Preventing and Managing Mpox
RELEASE DATE
April 1, 2023
EXPIRATION DATE
April 30, 2025
FACULTY
Allana Sucher, PharmD, BCPS, BCIDP
Professor of Pharmacy Practice
Regis University School of Pharmacy
Denver, Colorado
Emily Clemens, PharmD, BCACP
Assistant Professor of Pharmacy Practice
Regis University School of Pharmacy
Denver, Colorado
Alexis Marsden, PharmD Candidate Class of 2023
Regis University School of Pharmacy
Denver, Colorado
Cynthia Sprowl, PharmD Candidate Class of 2023
Regis University School of Pharmacy
Denver, Colorado
FACULTY DISCLOSURE STATEMENTS
Dr. Sherman has no actual or potential conflicts of interest in relation to this activity.
Postgraduate Healthcare Education, LLC does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.
ACCREDITATION STATEMENT
Pharmacy
Postgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
UAN: 0430-0000-22-055-H01-P
Credits: 2.0 hours (0.20 ceu)
Type of Activity: Knowledge
TARGET AUDIENCE
This accredited activity is targeted to pharmacists. Estimated time to complete this activity is 120 minutes.
Exam processing and other inquiries to:
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DISCLAIMER
Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
GOAL
To educate pharmacists about the clinical presentation, complications, prevention measures, and treatment of mpox (monkeypox) based on current recommendations
OBJECTIVES
After completing this activity, the participant should be able to:
- Identify the routes of transmission, clinical presentation, and complications of mpox.
- Outline a patient-specific treatment plan for the management of mpox.
- Discuss appropriate nonpharmacotherapy selfcare of mpox, including measures to prevent the transmission of infection.
- Select an appropriate vaccine for the prevention of mpox based on patient-specific factors.
ABSTRACT: Mpox (formerly known as monkeypox) is an infection caused by the monkeypox virus, which is in the Orthopoxvirus genus. Mpox has a characteristic rash that transforms through four stages of macules, papules, vesicles, and pustules. Current clinical management includes infection prevention measures and supportive care, with the antiviral agent tecovirimat considered for use in those with or who have risk factors for severe disease. Vaccination can be considered for individuals at high risk for exposure to mpox. Pharmacists are in a key position to actively work with other healthcare professionals to ensure appropriate prevention and management of mpox infection.
Mpox (formerly known as monkeypox) was discovered in 1958 after it caused disease in colonies of monkeys kept for research, and it was first identified in humans in 1970 in the Democratic Republic of the Congo.1-3 It is caused by the monkeypox virus, a DNA virus that is a member of the Orthopoxvirus genus, and also includes the viruses that cause smallpox and cowpox.4-6
The original animal source of mpox is not known as various animals, including African rodents, tree squirrels, and nonhuman primates, are susceptible to and may harbor the virus.2,3 Human mpox has been increasingly reported from central and western Africa, with the majority of cases outside of Africa linked to travel or imported animals.2,3 However, since May 2022, mpox cases and clusters of incidences were reported in patients from several countries where the disease is not considered endemic and in patients with a travel history to nonendemic countries in Europe and North America.7 This is being refered to as the 2022 mpox outbreak, and as of March 1, 2023, there have been over 86,000 confirmed cases worldwide, including over 30,000 cases in the United States.7,8
TRANSMISSION
Mpox is primarily transmitted from close person-toperson contact through direct contact with the rash, scabs, respiratory secretions, or saliva of an infected individual or through activities associated with intimate contact with an infected individual, including oral, anal, or vaginal sex or touching the genital areas or anus.9,10 Other routes of person-to-person transmission include during pregnancy, through skin piercing or tattooing, and occupational exposure from a skin-penetrating injury with a device that was used to sample a skin lesion from an infected individual.9,10 Mpox may also be transmitted from animals to humans through direct contact with lesions, respiratory secretions, blood, body fluids, urine, or feces of an infected animal.9,10 New data show that some infected individuals have spread mpox to others between 1 and 4 days before the onset of their symptoms; however, there have not been any cases of transmission linked to exposure from a person who never developed symptoms.9 Additionally, the risk of acquiring infection from touching objects (including fabrics such as bedding, clothing, or towels) that have been used by an infected individual is considered low.9,10
CLINICAL PRESENTATION AND COMPLICATIONS
Mpox has an average incubation period of 3 to 17 days (but can range up to 21 days), and after this period of time, a rash develops that progresses through four stages.2,11,12 Mpox lesions initially present as macules or flat lesions, which transform after 1 to 2 days to papules or raised lesions.11 One to 2 days later, papules form into vesicles, which are raised and filled with clear fluid. Vesicles ultimately transform into pustules, which last for about 5 to 7 days before starting to crust. These pustules are the characteristic rash associated with mpox and are described as well-circumscribed, deep-seated, and with a depression in the center, which may look like a dot on top of the lesion (known as umbilication). The pustules will eventually form scabs, which are present for about 1 to 2 weeks prior to falling off. After scabs have fallen off, scars or areas of discoloration may remain on the skin.11
Lesions from the current mpox outbreak are frequently occurring in the genital/anorectal areas or the mouth, and the rash may consist of only a single lesion or a few lesions, with the lesions described as painful until they crust over (at which point they are described as itchy).11,12 Additionally, rectal symptoms, including rectal pain, bleeding, and/or purulent or bloody stools, have been commonly reported by infected individuals. Respiratory symptoms and prodromal symptoms such as fever, malaise, myalgias, lymphadenopathy, and headache may also be present; a rash typically develops 1 to 4 days after these flu-like symptoms.11,12 Overall, the duration of illness from mpox is estimated to be between 2 and 4 weeks in most cases.11
The clinical course of mpox infection depends on an individual’s immune response, with most patients having a self-limited infection.2,11,13 However, severe manifestations of infection, including ocular/periorbital infection, encephalitis, severe lymphadenopathy, infection characterized by a high number of lesions that may coalesce or become necrotic (requiring debridement or amputation), lesions that occur in an area that may cause severe pain or scarring/ strictures, secondary bacterial/fungal skin infections, and other severe clinical manifestations requiring hospitalization have been reported.13-15
The CDC provided clinical consultations on 57 adult patients who were hospitalized between August and October 2022 with severe manifestations of mpox and released a report in October 2022 describing these patients.15 They noted that 47 out of the 57 hospitalized patients (82%) were infected with HIV, and of the 43 patients with a known CD4 count, 72% had a CD4 count less than 50 cells/mm3. Seventeen of the 57 patients (30%) required intensive care unit-level care, and mpox was determined to be the cause of death or contributing factor in five of the 12 patients who died. One death was not caused by mpox, and six deaths remained under investigation. Based on their findings, the CDC states providers should be aware that severe morbidity and mortality related to mpox have been found during the current outbreak, especially in those who are highly immunocompromised. The CDC recommends to test for HIV in all sexually active patients with suspected mpox (unless they are already known to be infected with HIV). Additionally, the CDC states providers should consider early mpox treatment in those who are highly immunocompromised, as further discussed in the treatment section.15
DIAGNOSTIC CONSIDERATIONS
Mpox should be suspected in an individual who has a new rash that has the features described in the previous section or in an individual who meets one of the CDC’s epidemiologic criteria for infection (see TABLE 1) and for which there is high clinical suspicion for infection.16 It is important to note that there are other infections that may have a rash or lesions (such as herpes, shingles, or syphilis), which may make the diagnosis of mpox rash more challenging, as well as the possibility of coinfections.16 The CDC has guidelines for collecting and handling specimens for mpox testing available at https:// www.cdc.gov/poxvirus/monkeypox/clinicians/prepcollection- specimens.html. These guidelines include the use of recommended personal protective equipment when collecting a specimen from an individual with suspected or confirmed infection and the collection of skin lesion material with sterile, synthetic swabs (collecting two swabs from each lesion) for laboratory testing.17
TREATMENT
Approach to Treatment
Supportive care, including pain control, management of itching, and methods for preventing spread of infection to others, are part of the management for mpox, with antiviral treatment recommended for select patients as discussed below in this section.18,19 Once an individual has been diagnosed with mpox, it is important that close contacts be notified as soon as possible.18
Supportive Care
Pain management should be individualized to a patient’s needs.18,19 An OTC systemic pain reliever such as acetaminophen, ibuprofen, or topical lidocaine may be used for pain, and oral salt-water rinses can be used to soothe a rash in the mouth. Patients should be counseled to contact their provider if they feel that their pain has become severe or unmanageable, as further evaluation is warranted and stronger prescription-strength pain relief (such as gabapentin or an opioid) may be needed. Agents such as oral antihistamines, topical creams/gels, calamine lotion, colloidal oatmeal, or a sitz bath may be useful for relief of itching. Patients should also be counseled to keep their rash covered and to try to avoid touching or scratching it, which may result in the spread of infection or a secondary bacterial infection. Gloves should be worn if applying topical medications, and hands should be cleaned by washing with soap and water or using an alcohol-based hand sanitizer after gloves are removed or if the rash is touched.18,19
Role of Antiviral Agents
Tecovirimat: Currently, there are no FDA-approved agents for the treatment or prevention of mpox.13,20,21 The antiviral agent tecovirimat (TPOXX) is approved for use in adults and children for the treatment of smallpox, another orthopoxvirus, but it is considered investigational for the treatment of mpox.13,20,21 Tecovirimat is available through enrollment in a phase III clinical trial called the Study of Tecovirimat for Human Monkeypox Virus (STOMP) that is sponsored by the National Institute of Allergy and Infectious Diseases or through an expanded-access investigational new drug (EA-IND) protocol, also referred to as compassionate use, that should be used along with the CDC’s guidance for treatment.13,20-22 For the STOMP trial, adults are randomized 2:1 to receive either 14 days of placebo or oral tecovirimat capsules, with the dosing based according to weight, while open-label oral tecovirimat capsules are given to those with severe disease, severe immunosuppression, significant skin conditions, who are younger than age 18 years, are pregnant or breastfeeding, or who are receiving an interacting medication.22
According to the CDC, providers should inform patients about and encourage enrollment through the STOMP trial, while the EA-IND protocol should be reserved for those who decline to participate in STOMP or cannot participate due to ineligibility or logistical issues, such as unavailability of a close clinical trial site.21 As of October 28, 2022, new providers and affiliated medical facilities providing tecovirimat through the EA-IND must register with the TPOXX IND Registry (https://www.cdc.gov/poxvirus/monkeypox/clinicians/obtaining-tecovirimat.html) as participating providers/sites.23
According to the CDC’s clinical guidance for the treatment of mpox, tecovirimat should be considered for use as primary or early empiric treatment in those with severe disease, including hemorrhagic disease, necrotic lesions, numerous lesions that have coalesced into larger lesions, infections that require surgical debridement, severe lymphadenopathy, involvement of multiple organ systems, presence of lesions in particular areas (eyes, mouth, throat, genitals, or anus) that may cause complications such as scarring or strictures, or in those who require hospitalization.13 The CDC also states that tecovirimat should be considered for those at high risk for severe disease, including those with severe immunocompromise (such as advanced or uncontrolled HIV infection, transplant recipients, generalized malignancy, leukemia, lymphoma, or receiving therapy with certain medications such as alkylating agents, antimetabolites, tumor necrosis factor inhibitors, or high-dose corticosteroids), children (especially those younger than age 1 year), pregnant or breastfeeding individuals, and those with an active condition that affects the skin, such as eczema or psoriasis.13 Tecovirimat should not be used for those with milder symptoms.20
Tecovirimat is available as an oral formulation and an IV formulation, and its dosing regimen as recommended in the IND protocol and considerations for use are included in TABLE 2.21 For those unable to swallow the capsules or for those who weigh <28 pounds (so that the recommended dose is less than that contained in one 200-mg capsule), the IND contains instructions for opening and mixing the capsules with water or food, as well as directions on how the medication should be administered, including that the mixture must be given within 30 minutes of preparation. Intravenous therapy should be considered for those who are unable to take or absorb oral medications or ingest a full meal; however, it is important to note that IV tecovirimat is contraindicated for use in those with a creatinine clearance less than 30 mL/minute due to potential accumulation of an excipient in the formulation. It is recommended to switch from IV to oral tecovirimat in those receiving the IV formulation as soon as the patient is eligible. Tecovirimat is given for a treatment duration of 14 days for patients of all ages.21
Role of Other Agents
Brincidofovir (Tembexa) is approved for use in adults and pediatric patients (including neonates) for the treatment of smallpox.13 It may be requested for the treatment of mpox through submitting a singlepatient emergency use IND to the FDA.13,24 Under the emergency use IND, brincidofovir may be considered for use in those who have severe mpox or who are at high risk for progression to severe disease and have one of the following: clinically significant disease progression while receiving tecovirimat; initial improvement and then worsening of disease while receiving tecovirimat; or a contraindication to receipt of oral or IV tecovirimat.13,24 Brincidofovir has several warnings and precautions, including elevations of hepatic transaminases and bilirubin, risk of fetal harm, risk of male infertility, and carcinogenicity in addition to drug interactions with concomitant use of agents that are OATP1B1 or 1B3 inhibitors, which increase exposure of brincidofovir and the potential for adverse reactions.25 Important counseling points include to not crush, divide, or break the tablets; report symptoms of liver injury; for those of childbearing potential to use contraception during treatment and for at least 2 months after the last dose; for partners of those of childbearing potential to use condoms during treatment and for at least 4 months after the last dose; and if concomitant use of an interacting medication is required, to postpone taking the dose for at least 3 hours after brincidofovir.25
Brincidofovir is a prodrug of the antiviral agent cidofovir (Vistide), which is approved for the treatment of cytomegalovirus retinitis in patients with AIDS.13 Cidofovir has been shown to have activity against orthopoxviruses in animals and in-vitro studies and may be considered for use in those with severe mpox. However, it is not approved for mpox and may have more safety concerns, particularly related to nephrotoxicity, than brincidofovir. It is important to note that brincidofovir should not be used concomitantly with cidofovir.13
Vaccinia immune globulin intravenous (VIGIV) is approved for the treatment of complications of vaccinia vaccination, and although not approved for mpox, it may be considered for use in severe cases in those with an impaired antibody response or for prophylactic use in an individual with severe T-cell immunodeficiency who has been exposed to mpox and has a contraindication to receipt of the vaccine. VIGIV is available from the CDC on a case-by-case basis upon clinician request.13
PREVENTION
General Methods
Mpox may be transmitted from an infected individual to others from 1 to 4 days before the start of symptoms until the rash has fully healed and a new, fresh layer of skin has formed.9,18 If possible, those infected with mpox should isolate at home until they are no longer considered infectious.26 Patients should be counseled to keep the skin clean and dry when not showering/bathing, to use gauze or bandages to cover the rash, to disinfect/clean any shared surfaces or objects, to wait to shave the area with the rash until all scabs have fallen off and a new layer of skin has formed, and to wear a mask when around others until the rash and other symptoms have resolved.18,26 It is important to counsel patients to try to avoid touching or scratching their rash; to avoid sharing objects such as towels, washcloths, and drinking glasses; and to avoid contact with pets and other animals.18,26 If contact with the rash occurs, hands should be washed with soap and water or cleaned with an alcohol-based hand sanitizer, and for those with rash on their hands, gloves should be worn when touching shared surfaces or objects.18
Vaccines
There are two vaccines available for the prevention of mpox: JYNNEOS and ACAM2000, as indicated in TABLE 3.27-30
JYNNEOS Vaccine: The CDC’s interim guidance recommends to consider vaccination with JYNNEOS to prevent mpox in those who are at high risk for infection, and this is the main vaccine that is being used during the current outbreak due to its better adverse-event profile.29 JYNNEOS is approved as a subcutaneous injection for the prevention of smallpox and mpox in those aged 18 years and older who are at high risk for infection.27 The FDA has issued an emergency use authorization (EUA) for its subcutaneous administration for prevention of mpox in those younger than age 18 years who are at high risk for infection and an EUA for an alternative regimen of intradermal administration in those aged 18 years and older who are at high risk for infection.28,29 The CDC states that when feasible, the alternative intradermal regimen is preferred because this route requires a lower volume of vaccine and the number of available doses is increased.29 However, the intradermal route of administration is not recommended for those who have a history of developing keloid scars. The subcutaneous and intradermal regimens are considered to be interchangeable, as long as the second dose is given at the recommended interval of 28 days after the first dose.29
REFERENCES
1. WHO. WHO recommends new name for monkeypox disease. www.who.int/news/item/28-11-2022-who-recommends-new-name-for-momkeypox-disease. Accessed February 28, 2023.
2. WHO. Monkeypox. www.who.int/news-room/fact-sheets/detail/monkeypox. Accessed February 28, 2023.
3. CDC. Mpox: about monkeypox. www.cdc.gov/poxvirus/monkeypox/about/index.html. Accessed February 28, 2023.
4. McCollum AM, Damon IK. Human monkeypox. Clin Infect Dis. 2014;58(2):260-267.
5. Lum FM, Torres-Ruesta A, Tay MZ, et al. Monkeypox: disease epidemiology, host immunity and clinical interventions. Nat Rev Immunol. 2022;22(10):597-613.
6. CDC. Poxvirus diseases. www.cdc.gov/poxvirus/diseases.html. Accessed February 28, 2023.
7. WHO. Mpox (monkeypox) outbreak, 2022. www.who.int/emergencies/situations/monkeypox-oubreak-2022. Accessed February 28, 2023.
8. CDC. Mpox: 2022 outbreak cases and data. www.cdc.gov/poxvirus/monkeypox/response/2022/index.html. Accessed March 1, 2023.
9. CDC. Mpox: how it spreads. www.cdc.gov/poxvirus/monkeypox/ifsick/transmission.html. Accessed February 28, 2023.
10. CDC. Mpox: science brief: detection and transmission of mpox (formerly monkeypox) virus during the 2022 clade IIb outbreak. www.cdc.gov/poxvirus/monkeypox/about/science-behind-transmission.html. Accessed February 28, 2023.
11. CDC. Mpox: clinical recognition. www.cdc.gov/poxvirus/monkeypox/clinicians/clinical-recognition.html. Accessed February 28, 2023.
12. CDC. Mpox: signs and symptoms. www.cdc.gov/poxvirus/monkeypox/symptoms/index.html. Accessed February 28, 2023.
13. CDC. Mpox: treatment information for healthcare professionals. www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html. Accessed February 28, 2023.
14. CDC Health Alert Network. Severe manifestations of monkeypox among people who are immunocompromised due to HIV or other conditions. https://emergency.cdc.gov/han/2022/han00475.asp . Accessed February 28, 2023.
15. Miller MJ, Cash-Goldwasser S, Marx GE, et al. Severe monkeypox in hospitalized patients–United States, August 10-October 10, 2022. MMWR Morb Mortal Wkly Rep. ePub October 26, 2022.
16. CDC. Mpox: case definitions for use in the 2022 monkeypox response. www.cdc.gov/poxvirus/monkeypox/clinicians/case-definition.html. Accessed February 28, 2023.
17. CDC. Mpox: guidelines for collecting and handling specimens for mpox testing. www.cdc.gov/poxvirus/monkeypox/clinicians/prep-collection-specimens.html. Accessed February 28, 2023.
18. CDC. Mpox: what to do if you are sick. www.cdc.gov/poxvirus/monkeypox/if-sick/what-to-do.html. Accessed February 28, 2023.
19. CDC. Mpox: clinical considerations for pain management of mpox. www.cdc.gov/poxvirus/monkeypox/clinicians/pain-management.html Accessed February 28, 2023.
20. CDC. Mpox: patient’s guide to mpox treatment with tecovirimat (TPOXX). www.cdc.gov/poxvirus/monkeypox/if-sick/treatment.html . Accessed February 28, 2023.
21. CDC. Expanded access IND protocol: use of tecovirimat (TPOXX) for treatment of human non-variola orthopoxvirus infections in adults and children. www.cdc.gov/poxvirus/monkeypox/pdf/Tecovirimat-INDProtocol-CDC-IRB.pdf. Accessed February 28, 2023.
22. ClinicalTrials.gov. Study of tecovirimat for human monkeypox virus (STOMP). https://clinicaltrials.gov/ct2/show/NCT05534984. Accessed February 28, 2023.
23. CDC. Mpox: information for healthcare providers: tecovirimat (TPOXX) for treatment of mpox. www.cdc.gov/poxvirus/monkeypox/clinicians/obtaining-tecovirimat.html. Accessed February 28, 2023.
24. FDA. FDA mpox response. www.fda.gov/emergency-preparednessand-response/mcm-issues/fda-monkeypox-response#therapeutics. Accessed February 28, 2023.
25. Tembexa (brincidofovir) package insert. Durham, NC: Chimerix, Inc; July 2021.
26. CDC. Mpox: preventing spread to others. www.cdc.gov/poxvirus/monkeypox/if-sick/preventing-spread.html. Accessed February 28, 2023.
27. Jynneos (Smallpox and Monkeypox Vaccine, Live, Non-replicating) suspension for subcutaneous injection package insert. Denmark: Bavarian Nordic A/S; April 2022.
28. FDA. Fact sheet for healthcare providers administering vaccine: emergency use authorization of Jynneos (smallpox and monkeypox vaccine, live, non-replicating) for prevention of monkeypox disease in individuals determined to be at high risk for monkeypox infection. www.fda.gov/media/160774/download. Accessed February 28, 2023.
29. CDC. Mpox: interim clinical considerations for use of Jynneos and ACAM2000 vaccines during the 2022 U.S. mpox outbreak. www.cdc.gov/poxvirus/monkeypox/clinicians/vaccines/vaccine-considerations.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fpoxvirus%2Fmonkeypox%2Fhealth-departments%2Fvaccine-considerations.html#print. Accessed February 28, 2023.
30. FDA. Medication guide: Smallpox (vaccinia) vaccine, live (ACAM2000). www.fda.gov/media/75800/download. Accessed February 28, 2023.
31. Rao AK, Petersen BW, Whitehill F, et al. Use of Jynneos (smallpox and monkeypox vaccine, live, nonreplicating) for preexposure vaccination of persons at risk for occupational exposure to orthopoxviruses: recommendations of the Advisory Committee on Immunization Practices–United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(22):734-742. Erratum in: MMWR Morb Mortal Wkly Rep. 2022;71(27):886.
32. CDC. Mpox: clinician FAQs. www.cdc.gov/poxvirus/monkeypox/clinicians/faq.html. Accessed February 28, 2023
