Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as indomethacin capsules. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue indomethacin capsules and evaluate the patient immediately.
Premature Closure of Fetal Ductus Arteriosus
Avoid use of NSAIDs, including indomethacin, in pregnant women at about 30 weeks gestation and later. NSAIDs, including indomethacin, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.
Oligohydramnios/Neonatal Renal Impairment
Use of NSAIDs, including indomethacin, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation.
Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit indomethacin use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if indomethacin treatment extends beyond 48 hours. Discontinue indomethacin if oligohydramnios occurs and follow up according to clinical practice [see Use in Specific Populations (8.1)].
Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with indomethacin capsules have any signs or symptoms of anemia, monitor hemoglobin or hematocrit.
NSAIDs, including indomethacin capsules, may increase the risk of bleeding events. Co-morbid conditions, such as coagulation disorders, or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding [see Drug Interactions ( 7) ].
Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically [see Warnings and Precautions (5.2, 5.3, 5.6)].
Indomethacin capsules may aggravate depression or other psychiatric disturbances, epilepsy, and parkinsonism, and should be used with considerable caution in patients with these conditions. Discontinue indomethacin capsules if severe CNS adverse reactions develop.
Indomethacin capsules may cause drowsiness; therefore, caution patients about engaging in activities requiring mental alertness and motor coordination, such as driving a car. Indomethacin may also cause headache. Headache which persists despite dosage reduction requires cessation of therapy with indomethacin capsules.
Corneal deposits and retinal disturbances, including those of the macula, have been observed in some patients who had received prolonged therapy with indomethacin capsules. Be alert to the possible association between the changes noted and indomethacin capsules. It is advisable to discontinue therapy if such changes are observed. Blurred vision may be a significant symptom and warrants a thorough ophthalmological examination. Since these changes may be asymptomatic, ophthalmologic examination at periodic intervals is desirable in patients receiving prolonged therapy. Indomethacin capsules are not indicated for long-term treatment.
- Cardiovascular Thrombotic Events [see Warnings and Precautions (5.1) ]
- GI Bleeding, Ulceration and Perforation [see Warnings and Precautions (5.2) ]
- Hepatotoxicity [see Warnings and Precautions (5.3) ]
- Hypertension [see Warnings and Precautions (5.4) ]
- Heart Failure and Edema [see Warnings and Precautions (5.5) ]
- Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.6) ]
- Anaphylactic Reactions [see Warnings and Precautions (5.7) ]
- Serious Skin Reactions [see Warnings and Precautions (5.9) ]
- Hematologic Toxicity [see Warnings and Precautions (5.12) ]
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In a gastroscopic study in 45 healthy subjects, the number of gastric mucosal abnormalities was significantly higher in the group receiving indomethacin capsules than in the group taking indomethacin suppositories or placebo.
In a double-blind comparative clinical study involving 175 patients with rheumatoid arthritis, however, the incidence of upper gastrointestinal adverse effects with indomethacin capsules or Suppositories was comparable. The incidence of lower gastrointestinal adverse effects was greater in the suppository group.
The adverse reactions for indomethacin capsules listed in the following table have been arranged into two groups: (1) incidence greater than 1%; and (2) incidence less than 1%. The incidence for group (1) was obtained from 33 double-blind controlled clinical trials reported in the literature (1,092 patients). The incidence for group (2) was based on reports in clinical trials, in the literature, and on voluntary reports since marketing. The probability of a causal relationship exists between indomethacin capsules and these adverse reactions, some of which have been reported only rarely.
The adverse reactions reported with indomethacin capsules may occur with use of the suppositories. In addition, rectal irritation and tenesmus have been reported in patients who have received the capsules.
|Incidence greater than 1%||Incidence less than 1%|
|nausea * with or without vomiting dyspepsia * (including indigestion, heartburn and epigastric pain) diarrhea abdominal distress or pain constipation||anorexia bloating (includes distension) flatulence peptic ulcer gastroenteritis rectal bleeding proctitis single or multiple ulcerations, including perforation and hemorrhage of the esophagus, stomach, duodenum or small and large intestines intestinal ulceration associated with stenosis and obstruction||gastrointestinal bleeding without obvious ulcer formation and perforation of preexisting sigmoid lesions (diverticulum, carcinoma, etc.) development of ulcerative colitis and regional ileitis ulcerative stomatitis toxic hepatitis and jaundice (some fatal cases have been reported) intestinal strictures (diaphragms) pancreatitis|
|CENTRAL NERVOUS SYSTEM|
|headache (11.7%) dizziness * vertigo somnolence depression and fatigue (including malaise and listlessness)||anxiety (includes nervousness) muscle weakness involuntary muscle movements insomnia muzziness psychic disturbances including psychotic episodes mental confusion drowsiness||light-headedness syncope paresthesia aggravation of epilepsy and parkinsonism depersonalization coma peripheral neuropathy convulsion dysarthria|
|tinnitus||ocular — corneal deposits and retinal disturbances, including those of the macula, have been reported in some patients on prolonged therapy with indomethacin capsules||blurred vision diplopia hearing disturbances, deafness|
|None||hypertension hypotension tachycardia chest pain||congestive heart failure arrhythmia; palpitations|
|None||edema weight gain fluid retention flushing or sweating||hyperglycemia glycosuria hyperkalemia|
|none||pruritus rash; urticaria petechiae or ecchymosis||exfoliative dermatitis erythema nodosum loss of hair Stevens-Johnson syndrome erythema multiforme toxic epidermal necrolysis|
|None||leukopenia bone marrow depression anemia secondary to obvious or occult gastrointestinal bleeding||aplastic anemia hemolytic anemia agranulocytosis thrombocytopenic purpura disseminated intravascular coagulation|
|None||acute anaphylaxis acute respiratory distress rapid fall in blood pressure resembling a shock-like state angioedema||dyspnea asthma purpura angiitis pulmonary edema fever|
|None||hematuria vaginal bleeding proteinuria nephrotic syndrome interstitial nephritis||BUN elevation renal insufficiency, including renal failure|
|None||epistaxis breast changes, including enlargement and tenderness, or gynecomastia|
|* Reactions occurring in 3% to 9% of patients treated with indomethacin capsules. (Those reactions occurring in less than 3% of the patients are unmarked.)|
Other reactions have been reported but occurred under circumstances where a causal relationship could not be established. However, in these rarely reported events, the possibility cannot be excluded. Therefore, these observations are being listed to serve as alerting information to physicians:
Although there have been several reports of leukemia, the supporting information is weak
A rare occurrence of fulminant necrotizing fasciitis, particularly in association with Group Aβ hemolytic streptococcus, has been described in persons treated with nonsteroidal anti-inflammatory agents, including indomethacin, sometimes with fatal outcome.
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.