Follow patients for signs and symptoms of respiratory depression and sedation.

Transcription

1 VALIUM brand f diazepam TABLETS R x Only WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS Cncmitant use f benzdiazepines and piids may result in prfund sedatin, respiratry depressin, cma, and death (see Drug Interactins). Reserve cncmitant prescribing f these drugs fr use in patients fr whm alternative treatment ptins are inadequate. Limit dsages and duratins t the minimum required. Fllw patients fr signs and symptms f respiratry depressin and sedatin. DESCRIPTION Valium (diazepam) is a benzdiazepine derivative. The chemical name f diazepam is 7-chlr-1,3-dihydr-1-methyl-5-phenyl-2H-1,4-benzdiazepin- 2-ne. It is a clrless t light yellw crystalline cmpund, insluble in water. The empirical frmula is C 16 H 13 ClN 2 O and the mlecular weight is The structural frmula is as fllws: Valium is available fr ral administratin as tablets cntaining 2 mg, 5 mg r 10 mg diazepam. In additin t the active ingredient diazepam, each tablet cntains the fllwing inactive ingredients: anhydrus lactse, crn starch, pregelatinized starch and calcium stearate with the fllwing dyes: 5-mg tablets cntain FD&C Yellw N. 6 and D&C Yellw N. 10; 10-mg tablets cntain FD&C Blue N. 1. Valium 2-mg tablets cntain n dye.

2 CLINICAL PHARMACOLOGY Diazepam is a benzdiazepine that exerts anxilytic, sedative, musclerelaxant, anticnvulsant and amnestic effects. Mst f these effects are thught t result frm a facilitatin f the actin f gamma aminbutyric acid (GABA), an inhibitry neurtransmitter in the central nervus system. Pharmackinetics Absrptin After ral administratin >90% f diazepam is absrbed and the average time t achieve peak plasma cncentratins is hurs with a range f 0.25 t 2.5 hurs. Absrptin is delayed and decreased when administered with a mderate fat meal. In the presence f fd mean lag times are apprximately 45 minutes as cmpared with 15 minutes when fasting. There is als an increase in the average time t achieve peak cncentratins t abut 2.5 hurs in the presence f fd as cmpared with 1.25 hurs when fasting. This results in an average decrease in C max f 20% in additin t a 27% decrease in AUC (range 15% t 50%) when administered with fd. Distributin Diazepam and its metablites are highly bund t plasma prteins (diazepam 98%). Diazepam and its metablites crss the bld-brain and placental barriers and are als fund in breast milk in cncentratins apprximately ne tenth f thse in maternal plasma (days 3 t 9 pst-partum). In yung healthy males, the vlume f distributin at steady-state is 0.8 t 1.0 L/kg. The decline in the plasma cncentratin-time prfile after ral administratin is biphasic. The initial distributin phase has a half-life f apprximately 1 hur, althugh it may range up t >3 hurs. Metablism Diazepam is N-demethylated by CYP3A4 and 2C19 t the active metablite N-desmethyldiazepam, and is hydrxylated by CYP3A4 t the active metablite temazepam. N-desmethyldiazepam and temazepam are bth further metablized t xazepam. Temazepam and xazepam are largely eliminated by glucurnidatin. Eliminatin The initial distributin phase is fllwed by a prlnged terminal eliminatin phase (half-life up t 48 hurs). The terminal eliminatin half-life f the active metablite N-desmethyldiazepam is up t 100 hurs. Diazepam and its metablites are excreted mainly in the urine, predminantly as their glucurnide cnjugates. The clearance f diazepam is 20 t 30 ml/min in yung adults. Diazepam accumulates upn multiple dsing and there is sme evidence that the terminal eliminatin half-life is slightly prlnged. 2

3 Pharmackinetics in Special Ppulatins Children In children 3-8 years ld the mean half-life f diazepam has been reprted t be 18 hurs. Newbrns In full term infants, eliminatin half-lives arund 30 hurs have been reprted, with a lnger average half-life f 54 hurs reprted in premature infants f weeks gestatinal age and 8-81 days pst-partum. In bth premature and full term infants the active metablite desmethyldiazepam shws evidence f cntinued accumulatin cmpared t children. Lnger half-lives in infants may be due t incmplete maturatin f metablic pathways. Geriatric Eliminatin half-life increases by apprximately 1 hur fr each year f age beginning with a half-life f 20 hurs at 20 years f age. This appears t be due t an increase in vlume f distributin with age and a decrease in clearance. Cnsequently, the elderly may have lwer peak cncentratins, and n multiple dsing higher trugh cncentratins. It will als take lnger t reach steady-state. Cnflicting infrmatin has been published n changes f plasma prtein binding in the elderly. Reprted changes in free drug may be due t significant decreases in plasma prteins due t causes ther than simply aging. Hepatic Insufficiency In mild and mderate cirrhsis, average half-life is increased. The average increase has been variusly reprted frm 2-fld t 5-fld, with individual half-lives ver 500 hurs reprted. There is als an increase in vlume f distributin, and average clearance decreases by almst half. Mean half-life is als prlnged with hepatic fibrsis t 90 hurs (range hurs), with chrnic active hepatitis t 60 hurs (range hurs), and with acute viral hepatitis t 74 hurs (range ). In chrnic active hepatitis, clearance is decreased by almst half. INDICATIONS Valium is indicated fr the management f anxiety disrders r fr the shrtterm relief f the symptms f anxiety. Anxiety r tensin assciated with the stress f everyday life usually des nt require treatment with an anxilytic. In acute alchl withdrawal, Valium may be useful in the symptmatic relief f acute agitatin, tremr, impending r acute delirium tremens and hallucinsis. Valium is a useful adjunct fr the relief f skeletal muscle spasm due t reflex spasm t lcal pathlgy (such as inflammatin f the muscles r jints, r 3

4 secndary t trauma), spasticity caused by upper mtr neurn disrders (such as cerebral palsy and paraplegia), athetsis, and stiff-man syndrme. Oral Valium may be used adjunctively in cnvulsive disrders, althugh it has nt prved useful as the sle therapy. The effectiveness f Valium in lng-term use, that is, mre than 4 mnths, has nt been assessed by systematic clinical studies. The physician shuld peridically reassess the usefulness f the drug fr the individual patient. CONTRAINDICATIONS Valium is cntraindicated in patients with a knwn hypersensitivity t diazepam and, because f lack f sufficient clinical experience, in pediatric patients under 6 mnths f age. Valium is als cntraindicated in patients with myasthenia gravis, severe respiratry insufficiency, severe hepatic insufficiency, and sleep apnea syndrme. It may be used in patients with pen-angle glaucma wh are receiving apprpriate therapy, but is cntraindicated in acute narrw-angle glaucma. WARNINGS Cncmitant use f benzdiazepines, including Valium, and piids may result in prfund sedatin, respiratry depressin, cma, and death. Because f these risks, reserve cncmitant prescribing f these drugs fr use in patients fr whm alternative treatment ptins are inadequate. Observatinal studies have demnstrated that cncmitant use f piid analgesics and benzdiazepines increases the risk f drug-related mrtality cmpared t use f piids alne. If a decisin is made t prescribe Valium cncmitantly with piids, prescribe the lwest effective dsages and minimum duratins f cncmitant use, and fllw patients clsely fr signs and symptms f respiratry depressin and sedatin. In patients already receiving an piid analgesic, prescribe a lwer initial dse f Valium than indicated in the absence f an piid and titrate based n clinical respnse. If an piid is initiated in a patient already taking Valium, prescribe a lwer initial dse f the piid and titrate based upn clinical respnse. Advise bth patients and caregivers abut the risks f respiratry depressin and sedatin when Valium is used with piids. Advise patients nt t drive r perate heavy machinery until the effects f cncmitant use with the piid have been determined (see Drug Interactins). Valium is nt recmmended in the treatment f psychtic patients and shuld nt be emplyed instead f apprpriate treatment. Since Valium has a central nervus system depressant effect, patients shuld be advised against the simultaneus ingestin f alchl and ther CNSdepressant drugs during Valium therapy. 4

5 As with ther agents that have anticnvulsant activity, when Valium is used as an adjunct in treating cnvulsive disrders, the pssibility f an increase in the frequency and/r severity f grand mal seizures may require an increase in the dsage f standard anticnvulsant medicatin. Abrupt withdrawal f Valium in such cases may als be assciated with a temprary increase in the frequency and/r severity f seizures. Pregnancy An increased risk f cngenital malfrmatins and ther develpmental abnrmalities assciated with the use f benzdiazepine drugs during pregnancy has been suggested. There may als be nn-teratgenic risks assciated with the use f benzdiazepines during pregnancy. There have been reprts f nenatal flaccidity, respiratry and feeding difficulties, and hypthermia in children brn t mthers wh have been receiving benzdiazepines late in pregnancy. In additin, children brn t mthers receiving benzdiazepines n a regular basis late in pregnancy may be at sme risk f experiencing withdrawal symptms during the pstnatal perid. Diazepam has been shwn t be teratgenic in mice and hamsters when given rally at daily dses f 100 mg/kg r greater (apprximately eight times the maximum recmmended human dse [MRHD=1 mg/kg/day] r greater n a mg/m 2 basis). Cleft palate and encephalpathy are the mst cmmn and cnsistently reprted malfrmatins prduced in these species by administratin f high, maternally txic dses f diazepam during rgangenesis. Rdent studies have indicated that prenatal expsure t diazepam dses similar t thse used clinically can prduce lng-term changes in cellular immune respnses, brain neurchemistry, and behavir. In general, the use f diazepam in wmen f childbearing ptential, and mre specifically during knwn pregnancy, shuld be cnsidered nly when the clinical situatin warrants the risk t the fetus. The pssibility that a wman f childbearing ptential may be pregnant at the time f institutin f therapy shuld be cnsidered. If this drug is used during pregnancy, r if the patient becmes pregnant while taking this drug, the patient shuld be apprised f the ptential hazard t the fetus. Patients shuld als be advised that if they becme pregnant during therapy r intend t becme pregnant they shuld cmmunicate with their physician abut the desirability f discntinuing the drug. Labr and Delivery Special care must be taken when Valium is used during labr and delivery, as high single dses may prduce irregularities in the fetal heart rate and hyptnia, pr sucking, hypthermia, and mderate respiratry depressin in the nenates. With newbrn infants it must be remembered that the enzyme system invlved in the breakdwn f the drug is nt yet fully develped (especially in premature infants). 5

6 Nursing Mthers Diazepam passes int breast milk. Breastfeeding is therefre nt recmmended in patients receiving Valium. PRECAUTIONS General If Valium is t be cmbined with ther psychtrpic agents r anticnvulsant drugs, careful cnsideratin shuld be given t the pharmaclgy f the agents t be emplyed - particularly with knwn cmpunds that may ptentiate the actin f diazepam, such as phenthiazines, narctics, barbiturates, MAO inhibitrs and ther antidepressants (see Drug Interactins). The usual precautins are indicated fr severely depressed patients r thse in whm there is any evidence f latent depressin r anxiety assciated with depressin, particularly the recgnitin that suicidal tendencies may be present and prtective measures may be necessary. Psychiatric and paradxical reactins are knwn t ccur when using benzdiazepines (see ADVERSE REACTIONS). Shuld this ccur, use f the drug shuld be discntinued. These reactins are mre likely t ccur in children and the elderly. A lwer dse is recmmended fr patients with chrnic respiratry insufficiency, due t the risk f respiratry depressin. Benzdiazepines shuld be used with extreme cautin in patients with a histry f alchl r drug abuse (see DRUG ABUSE AND DEPENDENCE). In debilitated patients, it is recmmended that the dsage be limited t the smallest effective amunt t preclude the develpment f ataxia r versedatin (2 mg t 2.5 mg nce r twice daily, initially, t be increased gradually as needed and tlerated). Sme lss f respnse t the effects f benzdiazepines may develp after repeated use f Valium fr a prlnged time. Infrmatin fr Patients T assure the safe and effective use f benzdiazepines, patients shuld be infrmed that, since benzdiazepines may prduce psychlgical and physical dependence, it is advisable that they cnsult with their physician befre either increasing the dse r abruptly discntinuing this drug. The risk f dependence increases with duratin f treatment; it is als greater in patients with a histry f alchl r drug abuse. Patients shuld be advised against the simultaneus ingestin f alchl and ther CNS-depressant drugs during Valium therapy. As is true f mst CNS- 6

7 acting drugs, patients receiving Valium shuld be cautined against engaging in hazardus ccupatins requiring cmplete mental alertness, such as perating machinery r driving a mtr vehicle. Drug Interactins Opiids The cncmitant use f benzdiazepines and piids increases the risk f respiratry depressin because f actins at different receptr sites in the CNS that cntrl respiratin. Benzdiazepines interact at GABA A sites and piids interact primarily at mu receptrs. When benzdiazepines and piids are cmbined, the ptential fr benzdiazepines t significantly wrsen piidrelated respiratry depressin exists. Limit dsage and duratin f cncmitant use f benzdiazepines and piids, and mnitr patients clsely fr respiratry depressin and sedatin. Centrally Acting Agents If Valium is t be cmbined with ther centrally acting agents, careful cnsideratin shuld be given t the pharmaclgy f the agents emplyed particularly with cmpunds that may ptentiate r be ptentiated by the actin f Valium, such as phenthiazines, antipsychtics, anxilytics/sedatives, hypntics, anticnvulsants, narctic analgesics, anesthetics, sedative antihistamines, narctics, barbiturates, MAO inhibitrs and ther antidepressants. Alchl Cncmitant use with alchl is nt recmmended due t enhancement f the sedative effect. Antacids Diazepam peak cncentratins are 30% lwer when antacids are administered cncurrently. Hwever, there is n effect n the extent f absrptin. The lwer peak cncentratins appear due t a slwer rate f absrptin, with the time required t achieve peak cncentratins n average minutes greater in the presence f antacids. Hwever, this difference was nt statistically significant. Cmpunds Which Inhibit Certain Hepatic Enzymes There is a ptentially relevant interactin between diazepam and cmpunds which inhibit certain hepatic enzymes (particularly cytchrme P450 3A and 2C19). Data indicate that these cmpunds influence the pharmackinetics f diazepam and may lead t increased and prlnged sedatin. At present, this reactin is knwn t ccur with cimetidine, ketcnazle, fluvxamine, fluxetine, and meprazle. 7

8 Phenytin There have als been reprts that the metablic eliminatin f phenytin is decreased by diazepam. Carcingenesis, Mutagenesis, Impairment f Fertility In studies in which mice and rats were administered diazepam in the diet at a dse f 75 mg/kg/day (apprximately 6 and 12 times, respectively, the maximum recmmended human dse [MRHD=1 mg/kg/day] n a mg/m 2 basis) fr 80 and 104 weeks, respectively, an increased incidence f liver tumrs was bserved in males f bth species. The data currently available are inadequate t determine the mutagenic ptential f diazepam. Reprductin studies in rats shwed decreases in the number f pregnancies and in the number f surviving ffspring fllwing administratin f an ral dse f 100 mg/kg/day (apprximately 16 times the MRHD n a mg/m 2 basis) prir t and during mating and thrughut gestatin and lactatin. N adverse effects n fertility r ffspring viability were nted at a dse f 80 mg/kg/day (apprximately 13 times the MRHD n a mg/m 2 basis). Pregnancy Categry D (see WARNINGS: Pregnancy). Pediatric Use Safety and effectiveness in pediatric patients belw the age f 6 mnths have nt been established. Geriatric Use In elderly patients, it is recmmended that the dsage be limited t the smallest effective amunt t preclude the develpment f ataxia r versedatin (2 mg t 2.5 mg nce r twice daily, initially t be increased gradually as needed and tlerated). Extensive accumulatin f diazepam and its majr metablite, desmethyldiazepam, has been nted fllwing chrnic administratin f diazepam in healthy elderly male subjects. Metablites f this drug are knwn t be substantially excreted by the kidney, and the risk f txic reactins may be greater in patients with impaired renal functin. Because elderly patients are mre likely t have decreased renal functin, care shuld be taken in dse selectin, and it may be useful t mnitr renal functin. Hepatic Insufficiency Decreases in clearance and prtein binding, and increases in vlume f distributin and half-life have been reprted in patients with cirrhsis. In such patients, a 2- t 5- fld increase in mean half-life has been reprted. Delayed eliminatin has als been reprted fr the active metablite desmethyldiazepam. Benzdiazepines are cmmnly implicated in hepatic 8

9 encephalpathy. Increases in half-life have als been reprted in hepatic fibrsis and in bth acute and chrnic hepatitis (see CLINICAL PHARMACOLOGY: Pharmackinetics in Special Ppulatins: Hepatic Insufficiency). ADVERSE REACTIONS Side effects mst cmmnly reprted were drwsiness, fatigue, muscle weakness, and ataxia. The fllwing have als been reprted: Central Nervus System: cnfusin, depressin, dysarthria, headache, slurred speech, tremr, vertig Gastrintestinal System: cnstipatin, nausea, gastrintestinal disturbances Special Senses: blurred visin, diplpia, dizziness Cardivascular System: hyptensin Psychiatric and Paradxical Reactins: stimulatin, restlessness, acute hyperexcited states, anxiety, agitatin, aggressiveness, irritability, rage, hallucinatins, psychses, delusins, increased muscle spasticity, insmnia, sleep disturbances, and nightmares. Inapprpriate behavir and ther adverse behaviral effects have been reprted when using benzdiazepines. Shuld these ccur, use f the drug shuld be discntinued. They are mre likely t ccur in children and in the elderly. Urgenital System: incntinence, changes in libid, urinary retentin Skin and Appendages: skin reactins Labratries: elevated transaminases and alkaline phsphatase Other: changes in salivatin, including dry muth, hypersalivatin Antegrade amnesia may ccur using therapeutic dsages, the risk increasing at higher dsages. Amnestic effects may be assciated with inapprpriate behavir. Minr changes in EEG patterns, usually lw-vltage fast activity, have been bserved in patients during and after Valium therapy and are f n knwn significance. Because f islated reprts f neutrpenia and jaundice, peridic bld cunts and liver functin tests are advisable during lng-term therapy. Pstmarketing Experience: Injury, Pisning and Prcedural Cmplicatins: There have been reprts f falls and fractures in benzdiazepine users. The risk is increased in thse taking cncmitant sedatives (including alchl), and in the elderly. 9

10 DRUG ABUSE AND DEPENDENCE Diazepam is subject t Schedule IV cntrl under the Cntrlled Substances Act f Abuse and dependence f benzdiazepines have been reprted. Addictin-prne individuals (such as drug addicts r alchlics) shuld be under careful surveillance when receiving diazepam r ther psychtrpic agents because f the predispsitin f such patients t habituatin and dependence. Once physical dependence t benzdiazepines has develped, terminatin f treatment will be accmpanied by withdrawal symptms. The risk is mre prnunced in patients n lng-term therapy. Withdrawal symptms, similar in character t thse nted with barbiturates and alchl have ccurred fllwing abrupt discntinuance f diazepam. These withdrawal symptms may cnsist f tremr, abdminal and muscle cramps, vmiting, sweating, headache, muscle pain, extreme anxiety, tensin, restlessness, cnfusin and irritability. In severe cases, the fllwing symptms may ccur: derealizatin, depersnalizatin, hyperacusis, numbness and tingling f the extremities, hypersensitivity t light, nise and physical cntact, hallucinatins r epileptic seizures. The mre severe withdrawal symptms have usually been limited t thse patients wh had received excessive dses ver an extended perid f time. Generally milder withdrawal symptms (e.g., dysphria and insmnia) have been reprted fllwing abrupt discntinuance f benzdiazepines taken cntinuusly at therapeutic levels fr several mnths. Cnsequently, after extended therapy, abrupt discntinuatin shuld generally be avided and a gradual dsage tapering schedule fllwed. Chrnic use (even at therapeutic dses) may lead t the develpment f physical dependence: discntinuatin f the therapy may result in withdrawal r rebund phenmena. Rebund Anxiety: A transient syndrme whereby the symptms that led t treatment with Valium recur in an enhanced frm. This may ccur upn discntinuatin f treatment. It may be accmpanied by ther reactins including md changes, anxiety, and restlessness. Since the risk f withdrawal phenmena and rebund phenmena is greater after abrupt discntinuatin f treatment, it is recmmended that the dsage be decreased gradually. OVERDOSAGE Overdse f benzdiazepines is usually manifested by central nervus system depressin ranging frm drwsiness t cma. In mild cases, symptms include drwsiness, cnfusin, and lethargy. In mre serius cases, symptms may include ataxia, diminished reflexes, hyptnia, hyptensin, respiratry depressin, cma (rarely), and death (very rarely). Overdse f benzdiazepines in cmbinatin with ther CNS depressants (including alchl) may be fatal and shuld be clsely mnitred. 10

11 Management f Overdsage Fllwing verdse with ral benzdiazepines, general supprtive measures shuld be emplyed including the mnitring f respiratin, pulse, and bld pressure. Vmiting shuld be induced (within 1 hur) if the patient is cnscius. Gastric lavage shuld be undertaken with the airway prtected if the patient is uncnscius. Intravenus fluids shuld be administered. If there is n advantage in emptying the stmach, activated charcal shuld be given t reduce absrptin. Special attentin shuld be paid t respiratry and cardiac functin in intensive care. General supprtive measures shuld be emplyed, alng with intravenus fluids, and an adequate airway maintained. Shuld hyptensin develp, treatment may include intravenus fluid therapy, repsitining, judicius use f vaspressrs apprpriate t the clinical situatin, if indicated, and ther apprpriate cuntermeasures. Dialysis is f limited value. As with the management f intentinal verdsage with any drug, it shuld be cnsidered that multiple agents may have been ingested. Flumazenil, a specific benzdiazepine-receptr antagnist, is indicated fr the cmplete r partial reversal f the sedative effects f benzdiazepines and may be used in situatins when an verdse with a benzdiazepine is knwn r suspected. Prir t the administratin f flumazenil, necessary measures shuld be instituted t secure airway, ventilatin and intravenus access. Flumazenil is intended as an adjunct t, nt as a substitute fr, prper management f benzdiazepine verdse. Patients treated with flumazenil shuld be mnitred fr resedatin, respiratry depressin and ther residual benzdiazepine effects fr an apprpriate perid after treatment. The prescriber shuld be aware f a risk f seizure in assciatin with flumazenil treatment, particularly in lng-term benzdiazepine users and in cyclic antidepressant verdse. Cautin shuld be bserved in the use f flumazenil in epileptic patients treated with benzdiazepines. The cmplete flumazenil package insert, including CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS, shuld be cnsulted prir t use. Withdrawal symptms f the barbiturate type have ccurred after the discntinuatin f benzdiazepines (see DRUG ABUSE AND DEPENDENCE). DOSAGE AND ADMINISTRATION Dsage shuld be individualized fr maximum beneficial effect. While the usual daily dsages given belw will meet the needs f mst patients, there will be sme wh may require higher dses. In such cases dsage shuld be increased cautiusly t avid adverse effects. 11

12 ADULTS: Management f Anxiety Disrders and Relief f Symptms f Anxiety. Symptmatic Relief in Acute Alchl Withdrawal. Adjunctively fr Relief f Skeletal Muscle Spasm. Adjunctively in Cnvulsive Disrders. Geriatric Patients, r in the presence f debilitating disease. USUAL DAILY DOSE: Depending upn severity f symptms 2 mg t 10 mg, 2 t 4 times daily 10 mg, 3 r 4 times during the first 24 hurs, reducing t 5 mg, 3 r 4 times daily as needed 2 mg t 10 mg, 3 r 4 times daily 2 mg t 10 mg, 2 t 4 times daily 2 mg t 2.5 mg, 1 r 2 times daily initially; increase gradually as needed and tlerated PEDIATRIC PATIENTS: Because f varied respnses t CNS-acting drugs, initiate therapy with lwest dse and increase as required. Nt fr use in pediatric patients under 6 mnths. 1 mg t 2.5 mg, 3 r 4 times daily initially; increase gradually as needed and tlerated HOW SUPPLIED Fr ral administratin, Valium is supplied as rund, flat-faced scred tablets with V-shaped perfratin and beveled edges. Valium is available as fllws: 2 mg, white - bttles f 100 (NDC ); 5 mg, yellw - bttles f 100 (NDC ) and 500 (NDC ); 10 mg, blue - bttles f 100 (NDC ) and 500 (NDC ). Engraved n tablets: 2 mg 2 VALIUM (frnt) ROCHE (twice n scred side) 5 mg 5 VALIUM (frnt) ROCHE (twice n scred side) 10 mg 10 VALIUM (frnt) ROCHE (twice n scred side) STORAGE Stre at rm temperature 59º t 86ºF (15º t 30ºC). Dispense in tight, lightresistant cntainers as defined in USP/NF. VALIUM is a registered trademark f Hffmann-La Rche, Inc. 12

13 Distributed by: Rche Labratries Inc. n behalf f Rche Prducts Inc. 150 Clve Rad Suite 8 Little Falls, NJ Revised: April Genentech, Inc. All rights reserved. 13

14 MEDICATION GUIDE VALIUM (VAL-ee-um) (diazepam) Tablets, C-IV What is the mst imprtant infrmatin I shuld knw abut VALIUM? VALIUM is a benzdiazepine medicine. Taking benzdiazepines with piid medicines, alchl, r ther central nervus system depressants (including street drugs) can cause severe drwsiness, breathing prblems (respiratry depressin), cma and death. VALIUM can make yu sleepy r dizzy, and can slw yur thinking and mtr skills. D nt drive, perate heavy machinery, r d ther dangerus activities until yu knw hw VALIUM affects yu. D nt drink alchl r take ther drugs that may make yu sleepy r dizzy while taking VALIUM withut first talking t yur healthcare prvider. When taken with alchl r drugs that cause sleepiness r dizziness, VALIUM may make yur sleepiness r dizziness much wrse. D nt take mre VALIUM than prescribed. What is VALIUM? VALIUM is a prescriptin medicine used: t treat anxiety disrders fr the shrt-term relief f the symptms f anxiety t relieve the symptms f alchl withdrawal including agitatin, shakiness (tremr), sudden and severe mental r nervus system changes (delirium tremens) and seeing r hearing things that thers d nt see r hear (hallucinatins) alng with ther medicines fr the relief f muscle spasms alng with ther medicines t treat seizure disrders VALIUM is a federal cntrlled substance (C-IV) because it can be abused r lead t dependence. Keep VALIUM in a safe place t prevent misuse and abuse. Selling r giving away VALIUM may harm thers, and is against the law. Tell yur healthcare prvider if yu have abused r been dependent n alchl, prescriptin medicines r street drugs. It is nt knwn if VALIUM is safe and effective in children under 6 mnths f age. It is nt knwn if VALIUM is safe and effective fr use lnger than 4 mnths. D nt take VALIUM if yu: are allergic t diazepam r any f the ingredients in VALIUM. See the end f this Medicatin Guide fr a cmplete list f ingredients in VALIUM. have a disease that can cause muscle weakness called myasthenia gravis have severe breathing prblems (severe respiratry insufficiency) have severe liver prblems have a sleep prblem called sleep apnea syndrme Befre yu take VALIUM, tell yur healthcare prvider abut all f yur medical cnditins, including if yu: have r have had depressin, md prblems, r suicidal thughts r behavir have lung disease r breathing prblems have liver r kidney prblems are pregnant r plan t becme pregnant. VALIUM may harm yur unbrn baby. Yu and yur healthcare prvider shuld decide if yu shuld take VALIUM while yu are pregnant. are breastfeeding r plan t breastfeed. VALIUM passes int yur breast milk and may harm yur baby. Talk t yur healthcare prvider abut the best way t feed yur baby if yu take VALIUM. D nt breastfeed while taking VALIUM. Tell yur healthcare prvider abut all the medicines yu take, including prescriptin and ver-the-cunter medicines, vitamins, and herbal supplements. Taking VALIUM with certain ther medicines can cause side effects r affect hw well VALIUM r the ther medicines wrk. D nt start r stp ther medicines withut talking t yur healthcare prvider. Hw shuld I take VALIUM? Take VALIUM exactly as yur healthcare prvider tells yu t take it. Yur healthcare prvider will tell yu hw much VALIUM t take and when t take it. Talk t yur healthcare prvider abut slwly stpping VALIUM t avid withdrawal symptms. If yu take t much VALIUM, call yur healthcare prvider r g t the nearest hspital emergency rm

15 right away. What shuld I avid while taking VALIUM? VALIUM can cause yu t be drwsy. D nt drive a car r perate heavy machinery until yu knw hw VALIUM affects yu. Yu shuld nt drink alchl while taking VALIUM. Drinking alchl can increase yur chances f having serius side effects. What are the pssible side effects f VALIUM? VALIUM may cause serius side effects, including: See What is the mst imprtant infrmatin I shuld knw abut VALIUM? Seizures. Taking VALIUM with ther medicines used t treat epilepsy can cause an increase in the number r severity f grand mal seizures. Withdrawal symptms. Yu may have withdrawal symptms if yu stp taking VALIUM suddenly. Withdrawal symptms can be serius and include seizures. Mild withdrawal symptms include a depressed md and truble sleeping. Talk t yur healthcare prvider abut slwly stpping VALIUM t avid withdrawal symptms. Like ther antiepileptic drugs, VALIUM may cause suicidal thughts r actins in a very small number f peple, abut 1 in 500. Call yur healthcare prvider right away if yu have any f these symptms, especially if they are new, wrse, r wrry yu: thughts abut suicide r dying new r wrse anxiety truble sleeping (insmnia) acting n dangerus impulses attempts t cmmit suicide feeling agitated r restless new r wrse irritability an extreme increase in activity and talking (mania) new r wrse depressin panic attacks acting aggressive, being angry, r vilent ther unusual changes in behavir r md Hw can I watch fr early symptms f suicidal thughts and actins? Pay attentin t any changes, especially sudden changes, in md, behavirs, thughts, r feelings. Keep all fllw-up visits with yur healthcare prvider as scheduled. Call yur healthcare prvider between visits as needed, especially if yu are wrried abut symptms. Suicidal thughts r actins can be caused by things ther than medicines. If yu have suicidal thughts r actins, yur healthcare prvider may check fr ther causes. Abuse and dependence. Taking VALIUM can cause physical and psychlgical dependence. Physical and psychlgical dependence is nt the same as drug addictin. Yur healthcare prvider can tell yu mre abut the differences between physical and psychlgical dependence and drug addictin. The mst cmmn side effects f VALIUM include: drwsiness muscle weakness fatigue lss f cntrl f bdy mvements (ataxia) These are nt all the pssible side effects f VALIUM. Call yur dctr fr medical advice abut side effects. Yu may reprt side effects t FDA at FDA Yu may als reprt side effects t Genentech at Hw shuld I stre VALIUM? Stre VALIUM in a tightly clsed cntainer between 68 F t 77 F (20 C t 25 C) and ut f the light. Keep VALIUM and all medicines ut f the reach f children. General infrmatin abut the safe and effective use f VALIUM. Medicines are smetimes prescribed fr purpses ther than thse listed in a Medicatin Guide. D nt use VALIUM fr a cnditin fr which it was nt prescribed. D nt give VALIUM t ther peple, even if they have the same symptms that yu have. It may harm them. Yu can ask yur pharmacist r healthcare prvider fr infrmatin abut VALIUM that is written fr health prfessinals. What are the ingredients in VALIUM? Active ingredient: diazepam Inactive ingredients: anhydrus lactse, crn starch, pregelatinized starch and calcium stearate Distributed by: Rche Labratries Inc. n behalf f Rche Prducts Inc. VALIUM is a registered trademark f Hffmann-La Rche, Inc. Fr mre infrmatin, g t r call This Medicatin Guide has been apprved by the U.S. Fd and Drug Administratin Revised: April 2017