PIFELTRO (Doravirine)

What Is PIFELTRO and What Is It Used For?

PIFELTRO contains the active substance doravirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI). NNRTIs are one of the key classes of antiretroviral drugs used in the treatment of human immunodeficiency virus type 1 (HIV-1). HIV is the virus that causes acquired immunodeficiency syndrome (AIDS), a condition in which the immune system becomes severely weakened and unable to fight infections and certain cancers effectively.

Doravirine was developed by Merck Sharp & Dohme (known as MSD) and received marketing authorization from the European Medicines Agency (EMA) and approval from the U.S. Food and Drug Administration (FDA). It represents a newer-generation NNRTI designed to have a higher barrier to resistance compared to some earlier drugs in its class, such as efavirenz and nevirapine. Clinical trials, including the landmark DRIVE-FORWARD and DRIVE-AHEAD studies, demonstrated that doravirine achieves comparable efficacy to other first-line antiretroviral regimens while maintaining a favorable side effect profile.

How Does PIFELTRO Work?

PIFELTRO works by binding to and inhibiting HIV-1 reverse transcriptase, an enzyme that the virus needs to convert its RNA genetic material into DNA. This step is essential for HIV to integrate into the host cell’s genome and produce new virus particles. By blocking reverse transcriptase, doravirine prevents the virus from replicating effectively within the body.

When used as part of a complete treatment regimen, PIFELTRO helps to:

• Reduce viral load: It lowers the amount of HIV in the blood (known as the “viral load”) to undetectable levels in most patients.
• Restore immune function: By suppressing viral replication, it allows CD4+ T-cell counts to increase, strengthening the immune system.
• Reduce transmission risk: Achieving and maintaining an undetectable viral load means the virus cannot be transmitted sexually (the concept known as U=U, or Undetectable = Untransmittable).
• Prevent disease progression: Effective viral suppression dramatically reduces the risk of opportunistic infections and AIDS-related complications.

It is critical to understand that PIFELTRO does not cure HIV. The virus persists in reservoir cells in the body, and discontinuing treatment will lead to a rebound in viral replication. Therefore, antiretroviral therapy, including PIFELTRO, must be taken consistently and indefinitely. You should not take PIFELTRO if your doctor has determined that the virus causing your infection is resistant to doravirine.

Approved Indications

PIFELTRO is approved for use in the following populations:

• Adults (18 years and older) with HIV-1 infection, either treatment-naïve (starting treatment for the first time) or virologically suppressed (switching from another regimen).
• Adolescents (12 to 17 years) who weigh at least 35 kg and have HIV-1 infection without known resistance to doravirine.

PIFELTRO is also available as a fixed-dose combination tablet called Delstrigo, which combines doravirine with lamivudine and tenofovir disoproxil fumarate (TDF) in a single pill, simplifying the treatment regimen to one tablet once daily.

What Should You Know Before Taking PIFELTRO?

Contraindications

You must not take PIFELTRO if any of the following apply to you:

• Hypersensitivity: You are allergic to doravirine or any of the other ingredients in the tablet (including lactose monohydrate, croscarmellose sodium, hypromellose acetate succinate, magnesium stearate, microcrystalline cellulose, and colloidal silicon dioxide).
• Co-administration with strong CYP3A inducers: These medications significantly lower doravirine blood levels, potentially causing treatment failure and the emergence of drug-resistant HIV. The contraindicated medications include:
  • Carbamazepine, oxcarbazepine, phenobarbital, or phenytoin (anticonvulsants)
  • Rifampicin or rifapentin (antibiotics used for tuberculosis)
  • St. John’s Wort (Hypericum perforatum) or products containing St. John’s Wort
  • Mitotane (used for adrenocortical carcinoma)
  • Enzalutamide (used for prostate cancer)
  • Lumacaftor (used for cystic fibrosis)

If you are unsure whether any of these apply to you, speak with your doctor, pharmacist, or nurse before taking PIFELTRO.

Warnings and Precautions

Immune reconstitution inflammatory syndrome (IRIS): When you begin antiretroviral therapy, your recovering immune system may mount an inflammatory response against previously hidden infections (such as tuberculosis, cytomegalovirus, Pneumocystis jirovecii pneumonia, or Mycobacterium avium complex). This can cause symptoms to worsen temporarily even though the underlying infection is being treated. Inform your doctor immediately if you develop new symptoms after starting HIV treatment.

Autoimmune disorders: In some patients, the recovering immune system may also begin attacking healthy tissue, leading to autoimmune conditions such as Graves’ disease (hyperthyroidism), Guillain-Barré syndrome, polymyositis, or autoimmune hepatitis. These may occur weeks to months after initiating antiretroviral therapy. Contact your doctor if you experience symptoms such as muscle weakness starting in the hands or feet, palpitations, tremor, or excessive restlessness.

Lactose content: PIFELTRO contains lactose monohydrate. If you have been diagnosed with lactose intolerance, discuss this with your doctor before starting treatment.

Pregnancy and Breastfeeding

If you are pregnant, think you may be pregnant, or are planning to become pregnant, discuss the risks and benefits of taking PIFELTRO with your healthcare provider. Use of this medicine during pregnancy should preferably be avoided, as it has not been adequately studied in pregnant women and the potential effects on the developing fetus are unknown. Your doctor may recommend switching to an antiretroviral regimen with more established safety data during pregnancy.

Breastfeeding is not recommended for women living with HIV, regardless of whether they are on antiretroviral treatment. HIV can be transmitted through breast milk, and even with effective treatment, there remains a small risk of transmission to the infant. Formula feeding is the recommended alternative. If you are currently breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.

Children and Adolescents

PIFELTRO should not be given to children under 12 years of age or those weighing less than 35 kg, as its use in this population has not been studied. For eligible adolescents (12 years and older, weighing at least 35 kg), the dosing is the same as for adults: one 100 mg tablet once daily.

Driving and Operating Machinery

Exercise caution when driving, cycling, or operating machinery if you experience fatigue, dizziness, or drowsiness while taking PIFELTRO. These are known side effects that may impair your ability to perform tasks requiring concentration and motor coordination, particularly during the initial weeks of treatment.

How Does PIFELTRO Interact with Other Drugs?

Drug interactions are a critical consideration when prescribing PIFELTRO. Doravirine is primarily metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme in the liver. Medications that strongly induce (speed up) this enzyme can dramatically lower doravirine blood levels, rendering the drug ineffective. Conversely, potent CYP3A4 inhibitors can raise doravirine levels, though this is generally better tolerated. Always tell your doctor, pharmacist, or nurse about all medicines you are taking, have recently taken, or plan to take, including herbal remedies and over-the-counter products.

Contraindicated Combinations

The following medications must never be taken with PIFELTRO because they are strong CYP3A inducers that reduce doravirine concentrations to subtherapeutic levels:

Dose Adjustment Required

If your doctor determines that you must take any of the following medications alongside PIFELTRO, the doravirine dose should be increased to 100 mg twice daily (approximately every 12 hours). These are moderate CYP3A inducers that reduce doravirine levels but not to the extent that treatment becomes impossible:

Monitoring Required

Your doctor may need to check your blood levels or monitor you more closely for side effects if you take PIFELTRO together with the following immunosuppressant medications:

• Sirolimus — used to prevent organ transplant rejection
• Tacrolimus — used to prevent organ transplant rejection

These medications have narrow therapeutic windows, meaning even small changes in their blood levels can lead to either toxicity or treatment failure. Regular blood tests will help your doctor maintain the correct dosing of these medicines.

What Is the Correct Dosage of PIFELTRO?

Always take PIFELTRO exactly as your doctor, pharmacist, or nurse has instructed. Do not change the dose or stop taking the medicine without consulting your healthcare provider first. Consistent adherence to your antiretroviral regimen is essential for maintaining viral suppression and preventing the development of drug resistance.

Adults and Adolescents (≥12 years, ≥35 kg)

Children Under 12 Years

PIFELTRO has not been studied in children under 12 years of age or those weighing less than 35 kg. It should not be used in this population. Your child’s doctor will recommend an appropriate alternative antiretroviral regimen.

Elderly Patients

There is limited clinical experience with doravirine in patients aged 65 years and older. No dose adjustment is considered necessary based on pharmacokinetic data, but older patients should be monitored for side effects, as they may have reduced liver or kidney function and may be taking multiple other medications that could interact with PIFELTRO.

Missed Dose

Missing doses can allow HIV to replicate, increasing the risk of developing drug resistance. If you find it difficult to remember to take your medication, consider strategies such as setting a daily alarm, using a pill organizer, or linking your medication to a routine daily activity.

Overdose

If you accidentally take more than the recommended dose of PIFELTRO, contact your doctor or go to the nearest emergency department. There is no specific antidote for doravirine overdose. Treatment would be supportive and based on symptoms. Because doravirine is highly protein-bound, dialysis is unlikely to significantly remove the drug from the body.

What Are the Side Effects of PIFELTRO?

Like all medicines, PIFELTRO can cause side effects, although not everyone experiences them. Most side effects are mild to moderate and tend to improve over the first few weeks of treatment. However, some reactions can be serious and require immediate medical attention. Do not stop taking your HIV medication without talking to your doctor first.

If you experience any side effect, including any not listed above, tell your doctor, pharmacist, or nurse. You can also report suspected side effects to your national medicines regulatory authority (for example, the FDA MedWatch program in the United States, or the Yellow Card Scheme in the United Kingdom). Reporting side effects helps regulators continuously monitor the benefit-risk balance of medications.

Immune Reconstitution Inflammatory Syndrome (IRIS)

When you start antiretroviral therapy, your immune system begins to recover and may react against infections that were previously dormant. This can temporarily worsen symptoms or cause new symptoms such as fever, swollen lymph nodes, cough, or skin lesions. IRIS is not a direct side effect of PIFELTRO itself, but rather a consequence of immune recovery during any antiretroviral treatment. It is most common in the first few weeks to months of therapy and is generally manageable with appropriate medical care.

How Should You Store PIFELTRO?

Proper storage of PIFELTRO ensures the medication remains effective throughout its use. Follow these guidelines:

• Keep out of sight and reach of children at all times.
• Check the expiration date printed on the bottle after “EXP.” Do not use the medicine after this date.
• Use within 35 days of opening the bottle. Mark the date you open the bottle so you can track this.
• Keep the desiccant in the bottle — the small packet of drying agent protects the tablets from moisture. Do not remove or discard it until you have taken all the tablets.
• Keep the bottle tightly closed to protect against moisture.
• No special temperature requirements — store at room temperature.

Do not dispose of medicines via wastewater or household waste. Ask your pharmacist about proper disposal of medications you no longer use. These measures help protect the environment.

What Does PIFELTRO Contain?

Active Ingredient

Each film-coated tablet contains 100 mg of doravirine.

Inactive Ingredients (Excipients)

Tablet core: croscarmellose sodium (E468), hypromellose acetate succinate, lactose monohydrate, magnesium stearate (E470b), microcrystalline cellulose (E460), and colloidal anhydrous silica (E551).

Film coating: carnauba wax (E903), hypromellose (E464), lactose monohydrate, titanium dioxide (E171), and triacetin (E1518).

Appearance and Packaging

PIFELTRO is a white, oval, film-coated tablet imprinted with the company logo and “700” on one side and plain on the other. It is available in the following pack sizes:

• 1 bottle containing 30 film-coated tablets
• 90 film-coated tablets (3 bottles of 30 tablets each)

Not all pack sizes may be marketed in all countries.