Included as part of the PRECAUTIONS section.
Adverse Reactions From Abrupt Withdrawal Of OZOBAX
Abrupt discontinuation of baclofen, regardless of the
cause, has resulted in adverse reactions that include hallucinations, seizures,
high fever, altered mental status, exaggerated rebound spasticity, and muscle
rigidity, that in rare cases has advanced to rhabdomyolysis, multiple
organ-system failure, and death. Therefore, reduce the dosage slowly when
OZOBAX is discontinued, unless the clinical situation justifies a rapid
Neonatal Withdrawal Symptoms
Withdrawal symptoms in neonates whose mothers were
treated with oral baclofen throughout pregnancy have been reported starting
hours to days after delivery. The symptoms of withdrawal in these infants have
included increased muscle tone, tremor, jitteriness, and seizure. If the
potential benefit justifies the potential risk to the fetus and OZOBAX is
continued during pregnancy, gradually reduce the dosage and discontinue OZOBAX
before delivery. If slow withdrawal is not feasible, advise the parents or
caregivers of the exposed neonate of the potential for neonatal withdrawal.
Drowsiness And Sedation
Drowsiness and sedation have been reported in up to 63% of
patients taking baclofen, the active ingredient in OZOBAX [see ADVERSE
REACTIONS]. Patients should avoid operation of automobiles or other
dangerous machinery and activities made hazardous by decreased alertness when
starting OZOBAX or increasing the dose until they know how the drug affects
them. Advise patients that the central nervous system depressant effects of
OZOBAX may be additive to those of alcohol and other CNS depressants.
Poor Tolerability In Stroke Patients
OZOBAX should be used with caution in patients who have
had a stroke. Baclofen has not significantly benefited patients with stroke.
These patients have also shown poor tolerability to the drug.
Exacerbation Of Psychotic Disorders, Schizophrenia, Or Confusional
OZOBAX should be used with caution in patients suffering
from psychotic disorders, schizophrenia, or confusional states. If treated with
OZOBAX, these patients should be kept under careful surveillance because
exacerbations of these conditions have been observed with oral baclofen
Exacerbation Of Autonomic Dysreflexia
OZOBAX should be used with caution in patients with a
history of autonomic dysreflexia. The presence of nociceptive stimuli or abrupt
withdrawal of OZOBAX may cause an autonomic dysreflexic episode.
Exacerbation Of Epilepsy
OZOBAX should be used with caution in patients with
epilepsy. Deterioration in seizure control has been reported in patients taking
Posture And Balance Effects
OZOBAX should be used with caution in patients where
spasticity is utilized to sustain upright posture and balance in locomotion or
whenever spasticity is utilized to obtain increased function.
A dose-related increase in incidence of ovarian cysts was
observed in female rats treated chronically with oral baclofen. Ovarian cysts
have been found by palpation in about 4% of the multiple sclerosis patients who
were treated with oral baclofen for up to one year. In most cases, these cysts
disappeared spontaneously while patients continued to receive the drug. Ovarian
cysts are estimated to occur spontaneously in approximately 1% to 5% of the
normal female population.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No increase in tumors was seen in rats receiving baclofen
orally for two years at approximately 30 to 60 times on a mg/kg basis, or 10 to
20 times on a mg/ m² basis, the maximum oral dose recommended for human use. Mutagenesis
Genetic toxicology assays have not been conducted for baclofen.
Impairment Of Fertility
Studies to evaluate the effects of baclofen on fertility
have not been conducted.
Use In Specific Populations
There are no adequate data on the developmental risk
associated with the use of OZOBAX in pregnant women. Oral administration of
baclofen to pregnant rats resulted in an increased incidence of fetal
structural abnormalities at a dose which was also associated with maternal
toxicity. The background risk of major birth defects and miscarriage for the
indicated population is unknown. 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.
Fetal/Neonatal Adverse Reactions
Ozobax may increase the risk of late-onset neonatal
withdrawal symptoms [see WARNINGS AND PRECAUTIONS].
Baclofen given orally has been shown to increase the
incidence of omphaloceles (ventral hernias) in fetuses of rats given
approximately 13 times on a mg/kg basis, or 3 times on a mg/m² basis, the
maximum oral dose recommended for human use; this dose also caused reductions
in food intake and weight gain in the dams. This abnormality was not seen in
mice or rabbits.
At recommended oral doses, baclofen is present in human
milk. There are no human data on the effects of baclofen on milk production.
There are no adequate data on the effects of baclofen on the breastfed infant.
Withdrawal symptoms can occur in breastfed infants when maternal administration
of OZOBAX is stopped, or when breastfeeding is stopped [see WARNINGS AND
The developmental and health benefits of breastfeeding
should be considered along with the motherÃ¢â¬™s clinical need for OZOBAX and any
potential adverse effects on the breastfed infant from OZOBAX or from the
underlying maternal condition.
Safety and effectiveness in pediatric patients below the
age of 12 have not been established.
In general, dose selection for an elderly patient should
be cautious, usually starting at the low end of the dosing range, reflecting
the greater frequency of decreased hepatic, renal, or cardiac function, and of
concomitant disease or other drug therapy.
Because baclofen is primarily excreted unchanged through
the kidneys, OZOBAX should be given with caution to patients with renal
impairment, and it may be necessary to reduce the dosage.