Table 2 and Table 3 summarize the clinical adverse events and laboratory abnormalities, respectively, that occurred in≥1% of patients in the comparative monotherapy trial (CPCRA 002) of HIVID vs didanosine (ddI), and the comparative combination trial (ACTG 175) of zidovudine (ZDV) monotherapy vs HIVID and zidovudine combination therapy, respectively. Other studies have found a higher or lower incidence of adverse experiences depending upon disease status, generally being lower in patients with less advanced disease.
Table 2 Percentage of Patients With Clinical Adverse Experience ≥ Grade 3
Grade 3 severity: event causing marked limitation in activity, requiring medical care and possible hospitalization.
Grade 4 severity: completely disabling, unable to care for self, requiring active medical intervention, probable hospitalization or hospice care. in ≥1% of Patients Receiving HIVID
ZDV Intolerant or Failure
|ACTG 175All relationships.|
0.750 mg q8h
250 mg q12h
200 mg q8h
0.750 mg q8h +200 mg q8h
|Body System/Adverse Event|
|Gastrointestinal|| || || || |
| Abdominal Pain||3.0||7.0||2.3||1.8|
| Oral Lesions/Stomatitis
| Abnormal Hepatic Function||8.9||7.0||
| Peripheral NeuropathyCPCRA 002 included patients who were dose-adjusted for Grade 2 events; ACTG 175 required dose adjustment for Grade 2 peripheral neuropathy but recorded only Grade 3 events.||28.3||13.0||3.1||3.3|
|Metabolic and Nutrition|
| Painful/Swollen Joints||0.4||0.0||0.3||1.0|
Table 3 Percentage of Patients With Laboratory Abnormalities — Protocol Grade 3/4
ZDV Intolerant or Failure
0.750 mg q8h
250 mg q12h
200 mg q8h
0.750 mg q8h +200 mg q8h n=615
|Anemia (<7.5 gm/dL)||8.4||7.4||1.8||3.1|
|Leukopenia (<1500 cells/mm3)||13.1||9.6||N/A
(>1000 cells/mm3 or 25%)
|Neutropenia (<750 cells/mm3)||16.9||11.7||1.9||4.2|
|CPK Elevation (>4× ULN)||0.8||0.0||5.8||5.7|
|ALT (SGPT) (>5 × ULN)||N/A||N/A||3.6||5.0|
|AST (SGOT) (>5 × ULN)||7.6||5.7||2.9||4.1|
|Bilirubin (>2.5 × ULN)||0.8||0.9||0.5||1.0|
|GGT (>5 × ULN)||N/A||N/A||0.5||1.0|
|Amylase (>2 × ULN)||5.1||3.9||1.0||1.5|
|Hyperglycemia (>250 mg/dL)||0.0||1.7||0.8||2.0|
Additional clinical adverse experiences associated with HIVID that occurred in <1% of patients in CPCRA 002 (at least possibly related, Grade 3 or higher), ACTG 175 (any relationship, Grade 3/4) or in other clinical studies are listed below by body system. Several of these events occurred in slightly higher rates in other studies. The incidence of adverse experiences varied in different studies, generally being lower in patients with less-advanced disease.
Body as a Whole: abnormal weight loss, asthenia, cachexia, chest tightness or pain, chills, cutaneous/allergic reaction, debilitation, difficulty moving, dry eyes/mouth, edema, facial pain or swelling, flank pain, flushing, increased sweating, lymphadenopathy, hypersensitivity reactions (see WARNINGS), malaise, night sweats, pain, pelvic/groin pain, rigors, redistribution/accumulation of body fat (see PRECAUTIONS: Fat Redistribution).
Cardiovascular: abnormal cardiac movement, arrhythmia, atrial fibrillation, cardiac failure, cardiac dysrhythmias, cardiomyopathy, heart racing, hypertension, palpitation, subarachnoid hemorrhage, syncope, tachycardia, ventricular ectopy.
Endocrine/Metabolic: abnormal triglycerides, abnormal lipase, altered serum glucose, decreased bicarbonate, diabetes mellitus, glycosuria, gout, hot flushes, hypercalcemia, hyperkalemia, hyperlipemia, hypernatremia, hyperuricemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, increased nonprotein nitrogen, lactic acidosis.
Gastrointestinal: abdominal bloating or cramps, acute pancreatitis, anal/rectal pain, anorexia, bleeding gums, bloody or black stools, colitis, dental abscess, dry mouth, dyspepsia, dysphagia, enlarged abdomen, epigastric pain, eructation, esophageal pain, esophageal ulcers, esophagitis, flatulence, gagging with pills, gastritis, gastrointestinal hemorrhage, gingivitis, glossitis, gum disorder, heartburn, hemorrhagic pancreatitis, hemorrhoids, increased saliva, left quadrant pain, melena, mouth lesion, odynophagia, painful sore gums, painful swallowing, pancreatitis, rectal hemorrhage, rectal mass, rectal ulcers, salivary gland enlargement, sore tongue, sore throat, tongue disorder, tongue ulcer, toothache, unformed/loose stools, vomiting.
Hematologic: absolute neutrophil count alteration, anemia, epistaxis, decreased hematocrit, granulocytosis, hemoglobinemia, leukopenia, neutrophilia, platelet alteration, purpura, thrombus, unspecified hematologic toxicity, white blood cell alteration.
Hepatic: abnormal lactate dehydrogenase, bilirubinemia, cholecystitis, decreased alkaline phosphatase, hepatitis, hepatocellular damage, hepatomegaly, increased alkaline phosphatase, jaundice.
Musculoskeletal: arthralgia, arthritis, arthropathy, arthrosis, back pain, backache, bone pains/aches, bursitis, cold extremities, extremity pain, joint inflammation, leg cramps, muscle aches, muscle weakness, muscle disorder, muscle stiffness, muscle cramps, myalgia, myopathy, myositis, neck pain, rib pain, stiff neck.
Neurological: abnormal coordination, aphasia, ataxia, Bell's palsy, confusion, decreased concentration, decreased neurological function, disequilibrium, dizziness, dysphonia, facial nerve palsy, focal motor seizures, grand mal seizure, hyperkinesia, hypertonia, hypokinesia, memory loss, migraine, neuralgia, neuritis, paralysis, seizures, speech disorder, status epilepticus, stupor, tremor, twitch, vertigo.
Psychological: acute psychotic disorder, acute stress reaction, agitation, amnesia, anxiety, confusion, decreased motivation, decreased sexual desire, depersonalization, emotional lability, euphoria, hallucination, impaired concentration, insomnia, manic reaction, mood swings, nervousness, paranoid state, somnolence, suicide attempt, dementia.
Respiratory: acute nasopharyngitis, chest congestion, coughing, cyanosis, difficulty breathing, dry nasal mucosa, dyspnea, flu-like symptoms, hemoptysis, nasal discharge, pharyngitis, rales/rhonchi, respiratory distress, sinus congestion, sinus pain, sinusitis, wheezing.
Skin: acne, alopecia, bullous eruptions, carbuncle/furuncle, cellulitis, cold sore, dermatitis, dry skin, dry rash desquamation, erythematous rash, exfoliative dermatitis, finger inflammation, follicular rash, impetigo, infection, itchy rash, lip blisters/lesions, macular/papular rash, maculopapular rash, moniliasis, mucocutaneous/skin disorder, nail disorder, photosensitivity reaction, pruritic disorder, pruritus, skin disorder, skin lesions, skin fissure, skin ulcer, urticaria.
Special Senses: abnormal vision, blurred vision, burning eyes, decreased taste, decreased vision, ear pain/problem, ear blockage, eye abnormality, eye inflammation, eye itching, eye pain, eye irritation, eye redness, eye hemorrhage, fluid in ears, hearing loss, increased tears, loss of taste, mucopurulent conjunctivitis, parosmia, photophobia, smell dysfunction, taste perversion, tinnitus, unequal-sized pupils, xerophthalmia, yellow sclera.
Urogenital: abnormal renal function, acute renal failure, albuminuria, bladder pain, dysuria, frequent urination, genital lesion/ulcer, increased blood urea nitrogen, increased creatinine, micturition frequency, nocturia, painful penis sore, pain on urination, penile edema, polyuria, renal cyst, renal calculus, testicular swelling, toxic nephropathy, urinary retention, vaginal itch, vaginal ulcer, vaginal pain, vaginal/cervix disorder, vaginal discharge.