Abacavir and lamivudine

Name: Abacavir and lamivudine

Abacavir and lamivudine side effects

Stop using this medicine and call your doctor at once if you have symptoms of an allergic reaction from two or more of these specific side effect groups:

  • Group 1 - fever;

  • Group 2 - rash;

  • Group 3 - nausea, vomiting, diarrhea, stomach pain;

  • Group 4 - general ill feeling, extreme tiredness, body aches;

  • Group 5 - shortness of breath, cough, sore throat.

Once you have an allergic reaction to abacavir, you must never use it again. If you stop taking this medicine for any reason, talk to your doctor before you start taking it again.

Abacavir and lamivudine can also cause serious or fatal side effects on the liver. Call your doctor at once if you have:

  • swelling around your midsection, upper stomach pain, unusual tiredness, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Early symptoms of lactic acidosis may get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired.

Abacavir and lamivudine may increase your risk of certain infections or autoimmune disorders by changing the way your immune system works. Symptoms may occur weeks or months after you start treatment with abacavir and lamivudine. Tell your doctor if you have:

  • signs of a new infection--fever, night sweats, swollen glands, mouth sores, diarrhea, stomach pain, weight loss;

  • chest pain (especially when you breathe), dry cough, wheezing, feeling short of breath;

  • cold sores, sores on your genital or anal area;

  • rapid heart rate, feeling anxious or irritable, weakness or prickly feeling, problems with balance or eye movement;

  • trouble speaking or swallowing, severe lower back pain, loss of bladder or bowel control; or

  • swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence, loss of interest in sex.

Common side effects include:

  • sleep problems (insomnia);

  • headache, dizziness, tiredness, depression;

  • nausea, diarrhea; or

  • changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and trunk).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Abacavir and lamivudine dosing information

Usual Adult Dose for HIV Infection:

1 tablet orally once a day

Use: In combination with other antiretroviral agents, for the treatment of HIV-1 infection

Usual Adult Dose for Nonoccupational Exposure:

US CDC recommendations: 1 tablet orally once a day
Duration of therapy: 28 days

Comments:
-Recommended as part of alternative regimens (NNRTI-based, protease inhibitor-based, or triple NRTI) for nonoccupational postexposure prophylaxis of HIV infection
-Prophylaxis should be started as soon as possible, within 72 hours of exposure.
-Current guidelines should be consulted for additional information.

Usual Adult Dose for Occupational Exposure:

US Public Health Service working group recommendations: 1 tablet orally once a day
Duration of therapy: 28 days, if tolerated

Comments:
-Only with expert consultation, as part of an alternative regimen for use as HIV postexposure prophylaxis
-Prophylaxis should be started as soon as possible, preferably within hours after exposure.
-The optimal duration of prophylaxis is unknown and may differ based on institution protocol.
-Current guidelines should be consulted for additional information.

Usual Pediatric Dose for HIV Infection:

At least 25 kg: 1 tablet orally once a day

Comments:
-Use of the individual components is recommended for patients less than 25 kg; the manufacturer product information for abacavir and lamivudine should be consulted.
-Before prescribing this drug, the ability to swallow tablets should be assessed.

Use: In combination with other antiretroviral agents, for the treatment of HIV-1 infection

Proper Use of abacavir and lamivudine

Take abacavir and lamivudine exactly as directed by your doctor. Do not take it more often, and do not take it for a longer time than your doctor ordered. Also, do not start or stop taking abacavir and lamivudine without checking first with your doctor.

abacavir and lamivudine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

abacavir and lamivudine can be taken with or without food.

When your supply of abacavir and lamivudine runs low, get more from your pharmacy or from your doctor. The amount of virus in your blood may increase if the medicine is stopped, even for a short time. The virus may develop resistance to abacavir and lamivudine and be harder to treat.

abacavir and lamivudine will be given together with other medicines for HIV infection. Take all of the medicines your doctor gives you at the right time of day. These medicines work best when there is a constant amount in the blood. To help keep the amount constant, do not miss any doses. If you need help in planning the best times to take your medicines, check with your doctor.

Abacavir and lamivudine combination contains a fixed amount of each medicine in the tablet.

Dosing

The dose of abacavir and lamivudine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of abacavir and lamivudine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For HIV infection:
      • Adults—One tablet once a day. Each tablet contains 600 milligrams (mg) of abacavir and 300 mg of lamivudine.
      • Children weighing at least 25 kilograms (kg)—One tablet once a day.
      • Children weighing less than 25 kg—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of abacavir and lamivudine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

How is this medicine (Abacavir and Lamivudine) best taken?

Use abacavir and lamivudine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take this medicine at the same time of day.
  • Take with or without food.
  • If you have trouble swallowing, talk with your doctor.
  • Keep taking abacavir and lamivudine as you have been told by your doctor or other health care provider, even if you feel well.
  • It is important that you do not miss or skip a dose of this medicine during treatment.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • If you are not sure what to do if you miss a dose, call your doctor.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Pharmacology

Nucleoside reverse transcriptase inhibitor combination.

Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.

Lamivudine is a cytosine analog. After lamivudine is triphosphorylated, the principle mode of action is inhibition of HIV reverse transcription via viral DNA chain termination; inhibits RNA-dependent DNA polymerase activities of reverse transcriptase.

Dosing Hepatic Impairment

Mild impairment (Child-Pugh class A): Use is not recommended.

Moderate and severe impairment (Child-Pugh class B or C): Use is contraindicated.

Administration

May be administered with or without food.

Adverse Reactions

See individual agents as well as other combination products for additional information. Rates of adverse reactions were defined during combination therapy with other antiretrovirals.

1% to 10%:

Central nervous system: Abnormal dreams, anxiety, depression, dizziness, fatigue, headache, insomnia, malaise, migraine, vertigo

Dermatologic: Skin rash

Gastrointestinal: Abdominal pain, diarrhea, gastritis

Hypersensitivity: Hypersensitivity (including multiorgan failure and anaphylaxis; ≤9%; higher incidence in subjects carrying the HLA-B*5701 allele)

Miscellaneous: Fever

<1% (Limited to important or life-threatening): Abnormal breath sounds, alopecia, anemia (including pure red cell aplasia and severe anemias progressing on therapy), aplastic anemia, erythema multiforme, exacerbation of hepatitis B, hepatitis, hyperglycemia, immune reconstitution syndrome, increased creatine phosphokinase, lactic acidosis, liver steatosis, lymphadenopathy, myasthenia, paresthesia, peripheral neuropathy, redistribution of body fat, rhabdomyolysis, seizure, splenomegaly, Stevens-Johnson syndrome, stomatitis, weakness, wheezing

For the Consumer

Applies to abacavir / lamivudine: oral tablet

Along with its needed effects, abacavir / 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 / lamivudine:

More common
  • Abdominal or stomach pain
  • cough
  • diarrhea
  • fever
  • headache
  • nausea
  • numbness or tingling of the face, feet, or hands
  • pain in the joints
  • pain in the muscles
  • skin rash
  • sore throat
  • swelling of the feet or lower legs
  • unusual feeling of discomfort or illness
  • unusual tiredness or weakness
  • vomiting
Incidence not known
  • Blistering, peeling, or loosening of the skin
  • bloating
  • burning, numbness, tingling, or painful sensations
  • chest pain
  • chills
  • constipation
  • convulsions
  • dark urine
  • decreased appetite
  • diarrhea
  • difficulty with swallowing
  • dizziness
  • fast heartbeat
  • fast, shallow breathing
  • feeling of fullness
  • general feeling of discomfort
  • hives or welts, itching
  • indigestion
  • light-colored stools
  • loss of appetite
  • loss of bladder control
  • muscle cramping
  • muscle spasm or jerking of all extremities
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • pale skin
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • red, irritated eyes
  • redness of the skin
  • red skin lesions, often with a purple center
  • sleepiness
  • sores, ulcers, or white spots on the lips or in the mouth
  • sudden loss of consciousness
  • swollen, painful, or tender lymph glands in the neck, armpit, or groin
  • tightness in the chest
  • troubled breathing with exertion
  • unsteadiness or awkwardness
  • unusual bleeding or bruising
  • upper right abdominal or stomach pain
  • weakness in the arms, hands, legs, or feet
  • yellow eyes and skin

Some side effects of abacavir / 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:

More common
  • Abnormal dreams
  • burning feeling in the chest or stomach
  • fear or nervousness
  • feeling of constant movement of self or surroundings
  • lightheadedness
  • sensation of spinning
  • severe and throbbing headache
  • stomach upset
  • tenderness in the stomach area
  • trouble sleeping
Incidence not known
  • Abnormal breathing sounds
  • blurred vision
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • dry mouth
  • flushed, dry skin
  • fruit-like breath odor
  • gaining weight around your neck, upper back, breast, face, or waist
  • hair loss
  • increased hunger
  • increased thirst
  • increased urination
  • muscle weakness
  • sweating
  • swelling or inflammation of the mouth
  • thinning of the hair
  • unexplained weight loss

Abacavir / lamivudine Breastfeeding Warnings

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: Yes 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 using 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.

(web3)