Summary

Commonly reported side effects of lamivudine/zidovudine include: nausea and nausea and vomiting. Other side effects include: neutropenia. Continue reading for a comprehensive list of adverse effects.

Applies to lamivudine / zidovudine: oral tablet.

Serious side effects

Along with its needed effects, lamivudine / zidovudine 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 lamivudine / zidovudine:

More common

• Chills
• fever
• pale skin
• sore throat
• unusual tiredness or weakness

Less common

• Burning, tingling, numbness, or pain in the hands, arms, feet, or legs
• muscle tenderness and weakness
• nausea
• severe stomach pain
• skin rash
• vomiting
• yellow eyes or skin

Incidence not known

• Blistering, peeling, or loosening of the skin
• canker sores
• chest discomfort or pain
• chills
• convulsions
• dark urine
• decreased appetite
• difficulty with breathing
• difficulty with swallowing
• dizziness
• faintness
• fast, irregular, or pounding heartbeat
• fast, shallow breathing
• feeling of fullness
• general feeling of discomfort
• general tiredness and weakness
• hives or welts, itching
• itching, puffiness, or swelling of the eyelids or around the eyes, face, lips, or tongue
• jerking of all extremities
• joint or muscle pain
• light-colored stools
• loss of bladder control
• muscle pain, spasms, stiffness, or cramping
• red skin lesions often with a purple center
• red, irritated eyes
• redness, soreness, or itching skin
• sensation of pins and needles
• sleepiness
• sores, ulcers, or white spots in the mouth or on the lips or tongue
• sores, welting or blisters
• stabbing pain
• sudden loss of consciousness
• swelling of the feet or lower legs
• tingling, burning, numbness, or pain in the hands, arms, feet, or legs
• tightness in the chest
• troubled with breathing
• unsteadiness or awkwardness

Other side effects

Some side effects of lamivudine / zidovudine 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

• Headache

Less common

• Coughing
• decreased appetite
• diarrhea
• dizziness
• mild stomach pain
• trouble sleeping

Incidence not known

• Blurred vision
• body fat redistribution or accumulation
• darkening of the skin and mucous membranes
• dry mouth
• flushed, dry skin
• fruit-like breath odor
• hair loss
• increased hunger
• increased thirst
• increased urination
• sweating
• swelling of the breasts or breast soreness in both females and males
• swollen, painful, or tender lymph glands in the neck, armpit, or groin
• thinning of the hair
• troubled breathing, unexplained

For Healthcare Professionals

Applies to lamivudine / zidovudine: oral tablet.

General

Side effects have been reported with lamivudine and zidovudine, administered separately or together. For many of these side effects, it was not clear if they were due to lamivudine, zidovudine, the other drugs used to treat HIV infection, or the underlying disease process.^[Ref]

Nervous system

In an advanced HIV disease study, headache (42%), somnolence (8%), dizziness (6%), paresthesia (6%), and taste perversion (5%) were reported with zidovudine; only headache was reported at a significantly greater rate than placebo. In this study, seizures, vertigo, hearing loss, hyperalgesia, tremor, and syncope were reported in less than 5% of patients using zidovudine.

In an asymptomatic HIV infection study, headache and dizziness were reported in 58% and 20.8% (using 1500 mg) and 62.5% and 17.9% (using 500 mg) of patients using zidovudine, respectively.^[Ref]

Very common (10% or more): Headache (up to 35.1%), neuropathy (up to 12.4%), dizziness (up to 10.4%)

Frequency not reported: Syncope, taste perversion

Postmarketing reports: Paresthesia, peripheral neuropathy, seizures

Lamivudine:

-Common (1% to 10%): Headache

-Rare (0.01% to 0.1%): Peripheral neuropathy/neuropathy, paresthesia

Zidovudine:

-Very common (10% or more): Headache, dizziness

-Common (1% to 10%): Neuropathy, paresthesia, somnolence, taste perversion

-Rare (0.01% to 0.1%): Convulsions

-Frequency not reported: Generalized seizures, status epilepticus, vertigo, Wernicke's syndrome, hearing loss, hyperalgesia, tremor, syncope^[Ref]

Gastrointestinal

Very common (10% or more): Nausea (33%), diarrhea (18%), nausea and vomiting (13%), abdominal discomfort and pain (up to 11.3%)

Common (1% to 10%): Abdominal cramps, dyspepsia, elevated amylase, fungal gastrointestinal (GI) infection, GI discomfort and pain, gaseous symptoms, vomiting

Uncommon (0.1% to 1%): Pancreatitis

Frequency not reported: Flatulence

Postmarketing reports: Oral mucosal pigmentation, stomatitis, pancreatitis

Lamivudine:

-Common (1% to 10%): Nausea, vomiting, abdominal discomfort and pain or cramps, diarrhea

-Uncommon (0.1% to 1%): Pancreatitis, abnormal pancreatic enzymes

-Rare (0.01% to 0.1%): Elevated serum amylase

Zidovudine:

-Very common (10% or more): Nausea, GI pain, diarrhea, vomiting

-Common (1% to 10%): Abdominal discomfort and pain, fungal GI infection, GI discomfort and pain, gaseous symptoms, elevated amylase, dyspepsia

-Uncommon (0.1% to 1%): Flatulence

-Rare (0.01% to 0.1%): Oral mucosa pigmentation, pancreatitis

-Frequency not reported: Constipation, dysphagia, tongue edema, eructation, bleeding gums, rectal hemorrhage, lip edema, mouth ulcer^[Ref]

Elevated amylase (greater than 2 times the upper limit of normal [2 x ULN]) has been reported in 4.2% of patients using lamivudine plus zidovudine and 1.5% of patients using zidovudine. Incidence was higher in patients with mild laboratory abnormalities at baseline.

In an advanced HIV disease study, nausea (46%), GI pain (20%), diarrhea (12%), vomiting (6%), and dyspepsia (5%) were reported with zidovudine; only nausea was reported at a significantly greater rate than placebo. In this study, constipation, dysphagia, tongue edema, eructation, flatulence, bleeding gums, rectal hemorrhage, lip edema, and mouth ulcer were reported in less than 5% of patients using zidovudine.

In the early symptomatic HIV disease study, nausea (61%), vomiting (25%), and dyspepsia (6%) were reported with zidovudine. In an asymptomatic HIV infection study, nausea, vomiting, and constipation were reported in 57.3%, 16.4%, and 8.1% (using 1500 mg) and 51.4%, 17.2%, and 6.4% (using 500 mg) of patients using zidovudine, respectively.^[Ref]

Other

In an advanced HIV disease study, asthenia (19%), fever (16%), and malaise (8%) were reported with zidovudine. In this study, chills, influenza syndrome, and chest pain were reported in less than 5% of patients using zidovudine.

In the early symptomatic HIV disease study, asthenia was reported in 69% of patients using zidovudine. In an asymptomatic HIV infection study, asthenia and malaise were reported in 10.1% and 55.6% (using 1500 mg) and 8.6% and 53.2% (using 500 mg) of patients using zidovudine, respectively.^[Ref]

Very common (10% or more): Malaise and fatigue (27%); ear, nose, and throat infection (up to 11.3%)

Common (1% to 10%): Fever or chills; viral ear, nose, and throat infection; viral infection

Postmarketing reports: Weakness

Lamivudine:

-Common (1% to 10%): Fatigue, malaise, fever

Zidovudine:

-Very common (10% or more): Asthenia, fever, malaise

-Common (1% to 10%): Ear, nose, and throat infection; viral ear, nose, and throat infection; viral infection

-Uncommon (0.1% to 1%): Generalized pain

-Rare (0.01% to 0.1%): Chills, chest pain, influenza-like syndrome

-Frequency not reported: Influenza syndrome

Antiretroviral therapy:

-Frequency not reported: Increased weight^[Ref]

Respiratory

Very common (10% or more): Nasal signs and symptoms (20%), cough (18%), throat and tonsil discomfort and pain (up to 11.6%)

Common (1% to 10%): Bronchitis, sinusitis, breathing disorders, upper respiratory inflammation

Frequency not reported: Dyspnea, rhinitis

Postmarketing reports: Abnormal breath sounds/wheezing

Lamivudine:

-Common (1% to 10%): Cough, nasal symptoms

Zidovudine:

-Common (1% to 10%): Throat and tonsil discomfort and pain, sinusitis, bronchitis, breathing disorders, upper respiratory inflammation, dyspnea

-Rare (0.01% to 0.1%): Cough

-Frequency not reported: Epistaxis, pharyngitis, rhinitis, hoarseness^[Ref]

In an advanced HIV disease study, dyspnea (5%) was reported with zidovudine. In this study, cough, epistaxis, pharyngitis, rhinitis, sinusitis, and hoarseness were reported in less than 5% of patients using zidovudine.^[Ref]

Musculoskeletal

Very common (10% or more): Musculoskeletal pain (up to 13.5%)

Common (1% to 10%): Myalgia, arthralgia

Postmarketing reports: Muscle weakness, elevated creatine phosphokinase (CPK), rhabdomyolysis

Lamivudine:

-Common (1% to 10%): Arthralgia, muscle disorders

-Rare (0.01% to 0.1%): Rhabdomyolysis

Zidovudine:

-Common (1% to 10%): Musculoskeletal pain, myalgia

-Uncommon (0.1% to 1%): Myopathy

-Frequency not reported: Symptomatic myopathy, myositis, back pain, arthralgia, muscle spasm, twitch

Combination antiretroviral therapy:

-Frequency not reported: Osteonecrosis^[Ref]

Myopathy and myositis (with pathological changes similar to that produced by HIV-1 disease) have been associated with prolonged zidovudine use.

In an advanced HIV disease study, myalgia (8%) was reported with zidovudine at a significantly greater rate than placebo. In this study, back pain, arthralgia, muscle spasm, twitch, and myopathy were reported in less than 5% of patients using zidovudine.

In 1 zidovudine study, myalgias and elevated CPK occurred in 8% of treated patients with a CD4 cell count less than 200/mm3, and in none of the patients with higher CD4 cell counts. Dose reduction has not affected the course of myopathy, although drug discontinuation sometimes resulted in improvement of symptoms, generally within a month. Muscle biopsy has shown atrophic and sometimes necrotic fibers, ragged-red fibers, and large accumulations of mitochondrial and fibrillar sarcoplasmic inclusions.^[Ref]

Psychiatric

In an advanced HIV disease study, insomnia (5%) was reported with zidovudine at a significantly greater rate than placebo. In this study, anxiety, confusion, depression, emotional lability, nervousness, and loss of mental acuity were reported in less than 5% of patients using zidovudine.^[Ref]

Very common (10% or more): Insomnia and other sleep disorders (up to 11.6%)

Common (1% to 10%): Depressive disorders

Lamivudine:

-Common (1% to 10%): Insomnia

Zidovudine:

-Common (1% to 10%): Sleep disorders, insomnia

-Rare (0.01% to 0.1%): Anxiety, depression, loss of mental acuity

-Frequency not reported: Mania, confusion, grandiosity, emotional lability, nervousness^[Ref]

Hepatic

Elevated ALT (greater than 5 x ULN), AST (greater than 5 x ULN), and bilirubin (greater than 2.5 x ULN) have been reported in 3.7%, 1.7%, and 0.8% of patients using lamivudine plus zidovudine, respectively, and 3.6%, 1.8%, and 0.4% of patients using zidovudine, respectively. Incidence was higher in patients with mild laboratory abnormalities at baseline.

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs.

Hepatic decompensation (some fatal) has been reported in patients coinfected with HIV-1 and hepatitis C virus (HCV) receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin.

Severe acute exacerbations of hepatitis have been reported in patients with hepatitis B after discontinuation of lamivudine.

In an advanced HIV disease study, changes in liver function tests (including increased AST levels) was reported in less than 5% of patients using zidovudine.

One patient with preexisting hepatitis B developed acute hepatic failure 2 weeks after starting zidovudine therapy.^[Ref]

Common (1% to 10%): Elevated ALT, elevated AST, abnormal liver function tests

Uncommon (0.1% to 1%): Elevated bilirubin

Frequency not reported: Severe hepatomegaly with steatosis, hepatic decompensation

Postmarketing reports: Hepatic steatosis, posttreatment exacerbation of hepatitis B

Lamivudine:

-Uncommon (0.1% to 1%): Elevated liver enzymes (AST, ALT)

-Rare (0.01% to 0.1%): Hepatitis, abnormal liver function tests

Zidovudine:

-Common (1% to 10%): Elevated liver enzyme levels in blood (including ALT, AST), elevated bilirubin levels in blood

-Rare (0.01% to 0.1%): Liver disorders (e.g., severe hepatomegaly with steatosis)

-Frequency not reported: Changes in liver function tests (including increased AST levels), acute hepatic failure^[Ref]

Hematologic

Common (1% to 10%): Neutropenia, anemia, lymphatic signs/symptoms, decreased white cells

Uncommon (0.1% to 1%): Thrombocytopenia

Postmarketing reports: Anemia (including pure red cell aplasia and anemias progressing on therapy), lymphadenopathy, splenomegaly

Lamivudine:

-Uncommon (0.1% to 1%): Neutropenia, anemia, thrombocytopenia, decreased white cells

-Very rare (less than 0.01%): Pure red cell aplasia

Zidovudine:

-Very common (10% or more): Granulocytopenia, anemia

-Common (1% to 10%): Neutropenia, leukopenia, lymphatic signs/symptoms, decreased white cells, thrombocytopenia

-Uncommon (0.1% to 1%): Pancytopenia (with marrow hypoplasia)

-Rare (0.01% to 0.1%): Pure red cell aplasia

-Very rare (less than 0.01%): Aplastic anemia

-Frequency not reported: Exacerbation of anemia, hemolytic anemia, hematologic toxicity (including neutropenia, severe anemia), lymphadenopathy^[Ref]

Neutropenia (absolute neutrophil count less than 750/mm3), anemia (hemoglobin less than 8 g/dL), and thrombocytopenia (platelets less than 50,000/mm3) have been reported in 7.2%, 2.9%, and 0.4% of patients using lamivudine plus zidovudine, respectively, and 5.4%, 1.8%, and 1.3% of patients using zidovudine, respectively. Incidence was higher in patients with mild laboratory abnormalities at baseline.

Occasionally, neutropenia and anemia reported with lamivudine were severe.

Granulocytopenia (less than 750/mm3) has been reported in 6.4% (CD4 up to 500 using 1500 mg), 1.8% (CD4 up to 500 using 500 mg), 4% (CD4 greater than 200 using 1200 mg), 10% (CD4 greater than 200 using 1500 mg), and 47% (CD4 less than 200 using 1500 mg) of patients using zidovudine. Anemia (hemoglobin less than 8 g/dL) has been reported in 6.4% (CD4 up to 500 using 1500 mg), 1.1% (CD4 up to 500 using 500 mg), 4% (CD4 greater than 200 using 1200 mg), 3% (CD4 greater than 200 using 1500 mg), and 29% (CD4 less than 200 using 1500 mg) of patients using zidovudine.

Zidovudine has been associated with hematologic toxicity (including neutropenia and severe anemia), particularly in patients with advanced HIV-1 disease. Anemia, neutropenia, and leukopenia were reported more often with higher doses (1200 to 1500 mg/day) and in patients with advanced HIV disease (especially with poor bone marrow reserve at baseline) and particularly in those with CD4 cell counts less than 100/mm3. These hematological effects were generally observed after 4 to 6 weeks of therapy. Incidence of neutropenia increased in patients with low neutrophil counts, hemoglobin levels, and serum vitamin B12 levels at baseline.

Exacerbation of anemia has been reported in HIV-1/HCV-coinfected patients using zidovudine and ribavirin.

In an advanced HIV disease study, lymphadenopathy was reported in less than 5% of patients using zidovudine.^[Ref]

Metabolic

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs.

In an advanced HIV disease study, anorexia (11%) was reported with zidovudine. In this study, redistribution/accumulation of body fat was reported in less than 5% of patients using zidovudine.

In an asymptomatic HIV infection study, anorexia was reported in 19.3% (using 1500 mg) and 20.1% (using 500 mg) of patients using zidovudine.

Redistribution/accumulation of body fat has been reported with antiretroviral therapy; causality has not been established.^[Ref]

Common (1% to 10%): Anorexia and/or decreased appetite

Postmarketing reports: Hyperglycemia, redistribution/accumulation of body fat, lactic acidosis

Lamivudine:

-Very rare (less than 0.01%): Lactic acidosis

-Postmarketing reports: Hyperlactatemia (common), lactic acidosis (rare), redistribution/accumulation of body fat

Zidovudine:

-Very common (10% or more): Anorexia

-Rare (0.01% to 0.1%): Lactic acidosis (without hypoxemia)

-Frequency not reported: Redistribution/accumulation of body fat, hyperlactatemia

Antiretroviral therapy:

-Frequency not reported: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance"), increased blood lipid levels, increased glucose levels^[Ref]

Dermatologic

Common (1% to 10%): Skin rashes, sweating, fungal skin infection, acne and folliculitis, viral skin infection

Frequency not reported: Pruritus

Postmarketing reports: Alopecia, erythema multiforme, Stevens-Johnson syndrome, urticaria

Lamivudine:

-Common (1% to 10%): Rash, alopecia

-Rare (0.01% to 0.1%): Angioedema

Zidovudine:

-Very common (10% or more): Rash

-Common (1% to 10%): Sweating/diaphoresis, fungal skin infection, acne and folliculitis, viral skin infection

-Uncommon (0.1% to 1%): Pruritus

-Rare (0.01% to 0.1%): Nail and skin pigmentation, urticaria

-Frequency not reported: Lipoatrophy, skin and nailbed pigmentation changes, toxic epidermal necrolysis, leukocytoclastic vasculitis (with eosinophilia and fever), nail hyperpigmentation (rarely accompanied by mucocutaneous pigmentation or hypertrichosis), body odor^[Ref]

In an advanced HIV disease study, rash (17%) and diaphoresis (5%) were reported with zidovudine. In this study, acne, pruritus, urticaria, nail pigmentation, and body odor were reported in less than 5% of patients using zidovudine.

Bluish or brownish-black discoloration of nails has developed during the first 1 or 2 months of zidovudine therapy and usually disappeared within 2 months if the drug is discontinued. Discoloration has occurred as longitudinal streaks or transverse bands.^[Ref]

Cardiovascular

In an advanced HIV disease study, vasodilation was reported in less than 5% of patients using zidovudine.^[Ref]

Frequency not reported: Phlebitis

Postmarketing reports: Cardiomyopathy, vasculitis

Zidovudine:

-Rare (0.01% to 0.1%): Cardiomyopathy

-Frequency not reported: Vasodilation^[Ref]

Immunologic

Frequency not reported: Immune reconstitution/reactivation syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)

Ocular

Frequency not reported: Disturbances of vision

Zidovudine:

-Frequency not reported: Amblyopia, photophobia, macular edema^[Ref]

In an advanced HIV disease study, amblyopia and photophobia were reported in less than 5% of patients using zidovudine.

At least 1 case of macular edema was deemed definitively associated with zidovudine in a patient with history of anterior uveitis secondary to syphilis.^[Ref]

Hypersensitivity

Postmarketing reports: Sensitization reactions (including anaphylaxis)

Zidovudine:

-Frequency not reported: Sensitization reactions (including anaphylaxis)^[Ref]

Endocrine

Postmarketing reports: Gynecomastia

Zidovudine:

-Rare (0.01% to 0.1%): Gynecomastia^[Ref]

Genitourinary

In an advanced HIV disease study, urinary frequency, urinary hesitancy, dysuria, and polyuria were reported in less than 5% of patients using zidovudine.^[Ref]

Zidovudine:

-Rare (0.01% to 0.1%): Urinary frequency

-Frequency not reported: Urinary hesitancy, dysuria, polyuria^[Ref]