Cyanokit (Page 5 of 5)

14.4 Cross-Study Findings

Experience with Dosing Greater than 10 g of Hydroxocobalamin

Across all four uncontrolled studies, 10 patients who did not demonstrate a full response to 5 or 10 g-doses of hydroxocobalamin were treated with more than 10 g of hydroxocobalamin. One of these 10 patients survived with unspecified neurological sequelae.

Effects on Blood Pressure

Initiation of hydroxocobalamin infusion as part of the therapeutic interventions generally resulted in increases in blood pressure and variable changes in heart rate (often normalization).

Survival of Patients Presenting in Cardiac Arrest

Of the 245 patients across all four studies, 68 (28%) presented in cardiac arrest. While blood pressure and heart rate may have been restored in many of these 68 patients, only five (7%) survived.

16 HOW SUPPLIED/STORAGE AND HANDLING

Each CYANOKIT carton (NDC 50633-310-11) consists of the following:

• One 250 mL glass vial, containing lyophilized hydroxocobalamin for injection, 5 g
• One sterile transfer spike
• One sterile intravenous infusion set
• One quick use reference guide
• One package insert

Diluent is not included.

Storage

Lyophilized form

Store at 25°C (77°F); excursions permitted to 15-30°C (59 to 86°F) [see USP Controlled Room Temperature].

CYANOKIT may be exposed during short periods to the temperature variations of usual transport (15 days submitted to temperatures ranging from 5 to 40°C (41 to 104°F), transport in the desert (4 days submitted to temperatures ranging from 5 to 60°C (41 to 140°F)) and freezing/defrosting cycles (15 days submitted to temperatures ranging from -20 to 40°C (-4 to 104°F)).

Reconstituted solution

Store up to 6 hours at a temperature not exceeding 40ºC (104°F). Do not freeze. Discard any unused portion after 6 hours.

17 PATIENT COUNSELING INFORMATION

CYANOKIT is indicated for cyanide poisoning and in this setting, patients will likely be unresponsive or may have difficulty in comprehending counseling information.

Erythema and Chromaturia

Advise patients that skin redness may last up to 2 weeks and urine coloration may last for up to 5 weeks after administration of CYANOKIT. While it is not known if the skin redness predisposes to photosensitivity, patients should be advised to avoid direct sun while their skin remains discolored.

Rash

Inform patients that an acneiform rash may appear anywhere from 7 to 28 days following hydroxocobalamin treatment. This rash will usually resolve without treatment within a few weeks.

Renal Function Monitoring

Advise patients that renal function will be monitored for 7 days following treatment with CYANOKIT or, in the event of renal impairment, until renal function returns to normal.

Pregnancy

Advise pregnant women that maternal cyanide poisoning results in fetal cyanide poisoning. Treatment for cyanide poisoning may be lifesaving for both the pregnant woman and fetus. Advise females of reproductive potential to notify their provider if they were pregnant during therapy with CYANOKIT [see USE IN SPECIFIC POPULATIONS (8.1)].

Lactation

Advise women that breastfeeding is not recommended during treatment with CYANOKIT [see USE IN SPECIFIC POPULATIONS (8.2)].

This Patient Information has been approved by the U.S. Food and Drug Administration.	Revised: 05/2021
Patient Information CYANOKIT (hydroxocobalamin for injection) for intravenous infusion
What is CYANOKIT? CYANOKIT is prescription medicine used for the treatment of known or suspected cyanide poisoning. Cyanide is a chemical poison. Cyanide poisoning can happen from:breathing smoke from household and industrial firesbreathing or swallowing cyanidehaving your skin exposed to cyanideThe effectiveness of CYANOKIT was based on a study in animals, because intentionally exposing humans to cyanide is not ethical. The safety of CYANOKIT was studied in animals and healthy people and derived from experience in patients exposed to cyanide.It is not known if CYANOKIT is safe and effective in children.Cyanide poisoning is a life-threatening condition because cyanide stops your body from being able to use oxygen. You can die if your body does not have enough oxygen.
Tell your healthcare provider if you: have had an allergic reaction to hydroxocobalamin or cyanocobalamin are pregnant or think you may have been pregnant during treatment with CYANOKIT. CYANOKIT may harm your unborn baby. However, treatment for cyanide poisoning may save your life and the life of your unborn baby. are breastfeeding. Breastfeeding is not recommended during treatment with CYANOKIT. Talk to your healthcare provider about the best way to feed your baby during this time.Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
How is CYANOKIT given? Your healthcare provider will give you CYANOKIT through a vein by intravenous (IV) infusion over 15 minutes. A second dose of CYANOKIT may be given to you if needed.
What should I avoid after I receive CYANOKIT? CYANOKIT may cause red colored skin. Skin redness is common during treatment with CYANOKIT and may last up to 2 weeks after treatment with CYANOKIT. You should avoid sunlight while your skin is red.
What are the possible side effects of CYANOKIT? CYANOKIT may cause serious side effects, including: Allergic reactions. Signs and symptoms of a serious allergic reaction include chest tightness, trouble breathing, swelling, hives, itching, and rash. Seek emergency help if you experience signs and/or symptoms of an allergic reaction. Kidney problems. CYANOKIT can cause kidney problems, including kidney failure. Tell your healthcare provider if you develop crystals in your urine. Your healthcare provider will monitor your kidney function for 7 days after treatment with CYANOKIT, or longer if needed. Increased blood pressure. Increased blood pressure is a common but serious side effect during treatment with CYANOKIT. Your healthcare provider will monitor your blood pressure during treatment with CYANOKIT. The most common side effects of CYANOKIT include:
red colored urine. Red colored urine redness may last up to 5 weeks after treatment with CYANOKIT. acne-like rash. Acne-like rash may appear 7 to 28 daysafter treatment with CYANOKIT. This rash usually goes away without any treatment.	nausea headache reactions at the site of infusion
These are not all the side effects with CYANOKIT.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of CYANOKIT. This Patient Information leaflet summarizes the most important information about CYANOKIT. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about CYANOKIT that is written for health professionals.
What are the ingredients in CYANOKIT? Active ingredient: hydroxocobalaminManufactured by: Merck Santé s.a.s., Semoy, FranceDistributed by BTG International Inc. West Conshohocken, PA 194281-877-377-3784BTG and the BTG roundel logo are registered trademarks of BTG International Ltd.For more information, go to www.CYANOKIT.com. 180_US_20211_NO

Principal Display Panel — 5 g OUTER CARTON

NDC 50633-310-11

CYANOKIT®

(hydroxocobalamin for injection)

5 g per vial

For Intravenous Use

To be reconstituted with 200 mL of 0.9% Sodium Chloride Injection

Diluent Not Included

Kit Contents:

1 Vial, containing Hydroxocobalamin for injection, 5 g

1 Intravenous administration set

1 Transfer spike

1 Quick Use Reference guide

1 Package Insert

BTG

Principal Display Panel — 250 mL Vial Label

CYANOKIT®

(hydroxocobalamin for injection)

5 g per vial

For Intravenous Use

To be reconstituted with 200 mL of 0.9% Sodium Chloride Injection

Diluent Not Included

Rx Only

Manufactured byMerck Sante s.a.s.

Semoy, France

Distributed by

BTG International Inc.

West Conshohocken, PA 19428

1-877-377-3784

BTG

CYANOKIT hydroxocobalamin injection, powder, lyophilized, for solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:50633-310 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Hydroxocobalamin (Hydroxocobalamin) Hydroxocobalamin 5 g in 250 mL

Inactive Ingredients Ingredient Name Strength hydrochloric acid

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:50633-310-11 1 VIAL, GLASS in 1 CARTON contains a VIAL, GLASS 1 250 mL in 1 VIAL, GLASS This package is contained within the CARTON (50633-310-11)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022041 12/15/2021

Labeler — BTG INTERNATIONAL INC. (617382395)

Establishment
Name	Address	ID/FEI	Operations
BTG INTERNATIONAL INC.		617382395	LABEL (50633-310)

Establishment
Name	Address	ID/FEI	Operations
Merck Santé s.a.s		384668112	MANUFACTURE (50633-310), PACK (50633-310), LABEL (50633-310), ANALYSIS (50633-310)

Revised: 05/2021 BTG INTERNATIONAL INC.