Clomipramine Capsules and Oseltamivir Phosphate

• Generic Name: clomipramine
• Dosage Forms: capsule
• Other Brand Names: Anafranil

Clomipramine is a tricyclic antidepressant. It affects chemicals in the brain that may be unbalanced.

Clomipramine is used to treat symptoms of obsessive-compulsive disorder (OCD) such as recurrent thoughts or feelings and repetitive actions.

Clomipramine may also be used for purposes not listed in this medication guide.

• Generic Name: oseltamivir
• Dosage Forms: n.a.
• Other Brand Names: Tamiflu

Treatment of acute, uncomplicated illness caused by influenza A or B viruses in adults, adolescents, and pediatric patients ≥2 weeks of age. Although safety and efficacy not established in neonates <2 weeks of age, also recommended when treatment of influenza considered necessary in this age group.

Although efficacy not established in immunocompromised patients, has been used to treat seasonal influenza A or B virus infections in bone marrow transplant (BMT) recipients and to treat seasonal influenza infections in hematopoietic stem cell transplant (HSCT) recipients.

CDC, US Public Health Service Advisory Committee on Immunization Practices (ACIP), AAP, and others recommend antiviral treatment of seasonal influenza illness initiated as soon as possible in all individuals with suspected or confirmed influenza who require hospitalization or have severe, complicated, or progressive illness (regardless of vaccination status or underlying illness). Early empiric antiviral treatment also recommended in individuals with suspected or confirmed influenza of any severity if they are at high risk of developing influenza-related complications because of age or underlying medical conditions. This includes children <2 years of age, adults ≥65 years of age, individuals of any age with certain chronic medical or immunosuppressive conditions, women who are pregnant women or up to 2 weeks postpartum, individuals <19 years of age receiving long-term aspirin therapy, American Indians, Alaskan natives, morbidly obese individuals with body mass index (BMI) ≥40, and residents of any age in nursing homes or other long-term care facilities.

CDC, ACIP, and AAP also state empiric antiviral treatment can be considered in previously healthy, symptomatic individuals with suspected or confirmed influenza who are not known to be at increased risk of developing severe or complicated illness if such treatment can be initiated within 48 hours of illness onset. Although these individuals typically do not require treatment, early empiric antiviral treatment might provide some benefit (e.g., shortened duration of illness).

If indicated, initiate antiviral treatment as soon as possible after illness onset (ideally within 48 hours); do not delay initiation of treatment while waiting for laboratory confirmation.

Although manufacturer states use for treatment of influenza only in patients who have been symptomatic for ≤48 hours, there is some evidence from observational studies of hospitalized patients that antiviral treatment might still be beneficial when initiated up to 4 or 5 days after illness onset. CDC, ACIP, and AAP recommend that antiviral treatment be initiated in all patients with severe, complicated, or progressive illness attributable to influenza and all hospitalized patients and patients at increased risk of influenza complications (either hospitalized or outpatient) who have suspected or confirmed influenza, even if it has been >48 hours after illness onset. Base decisions regarding use of empiric antiviral treatment in outpatients, especially high-risk patients, on disease severity and progression, age, underlying medical conditions, likelihood of influenza, and time since onset of symptoms. If empiric antiviral treatment considered warranted in previously healthy, symptomatic outpatients not considered at increased risk of influenza complications, initiate within 48 hours after illness onset, but some experts state treatment can be considered in such patients even if it has been >48 hours after illness onset.

When treatment of suspected or confirmed acute, uncomplicated seasonal influenza indicated, use age-appropriate antiviral (oral oseltamivir, IV peramivir, inhaled zanamivir). Oseltamivir usually preferred for hospitalized patients and patients with severe or complicated influenza since data are lacking regarding use of IV peramivir or inhaled zanamivir in such patients. Oseltamivir also preferred for treatment of suspected or confirmed influenza in pregnant women.

Consider viral surveillance data available from local and state health departments and CDC when selecting an antiviral for treatment of seasonal influenza. Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve; emergence of oseltamivir-resistant influenza virus may decrease effectiveness of the drug. Although influenza A and B viruses circulating in US during last few years generally have been susceptible to oseltamivir, consult most recent information.

CDC issues recommendations concerning use of antiviral agents for treatment of influenza, and these recommendations are updated as needed during each influenza season. Information regarding influenza surveillance and updated recommendations for treatment of seasonal influenza are available from CDC.

Prevention of Seasonal Influenza A and B Virus Infections

Prevention of illness caused by seasonal influenza A or B viruses in adults, adolescents, and children ≥1 year of age.

Although efficacy not established in immunocompromised patients, oseltamivir has been used for prophylaxis of seasonal influenza in immunocompromised individuals, including cancer patients, BMT recipients, HSCT recipients, and solid organ transplant recipients.

Annual vaccination with seasonal influenza virus vaccine, as recommended by ACIP, is the primary means of preventing seasonal influenza and its severe complications. Prophylaxis with an appropriate antiviral active against circulating influenza strains is considered an adjunct to vaccination for control and prevention of influenza.

Indiscriminate use of antivirals for prophylaxis may promote resistance or reduce availability of antivirals for treatment. Base decisions regarding use of antivirals for prophylaxis of influenza on exposed person's risk for influenza complications, vaccination status, type and duration of contact, recommendations from local or public health authorities, and clinical judgment. Generally use postexposure prophylaxis only if it can be initiated within 48 hours of most recent exposure.

When seasonal influenza viruses are circulating in the community, postexposure prophylaxis with oseltamivir or zanamivir can be considered for certain individuals, including those at high risk of developing influenza complications for whom influenza vaccine is contraindicated, unavailable, or expected to have low efficacy (e.g., immunocompromised individuals). Other possible candidates for antiviral prophylaxis include unvaccinated health care personnel, public health workers, and first responders with unprotected, close-contact exposure to a patient with confirmed, probable, or suspected influenza during the time when the patient was infectious. Also consider antiviral prophylaxis for controlling influenza outbreaks in nursing and long-term care facilities or other closed or semi-closed settings with large numbers of individuals at high risk for influenza complications. In individuals at high risk of influenza complications who receive influenza virus vaccine inactivated, prophylaxis can be considered during the 2 weeks after vaccination to provide protection until an adequate immune response develops.

Consider viral surveillance data available from local and state health departments and CDC when selecting an antiviral for prophylaxis of influenza. The most appropriate antiviral for prevention of influenza is based on the likelihood that the influenza strain is susceptible and the known adverse effects of the drug. Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve; emergence of oseltamivir-resistant influenza virus may decrease effectiveness of the drug.

CDC issues recommendations concerning use of antivirals for prophylaxis of influenza, and these recommendations are updated as needed during each influenza season. Information regarding influenza surveillance and updated recommendations for prevention of seasonal influenza are available from CDC.

Avian Influenza A Virus Infections

Treatment or prevention of infections caused by avian influenza A viruses (e.g., H1N1, H7N3, H7N7, H7N9).

CDC and WHO state that oseltamivir is drug of choice for treatment or prophylaxis of infections caused by highly pathogenic avian influenza A (H5N1); zanamivir is an alternative.

Oseltamivir also drug of choice for treatment of infections caused by avian influenza A (H7N9), especially in hospitalized patients and patients with severe or complicated illness. Because of limited data, zanamivir not recommended for treatment of severe avian influenza A (H7N9) infections, but may be considered in uncomplicated infections. Either oseltamivir or zanamivir can be used for prophylaxis in close contacts of patients with confirmed or probable avian influenza A (H7N9) infection.

Most recent information regarding avian influenza A infections is available at WHO website and CDC website.

Variant Influenza Virus Infections

Treatment of infections cause by variant influenza viruses.

Influenza viruses that circulate in swine are called swine influenza viruses when isolated from swine, but are called variant influenza viruses when isolated from humans. Influenza A (H1N1) variant (H1N1v), influenza A (H1N2) variant (H1N2v), and influenza A (H3N2) variant (H3N2v) infections reported in US. Limited data to date indicate variant influenza viruses are susceptible to neuraminidase inhibitor antivirals (oseltamivir, peramivir, zanamivir).

CDC states management of infections caused by variant influenza viruses is similar to management of seasonal influenza virus infections. Early initiation of oseltamivir recommended by CDC for treatment of hospitalized patients, those with severe and progressive illness, and any high-risk patient with suspected or confirmed variant influenza virus infection. Antiviral treatment with a neuraminidase inhibitor also recommended for outpatients with suspected influenza, including variant influenza virus infection, if individual considered at high risk for influenza complications. Antiviral treatment can be considered for any previously healthy, symptomatic outpatient not at high risk who has confirmed or suspected variant virus infection on the basis of clinical judgment, if treatment can be initiated ≤48 hours after illness onset.

CDC does not recommend antiviral prophylaxis before or after exposure to swine.

Pandemic Influenza

Treatment or prevention of pandemic influenza caused by susceptible strains of influenza virus.

Influenza viruses can cause pandemics, during which rates of illness and death from influenza-related complications can increase dramatically worldwide.

Most recent influenza pandemic occurred during 2009 and was related to a novel influenza A (H1N1) strain, influenza A (H1N1)pdm09. In the US, the pandemic was characterized by a substantial increase in influenza activity that peaked in late October and early November 2009 and returned to seasonal baseline levels by January 2010. During that time, ≥99% of influenza viruses circulating in the US were influenza A (H1N1)pdm09. In August 2010, the WHO declared that the world was in a post-pandemic period; since that time, influenza A (H1N1)pdm09 has become a seasonal influenza virus and continues to circulate with other seasonal viruses.

The spread of the highly pathogenic H5N1 strain of avian influenza A in poultry in Asia and other countries that was first identified in 2003 represents a potential future pandemic threat.

Consult CDC pandemic influenza website (https://www.cdc.gov/flu/pandemic-resources/index.htm) for information on pandemic influenza preparation and response, including use of antiviral agents.