Diclofenac Potassium

Prototypical NSAIA;1 2 3 4 5 6 7 8 9 189 302 303 317 318 phenylacetic acid derivative;1 2 3 4 5 6 7 8 9 189 262 structurally related to meclofenamate sodium and mefenamic acid.203

Inflammatory Diseases

Orally for symptomatic treatment of osteoarthritis,1 81 82 83 84 85 86 89 90 107 108 109 110 111 112 113 114 121 125 126 133 274 302 303 rheumatoid arthritis,1 74 75 76 77 78 79 80 87 88 107 115 116 117 118 119 121 125 126 129 254 302 303 and ankylosing spondylitis.1 91 120 121 125 127 274

Orally in fixed combination with misoprostol for the symptomatic treatment of osteoarthritis and rheumatoid arthritis in patients at high risk for developing NSAIA-induced gastric or duodenal ulcers and in patients at high risk for developing complications from these ulcers.284

Topically (as gel) for the symptomatic treatment of osteoarthritis-related joint pain.318 321 Used for joints amenable to topical therapy (e.g., hands, knees); has not been evaluated on joints of the spine, hip, or shoulder.318

Orally for management of juvenile rheumatoid arthritis†.3 128 210

Orally for symptomatic relief of acute gouty arthritis†.121 130 131 132

Orally or topically for symptomatic treatment of infusion-related superficial thrombophlebitis†.310 311

Pain

Orally for relief of pain, including postoperative (e.g., orthopedic, gynecologic, oral) pain, in adults.276 277 278 279 303

Transdermally for relief of acute pain due to minor strains, sprains, and contusions.317 319

Dysmenorrhea

Orally for symptomatic management of primary dysmenorrhea.303

Protein-bound Drugs

Only minimally displaces other highly protein-bound drugs from binding sites; however, may be displaced from binding sites by other highly protein-bound drugs.51 52 59 61

Specific Drugs

Diclofenac Potassium tablets are contraindicated in the following patients:

General

Diclofenac Potassium 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 Potassium 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 Potassium tablets and periodically during the course of ongoing therapy.

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).

Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their healthcare 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 WARNINGS: Gastrointestinal Bleeding, Ulceration, and Perforation).

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 Potassium tablets and seek immediate medical therapy (see WARNINGS: Hepatotoxicity).

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).

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).

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

Advise females of reproductive potential who desire pregnancy that NSAIDs, including VOLTAREN®, may be associated with a reversible delay in ovulation (see PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility).

Inform pregnant women to avoid use of Diclofenac Potassium 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).

Inform patients that the concomitant use of Diclofenac Potassium 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.

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

Masking of Inflammation and Fever

The pharmacological activity of Diclofenac Potassium tablets in reducing fever and inflammation, and possibly fever, may diminish the utility of these 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term carcinogenicity studies in rats given diclofenac sodium up to 2 mg/kg/day (approximately 0.1 times the maximum recommended human dose (MRHD) of Diclofenac Potassium tablets, 200 mg/day, based on body surface area (BSA) comparison) have revealed no significant increase in tumor incidence. A 2-year carcinogenicity study conducted in mice employing diclofenac sodium at doses up to 0.3 mg/kg/day (approximately 0.007 times the MRHD based on BSA comparison) in males and 1 mg/kg/day (approximately 0.02 times the MRHD based on BSA comparison) in females did not reveal any oncogenic potential.

Diclofenac sodium did not show mutagenic activity in in vitro point mutation assays in mammalian (mouse lymphoma) and microbial (yeast, Ames) test systems and was nonmutagenic in several mammalian in vitro and in vivo tests, including dominant lethal and male germinal epithelial chromosomal studies in mice, and nucleus anomaly and chromosomal aberration studies in Chinese hamsters.

Diclofenac sodium administered to male and female rats at 4 mg/kg/day (approximately 0.2 times the MRHD based on BSA comparison) did not affect fertility.

Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including Diclofenac Potassium tablets, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including Diclofenac Potassium tablets, in women who have difficulties conceiving or who are undergoing investigation of infertility.

Pregnancy

Use of NSAIDs, including Diclofenac Potassium tablets, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Diclofenac Potassium tablets, in pregnant women starting at 30 weeks of gestation (third trimester) (see WARNINGS: Premature Closure of Fetal Ductus Arterious).

There are no adequate and well-controlled studies of Diclofenac Potassium tablets in pregnant women. Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In the general U.S. population, all clinically recognized pregnancies, regardless of drug exposure, have a background rate of 2-4% for major malformations, and 15-20% for pregnancy loss. In animal reproduction studies, no evidence of teratogenicity was observed in mice, rats, or rabbits given diclofenac during the period of organogenesis at doses up to approximately 0.5, 0.5, and 1 times, respectively, the maximum recommended human dose (MRHD) of Diclofenac Potassium tablets, despite the presence of maternal and fetal toxicity at these doses [see Data]. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as diclofenac, resulted in increased pre- and post-implantation loss.

Animal Data

Reproductive and developmental studies in animals demonstrated that diclofenac sodium administration during organogenesis did not produce teratogenicity despite the induction of maternal toxicity and fetal toxicity in mice at oral doses up to 20 mg/kg/day (approximately 0.5 times the maximum recommended human dose [MRHD] of Diclofenac Potassium tablets, 200 mg/day, based on body surface area (BSA) comparison), and in rats and rabbits at oral doses up to 10 mg/kg/day (approximately 0.5 and 1 times, respectively, the MRHD based on BSA comparison). In a study in which pregnant rats were orally administered 2 mg/kg or 4 mg/kg diclofenac (0.1 and 0.2 times the MRHD based on BSA) from Gestation Day 15 through Lactation Day 21, significant maternal toxicity (peritonitis, mortality) was noted. These maternally toxic doses were associated with dystocia, prolonged gestation, reduced fetal weights and growth, and reduced fetal survival. Diclofenac has been shown to cross the placental barrier in mice, rats, and humans.

Labor or Delivery

There are no studies on the effects of Diclofenac Potassium tablets during labor or delivery. In animal studies, NSAIDs, including diclofenac, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth.

Nursing Mothers

Based on available data, diclofenac may be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Diclofenac Potassium tablets and any potential adverse effects on the breastfed infant from the Diclofenac Potassium tablets or from the underlying maternal condition.

One woman treated orally with a diclofenac salt, 150 mg/day, had a milk diclofenac level of 100 mcg/L, equivalent to an infant dose of about 0.03 mg/kg/day. Diclofenac was not detectable in breast milk in 12 women using diclofenac (after either 100 mg/day orally for 7 days or a single 50 mg intramuscular dose administered in the immediate postpartum period).

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions, If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects (see WARNINGS: Cardiovascular Thrombotic Events, Gastrointestinal Bleeding, Ulceration, and Perforation, Hepatotoxicity, Renal Toxicity and Hyperkalemia, PRECAUTIONS: Laboratory Monitoring).

Diclofenac is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY, ADVERSE REACTIONS).

NDC 0378-2474-01

Diclofenac
Potassium
Tablets, USP
50 mg

PHARMACIST: Dispense the accompanying
Medication Guide to each patient.

Rx only     100 Tablets

Each film-coated tablet
contains: Diclofenac
potassium, USP 50 mg

Dispense in a tight, light-resistant
container as defined in the USP
using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication
out of the reach of children.

Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]

Protect from moisture.

Usual Dosage: See accompanying
prescribing information.

Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.

Mylan.com
RM2474A5