Prescribing Tamiflu

Directions for the Emergency Compounding of an Oral Suspension From Tamiflu Capsules (Final Concentration = 15 mg/mL)1

In November 2006, the FDA approved the addition of directions for the emergency compounding of a Tamiflu oral suspension from Tamiflu Capsules (15 mg/mL) to the label.

These directions are provided for use only during emergency situations when Tamiflu Oral Suspension is not commercially available in a pharmacy.

Commercially manufactured Tamiflu Oral Suspension (12 mg/mL) is the preferred product:

In the event that the commercially manufactured Tamiflu Oral Suspension is not available, the pharmacist may compound a suspension (15 mg/mL) from Tamiflu (oseltamivir phosphate) Capsules 75 mg using either of two vehicles: Cherry Syrup (Humco®)* or Ora-Sweet® SF (sugar-free).† Other vehicles have not been studied.
This compounded suspension should not be used for convenience or when the FDA-approved Tamiflu Oral Suspension is commercially available.

Compounding an oral suspension with this procedure will provide one patient with enough medication for:

Compounding Calculations

First, calculate the Total Volume of oral suspension needed to be compounded and dispensed for each patient. The Total Volume required is determined by the weight of each patient. Refer to Table 3. Please note that the table numbers included in these directions (Tables 3, 4, and 5) correspond to the table numbers in the Tamiflu package insert.

Table 3
Volume of oral suspension (15 mg/mL) needed to be compounded based upon the patient's weight

Body Weight (kg) Body Weight (lbs) Total Volume to Compound
per patient (mL)
≤15 kg ≤33 lbs 30 mL
> 15 to 23 kg > 33 to 51 lbs 40 mL
> 23 to 40 kg > 51 to 88 lbs 50 mL
40 kg or more 88 lbs or more 60 mL

Next, determine the number of capsules and the amount of vehicle (Cherry Syrup or Ora-Sweet SF) that are needed to prepare the Total Volume (calculated from Table 3: 30 mL, 40 mL, 50 mL, or 60 mL) of compounded oral suspension (15 mg/mL). Refer to Table 4.

Table 4
Number of Tamiflu 75 mg Capsules and Amount of Vehicle (Cherry Syrup OR Ora-Sweet SF) Needed to Prepare the Total Volume of a Compounded Oral Suspension (15 mg/mL)

Total Volume of Compounded Oral Suspension needed to be Prepared 30 mL 40 mL 50 mL 60 mL
Required number of Tamiflu 75 mg Capsules 6 capsules (450 mg oseltamivir) 8 capsules (600 mg oseltamivir) 10 capsules (750 mg oseltamivir) 12 capsules (900 mg oseltamivir)
Required volume of vehicle
Cherry Syrup (Humco) OR Ora-Sweet SF (Paddock Laboratories)		 29 mL 38.5 mL 48 mL 57 mL

Consider dispensing the suspension with a graduated oral syringe for measuring small amounts of suspension. If possible, mark or highlight the graduation corresponding to the appropriate dose (2 mL, 3 mL, 4 mL, or 5 mL) on the oral syringe for each patient. The dosing device dispensed with the commercially available Tamiflu for oral suspension should NOT be used with the compounded suspension since the two formulations have different final concentrations.

Compounding Procedure1

Follow the procedure below for compounding the oral suspension (15 mg/mL) from Tamiflu Capsules 75 mg.

  1. Carefully separate the capsule body and cap and transfer the contents of the required number of Tamiflu 75 mg Capsules into a clean mortar.
  2. Triturate the granules to a fine powder.
  3. Slowly add a small amount of vehicle (approximately 1 mL per 6 capsule contents) to the triturated Tamiflu powder and levigate well with the pestle (approximately 2-3 minutes) to a smooth mass. Continue adding very slowly the remainder of one-third (1/3) of the total amount of vehicle in 3 small portions to the mortar while triturating with the pestle until a uniform suspension is achieved each time.
  4. Transfer the suspension to an amber glass or amber polyethyleneterephthalate (PET) bottle. A funnel may be used to eliminate any spillage.
  5. Add the second one-third (1/3) of the vehicle to the mortar, rinse the pestle and mortar by a triturating motion and transfer the vehicle into the bottle.
  6. Repeat the rinsing (Step 5) with the remaining one-third (1/3) of the vehicle.
  7. Close the bottle using a child-resistant cap.
    Shake well to completely dissolve the active drug and to ensure homogeneous distribution of the dissolved drug in the resulting suspension. (Note: The active drug, oseltamivir phosphate, readily dissolves in the specified vehicles. The suspension is caused by some of the inert ingredients of Tamiflu Capsules which are insoluble in these vehicles.)
  8. Put an ancillary label on the bottle indicating "Shake Gently Before Use". Note: This compounded suspension should be gently shaken prior to administration to minimize the tendency for air entrapment, particularly with the Ora-Sweet SF preparation. The need to shake the compounded oral suspension gently prior to administration should be reviewed with the parent or guardian when the suspension is dispensed.
  9. 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.
  10. Place an appropriate expiration date label according to storage conditions (see below).

Storage of Pharmacy-Compounded Suspension1

Refrigeration: Stable for 5 weeks (35 days) when stored in a refrigerator at 2° to 8°C (36° to 46°F). Room Temperature: Stable for five days (5 days) when stored at room temperature, 25°C (77°F). Note: The storage conditions are based on stability studies of compounded oral suspensions, using the above mentioned vehicles, which were placed in amber glass and amber polyethyleneterephthalate (PET) bottles. Stability studies have not been conducted with other vehicles or bottle types.

Place a pharmacy label on the bottle that includes the patient's name, dosing instructions, and drug name and any other required information to be in compliance with all State and Federal Pharmacy Regulations. Refer to Table 5 for the proper dosing instructions.

Note: This compounding procedure results in a 15 mg/mL suspension, which is different from the commercially available Tamiflu for Oral Suspension, which has a concentration of 12 mg/mL.

Dosage for Pharmacy Compound1

Table 5
Dosing Chart for Pharmacy-Compounded Suspension from Tamiflu Capsules 75 mg

Body Weight (kg) Body Weight (lbs) Dose (mg) Volume per Dose 15 mg/mL Treatment Dose (for 5 days) Prophylaxis Dose (for 10 days)
≤15 kg ≤33 lbs 30 mg 2 mL 2 mL two times a day 2 mL once daily
> 15 to 23 kg > 33 to 51 lbs 45 mg 3 mL 3 mL two times a day 3 mL once daily
> 23 to 40 kg > 51 to 88 lbs 60 mg 4 mL 4 mL two times a day 4 mL once daily
>40 kg >88 lbs 75 mg 5 mL 5 mL two times a day 5 mL once daily

Note: 1 teaspoon = 5 mL

Instructions for Oral Dosage Device1

Consider dispensing the suspension with an oral dosing device (a graduated oral syringe or spoon) suitable for measuring small amounts of suspension. If possible, mark or highlight the graduation corresponding to the appropriate dose (2 mL, 3 mL, 4 mL, or 5 mL) on the oral syringe or spoon for each patient.

The dosing device dispensed with the commercially available Tamiflu for Oral Suspension should NOT be used with the compounded suspension since it has a different concentration (concentration = 12 mg/mL) than the suspension prepared through the emergency compounding procedure described here (concentration = 15 mg/mL).

While preparing Tamiflu prescriptions for your patients, please remember:

To ensure the conformity of Tamiflu Oral Suspension prescribed does with oral dispenser to patient/caregiver:

Note:
*Humco® is a registered trademark of Humco Holding Group, Inc.
†Ora-Sweet® SF is a registered trademark of Paddock Laboratories
‡ Data on file

Did you know?

In a clinical study, children aged 1-12 years who received Tamiflu within 48 hours of first flu symptoms recovered up to 26% (36 hours) faster than those who didn't receive Tamiflu.8

Learn more ›

Indications

TAMIFLU is indicated for the treatment of uncomplicated influenza caused by viruses types A and B in patients 1 year and older who have been symptomatic for no more than 2 days.

TAMIFLU is also indicated for the prophylaxis of influenza in patients 1 year and older.

Efficacy of TAMIFLU in patients who begin treatment after 48 hours of symptoms has not been established.

TAMIFLU is not a substitute for early and annual vaccination as recommended by the Centers for Disease Control’s Advisory Committee on Immunization Practices (ACIP).

There is no evidence for efficacy of TAMIFLU in any illness caused by agents other than influenza viruses Types A and B.

Influenza viruses change over time. Emergence of resistance mutations could decrease drug effectiveness. Other factors (for example, changes in viral virulence) might also diminish clinical benefits of antiviral drugs. Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use Tamiflu.

Important Safety Information1

TAMIFLU is contraindicated in patients who have had severe allergic reactions such as anaphylaxis or serious skin reactions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, or erythema multiforme to any component of TAMIFLU.

In postmarketing experience, rare cases of anaphylaxis and serious skin reactions, including toxic epidermal necrolysis, Stevens-Johnson syndrome and erythema multiforme, have been reported with TAMIFLU. Tamiflu should be stopped and appropriate treatment instituted if an allergic-like reaction occurs or is suspected.

Influenza can be associated with a variety of neurologic and behavioral symptoms, which can include events such as hallucinations, delirium and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease. There have been postmarketing reports (mostly from Japan) of delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, in patients with influenza who were receiving TAMIFLU. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made but they appear to be uncommon based on TAMIFLU usage data. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of TAMIFLU to these events has not been established. Patients with influenza should be closely monitored for signs of abnormal behavior. If neuropsychiatric symptoms occur, the risks and benefits of continuing treatment should be evaluated for each patient.

Serious bacterial infections may begin with influenza-like symptoms or may co-exist with or occur as complications during the course of influenza. TAMIFLU has not been shown to prevent such complications.

Treatment efficacy in subjects with chronic cardiac and/or respiratory disease has not been established. No difference in the incidence of complications was observed between the treatment and placebo groups in this population. No information is available regarding treatment of influenza in patients at imminent risk of requiring hospitalization.

Efficacy of TAMIFLU has not been established in immunocompromised patients.

The concurrent use of TAMIFLU with live attenuated influenza vaccine (LAIV) intranasal has not been evaluated. However, because of the potential for interference between these products, LAIV should not be administered within 2 weeks before or 48 hours after administration of TAMIFLU, unless medically indicated.

Adverse events that occurred more frequently in patients treated with TAMIFLU than in patients taking placebo and occurred in ≥2% of patients were (TAMIFLU %, placebo %):

  • Treatment in adults - nausea (10%, 6%), vomiting (9%, 3%), bronchitis (2%, 2%)
  • Treatment in pediatrics - vomiting (15%, 9%), abdominal pain (5%, 4%), epistaxis (3%, 3%), ear disorder (2%, 1%)
  • Prophylaxis of adults - headache (18%, 18%), nausea (7%, 3%), diarrhea (3%, 2%), vomiting (2%, 1%), abdominal pain (2%, 1%)
  • Prophylaxis of pediatrics - vomiting (10%, 2%), abdominal pain (3%, 0%), nausea (4%, 1%)

Please see the TAMIFLU full Prescription Information for complete safety information.


Learn More
View CDC guidelines ›