Givosiran

• Givosiran is a prescription medication used for the treatment of Acute Hepatic Porphyria. 

Givosiran is available under the following different brand names: Givlaari.

Common side effects of Givosiran include:

• Nausea, and
• Pain, itching, rash, discoloration, or swelling where an injection was given

Serious side effects of Givosiran include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat, and
• Severe dizziness

Rare side effects of Givosiran include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injection, SC solution

• 189 mg/mL (single-dose vial)

Acute Hepatic Porphyria

Adult dosage

• 2.5 mg/kg subcutaneously every month; dose based on actual body weight.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Givosiran has severe interactions with no other drugs.
• Givosiran has serious interactions with at least 87 other drugs.
• Givosiran has moderate interactions with the following drugs:
  • oliceridine
  • warfarin
• Givosiran has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Severe hypersensitivity, including anaphylaxis.

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Givosiran?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Givosiran?”

Cautions

• Anaphylaxis observed; ensure medical support is available to appropriately manage anaphylactic reactions when administering; monitor for signs and symptoms of anaphylaxis.
• Transaminase elevations (ALT) of more than 3 times the ULN observed in the placebo-controlled trial; primarily occurred 3-5 months after initiating treatment; monitor.
• Increased serum creatinine levels and decreased eGFR were reported; monitor renal function as clinically indicated.
• Injection-site reactions reported; symptoms included erythema, pain, pruritus, rash, discoloration, or swelling.
• Blood homocysteine
  • Increases in blood homocysteine levels reported in patients receiving therapy, the clinical relevance of elevations in blood homocysteine during therapy are unknown.
  • Measure blood homocysteine levels before initiating treatment and monitor for changes during treatment.
  • In patients with elevated blood homocysteine levels, assess folate, vitamins B12 and B6; consider treatment with a supplement containing vitamin B6 (as monotherapy or a multivitamin preparation)
• Drug interaction overview
  • In vitro studies indicate that givosiran does not directly inhibit or induce CYP enzymes; however, because of its pharmacological effects on the hepatic heme biosynthesis pathway, givosiran has the potential to reduce the activity of CYP enzymes in the liver.
  • Sensitive CYP1A2 or CYP2D6 substrates
    • Sensitive CYP1A2 substrates: Coadministration increased caffeine (sensitive CYP1A2 substrate) AUC by 3.1-fold and Cmax by 1.3-fold.
    • Sensitive CYP2D6 substrates: Coadministration increased dextromethorphan (sensitive CYP2D6 substrate) AUC by 2.4-fold and Cmax by 2-fold.
    • Avoid use with CYP1A2 or CYP2D6 substrates, for which minimal concentration changes may lead to serious or life-threatening toxicities.
    • If concomitant use is unavoidable, decrease CYP1A2 or CYP2D6 substrate dosage by its prescribing information.

Pregnancy and Lactation

• Data are not available regarding the use in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
• Clinical considerations
  • Porphyria attacks during pregnancy, often triggered by hormonal changes, occur in 24-95% of patients with AHP, with maternal mortality ranging from 2-42%
  • Pregnancy in patients with AHP is associated with higher rates of spontaneous abortion, hypertension, and low-birthweight infants.
• Lactation
  • Data are not available regarding use in breastfeeding women.