NHS Greater Glasgow & Clyde Area Drug and Therapeutics Committee
Greater Glasgow and Clyde Medicines
Medicines Update

PostScript 78 (November 2013)

This edition contains articles on:

 

  • HIV treatments and drug interactions
  • Adding “non-primary care” drugs to GP records
  • Nalmefene for reduced alcohol consumption
  • Safety updates: new oral anticoagulants
  • Other formularies
  • Respiratory inhalers
  • ADTC decisions summary
  • Webwatch: Chronic pain resources, new guidelines
  • SMC call for clinical experts

 

HIV treatments and drug interactions

Dr Rebecca Acquah, Specialist Trainee, Sexual Health and HIV medicine and Dr Andrew Winter, Consultant in Sexual Health and HIV, provide an update on some issues that may arise for any prescriber dealing with a patient who is being treated for HIV infection.

 

Potential or actual drug-drug interactions (PDDIs) have been a concern since the introduction of antiretroviral therapy (ART). HIV prevalence is rising across the UK and over 1,400 patients now attend the Brownlee Centre in Glasgow for HIV care. There have been major advances in HIV treatment in the last year, with three “single tablet regimens” now licensed to control HIV infection with a one-pill once-a-day approach. These fixed-dose combinations make it harder than ever to spot potential drug-drug interactions. 

 

Some fixed-dose combinations used in HIV infection

Constituents         Trade name Comment  
 lopinavir / ritonavir  Kaletra®   Protease inhibitor

CYP3A4 inhibitor

 tenofovir / emtricitabine / efavirenz   Atripla®   Neuropsychiatric side effects
 fovir / emtricitabine / rilpivirine  Eviplera®   Efficacy reduced by proton-pump inhibitors
 tenofovir / emtricitabine / elvitegravir / cobicistat     Stribild®  

 CYP3A4 inhibitor

Increases serum creatinine

      

                       

One danger is inadvertent potentiation of co-prescribed medications. A recent case illustrates this.

A man was seen in the ENT outpatient clinic with a complaint of nasal stuffiness. He had stable HIV infection treated with Kivexa® and Kaletra®. He was advised to get a prescription for Avamys® from his GP. The letter was copied to his HIV consultant who intercepted the patient before he obtained his new nasal spray. Avamys contains fluticasone which is greatly potentiated by co-prescription of Kaletra®, a powerful CYP3A4 inhibitor. Fortunately no harm resulted in this case.

 

Key points:

  • Check the constituent parts of combination antiretrovirals and brand name prescriptions.
  • Always check for cautions, contraindications and potential interactions. Always seek specialist advice, eg from the HIV specialist pharmacist team on 0141 211 3317 or page 5388.
  • Check the SPC, BNF and Liverpool drug-drug interaction website .
  • In primary care, consider adding antiretroviral drugs to the patient’s medical record as described on page 2.
  • Ensure patients are aware of the need to check Over the Counter (OTC) medicines, including herbal medicines, for possible interactions.

 

Potentiation of other drugs

There have been over 50 case reports of inhaled or intranasal steroids causing iatrogenic Cushing’s syndrome in HIV patients due to drug interactions with some cases requiring hospital admission. Fluticasone is of particular concern due to its high gluco-corticosteroid relative receptor binding affinity and its exclusive CYP3A4 metabolism. Fluticasone is found in a variety of brands including Avamys, Dymista, Flixonase, Nasofan and Seretide.

 

Many statins are potentiated by CYP3A4 inhibitors such as ritonavir, possibly leading to rhabdomyolysis.  This is a particular risk with simvastatin.

 

The most recently licensed fixed dose combination treatment for HIV is Stribild® (tenofovir, emtricitabine, elvitegravir and cobicistat). Cobicistat is a pharmacokinetic boosting agent used to maintain elvitegravir levels by inhibition of cytochrome p450. Unlike ritonavir (the other antiretroviral booster), cobicistat has no antiretroviral properties itself and should have less metabolic side effects. As well as drug interactions, it increases creatinine, affecting calculations of eGFR.

 

Common medications which are contraindicated with Stribild include rifampicin, some anticonvulsants, St John’s wort and simvastatin.  Other potentially significant reactions can occur with antacids, cardiovascular drugs, nephrotoxic drugs, antidepressants, steroids, hormonal contraceptives and sedatives.

 

For advice on any of these interactions or issues; please contact the specialist service.

 

Undermining HIV treatment

There is also a risk of undermining the efficacy of prescribed ART due to a decrease in plasma concentration of the active agent secondary to co-prescribed medications. PPIs are a particular problem and are contraindicated with some treatments. They reduce levels of rilpivirine (in Eviplera®) and atazanavir which can lead to virological and treatment failure and possible permanent resistance to a whole class of ART making future treatment more complex for both the physician and patient involved. A four-week prescription of lansoprazole might affect an HIV patient’s therapy choice for the rest of his or her life.

 

Additive toxicity

Finally, harm may result from additive toxicity, most importantly QT prolongation. This can result both from combination of effect and pharmacokinetic potentiation, eg clarithromycin is potentiated by ritonavir. In one recent study, 39% of all HIV patients had drug interactions expected to increase QTc.  Only 30% of that cohort had been evaluated by ECG, 27% of whom had an abnormal QTc. 

 

This emphasises the importance of careful medicines reconciliation and for patients taking ART, the need at each prescription episode, to check for PDDIs using recognised sources, eg University of Liverpool drug interactions (www.hiv-druginteractions.com). The constituents of commonly used medications need to be reviewed by the prescriber, and attention paid even to topical, inhaled or injected agents.

 

Adding "non-primary care" drugs to the GP record.

There have been several cases of patient harm and near misses involving patients not receiving therapy, or being prescribed interacting medication, as a result of an "incomplete" prescribing record. This included clozapine being omitted on admission to an acute hospital resulting in a worsening of mental state and subsequent admission to a mental health hospital. Restarting clozapine after missed doses without appropriate titration is also potentially dangerous.

 

Although it is not a contractual requirement, for both patient and prescriber safety, we recommend any "non-primary care" drugs are recorded on the GP record. Good practice guidance on how to do this is available on our website and selecting "Adding Medicines to EMIS and VISION that are not supplied by GP practices".

 

The benefits include:

  • Increased patient safety: Emergency Care Summary (ECS) will be more accurate so reduced risk of duplication of therapy.
  • Increased prescriber safety: prescribing record is complete allowing clinical decision support to flag drug interactions etc. Prescribers can form a more complete assessment when making prescribing decisions.
  • Improved medicines reconciliation at the interface due to accurate ECS.

 

The main risk with the EMIS system in recording such drugs on the GP record is the potential to issue a prescription, however if the guidance in the link above is followed, the risk is minimised as several warnings need to be overridden to do so. It does also mean that these drugs will be listed on a patient’s repeat prescription slip so will be visible to their community pharmacist.

 

These cases also highlight the importance of using at least two sources of information to carry out medicines reconciliation effectively on admission and of good communication between hospitals, out-patient clinics and other specialist services in clearly communicating medication treatment plans with GP practices in a timely manner.

 

There is no definitive list of drugs that should be added and this is left at individual discretion. The most common ones include:

  • Addiction services: methadone, disulfiram
  • Smoking cessation / community pharmacy: varenicline
  • Mental health: clozapine, antipsychotic depot injections
  • Sexual health/HIV: HIV drugs, contraception via Sandyford
  • Rheumatology: eg etanercept, adalimumab
  • Endocrinology: IV bisphosphonates, eg zoledronic acid
  • Chemotherapy
  • Homecare, eg darbopoetin, immunoglobulins

 

We believe recording such medicines is an important step to improve patient and prescriber safety and would welcome your support and feedback in doing so.

 

Nalmefene for reduction of alcohol consumption

The ADTC has added nalmefene film coated tablets (Selincro®) to the NHSGGC Adult Formulary after SMC accepted it for use in Scotland. 

 

Nalmefene is an opioid receptor modulator with antagonistic activity at the mu and delta receptors and partial agonist activity at the kappa receptor. It is licensed for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking risk level (DRL), without physical withdrawal symptoms and who do not require immediate detoxification. The licence dictates that nalmefene should only be prescribed in conjunction with continuous psychosocial support focused on treatment adherence and reducing alcohol consumption; and should be initiated only in patients who continue to have a high DRL two weeks after initial assessment.

 

Nalmefene tablets are to be taken as-needed: one tablet on each day the patient perceives a risk of drinking alcohol, preferably one to two hours prior to the anticipated time of drinking. If the patient has started drinking alcohol without taking nalmefene, the patient should take one tablet as soon as possible. The maximum dose is one tablet per day. Nalmefene can be taken with or without food.

 

As this medicine is a new concept in alcohol care and treatment, ie a harm reduction rather than an abstinence approach it does not clearly fit within current specialist services.  It has been added to the Formulary and is available for prescribers to consider in suitable patients where the full package of care including continuous psychosocial support can be provided.

 

Safety updates

Contraindications to apixaban, dabigatran and rivaroxaban

The MHRA previously clarified contraindications for dabigatran to include a range of clinical conditions where the patient is at significant risk of major bleeding, as well as in combination with other anticoagulant agents. Because similar risks are associated with the other new oral anticoagulants (apixaban and rivaroxaban), these contraindications have been applied across all three of these agents for all indications and doses. For full details, refer to the MHRA website.

 

Special care should be taken when prescribing these anticoagulant medicines to patients with other conditions, procedures, and concomitant treatments (eg, non-steroidal anti-inflammatory drugs, antiplatelets), which may increase the risk of major bleeding. There is no specific antidote for any of the new oral anticoagulants. Please consult the product information for advice on treatment in the event of bleeding complications, or overdose or the guidelines listed in PostScript 76.

 

Other Formularies

The NHSGGC Paediatric Formulary, the Catheter Formulary, the Community Pharmacy Minor Ailments Service Formulary and Primary Care Wound Dressings Formulary can all be accessed here. On the left hand side please scroll down to Other Formularies and you will see links to each of these documents.

 

Respiratory inhalers identification guide

A new identification guide for respiratory inhalers is now available. This is mainly designed for use in acute care. It contains images of different inhaler preparations and spacer devices as an aid to identification. There is some limited dosage advice and examples of how inhalers should be prescribed on the medicine prescription form (Kardex). The main aim of the guide is to ensure patients receive the correct inhaler device during admission to hospital and reduce the wastage associated with the wrong inhalers being issued. Printed copies will be available for all wards in due course.

 

ADTC decisions summary

See here for full list of medicines and details of indications and restrictions.

 

Some additions to the Adult Total Formulary:

  • Crizotinib for treatment of adults with previously treated anaplastic lymphoma kinase positive advanced non-small cell lung cancer. Only 5% of patients will have this genetic marker. Included pending protocol.
  • Lixisenatide for type 2 diabetes in combination with oral products and / or basal insulin when adequate glycaemic control is not achieved. Restricted to specialist initiation.
  • Nalmefene for reduction of alcohol consumption (se above for details).
  • Rifaximin for reduction in recurrence of episodes of overt hepatic encephalopathy in patients 18 years of age or older. Restricted to initiation by a consultant gastroenterologist.

The following medicines were among those added to the Paediatric Formulary

  • Aripiprazole for up to 12 weeks treatment of moderate to severe maniac episodes in Bipolar Disorder I in adolescents aged 13 years and older. Restricted to specialist initiation and management under the supervision of a child/ adolescent psychiatrist.

 

Webwatch: Management of Chronic Pain

The NHSGGC Chronic Pain MCN Education Subgroup announces the launch of its new pain website. Aimed at clinicians and patients it contains general information, patient information leaflets and educational resources relating to all aspects of chronic pain management. Additional educational material and patient resources will be added as they become available.

 

Clinicians can access

  • An opioid dose converter tool which gives 24 hour equi-analgesic doses. The tool can convert multiple opioids and automatically calculates the recommended 25% dose reduction when switching opioids.
  • Video files of MCN educational presentations delivered to primary care.
  • Links to a new Chronic Pain Learn-Pro module consisting of five parts:
  • Physiology of chronic pain
  • Assessment of chronic pain
  • Physiotherapy for chronic pain
  • Non–pharmacological therapies for chronic pain
  • Pharmacological therapies for chronic pain.
  • Links to current guidelines, audits and a notice-board detailing upcoming pain meetings and a forum for discussions.

 

Patients can access

  • Information on drugs used in the management of chronic pain, including drug information leaflets with titration guidance.
  • Links to supporting websites.
  • A pain diary app for android devices which both records pain scores and also provides a portal to information contained on the website.
  • A link to research currently being undertaken in the Pain Service and a patient forum for feedback on the site.

 

New NHSGGC guidelines

The new guideline covering Vitamin D deficiency / insufficiency management for adult patients has been published. It provides advice on a number of aspects of care for risk groups such as measuring vitamin D levels, dietary sources of vitamin D and sun exposure. 

The groups considered are:

  • Pregnant or breastfeeding women
  • Housebound patients aged 65 years and older
  • Patients with vitamin D < 25nmol/L or 25-50nmol/L and symptoms of osteomalacia or osteoporosis
  • Other high-risk asymptomatic patient groups

A future bulletin will cover common questions and answers raised by this guideline.

 

The clinical guidelines below were also posted onto Staffnet:

 

Call for clinical experts: Scottish Medicine Consortium

The SMC consults with a number of clinical experts from acute and primary care when gathering opinion on new medicines (including anticipated place in therapy, unmet need and scale of uptake). This is an increasingly important and valuable part of the assessment process. This database is being refreshed and NHSGGC clinicians are invited to register an interest directly with the ADTC Chair. Some further information is available on the SMC website.