- Ertugliflozin recommended as monotherapy or with metformin for type 2 diabetes in final guidance.
- Final draft guidance recommends:
- Durvalumab for lung cancer through CDF.
- Brentuximab vedotin for CD30-positive cutaneous T-cell lymphoma.
- Lung cancer: diagnosis and management clinical guideline updated.
- Consultation open for:
- Ultrasound-guided high-intensity transcutaneous focused ultrasound for symptomatic uterine fibroids.
- Transurethral laser ablation for recurrent non-muscle-invasive bladder cancer.
- Twin and triplet pregnancy draft guideline open for consultation.
- EU actions to prevent medicine shortages due to Brexit: Q&A published.
- Class 2 medicines recall: Losartan Potassium 50mg Film-coated Tablets, and Losartan Potassium 100mg Film-coated Tablets - nitrosamine contamination.
- New restricted indications for fluoroquinolone antibiotics due to reports of disabling and potentially long-lasting or irreversible side effects.
- Safety advice: Onivyde (irinotecan, liposomal formulations) - reports of serious and fatal thromboembolic events.
- New guidance published on contraceptive methods and pregnancy testing frequency to reduce exposure to medicines of teratogenic potential.
- Emergency readmissions in England increase by 1.3 percentage points.
NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE
ERTUGLIFLOZIN RECOMMENDED AS MONOTHERAPY OR WITH METFORMIN FOR TYPE 2 DIABETES
NICE has published final guidance which recommends ertugliflozin (Steglatro) as monotherapy for treating type 2 diabetes in adults for whom metformin is contraindicated or not tolerated and when diet and exercise alone do not provide adequate glycaemic control, only if:
- a dipeptidyl peptidase 4 (DPP‑4) inhibitor would otherwise be prescribed and
- a sulfonylurea or pioglitazone is not appropriate.
Ertugliflozin is also recommended in a dual-therapy regimen in combination with metformin as an option for treating type 2 diabetes, only if:
- a sulfonylurea is contraindicated or not tolerated or
- the person is at significant risk of hypoglycaemia or its consequences.
According to NICE, indirect comparisons show that the sodium-glucose cotransporter 2 (SGLT‑2) inhibitor ertugliflozin has similar overall health benefits to canagliflozin, dapagliflozin and empagliflozin, which are options for treating type 2 diabetes in adults either in combination with metformin or as monotherapy if metformin is not appropriate. The acquisition cost of ertugliflozin is lower than the acquisition costs of these other drugs, which is why it is recommended, in line with the previous recommendations for SGLT‑2 inhibitors.
DRAFT FINAL GUIDANCE RECOMMENDS DURVALUMAB FOR LUNG CANCER THROUGH CDF
NICE has published draft final guidance recommending the PD-L1 inhibitor durvalumab (Imfinzi) for lung cancer. It will be made available on the NHS in England through the Cancer Drugs Fund (CDF). Durvalumab helps the body’s immune system to find and attack cancer cells, by blocking the PD-L1 protein which disguises cancer. A clinical trial showed that people taking it went for an average of around two years without the disease progressing, versus six months for those without. NICE committee agreed that it was plausible that between 27% and 40% of people taking durvalumab would have five years of progression-free survival. The final appraisal document notes that clinical experts advised NICE’s independent technology appraisal committee that durvalumab was “a potentially curative treatment”. However, the committee agreed that clinical trial data were too immature for this to be certain. The committee concluded that durvalumab had the potential to be cost-effective for NHS use, but that there was a high level of uncertainty in clinical evidence surrounding it, which is why it is recommended for use within the CDF, while more data is collected.
LUNG CANCER: DIAGNOSIS AND MANAGEMENT CLINICAL GUIDELINE UPDATED
NICE has published an updated clinical guideline on the diagnosis and management of lung cancer. Changes made since the guideline was last updated in 2011 include clearer recommendations on when brain imaging should be offered to spot if the cancer has spread, and on the assessment and treatment options for people whose disease has spread to the lymph nodes. The guideline also includes recommendations on: radical radiotherapy (including stereotactic ablative radiotherapy [SABR]) for people with non-small-cell lung cancer; chemoradiotherapy and surgery for people with stage NIIIA-N2 non-small-cell lung cancer; and thoracic radiotherapy and prophylactic cranial irradiation for people with small-cell lung cancer. In addition, NICE has also produced two algorithms covering systemic treatment options for people with advanced squamous or non-squamous non-small-cell lung cancer, and an algorithm covering intrathoracic staging before radical treatment.
BRENTUXIMAB VEDOTIN RECOMMENDED FOR CD30-POSITIVE CUTANEOUS T-CELL LYMPHOMA
NICE has published final draft guidance which recommends Brentuximab vedotin as an option for treating CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one systemic therapy in adults, only if:
- they have mycosis fungoides stage IIB or over, primary cutaneous anaplastic large cell lymphoma or Sézary syndrome and
- the company provides brentuximab vedotin according to the commercial arrangement.
According to NICE committee, clinical trial evidence shows that brentuximab vedotin is better than methotrexate or bexarotene in terms of response rates and extending how long people live without their disease getting worse. For some people with CTCL, brentuximab vedotin will be used as a bridge to a stem cell transplant. The most plausible cost-effectiveness estimates for brentuximab vedotin compared with current treatments are less than £30,000 per quality-adjusted life year gained, which is within the range considered to be a cost-effective use of NHS resources. However, these estimates are based on data from people with specific subtypes of advanced disease (mycosis fungoides stage IIB or over, primary cutaneous anaplastic large cell lymphoma and Sézary syndrome), which is why brentuximab vedotin is only recommended for these subtypes.
CONSULTATION: ULTRASOUND-GUIDED HIGH-INTENSITY TRANSCUTANEOUS FOCUSED ULTRASOUND FOR SYMPTOMATIC UTERINE FIBROIDS
NICE has published a consultation document on the use of ultrasound-guided high-intensity transcutaneous focused ultrasound for symptomatic uterine fibroids. It says current evidence on the safety of ultrasound-guided high-intensity transcutaneous focused ultrasound for symptomatic uterine fibroids shows there are well-recognised complications including skin burns. The evidence on efficacy is limited in quality. Therefore, NICE is recommending this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Closing date for comments is 18 April 2019.
CONSULTATION: TRANSURETHRAL LASER ABLATION FOR RECURRENT NON-MUSCLE-INVASIVE BLADDER CANCER
NICE has published another consultation document on the use of transurethral laser ablation for recurrent non-muscle-invasive bladder cancer. It says the evidence on the safety of procedure shows that there are no major safety concerns. However, current evidence on its efficacy is limited in quality and quantity. NICE therefore recommends this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. Closing date for comments is 18 April 2019.
TWIN AND TRIPLET PREGNANCY DRAFT GUIDELINE OPEN FOR CONSULTATION
NICE has published a draft guideline which covers the care that should be offered to women with a twin or triplet pregnancy that is additional to the routine care offered to all women during pregnancy. It aims to reduce the risk of complications and improve outcomes for women and their babies. This guideline will update NICE guideline CG129. The consultation closes 9 May 2019.
EUROPEAN MEDICINES AGENCY
EU ACTIONS TO PREVENT MEDICINE SHORTAGES DUE TO BREXIT: Q&A PUBLISHED
The European Medicines Agency (EMA) has published a questions-and-answers (Q&A) document for patients, healthcare professionals and the general public on the preparatory work that European Union authorities are doing to prevent medicine shortages due to the United Kingdom’s withdrawal from the EU. It explains that in case of a withdrawal agreement, there will be a transition period during which EU law will continue to apply in the United Kingdom. This means that access to medicines will not be affected. If the UK leaves without a withdrawal agreement or deal, EU law will cease to apply in the UK. In this case, in order to be able to continue to supply medicines in the EU, companies carrying out certain activities in the UK will need to make changes to comply with EU law. The Q&As explain how the EMA, the European Commission and EU/EEA Member States have been working closely together since May 2017 to advise companies on how to apply for the necessary changes in order to minimise the impact on the supply of medicines, if the UK leaves the EU without a withdrawal agreement. Furthermore, the document underlines that Brexit will not impact the safety of medicines, nor the way they are evaluated. The EMA and the Member States will continue to monitor the safety and efficacy of medicines without any changes.
MEDICINES AND HEALTHCARE PRODUCTS REGULATORY AGENCY
CLASS 2 MEDICINES RECALL: LOSARTAN POTASSIUM 50MG FILM-COATED TABLETS, AND LOSARTAN POTASSIUM 100MG FILM-COATED TABLET - NITROSAMINE
Further to previous recalls of Valsartan and Irbesartan containing products, which were potentially contaminated with N-nitrosodimethylamine (NDMA) or N-nitrosodiethylamine (NDEA), the Medicines and Healthcare products Regulatory Agency (MHRA) has become aware of products containing Losartan Potassium that are contaminated with a different nitrosamine, N-nitroso-N-methylamino butyric acid (NMBA). Losartan Potassium containing products from Accord Healthcare Limited are affected and certain batches are being recalled. Healthcare Professionals are advised to:
- Stop supplying the listed batches immediately. Quarantine all remaining stock and return it to the supplier using the supplier’s approved process.
- If queries about this issue are received from patients, advise them to continue taking their medication as the health risk of discontinuing the medicine is higher than the potential risk presented by the contaminant. A treatment review is not necessary until the next routine appointment.
- The MRHA does not anticipate any shortages of Losartan Potassium containing products. In case of local supply issues, patients are advised to speak to their doctor to discuss alternative treatments.
NEW RESTRICTED INDICATIONS FOR FLUOROQUINOLONE ANTIBIOTICS DUE TO REPORTS OF DISABLING AND POTENTIALLY LONG-LASTING OR IRREVERSIBLE SIDE EFFECTS
The MHRA has published a drug safety update for fluoroquinolone antibiotics. Disabling, long-lasting or potentially irreversible adverse reactions affecting musculoskeletal and nervous systems have been reported very rarely with fluoroquinolone antibiotics. Fluoroquinolone treatment should be discontinued at the first signs of a serious adverse reaction, including tendon pain or inflammation. Advice for healthcare professionals includes:
- systemic (by mouth, injection, or inhalation) fluoroquinolones can very rarely cause long-lasting (up to months or years), disabling, and potentially irreversible side effects, sometimes affecting multiple systems, organ classes, and senses
- advise patients to stop treatment at the first signs of a serious adverse reaction, such as tendinitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy, and central nervous system effects, and to contact their doctor immediately for further advice – sheet for patients
- do not prescribe fluoroquinolones:
- for non-severe or self-limiting infections, or non-bacterial conditions
- for some mild to moderate infections (such as in acute exacerbation of chronic bronchitis and chronic obstructive pulmonary disease; refer to revised indications in the Summary of Product Characteristics) unless other antibiotics that are commonly recommended for these infections are considered inappropriate
- ciprofloxacin or levofloxacin should no longer be prescribed for uncomplicated cystitis unless other antibiotics that are commonly recommended are considered inappropriate
- avoid use in patients who have previously had serious adverse reactions with a quinolone or fluoroquinolone antibiotic
- prescribe with special caution for people older than 60 years and for those with renal impairment or solid-organ transplants because they are at a higher risk of tendon injury
- avoid use of a corticosteroid with a fluoroquinolone since coadministration could exacerbate fluoroquinolone-induced tendinitis and tendon rupture
- report suspected adverse drug reactions to fluoroquinolone antibiotics on the Yellow Card website.
ONIVYDE (IRINOTECAN, LIPOSOMAL FORMULATIONS): REPORTS OF SERIOUS AND FATAL THROMBOEMBOLIC EVENTS
The MHRA has issued a drug safety update concerning Onivyde (irinotecan, liposomal formulations) due to reports of serious thromboembolic events, such as pulmonary embolism, venous thrombosis, and arterial thromboembolism. A routine EU review assessed cases of serious thromboembolic events reported in patients receiving Onivyde. In the cumulative review (October 2015 – April 2018), 23 serious reports of thromboembolic events were identified, of which four were fatal. 20 cases of serious thromboembolic events were reported in a six-month reporting period (October 2017 – April 2018) in the EU. The MHRA have no Yellow Card reports of this reaction with this formulation in the UK and usage in the UK is very low, however all prescribers should be aware of this risk when using Onivyde. Healthcare professionals are advised to:
- be aware of reports of serious and fatal cases of thromboembolic events in patients receiving Onivyde for metastatic adenocarcinoma of the pancreas.
- Obtain a thorough medical history in order to identify patients with multiple risk factors in addition to the underlying neoplasm
- advise patients to seek medical advice immediately if signs or symptoms of thromboembolism occur (for example, sudden pain and swelling in a leg or an arm, sudden onset of coughing, chest pain or difficulty breathing)
- report suspected adverse drug reactions to the Yellow Card Scheme.
NEW GUIDANCE PUBLISHED ON CONTRACEPTIVE METHODS AND PREGNANCY TESTING FREQUENCY TO REDUCE EXPOSURE TO MEDICINES OF TERATOGENIC POTENTIAL
The MHRA has published new guidance on contraceptive methods and frequency of pregnancy testing to reduce inadvertent exposures during pregnancy in a woman taking a medicine of teratogenic potential. It also provides a new resource to help prescribers of medicines with teratogenic potential to do so safely. In order to avoid inadvertent exposures, a pregnancy test should be performed before prescribing these medicines as a woman may be unaware she is pregnant at the start of treatment or be in the early stages of pregnancy at the time of repeat prescribing due to contraceptive failure. The MHRA continues to receive reports of inadvertent exposure to such medicines during early pregnancyThe Medicines for Women’s Health Expert Advisory Group of the Commission on Human Medicines has developed an aide-memoire table to provide guidance to prescribers of medicines with teratogenic potential on the frequency of pregnancy testing needed to avoid exposure in pregnancy during treatment, depending on the chosen contraceptive method. The aide-memoire table provides a summary of the pregnancy testing advice for the most common contraceptive methods. The table is colour-coded according to the most reliable methods. It is available to download and print, so can be used as a poster in clinics and to update local guidance, as needed.
EMERGENCY READMISSIONS IN ENGLAND INCREASE BY 1.3 PERCENTAGE POINTS
New experimental statistics have been released by NHS Digital, showing emergency readmissions for hospitals in England between 2013/14 and 2017/18. These figures show that emergency readmissions nationally have increased by 1.3 percentage points from 12.5% in 2013/14 to 13.8% in 2017/18. These are based on ordinary general hospital admissions with cancer and obstetrics spells excluded. The data also shows that emergency readmissions range from 14.9% in the most deprived areas to 12.7% in the least deprived areas. The new data can be found in the CCG Outcomes Indicator Set and the NHS Outcomes Framework and show the percentage of emergency readmissions within 30 days of discharge from hospital, including breakdowns by Clinical Commissioning Group, deprivation quintile and gender.