Givosiran

What is Givosiran?

Givosiran (GIVLAARI) is an aminolevulinate synthase 1-directed small interfering RNA used for the treatment of adults with acute hepatic porphyria.

What are the uses of this medicine?

This medicine is used for the treatment of adults with acute hepatic porphyria (AHP).

How does this medicine work?

• Givosiran is a double-stranded small interfering RNA that causes degradation of aminolevulinate synthase 1 (ALAS1) mRNA in hepatocytes through RNA interference, reducing the elevated levels of liver ALAS1 mRNA.
• This leads to reduced circulating levels of neurotoxic intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG), factors associated with attacks and other disease manifestations of AHP.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• known severe hypersensitivity to givosiran.
• Reactions have included anaphylaxis.

What drug interactions can this medicine cause?

• Avoid concomitant use of GIVLAARI with CYP1A2 or CYP2D6 substrates, for which minimal concentration changes may lead to serious or life-threatening toxicities.
• If concomitant use is unavoidable, decrease the CYP1A2 or CYP2D6 substrate dosage in accordance with approved product labeling.

Is this medicine FDA approved?

• It was approved for use in the United States in 2019.

How should this medicine be used?

Recommended Dosage

• The recommended dose of GIVLAARI is 2.5 mg/kg administered via subcutaneous injection once monthly.
• Dosing is based on actual body weight.

Dose Modification for Adverse Reactions

• In patients with severe or clinically significant transaminase elevations, who have dose interruption and subsequent improvement, reduce the dose to 1.25 mg/kg once monthly.

Administration

• GIVLAARI is intended for subcutaneous use by a healthcare professional only.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
• GIVLAARI is supplied in a single-dose vial, as a ready-to-use solution that does not require additional reconstitution or dilution prior to administration.
• Use aseptic technique.
• Calculate the required volume of GIVLAARI based on the recommended weight-based dosage.
• Withdraw the indicated injection volume of GIVLAARI using a 21-gauge or larger needle.
• Divide doses requiring volumes greater than 1.5 mL equally into multiple syringes.
• Replace the 21-gauge or larger needle with either a 25-gauge or 27-gauge needle with 1/2" or 5/8" needle length.
• Avoid having GIVLAARI on the needle tip until the needle is in the subcutaneous space.
• Administer injection into the abdomen, the back or side of the upper arms, or the thighs. Rotate injection sites. An injection should never be given into scar tissue or areas that are reddened, inflamed, or swollen.
• If injecting into the abdomen, avoid a 5 cm diameter circle around the navel.
• If more than one injection is needed for a single dose of GIVLAARI, the injection sites should be at least 2 cm apart from previous injection locations.
• Discard unused portion of the drug.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Injection: 189 mg/mL in a single-dose vial

This medicine is available in fallowing brand namesː

• GIVLAARI

What side effects can this medication cause?

The most common side effects of this medicine include:

• Nausea
• Injection site reactions
• Rash
• Serum creatinine increase
• Transaminase elevations
• Fatigue

What special precautions should I follow?

• Anaphylaxis has occurred with GIVLAARI treatment. Monitor for signs and symptoms of anaphylaxis. If anaphylaxis occurs, immediately discontinue administration of GIVLAARI and institute appropriate medical treatment.
• This medicine may cause hepatic toxicity. Measure liver function at baseline and periodically during treatment with GIVLAARI. Interrupt or discontinue treatment with GIVLAARI for severe or clinically significant transaminase elevations.
• Increases in serum creatinine levels and decreases in estimated glomerular filtration rate (eGFR) have been reported during treatment with GIVLAARI.Monitor renal function during treatment with GIVLAARI as clinically indicated.
• Injection site reactions (examples include redness, pain, itching, rash, discoloration, or localized swelling) have been reported in patients receiving GIVLAARI in the placebo-controlled trial. Monitor for reactions and manage clinically as needed.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• There are no available data with GIVLAARI use in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Can this medicine be used in children?

• Safety and effectiveness in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• givosiran sodium

Inactive ingredients:

• WATER

Who manufactures and distributes this medicine?

• Manufactured for: Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142
• Manufactured by: Ajinomoto Althea, Inc., 11049 Roselle Street, San Diego, CA 92121

What should I know about storage and disposal of this medication?

• Store at 2°C to 25°C (36°F to 77°F).
• Store GIVLAARI in its original container until ready for use.

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Givosiran Resources
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• Dailymed label info on Givosiran
• FDA Givosiran

Givosiran Resources
Need Help Finding a Doctor? Need help finding a doctor or specialist anywhere in the world? Explore our world directory. WikiMD's DocFinder can assist you in locating millions of physicians.	Medical Knowledge Access the latest research - Most recent articles Ongoing trials.

Translate to: East Asian 中文, 日本, 한국어, South Asian हिन्दी, Urdu, বাংলা, తెలుగు, தமிழ், ಕನ್ನಡ,
Southeast Asian Indonesian, Vietnamese, Thai, မြန်မာဘာသာ, European español, Deutsch, français, русский, português do Brasil, Italian, polski