Dovato (Dolutegravir/Lamivudine)

How does Dovato work?

The medications in Dovato work to reduce viral replication, but they accomplish this through two distinct mechanisms. Dolutegravir is an HIV integrase inhibitor. This drug prevents the virus from incorporating its DNA into healthy host cells. Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) that inhibits the virus from making copies of itself. Viral replication is a multi-step process, and Dovato targets two distinct points within that replication cycle.

Dosage

Dovato is available in the following strength:

• 50 mg/300 mg

The dose of Dovato is started and maintained at 50 mg/300 mg once daily. If you are also on carbamazepine or rifampin, an additional 50 mg dose of dolutegravir can be taken 12 hours after your regular Dovato dose. With all HIV therapies, the goal is to reduce a patient’s viral load to an undetectable level. In a clinical trial, 91% of patients taking Dovato for 48 weeks reached undetectable levels of less than 50 copies per mL.

The maximum daily dose should not exceed 100 mg of dolutegravir and 300 mg of lamivudine.

Overdose

Signs or symptoms indicating an overdose have not been documented for this medication. Continuous hemodialysis may remove lamivudine from the body if an overdose is suspected. If you suspect an overdose, immediately reach out for emergency medical care or call the Poison Help line at 800-222-1222.

Side Effects

The most common side effects of Dovato include the following:

• Diarrhea
• Nausea
• Headache
• Anxiety
• Tiredness
• Trouble sleeping

Tell your doctor if you notice:

• Symptoms of an allergic reaction such as redness or swelling of the eyes, mouth, lips, or tongue, peeling or blistering of the skin and mouth, and difficulty breathing.
• Symptoms of liver dysfunction such as yellowing of the skin and eyes, dark urine, abdominal pain, nausea and vomiting, and loss of appetite.
• Symptoms of lactic acidosis such as excessive stomach and muscle pain, changes in heart rate, extreme tiredness, and cold extremities.

Contact your doctor immediately if you suspect liver dysfunction, lactic acidosis or are experiencing an allergic reaction.

Warnings & Precautions

Children

Dovato has not been studied or approved in children under 12 years old.

Pregnancy and Breastfeeding

Taking Dovato while pregnant can increase the risk of neural tube defects and mitochondrial dysfunction, especially in the first trimester. Starting this medication while you are pregnant or trying to become pregnant is not recommended.

HIV-1 and HBV Coinfection

All patients should be screened for both HIV and hepatitis B virus (HBV). It is common for patients to have both viral infections. There are special treatment considerations for these patients due to the risk of developing severe side effects. Lamivudine resistance may develop, and you may experience worsening HBV when discontinuing Dovato.

Hypersensitivity

Hypersensitivity occurs more frequently with dolutegravir. The symptoms of hypersensitivity may include any of the following: muscle and joint pain, difficulty breathing, severe rash, blistering of the skin or oral ulcers, and painful swelling in the face or tongue. If you have had hypersensitivity reactions to either dolutegravir or lamivudine, you should not take Dovato.

Immune Reconstitution Syndrome

Immune reconstitution syndrome is an inflammatory response that develops when first starting Dovato, which causes dormant infections to resurface. Autoimmune disorders may also develop when first starting this drug.

Serum Lipids and Blood Glucose

Patients may experience increased serum lipids and blood glucose levels.

Kidney Problems

Dovato should not be used in patients with a creatinine clearance of less than 30 mL/min. The dose cannot be safely adjusted. This drug can be taken by patients with a creatinine clearance between 30 and 49 mL/min, but close monitoring will be needed.

Liver Problems

Dovato can be dangerous for patients with severe liver disease (Child-Pugh C). It should be used cautiously in patients with a history of heavy alcohol use or early liver disease (Child-Pugh B). Patients may develop liver dysfunction from taking this drug. Monitoring liver function is often recommended while on Dovato.

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis can be fatal and is related to severe liver dysfunction. Severe hepatomegaly occurs when your liver is enlarged and has a fat buildup; it is also referred to as fatty liver disease. Treatment should be stopped if lactic acidosis or hepatomegaly is suspected.

Hematological

Dovato may cause red cell aplasia, a rare disorder where the bone marrow does not produce enough red blood cells. Red blood cell counts typically return to normal after the drug has been stopped.

Dietary Considerations

Dovato can be taken with or without food.

Drug Interactions

This is not a complete list of drug interactions. Notify your doctor of all your medications, including vitamins and over-the-counter supplements.

Dofetilide

Dofetilide is an antiarrhythmic used for certain heart conditions. Dovato causes an increased amount of dofetilide in the blood, which can be life-threatening. The use of these two medications together is contraindicated.

Cladribine

Cladribine is a chemotherapeutic agent which can be used in leukemias and multiple sclerosis. Taking cladribine with Dovato is contraindicated because of the decreased efficacy of cladribine.

Organic Cation Transporters (OCT-1 and OCT-2) Substrates and Inhibitors

Caution should be used when taking Dovato in combination with drugs that are either substrates or inhibitors of OCT-1 and OCT-2. E.g., clofarabine, erdafitinib, fexinidazole, gilteritinib, pacritinib, and tafenoquine. These combinations increase the risk of developing side effects or decreasing treatment efficacy.

Dalfampridine

Dalfampridine is a potassium channel blocker used for patients with multiple sclerosis. Taking Dovato in combination with dalfampridine may increase the risk of seizures. Caution should be exercised when taking both medications.

Anticonvulsants

Anticonvulsants such as oxcarbazepine, phenytoin, and phenobarbital can impact the efficacy of Dovato. Carbamazepine may also reduce the effectiveness but taking an additional 50 mg dose of dolutegravir can offset this. The additional dose of dolutegravir should be separated by 12 hours from your Dovato dose.

Metformin

Metformin is an antidiabetic medication. The amount of metformin in the blood may increase when taking Dovato. Monitoring for complications while taking both drugs is recommended because the metformin dose may need adjustment.

Rifampin

Rifampin is used to treat certain infections. This combination decreases the amount of dolutegravir in the blood, which could impact the efficacy of Dovato. Data shows that an additional 50 mg dose of dolutegravir should be taken. This dose should be separated by 12 hours from your Dovato dose.

St. John’s Wort (Hypericum perforatum)

St. John’s Wort is a common herbal product that decreases the amount of dolutegravir in the blood; it is not recommended to be taken with Dovato.

Polyvalent Cationic Drugs

Drugs containing polyvalent cations, including antacids, laxatives, and sucralfate, decrease the efficacy of Dovato. Your dose should be taken 2 hours before or 6 hours after taking these polyvalent cationic drugs.

Oral calcium and iron supplements

The amount of dolutegravir in the blood decreases when taking oral calcium, oral iron, or multivitamins that contain calcium or iron. Dovato should be taken 2 hours before or 6 hours after taking calcium or iron-containing medications. However, if these drugs are taken with food, they can all be taken simultaneously.

Sorbitol

Sorbitol may lead to a decreased amount of lamivudine in the blood. Taking sorbitol-containing drugs while on Dovato is not recommended and may require monitoring.

Alternative Medications

Notify your doctor of all prescriptions and supplements you are currently taking. There are individual treatments not listed that you may want to discuss with your doctor.

Complete Regimen

These medications have fixed doses of various drugs that manage HIV through different mechanisms. This often decreases the total number of pills patients must take.

• Atripla (efavirenz + tenofovir disoproxil fumarate + emtricitabine)
• Biktarvy (bictegravir + tenofovir alafenamide + emtricitabine)
• Cabenuva (cabotegravir + rilpivirine)
• Complera (rilpivirine + tenofovir disoproxil fumarate + emtricitabine)
• Delstrigo (doravirine + tenofovir disoproxil fumarate + lamivudine)
• Genvoya (elvitegravir + cobicistat + tenofovir alafenamide + emtricitabine)
• Juluca (dolutegravir + rilpivirine)
• Odefsey (rilpivirine + tenofovir alafenamide + emtricitabine)
• Stribild (elvitegravir + cobicistat + tenofovir disoproxil fumarate + emtricitabine)
• Symfi And Symfi Lo (efavirenz + tenofovir disoproxil fumarate + lamivudine)
• Symtuza (darunavir + cobicistat + tenofovir alafenamide + emtricitabine)
• Triumeq (dolutegravir + abacavir + lamivudine)