Lenacapavir - Dosage, Indications, and Side Effects

What Is Lenacapavir?

Doctors may recommend Lenacapavir if a person has used HIV treatments in the past that are no longer working well, cause side effects, or if the virus has become resistant (meaning the virus no longer responds to certain medicines).

Lenacapavir is called an HIV capsid inhibitor (a type of drug that blocks the protective outer shell of the virus so it cannot grow and spread). This helps lower the amount of HIV in the blood by stopping the virus from multiplying (making more copies of itself).

Lenacapavir does not cure HIV, but it can reduce the risk of developing AIDS (advanced stage of HIV where the immune system becomes very weak) and other serious health problems, including infections and some cancers. People with weakened immunity may also experience problems like yeast infections after unprotected sex, so safer sexual practices are still very important.

How Effective Is Lenacapavir?

• Lenacapavir is a recently approved drug used to treat adults with multidrug-resistant HIV (HIV that does not respond to many other medicines).

• It is currently the longest-acting HIV medicine (meaning it stays in the body and works for a long time).

• Lenacapavir is a potent multistage inhibitor of the HIV-1 capsid (blocks the virus at different steps by targeting its protective outer shell so it cannot grow and spread).

• The medicine is highly effective, and the subcutaneous dose (an injection given under the skin) only needs to be taken twice a year.

• Studies show that Lenacapavir is safe and has strong antiviral effectiveness (it successfully reduces the amount of virus in the body) without lowering the quality of life of patients.

• Daily oral pre-exposure prophylaxis (PrEP - a pill taken every day to prevent HIV before exposure) is also very effective when taken correctly and helps prevent the transmission of HIV-1 to others.

How Does Lenacapavir Work?

• Lenacapavir is a type of HIV capsid inhibitor (targets the outer shell of the HIV virus) and helps lower the amount of HIV in the blood.

• It binds to the HIV capsid (the structural component that protects the virus) at multiple stages of the virus’s lifecycle, which stops the virus from making copies of itself and inhibits viral replication.

• Using this medicine along with healthy lifestyle changes and practicing safer sex (like using condoms and avoiding sharing needles) can help reduce the risk of spreading HIV to others.

For Patients

How Should Lenacapavir Be Taken?

Lenacapavir treatment includes both tablets and injections. A healthcare provider gives the Lenacapavir injection under the skin (subcutaneously) in the abdomen.

There are two possible treatment plans:

Option 1

• Two Lenacapavir injections.

• Plus two Lenacapavir tablets.

• Then two more tablets on day two.

Option 2

• Two Lenacapavir tablets on day one.

• Two tablets again on day two.

• One tablet on day eight.

• Then two injections on day 15.

After completing either option, patients will then receive Lenacapavir injections every six months (twice a year) starting from the last dose.

It is important to keep taking this treatment even if you feel better. Do not stop using Lenacapavir without talking to your doctor, as stopping suddenly may allow the virus to grow again.

What Are the Side Effects of Lenacapavir?

Some of the side effects of Lenacapavir include:

• Nausea.

• Fever.

• Skin rash (red, itchy, or irritated skin).

• Fatigue (feeling very tired or lacking energy).

• Body ache.

• Stomach pain.

• Muscle weakness (feeling unable to move muscles strongly).

• Joint pain (pain or stiffness in the knees, elbows, or other joints)

• Swelling (puffiness in any part of the body).

• Injection site reactions (such as pain, redness, itching, and lump formation.

What Must the Patient Inform the Doctor Before Taking Lenacapavir?

• Patients should tell their doctor if they are allergic to Lenacapavir, its ingredients, or any other medicines before starting treatment.

• Some medicines can interact with Lenacapavir, so patients should talk to their doctor before changing or stopping any current medicines.

• Patients must inform the doctor if they are taking vitamins, herbal supplements (such as St. John’s wort), over-the-counter medicines, or any other drugs before starting Lenacapavir.

• Female patients should tell their doctor if they are pregnant, planning to become pregnant, or breastfeeding before using Lenacapavir.

What Are the Precautionary Measures to Be Followed While Taking Lenacapavir?

• If any signs of infection or inflammation (such as fever, swelling, or redness) appear, patients should tell their doctor right away. These can happen soon after starting HIV treatment.

• It is important to keep taking the medication and attend all scheduled appointments to keep the virus under control and lower the risk of drug resistance.

• Lenacapavir can interact with other medicines for up to nine months after the last dose. Always tell the doctor when you last received Lenacapavir before starting any new medication.

• Women should not breastfeed while taking Lenacapavir or if they have HIV, because the virus can be passed to the baby through breast milk.

• During treatment, injection site reactions such as pain, swelling, redness, itching, or small lumps may occur where the medicine was injected.

Dietary Considerations

Consuming grapefruit or its juice must be avoided while taking Lenacapavir. No other dietary considerations are required unless advised by the prescribing doctor.

Lenacapavir- Dosage, Indications, and Side Effects

Lenacapavir dosing:

Lenacapavir comes as:

• Oral tablets (can be taken with or without food).

• Single-dose vials for injection (given under the skin by a healthcare provider).

Treatment is started using one of the two recommended dosing options:

Option 1

• Day 1: 927 mg injection under the skin (two injections of 1.5 mL each). 600 mg of oral tablets (two tablets, 300 mg each).

• Day 2: 600 mg of oral tablets (two tablets, 300 mg each).

Option 2

• Day 1 and Day 2: 600 mg of oral tablets each day (two tablets, 300 mg each).

• Day 8: One 300 mg oral tablet.

• Day 15: 927 mg injection under the skin (two injections of 1.5 mL each).

Maintenance Dose: Both option one and option two are followed by a maintenance dose of 927 mg of subcutaneous Lenacapavir injection (two doses of 1.5 ml each) once every six months or 26 weeks.

Missed Dose:

• Lenacapavir treatment requires regular, scheduled appointments with a healthcare provider.

• The medicine may not work properly if doses are delayed or missed.

• If a dose is missed for more than 28 weeks, the Lenacapavir treatment must be restarted using the initial dosing regimen.

Overdose:

Much information is not available about the Lenacapavir overdose in people. But when it occurs, it needs to be treated immediately, and vital signs must be monitored.

Storage:

Leanacapavir tablets and vials must be stored in their original packaging at 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit), away from excess light and moisture.

Indications of Lenacapavir

Lenacapavir is used together with other antiretroviral medicines to treat HIV-1 in adults. It is recommended for patients who have tried many HIV treatments in the past (heavily treatment-experienced).

Lenacapavir is helpful for people whose current HIV medicines are not working well because of:

• Intolerance (cannot handle side effects).

• Resistance (virus no longer responds to the medicine).

• Safety concerns (medicine may cause harmful effects).

Contraindications of Lenacapavir

• Lenacapavir is not recommended for children, pregnant women, or lactating women.

• It is also not indicated for patients with severe liver disorders.

Warnings and precautions:

• Combination antiretroviral therapy can cause some patients' immune reconstitution syndrome (hyperinflammatory response). This can lead to inflammation, lung infections, such as pneumonia, tuberculosis, other residual opportunistic infections (infections occurring when the immune system is impaired), and autoimmune disorders (diseases caused by the immune system attacking healthy cells), thus requiring further evaluation and treatment.

• After the last subcutaneous dose, residual concentrations of Lenacapavir can be present in the systemic circulation for around 12 months or longer (prolonged period). Therefore, maintenance therapy is required every six months, and missing doses or non-adherence to treatment can cause resistance to or ineffectiveness of the drug.

• If Lenacapavir is discontinued, an alternative, fully suppressive antiretroviral therapy must be initiated not later than 28 weeks after the final dose of Lenacapavir.

• Following the administration of Lenacapavir, injection site reactions such as pain, swelling, pruritus (itching), induration (thickening of the skin), erythema (redness), nodules (lumps), extravasation (leakage of body fluids), or mass formation can occur. Hence, appropriate evaluation and treatment must be considered for such patients.

Adverse effects of Lenacapavir

Some of the adverse effects of Lenacapavir include:

• Nausea and vomiting.

• Injection site reactions.

• Fever.

• Joint pain.

• Skin rash.

• Abdominal pain.

• Yellowish discoloration of the skin and eyes.

• Numbness or weakness of the arms and legs.

• Unusual tiredness.

• Dark urine.

• Light-colored stools.

For Doctors

Pharmacological aspects of Lenacapavir-

Mechanism of action:

• Lenacapavir is a long lasting HIV-1 drug.

• It works by binding to parts of the HIV capsid (the virus’s outer shell).

• This action interferes with multiple steps in the virus’s life cycle.

• It is a long-acting and powerful inhibitor of the HIV capsid protein.

• Lenacapavir shows activity in the lab (in vitro) against virus strains that are resistant to other HIV medicines.

• The drug blocks viral replication during both early and late stages of the HIV life cycle.

• It has an extended pharmacokinetic profile (it stays in the body and works for a long time).

Pharmacodynamics:

Lenacapavir demonstrated antiviral activity against all major subtypes of HIV-1. It selectively inhibits the function of the HIV-1 capsid and HIV-1 replication by directly binding to the capsid protein subunit interface.

This occurs at multiple stages of the virus's lifecycle, including nuclear import, virion assembly, and capsid core assembly. In vitro studies have suggested that Lenacapavir, combined with drugs such as Rilpivirine, Cabotegravir, and Islatravir, has an additive antiviral effect, specifically at higher doses.

Pharmacokinetics:

• Absorption: Lenacapavir is completely absorbed via subcutaneous administration, but the drug is slowly released. The absorption profile is complex, and the peak plasma concentration occurs 84 days post-dose. After an oral administration, the peak plasma concentration (Cmax) occurs approximately four hours after the administration, and the absolute bioavailability is around 6 to 10 percent.

• Distribution: About 99.8 percent of Lenacapavir is bound to plasma proteins, and the steady-state volume of distribution in heavily treatment-experienced patients was around 976 liters.

• Biotransformation: Lenacapavir is metabolized primarily by the CYP3A4 and UGT1A1 enzymes. After a single intravenous dose of radiolabeled Lenacapavir was administered to healthy subjects, approximately 76 percent of the total radioactivity was recovered in the feces, and less than one percent was present in urine.

• Elimination: The median half-life of Lenacapavir after oral and subcutaneous administration was 10 to 12 days and 8 to 12 weeks, respectively. The clearance of the drug in heavily treatment-experienced patients with HIV-1 infection was based on population pharmacokinetic analysis and was approximately 3.62 L/h (liters per hour).

Drug interactions:

Some of the drugs that interact with Lenacapavir include:

• Carbamazepine.

• Phenytoin.

• Rifampin.

• St.John’s wort.

• Apalutamide.

• Enzalutamide.

• Apixaban.

• Budesonide.

• Codeine.

• Cyclosporine.

• Dexamethasone.

• Ergotamine.

• Itraconazole.

• Ketoconazole.

• Sildenafil.

• Tramadol.

• Tadalafil.

• Vardenafil.

• Venetoclax.

Clinical studies:

• Lenacapavir was studied in a 52-week clinical trial called CAPELLA to check its safety and effectiveness.

• The trial included 72 adults with HIV-1 who had multidrug resistance and a viral load of at least 400 copies/mL.

• Participants had resistance to at least two drugs in three of the four major HIV medicine classes (PI, INSTI, NRTI, NNRTI).

• Patients were divided into Cohort 1 and Cohort 2 based on their response before treatment.

• Cohort 1 showed a CD4 cell count increase of 81 cells/mm³ at 26 weeks and 82 cells/mm³ at 52 weeks.

• Cohort 2 showed a CD4 cell count increase of 97 cells/mm³ at 26 weeks and 113 cells/mm³ at 52 weeks.

Nonclinical toxicology:

• Carcinogenesis: Lenacapavir was found to be non-carcinogenic in male and female mice at doses of up to 300 mg/kg/dose (milligrams per kilogram per dose) administered every 13 weeks for six months.

• Mutagenesis: In vitro and in vivo assays demonstrated that Lenacapavir was not mutagenic, including chromosome aberration, micronucleus assay, and microbial mutation.

• Impairment of fertility: During research, no significant impact on fertility was noticed in rats with Lenacapavir administration, even at doses five times higher than the human dose exposure.

Specific considerations:

• Pregnancy: Lenacapavir-related birth defects, miscarriage, or any other side effects in the fetus or pregnant woman have not yet been detected.

• Lactation: It is unclear whether Lenacapavir is present in breast milk, its effects on the breastfed infant, or milk production.

• Pediatric use: Lenacapavir is not recommended for children, as the safety and effectiveness of the drug have not been determined in this population.

• Geriatric use: The clinical studies of Lenacapavir did not include a sufficient number of individuals above 65 years of age to determine the difference in response compared to younger adults.

• Hepatic and renal impairment: Dose modification is not required in patients with mild, moderate, or severe renal disorders and mild or moderate liver impairment. However, Lenacapavir is not recommended in patients with severe hepatic impairment.