Ruconest

Recommended Dosing

• Initiate treatment with RUCONEST under the supervision of a qualified healthcare professional experienced in the treatment of HAE.
• Appropriately trained patients may self-administer upon recognition of an HAE attack.
• The recommended dose of RUCONEST is 50 U per kg with a maximum of 4200 U to be administered as a slow intravenous injection over approximately 5 minutes.

If the attack symptoms persist, an additional (second) dose can be administered at the recommended dose level. Do not exceed 4200 U per dose. No more than two doses should be administered within a 24 hour period.

Preparation and Handling

• Store RUCONEST in the original carton and protect from light prior to reconstitution.
• Do not use after expiration date on the product vial label.
• Water for Injection is not included in the RUCONEST package.
• Use aseptic technique to reconstitute, mix the solution, and to combine the reconstituted solution from more than one vial ( see Reconstitution [ 2.3] and Administration [ 2.4]).
• Do not mix or administer RUCONEST with other medicinal products or solutions.
• Discard all partially used vials after treatment.

Reconstitution

Each package contains one single-use vial of RUCONEST. To reconstitute, the following are also required:

• Sterile Water for Injection (diluent) - At least 14 mL per vial of RUCONEST requiring reconstitution.
• Alcohol swab
• Syringe
• Commercially available vial adapter with vented vial spike and syringe luer lock or large bore needle. If using a syringe with vial adapter, use a new vial adapter for each vial of RUCONEST and diluent.

The procedures below are provided as general guidelines for the reconstitution and administration of RUCONEST.

• Ensure that the RUCONEST vial and diluent vial are at room temperature.
• Remove the flip caps from the RUCONEST and diluent vials. Treat the vial stoppers with the alcohol swab and allow to dry.
• Using the syringe/needle or syringe/vial adapter, withdraw 14 mL of sterile water for injection from the diluent vial.
• Remove the syringe and transfer the diluent to the RUCONEST vial. Add the diluent slowly to avoid forceful impact on the powder. Swirl the vial slowly to mix and avoid foaming.
• Repeat this procedure using another 14 mL of diluent and a second vial of RUCONEST.
• If the same patient is to receive more than one vial, the contents of multiple vials may be pooled into a single administration device (i.e., syringe).
• Inspect RUCONEST visually for particulate matter and discoloration after reconstitution and prior to administration. The reconstituted solution should be colorless, clear, and free from visible particles. Do not use if the solution is cloudy, colored, or contains particulates.
• RUCONEST vial is for single-use only.
• Use the reconstituted product immediately, or within 8 hours stored at 2°C - 8°C (36°F - 46°F). Discard partially used vials.
• Do not freeze the reconstituted solution.

Administration

• Do not mix RUCONEST with other medicinal products. Administer RUCONEST by a separate infusion line.
• Use aseptic technique when administering RUCONEST.
• Follow recommended venipuncture guidelines for initiating intravenous therapy.
• Administer RUCONEST by slow intravenous injection over approximately 5 minutes.
• For self-administration, provide the patient with instructions and training for intravenous injection outside of a clinic setting so patients may self-administer RUCONEST upon recognition of symptoms of an HAE attack ( see Patient Counseling Information [ 17]).
• After administration, immediately discard any unused product and all used disposable supplies in accordance with local requirements.

Pregnancy

Pregnancy Category B. Studies performed in rats and rabbits at doses up to 12.5 times the human dose of 50 U/kg could not exclude an effect on embryofetal development. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, RUCONEST should only be used during pregnancy if clearly needed.

Labor and Delivery

The safety and efficacy of RUCONEST administration prior to or during labor and delivery have not been established. Use only if clearly needed.

Nursing Mothers

It is not known if RUCONEST is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when RUCONEST is administered to a nursing woman.

Pediatric Use

The safety and efficacy of RUCONEST were evaluated in 17 adolescent patients (13-17 years of age) treated for 52 HAE attacks.  Eight out of 17 (47%) adolescent patients experienced adverse reactions. No serious adverse reactions were reported in these patients.  The most common reactions (occurring in at least 2 patients) were: abdominal pain, headache, and oropharyngeal pain.

Geriatric Use

The clinical studies of RUCONEST included seven patients older than 65 years. The clinical studies included an insufficient number of patients in this age group to determine if they respond differently from younger patients.

Hypersensitivity

Severe hypersensitivity reactions may occur [see Patient Counseling Information (17)].   The signs and symptoms of hypersensitivity reactions may include hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and/or anaphylaxis during or after injection of RUCONEST. Should symptoms occur, discontinue RUCONEST and institute appropriate treatment.  Because hypersensitivity reactions may have symptoms similar to HAE attacks, treatment methods should be carefully considered. 

Thromboembolic Events

Serious arterial and venous thromboembolic (TE) events have been reported at the recommended dose of plasma derived C1 esterase inhibitor products in patients with risk factors.  Risk factors may include the presence of an indwelling venous catheter/access device, prior history of thrombosis, underlying atherosclerosis, use of oral contraceptives or certain androgens, morbid obesity, and immobility.  Monitor patients with known risk factors for TE events during and after RUCONEST administration.