ADVERSE REACTIONS
Adults
Treatment-Emergent Adverse Events
KALETRA has been studied in 891 patients as combination therapy in Phase I/II and Phase III clinical trials. The most common adverse event associated with KALETRA therapy was diarrhea, which was generally of mild to moderate severity. Rates of discontinuation of randomized therapy due to adverse events were 5.8% in KALETRA-treated and 4.9% in nelfinavir-treated patients in Study 863. The incidence of diarrhea was greater for KALETRA once-daily compared to KALETRA twice-daily in Study 418 (see Table 12 and INDICATIONS AND USAGE).
Treatment-Emergent clinical adverse events of moderate or severe intensity in ≥ 2% of patients treated with combination therapy for up to 48 weeks (Phase III) and for up to 360 weeks (Phase I/II) are presented in Table 12. For other information regarding observed or potentially serious adverse events, please see WARNINGS and PRECAUTIONS.
Table 12. Percentage of Patients with Selected Treatment-Emergent1 Adverse Events of Moderate or Severe Intensity Reported in ≥ 2% of Adult Antiretroviral-Naïve Patients | Study 863
(48 Weeks) | Study 418
(48 Weeks) | Study 720
(360 Weeks) |
| KALETRA 400/100 mg BID + d4T + 3TC
(N=326) | Nelfinavir 750 mg TID + d4T + 3TC
(N=327)
| KALETRA 800/200 mg QD + TDF + FTC
(N=115) | KALETRA 400/100 mg BID + TDF + FTC
(N=75) | KALETRA BID2 + d4T + 3TC
(N=100) |
|
1 Includes adverse events of possible, probable, or unknown relationship to study drug.
2 Includes adverse event data from dose group I (200/100 mg BID [N=16] and 400/100 mg BID [N=16]) and dose group II (400/100 mg BID [N=35] and 400/200 mg BID [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.
|
| Body as a Whole | | | | | |
Abdominal
Pain | 4% | 3% | 3% | 3% | 11% |
| Asthenia | 4% | 3% | 0% | 0% | 9% |
| Headache | 2% | 2% | 3% | 3% | 6% |
| Cardiovascular System | | | | | |
| Vein distended | 0% | 0% | 0% | 0% | 3% |
| Digestive System | | | | | |
| Anorexia | 1% | <1% | <1% | 1% | 2% |
| Diarrhea | 16% | 17% | 16% | 5% | 28% |
| Dyspepsia | 2% | <1% | 0% | 1% | 6% |
| Flatulence | 2% | 1% | 2% | 1% | 4% |
| Nausea | 7% | 5% | 9% | 8% | 16% |
| Vomiting | 2% | 2% | 3% | 4% | 6% |
| Metabolic and Nutritional | | | | | |
| Weight Loss | 1% | <1% | 0% | 0% | 2% |
| Musculoskeletal | | | | | |
| Myalgia | 1% | 1% | 0% | 0% | 2% |
| Nervous System | | | | | |
| Depression | 1% | 2% | 1% | 0% | 0% |
| Insomnia | 2% | 1% | 0% | 0% | 3% |
Libido
decreased | <1% | <1% | 0% | 1% | 2% |
| Paresthesia | 1% | 1% | 0% | 0% | 2% |
| Respiratory | | | | | |
| Bronchitis | 0% | 0% | 0% | 0% | 2% |
| Skin and Appendages | | | | | |
| Rash | 1% | 2% | 1% | 0% | 5% |
| Urogenital | | | | | |
Hypogonadism
male | 0% | 0% | 0% | 0% | 2% |
Table 13. Percentage of Patients with Selected Treatment-Emergent1 Adverse Events of Moderate or Severe Intensity Reported in ≥ 2% of Adult Protease Inhibitor-Experienced Patients | Study 888 (48 Weeks) | Study 9572 and Study 7653 (84-144 Weeks) |
| KALETRA 400/100 mg BID + NVP + NRTIs
(N=148) | Investigator-selected protease inhibitor(s) + NVP + NRTIs
(N=140) | KALETRA BID + NNRTI + NRTIs
(N=127) |
|
1 Includes adverse events of possible,probable, or unknown relationship to study drug.
2 Includes adverse event data from patients receiving 400/100 mg BID (n=29) or 533/133 mg BID (n=28) for 84 weeks. Patients receiving KALETRA in combination with NRTIs and efavirenz.
3 Includes adverse event data from patients receiving 400/100 mg BID (n=36) or 400/200 mg BID (n=34) for 144 weeks. Patients received KALETRA in combination with NRTIs and nevirapine.
|
| Body as a Whole | | | |
| Abdominal Pain | 2% | 2% | 4% |
| Asthenia | 3% | 6% | 9% |
| Chills | 2% | 0% | 0% |
| Fever | 2% | 1% | 2% |
| Headache | 2% | 3% | 2% |
| Cardiovascular | | | |
| Hypertension | 0% | 0% | 2% |
| Digestive System | | | |
| Anorexia | 1% | 3% | 0% |
| Diarrhea | 7% | 9% | 23% |
| Dyspepsia | 1% | 1% | 2% |
| Dysphagia | 2% | 1% | 0% |
| Flatulence | 1% | 2% | 2% |
| Nausea | 7% | 16% | 5% |
| Vomiting | 4% | 12% | 2% |
| Metabolic and Nutritional | | | |
| Weight loss | 0% | 1% | 3% |
| Musculoskeletal | | | |
| Myalgia | 1% | 1% | 2% |
| Nervous System | | | |
| Depression | 1% | 2% | 2% |
| Insomnia | 0% | 2% | 2% |
| Paresthesia | 1% | 0% | 2% |
| Skin and Appendages | | | |
| Rash | 2% | 1% | 2% |
Treatment-emergent adverse events occurring in less than 2% of adult patients receiving KALETRA in all phase II/III clinical trials and considered at least possibly related or of unknown relationship to treatment with KALETRA and of at least moderate intensity are listed below by body system.
Body as a Whole
Allergic reaction, back pain, chest pain, chest pain substernal, cyst, drug interaction, drug level increased, face edema, flu syndrome, hypertrophy, infection bacterial, malaise, neoplasm, and viral infection.
Cardiovascular System
Atrial fibrillation, cerebral infarct, deep thrombophlebitis, deep vein thrombosis, migraine, myocardial infarct, palpitation, postural hypotension, thrombophlebitis, varicose vein, and vasculitis.
Digestive System
Cholangitis, cholecystitis, constipation, dry mouth, enteritis, enterocolitis, eructation, esophagitis, fecal incontinence, gastritis, gastroenteritis, hemorrhagic colitis, hepatitis, hepatomegaly, increased appetite, jaundice, liver fatty deposit, liver tenderness, mouth ulceration, pancreatitis, periodontitis, sialadenitis, stomatitis, and ulcerative stomatitis.
Endocrine System
Cushing's syndrome, diabetes mellitus, and hypothyroidism.
Hemic and Lymphatic System
Anemia, leukopenia, and lymphadenopathy.
Metabolic and Nutritional Disorders
Avitaminosis, dehydration, edema, glucose tolerance decreased, lactic acidosis, obesity, peripheral edema, and weight gain.
Musculoskeletal System
Arthralgia, arthrosis, bone necrosis, joint disorder, and myasthenia.
Nervous System
Abnormal dreams, agitation, amnesia, anxiety, apathy, ataxia, confusion, convulsion, dizziness, dyskinesia, emotional lability, encephalopathy, extrapyramidal syndrome, facial paralysis, hypertonia, nervousness, neuropathy, peripheral neuritis, somnolence, thinking abnormal, tremor, and vertigo.
Respiratory System
Asthma, cough increased, dyspnea, lung edema, pharyngitis, rhinitis, and sinusitis.
Skin and Appendages
Acne, alopecia, dry skin, eczema, exfoliative dermatitis, furunculosis, maculopapular rash, nail disorder, pruritis, seborrhea, skin benign neoplasm, skin discoloration, skin striae, skin ulcer, and sweating.
Special Senses
Abnormal vision, eye disorder, otitis media, taste loss, taste perversion, and tinnitus.
Urogenital System
Abnormal ejaculation, amenorrhea, breast enlargement, gynecomastia, impotence, kidney calculus, nephritis, and urine abnormality.
Post-marketing Experience
The following adverse reactions have been reported during post-marketing use of KALETRA. Because these reactions are reported voluntarily from a population of unknown size, it is not 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 PRECAUTIONS – Fat Redistribution).
Cardiovascular
Bradyarrhythmias.
Skin and Appendages
Stevens Johnson Syndrome and erythema multiforme.
Laboratory Abnormalities
The percentages of adult patients treated with combination therapy with Grade 3-4 laboratory abnormalities are presented in Table 14 and Table 15.
Table 14. Grade 3-4 Laboratory Abnormalities Reported in ≥ 2% of Adult Antiretroviral-Naïve Patients | | Study 863 (48 Weeks) | Study 418 (48 Weeks) | Study 720 (360 Weeks) |
| Variable | Limit1 | KALETRA 400/100 mg BID + d4T +3TC
(N=326) | Nelfinavir 750 mg TID + d4T + 3TC
(N=327) | KALETRA 800/200 mg QD + TDF + FTC
(N=115) | KALETRA 400/100 mg BID + TDF + FTC
(N=75) | KALETRA BID + d4T + 3TC
(N=100) |
|
1 ULN = upper limit of the normal range; N/A = Not Applicable.
|
| Chemistry | High | | | | | |
| Glucose | >250 mg/dL | 2% | 2% | 3% | 1% | 4% |
| Uric Acid | >12 mg/dL | 2% | 2% | 0% | 3% | 5% |
SGOT/
AST | >180 U/L | 2% | 4% | 5% | 3% | 10% |
SGPT/
ALT | >215 U/L | 4% | 4% | 4% | 3% | 11% |
| GGT | >300 U/L | N/A | N/A | N/A | N/A | 10% |
Total
Cholesterol | >300 mg/dL | 9% | 5% | 3% | 3% | 27% |
| Triglycerides | >750 mg/dL | 9% | 1% | 5% | 4% | 29% |
| Amylase | >2 x ULN | 3% | 2% | 7% | 5% | 4% |
| Hematology | Low | | | | | |
| Neutrophils | 0.75 x 109/L | 1% | 3% | 5% | 1% | 5% |
Table 15. Grade 3-4 Laboratory Abnormalities Reported in ≥ 2% of Adult Protease Inhibitor-Experienced Patients | | Study 888 (48 Weeks) | Study 9572 and Study 7653 (84-144 Weeks) |
| Variable | Limit1 | KALETRA 400/100 mg BID + NVP + NRTIs
(N=148) | Investigator-selected protease inhibitor(s) + NVP + NRTIs
(N=140) | KALETRA BID + NNRTI + NRTIs
(N=127) |
|
1 ULN = upper limit of the normal range; N/A = Not Applicable.
2 Includes clinical laboratory data from patients receiving 400/100 mg BID (n=29) or 533/133 mg BID (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 BID (n=36) or 400/200 mg BID (n=34) for 144 weeks. Patients received KALETRA in combination with NRTIs and nevirapine.
|
| Chemistry | High | | | |
| Glucose | >250 mg/dL | 1% | 2% | 5% |
| Total Bilirubin | >3.48 mg/dL | 1% | 3% | 1% |
| SGOT/AST | >180 U/L | 5% | 11% | 8% |
| SGPT/ALT | >215 U/L | 6% | 13% | 10% |
| GGT | >300 U/L | N/A | N/A | 29% |
Total
Cholesterol | >300 mg/dL | 20% | 21% | 39% |
| Triglycerides | >750 mg/dL | 25% | 21% | 36% |
| Amylase | >2 x ULN | 4% | 8% | 8% |
| Chemistry | Low | | | |
Inorganic
Phosphorus | <1.5 mg/dL | 1% | 0% | 2% |
| Hematology | Low | | | |
| Neutrophils | 0.75 x 109/L | 1% | 2% | 4% |
Pediatrics
Treatment-Emergent Adverse Events
KALETRA has been studied in 100 pediatric patients 6 months to 12 years of age. The adverse event profile seen during a clinical trial was similar to that for adult patients.
Taste aversion, vomiting, and diarrhea were the most commonly reported drug related adverse events of any severity in pediatric patients treated with combination therapy including KALETRA for up to 48 weeks in Study 940. A total of 8 children experienced moderate or severe adverse events at least possibly related to KALETRA. Rash (reported in 3%) was the only drug-related clinical adverse event of moderate to severe intensity observed in ≥ 2% of children enrolled.
Laboratory Abnormalities
The percentages of pediatric patients treated with combination therapy including KALETRA with Grade 3-4 laboratory abnormalities are presented in Table 16.
Table 16. Grade 3-4 Laboratory Abnormalities Reported in ≥ 2% Pediatric Patients | Variable | Limit1 | KALETRA BID+ RTIs
(N = 100) |
|
1 ULN = upper limit of the normal range.
2 Subjects with Grade 3-4 amylase confirmed by elevations in pancreatic amylase.
|
| 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% |
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REPORTS OF SUSPECTED KALETRA SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Kaletra. The information is not vetted and should not be considered as verified clinical evidence.
Possible Kaletra side effects / adverse reactions in 61 year old female
Reported by a health professional (non-physician/pharmacist) from Switzerland on 2011-10-04
Patient: 61 year old female
Reactions: Dyspnoea, Hypersensitivity, Localised Oedema, Drug Interaction
Suspect drug(s):
Kaletra
Other drugs received by patient possibly interacting with the suspect drug:
Cinacalcet
Indication: Parathyroid Disorder
Saquinavir Mesilate
Administration route: Oral
Indication: Asymptomatic HIV Infection
Kaletra
Dosage: 533.2/133.3mg
Administration route: Oral
Cinacalcet
Dosage: 1 tablet at night for 3 nights
Administration route: Oral
Indication: Hyperparathyroidism
Start date: 2009-01-01
End date: 2009-01-01
Other drugs received by patient: Calcitriol; Moxifloxacin; Lamivudine (Epivir Hbv); Venofer; Erythropoietin Human
Possible Kaletra side effects / adverse reactions in 40 year old male
Reported by a physician from Japan on 2011-10-04
Patient: 40 year old male
Reactions: Rhabdomyolysis, Diarrhoea, Renal Failure Acute
Adverse event resulted in: hospitalization
Suspect drug(s):
Alcohol
Indication: Product Used FOR Unknown Indication
Tenofovir Disoproxil Fumarate
Indication: HIV Infection
Kaletra
Indication: HIV Infection
Emtricitabine
Indication: HIV Infection
Possible Kaletra side effects / adverse reactions in 39 year old female
Reported by a physician from United States on 2011-10-05
Patient: 39 year old female
Reactions: Thrombosis, Premature Separation of Placenta, Inflammation
Suspect drug(s):
Kaletra
Dosage: 4 tablets daily, taken at conception
Administration route: Oral
Indication: Antiviral Treatment
Start date: 2010-07-15
Epivir
Dosage: 300 mg daily, taken at conception
Administration route: Oral
Indication: Antiviral Treatment
Start date: 2010-07-15
Viread
Dosage: 300 mg daily, taken at conception
Administration route: Oral
Indication: Antiviral Treatment
Start date: 2010-07-15
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