ONFI® (clobazam) CIV Dosing Guide
Two Formulations Available
ONFI is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older.
Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.
Please see Indication and Important Safety Information, including Boxed Warning for risks from concomitant use with opioids; abuse, misuse, and addiction; and dependence and withdrawal reactions, on pages 6 - 9. Please see the accompanying full Prescribing Information, including Boxed Warning, Medication Guide, and Instructions for Use, or go to ONFI.com for more information. ONFI® (clobazam) CIV Oral Suspension Provides Dosing in a Liquid Formulation
Oral Suspension Formulation: 2.5 mg/mL1
Berry flavor Store at room Can be taken with temperature or without food
Available in a 120 mL glass bottle • Shake well before each use
Oral Suspension: Recommended Total Daily Dosing by Weight Group1
≤30 kg Body Weight >30 kg Body Weight
Starting Dose 5 mg (2 mL) 10 mg (4 mL)
Starting Day 7 10 mg (4 mL) 20 mg (8 mL)
Starting Day 14 20 mg (8 mL) 40 mg (16 mL)
The total daily dose should be divided and given twice daily. A 5 mg (2 mL) daily dose can be given once daily.
• Do not proceed with dose escalation more rapidly than weekly1 • Titration schedule and final dose should be based on response to therapy and tolerability1 • The relative bioavailability between ONFI tablets and oral suspension is approximately 100% • Advise patients to use within 90 days of first opening bottle • Store and dispense in the original bottle in an upright position • Instruct patients to read the “Instructions for Use” carefully ONFI oral suspension contains potential carbohydrates in the form of sucralose, propylene glycol, and maltitol. The potential carbohydrate content is 0.19 g/mL.2
Please see Indication and Important Safety Information, including Boxed Warning for risks from concomitant use with opioids; abuse, misuse, and addiction; and dependence and withdrawal reactions, on pages 6 - 9.
2 ONFI® (clobazam) CIV Scored Tablets Can Be Broken in Half or Administered Whole
Scored Tablets: 10 mg and 20 mg
Apply pressure on the score to split Available in 10 mg Can be taken with tablet and 20 mg scored tablets or without food (not actual size)
• Can be administered whole, halved along the score, or crushed and mixed with applesauce
Scored Tablets: Recommended Total Daily Dosing by Weight Group1
≤30 kg Body Weight >30 kg Body Weight
Starting Dose 5 mg 10 mg
Starting Day 7 10 mg 20 mg
Starting Day 14 20 mg 40 mg
The total daily dose should be divided and given twice daily. A 5 mg daily dose can be given once daily. • As with all antiepileptic drugs (AEDs) and benzodiazepines, withdraw ONFI gradually. Taper by decreasing the total daily dose by 5 - 10 mg/day on a weekly basis until discontinued1 • ONFI causes somnolence and sedation. In clinical trials, somnolence or sedation was reported at all effective doses and was dose-related. In general, somnolence and sedation begin within the first month of treatment and may diminish with continued treatment. Monitor patients for somnolence and sedation, particularly with concomitant use of other CNS depressants1
Please see Indication and Important Safety Information, including Boxed Warning for risks from concomitant use with opioids; abuse, misuse, and addiction; and dependence and withdrawal reactions, on pages 6 - 9.
3 Additional Dosing Recommendations
Recommended Dosing in Specific Populations1
Specific Populations Starting Titration Based Starting ose scalation oul Dose on Weight Day 21 rocee lowly
eriatric ne al o t e a imum nown C C oor metaboli ers mg ay recommen e osage o il to mo erate e atic im airment total aily ose or mg ay
*If necessary and based on clinical response, an additional titration to the maximum dose may be started on day 21.
• No dose adjustment is required for patients with mild and moderate renal impairment • No definitive data available in patients with severe hepatic impairment, severe renal impairment, or end-stage renal disease
Combining ONFI® (clobazam) CIV With Other AEDs1 The effects of concomitant AEDs were evaluated using data from clinical trials. • CYP3A4 inducers (phenobarbital, phenytoin, and carbamazepine) • CYP2C19 inducers (valproic acid, phenobarbital, phenytoin, and carbamazepine) • CYP2C19 inhibitors (felbamate and oxcarbazepine) Results of population pharmacokinetic analysis show that these concomitant AEDs did not significantly alter the pharmacokinetics of clobazam or N-desmethylclobazam at steady state.
Please see Indication and Important Safety Information, including Boxed Warning for risks from concomitant use with opioids; abuse, misuse, and addiction; and dependence and withdrawal reactions, on pages 6 - 9.
4 Special Considerations Opioids1 • Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death • When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists • Limit dosage and duration of concomitant use of benzodiazepines and opioids, and follow patients closely for respiratory depression and sedation CNS Depressants and Alcohol1 • Concomitant use with other CNS depressants may increase the risk of sedation and somnolence • Alcohol, as a CNS depressant, will interact with ONFI in a similar way and also increases the maximum plasma exposure of clobazam by approximately 50% Effect of ONFI® (clobazam) CIV on Other Drugs1 • ONFI is a weak CYP3A4 inducer. As some hormonal contraceptives are metabolized by CYP3A4, their effectiveness may be diminished when given with ONFI. Additional non-hormonal forms of contraception are recommended when using ONFI • ONFI is a CYP2D6 inhibitor. Dose adjustment of drugs metabolized by CYP2D6 may be necessary Effect of Other Drugs on ONFI1 • Dosage adjustment of ONFI may be necessary when coadministered with strong CYP2C19 inhibitors (eg, fluconazole, fluvoxamine, ticlopidine) or moderate CYP2C19 inhibitors (eg, omeprazole) due to increased risk of dose-related adverse events Pregnancy and Nursing1 • Based on animal data, ONFI may cause fetal harm and should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus • ONFI is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from ONFI, discontinue nursing or discontinue the drug Please see Indication and Important Safety Information, including Boxed Warning for risks from concomitant use with opioids; abuse, misuse, and addiction; and dependence and withdrawal reactions, on pages 6 - 9.
5 Indications and Usage ONFI® (clobazam) CIV is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older.
Important Safety Information
WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS See full Prescribing Information for complete boxed warning.
Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. • Reserve concomitant prescribing of these drugs for patients for whom alternative treatment options are inadequate. • Limit dosages and durations to the minimum required. • Follow patients for signs and symptoms of respiratory depression and sedation.
The use of benzodiazepines, including ONFI, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. • Before prescribing ONFI and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction.
Abrupt discontinuation or rapid dosage reduction of ONFI after continued use may precipitate acute withdrawal reactions, which can be life-threatening. • To reduce the risk of withdrawal reactions, use a gradual taper to discontinue or reduce the dosage of ONFI.
Contraindication: Hypersensitivity ONFI is contraindicated in patients with a history of hypersensitivity to the drug or its ingredients. Hypersensitivity reactions have included serious dermatological reactions.
6 Please see additional Important Safety Information on next page. 6 Important Safety Information for ONFI® (clobazam) CIV continued
WARNING: Risks from Concomitant Use with Opioids Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe ONFI concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use. Advise both patients and caregivers about the risks of respiratory depression and sedation when ONFI is used with opioids.
WARNING: Abuse, Misuse, and Addiction Abuse and misuse of benzodiazepines often (but not always) involves the use of doses greater than the maximum recommended dosage and commonly involves concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death.
Use of ONFI, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of ONFI along with monitoring for signs and symptoms of abuse, misuse, and addiction. Prescribe the lowest effective dosage; avoid or minimize concomitant use of Central Nervous System (CNS) depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. If a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate.
WARNING: Dependence and Withdrawal Reactions Patients at an increased risk of withdrawal reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages and those who have had longer durations of use.
The continued use of benzodiazepines, including ONFI, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of ONFI after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures).
In some cases, benzodiazepine users have developed protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months.
Please see additional Important Safety Information on next page. 7 Important Safety Information for ONFI® (clobazam) CIV continued
Potentiation of Sedation from Concomitant Use with CNS Depressants ONFI has a CNS depressant effect. Caution patients or their caregivers against simultaneous use with other CNS depressant drugs or alcohol, and that the effects of other CNS depressant drugs or alcohol may be potentiated.
Somnolence or Sedation ONFI causes somnolence and sedation. In clinical trials, somnolence or sedation was reported at all effective doses and was dose-related. In general, somnolence and sedation begin within the first month of treatment and may diminish with continued treatment. Monitor patients for somnolence and sedation, particularly with concomitant use of other CNS depressants. Caution patients against engaging in hazardous activities that require mental alertness, such as operating dangerous machinery or motor vehicles, until the effect of ONFI is known.
Serious Dermatological Reactions Serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with ONFI in both children and adults during the post-marketing period. Discontinue ONFI at the first sign of rash, unless the rash is clearly not drug-related.
Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including ONFI, increase the risk of suicidal thoughts or behavior in patients. Inform patients, their caregivers, and families of the risk and advise them to monitor and report any emergence or worsening of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts of self-harm. If these symptoms occur, consider whether it may be related to the AED or illness, because epilepsy itself can increase these risks.
Pregnancy, Registry and Nursing Mothers • Based on animal data, ONFI may cause fetal harm and should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. º Talk to your patients about enrolling in the North American Antiepileptic Drug Pregnancy Registry; encourage them to call 1-888-233-2334 or visit http://www.aedpregnancyregistry.org/.
8 Please see additional Important Safety Information on next page. 8 Important Safety Information for ONFI® (clobazam) CIV continued
• ONFI is excreted in human milk. Because of the potential for serious adverse reactions from ONFI in nursing infants, discontinue nursing or discontinue the drug.
Adverse Reactions The most commonly observed adverse reactions reported in an LGS randomized, double-blind, placebo-controlled, parallel group clinical trial of patients who received clobazam as adjunctive therapy (≥10% in any treatment group and at least 5% greater than placebo, respectively) were somnolence or sedation (32% vs. 15%), somnolence (25% vs. 12%), pyrexia (17% vs. 3%), lethargy (15% vs. 5%), aggression (14% vs. 5%), drooling (14% vs. 3%), irritability (11% vs. 5%), ataxia (10% vs. 3%), and constipation (10% vs. 0%).
Please see the accompanying full Prescribing Information, including Boxed Warning, Medication Guide, and Instructions for Use, or go to ONFI.com for more information.
References: 1. ONFI [package insert]. Deerfield, IL: Lundbeck.2. Data on file. Lundbeck, Deerfield, IL.
9 Contact your account manager or visit ONFIhcp.com to learn more.
©2021 Lundbeck. All rights reserved. ONFI is a registered trademark of Lundbeck. CLB-B-100073v2
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3DJHRI $GYLVHSDWLHQWVWKDWWKHUHLVDSUHJQDQF\H[SRVXUHUHJLVWU\WKDWFROOHFWVLQIRUPDWLRQ DERXWWKHVDIHW\RIDQWLHSLOHSWLFGUXJVGXULQJSUHJQDQF\>VHH8VHLQ6SHFLILF 3RSXODWLRQV @ 1XUVLQJ &RXQVHOSDWLHQWVWKDW21),LVH[FUHWHGLQEUHDVWPLON,QVWUXFWSDWLHQWVWRQRWLI\WKHLU SK\VLFLDQLIWKH\DUHEUHDVWIHHGLQJRULQWHQGWREUHDVWIHHGGXULQJWKHUDS\DQGFRXQVHO QXUVLQJPRWKHUVWRREVHUYHWKHLULQIDQWVIRUSRRUVXFNLQJDQGVRPQROHQFH>VHH8VHLQ 6SHFLILF3RSXODWLRQV @ 7DEOHWVPDQXIDFWXUHGE\ &DWDOHQW3KDUPD6ROXWLRQV//& :LQFKHVWHU.< 86$ 2UDOVXVSHQVLRQPDQXIDFWXUHGE\ 5RVHPRQW3KDUPDFHXWLFDOV/WG /HHGV:HVW ONFI is a registered trademark of Lundbeck 3DJH RI 0(',&$7,21*8,'( 21),(ON-fee) FORED]DP WDEOHWVDQGRUDOVXVSHQVLRQ&,9 :KDWLVWKHPRVWLPSRUWDQWLQIRUPDWLRQ,VKRXOGNQRZDERXW21)," x 21),LVDEHQ]RGLD]HSLQHPHGLFLQH7DNLQJEHQ]RGLD]HSLQHVZLWKRSLRLGPHGLFLQHVDOFRKRORURWKHUFHQWUDO QHUYRXVV\VWHP &16 GHSUHVVDQWV LQFOXGLQJVWUHHWGUXJV FDQFDXVHVHYHUHGURZVLQHVVEUHDWKLQJ SUREOHPV UHVSLUDWRU\GHSUHVVLRQ FRPDDQGGHDWK*HWHPHUJHQF\KHOSULJKWDZD\LIDQ\RIWKHIROORZLQJ KDSSHQV o VKDOORZRUVORZHGEUHDWKLQJ o EUHDWKLQJVWRSV ZKLFKPD\OHDGWRWKHKHDUWVWRSSLQJ o H[FHVVLYHVOHHSLQHVV VHGDWLRQ 'RQRWGULYHRURSHUDWHKHDY\PDFKLQHU\XQWLO\RXNQRZKRZWDNLQJ21),ZLWKRSLRLGVDIIHFWV\RX x 5LVNRIDEXVHPLVXVHDQGDGGLFWLRQ7KHUHLVDULVNRIDEXVHPLVXVHDQGDGGLFWLRQZLWKEHQ]RGLD]HSLQHV LQFOXGLQJ21),ZKLFKFDQOHDGWRRYHUGRVHDQGVHULRXVVLGHHIIHFWVLQFOXGLQJFRPDDQGGHDWK o 6HULRXVVLGHHIIHFWVLQFOXGLQJFRPDDQGGHDWKKDYHKDSSHQHGLQSHRSOHZKRKDYHDEXVHGRUPLVXVHG EHQ]RGLD]HSLQHVLQFOXGLQJ21),7KHVHVHULRXVVLGHHIIHFWVPD\DOVRLQFOXGHGHOLULXPSDUDQRLDVXLFLGDO WKRXJKWVRUDFWLRQVVHL]XUHVDQGGLIILFXOW\EUHDWKLQJ&DOO\RXUKHDOWKFDUHSURYLGHURUJRWRWKHQHDUHVW KRVSLWDOHPHUJHQF\URRPULJKWDZD\LI\RXJHWDQ\RIWKHVHVHULRXVVLGHHIIHFWV o 3DJHRI :KDWDUHWKHSRVVLEOHVLGHHIIHFWVRI21)," 21),PD\FDXVHVHULRXVVLGHHIIHFWVLQFOXGLQJ 6HH³:KDWLVWKHPRVWLPSRUWDQWLQIRUPDWLRQ,VKRXOGNQRZ DERXW21),"´ 7KHPRVWFRPPRQVLGHHIIHFWVRI21),LQFOXGH x VOHHSLQHVV x GURROLQJ x FRQVWLSDWLRQ xFRXJK x SDLQZLWKXULQDWLRQ x IHYHU x DFWLQJDJJUHVVLYHEHLQJDQJU\RUYLROHQW x GLIILFXOW\VOHHSLQJ x VOXUUHGVSHHFK x WLUHGQHVV x SUREOHPVZLWKEUHDWKLQJ 7KHVHDUHQRWDOOWKHSRVVLEOHVLGHHIIHFWVRI21),&DOO\RXUGRFWRUIRUPHGLFDODGYLFHDERXWVLGHHIIHFWV 3DJHRI Instructions for Use ONFI® (ON-fee) (clobazam) Oral Suspension, CIV Read this Instructions for Use before using ONFI oral suspension and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or treatment. Prepare ONFI Oral Suspension Dose You will need the following supplies: See Figure A x ONFI oral suspension bottle x Bottle adapter x Oral dosing syringe (2 dosing syringes are included in the ONFI oral suspension box). x Use only 1 syringe to take your dose of ONFI oral suspension. If you lose or damage the syringe, or cannot read the markings, use the other syringe. Figure A Step 1. Remove the ONFI oral suspension bottle, bottle adapter, and 1 syringe from the box. Step 2. Shake the bottle well before each use. See Figure B 3DJHRI Figure B Step 3. Uncap the bottle and firmly insert the bottle adapter into the bottle until the adapter top is even with the bottle top. See Figure C Figure C Once the bottle adapter is in place, it should not be removed. Step 4. Check your dose in milliliters (mL) as prescribed by your healthcare provider. Find this number on the syringe. Do not take more than the prescribed total dose in 1 day. See Figure D 3DJHRI Figure D Step 5. Push the plunger all the way down and then insert the syringe into the upright bottle through the opening in the bottle adapter. See Figure E Figure E Step 6. With the syringe in place, turn the bottle upside down. Pull the plunger to the number of mLs needed (the amount of liquid medicine in Step 4). See Figure F 3DJHRI Figure F Measure the mLs of medicine using the black ring on the white plunger. See Figure G Figure G 3DJHRI Step 7. Remove the syringe from the bottle adapter. Slowly squirt ONFI oral suspension directly into the corner of your mouth or your child’s mouth until all of the liquid medicine in the syringe is given. See Figure H Figure H Step 8. Cap the bottle tightly with the adapter in place. If the cap does not fit securely, check to see if the adapter is fully inserted. See Figure I x Store and dispense ONFI oral suspension in its original bottle in an upright position at 68°F to 77°F (20°C to 25°C). x Use ONFI oral suspension within 90 days of first opening bottle. x After 90 days safely throw away any ONFI oral suspension that has not been used. 3DJHRI Figure I Step 9. Wash the oral syringe after each use. x To clean the oral syringe, take apart by removing the plunger completely. Pull plunger straight out of the barrel. x The barrel and plunger can be washed with soap and water, rinsed, and allowed to dry. x Do not wash the oral syringe in the dishwasher. This Instruction for Use has been approved by the U.S. Food and Drug Administration. Marketed by: Lundbeck, Deerfield, IL 60015, U.S.A. ONFI is a registered trademark of Lundbeck 12/2016 3DJHRI