Diclofenac Potassium (Page 3 of 8)

5.10 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as diclofenac potassium 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 diclofenac potassium capsules and evaluate the patient immediately.

5.11 Fetal Toxicity

Premature Closure of Fetal Ductus Arteriosus

Avoid use of NSAIDs, including diclofenac potassium capsules, in pregnant women at about 30 weeks gestation and later. NSAIDs, including diclofenac potassium capsules, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.

Oligohydramnios/Neonatal Renal Impairment

Use of NSAIDs, including diclofenac potassium capsules, 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 diclofenac potassium capsules use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if diclofenac potassium capsules treatment extends beyond 48 hours. Discontinue diclofenac potassium capsules if oligohydramnios occurs and follow up according to clinical practice [ see Use in Specific Populations (8.1) ].

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5.12 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 diclofenac potassium capsules has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.

NSAIDs, including diclofenac potassium 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) ].

5.13 Masking of Inflammation and Fever

The pharmacological activity of diclofenac potassium capsules in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.

5.14 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) ].

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 clinical trials of a drug cannot be directly compared with the rates in clinical trials of another drug and may not reflect the rates observed in practice.

The safety of diclofenac potassium was evaluated in 965 adult subjects. In patients treated with diclofenac potassium 25 mg (N = 345) or a higher dose, three or four times a day, for 4 days to 5 days, the most common adverse reactions (i.e., reported in ≥ 1% of diclofenac potassium treated patients) were as follows: gastrointestinal experiences including abdominal pain, constipation, diarrhea, dyspepsia, nausea, vomiting, dizziness, headache, somnolence, pruritus, and increased sweating. (see Table 1).

Table 1 Incidence of Treatment Emergent Adverse Reactions with Incidence ≥ 1% of Diclofenac Potassium Treated Patients in Multiple-Dose Studies

*There was greater use of concomitant opioid rescue medication in placebo treated patients than in diclofenac potassium treated patients.
MedDRA System Organ Class and Preferred Term		Diclofenac Potassium * 25 mg n = 345 n (%)		Placebo * n = 327 n (%)
Any Adverse Events		144 (41.7)		181 (55.4)
Nausea		57 (16.5)		66 (20.2)
Headache		43 (12.5)		56 (17.1)
Abdominal Pain		24 (7.0)		11 (3.4)
Vomiting		20 (5.8)		17 (5.2)
Dizziness		12 (3.5)		66 (20.2)
Constipation		11 (3.2)		9 (2.8)
Somnolence		9 (2.6)		6 (1.8)
Diarrhea		8 (2.3)		9 (2.8)
Pruritus		5 (1.4)		6 (1.8)
Dyspepsia		4 (1.2)		8 (2.4)
Sweating Increase		4 (1.2)		2 (0.6)

In patients taking other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1% to 10% of patients are:

Gastrointestinal experiences including: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal) and vomiting.

Abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritus, rashes, and tinnitus.

Additional adverse experiences reported in patients taking other NSAIDs occasionally include:

Body as a Whole: fever, infection, sepsis

Cardiovascular System: congestive heart failure, hypertension, tachycardia, syncope

Digestive System: dry mouth, esophagitis, gastric/peptic ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice

Hemic and Lymphatic System: ecchymosis, eosinophilia, leukopenia, melena, purpura, rectal bleeding, stomatitis, thrombocytopenia

Metabolic and Nutritional: weight changes

Nervous System: anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia, malaise, nervousness, paresthesia, somnolence, tremors, vertigo

Respiratory System: asthma, dyspnea

Skin and Appendages: alopecia, photosensitivity, sweating increased

Special Senses: blurred vision

Urogenital System: cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure

Other adverse reactions in patients taking other NSAIDs, which occur rarely are:

Body as a Whole: anaphylactic reactions, appetite changes, death

Cardiovascular System: arrhythmia, hypotension, myocardial infarction, palpitations, vasculitis

Digestive System: colitis, eructation, liver failure, pancreatitis

Hemic and Lymphatic System: agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, pancytopenia

Metabolic and Nutritional: hyperglycemia

Nervous System: convulsions, coma, hallucinations, meningitis

Respiratory System: respiratory depression, pneumonia

Skin and Appendages: angioedema, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson Syndrome, urticaria

Special Senses: conjunctivitis, hearing impairment

Pediatric use information is approved for Assertio Therapeutics Inc’s ZIPSOR (diclofenac potassium) Capsules. However, due to Assertio Therapeutics Inc’s marketing exclusivity rights, this drug product is not labeled with that information.