Indomethacin (Page 3 of 7)
5.10 Premature Closure of Fetal Ductus Arteriosus
Indomethacin may cause premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including indomethacin, in pregnant women starting at 30 weeks of gestation (third trimester) [see Use in Specific Populations (8.1) ].
5.11 Hematologic Toxicity
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 has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.
NSAIDs, including indomethacin, 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) ].
5.12 Masking of Inflammation and Fever
The pharmacological activity of indomethacin in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.
5.13 Laboratory Monitoring
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)].
5.14 Central Nervous System Effects
Indomethacin 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 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.
5.15 Ocular Effects
Corneal deposits and retinal disturbances, including those of the macula, have been observed in some patients who had received prolonged therapy with indomethacin. Be alert to the possible association between the changes noted and indomethacin. 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 is not indicated for long-term treatment.
6 ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
• 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 (5.11) ]
6.1 Clinical Trials Experience
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 Suppositories or Capsules 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 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.Table 1: Summary of Adverse reactions for Indomethacin Capsules
Incidence greater than 1% | Incidence less than 1% | |
GASTROINTESTINAL | ||
nausea* with or without vomiting dyspepsia* (including indigestion, heartburn and epigastric pain) diarrhea abdominal distress or pain constipation | anorexiabloating (includes distension) flatulencepeptic ulcergastroenteritisrectal bleedingproctitissingle or multiple ulcerations, including perforation andhemorrhageof the esophagus, stomach, duodenum or small and large intestinesintestinal ulcerationassociated withstenosis and obstruction | gastrointestinal bleeding withoutobvious ulcer formation andperforation of preexisting sigmoid lesions (diverticulum,carcinoma, etc.) development of ulcerative colitis and regional ileitisulcerative stomatitistoxic hepatitis and jaundice (some fatal cases have been reported)intestinal strictures (diaphragms) |
CENTRAL NERVOUS SYSTEM | ||
headache (11.7%) dizziness*vertigo somnolencedepression and fatigue (including malaise and listlessness) | anxiety (includes nervousness) muscle weakness involuntary muscle movements insomnia muzziness psychic disturbances including psychotic episodes mental confusiondrowsiness | light-headednesssyncopeparesthesiaaggravation of epilepsy and parkinsonism depersonalizationcomaperipheral neuropathyconvulsiondysarthria |
SPECIAL SENSES | ||
tinnitus | ocular — corneal depositsand retinal disturbances, including those of the macula, have beenreported in some patients on prolongedtherapy with indomethacin capsules | blurred visiondiplopiahearing disturbances, deafness |
CARDIOVASCULAR | ||
None | hypertension hypotension tachycardia chest pain | congestive heart failure arrhythmia; palpitations |
METABOLIC | ||
None | Edema weight gain fluid retentionflushing or sweating | hyperglycemia glycosuria hyperkalemia |
INTEGUMENTARY | ||
none | Pruritus rash; urticaria petechiae or ecchymosis | exfoliative dermatitis erythema nodosum loss of hair Stevens-Johnson syndrome erythema multiforme toxic epidermal necrolysis |
HEMATOLOGIC | ||
None | Leucopenia bone marrow depression anemia secondary to obviousor occult gastrointestinal bleeding | aplastic anemia hemolytic anemia agranulocytosis thrombocytopenic purpura disseminated intravascular coagulation |
HYPERSENSITIVITY | ||
None | acute anaphylaxisacute respiratory distressrapid fall in blood pressure resemblinga shock-like stateangioedema | dyspneaasthma purpura angiitispulmonary edema fever |
GENITOURINARY | ||
None | hematuria vaginal bleeding proteinuria nephrotic syndromeinterstitial nephritis | BUN elevation renal insufficiency, including renal failure |
MISCELLANEOUS | ||
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.) |
Causal relationship unknown: 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:
Cardiovascular: Thrombophlebitis
Hematologic: Although there have been several reports of leukemia, the supporting information is weak
Genitourinary: Urinary frequency
A rare occurrence of fulminant necrotizing fasciitis, particularly in association with Group Aβ hemolytic streptococcus, has been described in persons treated with non-steroidal 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.