Abacavir, dolutegravir, and lamivudine

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For abacavir, dolutegravir, and lamivudine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to abacavir, dolutegravir, and lamivudine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of abacavir, dolutegravir, and lamivudine combination in the pediatric population. Safety and efficacy have not been established.

Geriatric

Although appropriate studies on the relationship of age to the effects of abacavir, dolutegravir, and lamivudine combination have not been performed in the geriatric population, no geriatric-specific problems have been documented to date. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution for patients receiving abacavir, dolutegravir, and lamivudine combination.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking abacavir, dolutegravir, and lamivudine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using abacavir, dolutegravir, and lamivudine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Dofetilide

Using abacavir, dolutegravir, and lamivudine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amprenavir
• Carbamazepine
• Dabrafenib
• Dasabuvir
• Efavirenz
• Enzalutamide
• Eslicarbazepine Acetate
• Etravirine
• Fosamprenavir
• Fosphenytoin
• Metformin
• Netupitant
• Nevirapine
• Orlistat
• Oxcarbazepine
• Phenytoin
• Primidone
• Ribavirin
• Rifampin
• Rifapentine
• St John's Wort
• Tipranavir

Using abacavir, dolutegravir, and lamivudine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aluminum
• Calcium
• Iron
• Magaldrate
• Magnesium
• Methadone
• Sucralfate
• Tipranavir
• Zinc

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of abacavir, dolutegravir, and lamivudine. Make sure you tell your doctor if you have any other medical problems, especially:

• Diabetes or
• Heart disease or
• Hyperlipidemia (high cholesterol or fats in the blood) or
• Hypertension (high blood pressure)—May increase risk for heart attack.

• Genetic condition (eg, gene variation called HLA-B*5701)—This condition may increase the risk for serious and life-threatening side effects.

• Hepatitis B or C, or history of—Use with caution. May make this condition worse.

• Kidney disease or
• Liver disease, mild—Use is not recommended in patients with these conditions.

• Liver disease, moderate or severe—Should not be used in patients with these conditions.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of too much lactic acid in the blood (lactic acidosis) like fast breathing, fast heartbeat, a heartbeat that does not feel normal, very bad upset stomach or throwing up, feeling very sleepy, shortness of breath, feeling very tired or weak, very bad dizziness, feeling cold, or muscle pain or cramps.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Very bad dizziness or passing out.
• Chest pain or pressure.
• Low mood (depression).
• Mouth sores.
• Eye irritation.
• Muscle pain or weakness.
• Joint pain.
• A burning, numbness, or tingling feeling that is not normal.
• Swelling.
• Change in body fat.
• Shortness of breath.
• Swollen gland.
• This medicine may help the immune system work. If you have an infection that you did not know you had, it may show up when you take abacavir, dolutegravir, and lamivudine. Tell your doctor right away if you notice any signs of infection like fever, sore throat, weakness, cough, or shortness of breath after you start this medicine.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Store in the original container. Do not take out the antimoisture cube or packet.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• Abacavir Sulfate, Dolutegravir, and Lamivudine
• Abacavir/Dolutegravir/Lamivudine
• Dolutegravir, Lamivudine, and Abacavir
• Lamivudine, Abacavir, and Dolutegravir

The combination of abacavir, dolutegravir, and lamivudine is used alone or along with other medications to treat HIV infection. Abacavir and lamivudine are in a class of medications called nucleoside analogue reverse transcriptase inhibitors (NRTIs) and dolutegravir is in a class of medications called integrase strand transfer inhibitors (INSTIs). They work by decreasing the amount of HIV in your blood and increasing the number of immune cells that help fight infections in your body. Although abacavir, dolutegravir, and lamivudine will not cure HIV, these medications may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other life-style changes may decrease the risk of getting or transmitting the HIV virus to other people.

The combination of abacavir, dolutegravir, and lamivudine comes as a tablet to take by mouth. It is usually taken, with or without food, once a day. Take abacavir, dolutegravir, and lamivudine at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take abacavir, dolutegravir, and lamivudine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Abacavir, dolutegravir, and lamivudine help to control HIV infection but do not cure it. Continue to take abacavir, dolutegravir, and lamivudine even if you feel well. Do not stop taking abacavir, dolutegravir, and lamivudine without talking to your doctor.

• Triumeq^®

Applies to abacavir / dolutegravir / lamivudine: oral tablet

Along with its needed effects, abacavir / dolutegravir / lamivudine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking abacavir / dolutegravir / lamivudine:

• Dark urine
• general tiredness and weakness
• light-colored stools
• nausea and vomiting
• upper right abdominal or stomach pain
• yellow eyes and skin

• Abdominal or stomach pain or discomfort
• blistering, peeling, or loosening of the skin
• bloody urine
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• burning, dry, or itching eyes
• chills
• confusion
• cough
• decreased appetite
• decreased frequency or amount of urine
• diarrhea
• difficulty with moving
• difficulty with swallowing
• discharge or excessive tearing
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fainting
• fast heartbeat
• fast, shallow breathing
• fever
• general feeling of discomfort or illness
• headache
• hives, itching, or rash
• increased thirst
• joint or muscle pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• light-colored stools
• lower back or side pain
• muscle pain, cramping, or stiffness
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid, shallow breathing
• red, irritated eyes
• redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
• sleepiness
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• stomach pain, continuing
• sweating
• swelling of the face, fingers, lower legs
• swelling or puffiness of the face
• swollen, painful, or tender lymph glands in the neck, armpit, or groin
• tightness in the chest
• troubled breathing
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
• weight gain

Some side effects of abacavir / dolutegravir / lamivudine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Discouragement
• feeling sad or empty
• irritability
• loss of interest or pleasure
• trouble concentrating
• trouble sleeping

• Acid or sour stomach
• belching
• difficulty with moving
• excess air or gas in the stomach or intestines
• full or bloated feeling
• heartburn
• indigestion
• passing gas
• pressure in the stomach
• sleepiness or unusual drowsiness
• stomach upset
• swelling of the abdominal or stomach area
• weight loss

• Hair loss
• thinning of the hair
• weight gain around your neck, upper back, breast, or waist

CrCl less than 50 mL/min: Not recommended; individual components should be used.

Data not available

Administration advice:
-May administer without regard to food
-Administer products containing polyvalent cations and supplements containing calcium or iron 6 hours before or 2 hours after this drug; calcium or iron supplements and this drug may be administered together with food.
-Consult the manufacturer product information regarding missed doses.

Storage requirements:
-Store and dispense in original container; protect from moisture; keep bottle tightly closed; do not remove desiccant.

General:
-Screening for HLA-B*5701 allele is recommended before starting this drug.
-Before starting this drug, medical history should be reviewed for prior exposure to any abacavir-containing product.
-This drug should not be used alone in patients with history of resistance to any of the active components.
-This drug should not be used alone in patients with resistance-associated integrase substitutions or clinically suspected integrase strand transfer inhibitor resistance; the dose of dolutegravir in this product is insufficient in such patients. The manufacturer product information for dolutegravir should be consulted.

Monitoring:
-Hepatic: Appropriate laboratory testing (before starting therapy) and for hepatotoxicity (during therapy) in patients with underlying hepatic disease such as hepatitis B or C; hepatic function of HIV-1/HBV coinfected patients with clinical and laboratory follow-up (for at least several months after stopping this drug)

Patient advice:
-Always read the Medication Guide and Warning Card (with information about abacavir hypersensitivity reaction) dispensed with each new and refill prescription; carry the Warning Card.
-Contact physician immediately if signs/symptoms of hypersensitivity develop; do not restart this or any other abacavir-containing product after a hypersensitivity reaction.
-If this drug is stopped for any reason besides hypersensitivity, do not restart it (or any other abacavir-containing product) without consulting physician; medical care must be readily accessible.

Breastfeeding is not recommended during use of this drug; if replacement feeding is not an option, a different drug may be preferred. Excreted into human milk: Unknown (dolutegravir); Yes (abacavir, lamivudine) Excreted into animal milk: Yes (dolutegravir) Comments: -The effects in the nursing infant are unknown. -The US CDC, American Academy of Pediatrics, and manufacturer advise HIV-infected women not to breastfeed to avoid postnatal transmission of HIV to a child who may not yet be infected. -Local guidelines should be consulted if replacement feeding is not an option.

ABACAVIR: Breast milk from 15 women and blood samples from 9 of their partially or exclusively breastfed infants were collected about 1 month postpartum; the mothers were using abacavir 300 mg twice a day for 53 to 182 days (with lamivudine and zidovudine). Breast milk was obtained right before a dose; whole breast milk abacavir levels averaged 0.057 mg/L (about 85% of maternal blood levels). Infant blood was obtained 11 to 17 hours after the last maternal dose and about 1 hour (range: 6 minutes to 35 hours) after the last breastfeeding; plasma abacavir levels were undetectable (less than 16 mcg/L) in 8 of 9 infants. LAMIVUDINE: Based on more than 200 mother/child pairs treated for HIV, serum lamivudine levels in breastfed infants of mothers treated for HIV are very low (less than 4% of maternal serum levels) and gradually decrease to undetectable levels by 24 weeks of age. Milk samples were obtained daily before breastfeeding. The milk lamivudine level averaged 1.2 mg/L (range: less than 0.5 to 6.1 mg/L) with 300 mg twice a day (n=10) and 0.9 mg/L (range: less than 0.5 to 8.2 mg/L) with 150 mg twice a day plus zidovudine (n=10). Milk samples from 20 women taking lamivudine 150 mg orally twice a day as part of combination antiretroviral therapy (cART) and serum levels from their infants were obtained at 2 or 5 months postpartum, about 4 hours (range: 1 to 8.5 hours) after the last dose. The drug level in breast milk averaged 1.8 mg/L and the infant serum lamivudine level averaged 28 mcg/L (range: less than 14 to 53 mcg/L). Breast milk from 15 women and blood samples from 24 of their partially or exclusively breastfed infants were collected about 1 month postpartum; the mothers were using lamivudine 150 mg twice a day for 53 to 182 days (with [abacavir or lopinavir-ritonavir] and zidovudine). Breast milk was obtained right before a dose; whole breast milk lamivudine levels averaged 0.14 mg/L (about 74% of maternal blood levels). Infant blood was obtained 11 to 18 hours after the last maternal dose and about 1 hour (range: 6 minutes to 35 hours) after the last breastfeeding. Plasma lamivudine levels were undetectable (less than 7 mcg/L) in all infant samples. Serum and breast milk from 58 mothers taking lamivudine 150 mg twice a day (with nevirapine and zidovudine) and serum levels from their 58 infants were analyzed. Mothers started lamivudine at 34 to 36 weeks gestation and continued until 6 months postpartum; they were instructed to exclusively breastfeed for 5.5 months. Breast milk and serum samples were collected within 24 hours after delivery and at 2, 6, 14, and 24 weeks postpartum; breast milk was collected at various times after the prior dose. The breast milk lamivudine level averaged 1214 mcg/L (all visits). The infant dried blood spot lamivudine levels averaged 67 mcg/L at delivery, 32 mcg/L at week 2, 24 mcg/L at week 6, 20 mcg/L at week 14, and were not measurable (less than 16 mcg/L) at week 24 postpartum. A fully breastfed infant would receive 182 mcg/kg/day of lamivudine (estimated). Blood and milk samples were obtained from 40 women on postpartum prophylaxis (with lamivudine, nevirapine, and [zidovudine or stavudine]; doses not provided) once during the first 3 days postpartum and once at 7 days postpartum. Samples were collected after a dose at 5.3 hours (range: 0 to 99 hours) for the first sample and 6 hours (range: 4.3 to 20 hours) for the second sample. Breast milk lamivudine levels averaged 0.4 mg/L (n=20) for the first sample and 0.4 mg/L (n=30) for the second sample; these levels were 2.9 to 3.3 times the coinciding maternal serum levels. Mothers using lamivudine (dose not provided) as part of cART provided 47 breast milk and serum samples at 6, 12, and 24 weeks postpartum. The breast milk lamivudine levels at about 14 hours after the last dose averaged 510 (17 samples), 387 (17 samples), and 310 mcg/L (13 samples). Milk levels were about 2.6 times (interquartile range: 1.1 to 3.5 times) the maternal plasma levels; milk to plasma ratio was 2.96 in 49 patients in a related study (same authors). Infant serum levels measured about 14 hours after the last maternal dose averaged 13, 10, and 5 mcg/L at 6 (17 samples), 12 (17 samples), and 24 (13 samples) weeks of age, respectively, which was 6% of the maternal serum level. A total of 206 milk samples were obtained at birth, 1, 3, and/or 6 months postpartum from 66 mothers using lamivudine 150 mg twice a day as part of cART and 64 blood samples from their breastfed infants were analyzed at 1, 3, and/or 6 months postpartum; samples were collected at about 4.5 hours (range: 3.5 to 6 hours) after the prior maternal dose and about 30 minutes (range: 20 to 60 minutes) after nursing. Breast milk lamivudine level averaged 446 mcg/L (range: 269 to 683 mcg/L). Infant plasma lamivudine level averaged 18 mcg/L (range: 7 to 35 mcg/L), which averaged 2% (range: 0 to 4%) of the maternal serum level. In a continuation of this study, 65 breast milk samples (after the same dose at 1, 3, and 6 months postpartum) and 22 blood samples (from 17 breastfed infants [extent not provided] between 1 and 6 months) were collected for drug analysis; lamivudine levels averaged 684 mcg/L in breast milk and 29.2 mcg/L in infant blood. Unclear if some of the same patients from the first study were in the latter study. Mothers (n=30) starting lamivudine 150 mg orally twice a day (with zidovudine and lopinavir-ritonavir) at delivery provided plasma and breast milk samples at 6, 12, or 24 weeks postpartum (n=10 at each time). Maternal plasma and breast milk samples were collected about 14.9 hours after the prior evening dose, before the morning dose, and 2, 4, and 6 hours after the dose. Infant plasma samples were collected before the first maternal dose and at 2, 4, and 6 hours after the maternal dose. Breastfeeding was not restricted during the study. Detectable lamivudine levels (at least 10 mcg/L) were found in 107 of 121 breast milk samples and 107 of 115 infant plasma samples; breast milk level averaged 0.94 mg/L over the 6 hours and infant plasma level averaged 180 mcg/L.