Applies to lamivudine / tenofovir: oral tablet.

Serious side effects

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

More common

• Fever
• pain
• stomach pain

Less common

• Chest pain
• chills
• cough
• difficulty in moving
• joint pain or swelling
• muscle ache, cramp, pain, or stiffness
• sneezing
• sore throat
• tightness in the chest
• troubled breathing

Incidence not known

• Bloating
• bloody urine
• blurred vision
• bone fractures, especially of the femur
• bone pain
• cloudy urine
• constipation
• dark urine
• decreased appetite
• decreased frequency or amount of urine
• diarrhea
• difficulty swallowing
• dizziness
• dry mouth
• fast heartbeat
• fast, shallow breathing
• flushed, dry skin
• frequent urination
• fruit-like breath odor
• general feeling of discomfort
• hives, itching, skin rash
• increased blood pressure
• increased hunger
• increased thirst
• increased urination
• increased volume of pale, dilute urine
• indigestion
• irregular heartbeat
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals
• light-colored stools
• loss of appetite
• lower back or side pain
• mood changes
• muscle weakness
• nausea
• numbness or tingling in the hands, feet, or lips
• 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
• seizures
• sleepiness
• stomach discomfort
• sweating
• swelling of the face, fingers, or lower legs
• troubled breathing with exertion
• unexplained weight loss
• unusual bleeding or bruising
• unusual tiredness or weakness
• upper right abdominal or stomach pain
• vomiting
• weight gain
• yellow eyes or skin

Other side effects

Some side effects of lamivudine / tenofovir 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

• Anxiety
• back pain
• belching
• burning, numbness, tingling, or painful sensations
• discouragement
• feeling sad or empty
• headache
• heartburn
• indigestion
• irritability
• lack or loss of strength
• loss of interest or pleasure
• redistribution or accumulation of body fat
• stomach upset
• tiredness
• trouble concentrating
• trouble sleeping
• unsteadiness or awkwardness
• weakness in the arms, hands, legs, or feet

Incidence not known

• Hair loss or thinning of hair

For Healthcare Professionals

Applies to lamivudine / tenofovir: oral tablet.

General

In a controlled trial with lamivudine, tenofovir disoproxil fumarate (DF), and efavirenz, the most common side effects were mild-to-moderate gastrointestinal events and dizziness. Mild side effects (grade 1) were common and included dizziness, diarrhea, and nausea.^[Ref]

Metabolic

Elevated fasting cholesterol (greater than 240 mg/dL) and fasting triglycerides (greater than 750 mg/dL) have been reported in 19% and 1% of patients using lamivudine, tenofovir DF, and efavirenz, respectively.

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

Hypokalemia and hypophosphatemia have occurred as a result of proximal renal tubulopathy.^[Ref]

Very common (10% or more): Elevated fasting cholesterol (19%)

Uncommon (0.1% to 1%): Lipodystrophy, elevated fasting triglycerides

Frequency not reported: Higher 1,25 vitamin D levels

Lamivudine:

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

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

Tenofovir DF:

-Very common (10% or more): Hypophosphatemia

-Uncommon (0.1% to 1%): Hypokalemia

-Rare (0.01% to 0.1%): Lactic acidosis

-Postmarketing reports: Lactic acidosis, hypokalemia, hypophosphatemia

Antiretroviral therapy:

-Frequency not reported: Increased glucose levels

Combination antiretroviral therapy:

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

Dermatologic

Very common (10% or more): Rash event (included rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash; 18%)

Lamivudine:

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

-Rare (0.01% to 0.1%): Angioedema

-Postmarketing reports: Urticaria, alopecia, pruritus

Tenofovir DF:

-Very common (10% or more): Rash

-Rare (0.01% to 0.1%): Angioedema

-Postmarketing reports: Rash^[Ref]

Nervous system

Very common (10% or more): Headache (14%)

Common (1% to 10%): Dizziness

Uncommon (0.1% to 1%): Peripheral neuropathy (included peripheral neuritis, neuropathy)

Lamivudine:

-Common (1% to 10%): Headache

-Very rare (less than 0.01%): Peripheral neuropathy/paresthesia

Tenofovir DF:

-Very common (10% or more): Dizziness

-Common (1% to 10%): Headache^[Ref]

Other

Very common (10% or more): Pain (13%)

Common (1% to 10%): Fever, asthenia

Lamivudine:

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

-Postmarketing reports: Weakness

Tenofovir DF:

-Very common (10% or more): Asthenia

-Common (1% to 10%): Fatigue

-Postmarketing reports: Asthenia

Antiretroviral therapy:

-Frequency not reported: Increased weight, increased blood lipid levels^[Ref]

Musculoskeletal

Elevated creatine phosphokinase (males: greater than 990 units/L; females: greater than 845 units/L) has been reported in 12% of patients using lamivudine, tenofovir DF, and efavirenz.

Proximal renal tubulopathy (including Fanconi syndrome) sometimes leading to bone abnormalities (infrequently contributing to fractures) has been reported.

Rhabdomyolysis, osteomalacia, muscular weakness, and myopathy have occurred as a result of proximal renal tubulopathy.^[Ref]

Very common (10% or more): Elevated creatine phosphokinase (12%)

Common (1% to 10%): Back pain, arthralgia, myalgia

Frequency not reported: Decreased bone mineral density, increased biochemical markers of bone metabolism (serum bone-specific alkaline phosphatase, serum osteocalcin, serum C telopeptide, urinary N telopeptide), clinically relevant fractures (excluding fingers and toes)

Lamivudine:

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

-Rare (0.01% to 0.1%): Rhabdomyolysis

-Postmarketing reports: Muscle weakness, elevated creatine phosphokinase, rhabdomyolysis

Tenofovir DF:

-Uncommon (0.1% to 1%): Rhabdomyolysis, muscular weakness

-Rare (0.01% to 0.1%): Myopathy

-Frequency not reported: Bone abnormalities (infrequently contributed to fractures)

-Postmarketing reports: Rhabdomyolysis, osteomalacia (manifested as bone pain and infrequently contributed to fractures), muscular weakness, myopathy

Combination antiretroviral therapy:

-Frequency not reported: Osteonecrosis^[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (11%)

Common (1% to 10%): Nausea, increased serum amylase, abdominal pain, vomiting, dyspepsia

Lamivudine:

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

-Rare (0.01% to 0.1%): Pancreatitis, elevated serum amylase

Tenofovir DF:

-Very common (10% or more): Diarrhea, vomiting, nausea

-Common (1% to 10%): Abdominal pain, abdominal distension, flatulence

-Uncommon (0.1% to 1%): Pancreatitis

-Postmarketing reports: Pancreatitis, increased amylase, abdominal pain^[Ref]

Increased serum amylase (greater than 175 units/L) has been reported in 9% of patients using lamivudine, tenofovir DF, and efavirenz.

Pancreatitis (some cases fatal) has been reported in antiretroviral nucleoside-experienced pediatric patients using lamivudine alone or in combination with other antiretroviral agents.^[Ref]

Psychiatric

Very common (10% or more): Depression (11%)

Common (1% to 10%): Anxiety, insomnia

Lamivudine:

-Common (1% to 10%): Insomnia^[Ref]

Genitourinary

Hematuria (greater than 100 RBC/high power field) has been reported in 7% of patients using lamivudine, tenofovir DF, and efavirenz.^[Ref]

Common (1% to 10%): Hematuria

Tenofovir DF:

-Postmarketing reports: Proteinuria, polyuria^[Ref]

Hepatic

Common (1% to 10%): Elevated AST, elevated ALT

Lamivudine:

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

-Rare (0.01% to 0.1%): Hepatitis

-Postmarketing reports: Hepatic steatosis, posttreatment exacerbation of hepatitis B

Tenofovir DF:

-Common (1% to 10%): Increased transaminases

-Rare (0.01% to 0.1%): Hepatic steatosis, hepatitis

-Frequency not reported: Acute exacerbation of hepatitis

-Postmarketing reports: Hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT, GGT)

Combination antiretroviral therapy:

-Frequency not reported: Hepatic decompensation^[Ref]

Elevated AST (males: greater than 180 units/L; females: greater than 170 units/L) and ALT (males: greater than 215 units/L; females: greater than 170 units/L) have been reported in 5% and 4% patients using lamivudine, tenofovir DF, and efavirenz, respectively.

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

Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HIV-1 and hepatitis B virus after discontinuation of lamivudine or tenofovir DF.

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

Hematologic

Decreased neutrophils (less than 750/mm3) has been reported in 3% of patients using lamivudine, tenofovir DF, and efavirenz.

Severe neutropenia and severe anemia have been reported occasionally with lamivudine.^[Ref]

Common (1% to 10%): Decreased neutrophils

Lamivudine:

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

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

-Postmarketing reports: Anemia (including pure red cell aplasia and severe anemias progressing on therapy)^[Ref]

Respiratory

Common (1% to 10%): Pneumonia

Lamivudine:

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

Tenofovir DF:

-Postmarketing reports: Dyspnea^[Ref]

Renal

Proximal renal tubulopathy generally resolved or improved after tenofovir DF was stopped; however, decreased CrCl did not completely resolve in some patients after stopping tenofovir DF. Patients at risk of renal dysfunction (e.g., baseline renal risk factors, advanced HIV disease, concomitant nephrotoxic drugs) were at increased risk of incomplete recovery of renal function despite stopping tenofovir DF.

Rhabdomyolysis, osteomalacia, bone abnormalities (infrequently contributing to fractures), hypokalemia, muscular weakness, myopathy, and hypophosphatemia have occurred as a result of proximal renal tubulopathy.^[Ref]

Tenofovir DF:

-Uncommon (0.1% to 1%): Increased creatinine, proximal renal tubulopathy (including Fanconi syndrome)

-Rare (0.01% to 0.1%): Renal impairment, renal failure, acute renal failure, acute tubular necrosis, nephrogenic diabetes insipidus

-Postmarketing reports: Renal insufficiency, acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, increased creatinine, nephritis (including acute interstitial nephritis)^[Ref]

Hypersensitivity

Lamivudine:

-Postmarketing reports: Anaphylaxis

Tenofovir DF:

-Postmarketing reports: Allergic reaction (including angioedema)^[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, autoimmune hepatitis)^[Ref]

Endocrine

Frequency not reported: Higher serum parathyroid hormone levels^[Ref]