Tivicay

• Dizziness: Some patients report a feeling of lightheadedness or vertigo.
• Abnormal Dreams: Vivid or unusual dreams have been reported, though less frequently than with other HIV medications like efavirenz.
• Vomiting and Abdominal Pain: More significant GI distress that may require medical consultation if it leads to dehydration.
• Rash: A mild skin rash may develop. If the rash is severe or accompanied by fever, seek medical attention immediately.

• Depression and Anxiety: While rare, some patients have reported mood changes, including suicidal ideation, particularly those with a pre-existing history of psychiatric illness.
• Myalgia: Muscle pain or weakness.
• Renal Insufficiency: Changes in kidney function markers, though Dolutegravir specifically affects creatinine secretion without necessarily decreasing actual glomerular filtration rate.

> Warning: Stop taking Dolutegravir and call your doctor immediately if you experience any of these serious symptoms:

• Hypersensitivity Reactions: This is a medical emergency. Symptoms include a severe skin rash, fever, general malaise, extreme tiredness, muscle or joint aches, blisters, oral lesions, or swelling of the face, lips, and tongue. If a hypersensitivity reaction occurs, Dolutegravir must be stopped immediately and never restarted.
• Hepatotoxicity (Liver Damage): Signs include yellowing of the skin or eyes (jaundice), dark-colored urine, light-colored stools, nausea, vomiting, or pain on the right side of the stomach area. Patients with Hepatitis B or C are at higher risk for liver enzyme elevations.
• Immune Reconstitution Inflammatory Syndrome (IRIS): As your immune system gets stronger, it may start to fight infections that were already in your body but hidden. This can cause an inflammatory response. Symptoms depend on the underlying infection (e.g., pneumonia, fungal infections).

With prolonged use of Dolutegravir, healthcare providers monitor for:

• Weight Gain: Recent clinical studies (such as the ADVANCE trial) have shown that INSTIs, including Dolutegravir, are associated with more significant weight gain than older drug classes, particularly when combined with tenofovir alafenamide (TAF).
• Metabolic Changes: While generally considered 'lipid-neutral,' long-term monitoring of cholesterol and blood sugar levels is standard practice.
• Bone Density: While less impactful than some other HIV drugs, bone health is always a consideration in long-term HIV management.

As of the current 2026 clinical guidelines, there are no FDA black box warnings specifically for Dolutegravir single-entity products. However, it is important to note that many combination products containing Dolutegravir (like Triumeq) carry black box warnings for other components (such as Abacavir's risk for hypersensitivity). Always check the specific labeling for the exact product you are prescribed.

Report any unusual symptoms or changes in your health to your healthcare provider immediately. Early detection of side effects is key to maintaining a successful long-term treatment plan.

To ensure Dolutegravir is safe and effective for you, your healthcare provider will require regular laboratory monitoring:

• Viral Load (HIV-1 RNA): To ensure the medication is suppressing the virus.
• CD4+ Cell Count: To monitor the health of your immune system.
• Liver Function Tests (LFTs): Specifically ALT, AST, and bilirubin levels, especially in patients co-infected with Hepatitis.
• Serum Creatinine: Dolutegravir can increase creatinine levels by inhibiting a specific transporter (OCT2) in the kidneys. This usually does not indicate a decrease in actual kidney function, but your doctor needs to monitor it to distinguish it from actual kidney damage.

Dolutegravir may cause dizziness or fatigue in some individuals. If you experience these side effects, use caution when driving or operating heavy machinery until you know how the medication affects you.

There is no direct contraindication between Dolutegravir and alcohol. However, excessive alcohol consumption can strain the liver and may make it harder to remember to take your medication on time. Discuss your alcohol intake with your doctor to ensure it does not interfere with your treatment goals.

Never stop taking Dolutegravir without consulting your doctor. Stopping HIV medication causes the viral load to rebound quickly, which can damage your immune system and lead to the development of drug-resistant strains of the virus. If you must stop the medication due to a side effect, your doctor will provide a plan to transition you to a different therapy.

> Important: Discuss all your medical conditions, including liver disease, kidney disease, and pregnancy plans, with your healthcare provider before starting Dolutegravir.

• Cation-containing Antacids and Supplements: Antacids containing aluminum, magnesium, or calcium, as well as iron or zinc supplements, can bind to Dolutegravir in the digestive tract and prevent it from being absorbed.
• Management Strategy: Take Dolutegravir at least 2 hours before or 6 hours after taking these supplements. Alternatively, Dolutegravir and supplements containing calcium or iron can be taken together if taken with food.

• High-Fat Meals: As mentioned, high-fat food increases the absorption of Dolutegravir. While not required for most patients, it is a useful strategy for those with some degree of drug resistance.
• Grapefruit: Unlike many other HIV drugs, Dolutegravir does not have a significant interaction with grapefruit juice.

• St. John's Wort: This herbal supplement is a potent inducer of drug-metabolizing enzymes. It can lower the levels of Dolutegravir in your blood to sub-therapeutic levels, leading to treatment failure and viral resistance. It should be avoided.
• Multivitamins: These often contain iron or zinc. Follow the same timing rules as described for antacids.

• Serum Creatinine: Dolutegravir consistently increases serum creatinine levels within the first few weeks of treatment. This is due to the inhibition of the tubular secretion of creatinine and does not reflect a change in the actual glomerular filtration rate (GFR). This can lead to a 'false' appearance of kidney decline if the clinician is not aware of this specific pharmacological effect.

For each interaction, the primary mechanism involves either the induction/inhibition of the UGT1A1 enzyme or the inhibition of the OCT2 renal transporter. The clinical consequence is either increased drug toxicity (as with Metformin or Dofetilide) or reduced efficacy of the HIV treatment (as with Rifampin or Antacids).

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter vitamins and minerals.

There is no evidence of broad cross-sensitivity between Dolutegravir and other classes of HIV medications (like NRTIs or Protease Inhibitors). However, if a patient has reacted to other integrase inhibitors (like Cabotegravir), healthcare providers should exercise extreme caution, although cross-reactivity is not guaranteed.

> Important: Your healthcare provider will evaluate your complete medical history, including any previous drug allergies and current heart health, before prescribing Dolutegravir.

Dolutegravir is approved for pediatric patients weighing at least 3 kg. It is one of the few integrase inhibitors with a dispersible tablet formulation (Tivicay PD) that allows for dosing in infants as young as 4 weeks. It has been shown to be safe and effective in children, with side effects similar to those seen in adults. It is not currently approved for infants weighing less than 3 kg.

Older adults may be at higher risk for side effects due to age-related declines in kidney or liver function. Furthermore, geriatric patients are more likely to be taking medications for hypertension, diabetes, or heart disease, increasing the risk of drug-drug interactions. Clinical monitoring should focus on renal function and potential weight gain.

No dose adjustment is needed for patients with kidney disease. However, for those on dialysis, Dolutegravir should be administered after the dialysis session, as it is not significantly removed by the procedure.

Patients with mild-to-moderate liver disease can take the standard dose. Those with severe cirrhosis (Child-Pugh C) should generally avoid Dolutegravir due to a lack of safety data in that specific population.

> Important: Special populations require individualized medical assessment and frequent monitoring to ensure the safest possible treatment outcomes.

| Parameter | Value |

|---|---|

| Bioavailability | Increased with food (not quantified as absolute %) |

| Protein Binding | >99% |

| Half-life | ~14 hours |

| Tmax | 2 - 3 hours |

| Metabolism | UGT1A1 (Primary), CYP3A4 (Minor) |

| Excretion | Fecal 53%, Renal 31% |

• Molecular Formula: C20H18F2N3O5Na (as sodium salt)
• Molecular Weight: 441.36 g/mol
• Solubility: Slightly soluble in water.
• Structure: It features a tricyclic core that is optimized for deep binding within the integrase-DNA complex, which contributes to its long 'dissociation half-life' (how long it stays stuck to the enzyme).

Dolutegravir belongs to the Integrase Strand Transfer Inhibitor (INSTI) class. Other drugs in this class include Raltegravir (Isentress), Elvitegravir (Vitekta), Bictegravir (in Biktarvy), and Cabotegravir (Vocabria/Vocabria).