Dolutegravir

Dolutegravir Uses, Dosage, Side Effects, Mechanism of Action, How Long Does it Take to Work? Dolutegravir is a brand name. Its generic name is Dolutegravir.

Introduction

Dolutegravir (branded as Tivicay) is a novel integrase inhibitor approved in the US in 2013 to treat HIV infection. It works to prevent HIV from replicating by inhibiting a viral enzyme called integrase. It is typically used in combination with other antiretroviral medications to treat HIV.

Uses for

Dolutegravir is used to treat HIV-1 infection in adults and children who weigh at least 13 kg (about 28 pounds). It is not used to treat HIV-2 infection.

Mechanism of Action

Dolutegravir works by inhibiting HIV activity by blocking the virus' integrase enzyme. This enzyme is responsible for the integration of viral genetic material into the host cell's deoxyribonucleic acid (DNA), which is necessary for the virus to replicate. By blocking this enzyme, dolutegravir works to stop HIV from replicating and prevent it from progressing to the late stages of infection.

How Long Does it Take to Work?

When used in combination with other antiretroviral medications, the effects of dolutegravir can be seen within the first two weeks, though some patients may start to show improvement even sooner.

Absorption

Dolutegravir is rapidly and completely absorbed following oral administration.

Route of Elimination

The primary route of elimination for dolutegravir is through the kidneys, where about 80% of the drug is eliminated.

Dosage

The recommended dosage of dolutegravir for adults is a 50mg tablet orally once daily with or without food. For HIV-infected adults with mild or no renal impairment, the recommended dosage is 50mg once daily. For adults with moderate renal impairment the recommended dosage is 25mg once daily. For adults with severe renal impairment the recommended dosage is 20mg once daily. For HIV-infected children who weigh at least 13 kg, the recommended dosage is 20mg once daily.

Administration

Dolutegravir should be taken with or without food once a day. It is important to take dolutegravir at the same time each day and to not take more than the recommended amount.

Side Effects

The most common side effects of dolutegravir include nausea, headache, dizziness, diarrhea, tiredness, rash, and vomiting. Other more serious side effects include severe diarrhea, heart problems, low white blood cell count, and liver problems.

Toxicity

Toxicities of dolutegravir are minimal. However, in rare instances, an increased risk of birth defects has been reported in women who take dolutegravir during pregnancy.

Precautions

Before beginning treatment with dolutegravir, patients should inform their doctor of all medications they may be taking, any pre-existing medical conditions, and any allergies they have. In addition, women who are pregnant or breastfeeding should not take dolutegravir unless instructed otherwise.

Interaction

Dolutegravir can interact with certain types of medications, including drugs that affect the liver, drugs that affect the kidneys, and drugs that are metabolized by the CYP3A4 enzyme. Patients should inform their doctor of all other medications they may be taking before starting treatment.

Disease Interaction

People with Hepatitis B or C, impaired renal function, and other liver diseases should take caution when taking dolutegravir as their body may be more sensitive to it.

Drug Interaction

Dolutegravir may interact with certain drugs, including antifungal medications, antiretroviral drugs, antimycobacterials, non-nucleoside reverse transcriptase inhibitors, integrase strand transfer inhibitors, protease inhibitors, potassium-sparing diuretics, street drugs, and oral contraceptives. Patients should inform their doctor of all other medications they may be taking.

Food Interaction

No significant food interactions have been identified when taking dolutegravir.

Pregnancy Use

Dolutegravir should not be used in pregnant women unless the potential benefit to the mother outweighs the potential risk to the fetus.

Lactation Use

Dolutegravir should not be used by women who are breastfeeding.

Acute Overdose

If an overdose of dolutegravir is suspected, seek medical attention immediately.

Contraindication

Dolutegravir is contraindicated in patients with hypersensitivity to it or any of its excipients, as well as patients with severe renal impairment (creatinine clearance below 15 ml/min).

Use Direction

Dolutegravir should be taken orally with or without food once daily.

Storage Condition

Dolutegravir should be stored at room temperature (15°C to 30°C) in a dry place, away from heat and direct light.

Volume of Distribution

Dolutegravir has a steady-state volume of distribution of 52.4 L ± 13.4 L.

Half Life

The elimination half-life of dolutegravir is approximately eight to nine hours in healthy adults.

Clearance

Dolutegravir has an estimated clearance of 47.6 L/hr ± 12.4 L/hr in healthy adults.

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