Paroxetine Contraindications and Precautions
- abrupt discontinuation
- anorexia nervosa
- bipolar disorder
- bleeding
- breast-feeding
- cardiac disease
- children
- dehydration
- driving or operating machinery
- elderly
- electroconvulsive therapy (ECT)
- hepatic disease
- hyponatremia
- mania
- neonates
- pregnancy
- renal failure
- renal impairment
- seizure disorder
- seizures
- suicidal ideation
Paroxetine Contraindications and Precautions
Paroxetine is contraindicated in those patients with a hypersensitivity to paroxetine or any of the formulation components.
Avoid abrupt discontinuation of any SSRI if possible. Gradual tapering is recommended during discontinuation of any SSRI to decrease or prevent the occurrence of potential withdrawal-like symptoms. Such symptoms have been reported with abrupt discontinuation of paroxetine. For example, the taper phase regimen used in some clinical trials of paroxetine involved an incremental decrease in the daily dose by 10 mg/day at weekly intervals. When a daily dose of 20 mg/day was reached, patients were continued on this dose for 1 week before treatment was stopped. Patients should be monitored for withdrawal when discontinuing treatment, regardless of the indication for which the SSRI is being prescribed. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, one may continue decreasing the dose but at a more gradual rate.
All effective antidepressants can transform depression into mania or hypomania in predisposed individuals. If a patient develops manic symptoms, paroxetine should be held and appropriate therapy initiated to treat the manic symptoms.
Paroxetine is not FDA-approved for the treatment of depression in pediatric patients. The possibility of a suicide attempt is inherent in patients with depressive symptoms, whether these occur in primary depression or in association with another primary disorder such as OCD. Patients with suicidal ideation, including both adult and pediatric patients, should be closely supervised, whether or not they are taking an antidepressant. In addition, all antidepressants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. In October, 2004, the FDA directed manufacturers of all antidepressants to include a Black Box warning detailing the risk of suicide in pediatric patients. A causal role for antidepressants in inducing suicidality has been established in pediatric patients. The risk of suicidality for these drugs was identified in a pooled analysis of 24 placebo-controlled trials (n=4400) lasting up to 16 weeks in pediatric patients with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants (SSRIs and others). The average risk of such events on drug was 4% and 2% for placebo; however, no suicides occurred in these trials. Based on these data, FDA has determined that the following points are appropriate for inclusion in the boxed warning: antidepressants increase the risk of suicidal thinking and behavior (suicidality) in pediatric patients with MDD and other psychiatric disorders (OCD, social anxiety disorder); anyone considering the use of an antidepressant in a pediatric patient for any clinical use must balance the risk of increased suicidality with the clinical need; patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly within the first few months of starting therapy or at the time of dose increases or decreases; such observation would generally include at least weekly face-to-face contact with patients, family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks; additional contact by telephone may be appropriate between face-to-face visits; adults with MDD or co-morbid depression in the setting of other psychiatric illness being treated with antidepressants should be observed similarly for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes; families and caregivers should be advised to closely observe the patient (adult or child) on a daily basis for the emergence of agitation, irritability, unusual changes in behavior, emergence of suicidality, and to communicate immediately with the prescriber. It is unknown if the suicidality risk in pediatric patients extends to longer-term therapy (i.e., beyond several months) or to adult patients. In patients who exhibit changes in symptoms, worsening of depression or emergent suicidality, a decision should be made to change or discontinue treatment. If discontinuing, medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described represent such a conversion is unknown. Patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder prior to initiating treatment. Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that paroxetine is not approved for use in treating bipolar depression.
Paroxetine is contraindicated for concomitant use in patients receiving MAO inhibitor therapy (see Drug Interactions).
Paroxetine should be used with caution in patients with a history of seizure disorder. Seizures have been reported rarely in patients taking SSRIs; however, they have occurred primarily in cases of overdose. Paroxetine’s effects during electroconvulsive therapy (ECT) have not been evaluated in clinical studies to date.
Paroxetine should be used with caution in elderly patients. Pharmacokinetic data indicates that paroxetine clearance is reduced in the elderly. Although no difference in safety has been recorded, slow titration of dosage is recommended in the elderly (see Dosage).
Paroxetine should be used with caution in patients with severe renal impairment or renal failure because clearance can be reduced. Lower doses or less frequent dosing may be necessary (see Dosage).
Patients with severe hepatic impairment have about a 2-fold increase in plasma concentrations of paroxetine compared to patients without liver disease. Thus, this drug should be used with caution in patients with hepatic impairment. If paroxetine is administered to a patient with hepatic disease, a lower dose or less frequent dosing interval may be necessary (see Dosage). Paroxetine has been infrequently associated with elevated hepatic enzymes.
Although clinical trial data indicate that paroxetine is not associated with the development of clinically significant ECG abnormalities, the use of paroxetine has not been systematically evaluated in patients with a recent history of myocardial infarction or unstable cardiac disease.
Paroxetine is not currently approved for use in pediatric patients < 18 years of age. In October, 2004, the FDA directed manufacturers of all antidepressants to include a Black Box warning detailing the risk of suicide in pediatric patients. A causal role for antidepressants in inducing suicidality has been established in pediatric patients (see Contraindications, suicidal ideation). Pediatric patients should be monitored closely for the risk of suicide with any antidepressant medication. Among the antidepressants, only fluoxetine is approved for use in treating depression in pediatric patients. Fluoxetine, sertraline, fluvoxamine, and clomipramine are approved for OCD in pediatric patients. None of the drugs is approved for other psychiatric indications in children. Pediatric patients being treated with antidepressants for any indication should be observed daily by caregivers for clinical worsening, as well as agitation, irritability, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. If concerns arise, contact with health care providers should be made immediately. Antidepressants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. A patient Medication Guide about using antidepressants in children and adolescents is available. Health care providers should instruct patients and caregivers to read the guide and discuss any questions with them. Paroxetine should also be used with caution in children of all ages with a known family history of cardiac disease, or in children who are taking other medications concomitantly that might result in drug interactions. QTc interval prolongation, tachycardias, and other side effects have been reported in children taking clomipramine in combination with paroxetine for the treatment of obsessive-compulsive disorder (OCD). Additional monitoring may be necessary.
Paroxetine can rarely precipitate a syndrome of inappropriate secretion of antidiuretic hormone (SIADH) that presents as hyposmolarity of serum and urine, and hyponatremia (see Adverse Reactions). The majority of these occurrences have been in elderly individuals, some in patients taking diuretics or who were otherwise volume depleted (i.e., dehydration).
Because paroxetine can cause weight loss, it should be used with caution in patients with anorexia nervosa or in other patients where weight loss is undesirable. Patients who are debilitated or elderly, or who are of body weights < 45 kg may require lower paroxetine dosages (see Dosage).
Paroxetine is classified as FDA pregnancy risk category C. A retrospective epidemiological study of > 3,500 pregnant women exposed to paroxetine and other antidepressants during the first trimester suggests an increased risk of major congenital malformations (OR 2.20; 95% confidence interval 1.34 - 3.63) and cardiovascular malformations (OR 2.20; 95% confidence interval 1.34 - 3.63) associated with paroxetine use. Ten of 14 infants with cardiovascular malformations had ventricular septal defects. However, a separate study based on the Swedish Medical Birth Registry evaluated 4,291 infants exposed to SSRIs in early pregnancy. This study reported no increased risk for overall major malformations in 708 infants born to women with paroxetine exposure in early pregnancy. Animal teratology studies failed to show an increased risk of fetal malformations, however, an increase in pup deaths during the first few days after birth has been noted in animals when paroxetine was initiated in the last trimester of gestation and continued during lactation. In animal studies, SSRIs appear to downregulate serotonin receptors in the fetal cortex; the changes are present for a period of time after birth but the effect on neurological development is uncertain; the applicability of these findings to humans is also unknown. A prospective, cohort study was conducted to evaluate the outcome of neonates born to 267 women who took an SSRI during pregnancy (of whom 97 took paroxetine). Compared with a neonatal control group, SSRI-exposed neonates had similar rates of major malformation, spontaneous and elective abortion, and stillbirth. In addition, mean birth weight and gestational age were similar among the two groups of neonates. A neonatal abstinence syndrome has been reported at birth following in utero paroxetine exposure (see Adverse Reactions); exposed neonates may need to be monitored for associated symptoms. A cohort study of 55 women revealed that 22% (12 of 55) of neonates exposed to paroxetine in the third trimester had complications requiring treatment or extended hospitalization vs. 6% in comparison groups (see Adverse Reactions). The manufacturer recommends the use of paroxetine during pregnancy only if the potential benefit to the mother outweighs the potential fetal risk. Health care providers are encouraged to discuss these findings as well as treatment alternatives with their patients.
Breast-feeding may be continued with caution during paroxetine use, but the infant should be observed for evidence of adverse effects. In one small trial, mothers ingested up to 50 mg/day PO of paroxetine for more than 10 days. Paroxetine was excreted into the breast milk, but at low concentrations (< 2 ng/ml). None of the breast-fed infants had detectable paroxetine serum concentrations and none experienced adverse effects from the medication. Other SSRIs (e.g., fluoxetine) are excreted in breast milk and have been reported to increase infant irritability. The long-term effects of paroxetine on a breast-feeding infant are unknown. The American Academy of Pediatrics suggests that SSRI use during breast-feeding may be of concern; however, other experts in psychiatry have suggested that paroxetine and some of the other SSRIs may be safely continued during lactation with appropriate caution in prescribing.
Because any psychoactive drug may impair judgment, thinking, or motor skills, patients should use caution when driving or operating machinery, until they are reasonably certain that paroxetine does not affect them adversely. Concurrent use of alcohol is not recommended. The US olympic committee has only banned the use of the SSRI-type antidepressants in sporting events that involve rifelry.
There have been several reports of abnormal bleeding (mostly ecchymosis and purpura) associated with paroxetine treatment, including a report of impaired platelet aggregation. While a causal relationship to paroxetine has not been established, impaired platelet aggregation may result from platelet serotonin depletion and may contribute to abnormal bleeding.
[ Last revised: 9/27/2005 4:54:00 PM ]
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