Colax

Colax® (Colax) is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older.

Colax (Colax) is a benzodiazepine (ben-zoe-dye-AZE-eh-peen). Colax affects chemicals in the brain that may be unbalanced in people with anxiety.

Colax 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.

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

Dosing Information

A daily dose of Colax greater than 5 mg should be administered in divided doses twice daily; a 5 mg daily dose can be administered as a single dose. Dose patients according to body weight. Individualize dosing within each body weight group, based on clinical efficacy and tolerability. Each dose in Table 1 (e.g. 5 to 20 mg in ≤ 30 kg weight group) has been shown to be effective, although effectiveness increases with increasing dose. Do not proceed with dose escalation more rapidly than weekly, because serum concentrations of Colax and its active metabolite require 5 and 9 days, respectively, to reach steady-state.

Table 1: Recommended Total Daily Dosing by Weight Group

Gradual Withdrawal

As with all antiepileptic drugs and benzodiazepines, withdraw Colax gradually. Taper by decreasing the total daily dose by 5-10 mg/day on a weekly basis until discontinued.

Important Administration Instructions

Instruct patients to read the “Instructions for Use” carefully for complete directions on how to properly dose and administer Colax oral suspension.

Colax Tablet

Oral Administration

Colax tablets can be taken with or without food.

Colax tablets can be administered whole, broken in half along the score, or crushed and mixed in applesauce.

Colax

Oral Suspension

Oral Administration

Colax oral suspension can be taken with or without food.

Shake Colax

Oral Suspension well before every administration. When administering the oral suspension, use only the oral dosing syringe provided with the product. Each carton includes two syringes, but only one syringe should be used for dosing. The second oral syringe is reserved as a replacement in case the first syringe is damaged or lost. Insert the provided adapter firmly into the neck of the bottle before first use and keep the adapter in place for the duration of the usage of the bottle. To withdraw the dose, insert the dosing syringe into the adapter and invert the bottle then slowly pull back the plunger to prescribed dose. After removing the syringe from the bottle adapter, slowly squirt Colax

Oral Suspension into the corner of the patient's mouth. Replace the cap after each use. The cap fits over the adapter when the adapter is properly placed. See Colax

Oral Suspension “Instructions for Use” for complete instruction on how to properly dose and administer the Colax

Oral Suspension.

Dosage Adjustments In Geriatric Patients

Plasma concentrations at any given dose are generally higher in the

Elderly: proceed slowly with dose escalation. The starting dose should be 5 mg/day for all elderly patients. Then titrate elderly patients according to weight, but to half the dose presented in Table 1, as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on weight) may be started on day 21.

Dosage Adjustments In CYP2C19 Poor Metabolizers

In CYP2C19 poor metabolizers, levels of N-desmethylclobazam, Colax's active metabolite, will be increased. Therefore, in patients known to be CYP2C19 poor metabolizers, the starting dose should be 5 mg/day and dose titration should proceed slowly according to weight, but to half the dose presented in Table 1, as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on the weight group) may be started on day 21.

Patients With Renal Impairment

No dose adjustment is required for patients with mild and moderate renal impairment. There is no experience with Colax in patients with severe renal impairment or end stage renal disease (ESRD). It is not known if Colax or its active metabolite, N-desmethylclobazam, is dialyzable.

Dosage Adjustments In Patients With Hepatic Impairment

Colax is hepatically metabolized; however, there are limited data to characterize the effect of hepatic impairment on the pharmacokinetics of Colax. For this reason, proceed slowly with dosing escalations. For patients with mild to moderate hepatic impairment (Child-Pugh score 5-9), the starting dose should be 5 mg/day in both weight groups. Then titrate patients according to weight, but to half the dose presented in Table 1, as tolerated. If necessary and based upon clinical response, start an additional titration on day 21 to the maximum dose (20 mg/day or 40 mg/day, depending on the weight group). There is inadequate information about metabolism of Colax in patients with severe hepatic impairment. Therefore no dosing recommendation in those patients can be given.

How supplied

Dosage Forms And Strengths

Tablets: 10 mg and 20 mg with a functional score for oral administration. Each Colax 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 Colax tablet contains 10 mg or 20 mg of Colax 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

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

Store and dispense Colax 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.

Marketed by: Lundbeck, Deerfield, IL 60015, U.S.A. Revised: Dec 2014

See also:
What is the most important information I should know about Colax?

You should not use Colax if you are allergic to it.

Before taking Colax, tell your doctor if you have kidney or liver disease, or a history of depression, suicidal thoughts, or addiction to drugs or alcohol.

You may have thoughts about suicide while taking this medication. Your doctor will need to check you at regular visits.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), depressed, or have thoughts about suicide or hurting yourself.

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 Colax.

Colax may be habit-forming and should be used only by the person it was prescribed for. Keep the medication in a secure place where others cannot get to it.

Use Colax as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Colax comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Colax refilled.
• Take Colax by mouth with or without food.
• Shake well before each use.
• Use the measuring device that comes with Colax to measure your dose. Ask your pharmacist for help if you are unsure of how to measure your dose.
• Replace the cap on Colax after each use.
• If you miss a dose of Colax, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Colax.

This medication is used to prevent cavities. It makes teeth stronger and more resistant to decay caused by acid and bacteria. Talk to your dentist or doctor about the benefits and risks of this product.

This medication is not recommended for use in infants less than 6 months of age.

This medication is not recommended for use in areas where the fluoride content in the water supply is greater than 0.6 parts per million. See Notes section for more information.

How to use Colax

Take this medication by mouth, usually once daily as directed by your doctor/dentist.

The dosage is based on your age and the fluoride content in your water supply.

If you are using the liquid form of this medication, measure the dose carefully using the specially marked medicine dropper that is provided. Drops may be swallowed directly, added to a small amount of juice, or mixed with a small amount of food such as applesauce. Do not mix with food containing milk or other dairy products.

If you are using the chewable form of this medication, chew or dissolve it in the mouth before swallowing so that the teeth will also absorb the fluoride. If you are using the lozenge, place the lozenge in your mouth and allow it to dissolve. Take the chewable medication or lozenge at bedtime after brushing your teeth or as directed by your doctor/dentist. For best results, do not rinse your mouth, eat, or drink for 30 minutes after taking these forms of the medication.

Take this medication 1 hour apart from products that contain calcium, aluminum, or magnesium. Some examples include dairy products (such as milk, yogurt), antacids, laxatives, and vitamins/minerals. These products can bind with fluoride, preventing its full absorption.

Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time each day.

See also:
What other drugs will affect Colax?

Effect Of Colax On Other Drugs

Hormonal Contraceptives

Colax is a weak CYP3A4 inducer. As some hormonal contraceptives are metabolized by CYP3A4, their effectiveness may be diminished when given with Colax. Additional non-hormonal forms of contraception are recommended when using Colax.

Drugs Metabolized By CYP2D6

Colax inhibits CYP2D6. Dose adjustment of drugs metabolized by CYP2D6 may be necessary.

Effect Of Other Drugs On Colax

Strong And Moderate Inhibitors Of CYP2C19

Strong and moderate inhibitors of CYP2C19 may result in increased exposure to Ndesmethylclobazam, the active metabolite of Colax. This may increase the risk of dose-related adverse reactions. Dosage adjustment of Colax may be necessary when co-administered with strong CYP2C19 inhibitors (e.g., fluconazole, fluvoxamine, ticlopidine) or moderate CYP2C19 inhibitors (e.g., omeprazole).

CNS Depressants And Alcohol

Concomitant use of Colax with other CNS depressants may increase the risk of sedation and somnolence.

Alcohol, as a CNS depressant, will interact with Colax in a similar way and also increases Colax's maximum plasma exposure by approximately 50%. Therefore, caution patients or their caregivers against simultaneous use with other CNS depressant drugs or alcohol, and caution that the effects of other CNS depressant drugs or alcohol may be potentiated.

Drug Abuse And Dependence

Controlled Substance

Colax contains Clobazam which is a Schedule IV controlled substance.

Abuse

Colax can be abused in a similar manner as other benzodiazepines, such as diazepam.

The pharmacological profile of Colax is similar to that of other benzodiazepines listed in Schedule IV of the Controlled Substance Act, particularly in its potentiation of GABAergic transmission through its action on GABAA receptors, which leads to sedation and somnolence.

The World Health Organization epidemiology database contains reports of drug abuse, misuse, and overdoses associated with Colax.

Drug abuse is the intentional non-therapeutic use of a drug, repeatedly or even sporadically, for its rewarding psychological or physiological effects.

Dependence

Dependence

Physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood levels of the drug, and/or administration of an antagonist. In clinical trials, cases of dependency were reported following abrupt discontinuation of Colax.

The risk of dependence is present even with use of Colax at the recommended dose range over periods of only a few weeks. The risk of dependence increases with increasing dose and duration of treatment. The risk of dependence is increased in patients with a history of alcohol or drug abuse.

Withdrawal

Abrupt discontinuation of Colax causes withdrawal symptoms. As with other benzodiazepines, Colax should be withdrawn gradually.

In Colax clinical pharmacology trials in healthy volunteers, the most common withdrawal symptoms after abrupt discontinuation were headache, tremor, insomnia, anxiety, irritability, drug withdrawal syndrome, palpitations, and diarrhea.

Other withdrawal reactions to Colax reported in the literature include restlessness, panic attacks, profuse sweating, difficulty in concentrating, nausea and dry retching, weight loss, blurred vision, photophobia, and muscle pain and stiffness. In general, benzodiazepine withdrawal may cause seizures, psychosis, and hallucinations.

See also:
What are the possible side effects of Colax?

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

• Somnolence or Sedation
• Potentiation of Sedation from Concomitant Use with Central Nervous System Depressants
• Withdrawal Symptoms
• Serious Dermatological Reactions
• Physical and Psychological Dependence
• Suicidal Behavior and Ideation

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, Colax 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). Only Study 1 included a placebo group, allowing comparison of adverse reaction rates on Colax at several doses to placebo.

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

The adverse reactions associated with Colax 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 Colax treated patients (at any dose), and at a rate greater than placebo treated patients, in the randomized, double-blind, 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

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

Colax belongs to the 1,5-benzodiazepine class of drugs and is expected to have a better side-effect profile compared to older 1,4-benzodiazepines. It has been marketed as an anxiolytic since 1975 and an anticonvulsant since 1984. The oral preparation was FDA approved on October 21, 2011. An oral suspension is expected to be available in 2013.