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Zerit (Stavudine) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Adults

Fatal lactic acidosis has occurred in patients treated with ZERIT in combination with other antiretroviral agents. Patients with suspected lactic acidosis should immediately suspend therapy with ZERIT. Permanent discontinuation of ZERIT should be considered for patients with confirmed lactic acidosis.

ZERIT therapy has rarely been associated with motor weakness, occurring predominantly in the setting of lactic acidosis. If motor weakness develops, ZERIT should be discontinued.

ZERIT therapy has also been associated with peripheral sensory neuropathy, which can be severe, is dose related, and occurs more frequently in patients being treated with other drugs that have been associated with neuropathy (including didanosine), in patients with advanced HIV infection, or in patients who have previously experienced peripheral neuropathy.

Patients should be monitored for the development of neuropathy, which is usually manifested by numbness, tingling, or pain in the feet or hands. Stavudine-related peripheral neuropathy may resolve if therapy is withdrawn promptly. In some cases, symptoms may worsen temporarily following discontinuation of therapy. If symptoms resolve completely, patients may tolerate resumption of treatment at one-half the dose (see DOSAGE AND ADMINISTRATION). If neuropathy recurs after resumption, permanent discontinuation of ZERIT should be considered.

Selected clinical adverse events that occurred in adult patients receiving ZERIT (stavudine) in a controlled monotherapy study (Study AI455-019) are provided in Table 7.

Table 7: Selected Clinical Adverse Events in Study AI455-019a (Monotherapy)
Percent (%)
Adverse Events ZERITb
(40 mg twice daily)
(n=412)
zidovudine
(200 mg 3 times daily)
(n=402)
a Any severity, regardless of relationship to study drug.
b Median duration of stavudine therapy = 79 weeks; median duration of zidovudine therapy = 53 weeks.
Headache 54 49
Diarrhea 50 44
Peripheral Neurologic
   Symptoms/Neuropathy
52 39
Rash 40 35
Nausea and Vomiting 39 44

Pancreatitis was observed in 3 of the 412 adult patients who received ZERIT in a controlled monotherapy study.

Selected clinical adverse events that occurred in antiretroviral-naive adult patients receiving ZERIT from two controlled combination studies are provided in Table 8.

Table 8: Selected Clinical Adverse Eventsa in START 1 and START 2b Studies (Combination Therapy)
Percent (%)
START 1 START 2b
Adverse Events ZERIT +
lamivudine +
indinavir
(n=100c)
zidovudine +
lamivudine +
indinavir
(n=102)
ZERIT +
didanosine +
indinavir
(n=102c)
zidovudine +
lamivudine +
indinavir
(n=103)
a Any severity, regardless of relationship to study regimen.
b START 2 compared two triple-combination regimens in 205 treatment-naive patients. Patients received either ZERIT (40 mg twice daily) plus didanosine plus indinavir or zidovudine plus lamivudine plus indinavir.
c Duration of stavudine therapy = 48 weeks.
Nausea 43 63 53 67
Diarrhea 34 16 45 39
Headache 25 26 46 37
Rash 18 13 30 18
Vomiting 18 33 30 35
Peripheral NeurologicSymptoms/
  Neuropathy
  8   7 21 10

Pancreatitis resulting in death was observed in patients treated with ZERIT plus didanosine in controlled clinical studies and in postmarketing reports.

Selected laboratory abnormalities reported in a controlled monotherapy study (Study AI455‑019) are provided in Table 9.

Table 9: Selected Adult Laboratory Abnormalities in Study AI455-019a,b
Percent (%)
Parameter ZERIT
(40 mg twice daily)
(n=412)
zidovudine
(200 mg 3 times daily)
(n=402)
a Data presented for patients for whom laboratory evaluations were performed.
b Median duration of stavudine therapy = 79 weeks; median duration of zidovudine therapy = 53 weeks.
ULN = upper limit of normal.
AST (SGOT)
  (>5.0 x ULN)
11 10
ALT (SGPT)
  (>5.0 x ULN)
13 11
Amylase
  (≥1.4 x ULN)
14 13

Selected laboratory abnormalities reported in two controlled combination studies are provided in Tables 10 and 11.

Table 10: Selected Laboratory Abnormalities in START 1 and START 2 Studies (Grades 3–4)
Percent (%)
START 1 START 2
Parameter ZERIT +
lamivudine +
indinavir
(n=100)
zidovudine +
lamivudine +
indinavir
(n=102)
ZERIT +
didanosine +
indinavir
(n=102)
zidovudine +
lamivudine +
indinavir
(n=103)
ULN = upper limit of normal.
Bilirubin
  (>2.6 x ULN)
7 6 16 8
AST (SGOT)
   (>5 x ULN)
5 2 7 7
ALT (SGPT)
   (>5 x ULN)
6 2 8 5
GGT
   (>5 x ULN)
2 2 5 2
Lipase
   (>2 x ULN)
6 3 5 5
Amylase
   (>2 x ULN)
4 <1 8 2
Table 11: Selected Laboratory Abnormalities in START 1 and START 2 Studies (All Grades)
Percent (%)
START 1 START 2
Parameter ZERIT +
lamivudine +
indinavir
(n=100)
zidovudine +
lamivudine +
indinavir
(n=102)
ZERIT +
didanosine +
indinavir
(n=102)
zidovudine +
lamivudine +
indinavir
(n=103)
  Total Bilirubin 65 60 68 55
  AST (SGOT) 42 20 53 20
  ALT (SGPT) 40 20 50 18
  GGT 15 8 28 12
  Lipase 27 12 26 19
  Amylase 21 19 31 17

Observed During Clinical Practice

The following events have been identified during post-approval use of ZERIT (stavudine). Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to their seriousness, frequency of reporting, causal connection to ZERIT, or a combination of these factors.

Body as a Whole—abdominal pain, allergic reaction, chills/fever, and redistribution/accumulation of body fat (see PRECAUTIONS: Fat Redistribution).

Digestive Disorders—anorexia.

Exocrine Gland Disorders—pancreatitis [including fatal cases (see WARNINGS)].

Hematologic Disorders—anemia, leukopenia, thrombocytopenia, and macrocytosis.

Liver—symptomatic hyperlactatemia/lactic acidosis and hepatic steatosis (see WARNINGS), hepatitis and liver failure.

Metabolic Disorders—diabetes mellitus and hyperglycemia.

Musculoskeletal—myalgia.

Nervous System—insomnia, severe motor weakness (most often reported in the setting of lactic acidosis, see WARNINGS).

Use with Didanosine- and Hydroxyurea-Based Regimens

When stavudine is used in combination with other agents with similar toxicities, the incidence of these toxicities may be higher than when stavudine is used alone. Thus, patients treated with ZERIT in combination with didanosine, with or without hydroxyurea, may be at increased risk for pancreatitis and hepatotoxicity, which may be fatal, and severe peripheral neuropathy. The combination of ZERIT and hydroxyurea, with or without didanosine, should be avoided (see WARNINGS and PRECAUTIONS).

Pediatric Patients

Adverse reactions and serious laboratory abnormalities in pediatric patients from birth through adolescence were similar in type and frequency to those seen in adult patients (see PRECAUTIONS: Pediatric Use).



REPORTS OF SUSPECTED ZERIT SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Zerit. The information is not vetted and should not be considered as verified clinical evidence.

Possible Zerit side effects / adverse reactions in 42 year old male

Reported by a health professional (non-physician/pharmacist) from Japan on 2011-10-03

Patient: 42 year old male

Reactions: Drug Resistance, Psychiatric Symptom

Suspect drug(s):
Ritonavir
    Indication: Antiretroviral Therapy

Darunavir
    Indication: Antiretroviral Therapy

Indinivir Sulfate
    Indication: Antiretroviral Therapy

Nelfinavir Mesylate
    Indication: Antiretroviral Therapy

Zidovudine
    Indication: Antiretroviral Therapy

Raltegravir
    Indication: Antiretroviral Therapy

Lopinavir
    Indication: Antiretroviral Therapy

Emtricitabine
    Indication: Antiretroviral Therapy

Enfuvirtide
    Indication: Antiretroviral Therapy

Abacavir
    Indication: Antiretroviral Therapy

Lamivudine
    Indication: Antiretroviral Therapy

Efavirenz
    Indication: Antiretroviral Therapy

Tenofovir Disoproxil Fumarate
    Indication: Antiretroviral Therapy

Videx
    Administration route: Oral
    Indication: Antiretroviral Therapy

Zerit
    Administration route: Oral
    Indication: Antiretroviral Therapy



Possible Zerit side effects / adverse reactions in 50 year old male

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-13

Patient: 50 year old male

Reactions: Pneumonia

Adverse event resulted in: hospitalization

Suspect drug(s):
Zerit

Reyataz

Epivir



Possible Zerit side effects / adverse reactions in 50 year old male

Reported by a pharmacist from United States on 2011-10-17

Patient: 50 year old male

Reactions: Pneumonia, Sepsis

Adverse event resulted in: hospitalization

Suspect drug(s):
Reyataz
    Indication: HIV Infection

Zerit
    Indication: HIV Infection

Epivir
    Indication: HIV Infection



See index of all Zerit side effect reports >>

Drug label data at the top of this Page last updated: 2010-08-12

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