DICLOFENAC SODIUM solution

Երկիր: Ամերիկայի Միացյալ Նահանգներ

Լեզու: անգլերեն

Աղբյուրը: NLM (National Library of Medicine)

Ակտիվ բաղադրիչ:

DICLOFENAC SODIUM (UNII: QTG126297Q) (DICLOFENAC - UNII:144O8QL0L1)

Հասանելի է:

Alembic Pharmaceuticals Inc.

Կառավարման երթուղին:

TOPICAL

Ռեկվիզորի տեսակը:

PRESCRIPTION DRUG

Թերապեւտիկ ցուցումներ:

Diclofenac sodium topical solution is indicated for the treatment of the pain of osteoarthritis of the knee(s). Diclofenac sodium topical solution is contraindicated in the following patients: - Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product [see Warnings and Precautions (5.7,5.9) ] - History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions (5.7,5.8) ] - In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.1) ] Risk Summary Use of NSAIDs, including diclofenac sodium topical solution, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of diclofenac sodium topical solution use between about 20 and 30 weeks of gestation, and avoid diclofenac sodium topical solution use at about 30 weeks of gestation and later in pregnancy (see Clinical Considerations, Data) . Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including diclofenac sodium topical solution, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In animal reproduction studies, no evidence of malformations were observed in mice, rats, or rabbits given diclofenac during the period of organogenesis at doses up to approximately 0.6, 0.6, and 1.3 times, respectively, the maximum recommended human dose (MRHD) of 162 mg diclofenac sodium via diclofenac sodium topical solution, 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. Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Premature Closure of the Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including diclofenac sodium topical solution, can cause premature closure of the fetal ductus arteriosus (see Data) . Oligohydramnios/Neonatal Renal Impairment: If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If diclofenac sodium topical solution treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue diclofenac sodium topical solution and follow up according to clinical practice (see Data) . Labor or Delivery There are no studies on the effects of diclofenac sodium topical solution during labor or delivery. In animal studies, NSAIDs, including diclofenac inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. Data Human Data Premature Closure of Fetal Ductus Arteriosus: Published literature reports that the use of NSAIDs at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus.   Oligohydramnios/Neonatal Renal Impairment: Published studies and postmarketing reports describe maternal NSAID use at about 20 weeks gestation or later in pregnancy associated with 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. In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. There have been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. Methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use. Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to NSAIDs through maternal use is uncertain. Animal data Reproductive and developmental studies in animals demonstrated that diclofenac sodium administration during organogenesis did not produce malformations despite the induction of maternal toxicity and fetal toxicity in mice at oral doses up to 20 mg/kg/day (approximately 0.6 times the maximum recommended human dose [MRHD] of diclofenac sodium topical solution, 162 mg diclofenac sodium/day, based on body surface area (BSA) comparison), and in rats and rabbits at oral doses up to 10 mg/kg/day (approximately 0.6 and 1.3-times, respectively, the MRHD based on BSA comparison). Published reproductive and developmental studies of dimethyl sulfoxide (DMSO, the solvent used in diclofenac sodium topical solution) are equivocal as to potential teratogenicity. In a study in which pregnant rats were orally administered 2 or 4 mg/kg diclofenac (0.12 and 0.24 times the MRHD, respectively, based on BSA comparison) 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 and rats. In published studies, diclofenac administration to pregnant rats prolonged gestation and produced liver toxicity and neuronal loss in offspring (1 mg/kg, IP; 0.06 times the MRHD based on BSA comparison), impaired nephrogenesis in the kidney (3.6 mg/kg, IP; 0.2 times the MRHD based on BSA comparison), and caused adverse effects on the developing testes (6.1 mg/kg, oral; 0.4 times the MRHD based on BSA comparison). Risk Summary 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 sodium topical solution and any potential adverse effects on the breastfed infant from the diclofenac sodium topical solution or from the underlying maternal condition. Data 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). Infertility Females Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including diclofenac sodium topical solution, 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 sodium topical solution, in women who have difficulties conceiving or who are undergoing investigation of infertility. Males Published studies in adult male rodents report that diclofenac, at clinically relevant doses, can produce adverse effects on male reproductive tissues. The impact of these findings on male fertility is not clear [See Nonclinical Toxicology (13.1)] . Safety and effectiveness in pediatric patients have not been established. 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 and Precautions (5.1,  5.2,  5.3,  5.6,5.14) ]. Of the 911 patients treated with diclofenac sodium topical solution 1.5% in seven controlled, Phase 3 clinical trials, 444 subjects were 65 years of age and over. There was no age-related difference in the incidence of adverse events. Of the 793 patients treated with diclofenac sodium topical solution 1.5% in one open-labeled safety trial, 334 subjects were 65 years of age and over including 107 subjects 75 and over. There was no difference in the incidence of adverse events with long-term exposure to diclofenac sodium topical solution 1.5% for this elderly population.

Ապրանքի ամփոփագիր:

Diclofenac sodium topical solution USP, 2% w/w, is supplied as a clear, colorless to faintly pink or orange solution containing 20 mg of diclofenac sodium per gram of solution, in a white polypropylene-dose pump bottle with a clear cap. Each pump actuation delivers 20 mg of diclofenac sodium in 1 gram of solution. NDC Number & Size 112 g bottle………………………………...NDC # 62332-487-12 Storage Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Լիազորման կարգավիճակը:

Abbreviated New Drug Application

Տեղեկատվական թերթիկ

Alembic Pharmaceuticals Inc.
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SPL MEDGUIDE
Medication Guide for Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
What is the most important information I should know about medicines
called Nonsteroidal Anti-inflammatory
Drugs (NSAIDs)?
NSAIDs can cause serious side effects, including:
● Increased risk of a heart attack or stroke that can lead to death.
This risk may happen early in treatment and may
increase:
•
with increasing doses of NSAIDs
•
with longer use of NSAIDs
Do not take NSAIDs right before or after a heart surgery called a
"coronary artery bypass graft (CABG)."
Avoid taking NSAIDs after a recent heart attack, unless your
healthcare provider tells you to. You may have an
increased risk of another heart attack if you take NSAIDs after a
recent heart attack.
● Increased risk of bleeding, ulcers, and tears (perforation) of the
esophagus (tube leading from the mouth to the
stomach), stomach and intestines:
o anytime during use
o without warning symptoms
o that may cause death
The risk of getting an ulcer or bleeding increases with:
•
past history of stomach ulcers, or stomach or intestinal bleeding with
use of NSAIDs
•
taking medicines called "corticosteroids", "anticoagulants", "SSRIs",
or "SNRIs"
•
increasing doses of NSAIDs
•
longer use of NSAIDs
•
smoking
•
drinking alcohol
•
older age
•
poor health
•
advanced liver disease
•
bleeding problems
NSAIDs should only be used:
○ exactly as prescribed
○ at the lowest dose possible for your treatment
○ for the shortest time needed
What are NSAIDs?
NSAIDs are used to treat pain and redness, swelling, and heat
(inflammation) from medical conditions such as
different types of arthritis, menstrual cramps, and other types of
short-term pain.
Who should not take NSAIDs?
Do not take NSAIDS:
•
if you have had an asthma attack, hives, or other allergic reaction
with aspirin or any other NSAIDs.
•
right before or after heart bypass surgery.
Before taking NSAIDs, tell your health care provider about all of your
medical conditi

Ապրանքի հատկությունները

DICLOFENAC SODIUM- DICLOFENAC SODIUM SOLUTION
ALEMBIC PHARMACEUTICALS INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
DICLOFENAC SODIUM
TOPICAL SOLUTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR DICLOFENAC
SODIUM TOPICAL SOLUTION.
DICLOFENAC SODIUM TOPICAL SOLUTION, FOR TOPICAL USE.
INITIAL U.S. APPROVAL:1988
WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) CAUSE AN INCREASED RISK
OF SERIOUS
CARDIOVASCULAR THROMBOTIC EVENTS, INCLUDING MYOCARDIAL INFARCTION, AND
STROKE, WHICH
CAN BE FATAL. THIS RISK MAY OCCUR EARLY IN TREATMENT AND MAY INCREASE
WITH DURATION
OF USE (5.1)
DICLOFENAC SODIUM TOPICAL SOLUTION IS CONTRAINDICATED IN THE SETTING
OF CORONARY
ARTERY BYPASS GRAFT (CABG) SURGERY (4, 5.1)
NSAIDS CAUSE AN INCREASED RISK OF SERIOUS GASTROINTESTINAL (GI)
ADVERSE EVENTS
INCLUDING BLEEDING, ULCERATION, AND PERFORATION OF THE STOMACH OR
INTESTINES, WHICH
CAN BE FATAL. THESE EVENTS CAN OCCUR AT ANY TIME DURING USE AND
WITHOUT WARNING
SYMPTOMS. ELDERLY PATIENTS AND PATIENTS WITH A PRIOR HISTORY OF PEPTIC
ULCER DISEASE
AND/OR GI BLEEDING ARE AT GREATER RISK FOR SERIOUS GI EVENTS (5.2)
INDICATIONS AND USAGE
Diclofenac sodium topical solution is a nonsteroidal anti-inflammatory
drug indicated for the treatment of
the pain of osteoarthritis of the knee(s). (1)
DOSAGE AND ADMINISTRATION
Use the lowest effective dosage for the shortest duration consistent
with individual patient treatment
goals.
The recommended dose is 2 pump actuations on each painful knee, 2
times a day. (2)
Apply diclofenac sodium topical solution, to clean, dry skin. (2.1)
Dispense 40 mg (2 pump actuations) directly onto the knee or first
into the hand and then onto the
knee. Spread evenly around front, back and sides of the knee. (2.1)
Wash hands completely after administering the product. (2.2)
Wait until the area is completely dry bef