Efavirenz, Lamivudine, and Tenofovir

This combination tablet treats HIV-1 infection.

• Efavirenz, lamivudine and tenofovir disoproxil fumarate tablets are used as a complete regimen for HIV-1 infection in adults and children weighing at least 40 kg.
• Symfi (oral film-coated tablet) has the same use.

HIV needs an enzyme called reverse transcriptase to make copies of itself. Efavirenz blocks this enzyme directly. Lamivudine and tenofovir are building-block look-alikes that get built into the viral DNA and stop the chain from growing.

Lamivudine and tenofovir also act against hepatitis B virus.

The tablet is taken by mouth once a day on an empty stomach, preferably at bedtime. Bedtime dosing may ease nervous system side effects. It is for people who weigh at least 40 kg and can swallow a solid tablet.

• Tests for hepatitis B, kidney function, urine glucose and protein, and liver function are done before and during treatment.
• Don't add other HIV medicines.

Follow your prescriber's instructions and the label.

The most common side effects are rash and dizziness. Others reported include:

Call your doctor right away about severe rash, serious mood or thought changes, signs of liver or kidney problems, or severe stomach pain.

• Hepatitis B flare after stopping (boxed warning). Don't stop without medical advice.
• Lactic acidosis and liver problems. Treatment should be suspended if signs appear. Female sex and obesity may raise the risk.
• Kidney injury. Tenofovir can cause kidney damage, including Fanconi syndrome. Avoid NSAIDs in high doses.
• Psychiatric symptoms. Severe depression, suicidal thoughts and aggression need immediate medical review.
• Nervous system symptoms. Dizziness and vivid dreams are common early and usually fade in 2 to 4 weeks. Late-onset problems with balance or confusion can occur.
• Rash. Usually mild, appearing in the first 2 weeks. Stop for severe rash.
• Other risks. Seizures, pancreatitis, higher cholesterol and triglycerides, bone density loss, immune reconstitution syndrome and body fat changes.

Many drugs can change how this tablet works or how other medicines work.

• Elbasvir/grazoprevir: contraindicated, because it can cause loss of hepatitis C treatment effect.
• Other HIV medicines: not to be combined, since this is a complete regimen.
• NSAIDs in high doses or multiples, acyclovir, valacyclovir, ganciclovir, cidofovir, aminoglycosides: can raise tenofovir levels and strain the kidneys.
• Rifampin, rifabutin, phenobarbital, phenytoin, carbamazepine: can lower efavirenz or the other drug's levels.
• Statins, immunosuppressants, methadone, bupropion, sertraline and calcium channel blockers: levels may drop, so doses may need adjusting.
• Hormonal birth control: use an added barrier method.
• QT-prolonging drugs: efavirenz can prolong the QT interval, so alternatives may be considered.
• Sorbitol-containing medicines: can lower lamivudine levels, so avoid when possible.

Efavirenz may also cause false-positive urine cannabinoid screens.

Not a complete list. The label covers the interactions the manufacturer studied or reported, and our own interaction database does not cover every medicine either. Bring your full medication list, including vitamins and herbal products, to your pharmacist.

• Do not use it if you have had a serious hypersensitivity reaction (such as Stevens-Johnson syndrome) to any component.
• Don't take it with elbasvir/grazoprevir.
• Get tested for hepatitis B first.
• Not recommended with creatinine clearance under 50 mL/min or kidney failure requiring hemodialysis.
• Not recommended with moderate or severe liver impairment. Use caution with mild impairment.
• Tell your doctor about psychiatric history, seizures, pancreatitis history, or risk of bone loss.
• Pregnancy: efavirenz may harm the fetus in the first trimester. Avoid pregnancy during treatment and for 12 weeks after, and use contraception and pregnancy testing.
• Breastfeeding is not recommended because of HIV transmission risk.
• Children: used in those weighing at least 40 kg who can swallow a tablet.

In people who accidentally took efavirenz twice the usual amount, nervous system symptoms increased, and one person had involuntary muscle contractions. There is no specific antidote. The label advises monitoring and supportive care, and activated charcoal may help remove unabsorbed drug.

Efavirenz can lengthen the QTc interval, a measure of heart rhythm timing. In a study, this was greater in people with a genetic variation (CYP2B6 *6/*6) that raises efavirenz levels. The higher the efavirenz concentration, the greater the effect.

Efavirenz peaks in about 3 to 5 hours, is broken down by liver enzymes (CYP3A and CYP2B6), and has a long half-life of roughly 40 to 76 hours. Lamivudine is mostly cleared unchanged by the kidneys, with a half-life of 5 to 7 hours. Tenofovir is also cleared by the kidneys and has a half-life of about 17 hours. Kidney impairment raises lamivudine and tenofovir levels. The effect of food on this combination has not been evaluated.

Store at 20° to 25°C (68° to 77°F), excursions permitted between 15° to 30°C (59° to 86°F). Dispense in original container.