Zerit XR Side Effects
Generic Name: stavudine
Note: This document contains side effect information about stavudine. Some of the dosage forms listed on this page may not apply to the brand name Zerit XR.
For the Consumer
Applies to stavudine: oral capsule, oral powder for solution, oral powder for suspension
Along with its needed effects, stavudine (the active ingredient contained in Zerit XR) 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:
- 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
- blood in the urine or stools
- blurred vision
- chest pain
- darkened urine
- decreased appetite
- depression or indentation of the skin
- difficulty in moving
- difficulty swallowing
- fast heartbeat
- fast, shallow breathing
- general feeling of discomfort
- general tiredness and weakness
- hives, itching, skin rash
- joint pain or swelling
- light-colored stools
- loss of appetite
- muscle cramping, pains, or stiffness
- 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)
- 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
- yellow eyes or skin
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:
Incidence Not Known
- Trouble sleeping
For Healthcare Professionals
Applies to stavudine: oral capsule, oral capsule extended release, oral powder for reconstitution
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.
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 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]
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]
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
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): 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
-Frequency not reported: Increased weight, increased blood lipid levels[Ref]
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): 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]
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]
Very common (10% or more): Myalgia (up to 32%), arthralgia (up to 23%), back pain (up to 19%)
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]
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
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)
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")
-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]
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]
Frequency not reported: Cough, rhinitis, pharyngitis, respiratory disorder, lung disorder, asthma, epistaxis, hypoventilation, pneumonia, hyperventilation, voice alteration, sinusitis, stridor[Ref]
Very common (10% or more): Chest pain (up to 11%)
Frequency not reported: Tachycardia, vasodilation[Ref]
Allergic reaction has also been reported during postmarketing experience.[Ref]
Common (1% to 10%): Neoplasms, benign skin neoplasm[Ref]
Uncommon (0.1% to 1%): Gynecomastia[Ref]
Frequency not reported: Conjunctivitis, eye disorder, abnormal vision, conjunctival edema[Ref]
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: Fanconi syndrome[Ref]
1. "Risk factors for lactic acidosis and severe hyperlactataemia in HIV-1-infected adults exposed to antiretroviral therapy." AIDS 21 (2007): 2455-64
2. Dunkle L, Anderson R, McLaren C, Cross A, Brown M, Gugliotti R, Adler M, Kaul S "Stavudine (d4T) a promising anti-retroviral agent." Int Conf AIDS 8 (1992): we47(ab.no.eb1011)
3. Nelson M, Azwa A, Sokwala A, Harania RS, Stebbing J "Fanconi syndrome and lactic acidosis associated with stavudine and lamivudine therapy." AIDS 22 (2008): 1374-6
4. Gallant JE "Drug resistance after failure of initial antiretroviral therapy in resource-limited countries." Clin Infect Dis 44 (2007): 453-5
5. Neff GW, Sherman KE, Eghtesad B, Fung J "Review article: current status of liver transplantation in HIV-infected patients." Aliment Pharmacol Ther 20 (2004): 993-1000
6. Petersen E, Ramirez-Ronda C, Schwartz R, Peterson D, Hardy W, Sacks H, Follansbee S "Findings from a phase II study of stavudine (d4T)." Int Conf AIDS 8 (1992): b90(ab.no.po3023)
7. Bolhaar MG, Karstaedt AS "A high incidence of lactic acidosis and symptomatic hyperlactatemia in women receiving highly active antiretroviral therapy in Soweto, South Africa." Clin Infect Dis 45 (2007): 254-60
8. Kakuda TN "Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity." Clin Ther 22 (2000): 685-708
9. Cerner Multum, Inc. "Australian Product Information." O 0
10. Brinkman K, terHofstede HJM, Burger DM, Smeitinkt JAM, Koopmans PP "Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway." AIDS 12 (1998): 1735-44
11. "Drugs for HIV infection." Med Lett Drugs Ther 43 (2001): 103-8
12. Piacenti FJ "An update and review of antiretroviral therapy." Pharmacotherapy 26 (2006): 1111-33
13. Currier JS "Sex differences in antiretroviral therapy toxicity: lactic acidosis, stavudine, and women." Clin Infect Dis 45 (2007): 261-2
14. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working Group of the Office of AIDS Research Advisory Council (OARAC) "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Available from: URL: https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf." ([2017, Oct 17]):
15. Walker UA, Bauerle J, Laguno M, et al. "Depletion of mitochondrial DNA in liver under antiretroviral therapy with didanosine, stavudine, or zalcitabine." Hepatology 39 (2004): 311-7
16. Hurst M, Noble S "Stavudine - An update of its use in the treatment of HIV infection." Drugs 58 (1999): 919-49
17. Thoden J, Lebrecht D, Venhoff N, Neumann J, Muller K, Walker UA "Highly active antiretroviral HIV therapy-associated fatal lactic acidosis: quantitative and qualitative mitochondrial DNA lesions with mitochondrial dysfunction in multiple organs." AIDS 22 (2008): 1093-4
18. Hammer SM, Saag MS, Schechter M, et al. "Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel." JAMA 296 (2006): 827-43
19. Delgado J, Harris M, Tesiorowski A, Montaner JS "Symptomatic elevations of lactic Acid and their response to treatment manipulation in human immunodeficiency virus-infected persons: a case series." Clin Infect Dis 33 (2001): 2072-4
20. Browne MJ, Mayer KH, Chafee SB, Dudley MN, Posner MR, Steinberg SM, Graham KK, Geletko SM, Zinner SH, Denman SL, et al "2' related complex: a phase I trial." J Infect Dis 167 (1993): 21-9
21. Mokrzycki MH, Harris C, May H, Laut J, Palmisano J "Lactic acidosis associated with stavudine administration: A report of five cases." Clin Infect Dis 30 (2000): 198-200
22. "Product Information. Zerit (stavudine)." Bristol-Myers Squibb, Princeton, NJ.
23. Sulkowski MS, Mehta SH, Torbenson M, et al. "Hepatic steatosis and antiretroviral drug use among adults coinfected with HIV and hepatitis C virus." AIDS 19 (2005): 585-592
24. Squires KE, Weiss W, Sacks H, Hassett J, Gugliotti R, Murray H "Effect of 2'3'-didehydro-3'deoxythymidine (d4T) on p24 antigenemia in patients with AIDS or ARC." Int Conf AIDS 6 (1990): 180(ab.no.th..241)
25. McComsey GA, Re VL 3rd, O'Riordan M, et al. "Effect of reducing the dose of stavudine on body composition, bone density, and markers of mitochondrial toxicity in HIV-infected subjects: a randomized, controlled study." Clin Infect Dis 46 (2008): 1290-6
26. Mandelbrot L, Kermarrec N, Marcollet A, et al. "Case report: nucleoside analogue-induced lactic acidosis in the third trimester of pregnancy." AIDS 17 (2003): 272-3
27. "Drugs for HIV infection." Treat Guidel Med Lett 7 (2009): 11-22
28. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
29. Soriano V, Puoti M, Sulkowski M, et al. "Care of patients coinfected with HIV and hepatitis C virus: 2007 updated recommendations from the HCV-HIV International Panel." AIDS 21 (2007): 1073-89
30. Johri S, Alkhuja S, Siviglia G, Soni A "Steatosis-lactic acidosis syndrome associated with stavudine and lamivudine therapy." Aids 14 (2000): 1286-7
31. Schiano TD, Lissoos TW, Ahmed A, Siano C, Zaitman D, Cohn G, Ehrenpreis ED "Lamivudine-stavudine-induced liver failure in hepatitis B cirrhosis." Am J Gastroenterol 92 (1997): 1563-4
32. Shalit P, Farrell P, Lindgren P "Long-term safety and efficacy of nevirapine, stavudine and lamivudine in a real-world setting." Aids 15 (2001): 804-5
33. Rey D, L'Heritier A, Lang JM "Severe Ototoxicity in a Health Care Worker Who Received Postexposure Prophylaxis with Stavudine, Lamivudine, and Nevirapine after Occupational Exposure to HIV." Clin Infect Dis 34 (2002): 418-9
34. Warnke D, Barreto J, Temesgen Z "Antiretroviral drugs." J Clin Pharmacol 47 (2007): 1570-9
35. Callens S, De Schacht C, Huyst V, Colebunders R "Pancreatitis in an HIV-infected person on a tenofovir, didanosine and stavudine containing highly active antiretroviral treatment." J Infect 47 (2003): 188-9
36. Manfredi R, Calza L, Chiodo F "Gynecomastia associated with highly antiretroviral therapy." Ann Pharmacother 35 (2001): 438-9
37. Ene L, Goetghebuer T, Hainaut M, Peltier A, Toppet V, Levy J "Prevalence of lipodystrophy in HIV-infected children: a cross-sectional study." Eur J Pediatr 166 (2006): 13-21
38. Martinez E, Mocroft A, GarciaViejo MA, PerezCuevas JB, Blanco JL, Mallolas J, Bianchi L, Conget I, Blanch J, Phillips A, Gatell "Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study." Lancet 357 (2001): 592-8
39. "Anti-HIV agents. New drugs, new hope, old lessons." TreatmentUpdate 19 (2007): 1-3
40. SaintMarc T, Touraine JL "The effects of discontinuing stavudine therapy on clinical and metabolic abnormalities in patients suffering from lipodystrophy." AIDS 13 (1999): 2188-9
41. SaintMarc T, Partisani M, PoizotMartin I, Bruno F, Rouviere O, Lang JM, Gastaut JA, Touraine JL "A syndrome of peripheral fat wasting (Lipodystrophy) in patients receiving long-term nucleoside analogue therapy." AIDS 13 (1999): 1659-67
42. Lichtenstein KA, Ward DJ, Moorman AC, et al. "Clinical assessment of HIV-associated lipodystrophy in an ambulatory population." AIDS 15 (2001): 1389-98
43. Mallal SA, John M, Moore CB, James IR, McKinnon EJ "Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection." Aids 14 (2000): 1309-16
44. Ter Hofstede HJ, Koopmans PP, Burger DM "Stavudine plasma concentrations and lipoatrophy." J Antimicrob Chemother 61 (2008): 933-8
45. Bergersen BM "Cardiovascular Risk in Patients with HIV Infection : Impact of Antiretroviral Therapy." Drugs 66 (2006): 1971-87
46. Brambilla AM, Novati R, Calori G, et al. "Stavudine or indinavir-containing regimens are associated with an increased risk of diabetes mellitus in HIV-infected individuals." AIDS 17 (2003): 1993-5
47. Guyot S, Hayoz D, Telenti A, Cavassini M "Peripheral oedema and high arterial blood flow as a complication of antiretroviral therapy." AIDS 18 (2004): 356-8
Some side effects may not be reported. You may report them to the FDA.
More about Zerit XR (stavudine)
- During Pregnancy or Breastfeeding
- Dosage Information
- Drug Interactions
- Drug class: nucleoside reverse transcriptase inhibitors (NRTIs)