Niravam

Name: Niravam

Niravam Overview

Niravam is a prescription medication used to treat anxiety and panic disorders. Niravam belongs to a group of drugs called benzodiazepines. It works by lowering abnormal excitement in the brain.

Niravam comes as an orally disintegrating tablet and is usually taken 3 times a day. It is placed on the tongue where it will disintegrate and be swallowed with saliva. Common side effects of Niravam include low blood pressure and coordination problems. Niravam can also cause drowsiness. Do not drive or operate heavy machinery until you know how Niravam affects you.

Niravam Drug Class

Niravam is part of the drug class:

  • Anxiolytic Benzodiazepine

Niravam and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed. Benzodiazepines are known to be excreted in human milk. Because of the possibility for adverse reactions in nursing infants from Niravam, a choice should be made whether to stop nursing or to stop use of Niravam. Determining the importance of the drug to the mother should be considered.

How should I take Niravam (alprazolam)?

Follow all directions on your prescription label. Never use alprazolam in larger amounts, or for longer than prescribed. Tell your doctor if the medicine seems to stop working as well in treating your symptoms.

Alprazolam may be habit-forming. Never share this medicine with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

Misuse of habit-forming medicine can cause addiction, overdose, or death. Selling or giving away this medicine is against the law.

Do not swallow the orally disintegrating tablet whole. Allow it to dissolve in your mouth without chewing.

Do not crush, chew, or break an extended-release tablet. Swallow it whole.

Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Call your doctor if this medicine seems to stop working as well in treating your panic or anxiety symptoms.

Do not stop using alprazolam suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using alprazolam.

If you use this medicine long-term, you may need frequent medical tests.

Store at room temperature away from moisture and heat.

Keep track of the amount of medicine used from each new bottle. Alprazolam is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

What are some things I need to know or do while I take Niravam?

  • Tell all of your health care providers that you take Niravam. This includes your doctors, nurses, pharmacists, and dentists.
  • This medicine may be habit-forming with long-term use.
  • If you have been taking this medicine for a long time or at high doses, it may not work as well and you may need higher doses to get the same effect. This is known as tolerance. Call your doctor if Niravam stops working well. Do not take more than ordered.
  • Avoid driving and doing other tasks or actions that call for you to be alert or have clear eyesight until you see how this medicine affects you.
  • Avoid drinking alcohol while taking Niravam.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
  • If you start or stop smoking, talk with your doctor. How much drug you take may need to be changed.
  • If you are taking digoxin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with this medicine.
  • If you have phenylketonuria (PKU), talk with your doctor. Some products have phenylalanine.
  • If you are 65 or older, use Niravam with care. You could have more side effects.
  • If you have been taking this medicine on a regular basis and you stop it all of a sudden, you may have signs of withdrawal. Do not stop taking Niravam all of a sudden without calling your doctor. Tell your doctor if you have any bad effects.
  • This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this medicine, call your doctor right away.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low mood (depression), thoughts of killing yourself, nervousness, emotional ups and downs, thinking that is not normal, anxiety, or lack of interest in life.
  • Change in balance.
  • Shortness of breath.
  • A burning, numbness, or tingling feeling that is not normal.
  • Chest pain or pressure or a fast heartbeat.
  • A heartbeat that does not feel normal.
  • Very bad dizziness or passing out.
  • Feeling confused.
  • Hallucinations (seeing or hearing things that are not there).
  • Memory problems or loss.
  • Trouble speaking.
  • Feeling very tired or weak.
  • Twitching.
  • Shakiness.
  • Dark urine or yellow skin or eyes.
  • Trouble passing urine.
  • Blurred eyesight.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Niravam?

  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Niravam - Clinical Pharmacology

Mechanism of Action

The exact mechanism of action of alprazolam is unknown. Benzodiazepines bind to gamma aminobutyric acid (GABA) receptors in the brain and enhance GABA-mediated synaptic inhibition; such actions may be responsible for the efficacy of alprazolam in anxiety disorder and panic disorder.

Pharmacokinetics

Absorption

Following oral administration, alprazolam is readily absorbed. The peak plasma concentration is reached about 1.5 to 2 hours after administration of Niravam given with or without water. When taken with water, mean Tmax occurs about 15 minutes earlier than when taken without water with no change in Cmax or AUC. Plasma levels are proportional to the dose given; over the dose range of 0.5 mg to 3.0 mg, peak levels of 8.0 to 37 ng/mL are observed. The elimination half-life of alprazolam is approximately 12.5 hours (range 7.9 - 19.2 hours) after administration of Niravam in healthy adults.

Food decreased the mean Cmax by about 25% and increased the mean Tmax by 2 hours from 2.2 hours to 4.4 hours after the ingestion of a high-fat meal. Food did not affect the extent of absorption (AUC) or the elimination half-life.

Distribution

In vitro, alprazolam is bound (80 percent) to human serum protein. Serum albumin accounts for the majority of the binding.

Metabolism/Elimination

Alprazolam is extensively metabolized in humans, primarily by cytochrome P450 3A4 (CYP3A4), to two major metabolites in the plasma: 4-hydroxyalprazolam and α-hydroxyalprazolam. A benzophenone derived from alprazolam is also found in humans. Their half-lives appear to be similar to that of alprazolam. The plasma concentrations of 4-hydroxyalprazolam and α-hydroxyalprazolam relative to unchanged alprazolam concentration were always less than 4%. The reported relative potencies in benzodiazepine receptor binding experiments and in animal models of induced seizure inhibition are 0.20 and 0.66, respectively, for 4-hydroxyalprazolam and α-hydroxyalprazolam. Such low concentrations and the lesser potencies of 4-hydroxyalprazolam and α-hydroxyalprazolam suggest that they are unlikely to contribute much to the pharmacological effects of alprazolam. The benzophenone metabolite is essentially inactive.

Alprazolam and its metabolites are excreted primarily in the urine.

Special Populations

Changes in the absorption, distribution, metabolism and excretion of benzodiazepines have been reported in a variety of disease states including alcoholism, impaired hepatic function and impaired renal function. Changes have also been demonstrated in geriatric patients. A mean half-life of alprazolam of 16.3 hours has been observed in healthy elderly subjects (range: 9.0 - 26.9 hours, n=16) compared to 11.0 hours (range: 6.3 - 15.8 hours, n=16) in healthy adult subjects. In patients with alcoholic liver disease, the half-life of alprazolam ranged between 5.8 and 65.3 hours (mean: 19.7 hours, n=17) as compared to between 6.3 and 26.9 hours (mean=11.4 hours, n=17) in healthy subjects. In an obese group of subjects, the half-life of alprazolam ranged between 9.9 and 40.4 hours (mean=21.8 hours, n=12) as compared to between 6.3 and 15.8 hours (mean=10.6 hours, n=12) in healthy subjects.

Because of its similarity to other benzodiazepines, it is assumed that alprazolam undergoes transplacental passage and that it is excreted in human milk.

Race Maximal concentrations (Cmax) and half-life of alprazolam are approximately 15% and 25% higher in Asians compared to Caucasians.

Pediatrics The pharmacokinetics of alprazolam in pediatric patients have not been studied. 

Gender Gender has no effect on the pharmacokinetics of alprazolam.

Cigarette Smoking Alprazolam concentrations may be reduced by up to 50% in smokers compared to non-smokers.

Drug-Drug Interactions

Alprazolam is primarily eliminated by metabolism via cytochrome P450 3A (CYP3A). Most of the interactions that have been documented with alprazolam are with drugs that inhibit or induce CYP3A.

Compounds that are potent inhibitors of CYP3A would be expected to increase plasma alprazolam concentrations. Drug products that have been studied in vivo, along with their effect on increasing alprazolam AUC, are as follows: ketoconazole, 3.98 fold; itraconazole, 2.70 fold; nefazodone, 1.98 fold; fluvoxamine, 1.96 fold; and erythromycin, 1.61 fold [see Contraindications (4), Warnings and Precautions (5.7), and Drug Interactions (7)].

CYP3A inducers would be expected to decrease alprazolam concentrations and this has been observed in vivo. The oral clearance of alprazolam (given in a 0.8 mg single dose) was increased from 0.90 ± 0.21 mL/min/kg to 2.13 ± 0.54 mL/min/kg and the elimination t1/2 was shortened (from 17.1 ± 4.9 to 7.7 ± 1.7 h) following administration of 300 mg/day carbamazepine for 10 days [see Drug Interactions (7)]. However, the carbamazepine dose used in this study was fairly low compared to the recommended doses (1000 mg - 1200 mg/day); the effect at usual carbamazepine doses is unknown.

The ability of alprazolam to induce or inhibit human hepatic enzyme systems has not been determined. However, this is not a property of benzodiazepines in general. Further, alprazolam did not affect the prothrombin or plasma warfarin levels in male volunteers administered sodium warfarin orally.

How Supplied/Storage and Handling

Niravam (alprazolam orally disintegrating tablets) 0.25 mg are yellow, round, orange-flavored, scored and engraved “SP 321” on the unscored side and “0.25” on the scored side. They are supplied as follows: Bottles of 100 NDC 18860-321-01

Niravam (alprazolam orally disintegrating tablets) 0.5 mg are yellow, round, orange-flavored, scored and engraved “SP 322” on the unscored side and “0.5” on the scored side. They are supplied as follows: Bottles of 100 NDC 18860-322-01

Niravam (alprazolam orally disintegrating tablets) 1 mg are white, round, orange-flavored, scored and engraved “SP 323” on the unscored side and “1” on the scored side. They are supplied as follows: Bottles of 100 NDC 18860-323-01

Niravam (alprazolam orally disintegrating tablets) 2 mg are white, round, orange-flavored, scored and engraved “SP 324” on the unscored side and “2” on the scored side. They are supplied as follows: Bottles of 100 NDC 18860-324-01

Storage

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86ºF) [See USP Controlled Room Temperature]. Protect from moisture.

Dispense in a tight container as defined in the USP/NF.

Principal Display Panel - 0.5 mg Tablets

NDC 18860-322-01

100 tablets

Niravam® 0.5 mg
(alprazolam orally disintegrating tablets)

Rx only   CIV

Jazz Pharmaceuticals

orally disintegrating tablets

Each orange-flavored, orally disintegrating tablet contains 0.5 mg alprazolam.

USUAL DOSAGE: See package insert for further information.

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86ºF) [See USP Controlled Room Temperature]. Protect from moisture.

Dispense in a tight container as defined in the USP/NF.

KEEP OUT OF REACH OF CHILDREN.

Distributed by:
Jazz Pharmaceuticals Commercial Corp.
Philadelphia, PA 19103

U.S. Patent Nos.
6,024,981 and 6,221,392

NIRAt-10-12
Rev. 05/12 3E

Niravam® is a registered trademark of UCB Manufacturing, Inc.

00017960

LOT:
EXP:

.50 mg Label

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