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Life-Threatening Drug-Induced Rashes

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161. Suspected neurological conditions: recognition and referral

, and some prescription, drugs alcohol affective disorders stress. Suspected neurological conditions: recognition and referral (NG127) © NICE 2019. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-and- conditions#notice-of-rights). Page 14 of 73For more information, see initial assessment in non-specialist settings in the NICE guideline on dementia. Memory problems as part of an anxiety disorder or a functional neurological disorder Memory problems as part of an anxiety (...) of Suspected neurological conditions: recognition and referral (NG127) © NICE 2019. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-and- conditions#notice-of-rights). Page 26 of 73people with suspected sepsis in the NICE guideline on sepsis. 1.19.3 For children with acute confusion who have a non-blanching rash or other signs or symptoms suggestive of meningococcal septicaemia, follow the recommendations on suspected meningococcal disease (meningitis with non- blanching rash

2019 National Institute for Health and Clinical Excellence - Clinical Guidelines

162. Pneumonia (community-acquired): antimicrobial prescribing

in children under 12 years is either contraindicated or cautioned for use in severe or life-threatening infections where there are no alternatives (BNF, August 2019). Fluoroquinolones have restrictions and precautions around their use because of rare reports of disabling and potentially long-lasting or irreversible side effects affecting musculoskeletal and nervous systems (MHRA Drug Safety Update, March 2019). They may also be associated with a small increased risk of aortic aneurysm and dissection (...) of antibiotics Antibiotic-associated diarrhoea is estimated to occur in 2% to 25% of people taking antibiotics, depending on the antibiotic used (NICE CKS on diarrhoea – antibiotic associated). About 10% of the general population claim to have a penicillin allergy; this is often because of a skin rash that occurred while taking a course of penicillin as a child. Fewer than 10% of people who think they are allergic to penicillin are truly allergic. See the NICE guideline on drug allergy for more information

2019 National Institute for Health and Clinical Excellence - Clinical Guidelines

163. Cellulitis and erysipelas: antimicrobial prescribing

to 2.7 g daily IV in two to four divided doses, increased if necessary in life-threatening infection to 4.8 g daily (maximum per dose 1.2 g) 6 Ceftriaxone (only for ambulatory care 8 ) 2 g once a day IV 6 Antibiotics to be added if MRSA infection is suspected or confirmed ( Antibiotics to be added if MRSA infection is suspected or confirmed (combination ther combination therap apy with y with an antibiotic listed abo an antibiotic listed abov ve e) ) 8 8 Vancomycin 9,10 15 to 20 mg/kg two or three (...) mg) for 7 days 5 or or 1 month to 17 years, 3.75 to 6.25 mg/kg four times a day IV, increased if necessary, in life- threatening infection to 10 mg/kg four times a day IV (maximum per dose 1.2 g); total daily dose may alternatively be given in three divided doses (maximum per dose 1.2 g) 6 Antibiotics to be added if suspected or confirmed MRSA infection ( Antibiotics to be added if suspected or confirmed MRSA infection (combination ther combination therap apy with y with an antibiotic listed abo

2019 National Institute for Health and Clinical Excellence - Clinical Guidelines

164. Pneumonia (hospital-acquired): antimicrobial prescribing

- associated pneumonia) is excluded from this definition. Pneumonia (hospital-acquired): antimicrobial prescribing (NG139) © NICE 2019. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-and- conditions#notice-of-rights). Page 13 of 23Summary of the e Summary of the evidence vidence This is a summary of the evidence. For full details, see the evidence review. Hospital-acquired pneumonia is a lower respiratory tract infection that may be life threatening. Early-onset hospital (...) Safety of antibiotics About 10% of the general population claim to have a penicillin allergy; this is often because of a skin rash that occurred while taking a course of penicillin as a child. Fewer than 10% of people who think they are allergic to penicillin are truly allergic. See the NICE guideline on drug allergy for more information. People with a history of immediate hypersensitivity to penicillins may also react to cephalosporins and other beta-lactam antibiotics (BNF, August 2019). Macrolides

2019 National Institute for Health and Clinical Excellence - Clinical Guidelines

165. Drug Treatment of Seizures

/day may be used. A ketogenic diet (a very high fat diet that induces ketosis) may help but is difficult to maintain. For juvenile myoclonic epilepsy, life-long treatment is usually recommended. Carbamazepine , oxcarbazepine , or gabapentin can exacerbate the seizures. Lamotrigine can be used as 2nd-line monotherapy or adjunctive therapy for juvenile myoclonic epilepsy; however, it can aggravate myoclonic seizures in some patients with juvenile myoclonic epilepsy. For febrile seizures, drugs (...) an allergic scarlatiniform or morbilliform rash. Some types of seizures may be worsened by certain antiseizure drugs. For example, pregabalin and lamotrigine may worsen myoclonic seizures; carbamazepine may worsen absence, myoclonic, and atonic seizures. Other adverse effects vary by drug (see ). Antiseizure drug use during pregnancy Antiseizure drugs are associated with an increased risk of teratogenicity. Fetal antiepileptic drug syndrome (cleft lip, cleft palate, cardiac defects, microcephaly, growth

2013 Merck Manual (19th Edition)

166. Antifungal Drugs

is usually started at ≥ 0.3 mg/kg IV once/day, increased as tolerated to the desired dose (0.4 to 1.0 mg/kg; generally not > 50 mg/day); many patients tolerate the target dose on the first day. For acute, life-threatening mycoses , amphotericin B deoxycholate may be started at 0.6 to 1.0 mg/kg IV once/day. Formulations There are 2 formulations of amphotericin: Deoxycholate (standard) Lipid-based The standard formulation , amphotericin B deoxycholate, must always be given in 5% D/W because salts can (...) interactions mentioned below are not intended as a complete listing; clinicians should refer to a specific drug interaction reference before using azole antifungal drugs. Pearls & Pitfalls Drug and food interactions are common with azole antifungals; review all concurrent drug use before prescribing them. Fluconazole This water-soluble drug is absorbed almost completely after an oral dose. Fluconazole is excreted largely unchanged in urine and has a half-life of > 24 h, allowing single daily doses. It has

2013 Merck Manual (19th Edition)

167. Drug Hypersensitivity

, arthralgias, and rash. Mechanism involves drug-antibody complexes and complement activation. Some patients have frank arthritis, edema, or GI symptoms. Symptoms are self-limited, lasting 1 to 2 wk. Beta-lactam and sulfonamide antibiotics, iron-dextran, and carbamazepine are most commonly implicated. : This disorder may develop when an antibody-drug-RBC interaction occurs or when a drug (eg, methyldopa ) alters the RBC membrane, uncovering an antigen that induces autoantibody production. DRESS (drug rash (...) effects: Some drugs induce respiratory symptoms (distinct from the wheezing that may occur with type I hypersensitivity), deterioration in pulmonary function, and other pulmonary changes (see ). Renal effects: is the most common allergic renal reaction; methicillin, antimicrobials, and cimetidine are commonly implicated. Other autoimmune phenomena: Hydralazine , propylthiouracil , and procainamide can cause an SLE-like syndrome. The syndrome may be mild (with arthralgias, fever, and rash) or fairly

2013 Merck Manual (19th Edition)

168. Drugs for Hypertension

inhibitor or angiotensin II receptor blocker and who do not drink at least 1400 mL (48 oz) of fluid daily. The increased mortality is probably related to diuretic-induced hyponatremia and hypotension. Table Oral Diuretics for Hypertension Drug Usual Dose* Selected Adverse Effects Thiazides and thiazide-type diuretics ( chlorthalidone and indapamide ) Bendroflumethiazide 2.5–5 mg once/day (maximum: 20 mg) Hypokalemia (which increases digitalis toxicity), hyperuricemia, glucose intolerance (...) mg once/day Rash, cough, angioedema, hyperkalemia (particularly in patients with renal insufficiency or taking NSAIDs, potassium-sparing diuretics, or potassium supplements), dysgeusia, reversible acute kidney injury if stenosis affecting one or both kidneys threatens renal function, proteinuria (rare at recommended doses), neutropenia (rare), hypotension with initiation of treatment (particularly in patients with high plasma renin activity or with hypovolemia due to diuretics or other conditions

2013 Merck Manual (19th Edition)

169. Adverse Drug Reactions

is not prolonged. Antihistamines (some): Drowsiness Opioids: Constipation Moderate A change in treatment (eg, modified dosage, addition of a drug), but not necessarily discontinuation of the drug, is required; hospitalization may be prolonged, or specific treatment may be required. Hormonal contraceptives: Venous thrombosis NSAIDs: Hypertension and edema Severe An ADR is potentially life threatening and requires discontinuation of the drug and specific treatment of the ADR. ACE inhibitors: Angioedema (...) Phenothiazines: Abnormal heart rhythm Lethal An ADR directly or indirectly contributes to a patient’s death. Acetaminophen overdosage: Liver failure Anticoagulants: Hemorrhage Allergic ADRs typically occur soon after a drug is taken but generally do not occur after the first dose; typically, they occur when the drug is given after an initial exposure. Symptoms include itching, rash, fixed-drug eruption, upper or lower airway edema with difficulty breathing, and hypotension. Idiosyncratic ADRs can produce

2013 Merck Manual (19th Edition)

170. Letermovir for preventing cytomegalovirus disease after a stem cell transplant

of 22Contents Contents 1 Recommendations 4 2 Information about letermovir 5 3 Committee discussion 6 Clinical need 6 Clinical management 6 Clinical evidence 7 Adverse events 10 Health-related quality of life 11 Cost-effectiveness model structure 12 Clinical data in the economic model 12 Utility values in the economic model 14 Resource use and costs 15 Cost-effectiveness estimates 16 Conclusion 17 Other factors 18 4 Implementation 20 5 Appraisal committee members and NICE project team 21 Appraisal committee (...) . The patient experts highlighted that CMV reactivation can have a substantial psychological effect on patients and their families, negatively affecting their mental health and wellbeing. Hospital admissions to treat CMV reactivation disrupt family and working life and are particularly stressful because of the worry and risk of further infections. Pre-emptive therapy for CMV reactivation (see section 3.2) can have serious side effects. The patient experts noted that better prevention of CMV reactivation

2019 National Institute for Health and Clinical Excellence - Technology Appraisals

171. Sore throat (acute): antimicrobial prescribing

of phenoxymethylpenicillin (low quality evidence). Sore throat (acute): antimicrobial prescribing (NG84) © NICE 2019. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-and- conditions#notice-of-rights). Page 18 of 24Committee discussions on antibiotic choice, dose and frequency of dosing Committee discussions on antibiotic choice, dose and frequency of dosing The committee discussed that, generally, if an antibiotic is needed to treat an infection that is not life threatening, narrow (...) -spectrum antibiotics should be used as the first choice. Indiscriminate use of broad-spectrum antibiotics is undesirable because it creates a selective advantage for bacteria resistant even to these 'last-line' broad-spectrum agents, and also kills normal commensal flora leaving people susceptible to antibiotic-resistant harmful bacteria such as Clostridium difficile. For infections that are not life threatening, broad-spectrum antibiotics need to be reserved for second-choice treatment when narrow

2018 National Institute for Health and Clinical Excellence - Clinical Guidelines

172. Otitis media (acute): antimicrobial prescribing

, December 2017). See the NICE guideline on drug allergy for more information. Antibiotic-associated diarrhoea occurs in 2 to 25% of people taking antibiotics, depending on the antibiotic used (NICE Clinical Knowledge Summary on diarrhoea – antibiotic associated). Adverse events (vomiting, diarrhoea or rash) were significantly increased in children with acute otitis media taking antibiotics compared with those taking placebo (moderate quality evidence). The number needed to harm (NNH) was 13 (range 9 (...) that, if an antibiotic is needed to treat an infection that is not life- threatening, a narrow-spectrum antibiotic should generally be first choice. Indiscriminate use of broad-spectrum antibiotics creates a selective advantage for bacteria resistant even to these 'last-line' broad-spectrum agents, and also kills normal commensal flora leaving people susceptible to antibiotic-resistant harmful bacteria such as Clostridium difficile. For infections that are not life-threatening, broad-spectrum antibiotics need

2018 National Institute for Health and Clinical Excellence - Clinical Guidelines

173. Urinary tract infection (recurrent): antimicrobial prescribing

therapy [HRT]) increase the risk of venous thromboembolism (when taken orally), stroke, endometrial cancer (reduced by a progestogen), breast cancer and ovarian cancer; there is an increased risk of coronary heart disease in women who start combined HRT more than 10 years after menopause (Medicines and Healthcare products Regulatory Agency [MHRA] Drug Safety Update, September 2007; British National Formulary [BNF], August 2018). Before prescribing HRT, health professionals should consider carefully (...) or carcinoma (MHRA Drug Safety Update, September 2007; BNF, August 2018). The NICE guideline on menopause recommends that women using vaginal oestrogen should report unscheduled vaginal bleeding to their GP . Urinary tract infection (recurrent): antimicrobial prescribing (NG112) © NICE 2019. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-and- conditions#notice-of-rights). Page 20 of 33Committee discussion on oestrogens Committee discussion on oestrogens Based on evidence

2018 National Institute for Health and Clinical Excellence - Clinical Guidelines

174. No evidence for antiepileptic drugs preventing seizures in people with brain tumours

No evidence for antiepileptic drugs preventing seizures in people with brain tumours PEARLS Practical Evidence About Real Life Situations PEARLS are succinct summaries of Cochrane Systematic Reviews for primary care practitioners. They are funded by the New Zealand Guidelines Group. PEARLS provide guidance on whether a treatment is effective or ineffective. PEARLS are prepared as an educational resource and do not replace clinician judgement in the management of individual cases. View PEARLS (...) , such as nausea, skin rash, sore gums, myelosuppression, vertigo, blurred vision, tremor and gait unsteadiness was higher for those taking antiepileptic drugs (NNH* 3). No studies were identified evaluating use of newer antiepileptic drugs. Antiepileptic drugs can also interact with chemotherapy agents and steroids. NNH = number needed to treat to cause harm in one individual. Context Up to 60% of people with brain tumours may present with seizures, or may have a seizure for the first time after diagnosis

2008 Cochrane PEARLS

175. Anaphylaxis

is clinical. Allergy testing is helpful only for secondary prophylaxis. Securing the airway and initiating prompt treatment with epinephrine (adrenaline) may save lives. Comorbidities (e.g., coronary artery disease and COPD) may pose a treatment challenge and warrant expert consultation Definition Anaphylaxis is an acute, severe, life-threatening allergic reaction in pre-sensitised individuals, leading to a systemic response caused by the release of immune and inflammatory mediators from basophils (...) Anaphylaxis Anaphylaxis - Symptoms, diagnosis and treatment | BMJ Best Practice You'll need a subscription to access all of BMJ Best Practice Search  Anaphylaxis Last reviewed: February 2019 Last updated: March 2019 Summary Sudden onset of respiratory or cardiovascular compromise, usually with a history of allergen exposure in sensitised individuals. Skin rash, wheezing and inspiratory stridor, hypotension, anxiety, nausea, and vomiting are the cardinal signs and symptoms. The diagnosis

2019 BMJ Best Practice

176. Soft-tissue sarcoma

, olaratumab received conditional marketing authorisation approval (one of the EU’s early access routes for medicines that target serious, debilitating, life-threatening, or rare disease) for the treatment of advanced soft tissue sarcoma not amenable to curative treatment, in combination with doxorubicin. At the time of approval, data on the effects of the treatment were limited due to the small number of patients included in the main study supporting the application. The marketing authorisation (...) ANNOUNCE trial has found. While full study results are awaited, the European Medicines Agency (EMA) recommends that: No new patients should start treatment with olaratumab Consideration may be given to continuing olaratumab in patients currently being treated with the medicine if they appear to benefit from it. Similar recommendations have been proposed by the US Food and Drug Administration. Based on the available information, there are no safety concerns with the medicine. In November 2016

2019 BMJ Best Practice

177. Ribociclib, Breast Neoplasms, Benefit Assessment, NCT02422615, NCT02278120

– RCT, direct comparison: ribociclib + fulvestrant vs. placebo + fulvestrant (postmenopausal women, initial endocrine therapy) 28 Table 15: Risk of bias across outcomes and outcome-specific risk of bias – RCT, direct comparison: ribociclib + fulvestrant vs. placebo + fulvestrant (postmenopausal women, initial endocrine therapy) 29 Table 16: (mortality, morbidity, health-related quality of life, side effects, time to event) – RCT, direct comparison: ribociclib + fulvestrant vs. placebo + fulvestrant (...) across outcomes and outcome-specific risk of bias – RCT, direct comparison: ribociclib + fulvestrant vs. placebo + fulvestrant (postmenopausal women who have received prior endocrine therapy) 48 Table 22: Results (mortality, morbidity, health-related quality of life, side effects, time to event) – RCT, direct comparison: ribociclib + fulvestrant vs. placebo + fulvestrant (postmenopausal women who have received prior endocrine therapy) 49 Table 23: Study pool – RCT, direct comparison: ribociclib

2019 Institute for Quality and Efficiency in Healthcare (IQWiG)

178. Nivolumab (renal cell carcinoma) - Benefit assessment according to §35a Social Code Book V

+ ipilimumab vs. sunitinib 22 Table 14: Results (mortality, side effects) – RCT, direct comparison: nivolumab + ipilimumab vs. sunitinib (research question 1: patients with intermediate risk) 24 Table 15: Results (morbidity, health-related quality of life) – RCT, direct comparison: nivolumab + ipilimumab vs. sunitinib (research question 1: patients with intermediate risk) 25 Table 16: Results (side effects) – RCT, direct comparison: nivolumab + ipilimumab vs. sunitinib (research question 1: patients (...) and Efficiency in Health Care (IQWiG) - v - Table 22: Results (morbidity, health-related quality of life) – RCT, direct comparison: nivolumab + ipilimumab in comparison with sunitinib (research question 2: patients with poor risk) 42 Table 23: Results (side effects) – RCT, direct comparison: nivolumab + ipilimumab in comparison with sunitinib (research question 2: patients with poor risk) 43 Table 24: Extent of added benefit at outcome level: nivolumab + ipilimumab vs. sunitinib (research question 2

2019 Institute for Quality and Efficiency in Healthcare (IQWiG)

179. A Case Management Tool for TB Prevention, Care and Control in the UK

assessment (Form: 3) 41 – DOT chart/log (Form: 4) 43 2. Sample DOT contract 44 3. Sample social/network questionnaire 46 4. Standard case management – flow chart 47 5. Tips for giving medication to children 48 6. Home isolation policy 49 7. Sample cohort review action log 52 8. Cohort review incident reporting form 53 9. Outreach and safe practice 54 10. Methadone and anti-tuberculous treatment containing rifamycins 55 11. Managing treatment interruptions 58 12. Drug therapy – adverse effects requiring (...) (ECM) commences from suspicion of disease and may include directly observed treatment (DOT), monitoring drug levels, hepatotoxicity, and/or a package of supportive care tailored to a patient’s needs which should be available in both high and low incidence areas. The service should include all socially and/or clinically complex patients, including those who are vulnerable (older people), those in denial of diagnosis, and those where there is interruption to TB treatment. ECM must be available to TB

2019 Royal College of Nursing

180. Diagnosis and Management of Acute Pulmonary Embolism

Integration of aggravating conditions and comorbidity into risk assessment of acute pulmonary embolism 20 5.6 Prognostic assessment strategy 20 6 Treatment in the acute phase 22 6.1 Haemodynamic and respiratory support 22 6.1.1 Oxygen therapy and ventilation 22 6.1.2 Pharmacological treatment of acute right ventricular failure 22 6.1.3 Mechanical circulatory support and oxygenation 23 6.1.4 Advanced life support in cardiac arrest 23 6.2 Initial anticoagulation 23 6.2.1 Parenteral anticoagulation 23 6.2.2 (...) 8.2 Anticoagulant-related bleeding risk 34 8.3 Regimens and treatment durations with non-vitamin K antagonist oral anticoagulants, and with other non-vitamin K antagonist antithrombotic drugs 34 8.5 Management of pulmonary embolism in patients with cancer 36 9 Pulmonary embolism and pregnancy 37 9.1 Epidemiology and risk factors for pulmonary embolism in pregnancy 37 9.2 Diagnosis of pulmonary embolism in pregnancy 37 9.2.1 Clinical prediction rules and D-dimers 37 9.2.2 Imaging tests 37 9.3

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2019 European Society of Cardiology

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