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Kaletra (Lopinavir / Ritonavir) - Side Effects and Adverse Reactions

 
 



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%
Asthenia4%3%0%0%9%
Headache2%2%3%3%6%
Cardiovascular System
Vein distended0%0%0%0%3%
Digestive System
Anorexia1%<1%<1%1%2%
Diarrhea16%17%16%5%28%
Dyspepsia2%<1%0%1%6%
Flatulence2%1%2%1%4%
Nausea7%5%9%8%16%
Vomiting2%2%3%4%6%
Metabolic and Nutritional
Weight Loss1%<1%0%0%2%
Musculoskeletal
Myalgia1%1%0%0%2%
Nervous System
Depression1%2%1%0%0%
Insomnia2%1%0%0%3%
Libido
decreased
<1%<1%0%1%2%
Paresthesia1%1%0%0%2%
Respiratory
Bronchitis0%0%0%0%2%
Skin and Appendages
Rash1%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 Pain2%2%4%
Asthenia3%6%9%
Chills2%0%0%
Fever2%1%2%
Headache2%3%2%
Cardiovascular
Hypertension0%0%2%
Digestive System
Anorexia1%3%0%
Diarrhea7%9%23%
Dyspepsia1%1%2%
Dysphagia2%1%0%
Flatulence1%2%2%
Nausea7%16%5%
Vomiting4%12%2%
Metabolic and Nutritional
Weight loss0%1%3%
Musculoskeletal
Myalgia1%1%2%
Nervous System
Depression1%2%2%
Insomnia0%2%2%
Paresthesia1%0%2%
Skin and Appendages
Rash2%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/dL2%2%3%1%4%
Uric Acid>12 mg/dL2%2%0%3%5%
SGOT/
AST
>180 U/L2%4%5%3%10%
SGPT/
ALT
>215 U/L4%4%4%3%11%
GGT>300 U/LN/AN/AN/AN/A10%
Total
Cholesterol
>300 mg/dL9%5%3%3%27%
Triglycerides>750 mg/dL9%1%5%4%29%
Amylase>2 x ULN3%2%7%5%4%
Hematology Low
Neutrophils0.75 x 109/L1%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/dL1%2%5%
Total Bilirubin>3.48 mg/dL1%3%1%
SGOT/AST>180 U/L5%11%8%
SGPT/ALT>215 U/L6%13%10%
GGT>300 U/LN/AN/A29%
Total
Cholesterol
>300 mg/dL20%21%39%
Triglycerides>750 mg/dL25%21%36%
Amylase>2 x ULN4%8%8%
Chemistry Low
Inorganic
Phosphorus
<1.5 mg/dL1%0%2%
Hematology Low
Neutrophils0.75 x 109/L1%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/L3%
     Total Bilirubin≥ 3.0 x ULN3%
     SGOT/AST> 180 U/L8%
     SGPT/ALT> 215 U/L7%
     Total Cholesterol> 300 mg/dL3%
     Amylase> 2.5 x ULN7%2
Chemistry Low
     Sodium< 130 mEq/L3%
Hematology Low
     Platelet Count< 50 x 109/L4%
     Neutrophils< 0.40 x 109/L2%



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



See index of all Kaletra side effect reports >>

Drug label data at the top of this Page last updated: 2007-07-23

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