Summary of Product Characteristics (SMPC)

1. Name of the Medicinal Product

TAPIVIR 50 - Dolutegravir 50 mg Tablets

TAPIVIR DT 10 - Dolutegravir 10 mg Dispersible Tablets

2. Qualitative and Quantitative Composition

TAPIVIR 50:

• Active substance: Dolutegravir (as sodium) 50 mg per tablet
• Excipients: Microcrystalline cellulose, croscarmellose sodium, magnesium stearate, hypromellose, titanium dioxide (E171), iron oxide red (E172), macrogol

TAPIVIR DT 10:

• Active substance: Dolutegravir (as sodium) 10 mg per tablet
• Excipients: Mannitol, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, aspartame (E951), strawberry flavor

Pharmaceutical Form

TAPIVIR 50: Film-coated tablets, round, pink colored with "DTG 50" embossed

TAPIVIR DT 10: Dispersible tablets, white to off-white, round shaped with strawberry flavor

Clinical Particulars

4.1 Therapeutic Indications

Dolutegravir is indicated for the treatment of human immunodeficiency virus (HIV-1) infection in combination with other antiretroviral agents in adults and pediatric patients weighing at least 3 kg.

4.2 Posology and Method of Administration

Adults: 50 mg once daily or 50 mg twice daily depending on concurrent medications

Pediatric patients: Dosing based on body weight (see dosage guide page for detailed information)

Administration: Tablets should be swallowed whole with water. May be taken with or without food.

4.3 Contraindications

• Hypersensitivity to dolutegravir or any excipients
• Concurrent use with dofetilide (risk of QT prolongation)

4.4 Special Warnings and Precautions for Use

• Hepatic impairment: Use with caution in patients with hepatic disease
• Renal impairment: No dose adjustment needed for mild to moderate renal impairment
• Immune reconstitution inflammatory syndrome (IRIS): May occur in patients with advanced HIV
• Hypersensitivity reactions: Discontinue immediately if signs of hypersensitivity develop
• Drug interactions: See section 4.5 for important interactions

4.5 Interaction with Other Medicinal Products

Drugs that may increase dolutegravir levels:

• Protease inhibitors (ritonavir, cobicistat)
• Certain antibiotics

Drugs that may decrease dolutegravir levels:

• Rifampicin (may require dose adjustment)
• Phenytoin, carbamazepine, phenobarbital
• St. John's Wort

Antacids and supplements: Dolutegravir should be taken 2 hours before or 6 hours after antacids containing aluminum or magnesium

4.6 Fertility, Pregnancy and Lactation

Pregnancy: Dolutegravir can be used during pregnancy. Adequate and well-controlled studies have shown no adverse effects on the fetus.

Lactation: It is unknown whether dolutegravir is excreted in human breast milk. Breastfeeding is not recommended in HIV-positive women.

4.7 Effects on Ability to Drive and Operate Machinery

Dolutegravir is not expected to affect the ability to drive or operate machinery.

4.8 Undesirable Effects

Common side effects (≥1/100 to <1/10):

• Headache
• Nausea
• Diarrhea
• Fatigue
• Insomnia

Uncommon side effects (≥1/1,000 to <1/100):

• Hypersensitivity reactions
• Rash
• Elevated liver enzymes

4.9 Overdose

There is no specific antidote for dolutegravir overdose. Treatment is supportive and symptomatic. Activated charcoal may reduce absorption if administered shortly after overdose.

Summary of Product Characteristics

5.1 Pharmacodynamic Properties

Mechanism of Action: Dolutegravir is an HIV integrase strand transfer inhibitor (INSTI). It inhibits the catalytic activity of HIV integrase, preventing integration of HIV DNA into the host genome.

Antiviral Activity: Dolutegravir demonstrates potent activity against HIV-1 with a 50% effective concentration (EC50) in the nanomolar range.

5.2 Pharmacokinetic Properties

Absorption: Dolutegravir is rapidly absorbed with peak plasma concentrations occurring 0.5-3 hours after oral administration.

Distribution: Highly protein bound (>99%) to human plasma proteins.

Metabolism: Primarily metabolized via glucuronidation by UGT1A1.

Elimination: Mainly eliminated in feces (approximately 53%) and urine (approximately 31%).

Half-life: Approximately 13-14 hours.

Pharmaceutical Particulars

6.1 List of Excipients

See section 2 for complete list of excipients

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

24 months when stored in original container

6.4 Special Precautions for Storage

Store below 30°C. Keep the container tightly closed. Protect from moisture.

6.5 Nature and Contents of Container

Blister packs containing 10, 30, or 90 tablets. Bottles containing 30, 60, or 90 tablets.

6.6 Special Precautions for Disposal

Dispose of unused medicinal product in accordance with local pharmaceutical waste disposal regulations.