Drug Action
Letermovir is a cytomegalovirus DNA terminase complex inhibitor that interferes with cytomegalovirus genome formation and virion maturation.
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Drug reference
Letermovir is a cytomegalovirus DNA terminase complex inhibitor that interferes with cytomegalovirus genome formation and virion maturation.
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Prevention of cytomegalovirus reactivation and disease [in recipients of an allogeneic haematopoietic stem cell transplant who are seropositive for the human cytomegalovirus] (initiated by a specialist) ▶BY MOUTH ▶Adult: 480 mg once daily for 100 days post-transplant, start within 28 days post-transplant, treatment beyond 100 days may be considered in some patients—consult product literature
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DUE TO INTERACTIONS ▶Manufacturer advises reduce dose to 240 mg once daily with concurrent use of ciclosporin.
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NICE decisions ▶Letermovir for preventing cytomegalovirus disease after a stem cell transplant (July 2019) NICE TA591 Letermovir (Prevymis ®) is recommended, within its marketing authorisation, as an option for preventing cytomegalovirus (CMV) reactivation and disease after an allogeneic haematopoietic stem cell transplant (HSCT) in adults who are seropositive for CMV. It is recommended only if the manufacturer provides it according to the commercial arrangement. www.nice.org.uk/guidance/ta591 Scottish Medicines Consortium (SMC) decisions SMC No. 1338/18 The Scottish Medicines Consortium has advised (March 2019) that letermovir (Prevymis ®) is accepted for use within NHS Scotland for the prophylaxis of cytomegalovirus (CMV) reactivation and disease in adult CMV-seropositive recipients [R+] of an allogeneic haematopoietic stem cell transplant. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower.
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→Appendix 1: letermovir
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▶Common or very common Diarrhoea. nausea. vomiting ▶Uncommon Abdominal pain. appetite decreased. fatigue. headache. muscle spasms. peripheral oedema. taste altered. vertigo
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The effect on human fertility is not known—impairment of fertility has been observed in animal studies.
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Manufacturer advises avoid—toxicity in animal studies.
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Manufacturer advises avoid—present in milk in animal studies.
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Manufacturer advises avoid in moderate impairment in those with co-existing moderate or severe renal impairment, and in severe impairment (risk of increased exposure).
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There can be variation in the licensing of different medicines containing the same drug. Tablet CAUTIONARY AND ADVISORY LABELS 25 ▶Prevymis (Merck Sharp & Dohme Ltd) A Letermovir 240 mg Prevymis 240mg tablets | 28 tablet P £3,723.16 6.5 HIV infection HIV infection Overview The human immunodeficiency virus (HIV) is a retrovirus that causes immunodeficiency by infecting and destroying cells of the immune system, particularly the CD4 cells. Acquired immune deficiency syndrome (AIDS) occurs when the number of CD4 cells fall to below 200 cells/microlitre; opportunistic infections and malignancies (AIDS-defining illnesses) can develop. The prognosis of HIV and AIDS has greatly improved due to more effective and better tolerated antiretroviral therapy (ART). The greatest risk to excess mortality and morbidity is delayed HIV diagnosis and treatment. Aims of treatment Treatment aims to achieve an undetectable viral load, to preserve immune function, to reduce the mortality and morbidity associated with chronic HIV infection, and to reduce onward transmission of HIV, whilst minimising drug toxicity. Treatment with a combination of ART aims to improve the physical and psychological well-being of infected people. Initiation of treatment g All patients with suspected or diagnosed HIV should be reviewed promptly by a HIV specialist. All patients diagnosed as being HIV positive should be offered immediate treatment, irrespective of CD4 cell counts. h Commitment to, and strict adherence to treatment over many years is required. Low adherence can be associated with drug resistance, progression to AIDS, and death. The treatment regimen should take into account dosing convenience, potential drug interactions, clinical symptoms, and comorbidities. g Treatment of HIV infection in treatment-naive patients is initiated with a combination of two nucleoside reverse transcriptase inhibitors (NRTIs) as a backbone regimen plus one of the following as a third drug: an integrase inhibitor (INI), a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a boosted protease inhibitor (PI). The regimen of choice contains a backbone of emtricitabine p. 687 and either tenofovir disoproxil p. 691 or tenofovir alafenamide p. 659. An alternative backbone regimen is abacavir p. 684 and lamivudine p. 689. The third drug of choice is either ritonavir p. 696-boosted atazanavir p. 693, or ritonavir-boosted darunavir p. 694, or dolutegravir p. 678, or cobicistat p. 698-boosted elvitegravir p. 680, or raltegravir p. 680, or rilpivirine p. 683. Efavirenz p. 681 may be used as an alternative third drug. Patients who require treatment for both HIV and chronic hepatitis B should be treated with antivirals active against Infection both diseases as part of fully suppressive combination ART. Regimens of choice are tenofovir disoproxil and emtricitabine, or tenofovir alafenamide p. 659 and emtricitabine. h For further information see British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy available at www.bhiva.org/ guidelines. Switching therapy g Deterioration of the condition (including clinical, virological, and CD4 cell count changes) may require a change in therapy. The choice of an alternative regimen should be guided by factors such as the response to previous treatment, tolerability, drug-drug interactions and the possibility of drug resistance. h For further information see British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy available at www.bhiva.org/guidelines. HIV infection in pregnancy g Management of HIV infection in pregnancy should focus on the well-being of the women living with HIV, by ensuring that their ART regimen maximally suppresses viral replication as early as possible (if possible before conception) in order to minimise vertical transmission of HIV. Information on the teratogenic potential of most antiretroviral drugs is limited, however, all pregnant women living with HIV who conceive whilst on effective ART should continue this treatment throughout their pregnancy. All other women should start ART during their pregnancy. The recommended regimen is a NRTI backbone of either tenofovir disoproxil or abacavir with either emtricitabine or lamivudine; the third drug should be efavirenz or ritonavir- boosted atazanavir. All treatment options require careful assessment by a specialist. h For further information, including alternative ART options, see British HIV Association guidelines for the management of HIV in pregnancy and postpartum available at www.bhiva.org/ guidelines. g Pregnancies in women with HIV and babies born to them should be reported prospectively to the National Study of HIV in Pregnancy and Childhood at www.ucl.ac.uk/nshpc/ and to the Antiretroviral Pregnancy Registry at www.apregistry. com. h HIV infection and breast-feeding g Breast-feeding by HIV-positive mothers may cause HIV infection in the infant and should be avoided. h For further information see British HIV Association guidelines for the management of HIV in pregnancy and postpartum available at www.bhiva.org/guidelines. HIV infection, pre-exposure prophylaxis The risk of acquiring HIV is increased in: . men or transgender individuals who have unprotected anal intercourse with men; . sexual partners of people who are HIV-positive with a detectable viral load; and . HIV-negative heterosexual individuals who have unprotected intercourse with a HIV-positive person, and are likely to repeat this with the same person or another person with a similar status. g Emtricitabine with tenofovir disoproxil p. 689 may be appropriate for pre-exposure prophylaxis to reduce the risk of sexually acquired HIV-1 infection in combination with safer sex practices in adults at high risk. Tenofovir disoproxil alone is an alternative for HIV-negative heterosexual individuals when emtricitabine is contra-indicated. h For further information see British HIV Association and British Association for Sexual Health and HIV guidelines on the use of HIV pre-exposure prophylaxis (PrEP) available at: www.bhiva.org/guidelines. Infection HIV infection, post-exposure prophylaxis The Department of Health advises prompt prophylaxis with antiretroviral drugs [unlicensed indication] may be appropriate following exposure to HIV-contaminated material. Immediate expert advice should be sought in such cases. National guidelines on post-exposure prophylaxis for healthcare workers have been developed (by the Chief Medical Officer’s Expert Advisory Group on AIDS), www.gov. uk/government/publications/eaga-guidance-on-hiv-post- exposure-prophylaxis and local ones may also be available. g Prompt prophylaxis with antiretroviral drugs [unlicensed indication] may also be appropriate following potential sexual exposure to HIV where there is a significant risk of viral transmission. The recommended treatment for post-exposure prophylaxis is emtricitabine with tenofovir disoproxil plus raltegravir for 28 days. h For further information see British Association for Sexual Health and HIV guidelines for the use of HIV post-exposure prophylaxis following sexual exposure available at www.bashh.org. Drug treatment Drugs that are licensed for the treatment of HIV/AIDS are listed below according to drug class. Nucleoside reverse transcriptase inhibitors (NRTI or ‘nucleoside analogue’): abacavir (ABC); emtricitabine (FTC), lamivudine (3TC); stavudine (d4T) p. 691, tenofovir alafenamide fumarate (TAF) p. 659, tenofovir disoproxil fumarate (TDF), and zidovudine (AZT) p. 692. Non-nucleoside reverse transcriptase inhibitors (NNRTI): doravirine (DOR) p. 681, efavirenz (EFV), etravirine (ETR) p. 682, nevirapine (NVP) p. 682, and rilpivirine p. 683 (RPV). Protease inhibitors (PI): atazanavir (ATZ), darunavir (DRV), fosamprenavir (FOS-APV) p. 695, lopinavir (LPV), ritonavir (RTV), saquinavir (SQV) p. 697, and tipranavir (TPV) p. 697. CCR5 antagonists: maraviroc (MVC) p. 698. Integrase inhibitors (INI): bictegravir (BIC), dolutegravir (DTG) below, elvitegravir (EVG) p. 680, and raltegravir (RAL). Fusion inhibitors: enfuvirtide (T-20) below. Pharmacokinetic enhancers: cobicistat p. 698 (c), and low-dose ritonavir (r). They boost the concentrations of other antiretrovirals metabolised by CYP3A4, but have no antiretroviral activity themselves. ANTIVIRALS › HIV-FUSION INHIBITORS
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480 mg once daily for 100 days post-transplant,
First-line fragment. Read the complete Indications and Dose section above.
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