Univestin, also called flavocoxid, is a plant-based anti-inflammatory product. It was recalled from the US market in 2017 after reports of serious liver injury and lung inflammation. Do not start this product. If you already take it, talk to your doctor before continuing.

Univestin is a fixed blend of two plant compounds called flavonoids. Baicalin comes from the root of Chinese skullcap (Scutellaria baicalensis), and catechins come from the bark of black catechu (Acacia catechu). It was sold in the US as a prescription "medical food", which is a different category from approved medicines. It was used for long-term (chronic) osteoarthritis, the wear-and-tear arthritis that causes joint pain and stiffness, most often in the knees.

Osteoarthritis happens when the cushioning cartilage inside a joint slowly wears down. The joint then becomes sore, stiff and harder to move. The body makes inflammation using chemical messengers, and two important groups are prostaglandins and leukotrienes. Many common pain medicines, such as naproxen, block only the prostaglandin pathway. Univestin acts on both pathways, which is why researchers call it a "dual inhibitor".

Univestin was sold for managing long-term osteoarthritis, but it was never an approved medicine for this use. In a 12-week trial of people with knee osteoarthritis, Univestin eased joint symptoms about as well as naproxen. It also caused fewer upper stomach, kidney-related and breathing-related side effects. In a large open-label study across rheumatology clinics, most people's stomachs handled it well.

Products made from plants can still cause serious side effects. Univestin has been linked to rare but serious liver injury. In a published case series, the people affected developed liver problems within 1 to 3 months of starting it. Their liver tests returned to normal within weeks of stopping. Skullcap raw material can sometimes be mixed with germander, a plant known to harm the liver, so quality testing of the raw material matters.

Rare cases of a lung reaction called hypersensitivity pneumonitis have also been reported. In one case, this reaction led to lasting lung scarring.

Because of these reports, flavocoxid was recalled from the US market in 2017. Do not start Univestin, and if you already take it, speak to your doctor about stopping. Stop taking it and get medical help straight away if you notice:

• yellowing of the skin or eyes
• dark urine or pale stools
• a new cough or breathlessness

1. Dual anti-inflammatory action - Univestin lowers both prostaglandins and leukotrienes, two groups of chemicals that drive joint inflammation.
2. Relief of osteoarthritis symptoms - In a 12-week trial, it eased knee osteoarthritis symptoms about as well as naproxen.
3. Stomach side effects in studies - In that trial, people taking Univestin had fewer upper stomach side effects than people taking naproxen. An observational study of insurance claims also found fewer hospital stays for stomach bleeding than with prescription NSAIDs (non-steroidal anti-inflammatory drugs, the common group of pain medicines).
4. Less kidney-related swelling - In the same trial, kidney-related side effects such as swelling (edema) were less common with Univestin than with naproxen.
5. Blood clotting in a small study - In a small study, it did not lengthen bleeding time, and early testing showed no effect on warfarin. Large studies have not confirmed this.

These possible benefits must be weighed against the rare but serious liver and lung reactions that led to the 2017 US recall.

Common Side Effects (Usually Mild)

• Mild stomach upset or indigestion

Serious Side Effects (Seek Urgent Medical Attention)

Stop taking Univestin and get medical help straight away if you notice any of the following.

• Drug-induced liver injury - This means the product itself damages the liver. It is rare, but it has been clearly reported with Univestin, usually within 1 to 3 months of starting. Warning signs include:
• yellow skin or eyes (jaundice)
• dark urine or pale stools
• itching or a fever
• unusual tiredness or nausea
• pain in the upper right side of the belly
• Raised liver enzymes on blood tests - These can show up even without symptoms. Your doctor may advise stopping the product.
• Hypersensitivity pneumonitis - This is an allergic-type inflammation of the lungs. It has been reported rarely with Univestin, sometimes within a couple of weeks of starting. Warning signs include breathlessness that gets worse with activity, a dry cough, fever, chills and chest pain. It can look like a chest infection that does not get better with antibiotics.
• Pulmonary fibrosis - This means scarring of the lungs. In one reported case, the lung reaction caused lasting scarring even after Univestin was stopped.
• Allergic reaction - Signs include rash, hives, swelling of the face, lips or throat, or trouble breathing.

• Talk to your doctor before you start or continue Univestin, because it was recalled from the US market in 2017.
• Univestin was sold as tablets. Swallow each tablet whole with a glass of plain water. Ask your pharmacist before breaking or crushing it.
• Take it the same way every day, either always with food or always on an empty stomach.
• In studies, Univestin was taken twice a day, about 12 hours apart.
• Stop taking Univestin straight away and contact your doctor if you notice yellow skin or eyes, dark urine, a new cough or breathlessness. For any other change, talk to your doctor first.
• Go to any blood tests your doctor orders, especially liver tests in the first few months.

When a joint is irritated, its cells release a fatty substance called arachidonic acid. Enzymes, which are proteins that speed up chemical reactions in the body, then turn this substance into inflammation messengers. Univestin acts at several points in this process:

• COX-1 and COX-2 (cyclooxygenase enzymes) - These enzymes make prostaglandins, which cause pain, swelling and heat in the joint. Univestin blocks the "peroxidase" site of these enzymes. This is the second working part of the COX enzyme, which finishes making prostaglandins. It acts on COX-1 and COX-2 about equally.
• 5-LOX (5-lipoxygenase) - This enzyme makes leukotrienes, another group of inflammation messengers. Univestin also slows 5-LOX.
• Phospholipase A2 - Lab studies show that Univestin also slows this enzyme, which releases arachidonic acid in the first place. Less raw material is then available to make inflammation messengers.
• Antioxidant effect - The flavonoids in Univestin also mop up harmful oxygen molecules that can add to tissue damage.

Baicalin (from Chinese skullcap) and catechins (from black catechu) work together to produce this combined effect.

• Flavocoxid was recalled from the US market in 2017. Talk to your doctor before starting or continuing Univestin. Stop straight away if liver or lung warning signs appear.
• Learn the liver warning signs: yellow eyes or skin, dark urine and pale stools.
• If you get a new cough or breathlessness, see a doctor, especially in the first weeks after starting.
• Tell every doctor you see that you take Univestin, even though it is plant-based.
• Do not take other herbal products that contain Chinese skullcap or catechu along with it.
• Regular gentle exercise and weight control can help ease osteoarthritis.

• Store at the temperature printed on the product label, in a cool and dry place.
• Keep the tablets in their original container, away from direct sunlight and moisture. Do not store them in the bathroom.
• Keep out of the reach and sight of children and pets.
• Do not use after the expiry date. Ask your pharmacist how to throw away unused tablets safely.

• Alcohol - Alcohol puts extra strain on the liver. Since Univestin can rarely injure the liver, avoid or limit alcohol.
• Herbal supplements with the same plants - Chinese skullcap (Scutellaria) and catechu (Acacia catechu) products contain the same compounds as Univestin. Taking them together adds to the total amount you take in.
• Regular meals - No specific food is known to block Univestin. Take it the same way each day, either always with meals or always without.

• Warfarin - In a small study, Univestin did not weaken or strengthen the blood-thinning effect of warfarin. Your doctor may still check your INR (a blood clotting test) as usual.
• Aspirin - In a small study, Univestin did not increase bleeding time when taken with aspirin. It also did not block aspirin's effect on blood clotting.
• Other pain and anti-inflammatory medicines (NSAIDs) - These include naproxen, ibuprofen and diclofenac. Univestin acts on similar inflammation pathways, so do not combine them unless your doctor advises it.
• Medicines that can affect the liver - These include:
• high doses of paracetamol (acetaminophen)
• tuberculosis medicines such as isoniazid
• some seizure medicines such as valproate

These medicines can harm the liver on their own. No direct interaction with Univestin has been proven, but taking them together may add to the strain on the liver. Tell your doctor about all the medicines you take.

• Liver disease - Avoid Univestin if you have liver disease. It has been linked to rare but serious liver injury.
• Previous reaction to flavocoxid - If you have ever had liver injury or lung inflammation while taking Univestin, never take it again.
• Lung disease - Rare cases of hypersensitivity pneumonitis have been reported, and one case led to lung scarring. Tell your doctor if you have asthma, another lung disease or long-lasting breathlessness.
• Allergy to the ingredients - Do not use Univestin if you have ever reacted to baicalin, Chinese skullcap, catechins or catechu.
• Kidney disease - Tell your doctor. No kidney-specific dosing has been studied.

• Univestin was sold as 250 mg and 500 mg tablets.
• In clinical studies, adults with knee osteoarthritis took 250 mg twice a day or 500 mg twice a day.
• It was taken twice in 24 hours.
• Take only the dose your doctor prescribed. Do not raise or lower it on your own.

• Taking too much may raise the chance of side effects, especially stomach upset and strain on the liver.
• If you or someone else has taken more than the prescribed amount, contact a doctor or go to the nearest emergency department straight away, even if there are no symptoms yet.
• Bring the pack with you so the medical team knows exactly what was taken and how much.
• In the days after, watch for liver warning signs such as yellow eyes or skin, dark urine or belly pain.

• Take the missed dose as soon as you remember.
• If it is almost time for your next dose, skip the missed one and take the next dose at the usual time.
• Never take two doses at once to make up for a missed one.
• A phone reminder for your morning and evening doses can help.

Stop Univestin and get medical help urgently if you notice:

• Yellowing of the skin or the whites of the eyes
• Dark urine, pale stools or itching all over
• Pain in the upper right side of the belly, nausea or loss of appetite
• Unusual tiredness, weakness or fever
• New or worsening breathlessness, especially when active
• A dry cough, chills or chest pain that does not settle, including a "chest infection" that does not improve with treatment
• Rash, hives, swelling of the face, lips or throat, or trouble breathing, which may mean an allergic reaction