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Home > Treatment > Charts & Tables > Non-ARV Adverse Events
Adverse Events Due to Nonantiretroviral Medications during Treatment of HIV-Related Infections and Complications
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Introduction
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Tables
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transparent imageAgents Used in the Management of Pneumocystis jiroveci Pneumonia (PCP)
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transparent imageAgents Used in the Management of Fungal Infections
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transparent imageAgents for the Management of Toxoplasmosis
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transparent imageAgents for the Management of Mycobacterial Infections
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transparent imageAgents for the Management of Cytomegalovirus Infections
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transparent imageAgents for the Treatment of Herpes Virus Infections
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transparent imageAgents for the Treatment of Hepatitis C
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transparent imageAgents for the Treatment of Malignancies
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transparent imageMetabolic Agents
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transparent imageHematopoietic Agents
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transparent imageAgents for the Treatment of Neuropathic Pain
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transparent imageAgents for the Treatment of Infectious Diarrhea
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References
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Introduction
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The following tables summarize selected adverse events associated with nonantiretroviral drugs commonly used to treat HIV-associated conditions. (Side effects of antiretroviral drugs are found in "Adverse Effects of Antiretroviral Drugs") Where available, frequencies of adverse events are included to guide the clinician on the likelihood of a particular side effect. Not all adverse reactions have a frequency listed, as some are not reported reliably in the literature or are dependent on many factors. Reference 1 was utilized for all the medications listed.

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Tables
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Agents Used in the Management of Pneumocystis jiroveci Pneumonia (PCP)
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AgentAdverse EventsComments
Atovaquone (2,3)
  • Rash (39%) (maculopapular, erythematous, or bullous), pruritus (5%)

  • Fever (40%), headache (28%)

  • Anemia (6%), neutropenia (3%)

  • Diarrhea (42%), nausea (26%), vomiting (15%), abdominal pain (20%), constipation (3%), anorexia (7%), dyspepsia (5%), abnormal taste (3%)

  • Elevated liver function tests (4-6%)

  • Rash usually is mild to moderate.

  • May be able to treat through the rash.

Clindamycin (4,5)
  • Maculopapular rash, generalized morbilliform rash

  • Nausea, vomiting, diarrhea, pseudomembranous colitis due to Clostridium difficile, abdominal pain, unpleasant or metallic taste

  • Elevated liver function tests

Dapsone (6)
  • Rash, hemolytic anemia, methemoglobinemia, leukopenia (<1%)

  • Anorexia, abdominal pain, nausea, vomiting

  • Hepatitis (<1%), cholestatic jaundice (<1%), elevated liver function tests

  • Peripheral neuropathy

  • Avoid in individuals with G6PD deficiency.

  • Approximately 40% of patients intolerant or allergic to TMP-SMX will be intolerant to dapsone.(7)

  • Peripheral neuropathy is more common with doses >100 mg per day.

Leucovorin
  • No significant adverse effects reported

  • Associated with increased rate of TMP-SMX treatment failure (8)

  • If used in conjunction with trimetrexate, continue leucovorin for 3-5 days after last trimetrexate dose to reduce risk of severe neutropenia.

Pentamidine (3,9)Aerosolized:
  • Bronchospasm, cough (63%)

Intravenous:
  • Acute hypoglycemia (5-24%), chronic hyperglycemia, diabetes mellitus

  • Elevated serum creatinine (25%), acute renal failure

  • Hyperkalemia

  • Hypocalcemia, hypomagnesemia

  • Hypotension

  • Rash (rare)

  • Leukopenia, thrombocytopenia, anemia

  • Nausea, anorexia

  • Pancreatitis (9%)

  • Elevated liver function tests

  • Bronchospasm and cough are associated with aerosolized administration and may be reduced by pretreatment with albuterol.

  • Requires frequent renal function and electrolyte monitoring during therapy.

  • Severe hypotension may develop after a single dose of intramuscular or intravenous pentamidine.

  • Hyperglycemia and diabetes mellitus, with or without preceding hypoglycemia, may develop several months after therapy.

  • Requires blood glucose monitoring during therapy and periodically thereafter.

Prednisone
  • Greater than 10%: insomnia, nervousness, diabetes mellitus, hyperglycemia

  • 1-10%: arthalgias, glaucoma, acne, Cushing syndrome, adrenal insufficiency, sodium and water retention, esophageal and gastric ulcerations, mood swings, euphoria

  • In severe PCP, documented benefits, as adjunct to antimicrobial treatment if arterial oxygen pressure <70 mm Hg or (A-a) gradient >35 mm Hg.

  • Start within 24-72 hours of initial PCP treatment.(10)

  • Dose: days 1-5: 40 mg PO BID; days 6-10: 40 mg PO QD; days 11-21: 20 mg PO QD.(10)

Primaquine
  • Rash (60%) when used with clindamycin for PCP (11)

  • Methemoglobinemia (1-5%)

  • Abdominal pain, nausea, vomiting

  • Avoid in individuals with G6PD deficiency.

  • Methemoglobinemia more common if administered to patients with NADH-methemoglobin reductase deficiency.

  • May take with meals to reduce frequency of gastrointestinal upset.

  • Contraindicated during pregnancy.

Trimethoprim-Sulfamethoxazole (2) (TMP-SMX)
  • Rare but potentially life-threatening reactions include Stevens-Johnson syndrome and hepatic necrosis

  • Rash (18-69%) (diffuse, erythematous, and maculopapular)(12)

  • Fever

  • Anemia, leukopenia (neutropenia), thrombocytopenia

  • Nausea, vomiting, anorexia

  • Elevated liver function tests

  • Hyperkalemia, hyponatremia

  • Several desensitization protocols have been published.(13,14)

  • Use with caution in patients with folate or G6PD deficiency.

  • Avoid sulfamethoxazole administration to at-term pregnant women.

  • Concurrent administration of folinic acid is associated with increased risk of therapeutic failure.(8)

Trimetrexate
  • Rash

  • Neutropenia, anemia, thrombocytopenia

  • Seizures, fever

  • Elevated liver function tests

  • Peripheral neuropathy

  • Leucovorin must be given to reduce risk of severe bone marrow suppression and other complications of folic acid deficiency.

  • Contraindicated during pregnancy.

List of abbreviations:
BID = twice daily
Hg = mercury
PO = orally
QD = once daily
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Agents Used in the Management of Fungal Infections
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AgentAdverse EventsComments
Amphotericin B
  • Acute infusion reaction (fever, chills, rigors, headache, nausea, vomiting)

  • Anemia (normocytic, normochromic)

  • Nephrotoxicity (lower risk with lipid-based or liposomal formulations)

  • Hypokalemia, hypomagnesemia

  • Infusion site thrombophlebitis

  • Acetaminophen, antihistamines, corticosteroids, and meperidine have been used for the prevention and treatment of the acute infusion reaction.

  • Appropriate intravenous hydration with normal saline recommended prior to amphotericin B administration to reduce the risk of nephrotoxicity.

Caspofungin (15)
  • Fever (7%), chills (5.3%)

  • Phlebitis/thrombophlebitis (3.5%)

  • Diarrhea (2.6%), nausea (1.8%), vomiting (3.5%)

  • Elevated liver function tests (2-4%)

  • Hypokalemia (10%)

Fluconazole (16,17)
  • Rash (5%), alopecia (12-20%)

  • Headache (2%), dizziness (2%)

  • Gastrointestinal symptoms (nausea, vomiting, abdominal pain diarrhea) (1-5%)

  • Severe jaundice (rare), acute hepatic necrosis (rare)

  • Alopecia is more common with higher doses and longer duration of treatment.

Flucytosine (18)
  • Rash, pruritus, urticaria, photosensitivity

  • Bone marrow suppression, especially leukopenia and thrombocytopenia (more common in patients with renal insufficiency)

  • Nausea, vomiting, anorexia, abdominal bloating, abdominal pain, diarrhea, dry mouth, duodenal ulcer, gastrointestinal hemorrhage, ulcerative colitis (rare)

  • Elevated liver function tests, liver necrosis (rare)

  • Hematologic toxicity is dose related.

  • Monitoring of blood cell counts is recommended.

  • Dosage reduction is required for patients with renal failure.

Itraconazole (17)
  • Elevated liver function tests

  • Rash (9%), pruritus (3%)

  • Headache (4%), fever (3%), dizziness (2%)

  • Nausea (11%), vomiting (5%), diarrhea (3-6%), symptomatic hepatitis (rare)

  • Hypokalemia (5%)

  • Edema (0.4-3.5%)

  • Rash is more common in immunosuppressed individuals.

  • For best absorption, capsules must be taken with food, although oral suspension must be taken on an empty stomach.

Ketoconazole
  • Pruritus (2%), rash (1%), dermatitis (1%), urticaria (1%)

  • Nausea/vomiting (5-10%), abdominal pain (1-2%)

  • Elevated liver function tests

  • Gynecomastia (inhibits testosterone synthesis)

  • Administer with food (requires acid for absorption).

  • May interact with other drugs by affecting P450 metabolism. Dosage adjustments may be required; certain combinations are contraindicated.

Micafungin (19)
  • Injection site reactions, rash, facial swelling, itching

  • Fever (2%), headache (3%)

  • Leukopenia (3%)

  • Nausea, dyspepsia, elevated liver function tests

  • Anaphylaxis (rare)

Posaconazole (20)
  • Rash (3-19%)

  • QT prolongation

  • Nausea, vomiting, diarrhea, abdominal pain

  • Hepatotoxicity

  • Hypokalemia (3-30%)

Voriconazole (21)
  • Visual disturbances (30%) (enhanced light perception, blurred vision, photophobia, or color vision changes)

  • Rash (6%) (facial and generalized erythema, dermatitis), photosensitivity (1-2%), Stevens-Johnson syndrome (rare)

  • Nausea, vomiting, diarrhea, abdominal pain

  • Hepatotoxicity (rare)

  • Visual events usually occur within 30 minutes of dosing and most frequently during the first week of therapy.

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Agents for the Management of Toxoplasmosis
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AgentAdverse EventsComments
Clindamycin (22)
  • See section discussing agents used to treat PCP

Pyrimethamine (22)
  • Megaloblastic anemia, leukopenia, thrombocytopenia, agranulocytosis

  • Anorexia, abdominal cramps, diarrhea, vomiting

  • Ataxia, tremors, seizures, respiratory failure (rare)

  • Leucovorin (10-25 mg PO QD) should be administered with pyrimethamine to prevent complications of folic acid deficiency.

Sulfadiazine (22)
  • Dermatologic reactions (rash, pruritus, urticaria, erythema nodosum, erythema multiforme, toxic epidermal necrolysis, photosensitivity)

  • Fever, headache

  • Granulocytopenia, leukopenia, thrombocytopenia, aplastic anemia, hemolytic anemia

  • Nausea, vomiting, abdominal pain, diarrhea

  • Hepatotoxicity (rare)

  • Nephrotoxicity due to crystalluria (23) (renal colic, nephritis, urolithiasis, toxic nephrosis)

  • Hemolytic anemia more common in individuals with G6PD deficiency.

  • Contraindicated during pregnancy.

List of abbreviations:
PO = orally
QD = once daily
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Agents for the Management of Mycobacterial Infections
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AgentAdverse EventsComments
Amikacin (24)
  • Nephrotoxicity (9%)

  • Ototoxicity (auditory > vestibular)

  • Second-line agent.

  • Monitoring of serum drug concentrations is recommended.

  • Dosing adjustment necessary in patients with renal insufficiency to reduce the risk of ototoxicity and nephrotoxicity.

  • Ototoxicity more common with the concurrent use of diuretics.

  • Baseline audiogram, vestibular testing, and Romberg testing recommended.

  • Contraindicated during pregnancy.

Azithromycin (25)
  • Rash, pruritus

  • Diarrhea, loose stools, nausea, abdominal pain

  • Hearing loss

Ciprofloxacin
  • Nausea, vomiting, diarrhea, abdominal pain or discomfort

  • Headache, restlessness, seizures (rare)

  • Avoid coadministration with antacids, enteral supplements, multiple vitamins, and iron.

  • Contraindicated during pregnancy.

Clarithromycin (25)
  • Headache (2%)

  • Abnormal taste (3%), diarrhea (3%), nausea (3%), dyspepsia (2%), abdominal discomfort (2%)

Clofazimine (26)
  • Pink to brownish-black discoloration of the skin (75-100%), ichthyosis and dry skin (8-38%)

  • Abdominal and epigastric pain, diarrhea, nausea, vomiting, gastrointestinal intolerance

  • Reversible, red-brown discoloration of the conjunctiva, cornea, and lacrimal fluid (38-57%)

  • '
  • Clofazimine should be used only when other agents are not tolerated or not available, since 1 study of Mycobacterium avium treatment showed increased mortality in patients receiving clofazimine.

  • Gastrointestinal side effects are more common in patients receiving >100 mg/day.

  • Ocular effects are dose related.

Cycloserine (24)
  • Hypersensitivity reactions and photosensitivity (rare)

  • Cardiac arrhythmia and sudden onset of congestive heart failure

  • Elevated liver function tests

  • Drowsiness, somnolence, dizziness, headache, lethargy, depression, tremor, dysarthria, hypererflexia, paresthesia, nervousness, anxiety, vertigo, confusion and disorientation with loss of memory, paresis, major and minor clonic seizures, convulsions, coma

  • Vitamin B12 deficiency, folic acid deficiency

  • Second-line agent.

  • CNS side effects appear to be dose related and occur within the first 2 weeks of therapy.

  • Pyridoxine (100-200 mg QD) may prevent some CNS side effects.

Ethambutol (27,28)
  • Optic neuritis (decrease in visual acuity, constriction of visual fields, central and peripheral scotomas, loss of red-green color discrimination)

  • Gastrointestinal upset, abdominal pain, nausea, vomiting, and anorexia

  • Elevated liver function tests

  • Hyperuricemia

  • Ocular toxicity is associated with higher doses (>15 mg/kg/day) and longer exposures to ethambutol.

Ethionamide (24)
  • Nausea, vomiting, diarrhea, abdominal pain, excessive salivation, metallic taste, stomatitis, anorexia, and weight loss

  • Elevated liver function tests, hepatotoxicity (2%)

  • Psychotic disturbances, mental depression, restlessness, drowsiness, dizziness, headache, postural hypotension, asthenia, peripheral neuritis, paresthesia, seizures, tremors, pellagra-like syndrome, hallucinations, diplopia, optic neuritis, blurred vision, olfactory disturbances

  • Gynecomastia, alopecia, hypothyroidism, erectile dysfunction, hypoglycemia (especially in diabetics)

  • Second-line agent.

  • Gastrointestinal side effects can be minimized by administering the drug in divided doses with meals, at bedtime, or with an antiemetic.

  • Pyridoxine (25-50 mg QD) may reduce CNS side effects.

Isoniazid (27,28)
  • Peripheral neuropathy

  • Elevated liver function tests, usually mild, transient (most common in alcoholics, individuals >35 years of age, individuals with pre-existing liver disease); fatal hepatitis (rare)

  • Hypersensitivity reactions (fever, rash, lymphadenopathy, vasculitis)

  • Nausea, vomiting, epigastric distress

  • Predisposing factors for peripheral neuropathy:

    • Malnourishment

    • Alcoholism

    • Diabetes mellitus

  • Pyridoxine (25-50 mg PO QD) should be administered with isoniazid to reduce the risk of neurotoxicity.

Ofloxacin
  • Nausea (3-10%), vomiting (1-3%), diarrhea (1-4%)

  • Headache (1-9%), insomnia (3-7%), dizziness (1-5%)

  • Rash (1-3%), pruritus (1-3%)

  • Avoid coadministration with antacids, enteral supplements, multiple vitamins, and iron.

  • Contraindicated during pregnancy.

Pyrazinamide (27,28)
  • Reports of severe liver injury and death when the combination of rifampin and pyrazinamide was used for the treatment of latent tuberculosis infection (29)

  • Hepatotoxicity; transient elevation in liver function tests, hepatitis (rare)

  • Nausea, vomiting, anorexia

  • Hyperuricemia

  • Arthralgia, myalgia

  • The combination of rifampin and pyrazinamide should not be used for the treatment of latent tuberculosis infection.

Rifabutin (28)
  • Red-orange coloration of body fluids

  • Uveitis

  • Elevated liver function tests

  • Rash (11%)

  • Neutropenia (25%)

  • Nausea (6%), vomiting (3%), abdominal pain (4%), taste perversion (3%), diarrhea (3%), dyspepsia (3%), eructation (3%)

  • Uveitis is dose related.

  • Soft contact lenses should not be used while receiving rifabutin due to the possibility of lens discoloration.

  • Potential for drug-drug interactions through induction of CYP450

Rifampin (27,28)
  • Reports of severe liver injury and death when the combination of rifampin and pyrazinamide was used for the treatment of latent tuberculosis infection (29)

  • Red-orange coloration of body fluids

  • Transient elevation in liver function tests, hepatitis (rare)

  • Heartburn, epigastric distress, nausea, vomiting, anorexia, abdominal cramps, flatulence, diarrhea

  • Rash, hypersensitivity reaction (rare)

  • The combination of rifampin and pyrazinamide should not be used for the treatment of latent tuberculosis infection.

  • Soft contact lenses should not be used while receiving rifampin due to the possibility of lens discoloration.

  • Potential for drug-drug interactions through induction of CYP450

Streptomycin (24)
  • Eosinophilia

  • Nephrotoxicity (2%)

  • Ototoxicity (vestibular and auditory)

  • Circumoral paresthesia

  • Postoperative respiratory muscle weakness when used in combination with muscle relaxant

  • Second-line agent.

  • Monitoring of serum drug concentrations is recommended.

  • Dosing adjustment necessary in patients with renal insufficiency to reduce the risk of ototoxicity and nephrotoxicity.

  • Ototoxicity more common with the concurrent use of diuretics.

  • Baseline audiogram, vestibular testing, and Romberg testing recommended.

  • Contraindicated during pregnancy.

List of abbreviations:
PO = orally
QD = once daily
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Agents for the Management of Cytomegalovirus Infections
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AgentAdverse EventsComments
Cidofovir (30,31)
  • Nephrotoxicity (53%), proteinuria (80%), elevations in serum creatinine (18%)

  • Headache (27%), asthenia (46%), fever (57%)

  • Rash (30%), alopecia (25%)

  • Neutropenia (31%), anemia (20%)

  • Nausea/vomiting (65%), diarrhea (27%), anorexia (22%), abdominal pain (17%)

  • Ocular hypotony

  • Requires appropriate intravenous hydration and concomitant administration of probenecid to reduce the risk of nephrotoxicity.

  • Dosage adjustment necessary in patients with renal insufficiency.

Fomivirsen
  • Ocular toxicity: anterior chamber inflammation, uveitis, vitreitis, increased intraocular pressure, abnormal vision, blurred vision, cataract, conjunctival hemorrhage, decreased visual acuity, loss of color vision, eye pain, photophobia, retinal detachment, retinal edema, retinal hemorrhage, retinal pigment changes

  • For intravitreal administration only.

Foscarnet (32)
  • Seizures (10%), fever (65%), headache (26%)

  • Anemia (33%)

  • Nausea (47%), diarrhea (30%), vomiting (26%)

  • Nephrotoxicity (27%)

  • Hypocalcemia (15%), hypophosphatemia (8%), hyperphosphatemia (6%), hypomagnesemia (15%), hypokalemia (16%)

  • Adverse events are dose related.

  • Dosage adjustment necessary in patients with renal insufficiency.

Ganciclovir
  • Neutropenia (25-50%), thrombocytopenia (20%), anemia (8%)

  • Fever (2%)

  • Confusion (1-3%)

  • Rash (2%)

  • Nausea/vomiting (2%)

  • Impaired renal function

  • Neutropenia more common during the first 2 weeks of induction therapy.

  • Dosage adjustment necessary in patients with renal insufficiency.

Probenecid
  • >10%: headache, insomnia, nausea, vomiting, anorexia

  • 1-10%: facial flushing, rash, renal calculi, sore gums, dizziness

  • <1%: anemia, leukopenia, hypersensitivity

  • Must be used concomitantly with cidofovir to reduce the risk of cidofovir-induced nephrotoxicity.

  • Administer with food.

  • Rash may occur in patients sensitive to sulfonamides.

Valganciclovir (33)
  • Neutropenia (27%), anemia (26%), thrombocytopenia (6%)

  • Fever (31%), headache (22%)

  • Diarrhea (41%), nausea (30%), vomiting (21%), abdominal pain (21%)

  • Side effects appear to be more frequent in patients with CD4 lymphocyte count <50 cells/mm3.(34)

  • Dosage adjustment necessary in patients with renal insufficiency.

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Agents for the Treatment of Herpes Virus Infections
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AgentAdverse EventsComments
Acyclovir
  • Transient elevation in serum creatinine or blood urea nitrogen (BUN) (5-10%)

  • Nausea (5-8%), vomiting (3-7%), diarrhea (2%)

  • Rash, pruritus, hives, headache, confusion (2%)

  • Elevation in serum creatinine and BUN more common with parenteral administration.

  • Dosage adjustment necessary in patients with renal insufficiency.

Famciclovir (35)
  • Headache (23%), paresthesia (3%), migraine

  • Nausea (11-13%), vomiting (5%), diarrhea (7-8%), anorexia (3%)

  • Fatigue, pruritus (4%)

  • Dosage adjustment necessary in patients with renal insufficiency.

Valacyclovir (36)
  • Headache, dizziness, nausea, vomiting, abdominal pain

  • Dosage adjustment necessary in patients with renal insufficiency.

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Agents for the Treatment of Hepatitis C
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AgentAdverse EventsComments
Boceprevir (37)
  • Anemia (50%), neutropenia

  • Nausea, vomiting, dysgeusia, diarrhea

  • Dry mouth

  • To be used only in combination with pegylated interferon + ribavirin

  • Has significant interactions with other medications, including most ARVs

Pegylated interferon (38)
  • Influenza-like symptoms (fever, headache, fatigue, myalgia)

  • Fatigue (50%)

  • Neuropsychiatric symptoms (depression [18%], anxiety, suicidal ideation), irritability, impaired concentration, impaired memory, insomnia

  • Lymphopenia (including decrease in CD4 counts), neutropenia, thrombocytopenia

  • Nausea, anorexia, diarrhea, weight loss

  • Autoimmune disorders (eg, hyperthyroidism, hypothyroidism, rheumatoid arthritis, systemic lupus erythematosus)

  • Ophthalmologic disorders

  • Injection-site reactions

  • Alopecia (23%)

  • Pruritus

  • Dosage reductions may be required

Ribavirin (39)
  • Hemolytic anemia (13%)

  • Fatigue (65%)

  • Neuropsychiatric symptoms (depression, anxiety)

  • Nausea, vomiting, anorexia, dyspepsia

  • Hyperbilirubinemia

  • Rash

  • Pneumonitis, dyspnea

  • Hypersensitivity reactions

  • Teratogenic/embryocidal (pregnancy category X); pregnancy must be avoided in female patients and female partners of male patients, during treatment and for 6 months after cessation of treatment.

  • Not effective as monotherapy

  • Dosage adjustment may be required in case of anemia

Telaprevir (40)
  • Rash (56%), drug rash with eosinophila and systemic symptoms (DRESS), Stevens-Johnson syndrome

  • Anemia (36%), leukopenia, thrombocytopenia

  • Fatigue (56%)

  • Nausea, vomiting, dysgeusia, diarrhea

  • Pruritus

  • Hemorrhoids, anorectal discomfort, anal pruritus

  • To be used only in combination with pegylated interferon + ribavirin

  • Significant interactions with other medications, including most ARVs

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Agents for the Treatment of Malignancies
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AgentAdverse EventsComments
CHOP (41,42)
    Cyclophosphamide
  • Acute hemorrhagic cystitis (7-40%)

  • Alopecia (frequent), rash

  • Leukopenia (recovery 7-10 days after discontinuation of therapy), thrombocytopenia

  • Cardiotoxicity (rare)

  • Sterility

  • Anorexia, nausea/vomiting, diarrhea, stomatitis

  • Fluid intake and frequent voiding may help prevent hemorrhagic cystitis.

  • Contraindicated during pregnancy.

    Doxorubicin
  • Alopecia (85-100%), palmar-plantar erythrodysesthesia (swelling, pain, erythema; occasional desquamation of the skin on hands and feet)

  • Stomatitis, mucositis

  • Vesiculation of the skin

  • Leukopenia (nadir = day 10-14, recovery by day 21), thrombocytopenia, anemia

  • Cardiotoxicity

  • Nausea/vomiting

  • Erythematous streaking over vein at injection site

  • Cardiac toxicity is dose related, more common when cumulative dosage approaches 550 mg/m2.

  • Contraindicated during pregnancy.

    Vincristine
  • Hypersensitivity reactions (eg, anaphylaxis, rash, edema) (rare)

  • Vesiculation of the skin

  • Alopecia

  • Anemia, leukopenia, thrombocytopenia

  • Constipation, paralytic ileus, oral ulceration, abdominal cramps, mild nausea, and vomiting

  • Syndrome of inappropriate antidiuretic hormone secretion (SIADH) (rare)

  • Bladder atony with polyuria and dysuria, urinary retention

  • Peripheral neuropathy, loss of deep-tendon reflexes, ataxia, foot drop, paralysis

  • Cranial nerve manifestations (isolated paresis or paralysis of muscles, most commonly extraocular and laryngeal muscles)

  • Double vision, transient blindness, optic atrophy

  • Severe pain (jaw, pharynx, parotid gland, bones, back, and limbs)

  • Myalgia

  • Neurotoxicity is dose related and cumulative, maximum cumulative dosage is 30-50 mg.

  • Neurotoxicity is reversible upon discontinuation but may persist for several months.

  • Constipation may be associated with impaction of stool in the upper colon; therefore, digital exam may not detect impaction.

  • Routine prophylaxis against constipation is recommended (stool softeners, laxatives). High enemas and laxatives are effective in the management of constipation.

  • Contraindicated during pregnancy.

    Prednisone
  • See adverse events listed under Agents Used in the Management of PCP section

Liposomal doxorubicin (43)
  • Acute infusion-associated reactions (7%) (flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in chest or throat, hypertension)

  • Palmar-plantar erythrodysesthesia (3.4%) (swelling, pain, erythema; occasionally desquamation of skin on hands and feet)

  • Alopecia (9%)

  • Leukopenia (nadir = 10-14 days, recovery by day 21), thrombocytopenia, anemia

  • Irreversible myocardial toxicity with delayed congestive heart failure

  • Nausea/vomiting (21-55%), mucositis

  • Hepatotoxicity (44)

  • Red discoloration of urine

  • Extravasation

  • Erythematous streaking over vein at the injection site

  • Infusion-associated reactions reduced by slowing the infusion rate.

  • Cardiac toxicity is dose related, and more common when cumulative dosage approaches 550 mg/m2.

  • Patients with elevated bilirubin require dosage adjustment to prevent increased toxicity.

  • In case of extravasation, local application of ice may reduce discomfort.

Paclitaxel (45)
  • Hypersensitivity reactions (9%) (flushing, rash, hypotension, dyspnea, tachycardia, hypertension, chills (rare), back pain (rare))

  • Alopecia

  • Neutropenia and leukopenia (95-100%) (onset = day 8-10, nadir = day 10-12, recovery = day 15-21), thrombocytopenia (27%) (onset = day 8-9), anemia (73%)

  • Febrile neutropenia

  • Bradycardia (25%), myocardial infarction

  • Nausea/vomiting (70%), diarrhea (79%), mucositis (28%)

  • Elevated liver function tests

  • Peripheral neuropathy (46%), pruritus (preceding the onset of peripheral neuropathy)

  • Arthralgia, myalgia

  • Hypersensitivity reaction may result from paclitaxel itself or from polyoxyl 35 castor oil in the preparation.

  • All patients receiving paclitaxel should be premedicated to avoid hypersensitivity reactions.

  • Premedication regimen:
    1. Dexamethasone 10 mg PO 12 and 6 hours before paclitaxel
    2. Diphenhydramine 50 mg intravenous 30-60 min before paclitaxel
    3. H2 blocker (ranitidine, cimetidine, or famotidine) intravenous 30-60 min before paclitaxel

  • Shorter paclitaxel infusion time (eg, 3 hours) may result in a lower frequency and severity of neutropenia.

  • Onset of peripheral neuropathy may be rapid (within a few days).

  • Paclitaxel-induced pruritus may be relieved by tricyclic antidepressants.

  • Contraindicated during pregnancy.

Rituximab
  • Infusion reaction complex (hypotension, angioedema, hypoxia or bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock)

  • Tumor lysis syndrome (TLS)

  • Severe mucocutaneous reactions (paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis)

  • Lymphopenia (40%), neutropenia (6%), leukopenia (4%), anemia (3%), thrombocytopenia (2%)

  • Cardiac arrhythmia, angina

  • Renal failure

  • Infusion reactions usually occur within 30-120 minutes of initiating the infusion.

  • In severe reaction, infusion should be interrupted and supportive care instituted (eg, intravenous fluids, vasopressors, oxygen, bronchodilators, diphenhydramine, and acetaminophen).

  • Infusion can be resumed at 50% reduction in rate when symptoms have completely resolved.

  • Patients at high risk for TLS should receive prophylaxis.

  • The mean duration of lymphopenia is 14 days.

  • The duration of cytopenias can extend beyond the treatment period.

  • Duration of treatment is associated with increased risk of grade 3 and 4 adverse effects.

Vinblastine
  • Alopecia, dermatitis, vesiculation of the skin, phototoxicity

  • Leukopenia (onset = day 4-7, nadir = day 4-10, recovery = day 7-14), thrombocytopenia

  • Hypertension, Raynaud phenomenon

  • Nausea (moderate emetic potential), vomiting, constipation, diarrhea, stomatitis, abdominal cramps, anorexia, metallic taste

  • Depression, malaise, headache, seizures

  • Contraindicated during pregnancy.

List of abbreviations:
PO = orally
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Metabolic Agents
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AgentAdverse EventsComments
Dronabinol (1,46)
  • Orthostatic hypotension, tachycardia

  • Drowsiness, dizziness, confusion, difficulty concentrating

  • Appetite stimulant.

  • Antiemetic.

  • Medication should be taken 30 minutes before each meal.

  • Weight gain occurs only in individuals who have decreased appetite (not effective in hypermetabolic patients with normal appetite).

Ezetimibe
  • Headache (8%)

  • Diarrhea (4%), abdominal pain (3%)

  • Use as add-on therapy in patients with inadequate LDL reduction on statin therapy.

Fibric acid derivatives (eg, gemfibrozil, fenofibrate)
  • Fatigue (4%)

  • Dyspepsia (20%)

  • Abdominal pain (10%), diarrhea (7%)

  • Greater risk for rhabdomyolysis exists when a fibric acid derivative is used in combination with a statin.

  • This class generally is more effective than statins in reducing triglyceride levels.

HMG-CoA reductase inhibitors ("statins")
  • Myalgia, myopathy, malaise, muscle weakness, rhabdomyolysis, renal failure

  • Headache (up to 20%), dizziness

  • Rash (1-4%)

  • Abdominal pain (up to 4%), diarrhea, dyspepsia, flatulence

  • Elevated liver function tests (1-3%)

  • Greater risk for rhabdomyolysis when a statin is used in combination with a fibric acid derivative.

  • May interact with other drugs. Dosage adjustments may be required; certain combinations are contraindicated.

  • Contraindicated during pregnancy.

Human growth hormone (47)
  • Swelling (hands and feet), musculoskeletal discomfort (pain, swelling, or stiffness)

  • Carpal tunnel syndrome

  • Elevated phosphorus, alkaline phosphatase, parathyroid hormone

  • Diabetes mellitus

  • Headache, weakness, intracranial hypertension (rare)

  • Facial changes due to growth of jaw or frontal bone

  • Analgesic therapy or decrease in dose or dosing frequency may alleviate swelling and pain.

  • Contraindicated during pregnancy.

L-carnitine
  • Nausea, vomiting, abdominal cramps, heartburn, gastritis, diarrhea

  • Body odor

  • Seizures

  • Adjunctive agent for the possible management of NRTI-related lactic acidosis and mitochondrial toxicity.

Megestrol acetate (1,46)
  • Decreased libido

  • Rash

  • Hypertension

  • Thromboembolism

  • Leukopenia, fever

  • Diarrhea, nausea, flatulence

  • Hepatomegaly

  • Hyperglycemia, dyslipidemia

  • Gynecomastia

  • Appetite stimulant (not effective in hypermetabolic patients if appetite is normal).

  • For ease of dosing, suspension is preferred over tablet formulation.

  • Contraindicated during pregnancy.

  • Women who are at risk of pregnancy should use effective contraception while using megestrol acetate.

Metformin
  • Diarrhea, nausea, vomiting, abdominal bloating, flatulence (up to 30%)

  • Lactic acidosis (rare, but potentially fatal)

  • Titrate up from 500 mg QD to BID with food to reduce frequency of diarrhea.

  • Contraindicated in renal insufficiency: Cr >=1.4 in women or >= 1.5 in men.

  • Contraindicated in congestive heart failure or hepatic impairment.

  • If iodinated radiographic contrast is to be given, metformin should be held on the day of the study and for at least 48 hours thereafter. Recheck Cr before restarting metformin.

  • Not associated with hypoglycemia.

Nandrolone (1,46)
  • Acne, gynecomastia, hirsuitism

  • Decreased HDL cholesterol; increased risk of CAD

  • Polycythemia

  • Cholestatic hepatitis

  • Bladder irritability

  • Prostatic hypertrophy

  • Insomnia, chills

  • Decreased libido

  • Aggressive behavior

  • Anabolic steroid.

  • Available as injection

  • May be effective in increasing lean body mass; therefore, sometimes used as an adjunct to an appetite stimulant.

  • Contraindicated during pregnancy.

Oxandrolone (1,46)
  • Acne, gynecomastia, hirsuitism

  • Decreased HDL cholesterol; increased risk of CAD

  • Polycythemia, bleeding

  • Hepatocellular carinoma, cholestatic hepatitis

  • Edema, fluid retention, bladder irritability, increased sodium, potassium, phosphate, and calcium

  • Diabetes

  • Prostatic hypertrophy

  • Insomnia, chills

  • Excitability

  • Decreased libido, testicular atrophy, erectile dysfunction

  • Anabolic steroid.

  • Available as oral tablets.

  • May be effective in increasing lean body mass; therefore, sometimes used as an adjunct to an appetite stimulant.

  • Contraindicated during pregnancy.

Sulfonylureas (glyburide, glipizide, etc)
  • Headache, dizziness

  • Rash (1.5%), pruritus

  • Nausea (1-2%), epigastric fullness (1-2%), heartburn

  • Hypoglycemia

  • Weight gain

  • Avoid use of glyburide in elderly patients, due to greater risk of hypoglycemia.

  • Avoid use of sulfonylureas in patients who use alcohol heavily, due to greater risk of hypoglycemia.

Tesamorelin (48)
  • Musculoskeletal discomfort (pain [13%], swelling, or stiffness), peripheral edema, carpal tunnel syndrome

  • Nausea, vomiting (2%)

  • Hyperglycemia, diabetes mellitus (4%)

  • Injection-site reactions (>8%)

  • Hypersensitivity reactions

  • Growth hormone-releasing factor analogue

  • Contraindicated during pregnancy (pregnancy category X)

Testosterone (1,46)
  • Acne, gynecomastia, hirsuitism

  • Decreased HDL cholesterol; increased risk of CAD

  • Polycythemia

  • Cholestatic hepatitis, hepatic necrosis

  • Prostatic hypertrophy

  • Increased progression of prostate cancer

  • Bladder irritability

  • Insomnia, chills

  • Aggressive behavior

  • Anabolic steroid.

  • Available as injection, gel, and patch.

  • May be effective in increasing lean body mass; therefore, sometimes used as an adjunct to an appetite stimulant.

  • Contraindicated during pregnancy.

Thalidomide (49,50)
  • Teratogenic (phocomelia)

  • Rash (25%)

  • Leukopenia (17-25%)

  • Diarrhea (17%), nausea (12%)

  • Peripheral neuropathy (symmetric painful paresthesias of hands and feet; sensory loss in lower limbs) (6-16%)

  • Dizziness (19%), drowsiness (36-38%), somnolence, headache (17-19%)

  • Contraindicated during pregnancy

  • Women who are at risk of pregnancy should use 2 forms of contraception while using thalidomide.

  • Peripheral neuropathy may be irreversible.

Thiazolidenediones (rosiglitazone, pioglitazone)
  • Headache (6%), fatigue (4%)

  • Elevated liver function tests

  • Edema (5-25%), shortness of breath

  • Weight gain

  • Monitor for edema, signs and symptoms suggestive of congestive heart failure exacerbation.

List of abbreviations:
BID = twice daily
CAD = coronary artery disease
Cr = creatinine
HDL = high-density lipoprotein
NRTI = nucleoside reverse transcriptase inhibitor
NSAIDs = nonsteroidal anti-inflammatory drugs
QD = once daily
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Hematopoietic Agents
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AgentAdverse EventsComments
Erythopoeitin
  • Headaches, seizures, dizziness, fever, fatigue

  • Polycythemia

  • Hypertension

  • Edema, chest pain

  • Nausea, vomiting, diarrhea

  • Arthralgia, weakness

  • Seizures most commonly occur as a result of a precipitous rise in blood pressure associated with rapid rise in hematocrit.

  • Hypertension more common in patients with chronic renal failure and a history of hypertension.

Filgrastim, pegfilgrastim, G-CSF
  • Medullary bone pain, mild to moderate (33%); generalized musculoskeletal pain

  • Nausea and vomiting, mild to moderate

  • Nonopiate oral analgesics can be used for the management of bone pain.

  • Filgrastim should not be administered from 24 hours before to 24 hours after the administration of antineoplastic agents.

Sargramostim, GM-CSF
  • First-dose reaction (pulmonary infiltrates, hypotension with flushing and syncope, tachycardia, bone pain)

  • Fever, asthenia, chills, headache

  • Edema, capillary leak syndrome, pleural effusion, pericardial effusion

  • Nausea, diarrhea

  • Bone pain, myalgia

  • Treatment of first-dose reaction includes oxygen, intravenous fluids, and acetaminophen or NSAIDs.

  • Theoretical possibility of stimulating an increase in HIV-infected macrophages.

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Agents for the Treatment of Neuropathic Pain
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AgentAdverse EventsComments
Duloxetine (51)
  • Dizziness (14%), somnolence (15%)

  • Nausea (22%), constipation (11%)

  • Increased sweating (6%)

  • Upon discontinuation, taper dosage slowly.

Gabapentin
  • Somnolence, dry mouth, dizziness, abnormal thinking, nervousness

  • Amblyopia

  • May dose BID instead of TID for treatment of peripheral neuropathy.

Lamotrigine
  • Rash (10%)

  • Headache (29%), nausea (10-25%), dizziness (39%), ataxia (22%), somnolence (14%)

  • Diplopia (28%), blurred vision (15%)

  • Little data available on efficacy as treatment of neuropathic pain.

Pregablin (52)
  • Dizziness (32%), somnolence (22%), blurred vision (10%)

  • Dry mouth (4%)

  • Edema (5%)

  • weight gain (12%)

  • Adjust dosage for renal insufficiency.

Tricyclic antidepressants (amitripyline, nortriptyline, etc)
  • Anticholinergic side effects (dry mouth, dry eyes, blurry vision, urinary retention)

  • Photosensitivity

  • Somnolence, dizziness

  • Weight gain

  • Secondary amines (desipramine, nortriptyline) may be better tolerated than tertiary amines (amitriptyline, imipramine, doxepin).

List of abbreviations:
BID = twice daily
TID = thrice daily
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Agents for the Treatment of Infectious Diarrhea
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AgentAdverse EventsComments
Albendazole
  • Headache, dizziness, vertigo, fever

  • Alopecia (reversible)

  • Abdominal pain, nausea/vomiting

  • Elevated liver function tests

Metronidazole
  • Nausea, vomiting, abdominal pain, metallic taste, diarrhea

  • Dizziness, headache, peripheral neuropathy (rare), seizures (rare)

  • Disulfiram-like reaction (flushing, nausea, and vomiting if consumed with ethanol)

  • Peripheral neuropathy is usually reversible after discontinuation of metronidazole but may persist with prolonged therapy and/or higher dosages.

Nitazoxanide (53)
  • Headache (1%)

  • Abdominal pain (8%), diarrhea (2%), vomiting (1%)

  • FDA approved for use in pediatric patients for the treatment of diarrhea caused by Cryptosporidium parvum and Giardia lamblia.

Paromomycin
  • Nausea, abdominal cramps, diarrhea, epigastric burning

  • Gastrointestinal absorption of paromomycin is poor; almost 100% of the drug is recovered in the stool.

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