NDC 69528-301 Ozobax

Baclofen

NDC Product Code 69528-301

NDC 69528-301-16

Package Description: 473 mL in 1 BOTTLE

NDC Product Information

Ozobax with NDC 69528-301 is a a human prescription drug product labeled by Metacel Pharmaceuticals, Llc. The generic name of Ozobax is baclofen. The product's dosage form is solution and is administered via oral form.

Labeler Name: Metacel Pharmaceuticals, Llc

Dosage Form: Solution - A clear, homogeneous liquid1 dosage form that contains one or more chemical substances dissolved in a solvent or mixture of mutually miscible solvents.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Ozobax Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • BACLOFEN 5 mg/5mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • ANHYDROUS CITRIC ACID (UNII: XF417D3PSL)
  • GLYCERIN (UNII: PDC6A3C0OX)
  • METHYLPARABEN (UNII: A2I8C7HI9T)
  • PROPYLPARABEN (UNII: Z8IX2SC1OH)
  • TRISODIUM CITRATE DIHYDRATE (UNII: B22547B95K)
  • SUCRALOSE (UNII: 96K6UQ3ZD4)
  • WATER (UNII: 059QF0KO0R)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • GABA A Agonists - [MoA] (Mechanism of Action)
  • GABA B Agonists - [MoA] (Mechanism of Action)
  • gamma-Aminobutyric Acid-ergic Agonist - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Metacel Pharmaceuticals, Llc
Labeler Code: 69528
FDA Application Number: NDA208193 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 09-18-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

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Ozobax Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

OZOBAX is indicated for the treatment of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity.OZOBAX may also be of some value in patients with spinal cord injuries and other spinal cord diseases.Limitations of UseOZOBAX is not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders.

Initiate OZOBAX with a low dosage, preferably in divided doses, administered orally. The following gradually increasing dosage regimen is suggested, but should be adjusted based on clinical response and tolerability:5 mL (5 mg) three times a day for three days 10 mL (10 mg) three times a day for three days 15 mL (15 mg) three times a day for three days 20 mL (20 mg) three times a day for three daysAdditional increases may be necessary up to the maximum recommended dosage of 80 mg daily (20 mg four times a day).

2.2 Discontinuation Of Ozobax

When discontinuing OZOBAX, reduce the dosage slowly and avoid abrupt withdrawn from the drug to help minimize the risk of adverse reactions [see Warnings and Precautions (5.1)].

3 Dosage Forms And Strengths

Oral Solution: 5 mg/5 mL baclofen as a clear, colorless solution with a grape aroma

4 Contraindications

OZOBAX is contraindicated in patients with hypersensitivity to baclofen.

5.1 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 withdrawal.

5.2 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.

5.3 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 (6.1)]. 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.

5.4 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.

5.5 Exacerbation Of Psychotic Disorders, Schizophrenia, Or Confusional States

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 administration.

5.6 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.

5.7 Exacerbation Of Epilepsy

OZOBAX should be used with caution in patients with epilepsy. Deterioration in seizure control has been reported in patients taking baclofen.

5.8 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.

5.9 Ovarian Cysts

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.

6 Adverse Reactions

  • The following clinically significant adverse reactions are described elsewhere in the labeling:Adverse Reactions from Abrupt Withdrawal of OZOBAX [see Warnings and Precautions (5.1)]Neonatal Withdrawal Symptoms [see Warnings and Precautions (5.2)]Drowsiness and Sedation [see Warnings and Precautions (5.3)]Poor Tolerability in Stroke Patients [see Warnings and Precautions (5.4)]Exacerbation of Psychotic Disorders, Schizophrenia, or Confusional States [see Warnings and Precautions (5.5)]Exacerbation of Autonomic Dysreflexia [see Warnings and Precautions (5.6)]Exacerbation of Epilepsy [see Warnings and Precautions (5.7)]Posture and Balance Effects [see Warnings and Precautions (5.8)]Ovarian Cysts [see Warnings and Precautions (5.9)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.The most common adverse reaction is transient drowsiness. In one controlled study of 175 patients, transient drowsiness was observed in 63% of those receiving baclofen compared to 36% of those in the placebo group. Other common adverse reactions (up to 15%) are dizziness and weakness. Adverse reactions with a frequency of ≥1% are listed in Table 1.Table 1. Common (≥1%) Adverse Reactions in Patients Treated with Baclofen for Spasticity ADVERSE REACTION  PERCENT Drowsiness 10-63%Dizziness  5-15%Weakness  5-15%Nausea  4-12% Confusion  1-11% Hypotension  0-9% Headache  4-8% Insomnia  2-7% Constipation  2-6% Urinary Frequency  2-6% Fatigue     2-4% The following adverse reactions not included in Table 1, classified by body system, were also reported:Neuropsychiatric: euphoria, excitement, depression, hallucinations, paresthesia, muscle pain, tinnitus, slurred speech, coordination disorder, tremor, rigidity, dystonia, ataxia, blurred vision, nystagmus, strabismus, miosis, mydriasis, diplopia, dysarthria, epileptic seizureCardiovascular: dyspnea, palpitation, chest pain, syncopeGastrointestinal: dry mouth, anorexia, taste disorder, abdominal pain, vomiting, diarrhea, and positive test for occult blood in stoolGenitourinary: enuresis, urinary retention, dysuria, impotence, inability to ejaculate, nocturia, hematuriaOther: rash, pruritus, ankle edema, excessive perspiration, weight gain, nasal congestionThe following laboratory tests have been found to be abnormal in patients receiving baclofen: increased SGOT, elevated alkaline phosphatase, and elevation of blood sugar.

7.1 Cns Depressants And Alcohol

OZOBAX can cause CNS depression, including drowsiness and sedation, which may be additive when used concomitantly with other CNS depressants or alcohol [see Warnings and Precautions (5.3)].

8.1 Pregnancy

Risk SummaryThere 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.Clinical ConsiderationsFetal/Neonatal adverse reactionsOzobax may increase the risk of late-onset neonatal withdrawal symptoms [see Warnings and Precautions (5.2)].DataAnimal DataBaclofen 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.

8.2 Lactation

Risk SummaryAt 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 Precautions (5.2)].The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for OZOBAX and any potential adverse effects on the breastfed infant from OZOBAX or from the underlying maternal condition.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients below the age of 12 have not been established.

8.5 Geriatric Use

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.

8.6 Renal Impairment

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.

10.1 Symptoms Of Baclofen Overdose

Patients may present in coma or with progressive drowsiness, lightheadedness, dizziness, somnolence, accommodation disorders, respiratory depression, seizures, or hypotonia progressing to loss of consciousness.

10.2 Treatment For Overdose

The treatment of baclofen overdose includes gastric decontamination, maintaining an adequate airway and respirations.

11 Description

OZOBAX (baclofen) oral solution is a gamma-aminobutyric acid (GABA-ergic) agonist available as 5 mg/5 mL solution for oral administration. Its chemical name is 4-amino-3-(4-chlorophenyl)-butanoic acid, and its structural formula is:Molecular formula is C1OH12ClNO2.Molecular Weight is 213.66.Baclofen USP is a white to off-white, odorless or practically odorless crystalline powder. It is slightly soluble in water, very slightly soluble in methanol, and insoluble in chloroform.The OZOBAX (baclofen) oral solution inactive ingredients are: citric acid anhydrous, glycerin, natural grape flavor, methylparaben, propylparaben, purified water, sodium citrate dihydrate, and sucralose. May also contain sodium hydroxide or hydrochloric acid for pH adjustment.

12.1 Mechanism Of Action

The precise mechanism of action of baclofen is not fully understood. Baclofen inhibits both monosynaptic and polysynaptic reflexes at the spinal level, possibly by decreasing excitatory neurotransmitter release from afferent terminals, although actions at supraspinal sites may also occur and contribute to its clinical effect. Baclofen is a structural analog of the inhibitory neurotransmitter gamma- aminobutyric acid (GABA), and may exert its effects by stimulation of the GABAB receptor subtype.

12.2 Pharmacodynamics

Baclofen has been shown to have general CNS depressant properties, as indicated by the production of sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression [see Warnings and Precautions (5.3), Adverse Reactions (6.1), and Overdosage (10.1)].

12.3 Pharmacokinetics

A pharmacokinetic study in heathy adult male subjects under fasting conditions at 20 mg dose level demonstrated similar bioavailability for baclofen oral solution and oral tablets. The peak plasma concentrations were achieved in about 0.75 hours from oral solution and the apparent elimination half-life is about 5.7 hours. Baclofen is excreted primarily by the kidney in unchanged form, and there is relatively large intersubject variation in absorption and/or elimination.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

CarcinogenesisNo 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.MutagenesisGenetic toxicology assays have not been conducted for baclofen. Impairment of FertilityStudies to evaluate the effects of baclofen on fertility have not been conducted.

14 Clinical Studies

The efficacy of OZOBAX is based upon a bioavailability study in healthy adults comparing baclofen oral tablets to OZOBAX [see Clinical Pharmacology (12.3)].

16.1 How Supplied

OZOBAX (baclofen) Oral Solution contains 5 mg/5 mL baclofen. It is a clear, colorless solution with a grape aroma and is supplied in bottles of 473 mL, NDC 69528-301-16.

16.2 Storage And Handling

Must be refrigerated. Store at 2°C to 8°C (36°F to 46°F). Dispense in a tight, light-resistant container with a child-resistant closure.

17 Patient Counseling Information

Administration InstructionsInstruct patients or caregivers to use an oral dosing syringe to correctly measure the prescribed amount of medication. Inform patients that oral dosing syringes may be obtained from their pharmacy.Risks Related to Sudden Withdrawal of OZOBAXAdvise patients and caregivers not to discontinue use of OZOBAX without consulting with their healthcare provider because sudden withdrawal of OZOBAX can result in serious complications that include hallucinations, seizures, high fever, confusion, muscle stiffness, multiple organ-system failure, and death [see Warnings and Precautions (5.1)]. Inform patients that early symptoms of OZOBAX withdrawal may include increased spasticity, itching, and tingling of extremities.Neonatal Withdrawal SymptomsAdvise patients to notify their healthcare provider if they are pregnant, plan to become pregnant, or plan to breastfeed [see Warnings and Precautions (5.2) and Use in Specific Populations (8.2)].Increased Risk of Drowsiness with Alcohol and Other CNS DepressantsAdvise patients that OZOBAX may cause drowsiness, and that they should avoid the operation of automobiles or other dangerous machinery, or activities made hazardous by decreased alertness when starting OZOBAX or increasing the dose until they know how the drug affects them [see Warnings and Precautions (5.3)]. Inform patients and their caregivers that the drowsiness associated with OZOBAX use can be worsened by alcohol and other CNS depressants. Advise patients to read all medicine labels carefully, and to tell their healthcare provider about all prescription and nonprescription drugs they may use.StorageInstruct patients to store OZOBAX in the refrigerator [see How Supplied/Storage and Handling (16.2)].Manufactured by:Entreprises Importfab, Inc.50 Hymus Blvd.Pointe-Claire, QC, Canada H9R 1C9Manufactured for:Metacel Pharmaceuticals, LLCAthens, GA 30601

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