Diclofenac Sodium (Page 4 of 7)

Serious Skin Reactions

NSAIDs, including diclofenac, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions and to discontinue the use of diclofenac sodium delayed-release tablets at the first appearance of skin rash or any other sign of hypersensitivity. Diclofenac sodium delayed-release tablets are contraindicated in patients with previous serious skin reactions to NSAIDs (see CONTRAINDICATIONS).

Premature Closure of Fetal Ductus Arteriosus

Diclofenac may cause premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including diclofenac sodium delayed-release tablets, in pregnant women starting at 30 weeks of gestation (third trimester) (see PRECAUTIONS: Pregnancy).

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 sodium delayed-release tablets, has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.

NSAIDs, including diclofenac sodium delayed-release tablets, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders, 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 PRECAUTIONS: Drug Interactions).

PRECAUTIONS

General

Diclofenac sodium delayed-release tablets, cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids and the patient should be observed closely for any evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis.

The pharmacological activity of diclofenac sodium delayed-release tablets in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Information for Patients

Advise the patient to read the FDA-approved patient labeling (Medication Guide) that accompanies each prescription dispensed. Inform patients, families, or their caregivers of the following information before initiating therapy with diclofenac sodium delayed-release tablets and periodically during the course of ongoing therapy.

Cardiovascular Thrombotic Events

Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their healthcare provider immediately (see WARNINGS: Cardiovascular Thrombotic Events).

Gastrointestinal Bleeding, Ulceration, and Perforation

Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their health care provider. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, inform patients of the increased risk for the signs and symptoms of GI bleeding (see WARNING: Gastrointestinal Bleeding, Ulceration, and Perforation).

Hepatotoxicity

Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur, instruct patients to stop diclofenac sodium delayed-release tablets and seek immediate medical therapy (see WARNINGS: Hepatotoxicity).

Heart Failure and Edema

Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur (see WARNINGS: Heart Failure and Edema).

Anaphylactic Reactions

Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). Instruct patients to seek immediate emergency help if these occur (see WARNINGS: Anaphylactic Reactions).

Serious Skin Reactions

Advise patients to stop diclofenac sodium delayed-release tablets immediately if they develop any type of rash and contact their healthcare provider as soon as possible (see WARNINGS: Serious Skin Reactions).

Female Fertility

Advise females of reproductive potential who desire pregnancy that NSAIDs, including diclofenac sodium delayed-release tablets, may be associated with a reversible delay in ovulation (see PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility).

Fetal Toxicity

Inform pregnant women to avoid use of diclofenac sodium delayed-release tablets and other NSAIDs, starting at 30 weeks gestation because of the risk of the premature closure of the fetal ductus arteriosus (see WARNINGS: Premature Closure of Fetal Ductus Arteriosus).

Avoid Concomitant Use of NSAIDs

Inform patients that the concomitant use of diclofenac sodium delayed-release tablets with other NSAIDs or salicylates (e.g., diflunisal, salsalate) is not recommended due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy (see WARNINGS: Gastrointestinal Bleeding, Ulceration, and Perforation and Drug Interactions). Alert patients that NSAIDs may be present in “over the counter” medications for treatment of colds, fever, or insomnia.

Use of NSAIDS and Low-Dose Aspirin

Inform patients not to use low-dose aspirin concomitantly with diclofenac sodium delayed-release tablets until they talk to their healthcare provider (see PRECAUTIONS: Drug Interactions).

Masking of Inflammation and Fever

The pharmacological activity of diclofenac sodium delayed-release tablets in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.

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: Gastrointestinal Bleeding, Ulceration and Perforation, and Hepatotoxicity).

Drug Interactions

See Table 2 for clinically significant drug interactions with diclofenac.

Table 2. Clinically Significant Drug Interactions with Diclofenac

Drugs That Interfere with Hemostasis

Clinical Impact:

  • •Diclofenac and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of diclofenac and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone.
  • •Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone.

Intervention:

Monitor patients with concomitant use of diclofenac sodium delayed-release tablets with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding (see WARNINGS: Hematologic Toxicity).

Aspirin

Clinical Impact:

Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone (see WARNINGS: Gastrointestinal Bleeding, Ulceration, and Perforation).

Intervention:

Concomitant use of diclofenac sodium delayed-release tablets and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding (see WARNINGS: Hematologic Toxicity).

Diclofenac sodium delayed-release tablets are not a substitute for low dose aspirin for cardiovascular protection.

ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers

Clinical Impact:

  • •NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol).
  • •In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible.

Intervention:

  • •During concomitant use of diclofenac sodium delayed-release tablets and ACE-inhibitors, ARBs, or beta- blockers, monitor blood pressure to ensure that the desired blood pressure is obtained.
  • •During concomitant use of diclofenac sodium delayed-release tablets and ACE-inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal function, monitor for signs of worsening renal function (see WARNINGS: Renal Toxicity and Hyperkalemia).
  • •When these drugs are administered concomitantly, patients should be adequately hydrated. Assess renal function at the beginning of the concomitant treatment and periodically thereafter.

Diuretics

Clinical Impact:

Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis.

Intervention:

During concomitant use of diclofenac sodium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects (see WARNINGS: Renal Toxicity and Hyperkalemia).

Digoxin

Clinical Impact:

The concomitant use of diclofenac with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin.

Intervention:

During concomitant use of diclofenac sodium delayed-release tablets and digoxin, monitor serum digoxin levels.

Lithium

Clinical Impact:

NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis.

Intervention:

During concomitant use of diclofenac sodium delayed-release tablets and lithium, monitor patients for signs of lithium toxicity.

Methotrexate

Clinical Impact:

Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction).

Intervention:

During concomitant use of diclofenac sodium delayed-release tablets and methotrexate, monitor patients for methotrexate toxicity.

Cyclosporine

Clinical Impact:

Concomitant use of diclofenac sodium delayed-release tablets and cyclosporine may increase cyclosporine’s nephrotoxicity.

Intervention:

During concomitant use of diclofenac sodium delayed-release tablets and cyclosporine, monitor patients for signs of worsening renal function.

NSAIDs and Salicylates

Clinical Impact:

Concomitant use of diclofenac with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy (see WARNINGS: Gastrointestinal Bleeding, Ulceration, and Perforation).

Intervention:

The concomitant use of diclofenac with other NSAIDs or salicylates is not recommended.

Pemetrexed

Clinical Impact:

Concomitant use of diclofenac sodium delayed-release tablets and pemetrexed may increase the risk of pemetrexed‑ associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information).

Intervention:

During concomitant use of diclofenac sodium delayed-release tablets and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity.

NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a period of two days before, the day of, and two days following administration of pemetrexed.

In the absence of data regarding potential interaction between pemetrexed and NSAIDs with longer half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration.

CYP2C9 Inhibitors or Inducers:

Clinical Impact:

Diclofenac is metabolized by cytochrome P450 enzymes, predominantly by CYP2C9. Co-administration of diclofenac with CYP2C9 inhibitors (e.g. voriconazole) may enhance the exposure and toxicity of diclofenac whereas co‑administration with CYP2C9 inducers (e.g. rifampin) may lead to compromised efficacy of diclofenac.

Intervention:

A dosage adjustment may be warranted when diclofenac is administered with CYP2C9 inhibitors or inducers (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

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.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.