Usage in Pregnancy

Risk Summary

Use of NSAIDs, including aspirin, 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 Orphengesic Forte Tablets use

between about 20 and 30 weeks of gestation, and avoid Orphengesic Forte Tablets use at about

30 weeks of gestation and later in pregnancy [see WARNINGS; Fetal Toxicity].

Premature Closure of Fetal Ductus Arteriosus

Use of NSAIDs, including aspirin, 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.

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 aspirin, 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 2-4% and 15-20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30

weeks gestation and later in pregnancy, because NSAIDs, including Orphengesic Forte Tablets,

can cause premature closure of the fetal ductus arteriosus (see WARNINGS; Fetal Toxicity).

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 Orphengesic Forte Tablets treatment

extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If

oligohydramnios occurs, discontinue Orphengesic Forte Tablets and follow up according to

clinical practice (see WARNINGS; Fetal Toxicity).

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.

Usage in Children

The safe and effective use of this drug in children has not been established. Usage of this drug in children under 12 years of age is not recommended.

Fetal Toxicity

Premature Closure of Fetal Ductus Arteriosus:

Avoid use of NSAIDs, including Norgesic Forte Tablets, in pregnant women at about 30

weeks gestation and later. NSAIDs including Orphengesic Forte Tablets, increase the risk of

premature closure of the fetal ductus arteriosus at approximately this gestational age.

Oligohydramnios/Neonatal Renal Impairment:

Use of NSAIDs, including Norgesic Forte Tablets, 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

Orphengesic Forte Tablets use to the lowest effective dose and shortest duration possible.

Consider ultrasound monitoring of amniotic fluid if Norgesic Forte Tablets treatment extends

beyond 48 hours. Discontinue if oligohydramnios occurs and follow

up according to clinical practice [see PRECAUTIONS; Pregnancy].

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 Orphengesic Forte Tablets. 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 and evaluate the patient immediately.

Storage

Store at 20°-25°C (68°-77° F) (see USP Controlled Room Temperature).

Protect from moisture.