AEGiS-ATN: Ritonavir Capsule Manufacturing Problems Will Require Switch to Liquid Formulation

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

Ritonavir Capsule Manufacturing Problems Will Require Switch to Liquid Formulation

AIDS TREATMENT NEWS Issue #300, August 7, 1998
John S. James

On June 27 Abbott held a conference call to inform the AIDS community that a manufacturing problem has halted production of ritonavir (Norvir(TM)) capsules. The supply on hand will start to run out in August (some pharmacies may still have capsules later), and then patients will need to switch to the liquid formulation of ritonavir, which remains available (or switch to a different treatment regimen). No one knows when the manufacturing of the capsules can be resumed.

The problem is that the ritonavir in the capsules started to crystallize. While the crystal is still the same chemical, it does not dissolve as fast, and therefore would be absorbed differently. Abbott discovered the problem during routine quality-assurance tests.

According to Abbott, all the capsules which have been shipped to pharmacies and distributors are OK.

Switching to Ritonavir (Norvir) Liquid

The liquid formulation (sometimes called "Norvir oral solution") provides the same drug as the capsules. Therefore the switch should not require a doctor's visit, although the pharmacist may have to call the doctor to get permission to substitute the different formulation when the prescription for the capsules needs to be refilled and the pharmacy has no more capsules in stock. It is likely that most people will change to the liquid formulation, since switching to a different protease inhibitor, or other HIV treatment, involves more difficult medical decisions.

The price of the drug should be about the same for either formulation.

The main disadvantage of the liquid is its very bad taste. The package insert suggests, "Patients may improve the taste of Norvir oral solution by mixing with chocolate milk, Ensure(R), or Advera(R) within one hour of dosing."

Until now the oral solution has been used mostly for children, so that they could be given the correct dose for their body size. Since the bad taste is a serious obstacle in getting children to take the drug, pediatricians have had the most experience in masking the taste. One suggestion is to take a spoonful of chocolate syrup before the dose, and then again after the dose. A popsicle may help reduce the bad taste by chilling the taste buds. Another suggestion is to use a straw to deliver the drug to the back of the throat. (We thank Search for a Cure for this information, which it learned from pediatricians who use the liquid formulation.)

Note that the oral solution (unlike the capsules) should *not* be refrigerated by the patient. According to the package insert:

"Recommended storage: Store Norvir oral solution at room temperature 68 degrees F to 77 degrees F (20 degrees C to 25 degrees C). Do not refrigerate. Shake well before each use. Use within 30 days from dispensing.

"Product should be stored and dispensed in the original container. Avoid exposure to excessive heat. Keep cap tightly closed."

What if the temperature in one's home goes above 77 degrees? A preliminary recommendation (which Search for a Cure heard from Abbott) is that if the temperature gets hotter than 86 degrees, put the drug in the refrigerator. But if any official recommendation is issued in the future, it is the one that should be followed.

The Norvir Web site (http://www.norvir.com) has measuring instructions:

"Each Norvir capsule contains 100 mg of active drug, and each mL of Norvir liquid contains 80 mg of active drug. For your convenience, Norvir liquid comes with a dosing cup that provides markings indicating the amount of liquid to be taken for the two most common doses. It is important to measure the correct dose of Norvir; therefore, the dosing cup has been specially designed to provide the right dose of Norvir liquid. This cup should be used to measure a dose. Please be advised that when measuring a dose, the cup should be placed on a flat surface at eye level, and the cup filled with Norvir liquid to the line showing the appropriate dose. You should wash the dosing cup with soap and warm water as soon as possible. The dosing cup is not dishwasher safe.

"The following conversion equation may be helpful:

"6 Norvir capsules (100 mg each) = 7.5 mL of Norvir liquid (1 1/2 teaspoons)

"4 Norvir capsules (100 mg each) = 5 mL of Norvir liquid (1 teaspoon)."

For More Information

For more information about the ritonavir capsule shortage and the oral solution, call your physician. Or check Abbott's Web site at http://www.norvir.com, or call the Norvir information hotline, 800-637-2400, 7:00 a.m. to 7:00 p.m. Central time.

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