Instgra — Dolutegravir 50 mg

Instgra is supplied in the form of film-coated tablets for oral administration. Each unit contains a fixed therapeutic dose:

• Active Compound: Dolutegravir sodium — equivalent to 50 mg of free base dolutegravir per tablet.
• Excipients: Mannitol, microcrystalline cellulose, sodium starch glycolate, povidone K29/32, sodium stearyl fumarate; film coating composition: purified talc, titanium dioxide, macrogol, polyvinyl alcohol, colorants.
• Appearance: Round, coated tablets. Supplied in high-density plastic bottles containing 30 tablets, fitted with a child-resistant cap, complete with a desiccant and a cardboard box.

Pharmacodynamics: Dolutegravir is an HIV-1 integrase inhibitor. It binds to the active site of the integrase and blocks the strand transfer step of retroviral DNA integration, preventing provirus formation and disrupting the HIV life cycle. The drug possesses high selectivity and does not inhibit human cellular enzymes.

Pharmacokinetics: Following oral administration, dolutegravir is rapidly absorbed, reaching peak plasma concentration within 2–3 hours. Food intake with high fat content moderately increases absorption. The drug is highly bound to plasma proteins (over 99%). It is primarily metabolized in the liver via the UGT1A1 enzyme and partially by the CYP3A4 isoenzyme. Excretion occurs mainly via feces (53%) and kidneys in urine (31% as metabolites).

Instgra 50 mg is utilized as part of combination antiretroviral therapy (ART) regimens as prescribed by an infectious disease specialist for the following conditions:

• 🔹 HIV-1 Infection in Adults: Treatment of both ART-naive patients (who have not received prior treatment) and individuals with prior experience of ineffective treatment with other drug classes.
• 🔹 HIV-1 Infection in Adolescents: Therapy for children and adolescents aged 12 years and older with a body weight of at least 40 kg, without known resistance mutations to integrase inhibitors.

The dosage regimen, modification of the scheme, and efficacy monitoring are managed strictly by an HIV specialist based on viral load and CD4 lymphocyte counts:

• Recommended Dosage: For most patients, the standard therapeutic dose is 50 mg (1 tablet) taken once daily. In cases of confirmed or suspected viral resistance to first-generation integrase inhibitors, or during co-administration with certain enzyme inducers, the dose is increased to 50 mg twice daily.
• Method of Administration: Tablets are swallowed whole with a sufficient amount of clean water, with or without food. Tablets must not be broken, crushed, or chewed to avoid altering the pharmacokinetic profile.
• Dosing Regimen: It is critically important to maintain a strict routine and take the drug daily at the same time. Missing doses is highly discouraged, as it can compromise the overall efficacy of ART.
• Duration of Treatment: Therapy with Instgra is long-term (lifelong) and is carried out continuously under regular laboratory safety monitoring.

The use of Instgra tablets is restricted or strictly contraindicated in the presence of the following clinical factors:

• ⛔ Hypersensitivity: Individual intolerance to dolutegravir or any excipient component included in the formulation.
• ⛔ Co-administration with Dofetilide: Absolute contraindication due to the risk of significant increases in dofetilide plasma concentrations, which can cause life-threatening arrhythmias.
• ⛔ Pediatric Use: Children under 12 years of age or weighing less than 40 kg (for this 50 mg strength).

Dolutegravir interacts with several medications, necessitating adjustment of timing or dosing:

• ❌ Antacids and Metal Cations: Preparations containing magnesium, aluminum, calcium, iron, or multivitamins decrease dolutegravir absorption. Instgra should be taken 2 hours before or 6 hours after such preparations.
• ❌ Enzyme Inducers (Rifampicin, Phenytoin): Significantly decrease blood plasma concentrations of dolutegravir. In these combinations, increasing the Instgra frequency to twice daily may be required.
• ❌ Metformin: Dolutegravir increases metformin plasma concentrations, requiring careful monitoring of blood glucose levels and potential dose adjustments of the hypoglycemic agent.

Prescribing the drug during pregnancy planning and gestation requires a balanced assessment of the benefits and potential risks:

• Pregnancy Risks: Current clinical data do not confirm a significant risk of neural tube defects in the fetus associated with dolutegravir intake; however, the final decision regarding the treatment scheme remains with the doctor.
• Contraception: Women of childbearing potential taking Instgra are advised to discuss reliable contraceptive methods with their doctor during the therapy period.
• Breastfeeding: HIV-infected women are strongly advised against breastfeeding to fully eliminate the risk of viral transmission to the child via breast milk, into which dolutegravir also penetrates.

In most instances, the medication is well-tolerated by patients, though the following adverse events may develop during therapy:

• 🟢 Nervous System (Common): Headache, dizziness, insomnia, abnormal or vivid dreams, fatigue.
• 🟡 Gastrointestinal Tract: Nausea, diarrhea, vomiting, flatulence, abdominal discomfort, or pain.
• 🟡 Allergic Reactions: Skin rash, pruritus; rare cases of severe hypersensitivity reactions accompanied by fever and liver dysfunction have been reported.
• 🟠 Laboratory Parameters: Transient asymptomatic increases in serum creatinine (due to inhibition of renal tubular secretion), elevated levels of creatine phosphokinase (CPK), ALT, and AST.
• ⚠️ Urgent Medical Attention: If signs of a severe skin rash appear, accompanied by facial swelling, difficulty breathing, high fever, or yellowing of the skin and sclera, the medication must be discontinued and immediate medical help sought.

Instances of acute specific overdose with dolutegravir in clinical practice are limited and do not display specific life-threatening patterns:

• Main Manifestations: Intake of ultra-high doses may result in increased severity of known side effects (pronounced dizziness, nausea, severe headache, lethargy).
• First Aid: In case of accidental ingestion of an excessive number of tablets, gastric lavage, administration of activated charcoal, or other enterosorbents is recommended.
• Treatment: There is no specific antidote. Supportive and symptomatic therapy under the control of vital signs is carried out. Hemodialysis is ineffective as dolutegravir is highly bound to plasma proteins.

Proper storage of the bottle guarantees the stability of the therapeutic properties of the integrase inhibitor throughout its entire shelf life:

• 🌡️ Temperature Regimen: Store in the original, tightly closed bottle in a dry place at a temperature not exceeding 30°C. Avoid sharp temperature fluctuations.
• 📦 Environmental Protection: Protect from excessive moisture and direct sunlight. Do not remove the silica gel desiccant from the bottle until all tablets have been used.
• 👶 Accessibility: The drug must be stored out of reach of children and pets.
• ⏳ Special Instructions: Do not use the tablets after the expiration date (24 months) indicated by Emcure on the package and bottle label. Unused medication must be disposed of properly.