoms, especially in initial stages of treatment). Long-term use at high doses associated with small, increased risk of arterial thrombotic events. Serious skin reactions (some fatal) reported very rarely (discontinue at first signs of hypersensitivity). History of hypertension/mild to moderate congestive heart failure (monitor for fluid retention and oedema). Uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, initiating longer-term treatment of patients with risk factors for cardiovascular events (assess risk/benefit). Supervise prolonged use. May mask signs of infection. Aseptic meningitis observed rarely. May impair female fertility. Driving/using machines.

Drug interactions: Only use warfarin or heparin under direct medical supervision. Avoid: Other NSAIDs including cyclooxygenase-2 selective inhibitors. Caution: Antihypertensives, beta-blockers, diuretics, ACE inhibitors, oral corticosteroids, anticoagulants, selective serotonin re-uptake inhibitors, antiplatelets. Cardiac glycosides, lithium, methotrexate, ciclosporin, aminoglycosides, cholestyramine, quinolones, sulfonylureas, probenecid, oral hypoglycaemic agents, mifepristone, tacrolimus, zidovudine, potent CYP2C9 inhibitors, ginkgo biloba.

Adverse drug reactions: Gastrointestinal disorders.

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

Tara Sweeney

The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) has reviewed the available evidence regarding the risk of osteonecrosis of the external auditory canal in patients taking bisphosphonates including data from the published literature and individual case reports. The review concluded that osteonecrosis of the external auditory canal has been reported very rarely with bisphosphonates, mainly in association with long-term therapy. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma.

Osteonecrosis of the external auditory canal is a rare condition affecting the tympanic bone that can occur in the absence of anti-resorptive therapy. The cause is unknown but it has been suggested that it may be a consequence of repeated trauma or due to relatively low vascular supply to the tympanic bone.

The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms including chronic ear infections. Patients should be advised to report any ear pain, discharge from the ear and/or an ear infection during bisphosphonate treatment. The number of reports of osteonecrosis of the external auditory canal reported in association with bisphosphonates is low in comparison with the number of cases reported of bisphosphonate-related osteonecrosis of the jaw (ONJ) which is a well-established side effect of bisphosphonates. However, cases have been reported in both men and women receiving intravenous and oral bisphosphonates for both cancer and osteoporosis indications.

Key message

• A small number of cases of osteonecrosis of the external auditory canal have been reported in patients taking bisphosphonates for both cancer and osteoporosis indications.
• Most cases were associated with long term bisphosphonate therapy and the majority of cases had possible risk factors including steroid use, chemotherapy and/or possible local risk factors such as local infection, or trauma.
• Healthcare professionals should be aware of the risk if patients taking bisphosphonates present with ear symptoms.

*Further details on bisphosphonates authorised in Ireland are available on www.hpra.ie and www.ema.europa.eu

Caroline McDermott

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The American College of Rheumatology (ACR) has recently released a new 2015 guideline for the pharmacological treatment of rheumatoid arthritis (RA). This new guideline has been developed due to the rapid accumulation of evidence and new therapies, advancement of guideline development methodologies, and the need to broaden the scope of its 2012 RA recommendations. It was decided that the guideline would address topics concerning the treatment of RA and not address any topics related to diagnosis, monitoring of disease activity, surgical interventions, or physical therapy interventions.

The ACR conducted systematic reviews to synthesise the evidence for the benefits and harms of various treatment options. They employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences.

This RA guideline should serve as a tool for clinicians and patients for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by clinicians and patients through a shared decision-making process taking into account patients’ values, preferences, and comorbidities.

Abbreviations/descriptions used in this guideline:

DMARD, disease-modifying anti-rheumatic drug.

NYHA, New York Heart Association.

HCQ, hydroxychloroquine. LEF, leflunomide. MTX, methotrexate. SSZ, sulfasalazine. TNFi, tumor necrosis factor inhibitor.

DMARDs, traditional/conventional DMARDs including HCQ, LEF, MTX, or SSZ (excludes azathioprine, cyclosporine, minocycline and gold), it does not include tofacitinib, which is considered separately.

DMARD monotherapy, most often defined as the use of MTX monotherapy, but may also be SSZ, HCQ, or LEF.

Double DMARD therapy, MTX plus SSZ, MTX plus HCQ, SSZ plus HCQ, or combinations with LEF.

Triple DMARD therapy, MTX plus SSZ plus HCQ.

DMARD combination therapy, double or triple traditional/conventional DMARD therapy.

Biologics, TNFi biologic or non-TNF biologic (excludes anakinra).

TNFi biologics, adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab.

Non-TNF biologics, abatacept, rituximab, or tocilizumab (excludes anakinra).

Anakinra was considered but not included in these guidelines due to its infrequent use in RA and lack of new data since 2012. Azathioprine, cyclosporine, minocycline and gold were considered but not included in these guidelines due to their infrequent use in RA and/ or lack of new data since 2012.

 Click on image to enlarge

Click on image to enlarge

Click on image to enlarge

Reference:

1. Singh JA et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care and Research. DOI 10.1002/acr.22783

Caroline McDermott

MIMS Ireland would like to draw your attention to the fact that an incorrect sport category was listed by us for Abasaglar (insulin glargine) in section 6.4 Hormones (Diabetes mellitus) of the January 2016 edition. This has now been corrected on our database.

The correct sport category for Abasaglar is sport prohibited as provided to us by Eirpharm on behalf of Sport Ireland, and as listed in both the prelims and section 6.4 when it was added as a new product to the December 2015 issue.

We regret that this error occurred and apologise for any confusion this may have caused. We have added an extra step to the strict editorial controls already in place to guard against this type of error in the future.

Tara Sweeney

Company: Boehringer Ingelheim Ltd.

Legal category: Prescription. Hospital only. Sport permitted.

Active ingredient: Idarucizumab 2.5g/50ml.

Description: Solution for injection/infusion.

Presentation: 2 x 50ml vials, €3000.00.

Indications: Reversal of anticoagulant effects of dabigatran in emergency surgery/urgent procedures or in life-threatening or uncontrolled bleeding.

Pharmacology: Idarucizumab is a humanised monoclonal antibody fragment (Fab) that binds to dabigatran with very high affinity, approximately 300-fold more potent than the binding affinity of dabigatran for thrombin. Idarucizumab potently and specifically binds to dabigatran and its metabolites and neutralises their anticoagulant effect.

Dosage: Adult: 5g (2 x 2.5g/50ml) administered intravenously as two consecutive infusions over 5-10 minutes each or as bolus injection. A second 5g dose may be considered in patients with prolonged clotting times and (a) recurrence of clinically relevant bleeding or (b) if potential re-bleeding would be life-threatening or (c) patients require a second emergency surgery/urgent procedure. Resume anticoagulant therapy as soon as medically appropriate (i.e. patient is stable and has adequate haemostasis); dabigatran can be re-initiated after 24 hours, other antithrombotics (e.g. low-molecular weight heparin) can be started at any time. Elderly: As per adults. Children: Under 18 years, not recommended.

Contraindications: None.

Special precautions: Does not reverse effects of other anticoagulants. Hypersensitivity to idarucizumab or to any of the excipients (assess risk/benefit). Discontinue immediately if anaphylactic reaction or other serious allergic reaction occurs. Recurrence of plasma concentrations of unbound dabigatran and concomitant prolongation of clotting tests may occur up to 24 hours after administration in some patients. Causes transient proteinuria. Pregnancy (assess risk/benefit). Contains sorbitol, sodium.

Drug interactions: None known.

Adverse drug reactions: None known.

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

Tara Sweeney

Company: Galen Ltd.

Legal category: Prescription. GMS reimbursable. Sport permitted.

Active ingredients: Macrogol 3350 6.563g, sodium chloride 175.4mg, sodium hydrogen carbonate 89.3mg, potassium chloride 25.1mg.

Description: Powder for oral solution in single-dose sachet.

Presentation: 30, €5.71.

Indications: Treatment of chronic constipation, faecal impaction.

Pharmacology: Macrogol 3350 acts by osmotic action in the gut, which induces a laxative effect. It increases the stool volume, which triggers colon motility via neuromuscular pathways. The physiological consequence is an improved propulsive colonic transportation of softened stools and facilitation of defaecation. Electrolytes combined with macrogol 3350 are exchanged across the intestinal barrier (mucosa) with serum electrolytes and excreted in faecal water without net gain or loss of sodium, potassium and water.

Dosage: Children: 12 years and older, use Laxido Orange. Dissolve each sachet in 62.5ml water. Chronic constipation: 2 to 6 years, 1 sachet daily; 7 to 11 years, 2 sachets daily. Adjust as required. Maximum dose needed does not normally exceed 4 sachets a day. Withdraw gradually. Under 2 years, not recommended. Faecal impaction: Take in divided doses within a 12 hour period for up to 7 days. 5 to 11 years, Days 1, 2, 3 and 4 take 4, 6, 8 or 10 sachets daily respectively, Days 5-7 take 12 sachets daily. Under 5 years, not recommended.

Contraindications: Hypersensitivity to the active substances. Intestinal obstruction or perforation caused by functional or structural disorder of the gut wall, ileus. Severe inflammatory conditions of intestinal tract.

Special precautions: Confirm faecal impaction diagnosis by appropriate physical/ radiological rectum and abdomen examination. Stop immediately if symptoms indicating shifts of fluids/electrolytes develop (e.g. oedema, shortness of breath, increasing fatigue, dehydration, cardiac failure); measure electrolytes and treat any abnormality appropriately. Not recommended for faecal impaction in cardiovascular or renal impairment. Caution: High doses in patients with impaired gag reflex, reflux oesophagitis or diminished levels of consciousness.

Drug interactions: Other medicines (see SPC). Medicines in solid dose form within one hour (faecal impaction).
Adverse drug reactions: Abdominal pain, borborygmi, nausea, diarrhoea, vomiting, anal discomfort.

Full prescribing information and references available from Galen Ltd. Telephone: +44 (0)28 3833 4974. Fax: +44 (0)28 3835 0206. E-mail: customer.services@galen-pharma.com

Tara Sweeney

Company: Clonmel Healthcare Ltd.

Legal category: Prescription. GMS reimbursable. Sport permitted.

Active ingredient: Duloxetine (as hydrochloride) 30mg, 60mg.

Description: Hard gastro-resistant capsules with white or green body and dark blue cap, respectively.

Presentation: 30mg-28, €8.20; 60mg-28, €13.56.

Indications: Treatment of major depressive disorder (MDD), generalised anxiety disorder (GAD), diabetic peripheral neuropathic pain.

Pharmacology: Duloxetine is a combined serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor. It weakly inhibits dopamine reuptake with no significant affinity for histaminergic, dopaminergic, cholinergic and adrenergic receptors.

Dosage: Adult: MDD: 60mg once daily for several months (response usually seen after 2-4 weeks). Patients with history of repeated episodes of major depression, consider further long-term treatment of 60-120mg/day. GAD: Initially 30mg once daily. Can increase to 60mg. Co-morbid MDD: 60mg once daily for several months. Can increase to up to 120mg. Diabetic peripheral neuropathic pain: 60mg daily. Can increase to 120mg/day. Evaluate after 2 months. Assess therapeutic benefit at least every three months. Elderly: Caution with use of 120mg/day for MDD or GAD. Children: Under 18 years, not recommended.

Contraindications: Hypersensitivity to the active substance or to any of the excipients. Liver disease resulting in hepatic impairment, severe renal impairment, uncontrolled hypertension. Pregnancy (unless essential), lactation.

Special precautions: Caution: History of mania, bipolar disorder, seizures, increased intraocular pressure or risk of acute narrow-angle glaucoma, conditions affected by increased heart rate or blood pressure (BP), bleeding tendencies, hyponatraemia risk (elderly, cirrhotic, dehydrated patients). Hypertensive crisis reported. Hypertension, cardiac disease; monitor BP especially during 1st month. Elderly. If sustained increase in BP occurs in any patient consider dose reduction or gradual discontinuation. Supervise patients closely for suicide-related events, especially those at risk (especially early treatment and following dose changes or discontinuation). Akathisia may develop (do not increase dose). Liver injury, including severe elevations of liver enzymes, hepatitis and jaundice reported. Withdraw gradually. Driving/using machines. Contains sucrose.

Drug interactions: Do not use linezolid. Contraindicated: Non-selective, irreversible monoamine oxidase inhibitors (within 14 days), potent CYP1A2 inhibitors. Avoid: More than 1 product containing duloxetine. Not recommended: Selective, reversible MAOIs. Caution: Anticoagulants, drugs affecting platelet function, diuretics, hepatic injury drugs, other centrally-acting and sedative drugs, other serotonergic agents, drugs that impair serotonin metabolism, antipsychotics, other dopamine antagonists, tricyclic antidrepressants, St John’s wort, triptans, tramadol, pethidine, tryptophan, CYP2D6 substrates (especially with a narrow therapeutic index). Warfarin. Smoking.

Adverse drug reactions: Headache, somnolence, gastrointestinal disorders, decreased appetite, decreased weight, decreased libido, insomnia, agitation, anxiety, abnormal orgasm, abnormal dreams, dizziness, lethargy, tremor, paraesthesia, blurred vision, tinnitus, palpitations, increased BP, increased sweating, flushing, yawning, rash, musculoskeletal pain, muscle spasm, dysuria.

Full prescribing information and references available from Clonmel Healthcare Ltd. Telephone: (052) 617 7777. Fax: (052) 617 7791. E-mail: medicalinformation@clonmel-health.ie

Tara Sweeney

Company: Boehringer Ingelheim Ltd.

Legal category: OTC.

Description: Comfort shaped single use rectal applicator.

Presentation: 3, €4.09.

Indications: For use with Dulcolax suppositories. Can also be used with other suitable suppositories. Under 12 years, not recommended.

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

Tara Sweeney

Company: Thea Pharmaceuticals Ltd.

Legal category: Prescription. GMS. Sport permitted.

Active ingredient: Dexamethasone (as sodium phosphate) 1mg/ml.

Description: Preservative-free sterile eye drops in single-dose container.

Presentation: 0.4ml-30, €7.20.

Indications: Treatment of non-infectious inflammatory conditions affecting anterior segment of eye.

Pharmacology: Dexamethasone sodium phosphate is a hydrosoluble inorganic ester of dexamethasone. It is a synthetic corticosteroid with an anti-inflammatory and anti-allergic action. Dexamethasone has more potent anti-inflammatory action compared to hydrocortisone (approximately 25:1) and prednisolone (approximately 5:1).

Dosage: Adult: Use only under close ophthalmic supervision. 1 drop 4-6 times daily in affected eye. If severe, start with 1 drop every hour and reduce to 1 drop every 4 hours when favourable response observed. Taper gradually. Maximum duration 14 days. Nasolacrimal occlusion by compression of lacrimal ducts may reduce systemic absorption. Elderly: As per adults. Children: Not recommended.

Contraindications: Hypersensitivity to the active substance or to any of the excipients. Eye infections not controlled by anti-infectious treatment, such as: Acute purulent bacterial infections including pseudomonas and mycobacterial infections, fungal infections, epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella zoster and most other viral infections of the cornea and conjunctiva, amoebic keratitis. Perforation, ulceration and injury of cornea with uncompleted epithelialisation, glucocorticosteroid-induced ocular hypertension. Pregnancy.

Special precautions: Not for undiagnosed red eye. Control eye infections prior to initiation and closely monitor during treatment. Monitor all patients frequently. Corneal ulcer (do not use unless inflammation is main cause of healing delay and appropriate aetiological treatment already prescribed); closely monitor. Particular inflammatory conditions such as episcleritis (only use if NSAIDS are contraindicated). Prolonged use may result in ocular hypertension/ glaucoma (especially for patients with previous intraocular pressure (IOP) induced by steroids or pre-existing high IOP or glaucoma) and cataract formation, especially in elderly. Thinning of cornea and sclera may increase risk of perforations during use. Switch to a phosphate-free preparation at first sign of corneal calcification. May occur:  Posterior subcapsular cataract (cumulative doses), opportunistic ocular infections. Diabetics more prone to develop subcapsular cataracts following administration. Only use for severe forms of allergic conjunctivitis not responding to standard therapy and only for a short period. Avoid contact lenses. Ensure clear vision before driving/ using machines.

Drug interactions: Apply 15 minutes before or after other eye drops. Topical beta-blockers.

Adverse drug reactions: Increased IOP, discomfort, irritation, burning, stinging, itching, blurred vision.

Full prescribing information and references available from Thea Pharmaceuticals Ltd. Telephone: +44 (8701) 923283.

Tara Sweeney

Company: Novartis Ireland Ltd.

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

Active ingredient: Secukinumab 150mg/ml.

Description: Solution for injection in pre-filled SensoReady pens.

Presentation: 2, price on request.

Indications: Treatment of moderate to severe plaque psoriasis in candidates for systemic therapy. Alone or in combination with methotrexate, for treatment of active psoriatic arthritis when disease-modifying anti-rheumatic drug therapy is inadequate. Treatment of active ankylosing spondylitis when conventional therapy is inadequate.

Pharmacology: Secukinumab is a fully human IgG1/k monoclonal antibody that selectively binds to and neutralises the proinflammatory cytokine interleukin-17A (IL-17A) by targeting it and inhibiting its interaction with the IL-17 receptor, which is expressed on various cell types including keratinocytes. As a result, secukinumab inhibits the release of proinflammatory cytokines, chemokines and mediators of tissue damage and reduces IL-17A-mediated contributions to autoimmune and inflammatory diseases.

Dosage: Adult: Administer by subcutaneous injection. Consider discontinuation if no response by 16 weeks of treatment. Avoid skin areas that show psoriasis. Psoriatic arthritis, ankylosing spondylitis: 150mg at Weeks 0, 1, 2 and 3, then monthly starting at Week 4. Plaque psoriasis, psoriatic arthritis patients with concomitant moderate to severe plaque psoriasis/ anti-TNFα inadequate response: 300mg at Weeks 0, 1, 2 and 3. Maintenance (starting at Week 4), 300mg monthly as two 150mg injections. Elderly: 65 years and older, as per adults. Children: Under 18 years, not recommended.

Contraindications: Severe hypersensitivity reactions to the active substance or to any of the excipients. Clinically important, active infection (e.g. active tuberculosis). Pregnancy (avoid), lactation (assess risk/benefit).

Special precautions: Caution: Chronic infection, history of recurrent infection, Crohn’s disease. Seek medical advice if signs of infection occur, suspend treatment if serious. Latent tuberculosis, consider anti-tuberculosis therapy prior to initiation. Discontinue immediately if anaphylactic or other serious allergic reactions occur. Removable cap contains latex derivative. Women should use contraception during and for at least 20 weeks after treatment.

Drug interactions: Do not use live vaccines. CYP450 substrates with narrow therapeutic index.

Adverse drug reactions: Upper respiratory tract infections, oral herpes, rhinorrhoea, diarrhoea.

Full prescribing information and references available from Novartis Ireland Ltd. Telephone: (01) 260 1255.

Tara Sweeney