Prescription Drug Information: ZOLPIDEM TARTRATE (Page 5 of 5)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Zolpidem was administered to mice and rats for 2 years at oral doses of 4, 18, and 80 mg base/kg/day. In mice, these doses are approximately 2, 9, and 40 times the MRHD of 12.5 mg/day (10 mg zolpidem base) based on mg/m2 body surface area and in rats, these doses are approximately 4, 18, and 80 times the MRHD based on mg/m2 body surface area. No evidence of carcinogenic potential was observed in mice. In rats, renal tumors (lipoma, liposarcoma) were seen at the mid and high doses.

Mutagenesis

Zolpidem was negative in in vitro (bacterial reverse mutation, mouse lymphoma, and chromosomal aberration) and in vivo (mouse micronucleus) genetic toxicology assays.

Impairment of Fertility

Zolpidem was administered to rats at 4, 20, and 100 mg base/kg/day, which are approximately 4, 20, and 100 times the MRHD of 12.5 mg/day (10 mg zolpidem base) based on mg/m2 body surface area, prior to and during mating, and continuing in females through postpartum day 25. Zolpidem caused irregular estrus cycles and prolonged precoital intervals at the highest dose tested, which is approximately 100 times the MRHD based on mg/m2 body surface area. The NOAEL for these effects is 20 times the MRHD based on mg/m2 body surface area. There was no impairment of fertility at any dose tested.

14 CLINICAL STUDIES

14.1 Controlled Clinical Trials

Zolpidem tartrate extended-release tablets were evaluated in three placebo-controlled studies for the treatment of patients with chronic primary insomnia (as defined in the APA Diagnostic and Statistical Manual of Mental Disorders, DSM IVTM).

Adult outpatients (18 to 64 years) with primary insomnia (N=212) were evaluated in a double-blind, randomized, parallel-group, 3-week trial comparing zolpidem tartrate extended-release tablets 12.5 mg and placebo. Zolpidem tartrate extended-release tablets 12.5 mg decreased wake time after sleep onset (WASO) for the first 7 hours during the first 2 nights and for the first 5 hours after 2 weeks of treatment. Zolpidem tartrate extended-release tablets 12.5 mg were superior to placebo on objective measures (polysomnography recordings) of sleep induction (by decreasing latency to persistent sleep [LPS]) during the first 2 nights of treatment and after 2 weeks of treatment. Zolpidem tartrate extended-release tablets 12.5 mg were also superior to placebo on the patient reported global impression regarding the aid to sleep after the first 2 nights and after 3 weeks of treatment.

Elderly outpatients (≥ 65 years) with primary insomnia (N=205) were evaluated in a double-blind, randomized, parallel-group, 3-week trial comparing zolpidem tartrate extended-release tablets 6.25 mg and placebo. Zolpidem tartrate extended-release tablets 6.25 mg decreased wake time after sleep onset (WASO) for the first 6 hours during the first 2 nights and the first 4 hours after 2 weeks of treatment. Zolpidem tartrate extended-release tablets 6.25 mg were superior to placebo on objective measures (polysomnography recordings) of sleep induction (by decreasing LPS) during the first 2 nights of treatment and after 2 weeks on treatment. Zolpidem tartrate extended-release tablets 6.25 mg were superior to placebo on the patient reported global impression regarding the aid to sleep after the first 2 nights and after 3 weeks of treatment.

In both studies, in patients treated with zolpidem tartrate extended-release tablets, polysomnography showed increased wakefulness at the end of the night compared to placebo-treated patients.

In a 24-week double-blind, placebo controlled, randomized study in adult outpatients (18 to 64 years) with primary insomnia (N=1025), zolpidem tartrate extended-release tablets 12.5 mg administered as needed (3 to 7 nights per week) was superior to placebo over 24 weeks, on patient global impression regarding aid to sleep, and on patient-reported specific sleep parameters for sleep induction and sleep maintenance with no significant increased frequency of drug intake observed over time.

14.2 Studies Pertinent to Safety Concerns for Sedative/Hypnotic Drugs

Next-Day Residual Effects

In five clinical studies (three controlled studies in adults [18 to 64 years of age] administered zolpidem tartrate extended-release tablets 12.5 mg and two controlled studies in the elderly [≥ 65 years of age] administered zolpidem tartrate extended-release tablets 6.25 mg or 12.5 mg), the effect of zolpidem tartrate extended-release tablets on vigilance, memory, or motor function were assessed using neurocognitive tests. In these studies, no significant decrease in performance was observed eight hours after a nighttime dose. In addition, no evidence of next-day residual effects was detected with zolpidem tartrate extended-release tablets 12.5 mg and 6.25 mg using self-ratings of sedation.

During the 3-week studies, next-day somnolence was reported by 15% of the adult patients who received 12.5 mg zolpidem tartrate extended-release tablets versus 2% of the placebo group; next-day somnolence was reported by 6% of the elderly patients who received 6.25 mg zolpidem tartrate extended-release tablets versus 5% of the placebo group [see ADVERSE REACTIONS (6)]. In a 6-month study, the overall incidence of next-day somnolence was 5.7% in the zolpidem tartrate extended-release tablets group as compared to 2% in the placebo group.

Rebound Effects

Rebound insomnia, defined as a dose-dependent worsening in sleep parameters (latency, sleep efficiency, and number of awakenings) compared with baseline following discontinuation of treatment, is observed with short- and intermediate-acting hypnotics. In the two 3-week placebo-controlled studies in patients with primary insomnia, a rebound effect was only observed on the first night after abrupt discontinuation of zolpidem tartrate extended-release tablets. On the second night, there was no worsening compared to baseline in the zolpidem tartrate extended-release tablets group.

In a 6-month placebo-controlled study in which zolpidem tartrate extended-release tablets were taken as needed (3 to 7 nights per week), within the first month a rebound effect was observed for Total Sleep Time (not for WASO) during the first night off medication. After this first month period, no further rebound insomnia was observed. After final treatment discontinuation no rebound was observed.

16 HOW SUPPLIED/STORAGE AND HANDLING

Zolpidem tartrate extended-release tablets USP, 6.25 mg are composed of two layers* and are pink colored, round, biconvex, film-coated tablets debossed with “E61” on one side and “LU” on the other side and supplied as:

NDC Number Package Configuration

68180-779-04 Bottle of 100

Zolpidem tartrate extended-release tablets USP, 12.5 mg are composed of two layers* and are blue colored, round, biconvex, film-coated tablets debossed with “E62” on one side and “LU” on the other side and supplied as:

NDC Number Package Configuration

68180-780-04 Bottle of 100

*Layers are covered by the coating and are indistinguishable.

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Inform patients and their families about the benefits and risks of treatment with zolpidem tartrate extended-release tablets. Inform patients of the availability of a Medication Guide and instruct them to read the Medication Guide prior to initiating treatment with zolpidem tartrate extended-release tablets and with each prescription refill. Review the zolpidem tartrate extended-release tablets Medication Guide with every patient prior to initiation of treatment. Instruct patients or caregivers that zolpidem tartrate extended-release tablets should be taken only as prescribed.

Complex Sleep Behaviors

Instruct patients and their families that zolpidem tartrate extended-release tablets may cause complex sleep behaviors, including sleep-walking, sleep-driving, preparing and eating food, making phone calls, or having sex while not being fully awake. Serious injuries and death have occurred during complex sleep behavior episodes. Tell patients to discontinue zolpidem tartrate extended-release tablets and notify their healthcare provider immediately if they develop any of these symptoms [see BOXED WARNING, WARNINGS AND PRECAUTIONS (5.1)].

CNSDepressant Effects and Next-Day Impairment

Tell patients that zolpidem tartrate extended-release tablets can cause next-day impairment even when used as prescribed, and that this risk is increased if dosing instructions are not carefully followed. Caution patients against driving and other activities requiring complete mental alertness the day after use. Inform patients that impairment can be present despite feeling fully awake. Advise patients that increased drowsiness and decreased consciousness may increase the risk of falls in some patients.

Severe Anaphylactic and Anaphylactoid Reactions

Inform patients that severe anaphylactic and anaphylactoid reactions have occurred with zolpidem. Describe the signs/symptoms of these reactions and advise patients to seek medical attention immediately if any of them occur.

Suicide

Tell patients to immediately report any suicidal thoughts.

Alcohol and other Drugs

Ask patients about alcohol consumption, medicines they are taking, and drugs they may be taking without a prescription. Advise patients not to use zolpidem tartrate extended-release tablets if they drank alcohol that evening or before bed.

Concomitant Use with Opioids

Inform patients and caregivers that potentially serious additive effects may occur if zolpidem tartrate extended-release tablets is used with opioids and not to use such drugs concomitantly unless supervised by a healthcare provider [WARNINGS AND PRECAUTIONS (5.2, 5.7), DRUG INTERACTIONS (7.1)].

Tolerance, Abuse, and Dependence

Tell patients not to increase the dose of zolpidem tartrate extended-release tablets on their own, and to inform you if they believe the drug “does not work.”

Administration Instructions

Patients should be counseled to take zolpidem tartrate extended-release tablets right before they get into bed and only when they are able to stay in bed a full night (7 to 8 hours) before being active again. Zolpidem tartrate extended-release tablets should not be taken with or immediately after a meal. Advise patients NOT to take zolpidem tartrate extended-release tablets if they drank alcohol that evening.

Pregnancy

Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with zolpidem tartrate extended-release tablets. Advise patients that use of zolpidem tartrate extended-release tablets late in the third trimester may cause respiratory depression and sedation in neonates. Advise mothers who used zolpidem tartrate extended-release tablets during the late third trimester of pregnancy to monitor neonates for signs of sleepiness (more than usual), breathing difficulties, or limpness [see USE IN SPECIFIC POPULATIONS (8.1)].

Lactation

Advise breastfeeding mothers using zolpidem tartrate extended-release tablets to monitor infants for increased sleepiness (more than usual), breathing difficulties, or limpness. Instruct breastfeeding mothers to seek immediate medical care if they notice these signs. A lactating woman may consider pumping and discarding breastmilk during treatment and for 23 hours after zolpidem tartrate extended-release tablets administration to minimize drug exposure to a breastfed infant [see USE IN SPECIFIC POPULATIONS (8.2)].

The brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products.

Manufactured for:

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States

Manufactured by:

Lupin Limited

Goa 403 722

INDIA

Revised: October 2023 ID#: 274728

MEDICATION GUIDE

Zolpidem Tartrate ( zole-PI-dem TAR-trate )

Extended-Release Tablets USP, 6.25 mg and 12.5 mg CIV

What is the most important information I should know about zolpidem tartrate extended-release tablets?

Zolpidem tartrate extended-release tablets may cause serious side effects, including:

  • Complex sleep behaviors. After taking zolpidem tartrate extended-release tablets, you may get up out of bed while not being fully awake and do an activity that you do not know you are doing. The next morning, you may not remember that you did anything during the night. These activities may happen with zolpidem tartrate extended-release tablets whether or not you drink alcohol or take other medicines that make you sleepy. Some of these complex sleep behaviors have caused serious injury and death.

People taking zolpidem tartrate extended-release tablets have reported:

  • sleep-walking
  • sleep-driving
  • making and eating food
  • talking on the phone
  • having sex

Stop taking zolpidem tartrate extended-release tablet and tell your healthcare provider right away if you find out that you have done any of the above activities after taking zolpidem tartrate extended-release tablets.

What is zolpidem tartrate extended-release tablet?

Zolpidem tartrate extended-release tablet is a prescription sleep medicine used for the treatment of adults who have trouble falling asleep or staying asleep (insomnia).

  • It is not known if zolpidem tartrate extended-release tablet is safe and effective in children under the age of 18 years. Zolpidem tartrate extended-release tablet is not recommended for use in children under the age of 18 years.
  • Zolpidem tartrate extended-release tablet is a federally controlled substance (C-IV) because it can be abused or lead to dependence. Keep zolpidem tartrate extended-release tablets in a safe place to protect it from theft. Never give your zolpidem tartrate extended-release tablet to anyone else because it can cause death or harm them. Selling or giving away this medicine is against the law.

Do not take zolpidem tartrate extended-release tablet if you:

  • have had complex sleep behaviors that happened after taking zolpidem tartrate extended-release tablet in the past. See “What is the most important information I should know about zolpidem tartrate extended-release tablet?
  • are allergic to zolpidem or any of the ingredients in zolpidem tartrate extended-release tablets. See the end of this Medication Guide for a complete list of ingredients in zolpidem tartrate extended-release tablets

Before taking zolpidem tartrate extended-release tablet tell your healthcare provider about all of your medical conditions, including if you:

  • have a history of depression, mental illness, or suicidal thoughts or actions.
  • have a history of drug or alcohol abuse or addiction
  • have kidney or liver disease
  • have a lung disease or breathing problems
  • have sleep apnea
  • have myasthenia gravis
  • are pregnant or plan to become pregnant. Taking zolpidem tartrate extended-release tablets in the third trimester of pregnancy may harm your unborn baby
    • Tell your healthcare provider if you become pregnant or plan to become pregnant during treatment with zolpidem tartrate extended-release tablets
    • Babies born to mothers who take zolpidem tartrate extended-release tablets during the third trimester of pregnancy may have symptoms of breathing problems and sedation (such as sleepiness or low muscle tone).
  • are breastfeeding or plan to breastfeed. Zolpidem tartrate extended-release tablets passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby while you take zolpidem tartrate extended-release tablets

Tell your healthcare provider about all of the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Zolpidem tartrate extended-release tablets and other medicines can interact with each other causing serious side effects. Zolpidem tartrate extended-release tablets may affect the way other medicines work, and other medicines may affect how zolpidem tartrate extended-release tablets works.

Especially tell your healthcare provider if you:

  • take benzodiazepines.
  • take opioids as it may increase the risk of breathing problems (respiratory depression).
  • take tricyclic antidepressants
  • take other medicines that can make you sleepy or affect your breathing (including other zolpidem medicines)
  • drink alcohol

You can ask your pharmacist for a list of medicines that interact with zolpidem tartrate extended-release tablets.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take zolpidem tartrate extended-release tablets?

  • Take zolpidem tartrate extended-release tablet exactly as prescribed. Do not change your dose on your own. Tell your healthcare provider if you think zolpidem tartrate extended-release tablet is not working for you
  • Zolpidem tartrate extended-release tablet is for short-term use only. Treatment with zolpidem tartrate extended-release tablet should be as short as possible because the risk of dependence increases the longer you are being treated
  • Take 1 zolpidem tartrate extended-release tablet a night right before bedtime
  • Do not take zolpidem tartrate extended-release tablet if you are not able to stay in bed a full night (7 to 8 hours) before you must be active again.
  • You should not take zolpidem tartrate extended-release tablet with or right after a meal. zolpidem tartrate extended-release tablet may help you fall asleep faster if you take it on an empty stomach.
  • Do not take zolpidem tartrate extended-release tablets if you drank alcohol that evening or before bed
  • Swallow zolpidem tartrate extended-release tablets whole. Do not divide, crush, or chew zolpidem tartrate extended-release tablets. If you cannot swallow zolpidem tartrate extended-release tablet whole, tell your healthcare provider. You may need a different medicine.
  • Call your healthcare provider if your sleep problems get worse or do not get better within 7 to 10 days. This may mean that there is another condition causing your sleep problems.
  • If you take too much zolpidem tartrate extended-release tablets call your healthcare provider or go to the nearest hospital emergency room right away.

What are the possible side effects of zolpidem tartrate extended-release tablets?

Zolpidem tartrate extended-release tablets may cause serious side effects including:

  • See “What is the most important information I should know about zolpidem tartrate extended-release tablet ?”
  • Zolpidem tartrate extended-release tablet can make you sleepy or dizzy and can slow your thinking and motor skills. Next-day sleepiness is common, but can be serious. Because zolpidem tartrate extended-release tablet can make you sleepy or dizzy you are at a higher risk for falls.
    • Do not drive, operate heavy machinery, or do other dangerous activities until you know how zolpidem tartrate extended-release tablet affects you
    • Do not drink alcohol or take opioids or other medicines that may make you sleepy or dizzy while taking zolpidem tartrate extended-release tablet without first talking to your healthcare provider. When taken with alcohol or other medicines that cause sleepiness or dizziness, zolpidem tartrate extended-release tablet may make your sleepiness or dizziness much worse
  • Severe allergic reactions. Symptoms include swelling of the tongue or throat, trouble breathing, and nausea and vomiting. Get emergency medical help if you get these symptoms after taking zolpidem tartrate extended-release tablet.
  • Abnormal thoughts and behavior. Symptoms include more outgoing or aggressive behavior than normal, confusion (delirium), acting strangely, agitation, hallucinations, worsening of depression, and suicidal thoughts or actions
  • Risk of suicide and worsening of depression. Worsening of depression, including suicidal thoughts and actions can happen during treatment with medicines like zolpidem tartrate extended-release tablets. Call your healthcare provider right away if you develop any thoughts of suicide, dying, or worsening depression during treatment with zolpidem tartrate extended-release tablet
  • Breathing problems. See “Before taking zolpidem tartrate extended-release tablets, tell your healthcare provider about all of your medical conditions, including if you:” Call your healthcare provider or get emergency medical help right away if you develop breathing problems during treatment with zolpidem tartrate extended-release tablets.
  • Problems with your nervous system caused by severe liver disease (hepatic encephalopathy)
  • Withdrawal symptoms. You may have withdrawal symptoms if you stop taking zolpidem tartrate extended-release tablets suddenly. Withdrawal symptoms can be serious and include stomach and muscle cramps, vomiting, sweating, shakiness, seizures, and confusion (delirium). Talk to your healthcare provider about slowly stopping zolpidem tartrate extended-release tablets to avoid withdrawal symptoms

The most common side effects of zolpidem tartrate extended-release tablets include headache and dizziness.

These are not all the side effects of zolpidem tartrate extended-release tablets.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store zolpidem tartrate extended-release tablets?

Store zolpidem tartrate extended-release tablets at room temperature, 59°F to 77°F (15°C to 25°C).

Keep zolpidem tartrate extended-release tablets and all medicines out of reach of children.

General Information about the safe and effective use of zolpidem tartrate extended-release tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use zolpidem tartrate extended-release tablets for a condition for which it was not prescribed. Do not give zolpidem tartrate extended-release tablets to other people, even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about zolpidem tartrate extended-release tablets that is written for healthcare professionals

What are the ingredients in zolpidem tartrate extended-release tablets?

Active Ingredient: Zolpidem tartrate

Inactive Ingredients: The 6.25 mg zolpidem tartrate extended-release tablets contain the following inactive ingredients: colloidal silicon dioxide, FD&C Blue # 2 aluminium lake, hypromellose, iron oxide red, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, potassium bitartrate, sodium starch glycolate and titanium dioxide. The 12.5 mg zolpidem tartrate extended-release tablets contain the following inactive ingredients: colloidal silicon dioxide, FD&C Blue # 2 aluminium lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, potassium bitartrate, sodium starch glycolate and titanium dioxide.

The brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured for:

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States

Manufactured by:

Lupin Limited

Goa 403 722

INDIA

Revised: April 2022 ID #: 270217

Zolpidem Tartrate Extended-Release Tablets USP, 6.25 mg

Rx only

NDC 68180-779-04: Bottle of 100 Tablets

Im-4
(click image for full-size original)

Zolpidem Tartrate Extended-Release Tablets USP, 12.5 mg

Rx only

NDC 68180-780-04: Bottle of 100 Tablets

Im-5
(click image for full-size original)
ZOLPIDEM TARTRATE zolpidem tartrate tablet, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:68180-779
Route of Administration ORAL DEA Schedule CIV
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ZOLPIDEM TARTRATE (ZOLPIDEM) ZOLPIDEM TARTRATE 6.25 mg
Product Characteristics
Color PINK Score no score
Shape ROUND Size 8mm
Flavor Imprint Code LU;E61
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:68180-779-06 30 TABLET, EXTENDED RELEASE in 1 BOTTLE None
2 NDC:68180-779-02 500 TABLET, EXTENDED RELEASE in 1 BOTTLE None
3 NDC:68180-779-03 1000 TABLET, EXTENDED RELEASE in 1 BOTTLE None
4 NDC:68180-779-01 100 TABLET, EXTENDED RELEASE in 1 BOTTLE None
5 NDC:68180-779-11 10 TABLET, EXTENDED RELEASE in 1 BLISTER PACK None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA078970 04/11/2014
ZOLPIDEM TARTRATE zolpidem tartrate tablet, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:68180-780
Route of Administration ORAL DEA Schedule CIV
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ZOLPIDEM TARTRATE (ZOLPIDEM) ZOLPIDEM TARTRATE 12.5 mg
Product Characteristics
Color BLUE Score no score
Shape ROUND Size 8mm
Flavor Imprint Code LU;E62
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:68180-780-06 30 TABLET, EXTENDED RELEASE in 1 BOTTLE None
2 NDC:68180-780-02 500 TABLET, EXTENDED RELEASE in 1 BOTTLE None
3 NDC:68180-780-03 1000 TABLET, EXTENDED RELEASE in 1 BOTTLE None
4 NDC:68180-780-01 100 TABLET, EXTENDED RELEASE in 1 BOTTLE None
5 NDC:68180-780-11 10 TABLET, EXTENDED RELEASE in 1 BLISTER PACK None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA078970 04/11/2014
Labeler — Lupin Pharmaceuticals, Inc. (089153071)
Registrant — LUPIN LIMITED (675923163)
Establishment
Name Address ID/FEI Operations
LUPIN LIMITED 677600414 MANUFACTURE (68180-779), MANUFACTURE (68180-780), PACK (68180-779), PACK (68180-780)

Revised: 01/2024 Lupin Pharmaceuticals, Inc.

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