Oseltamivirdosage

2 DOSAGE & ADMINISTRATION Treatment of influenza

Adults and adolescents (13 years and older): 75 mg twice daily for 5 days

Pediatric patients 1 to 12 years of age: Based on weight twice daily for 5 days

Pediatric patients 2 weeks to less than 1 year of age: 3 mg/kg twice daily for 5 days

Renally impaired adult patients (creatinine clearance >30 to 60 mL/min): Reduce to 30 mg twice daily for 5 days

Renally impaired adult patients (creatinine clearance >10 to 30 mL/min): Reduce to 30 mg once daily for 5 days

ESRD patients on hemodialysis: Reduce to 30 mg immediately and then 30 mg after every hemodialysis cycle. Treatment duration not to exceed 5 days

ESRD patients on CAPD: Reduce to a single 30 mg dose immediately Prophylaxis of influenza

Adults and adolescents (13 years and older): 75 mg once daily for at least 10 days - Community outbreak: 75 mg once daily for up to 6 weeks

Pediatric patients 1 to 12 years of age: Based on weight once daily for 10 days - Community outbreak: Based on weight once daily for up to 6 weeks

Renally impaired adult patients (creatinine clearance >30 to 60 mL/min): Reduce to 30 mg once daily

Renally impaired adult patients (creatinine clearance >10 to 30 mL/min): Reduce to 30 mg once every other day

ESRD patients on hemodialysis: Reduce to 30 mg immediately and then 30 mg after alternate hemodialysis cycles for the recommended duration of prophylaxis

ESRD patients on CAPD: Reduce to 30 mg immediately and then 30 mg once weekly for the recommended duration of prophylaxis

2.1 Dosage and

Administration Overview Administer oseltamivir phosphate capsules for the treatment of influenza in patients 2 weeks of age or older or for prophylaxis of influenza in patients 1 year and older using:

Oseltamivir phosphate capsules The capsules may be taken with or without food; however, tolerability may be enhanced if oseltamivir phosphate capsule are taken with food. Adjust the oseltamivir phosphate capsules dosage in patients with moderate or severe renal impairment. For patients who cannot swallow capsules, oseltamivir phosphate for oral suspension is the preferred formulation. When oseltamivir phosphate for oral suspension is not available from wholesaler or the manufacturer, oseltamivir phosphate capsules may be opened and mixed with sweetened liquids such as regular or sugar-free chocolate syrup, corn syrup, caramel topping, or light brown sugar (dissolved in water). During emergency situations and when neither the oral suspension or the age-appropriate strengths of oseltamivir phosphate capsules to mix with sweetened liquids are available, then a pharmacist may prepare an emergency supply of oral suspension from oseltamivir phosphate 75 mg capsules.

2.2 Recommended

Dosage for Treatment of Influenza Initiate treatment with oseltamivir phosphate capsules within 48 hours of influenza symptom onset. Adults and Adolescents (13 years of age and older) The recommended oral dosage of oseltamivir phosphate capsules for treatment of influenza in adults and adolescents 13 years and older is 75 mg twice daily (one 75 mg capsule twice daily) for 5 days. Pediatric Patients (2 weeks of age through 12 years of age) Table 1 displays the recommended oral dosage of oseltamivir phosphate capsules for treatment of influenza in pediatric patients 2 weeks of age through 12 years of age and provides information about prescribing the capsule or the formulation for oral suspension.

2.3 Recommended

Dosage for Prophylaxis of Influenza Initiate post-exposure prophylaxis with oseltamivir phosphate capsules within 48 hours following close contact with an infected individual. Initiate seasonal prophylaxis with oseltamivir phosphate capsules during a community outbreak. Adults and Adolescents (13 years of age and older) The recommended dosage of oseltamivir phosphate capsules for prophylaxis of influenza in adults and adolescents 13 years and older is 75 mg orally once daily (one 75 mg capsule once daily) for at least 10 days following close contact with an infected individual and up to 6 weeks during a community outbreak. In immunocompromised patients, oseltamivir phosphate capsules may be continued for up to 12 weeks. The duration of protection lasts for as long as oseltamivir phosphate capsules dosing is continued. Pediatric Patients (1 year to 12 years of age) Table 1 displays the recommended oral dosage of oseltamivir phosphate for prophylaxis of influenza in pediatric patients 1 year to 12 years of age based on body weight and provides information about prescribing the capsule or the formulation for oral suspension. Prophylaxis in pediatric patients is recommended for 10 days following close contact with an infected individual and up to 6 weeks during a community outbreak. Table 1 Oseltamivir Phosphate Dosage Recommendations in Pediatric Patients for Treatment and Prophylaxis of Influenza Weight Treatment Dosage for 5 days Prophylaxis Dosage for 10 days* Volume of Oral Suspension (6 mg/mL) for each Dose † Number of Bottles of Oral Suspension to Dispense Number of Capsules to Dispense (Strength) ‡ Patients from 2 Weeks to less than 1 Year of Age Any weight 3 mg/kg twice daily Not applicable 0.5 mL/kg § 1 bottle Not applicable Patients 1 to 12 Years of Age Based on Body Weight 15 kg or less 30 mg twice daily 30 mg once daily 5 mL 1 bottle 10 Capsules (30 mg) 15.1 kg to 23 kg 45 mg twice daily 45 mg once daily 7.5 mL 2 bottles 10 Capsules (45 mg) 23.1 kg to 40 kg 60 mg twice daily 60 mg once daily 10 mL 2 bottles 20 Capsules (30 mg) 40.1 kg or more 75 mg twice daily 75 mg once daily 12.5 mL 3 bottles 10 Capsules (75 mg) * The recommended duration for post-exposure prophylaxis is 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients). The amount supplied (e.g., number of bottles or capsules) for seasonal prophylaxis may be greater than for post-exposure prophylaxis. † Use an oral dosing dispensing device that measures the appropriate volume in mL with the oral suspension. ‡ Oseltamivir phosphate capsules for oral suspension is the preferred formulation for patients who cannot swallow capsules. § For patients less than 1 year of age, provide an appropriate dosing device that can accurately measure and administer small volumes.

2.4 Dosage in

Patients with Renal Impairment Table 2 displays the dosage recommendations for the treatment and prophylaxis of influenza in adults with various stages of renal impairment (estimated creatinine clearance of less than or equal to 90 mL per minute). Dosage modifications are recommended in adults with an estimated creatinine clearance less than or equal to 60 mL per minute. Table 2 Recommended Dosage Modifications for Treatment and Prophylaxis of Influenza in Adults with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis Renal Impairment (Creatinine Clearance) Recommended Treatment Regimen* Recommended Prophylaxis Regimen*† Mild (>60-90 mL/minute) 75 mg twice daily for 5 days 75 mg once daily Moderate (>30-60 mL/minute) 30 mg twice daily for 5 days 30 mg once daily Severe (>10-30 mL/minute) 30 mg once daily for 5 days 30 mg every other day ESRD Patients on Hemodialysis (≤ 10 mL/minute) 30 mg immediately and then 30 mg after every hemodialysis cycle (treatment duration not to exceed 5 days) 30 mg immediately and then 30 mg after alternate hemodialysis cycles ESRD Patients on Continuous Ambulatory Peritoneal Dialysis‡ (≤10 mL/minute) A single 30 mg dose administered immediately 30 mg immediately and then 30 mg once weekly ESRD Patients not on Dialysis Oseltamivir phosphateis not recommended Oseltamivir phosphate is not recommended * Capsules or oral suspension can be used for 30 mg dosing. † The recommended duration for post-exposure prophylaxis is at least 10 days and the recommended duration for community outbreak (seasonal/pre-exposure) prophylaxis is up to 6 weeks (or up to 12 weeks in immunocompromised patients). ‡ Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.

2.6 Emergency

Preparation of Oral Suspension from 75 mg Oseltamivir Phosphate Capsules The following directions are provided for use only during emergency situations and when FDA-approved, commercially manufactured oseltamivir phosphate for oral suspension is not available from wholesalers or the manufacturer. The following emergency preparation instructions will provide one patient with enough oseltamivir phosphate capsules for a 5-day course of treatment of influenza or a 10-day course of prophylaxis of influenza: Step #1: Determine the dosage of oseltamivir phosphate capsules for the patient then determine the total volume of oral suspension needed to be prepared (see Table 3). Table 3 Emergency Preparation: Volume of Prepared Oral Suspension (6 mg per mL) Based Upon Oseltamivir Phosphate Capsules Dose Oseltamivir Phosphate Capsules Dose* Total Volume to Prepare per Patient 15 mg or less 37.5 mL 30 mg 75 mL 45 mg 100 mL 60 mg 125 mL 75 mg 150 mL * If the oseltamivir phosphate capsules dose is between the doses listed, use the greater listed dose to determine the total volume of prepared oral suspension. Step #2: Preparation must be performed with only one of the following vehicles (other vehicles have not been studied): Cherry Syrup (Humco®), Ora-Sweet® SF (sugar-free) (Paddock Laboratories), or simple syrup. Determine the number of capsules and the amount of water and vehicle needed to prepare the total volume (see Table 3) of prepared oral suspension (6 mg per mL) for a complete treatment or prophylaxis course (see Table 4). Table 4 Emergency Preparation: Number of Oseltamivir Phosphate 75 mg Capsules and Amount of Water and Vehicle Needed to Prepare the Total Volume of a Prepared Oral Suspension (6 mg per mL) Total Volume of Prepared Oral Suspension 37.5 mL 75 mL 100 mL 125 mL 150 mL Number of Oseltamivir Phosphate 75 mg Capsules (Total Strength)* 3 (225 mg) 6 (450 mg) 8 (600 mg) 10 (750 mg) 12 (900 mg) Amount of Water 2.5 mL 5 mL 7 mL 8 mL 10 mL Volume of Vehicle Cherry Syrup (Humco ® ) OR Ora-Sweet ® SF (Paddock Laboratories) OR simple syrup 34.5 mL 69 mL 91 mL 115 mL 137 mL *Includes overage to ensure all doses can be delivered Step #3: Follow the instructions below for preparing the 75 mg oseltamivir phosphate capsules to produce the oral suspension (6 mg per mL): a. Place the specified amount of water into a polyethyleneterephthalate (PET) or glass bottle (see Table 4). Constitution in other bottle types is not recommended because there is no stability data with other bottle types. b. Carefully separate the capsule body and cap and pour the contents of the required number of oseltamivir phosphate 75 mg capsules into the PET or glass bottle. c. Gently swirl the suspension to ensure adequate wetting of the oseltamivir phosphate powder for at least 2 minutes. d. Slowly add the specified amount of vehicle to the bottle. e. Close the bottle using a child-resistant cap and shake well for 30 seconds to completely dissolve the active drug and to ensure homogeneous distribution of the dissolved drug in the resulting suspension. The active drug, oseltamivir phosphate, readily dissolves in the specified vehicles. The suspension is caused by inert ingredients of oseltamivir phosphate capsules which are insoluble in these vehicles. f. Put an ancillary label on the bottle indicating “Shake Well Before Use.” g. Instruct the parent or caregiver that any unused suspension remaining in the bottle following completion of therapy must be discarded by either affixing an ancillary label to the bottle or adding a statement to the pharmacy label instructions. h. Place a pharmacy label on the bottle that includes the patient’s name, dosing instructions, drug name and any other required information to be in compliance with all State and Federal Pharmacy Regulations. Place an appropriate expiration date on the label according to storage conditions below. i. Include the recommended dosage on the pharmacy label as per Tables 1 and 2. j. Store the prepared oral suspension in glass or PET bottles either:

In a refrigerator [2o to 8oC (36° to 46°F)]: Stable for 5 weeks when stored in a refrigerator.

At room temperature [25oC (77°F)]: Stable for 5 days when stored at room temperature.