Symfi/Symfi Lo

Reviewed by: HU Medical Review Board | Last reviewed: March 2023

Symfi and Symfi Lo are combination medications that contain efavirenz, lamivudine, and tenofovir disoproxil fumarate. The major difference between Symfi and Symfi Lo is their dosages. Symfi Lo contains less efavirenz per dose in an attempt to decrease side effects for those who cannot tolerate the higher dose.

Symfi and Symfi Lo are not used together and are meant to be a standalone antiretroviral therapy (ART) regimens for HIV-1 in adults and children. Neither drug should be given with other HIV medications. Symfi is for individuals weighing at least 88 pounds (40 kg), while Symfi Lo can be used in slightly smaller individuals, starting at 77 pounds (35 kg).

Although Symfi/Symfi Lo are not cures for HIV, when taken as directed, they allow for the virus to be suppressed. This prevents further transmission of HIV and allows an individual’s immune system to improve through increasing CD4 cell counts and decreasing the amount of active virus in the blood (viral load).

What are the ingredients in Symfi/Symfi Lo?

The main ingredients in Symfi/Symfi Lo are efavirenz, lamivudine, and tenofovir disoproxil fumarate. Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI), while lamivudine, and tenofovir disoproxil fumarate are nucleoside reverse transcriptase inhibitors (NRTIs).

How does Symfi/Symfi Lo work for HIV?

Symfi/Symfi Lo each contain a combination of two NRTI medications and one NNRTI medication. Both types of drugs stop the reverse transcription step of the HIV life cycle. Normally, HIV uses its reverse transcriptase enzyme to build a strand of DNA from its original RNA form. In order to do this, it uses genetic building blocks called nucleosides that come from the host cell. These nucleosides are strung together one at a time, like beads on a string, to create the final DNA product.

How do NRTIs work?

NRTIs act as nucleoside mimics that stop the DNA-building process. NRTIs look like normal nucleosides, except they’re missing a special chemical group on one side. Without this group, the reverse transcriptase enzyme is unable to attach more nucleosides to the chain after them.

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How do NNRTIs work?

NNRTIs bind to the reverse transcriptase enzyme itself to stop the DNA-building process. When an NNRTI binds to reverse transcriptase, the enzyme is unable to attach more nucleosides to the chain. Both of these mechanisms block the full string of DNA from being formed, preventing HIV RNA from making it all the way through the reverse transcription process and into host DNA for further replication.

What are the possible side effects of Symfi/Symfi Lo?

The most common side effects of Symfi Lo include, but are not limited to:

  • Rash
  • Dizziness

The most common side effects of Symfi include, but are not limited to:

  • Nausea
  • Diarrhea
  • Dizziness
  • Weakness
  • Depression
  • Insomnia
  • Abnormal dreams
  • Impaired concentration
  • Pain
  • Fatigue
  • Headache
  • Rash
  • Cough
  • Nasal symptoms

You may get a rash within 2 weeks of starting Symfi/Symfi Lo. This rash usually gets better within 4 weeks. Discontinue Symfi/Symfi Lo if you develop a severe rash.

These are not all the possible side effects of Symfi/Symfi Lo. Talk to your doctor about what to expect when taking Symfi/Symfi Lo. You also should call your doctor if you have any changes that concern you when taking Symfi/Symfi Lo.

Things to note about Symfi/Symfi Lo

Symfi/Symfi Lo has a boxed warning, the strictest warning from the US Food and Drug Administration (FDA). It has this warning because of the possibility of serious side effects as described below.

As with any medication, there are several very rare but serious risks that need to be considered before taking Symfi/Symfi Lo. Your healthcare provider can help determine what issues you may be at risk for and help determine what treatment options are the safest for you. It’s also important to remember that the risk of one or more of these issues occurring is low, and the benefits of treating the virus often greatly outweigh the risks.

Several of these rare but serious side effects of Symfi/Symfi Lo include liver issues and an increase of lactic acid in the blood (lactic acidosis). Signs of liver issues include, but are not limited to:

  • Dark-colored urine
  • Loss of appetite
  • Nausea
  • Yellowing of the whites of the eyes or skin
  • Light-colored bowel movements
  • Pain or tenderness on the right side of your stomach

Signs of lactic acidosis include, but are not limited to:

  • Trouble breathing
  • Feeling cold, especially in the limbs
  • Dizziness or lightheadedness
  • Feeling tired or weak
  • Muscle pain
  • Nausea and vomiting
  • Irregular or fast heartbeat

If you have hepatitis B virus and start taking Symfi/Symfi Lo, your hepatitis B may get worse. Symfi/Symfi Lo may also cause new or worsening kidney issues. This includes an increased risk of kidney failure. Your healthcare provider will need to monitor your kidney function before you start and while taking Symfi/Symfi Lo. Bone issues may also happen while taking Symfi/Symfi Lo, including, but not limited to, bone pain, thinning, or softening. These problems may lead to bone fractures.

Serious mental health issues may occur in some individuals. Contact your healthcare provider as soon as possible if you:

  • Have trouble speaking
  • Feel sad or hopeless
  • Hear or see things that aren’t real
  • Are not able to tell the difference between what is real/true and unreal/false
  • Feel anxious or restless
  • Do not trust other people
  • Have tried to hurt yourself or others
  • Have thoughts of hurting yourself or committing suicide

Rarely, skin reaction or allergic reactions can occur while taking Symfi/Symfi Lo. Signs of a serious reaction that need immediate medical attention include, but are not limited to:

  • Itching
  • Rash
  • Swelling of the face
  • Mouth sores
  • Red or inflamed eyes
  • Peeling skin
  • Blisters or skin lesions
  • Fever

Watch out for a serious skin reaction called Stevens-Johnson syndrome or toxic epidermal necrolysis. This reaction can cause red, swollen, blistered, or peeling skin. It may also involve red or irritated eyes and sores in the mouth, throat, nose, or eyes.

Also look for signs of an allergic reaction. These include:

  • Rash
  • Hives
  • Itching, red, swollen, blistered, or peeling skin
  • Wheezing
  • Tightness in the chest or throat
  • Difficulty breathing, swallowing, or talking
  • Unusual hoarseness
  • Swelling of the mouth, face, lips, tongue, or throat

On rare occasions, Symfi/Symfi Lo may increase an individual’s risk of seizures, which can be serious or life-threatening. Additionally, nervous system dysfunction, changes in blood fat levels, and alterations in the electrical activity of the heart called QT prolongation may occur. Individuals taking medications called elbasvir or grazoprevir should not take Symfi/Symfi Lo.

Before starting Symfi/Symfi Lo, tell your doctor if you:

  • Have or previously had hepatitis B virus
  • Have or previously had hepatitis C virus
  • Have a history of liver or kidney problems
  • Have a history of heart problems, including a condition called QT prolongation
  • Have a history of bone problems
  • Have a history of seizures
  • Have a history of mental illness
  • Are using drugs or alcohol or have a history of drug or alcohol abuse
  • Are pregnant or planning to become pregnant
  • Are breastfeeding or planning to breastfeed
  • Are taking any over-the-counter vitamins, supplements, medicines, or herbal remedies
  • Are on any other medications or are about to start any other medications, including hormonal birth control, seizure medications, or medications for hepatitis viruses

Symfi/Symfi Lo may cause a condition called IRIS (immune reconstitution inflammatory syndrome). IRIS occurs when an individual’s immune system gets stronger after being weak and responds aggressively to previously hidden infections. This heightened response may make the person fighting the infection feel worse. Alert your healthcare provider immediately if you begin to have new symptoms after taking Symfi/Symfi Lo. Symfi/Symfi Lo may also cause changes in body fat, especially around the breast, trunk, upper back, and neck regions.

This medication should be used cautiously in children with a history of pancreatitis. Please consult your doctor.