【药品名称】

  通用名称：扎那米韦 

  商品名称：扎那米韦 

  英文名称：Zanamivir  

\【主要成份】 扎那米韦。

【成 份】

   分子量：C12H20N4O7

【性 状】 本品为白色或灰白色粉末。

【适应症/功能主治】 成年患者和12岁以上的青少年患者，治疗由A型和B型流感病毒引起的流感。

【用法用量】 本品可用于成年患者和12岁以上的青少年患者，每日两次，间隔约12 h。每次10 mg，分两次吸入，或者一次5 mg，连用5 d。随后数日两次的服药时间应尽可能保持一致，剂量间隔12 h(如早晨或傍晚)。

【不良反应】 鼻部症状，头痛，头晕，胃肠功能紊乱，咳嗽，感染，皮疹，支气管炎。罕见过敏反应，心律不齐,支气管痉挛,呼吸困难，面部水肿，惊厥和昏厥。

【禁 忌】 对扎那米韦吸入粉雾剂过敏者禁用。

【注意事项】 1.妊娠和哺乳期妇女慎用。 2.慢性呼吸系统疾病患者用药后发生支气管痉挛的风险较高。 3.哮喘/COPD患者应给予速效性支气管扩张剂。避免用于严重哮喘患者。 4.在使用本药前先吸入支气管扩张剂。如果出现支气管痉挛或呼吸功能减退，应停药。
请仔细阅读说明书并遵医嘱使用。

【儿童用药】 尚不明确。

【老年患者用药】 尚不明确。

【孕妇及哺乳期妇女用药】 孕妇及哺乳期妇女慎用。

【药物相互作用】 鼻内吸入本药前2周内及后48小时内不要接种减毒活流感疫苗。

【药理毒理】 本品通过抑制流感病毒的神经氨酸酶，从而改变了流感病毒在感染细胞内的聚集和释放。体外试验时发现，当药物浓度不断增加时，仍有流感病毒对扎那米韦的敏感性下降。经分析，这与病毒突变引起神经氨酸酶及血细胞凝集素二者或其一的氨基酸发生改变有关。

【药代动力学】 1.口腔吸入本品10 mg后，1～2 h内4%～17%的药物被全身吸收，药物峰浓度范围17～142 ng.ml-1，药时曲线下面积为111～1364 ng.h.ml-1。本品的血浆蛋白结合率低于10%。药物以原形在24 h内由肾排出，尚未检测到其代谢物。血清半衰期为2.5～5.1 h不等。总清除率为2.5～10.9 L.h-1。 2.轻(中)度或重度肾功能不良的患者分别静脉输注扎那米韦4 mg或2 mg后，肾清除率明显下降：正常人总清除率平均为5.3 L.h-1，轻(中)度肾功能不良者为2.7 L.h-1，重度肾功能不良者为0.8 L.h-1。半衰期明显增加：正常人平均为3.1 h，轻(中)度肾功能不良者为4.7 h，重度肾功能不良者为18.5 h。

【贮 藏】 置于阴凉处。

【包 装】 每盒20泡。

【有 效 期】 24 月

Zanamivir

Medically reviewed on Nov 15, 2018

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Aerosol Powder Breath Activated, Inhalation:

Relenza Diskhaler: 5 mg/blister (20 ea) [contains lactose]

· Relenza Diskhaler

· Antiviral Agent

· Neuraminidase Inhibitor

Zanamivir inhibits influenza virus neuraminidase enzymes, potentially altering virus particle aggregation and release.

Inhalation: Systemic: ~4% to 17%

Vd: ~16 L

None

Urine (as unchanged drug); feces (unabsorbed drug)

1-2 hours

Serum: 2.5 to 5.1 hours

Plasma: <10%

Systemic exposure is increased after an IV dose.

Influenza:

Prophylaxis: Prophylaxis of influenza in adults and pediatric patients 5 years and older.

Treatment: Treatment of uncomplicated acute illness caused by influenza A and B virus in adults and pediatric patients 7 years and older who have been symptomatic for no more than 2 days.

The Advisory Committee on Immunization Practices (ACIP) recommends that treatment be considered for the following:

• Persons with severe, complicated or progressive illness

• Hospitalized persons

• Persons at higher risk for influenza complications:

- Children <2 years of age (highest risk in children <6 months of age)

- Adults ≥65 years of age

- Persons with chronic disorders of the pulmonary (including asthma) or cardiovascular systems (except hypertension)

- Persons with chronic metabolic diseases (including diabetes mellitus), hepatic disease, renal dysfunction, hematologic disorders (including sickle cell disease), or immunosuppression (including immunosuppression caused by medications or HIV)

- Persons with neurologic/neuromuscular conditions (including conditions such as spinal cord injuries, seizure disorders, cerebral palsy, stroke, mental retardation, moderate to severe developmental delay, or muscular dystrophy) which may compromise respiratory function, the handling of respiratory secretions, or that can increase the risk of aspiration

- Pregnant or postpartum women (≤2 weeks after delivery)

- Persons <19 years of age on long-term aspirin therapy

- American Indians and Alaskan Natives

- Persons who are morbidly obese (BMI ≥40)

- Residents of nursing homes or other chronic care facilities

• Use may also be considered for previously healthy, nonhigh-risk outpatients with confirmed or suspected influenza based on clinical judgment when treatment can be started within 48 hours of illness onset.

The ACIP recommends that prophylaxis be considered for the following:

• Postexposure prophylaxis may be considered for family or close contacts of suspected or confirmed cases, who are at higher risk of influenza complications, and who have not been vaccinated against the circulating strain at the time of the exposure.

• Postexposure prophylaxis may be considered for unvaccinated healthcare workers who had occupational exposure without protective equipment.

• Pre-exposure prophylaxis should only be used for persons at very high risk of influenza complications who cannot be otherwise protected at times of high risk for exposure.

• Prophylaxis should also be administered to all eligible residents of institutions that house patients at high risk when needed to control outbreaks.

Hypersensitivity to zanamivir or any component of the formulation (contains milk proteins)

Influenza: Oral inhalation:

Prophylaxis (household exposure): Two inhalations (10 mg) once daily for 7 days after last known exposure (CDC 2015)

Prophylaxis (institutional outbreak) (off-label): Two inhalations (10 mg) once daily; continue for ≥2 weeks and until ~7 days after identification of illness onset in the last patient (CDC 2015). Zanamivir is to be used to control institutional outbreaks of influenza when circulating strains are suspected of being resistant to oseltamivir (CDC 2011).

Prophylaxis (community outbreak): Two inhalations (10 mg) once daily; continue until influenza activity in community subsides or immunity obtained from immunization; up to 28 days has been well tolerated (CDC 2011; CDC 2015)

Treatment: Two inhalations (10 mg) twice daily for 5 days. Doses on first day should be separated by at least 2 hours; on subsequent days, doses should be spaced by ~12 hours. Begin within 2 days of signs or symptoms. Longer treatment may be considered for patients who remain severely ill after 5 days (CDC 2015).

Missed dose: If a dose is missed, administer as soon as possible unless it is ≤2 hours before the next scheduled dose. Then, continue administration at the previous schedule; do not administer a double dose.

Refer to adult dosing.

Influenza: Oral inhalation:

Prophylaxis (household exposure): Children ≥5 years and Adolescents: Refer to adult dosing.

Prophylaxis (institutional outbreak) (off-label): Children ≥5 years and Adolescents: Refer to adult dosing.

Prophylaxis (community outbreak): Children ≥5 years (off-label) and Adolescents: Refer to adult dosing.

Treatment: Children ≥7 years and Adolescents: Refer to adult dosing.

Missed dose: If a dose is missed, administer as soon as possible unless it is ≤2 hours before the next scheduled dose. Then, continue administration at the previous schedule; do not administer a double dose.

No dosage adjustment necessary; however, the potential for drug accumulation should be considered.

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Oral inhalation: Must be used with Diskhaler delivery device. The foil blister disk containing zanamivir inhalation powder should not be manipulated, solubilized, or administered via a nebulizer. Patients scheduled to use an inhaled bronchodilator at the same time as zanamivir should use their bronchodilator prior to zanamivir. With the exception of the initial dose when used for treatment, administer at approximately the same time each day.

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not puncture blister until taking a dose using the Diskhaler.

Influenza Virus Vaccine (Live/Attenuated): Antiviral Agents (Influenza A and B) may diminish the therapeutic effect of Influenza Virus Vaccine (Live/Attenuated). Management: Avoid anti-influenza antivirals during the period beginning 48 hours prior to and ending 2 weeks after live influenza virus vaccine administration. Consider therapy modification

Most adverse reactions occurred at a frequency that was less than or equal to the control (lactose vehicle).

>10%:

Central nervous system: Headache (prophylaxis: 13% to 24%; treatment: 2%)

Gastrointestinal: Sore throat (or discomfort; prophylaxis: ≤19%)

Infection: Viral infection (prophylaxis: 3% to 13%)

Respiratory: Nasal signs and symptoms (prophylaxis: 12% to 20%; treatment: 2%), tonsil disease (discomfort or pain; prophylaxis: ≤19%), cough (prophylaxis: 7% to 17%; treatment: ≤2%)

1% to 10%:

Central nervous system: Chills (prophylaxis: ≤9%; treatment: <2%), fatigue (prophylaxis: 5% to 8%; treatment: <2%), malaise (prophylaxis: 5% to 8%; treatment: <2%), dizziness (treatment: 1% to 2%)

Dermatologic: Urticaria (treatment: <2%)

Gastrointestinal: Anorexia (prophylaxis: ≤4%), decreased appetite (prophylaxis: ≤4%), increased appetite (prophylaxis: 2% to 4%), nausea (prophylaxis: 1% to 2%; treatment: ≤3%), diarrhea (2% to 3%), vomiting (1% to 2%), abdominal pain (treatment: <2%)

Neuromuscular & skeletal: Myalgia (prophylaxis: 3% to 8%; treatment: <2%), musculoskeletal pain (prophylaxis: 6%), arthralgia (≤2%), rheumatic disease (prophylaxis: ≤2%)

Respiratory: ENT infection (treatment: 1% to 5%; prophylaxis: 2%), sinusitis (treatment: 3%), bronchitis (treatment: 2%), rhinitis (prophylaxis: 1%)

Miscellaneous: Fever (prophylaxis: ≤9%; treatment: <2%)

<1%, postmarketing and/or case reports: Abnormal behavior, agitation, anxiety, asthma, bronchospasm, cardiac arrhythmia, delusions, dyspnea, facial edema, hallucination, hemorrhage (ear/nose/throat), hypersensitivity reaction (or hypersensitivity-like reaction; includes oropharyngeal edema), impaired consciousness, nightmares, psychiatric disturbance (confusion, delirium, self-injury), seizure, skin rash (including serious cutaneous reactions [eg, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis]), syncope

Concerns related to adverse effects:

• Allergic reactions: Allergic-like reactions, including anaphylaxis, oropharyngeal edema, and serious skin rashes have been reported. Discontinue use and institute appropriate treatment if an allergic reaction occurs.

• Neuropsychiatric events: Rare occurrences of neuropsychiatric events (including confusion, delirium, hallucinations, seizure, and/or self-injury) have been reported, primarily in pediatric patients; may be abrupt in onset. Direct causation is difficult to establish; influenza infection may also be associated with behavioral and neurologic changes.

• Respiratory effects: Bronchospasm, including serious cases and some with fatal outcomes, and decreased lung function have been reported in patients with and without airway disease; discontinue with bronchospasm or decreased lung function. For a patient with an underlying airway disease where a medical decision has been made to use zanamivir, a fast-acting bronchodilator should be made available.

Disease-related concerns:

• Respiratory disease: Not recommended for use in patients with underlying respiratory disease, such as asthma or COPD, due to lack of efficacy in influenza treatment and risk of serious bronchospasm. If zanamivir is prescribed in such patients, closely monitor respiratory function.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Nursing home patients: Effectiveness has not been established for prophylaxis of influenza in nursing home patients (per manufacturer). The CDC recommends zanamivir to be used to control institutional outbreaks of influenza when circulating strains are suspected of being resistant to oseltamivir (refer to current guidelines) (CDC 2011).

Dosage form specific issues:

• Lactose: Powder for oral inhalation contains lactose; use contraindicated in patients allergic to milk proteins.

Other warnings/precautions:

• Administration: Relenza inhalation powder should only be administered via inhalation using the provided Diskhaler delivery device. The commercially available formulation is a lactose containing powder and is not intended to be solubilized or administered via any nebulizer/mechanical ventilator; inappropriate administration has resulted in death.

• Appropriate use: Antiviral treatment should begin within 48 hours of symptom onset. However, the CDC recommends that treatment may still be beneficial and should be started in hospitalized patients with severe, complicated or progressive illness if >48 hours. Treatment should not be delayed while awaiting results of laboratory tests for influenza (CDC 2015). Nonhospitalized persons who are not at high risk for developing severe or complicated illness and who have a mild disease are not likely to benefit if treatment is started >48 hours after symptom onset. Nonhospitalized persons who are already beginning to recover do not need treatment (CDC 2011). Safety and efficacy have not been established in patients with significant underlying medical conditions. Not a substitute for annual flu vaccination; has not been shown to reduce risk of transmission of influenza to others. Patients must be instructed in the use of the delivery system. Consider primary or concomitant bacterial infections. Safety and efficacy of repeated courses have not been established.

An increased risk of adverse neonatal or maternal outcomes has not been observed following use of zanamivir during pregnancy (CDC 60[1] 2011).

Untreated influenza infection is associated with an increased risk of adverse events to the fetus and an increased risk of complications or death to the mother. Although neuraminidase inhibitors are currently recommended for the treatment or prophylaxis of influenza in pregnant women and women up to 2 weeks' postpartum, zanamivir is not the preferred agent (ACOG 2018; CDC 60[1] 2011).

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, diarrhea, nausea, vomiting, rhinitis, pharyngitis, cough, or dizziness. Have patient report immediately to prescriber shortness of breath, difficulty breathing, angina, signs of ear, nose, or throat infection, behavioral changes, confusion, difficulty speaking, tremors, seizures, or hallucinations (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.