oseltamivir (Rx)

1-10%

Abdominal pain

Conjunctivitis

Ear disorder

Epistaxis

Insomnia

Nausea

Vomiting

Vertigo

<1%

Aggravation of diabetes

Anemia

Arrhythmia

Confusion

Delirium

Hemorrhagic colitis

Hepatitis

Humerus fracture

Peritonsillar abscess

Pneumonia

Pseudomembranous colitis

Pyrexia

Rash

Seizure

Transaminases increased

Toxic epidermal necrolysis

Unstable angina

Swelling of face or tongue

Postmarketing Reports

Hypothermia

Diaper rash (2 weeks to <1 year of age)

Dermatitis

Urticaria

Eczema

Stevens-Johnson Syndrome

Erythema multiforme

Gastrointestinal bleeding

Abnormal liver function tests

Contraindications

Hypersensitivity

Cautions

Use caution in patients with chronic cardiac disease, severre hepatic impairment, renal imapairment, respiratory disease

Delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, reported in patients with influenza who were receiving therapy; relationship to therapy not established

Most effective when used within 24-48 hr of onset of symptoms

Safety and efficacy for prophylaxis of influenza not established for <1year of age

Oral suspension should be mixed prior to dispensing

Safety and efficacy in immunocompromised patients not established

Therapy is not a substitute for influenza virus vaccine

Serious skin/hypersensitivity reactions such as Stevens-Johnson Syndrome, toxic epidermal necrolysis and erythema multiforme; discontinue therapy and initiate appropriate treatment if allergic-like reactions occur or are suspected

Prescribers should be alert to potential for secondary bacterial infections and treat them as appropriate

Neuropsychiatric events

• Delirium and abnormal behavior leading to injury, including fatalities, reported postmarketing in patients with influenza receiving oseltamivir
• Because these events were reported voluntarily during clinical practice, frequency cannot be estimated, but occurrence is uncommon
• Reported primarily among pediatric patients and often had an abrupt onset and rapid resolution
• Unable to establish causality between these events and oseltamivir
• These events may occur in the setting of encephalitis or encephalopathy, but can occur without obvious severe disease; closely monitor oseltamivir-treated patients with influenza for signs of abnormal behavior

Oral suspension and hereditary fructose intolerance

• Fructose can be harmful to patients with hereditary fructose intolerance
• One dose of 75 mg oral suspension delivers 2 g of sorbitol; this is above the daily maximum limit of sorbitol for patients with hereditary fructose intolerance, and may cause dyspepsia and diarrhea

Pregnancy

There are no adequate and well–controlled studies in pregnant women to inform a drug–associated risk of adverse developmental outcomes; available published epidemiological data suggest that the drug, taken in any trimester, is not associated with an increased risk of birth defects; however, these studies individually are limited by small sample sizes, use of different comparison groups, and some lacked information on dose, which preclude a definitive assessment of the risk

Pregnant women are at higher risk of severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes including maternal death, still births, birth defects, preterm delivery, low birth weight and small for gestational age

Animal data

• In animal reproduction studies, no adverse developmental effects were observed at clinically relevant exposures

Lactation

Based on limited published data, have shown the drug to be present in human milk at low levels considered unlikely to lead to toxicity in the breastfed infant; postmarketing experience has not reported any information to suggest serious adverse effects to drug exposure via breast milk in infants; it is not known if drug affects human milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Inhibits viral neuraminidases; stops release of virus from cells and prevents virus from crossing mucous lining of respiratory tract

Absorption

Bioavailability: 75%

Peak plasma time: 2.5-6 hr

Distribution

Protein bound: 3% (oseltamivir carboxylase); 42% (oseltamivir)

Vd: 23-26 L

Elimination

Half-life: 1-3hr (oseltamivir); 6-10 hr (oseltamivir carboxylate)

Excretion: Feces; urine (>90% as oseltamivir carboxylate)

Oral Administration

Tablets and oral suspension may be take with or without food

Tolerability may be enhanced if taken with food

Emergency Preparation of Oral Suspension from 75 mg Capsules

Extemporaneously prepared oral suspension from capsules may be needed if commercially available oral suspension unavailable

Instructions below are for 100 mL of 6 mg/mL suspension

1. Place 7 mL of distilled water into a polyethyleneterephthalate (PET) or glass bottle

2. Empty content of eight 75-mg capsules (ie, 600 mg) into bottle

3. Gently swirl the suspension to ensure adequate wetting of the powder for at least 2 minutes

4. Slowly add 91 mL of Ora-Sweet, cherry syrup, or simple syrup

5. Close bottle and shake well for about 30 minutesInstruct patient to shake well before use

Stable for 5 days at room temperature or 5 weeks refrigerated at 2-8°C (36-46°F)