Givlaari (givosiran) is a treatment for Acute Hepatic Porphyria (AHP) that helps reduce the number of acute attacks and the use of intravenous heme. Acute hepatic porphyria is a rare genetic disorder that can cause life-threatening attacks on the nervous system with symptoms of severe stomach pain, nausea and vomiting, numbness, weakness, or mental status change.

In acute hepatic porphyria a genetic mutation disrupts the normal process of heme production, heme is a component of hemoglobin in your blood. This process disruption leads to the accumulation of toxic compounds known as porphyrin precursors in the liver, which eventually enter the bloodstream and cause symptoms associated with AHP. In the liver, the production of heme is controlled by an enzyme called aminolevulinic acid synthase 1 (ALAS1).

Givlaari is an aminolevulinate synthase 1-directed small interfering RNA (siRNA) which works by decreasing the amount of ALAS1 in the liver; this leads to a reduction in levels of the toxic compounds and so helps improve AHP symptoms. 

Givlaari is a subcutaneous injection that is usually given monthly.

This disorder is more common in women during their childbearing years.

You will need to have frequent blood tests and your next dose may be delayed based on the results.

Follow all directions and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Givlaari is injected under the skin (subcutaneously) usually once per month. A healthcare provider will give you this injection.

Givlaari doses are based on weight. Your dose needs may change if you gain or lose weight.

You will need frequent blood tests to check your liver function before and during treatment with Givlaari. Your next dose may be delayed based on the results.

Your kidney function may also need to be checked.

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

Givlaari injections are given 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.

You should not use Givlaari if you are allergic to it, or any of the inactive ingredients.

Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant. It is not known whether Givlaari will harm an unborn baby. However, having acute hepatic porphyria during pregnancy may cause serious medical problems in both mother and baby. The benefit of treating this disorder may outweigh any risks to the baby.

Breastfeeding 

It may not be safe to breastfeed while using Givlaari. Ask your doctor about the best way to feed your baby if taking Givlaari.

Get the missed injection as soon as possible, and then go back to your regular injection schedule. Do not use two doses at one time.

Since Givlaari is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Your injections may be delayed or permanently discontinued if you have certain side effects.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Check with your doctor right away if you have bloody urine, a decrease in frequency or amount of urine, an increase in blood pressure, increased thirst, loss of appetite, lower back or side pain, nausea, swelling of the face, fingers, or lower legs, trouble breathing, unusual tiredness or weakness, vomiting, or weight gain. These could be symptoms of a serious kidney problem.

Call your doctor right away if you have redness, burning, swelling, or pain at the injection site.

This medicine may increase homocysteine (an amino acid) levels in your blood. You may receive vitamin supplements (eg, vitamin B6 supplement) to treat this blood problem.

Common side effects of Givlaari may include:

• nausea; or
• pain, itching, rash, discoloration, or swelling where an injection was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Using Givlaari with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alosetron
• Atomoxetine
• Caffeine
• Desipramine
• Dextromethorphan
• Duloxetine
• Eliglustat
• Metoprolol
• Nebivolol
• Perphenazine
• Ramelteon
• Tacrine
• Tasimelteon
• Theophylline
• Thioridazine
• Tizanidine
• Tolterodine
• Venlafaxine

Other drugs may affect Givlaari, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.