Givlaari Side Effects: What to Expect and When to Call Your Doctor

Givlaari (givosiran) is an effective medication for reducing porphyria attacks in adults with acute hepatic porphyria (AHP) — but like all medications, it carries potential side effects. Understanding what to expect can help you recognize problems early, maintain your monitoring schedule, and know when to contact your healthcare provider.

This guide covers everything you need to know about Givlaari side effects, from common and manageable to rare and serious.

Common Side Effects of Givlaari (>20% of Patients)

In clinical trials (the ENVISION study), the following side effects occurred in more than 20% of patients receiving Givlaari:

• Nausea (27%): Nausea is the most commonly reported side effect. It is usually mild to moderate. Eating a small meal before your injection and avoiding large meals immediately after may help. Tell your doctor if nausea is severe or persistent.
• Injection site reactions (25%): These include redness, swelling, pain, or pruritus (itching) at the injection site. Recall reactions (reactions at the site of a previous injection) have also been reported. Tell your provider if these are worsening or not resolving.

Serious Side Effects of Givlaari

Givlaari has several serious potential side effects that require monitoring and, in some cases, dose modification or discontinuation:

1. Hepatic Toxicity (Liver Damage)

Liver enzyme elevations (ALT) of at least 3 times the upper limit of normal occurred in 15% of patients in clinical trials. These elevations primarily occurred between 3 and 5 months after starting treatment. Permanent discontinuation due to elevated liver enzymes occurred in 1 patient (2.1%) in clinical trials.

Your doctor must measure liver function tests (LFTs) before starting Givlaari, then monthly for the first 6 months, and periodically thereafter. Contact your doctor immediately if you experience:

• Yellowing of the skin or whites of the eyes (jaundice)
• Severe pain in the upper right side of your abdomen
• Dark urine (different from the porphyrin-dark urine of AHP attacks)
• Unusual tiredness or weakness

2. Renal Toxicity (Kidney Problems)

Changes in kidney function, including decreased estimated glomerular filtration rate (eGFR) and increased serum creatinine, have been observed in patients taking Givlaari. Your doctor may periodically check your kidney function labs. Contact your doctor right away if you notice swelling in your legs or ankles, decreased urine output, or unusual fatigue.

3. Anaphylaxis (Severe Allergic Reaction)

Anaphylaxis occurred in less than 1% of patients in clinical trials. Because of this risk, Givlaari is administered by a healthcare professional with medical support available — not self-injected at home. Symptoms of anaphylaxis include:

• Hives, itching, or flushing of the skin
• Difficulty breathing or wheezing
• Swelling of the face, lips, tongue, or throat
• Dizziness, lightheadedness, or loss of consciousness

If you experience any anaphylaxis symptoms, call 911 immediately. Givlaari must be discontinued immediately if anaphylaxis is confirmed.

4. Elevated Homocysteine

Givlaari can increase blood homocysteine levels, which at high levels has been linked to cardiovascular risk. Your doctor should measure homocysteine before starting treatment. They may recommend vitamin B6 supplementation or a multivitamin to help manage elevated homocysteine levels. Make sure to keep all monitoring appointments.

5. Pancreatitis (Post-Marketing Report)

Pancreatitis (inflammation of the pancreas) has been reported during post-approval use of Givlaari. Contact your doctor right away if you experience severe pain in the upper abdomen that radiates to your back, nausea, or vomiting.

Required Monitoring Schedule

To safely continue Givlaari, the FDA label requires this monitoring:

• Liver function tests (LFTs) — monthly for the first 6 months, then as clinically indicated
• Kidney function (creatinine, eGFR) — periodically
• Blood homocysteine — at baseline and during treatment

Your next dose of Givlaari may be delayed based on lab results. Never skip monitoring appointments — these labs are required not only for safety but also for insurance renewal.

Special Populations: Pregnancy and Breastfeeding

It is not known whether Givlaari will harm an unborn baby. Animal studies showed adverse developmental effects at high doses. However, pregnancy in AHP patients is itself associated with significant risk, including maternal mortality in some cases. Discuss the risks and benefits thoroughly with your specialist if you are pregnant or planning to become pregnant. It is also not known if Givlaari passes into breast milk. Talk to your doctor before breastfeeding.

For information on drug interactions that can affect Givlaari's safety profile, see our guide on Givlaari drug interactions.

If you are navigating access or availability challenges on top of managing side effects, medfinder can help you locate specialty pharmacies and administration sites so that monitoring and dosing stay on schedule.