Clobazam Tablets and Oral Suspension

Name: Clobazam Tablets and Oral Suspension

Description

Table 4. Description

Proprietary Name: ONFI®
Established Name: Clobazam
Dosage Forms: Tablet and Oral Suspension
Route of Administration: Oral
Established Pharmacologic Class of Drug: Benzodiazepine
Chemical Name: 7-Chloro-1-methyl-5-phenyl-1H-1,5 benzodiazepine-2,4(3H,5H)-dione
Structural Formula:

Clobazam is a white or almost white, crystalline powder with a slightly bitter taste; is slightly soluble in water, sparingly soluble in ethanol, and freely soluble in methylene chloride. The melting range of clobazam is from 182°C to 185°C. The molecular formula is C16H13O2N2Cl and the molecular weight is 300.7.

Each ONFI tablet contains 10 mg or 20 mg of clobazam. Tablets also contain as inactive ingredients: corn starch, lactose monohydrate, magnesium stearate, silicon dioxide, and talc.

ONFI is also available for oral administration as an off-white suspension containing clobazam at a concentration of 2.5 mg/mL. Inactive ingredients include magnesium aluminum silicate, xanthan gum, citric acid monohydrate, disodium hydrogen phosphate dihydrate, simethicone emulsion, polysorbate 80, methylparaben, propylparaben, propylene glycol, sucralose, maltitol solution, berry flavor, purified water.

How supplied

Dosage Forms And Strengths

Tablets

10 mg and 20 mg with a functional score for oral administration. Each ONFI tablet is a white to off-white, oval tablet with a functional score on one side and either a “1” and “0” or a “2” and “0” debossed on the other side.

Oral Suspension

2.5 mg/mL for oral administration. Each bottle contains 120 mL of an off-white suspension.

Storage And Handling

Each ONFI tablet contains 10 mg or 20 mg of clobazam and is a white to off-white, oval tablet with a functional score on one side and either a “1” and “0” or a “2” and “0” debossed on the other side.

NDC 67386-314-01: 10 mg scored tablet, Bottles of 100
NDC 67386-315-01: 20 mg scored tablet, Bottles of 100

ONFI oral suspension is a berry flavored off-white liquid supplied in a bottle with childresistant closure. The oral suspension is packaged with a dispenser set which contains two calibrated oral dosing syringes and a bottle adapter.

Store and dispense ONFI oral suspension in its original bottle in an upright position. Use within 90 days of first opening the bottle, then discard any remainder.

NDC 67386-313-21: 2.5 mg/mL supplied in a bottle containing 120 mL of suspension.

Store tablets and oral suspension at 20°C to 25°C (68°F to 77°F). See USP controlled room temperature.

Tablets manufactured by:: Catalent Pharma Solutions, LLC, Winchester, KY 40391, U.S.A. Oral suspension Manufactured by: Rosemont Pharmaceuticals, Ltd. Leeds, West Yorkshire LS11 9XE, U.K. Revised: Dec 2016

Side effects

Clinically significant adverse reactions that appear in other sections of the labeling include the following:

  • Risks from Concomitant Use with Opioids [see WARNINGS AND PRECAUTIONS]
  • Potentiation of Sedation from Concomitant Use with Central Nervous System Depressants [see WARNINGS AND PRECAUTIONS]
  • Somnolence or Sedation [see WARNINGS AND PRECAUTIONS]
  • Withdrawal Symptoms [see WARNINGS AND PRECAUTIONS]
  • Serious Dermatological Reactions [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS]
  • Physical and Psychological Dependence [see WARNINGS AND PRECAUTIONS]
  • Suicidal Behavior and Ideation [see WARNINGS AND PRECAUTIONS]

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.

During its development for the adjunctive treatment of seizures associated with LGS, ONFI was administered to 333 healthy volunteers and 300 patients with a current or prior diagnosis of LGS, including 197 patients treated for 12 months or more. The conditions and duration of exposure varied greatly and included single- and multipledose clinical pharmacology studies in healthy volunteers and two double-blind studies in patients with LGS (Study 1 and 2) [see Clinical Studies]. Only Study 1 included a placebo group, allowing comparison of adverse reaction rates on ONFI at several doses to placebo.

Adverse Reactions Leading To Discontinuation In An LGS Placebo Controlled Clinical Trial (Study 1)

The adverse reactions associated with ONFI treatment discontinuation in ≥1% of patients in decreasing order of frequency included lethargy, somnolence, ataxia, aggression, fatigue, and insomnia.

Most Common Adverse Reactions In An LGS Placebo Controlled Clinical Trial (Study 1)

Table 3 lists the adverse reactions that occurred in ≥5% of ONFI-treated patients (at any dose), and at a rate greater than placebo-treated patients, in the randomized, doubleblind, placebo-controlled, parallel group clinical study of adjunctive AED therapy for 15 weeks (Study 1).

Table 3. Adverse Reactions Reported for ≥5% of Patients and More Frequently than Placebo in Any Treatment Group

  Placebo
N=59
%
ONFI Dose Level All ONFI
N=179
%
Lowa
N=58
%
Mediumb
N=62
%
Highc
N=59
%
Gastrointestinal Disorders
  Vomiting 5 9 5 7 7
  Constipation 0 2 2 10 5
  Dysphagia 0 0 0 5 2
General Disorders and Administration Site Conditions
  Pyrexia 3 17 10 12 13
  Irritability 5 3 11 5 7
  Fatigue 2 5 5 3 5
Infections and Infestations
  Upper respiratory tract infection 10 10 13 14 12
  Pneumonia 2 3 3 7 4
  Urinary tract infection 0 2 5 5 4
  Bronchitis 0 2 0 5 2
Metabolism and Nutrition Disorders
  Decreased appetite 3 3 0 7 3
  Increased appetite 0 2 3 5 3
Nervous System Disorders
  Somnolence or Sedation 15 17 27 32 26
    Somnolence 12 16 24 25 22
    Sedation 3 2 3 9 5
  Lethargy 5 10 5 15 10
  Drooling 3 0 13 14 9
  Ataxia 3 3 2 10 5
  Psychomotor hyperactivity 3 3 3 5 4
  Dysarthria 0 2 2 5 3
Psychiatric Disorders
  Aggression 5 3 8 14 8
  Insomnia 2 2 5 7 5
Respiratory Disorders
  Cough 0 3 5 7 5
aMaximum daily dose of 5 mg for ≤30 kg body weight; 10 mg for >30 kg body weight
bMaximum daily dose of 10 mg for ≤30 kg body weight; 20 mg for >30 kg body weight
cMaximum daily dose of 20 mg for ≤30 kg body weight; 40 mg for >30 kg body weight

Post Marketing Experience

These reactions are reported voluntarily from a population of uncertain size; therefore, it is not possible to estimate their frequency or establish a causal relationship to drug exposure. Adverse reactions are categorized by system organ class.

Blood Disorders: Anemia, eosinophilia, leukopenia, thrombocytopenia

Eye Disorders: Diplopia, vision blurred

Gastrointestinal Disorders: Abdominal distention

General Disorders and Administration Site Conditions: Hypothermia

Investigations: Hepatic enzyme increased

Musculoskeletal: Muscle spasms

Psychiatric Disorders: Agitation, anxiety, apathy, confusional state, depression, delirium, delusion, hallucination

Renal and Urinary Disorders: Urinary retention

Respiratory Disorders: Aspiration, respiratory depression

Skin and Subcutaneous Tissue Disorders: Rash, urticaria, angioedema, and facial and lip edema

What is clobazam (onfi)?

Clobazam is a benzodiazepine (ben-zoe-dye-AZE-eh-peen). Clobazam affects chemicals in the brain that may become unbalanced and cause anxiety.

Clobazam is used in combination with other medications to treat seizures caused by Lennox-Gastaut syndrome, a severe form of childhood epilepsy that also causes developmental and behavior problems.

Clobazam may also be used for purposes not listed in this medication guide.

What happens if i miss a dose (onfi)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What should i avoid while taking clobazam (onfi)?

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Do not drink alcohol while taking clobazam.

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