Skip to main content

The following adverse reactions are discussed in greater detail in other sections of the labeling.

  • QT Interval Prolongation, PR Interval Prolongation [see WARNINGS AND PRECAUTIONS]
  • Drug Interactions [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY]
  • Pancreatitis [see WARNINGS AND PRECAUTIONS]
  • Hepatotoxicity [see WARNINGS AND PRECAUTIONS, and Use in Specific Populations]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adult Clinical Trial Experience

The safety profile of KALETRA in adults is primarily based on 1964 HIV-1 infected patients in clinical trials.

The most common adverse reaction was diarrhea, which was generally of mild to moderate severity. In study 418, the incidence of diarrhea was greater for KALETRA Capsules once daily compared to KALETRA Capsules twice-daily (57% vs. 35% - events of all grades and probably or possibly related to drug; 16% vs. 5% - events of at least moderate severity and probably or possibly related to drug). In study 730, the incidence of diarrhea of any severity during 48 weeks of therapy was 60% in patients receiving KALETRA Tablets once daily compared to 57% in patients receiving KALETRA Tablets twice daily. More patients receiving KALETRA Tablets once daily (14, 4.2%) had ongoing diarrhea at the time of discontinuation as compared to patients receiving KALETRA Tablets twice daily (6, 1.8%). In study 730, discontinuations due to any adverse reaction were 4.8% in patients receiving KALETRA Tablets once daily as compared to 3% in patients receiving KALETRA Tablets twice daily. In study 802, the incidence of diarrhea of any severity during 48 weeks of therapy was 50% in patients receiving KALETRA Tablets once daily compared to 39% in patients receiving KALETRA Tablets twice daily. Moderate or severe drug-related diarrhea occurred in 14% of patients receiving KALETRA Tablets once daily as compared to 11% in patients receiving KALETRA Tablets twice daily. At the time of discontinuation, 19 (6.3%) patients receiving KALETRA Tablets once daily had ongoing diarrhea, as compared to 11 (3.7%) patients receiving KALETRA Tablets twice daily. Discontinuations due to any adverse reaction occurred in 4.3% of patients receiving KALETRA Tablets once daily compared to 7.0% in patients receiving KALETRA Tablets twice daily. In study 863, discontinuations of randomized therapy due to adverse reactions were 3.4% in KALETRA-treated and 3.7% in nelfinavir-treated patients.

Selected treatment-emergent clinical adverse reactions of moderate or severe intensity in greater than or equal to 2% of patients treated with combination therapy for up to 48 weeks (Studies 863, 418, and 730) and for up to 360 weeks (Study 720) are presented in Table 2 (treatment-naïve patients); and for up to 48 weeks (Studies 888 and 802), 84 weeks (Study 957) and 144 weeks (Study 765) in Table 3 (protease inhibitor-experienced patients).

Table 2: Percentage of Adult Patients with Selected Treatment-Emergent1 Adverse Reactions of Moderate or Severe Intensity Reported in greater than or equal to 2% of Adult Antiretroviral-Naïve Patients

  Study 863 (48 Weeks) Study 720 (360 Weeks) Study 418 (48 Weeks) Study 730 (48 Weeks)
KALETRA 400/100 mg Twice Daily + d4T + 3TC
(N = 326)
Nelfinavir 750 mg Three Times Daily + d4T + 3TC
(N = 327)
KALETRA Twice Daily2 + d4T + 3TC
(N = 100)
KALETRA 800/200 mg Once Daily + TDF + FTC
(N=115)
KALETRA 400/100 mg Twice Daily + TDF + FTC
(N=75)
KALETRA 800/200 mg Once Daily + TDF +FTC
(N=333)
KALETRA 400/100 mg Twice Daily + TDF +FTC
(N=331)
Endocrine Disorders
Hypogonadism 0% 0% 2% 0% 0% 0% 0%
Gastrointestinal Disorders
Diarrhea 16% 17% 28% 16% 5% 17% 15%
Nausea 7% 5% 16% 9% 8% 7% 5%
Vomiting 2% 2% 6% 3% 4% 3% 4%
Abdominal Pain 4% 3% 11% 3% 3% 1% 1%
Dyspepsia 2% < 1% 6% 0% 1% 0% 0%
Flatulence 2% 1% 4% 2% 1% 1% 1%
General Disorders and Administration Site Conditions
Asthenia 4% 3% 9% 0% 0% < 1% < 1%
Infections and Infestations
Bronchitis 0% 0% 2% 0% 0% 0% < 1%
Investigations
Weight Decreased 1% < 1% 2% 0% 0% 0% < 1%
Metabolism and Nutrition Disorders
Anorexia 1% < 1% 2% < 1% 1% < 1% 1%
Musculoskeletal and Connective Tissue Disorders
Myalgia 1% 1% 2% 0% 0% 0% 0%
Nervous System Disorders
Headache 2% 2% 6% 3% 3% 2% 2%
Paresthesia 1% 1% 2% 0% 0% 0% 0%
Psychiatric Disorders
Insomnia 2% 1% 3% 0% 0% 1% 0%
Depression 1% 2% 0% 1% 0% 0% 0%
Libido Decreased < 1% < 1% 2% 0% 1% 0% < 1%
Skin and Subcutaneous Tissue Disorders
Rash 1% 2% 5% 1% 0% < 1% 1%
Vascular Disorders
Vasodilation 0% 0% 3% 0% 0% 0% 0%
1 Includes adverse reactions of possible or probable relationship to study drug.
2 Includes adverse reaction data from dose group I (200/100 mg twice daily [N = 16] and 400/100 mg twice daily [N = 16]) and dose group II (400/100 mg twice daily [N = 35] and 400/200 mg twice daily [N = 33]). Within dosing groups, moderate to severe nausea of probable/possible relationship to KALETRA occurred at a higher rate in the 400/200 mg dose arm compared to the 400/100 mg dose arm in group II. Definitions: d4T = Stavudine; 3TC = Lamivudine; TDF = Tenofovir Disoproxil Fumarate; FTC = Emtricitabine

Table 3: Percentage of Adult Patients with Selected Treatment-Emergent1 Adverse Reactions of Moderate or Severe Intensity Reported in greater than or equal to 2% of Adult Protease Inhibitor-Experienced Patients

  Study 888 (48 Weeks) Study 9572 and Study 7653 (84-144 Weeks) Study 802 (48 Weeks)
KALETRA 400/100 mg Twice Daily + NVP + NRTIs
(N = 148)
Investigator-Selected Protease Inhibitor(s) + NVP + NRTIs
(N = 140)
KALETRA Twice Daily + NNRTI + NRTIs (N = 127) KALETRA 800/200 mg Once Daily +NRTIs
(N=300)
KALETRA 400/100 mg Twice Daily + NRTIs
(N=299)
Gastrointestinal Disorders
Diarrhea 7% 9% 23% 14% 11%
Nausea 7% 16% 5% 3% 7%
Vomiting 4% 12% 2% 2% 3%
Abdominal Pain 2% 2% 4% 2% < 1%
Abdominal Pain Upper N/A N/A N/A 1% 2%
Dyspepsia 1% 1% 2% 1% < 1%
Flatulence 1% 2% 2% 1% 1%
Dysphasia 2% 1% 0% 0% 0%
General Disorders and Administration Site Conditions
Asthenia 3% 6% 9% < 1% < 1%
Pyrexia 2% 1% 2% 0% < 1%
Chills 2% 0% 0% 0% 0%
Investigations
Weight Decreased 0% 1% 3% < 1% < 1%
Metabolism and Nutrition Disorders
Anorexia 1% 3% 0% 0% 1%
Musculoskeletal and Connective Tissue Disorders
Myalgia 1% 1% 2% 0% 0%
Nervous System Disorders
Headache 2% 3% 2% < 1% 0%
Paresthesia 0% 1% 2% 0% 0%
Psychiatric Disorders
Depression 1% 2% 3% < 1% 0%
Insomnia 0% 2% 2% 0% < 1%
Skin and Subcutaneous Tissue Disorders
Rash 2% 1% 2% 0% 0%
Vascular Disorders
Hypertension 0% 0% 2% 0% 0%
1 Includes adverse reactions of possible or probable relationship to study drug.
2 Includes adverse reaction data from patients receiving 400/100 mg twice daily (n = 29) or 533/133 mg twice daily (n = 28) for 84 weeks. Patients received KALETRA in combination with NRTIs and efavirenz.
3 Includes adverse reaction data from patients receiving 400/100 mg twice daily (n = 36) or 400/200 mg twice daily (n = 34) for 144 weeks. Patients received KALETRA in combination with NRTIs and nevirapine. Definitions: NVP = Nevirapine; NRTI = Nucleoside Reverse Transcriptase Inhibitors; NNRTI = Non-nucleoside Reverse Transcriptase Inhibitors

Less Common Adverse Reactions

Treatment-emergent adverse reactions (includes selected adverse reactions based on investigator causality assessment and Abbott medical review) occurring in less than 2% of adult patients receiving KALETRA during Abbott clinical trials and of at least moderate intensity are listed below by system organ class.

Blood and Lymphatic System Disorders

Anemia, leukopenia, lymphadenopathy, neutropenia, and splenomegaly.

Cardiac Disorders

Angina pectoris, atrial fibrillation, atrioventricular block, myocardial infarction, palpitations, and tricuspid valve incompetence.

Ear and Labyrinth Disorders

Hyperacusis, tinnitus, and vertigo.

Endocrine Disorders

Cushing's syndrome and hypothyroidism.

Eye Disorders

Eye disorder and visual disturbance.

Gastrointestinal Disorders

Abdominal discomfort, abdominal distension, abdomen pain lower, constipation, duodenitis, dry mouth, enteritis, enterocolitis, enterocolitis hemorrhagic, eructation, esophagitis, fecal incontinence, gastric disorder, gastric ulcer, gastritis, gastroesophageal reflux disease, hemorrhoids, mouth ulceration, pancreatitis, periodontitis, rectal hemorrhage, stomach discomfort, and stomatitis.

General Disorders and Administration Site Conditions

Chest pain, cyst, drug interaction, edema, edema peripheral, face edema, fatigue, hypertrophy, and malaise.

Hepatobiliary Disorders

Cholangitis, cholecystitis, cytolytic hepatitis, hepatic steatosis, hepatitis, hepatomegaly, jaundice, and liver tenderness.

Immune System Disorders

Drug hypersensitivity, hypersensitivity, and immune reconstitution syndrome.

Infections and Infestations

Bacterial infection, bronchopneumonia, cellulitis, folliculitis, furuncle, gastroenteritis, influenza, otitis media, perineal abscess, pharyngitis, rhinitis, sialoadenitis, sinusitis, and viral infection.

Investigations

Drug level increased, glucose tolerance decreased, and weight increased.

Metabolism and Nutrition Disorders

Decreased appetite, dehydration, diabetes mellitus, hypovitaminosis, increased appetite, lactic acidosis, lipomatosis, and obesity.

Musculoskeletal and Connective Tissue Disorders

Arthralgia, arthropathy, back pain, muscular weakness, osteoarthritis, osteonecrosis, and pain in extremity.

Neoplasms Benign, Malignant and Unspecified (incl Cysts and Polyps)

Benign neoplasm of skin, lipoma, and neoplasm.

Nervous System Disorders

Ageusia, amnesia, ataxia, balance disorder, cerebral infarction, convulsion, dizziness, dysgeusia, dyskinesia, encephalopathy, extrapyramidal disorder, facial palsy, hypertonia, migraine, neuropathy, neuropathy peripheral, somnolence, and tremor.

Psychiatric Disorders

Abnormal dreams, affect lability, agitation, anxiety, apathy, confusional state, disorientation, mood swings, nervousness, and thinking abnormal.

Renal and Urinary Disorders

Hematuria, nephritis, nephrolithiasis, renal disorder, urine abnormality, and urine odor abnormal.

Reproductive System and Breast Disorders

Breast enlargement, ejaculation disorder, erectile dysfunction, gynecomastia, and menorrhagia.

Respiratory, Thoracic and Mediastinal Disorders

Asthma, cough, dyspnea, and pulmonary edema.

Skin and Subcutaneous Tissue Disorders

Acne, alopecia, dermatitis acneiform, dermatitis allergic, dermatitis exfoliative, dry skin, eczema, hyperhidrosis, idiopathic capillaritis, nail disorder, pruritis, rash generalized, rash maculo-papular, seborrhea, skin discoloration, skin hypertrophy, skin striae, skin ulcer, and swelling face.

Vascular Disorders

Deep vein thrombosis, orthostatic hypotension, thrombophlebitis, varicose vein, and vasculitis.

Laboratory Abnormalities

The percentages of adult patients treated with combination therapy with Grade 3-4 laboratory abnormalities are presented in Table 4 (treatment-naïve patients) and Table 5 (treatmentexperienced patients).

Table 4: Grade 3-4 Laboratory Abnormalities Reported in greater than or equal to 2% of Adult Antiretroviral-Naïve Patients

Variable Limit1 Study 863 (48 Weeks) Study 720 (360 Weeks) Study 418 (48 weeks) Study 730 (48 Weeks)
KALETRA 400/100 mg Twice Daily + d4T +3TC
(N = 326)
Nelfinavir 750 mg Three Times Daily + d4T + 3TC
(N = 327)
KALETRA Twice Daily + d4T + 3TC
(N = 100)
KALETRA 800/200 mg Once Daily + TDF + FTC
(N=115)
KALETRA 400/100 mg Twice Daily + TDF + FTC
(N=75)
KALETRA Once Daily + TDF +FTC
(N=333)
KALETRA Twice Daily + TDF +FTC
(N=331)
Chemistry High              
Glucose > 250 mg/dL 2% 2% 4% 3% 1% 0% < 1%
Uric Acid > 12 mg/dL 2% 2% 5% 0% 3% < 1% 1%
SGOT/ AST2 > 180 U/L 2% 4% 10% 5% 3% 1% 2%
SGPT/ ALT2 > 215 U/L 4% 4% 11% 4% 3% 1% 1%
GGT > 300 U/L N/A N/A 10% N/A N/A N/A N/A
Total Cholesterol > 300 mg/dL 9% 5% 27% 3% 3% 4% 3%
Triglycerides > 750 mg/dL 9% 1% 29% 5% 4% 3% 6%
Amylase > 2 x ULN 3% 2% 4% 7% 5% N/A N/A
Lipase > 2 x ULN N/A N/A N/A N/A N/A 3% 5%
Chemistry Low
Calculated Creatinine Clearance < 50 mL/min N/A N/A N/A N/A N/A 2% 2%
Hematology Low
Neutrophils < 0.75 x 109/L 1% 3% 5% 5% 1% 2% 1%
1 ULN = upper limit of the normal range; N/A = Not Applicable.
2 Criterion for Study 730 was > 5x ULN (AST/ALT).

Table 5: Grade 3-4 Laboratory Abnormalities Reported in greater than or equal to 2% of Adult Protease Inhibitor-Experienced Patients

Variable Limit1 Study 888 (48 Weeks) Study 9572 and Study 7653 (84-144 Weeks) Study 802 (48 Weeks)
KALETRA 400/100 mg Twice Daily + NVP + NRTIs
(N = 148)
Investigator-Selected Protease Inhibitor(s) + NVP + NRTIs
(N = 140)
KALETRA Twice Daily + NNRTI + NRTIs
(N = 127)
KALETRA 800/200 mg Once Daily +NRTIs
(N=300)
KALETRA 400/100 mg Twice Daily +NRTIs
(N=299)
Chemistry High          
Glucose > 250 mg/dL 1% 2% 5% 2% 2%
Total Bilirubin > 3.48 mg/dL 1% 3% 1% 1% 1%
SGOT/AST4 > 180 U/L 5% 11% 8% 3% 2%
SGPT/ALT4 > 215 U/L 6% 13% 10% 2% 2%
GGT > 300 U/L N/A N/A 29% N/A N/A
Total Cholesterol > 300 mg/dL 20% 21% 39% 6% 7%
Triglycerides > 750 mg/dL 25% 21% 36% 5% 6%
Amylase > 2 x ULN 4% 8% 8% 4% 4%
Lipase > 2 x ULN N/A N/A N/A 4% 1%
Creatine Phosphokinase > 4 x ULN N/A N/A N/A 4% 5%
Chemistry Low
Calculated Creatinine Clearance < 50 mL/min N/A N/A N/A 3% 3%
Inorganic Phosphorus < 1.5 mg/dL 1% 0% 2% 1% < 1%
Hematology Low
Neutrophils < 0.75 x 109/L 1% 2% 4% 3% 4%
Hemoglobin < 80 g/L 1% 1% 1% 1% 2%
1 ULN = upper limit of the normal range; N/A = Not Applicable.
2 Includes clinical laboratory data from patients receiving 400/100 mg twice daily (n = 29) or 533/133 mg twice daily (n = 28) for 84 weeks. Patients received KALETRA in combination with NRTIs and efavirenz.
3 Includes clinical laboratory data from patients receiving 400/100 mg twice daily (n = 36) or 400/200 mg twice daily (n = 34) for 144 weeks. Patients received KALETRA in combination with NRTIs and nevirapine.
4 Criterion for Study 802 was > 5x ULN (AST/ALT).

Pediatric Clinical Trial Experience

KALETRA Oral Solution dosed up to 300/75 mg per m² has been studied in 100 pediatric patients 6 months to 12 years of age. The adverse reaction profile seen during Study 940 was similar to that for adult patients.

Dysgeusia (22%), vomiting (21%), and diarrhea (12%) were the most common adverse reactions of any severity reported in pediatric patients treated with combination therapy for up to 48 weeks in Study 940. A total of 8 patients experienced adverse reactions of moderate to severe intensity. The adverse reactions meeting these criteria and reported for the 8 subjects include: hypersensitivity (characterized by fever, rash and jaundice), pyrexia, viral infection, constipation, hepatomegaly, pancreatitis, vomiting, alanine aminotransferase increased, dry skin, rash, and dysgeusia. Rash was the only event of those listed that occurred in 2 or more subjects (N = 3).

KALETRA Oral Solution and Soft Gelatin Capsules dosed at higher than recommended doses including 400/100 mg per m² (without concomitant NNRTI) and 480/120 mg per m² (with concomitant NNRTI) have been studied in 26 pediatric patients 7 to 18 years of age in Study 1038. Patients also had saquinavir mesylate added to their regimen at Week 4. Rash (12%), blood cholesterol abnormal (12%) and blood triglycerides abnormal (12%) were the only adverse reactions reported in greater than 10% of subjects. Adverse drug reactions of moderate to severe intensity occurring in 2 or more subjects included rash (N=3), blood triglycerides abnormal (N=3), and electrocardiogram QT prolonged (N=2). Both subjects with QT prolongation had additional predisposing conditions such as electrolyte abnormalities, concomitant medications, or pre-existing cardiac abnormalities.

Laboratory Abnormalities

The percentages of pediatric patients treated with combination therapy including KALETRA with Grade 3-4 laboratory abnormalities are presented in Table 6.

Table 6: Grade 3-4 Laboratory Abnormalities Reported in greater than or equal to 2% Pediatric Patients in Study 940

Variable Limit1 KALETRA Twice Daily + RTIs
(N = 100)
Chemistry High  
Sodium > 149 mEq/L 3%
Total Bilirubin ≥ 3.0 x ULN 3%
SGOT/AST > 180 U/L 8%
SGPT/ALT > 215 U/L 7%
Total Cholesterol > 300 mg/dL 3%
Amylase > 2.5 x ULN 7%2
Chemistry Low
Sodium < 130 mEq/L 3%
Hematology Low
Platelet Count < 50 x 109/L 4%
Neutrophils < 0.40 x 109/L 2%
1 ULN = upper limit of the normal range.
2 Subjects with Grade 3-4 amylase confirmed by elevations in pancreatic amylase.

Postmarketing Experience

The following adverse reactions have been reported during postmarketing use of KALETRA. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to KALETRA exposure.

Body as a Whole

Redistribution/accumulation of body fat has been reported [see WARNINGS AND PRECAUTIONS].

Cardiovascular

Bradyarrhythmias. First-degree AV block, second-degree AV block, third-degree AV block, QTc interval prolongation, torsades (torsade) de pointes [see WARNINGS AND PRECAUTIONS].

Skin and Appendages

Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome and erythema multiforme.