Note: This document contains side effect information about stavudine. Some dosage forms listed on this page may not apply to the brand name Zerit.

Summary

Common side effects of Zerit include: increased serum alanine aminotransferase, increased serum amylase, increased serum aspartate aminotransferase, and increased serum lipase. Continue reading for a comprehensive list of adverse effects.

Applies to stavudine: oral capsule.

Serious side effects of Zerit

Along with its needed effects, stavudine (the active ingredient contained in Zerit) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking stavudine:

More common

• Burning, numbness, tingling, or painful sensations
• unsteadiness or awkwardness
• weakness in the arms, hands, legs, or feet

Incidence not known

• Black, tarry stools
• bleeding gums
• bloating
• blood in the urine or stools
• blurred vision
• chest pain
• chills
• constipation
• cough
• darkened urine
• decreased appetite
• depression or indentation of the skin
• diarrhea
• difficulty in moving
• difficulty swallowing
• fast heartbeat
• fast, shallow breathing
• fever
• general feeling of discomfort
• general tiredness and weakness
• hives, itching, skin rash
• indigestion
• joint pain or swelling
• light-colored stools
• loss of appetite
• muscle cramping, pains, or stiffness
• nausea
• painful or difficult urination
• pains in the stomach, side, or abdomen, possibly radiating to the back
• pale skin
• pinpoint red spots on the skin
• shakiness and unsteady walk, unsteadiness, trembling, or other problems with muscle control or coordination (severe)
• sleepiness
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• stomach pain or discomfort
• swollen glands
• tightness in the chest
• trembling or other problems with muscle control or coordination
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness
• upper right abdominal pain
• vomiting
• yellow eyes or skin

Other side effects of Zerit

Some side effects of stavudine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Headache

Incidence not known

• Trouble sleeping

For Healthcare Professionals

Applies to stavudine: oral capsule, oral capsule extended release, oral powder for reconstitution.

General

This drug was associated with many side effects (e.g., polyneuropathy, lactic acidosis, lipoatrophy) for which mitochondrial toxicity was a potential underlying mechanism.^[Ref]

Hepatic

Very common (10% or more): Elevated bilirubin (up to 68%), elevated ALT (up to 65%), elevated AST (up to 63%), elevated GGT (up to 28%), elevated hepatic transaminases (up to 13%)

Uncommon (0.1% to 1%): Hepatitis/jaundice

Frequency not reported: Severe hepatomegaly with steatosis, fatal hepatic events, hepatosplenomegaly

Postmarketing reports: Hepatic steatosis, hepatitis, liver failure, hepatotoxicity resulting in death^[Ref]

In a monotherapy trial, elevated ALT (greater than 5 times the upper limit of normal [5 x ULN]), AST (greater than 5 x ULN), and bilirubin (greater than 2.5 x ULN) were reported in 13%, 11%, and 2% of patients, respectively. Elevated ALT (up to 5 x ULN) and AST (up to 5 x ULN) were reported in 65% and 63% of patients, respectively.

In combination therapy trials, elevated AST (grades 3 to 4: up to 7%; all grades: up to 53%), ALT (grades 3 to 4: up to 8%; all grades: up to 50%), bilirubin (grades 3 to 4: up to 16%; all grades: up to 68%), and GGT (grades 3 to 4: up to 5%; all grades: up to 28%) were reported; grades 3 to 4 AST, ALT, and GGT elevations were greater than 5 x ULN and grades 3 to 4 bilirubin elevations were greater than 2.6 x ULN.

In clinical trials, modest elevations of hepatic transaminases not requiring dose adjustment were reported in up to 13% of patients.

Hepatosplenomegaly (up to 72%) was reported in children; this side effect was not listed for adults.

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs alone or in combination, including this drug and other antiretroviral agents.

Fatal hepatic events were reported most often in patients treated with this drug in combination with hydroxyurea and didanosine.^[Ref]

Nervous system

Very common (10% or more): Headache (up to 54%), peripheral neurologic symptoms/neuropathy (up to 52%), peripheral neuropathy (up to 24%), dizziness (up to 11%)

Common (1% to 10%): Paresthesia, peripheral neuritis, somnolence

Frequency not reported: Peripheral sensory neuropathy, ototoxicity, syncope, encephalopathy, abnormal gait, tremor, hyperkinesia, speech disorder, ear disorder, ear pain, otitis media

Postmarketing reports: Motor weakness (including severe cases)^[Ref]

In clinical trials, peripheral neuropathy requiring or leading to dose adjustment (regardless of severity) was reported in up to 24% of patients. Other peripheral neurological symptoms not requiring dose changes were reported in up to 39% of patients. Neuropathy requiring dose adjustment was reported in up to 14% of patients.

Peripheral sensory neuropathy (generally characterized by numbness, tingling, or pain in the feet or hands) has been reported. Peripheral neuropathy (some cases severe) was dose-related and occurred more often in patients with advanced HIV disease, with history of peripheral neuropathy, or using other drugs associated with neuropathy. Symptoms generally resolved after dose reduction or interruption of this drug.

Syncope (up to 15%), encephalopathy (up to 17%), abnormal gait (up to 11%), tremor (up to 11%), hyperkinesia (up to 10%), ear disorder (up to 39%), ear pain (up to 45%), otitis media (up to 15%), and speech disorder (up to 10%) were reported in children; these side effects were not listed for adults.

Most cases of motor weakness occurred in the setting of symptomatic hyperlactatemia or lactic acidosis syndrome. Symptoms have continued or worsened after therapy was stopped.^[Ref]

Gastrointestinal

In a monotherapy trial, elevated amylase (at least 1.4 x ULN) was reported in 14% of patients.

In combination therapy trials, elevated amylase (grades 3 to 4: up to 8%; all grades: up to 31%) and lipase (grades 3 to 4: up to 6%; all grades: up to 26%) were reported; grades 3 to 4 amylase and lipase elevations were greater than 2 x ULN.

Ulcerative stomatitis (up to 45%), melena (up to 11%), tooth caries (up to 11%), dysphagia (up to 15%), aphthous stomatitis (up to 10%), cheilitis (up to 10%), gastrointestinal disorder (up to 15%), and glossitis (up to 10%) were reported in children; these side effects were not listed for adults.

Abdominal pain, elevated lipase, and pancreatitis (including fatal cases) have also been reported during postmarketing experience.^[Ref]

Very common (10% or more): Nausea (up to 53%), diarrhea (up to 50%), nausea/vomiting (up to 39%), abdominal pain (up to 34%), vomiting (up to 30%), elevated amylase (up to 31%), elevated lipase (up to 26%), dyspepsia (up to 12%)

Common (1% to 10%): Pancreatitis (including fatal cases), constipation

Frequency not reported: Ulcerative stomatitis, melena, tooth caries, dysphagia, aphthous stomatitis, cheilitis, gastrointestinal disorder, glossitis^[Ref]

Other

Infection (up to 95%), accidental injury (up to 80%), AIDS (up to 22%), death (up to 17%), face edema (up to 25%), mucous membrane disorder (up to 11%), peripheral edema (up to 10%), and enlarged abdomen (up to 10%) were reported in children; these side effects were not listed for adults.

Edema has been reported with use of this drug although no causal relationship has been established.

Chills/fever have also been reported during postmarketing experience.^[Ref]

Very common (10% or more): Chills/fever (up to 50%), asthenia (up to 35%), pain (up to 21%), malaise (up to 20%)

Common (1% to 10%): Fatigue

Frequency not reported: Edema, infection, accidental injury, AIDS, death, face edema, mucous membrane disorder, enlarged abdomen, peripheral edema

Antiretroviral therapy:

-Frequency not reported: Increased weight, increased blood lipid levels^[Ref]

Dermatologic

Very common (10% or more): Rash (up to 40%), sweating (up to 18%), pruritus (up to 15%)

Common (1% to 10%): Maculopapular rash, lipoatrophy

Uncommon (0.1% to 1%): Urticaria

Frequency not reported: Subcutaneous fat loss, progressive subcutaneous fat wasting, ecchymosis, lesions, vesiculobullous rash, dry skin, skin discoloration, seborrhea, skin disorder, fungal dermatitis, nail disorder, petechial rash, skin ulcer, herpes zoster

Postmarketing reports: Lipodystrophy^[Ref]

Subcutaneous fat loss was most apparent in the face, limbs, and buttocks. The incidence and severity of lipoatrophy have been linked to cumulative exposure. Often, lipoatrophy was not reversible when this drug was discontinued.

Ecchymosis (up to 30%), lesions (up to 55%), vesiculobullous rash (up to 25%), dry skin (up to 35%), skin discoloration (up to 20%), seborrhea (up to 11%), skin disorder (up to 15%), fungal dermatitis (up to 15%), nail disorder (up to 15%), petechial rash (up to 15%), skin ulcer (up to 10%), and herpes zoster (up to 15%) were reported in children; these side effects were not listed for adults.

Lipoatrophy has also been reported during postmarketing experience.^[Ref]

Musculoskeletal

Very common (10% or more): Myalgia (up to 32%), arthralgia (up to 23%), back pain (up to 19%)

Frequency not reported: Osteonecrosis, muscle weakness, decreased bone mineral density, arthrosis^[Ref]

Arthrosis (up to 11%) was reported in children; this side effect was not listed for adults.

Myalgia has also been reported during postmarketing experience.^[Ref]

Psychiatric

Very common (10% or more): Insomnia (up to 29%), depression (up to 24%), anxiety (up to 22%), nervousness (up to 12%)

Common (1% to 10%): Abnormal dreams, abnormal thinking

Uncommon (0.1% to 1%): Emotional lability

Frequency not reported: Personality disorder^[Ref]

Personality disorder (up to 11%) was reported in children; this side effect was not listed for adults.

Insomnia has also been reported during postmarketing experience.^[Ref]

Hematologic

In a monotherapy trial, decreased neutrophils (less than 750/mm3) and platelets (less than 50,000/mm3) were reported in 5% and 3% of patients, respectively.

Low hemoglobin (less than 8 g/dL) was reported in less than 1% of patients^[Ref]

Very common (10% or more): Lymphadenopathy (up to 20%)

Common (1% to 10%): Decreased neutrophils, decreased platelets, low hemoglobin

Postmarketing reports: Anemia, leukopenia, neutropenia, macrocytosis, thrombocytopenia^[Ref]

Metabolic

Very common (10% or more): Anorexia (up to 19%)

Common (1% to 10%): Asymptomatic hyperlactatemia

Uncommon (0.1% to 1%): Lactic acidosis (some cases involved motor weakness)

Frequency not reported: Hyperlipidemia, cachexia, dehydration

Postmarketing reports: Symptomatic hyperlactatemia, diabetes mellitus, hyperglycemia, redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance")

Antiretroviral therapy:

-Frequency not reported: Increased glucose levels^[Ref]

Cachexia (up to 15%) and dehydration (up to 10%) were reported in children; these side effects were not listed for adults.

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals. Fatal lactic acidosis has been reported in pregnant women who received this drug plus didanosine with other antiretroviral agents.

Anorexia and lactic acidosis have also been reported during postmarketing experience.^[Ref]

Respiratory

Very common (10% or more): Influenza syndrome (up to 15%), dyspnea (up to 15%)

Frequency not reported: Cough, rhinitis, pharyngitis, respiratory disorder, lung disorder, asthma, epistaxis, hypoventilation, pneumonia, hyperventilation, voice alteration, sinusitis, stridor^[Ref]

Cough (up to 95%), rhinitis (up to 100%), pharyngitis (up to 56%), respiratory disorder (up to 60%), lung disorder (up to 44%), asthma (up to 45%), epistaxis (up to 28%), hypoventilation (up to 22%), pneumonia (up to 22%), hyperventilation (up to 15%), voice alteration (up to 25%), sinusitis (up to 10%), and stridor (up to 20%) were reported in children; these side effects were not listed for adults.^[Ref]

Cardiovascular

Very common (10% or more): Chest pain (up to 11%)

Frequency not reported: Tachycardia, vasodilation^[Ref]

Tachycardia (up to 10%) and vasodilation (up to 15%) were reported in children; these side effects were not listed for adults.^[Ref]

Hypersensitivity

Allergic reaction has also been reported during postmarketing experience.^[Ref]

Common (1% to 10%): Allergic reactions^[Ref]

Oncologic

Common (1% to 10%): Neoplasms, benign skin neoplasm^[Ref]

Endocrine

Uncommon (0.1% to 1%): Gynecomastia^[Ref]

Ocular

Frequency not reported: Conjunctivitis, eye disorder, abnormal vision, conjunctival edema^[Ref]

Conjunctivitis (up to 44%), eye disorder (up to 17%), abnormal vision (up to 11%), and conjunctival edema (up to 20%) were reported in children; these side effects were not listed for adults.^[Ref]

Genitourinary

Genital pain (up to 17%) and urinary incontinence (up to 11%) were reported in children; these side effects were not listed for adults.^[Ref]

Frequency not reported: Genital pain, urinary incontinence^[Ref]

Immunologic

Frequency not reported: Immune reconstitution/reactivation syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)^[Ref]

Renal

Frequency not reported: Fanconi syndrome^[Ref]