PACKAGE LEAFLET: need to be reduced before you can take Ativan Injection. You

should also tell your doctor if you are taking a drug called

M^rUnlVIMMUN run in^{E USER} scopolamine, which may be used for gut problems or before

an operation.

® Taking Ativan Injection with food and drink

^{A ||V}MN ^INJECM^ON You should avoid alcohol for at least 24 to 48 hours after l°ra^zepam receiving Ativan Injection.

Read all of this leaflet carefully before you start taking this Pregnancy and breast-feeding

^medicine: If you are pregnant or might become pregnant do not take this

•    Keep this leaflet. You may need to read it again. medicine without consulting your doctor first. Benzodiazepines

•    If you have further questions, please ask your doctor or ^including ^{Ativan Injectior1, ma}y ^{cause dama}g^{e to the foetus if} ph_armaci_st taken during early pregnancy. If you take this medicine during

late pregnancy or during labour, your baby, when born, may be

•    ^{If an}y o ^th^{e sid}e efltectsgets serous, ^or you ndr* ^any ^ Active than other bibies, have a low body temperature ^sideeffects. ⁿ(^{ot listed in this leaflet}, p^{lease te}" y^{our doctor} be floppy or have breathing or feeding difficulties for a while.

Your baby’s response to the cold might be temporarily impairec IN THIS LEAFLET' also. If this medicine is taken regularly in late pregnancy, your

1.    What Ativan Injection is and what it is used for. ^baby ^may ^develop ^{withdrawal s}y^mp^{toms after birth}.

2.    Before you take Ativan Injection. Talk to your doctor or pharmacist if you are breast-feeding,

3.    Receiving Ativan Injection. since the drug may pass into breast milk.

4.    Possible side effects.

5.    How to store Ativan Injection. ^Driving ^{and usin}g ^machines

B. F_urther i_nf_ormati_on. Do not drive or use machinery within 24 to 48 hours of

receiving Ativan Injection. The medicine can affect your ability

1.    WHAT ATIVAN INJECTION IS AND WHAT IT IS to drive as it may make you sleepy or dizzy.

^USE^{D FOR} • Do not drive while taking this medicine until you know how The name of your medicine is Ativan Injection. The active ^{it affects you}.

ngredient in Ativan Injection is lorazepam, which is a member • It is an offence to drive if this medicine affects your ability of a group of medicines called benzodiazepines. It helps to to drive.

^{relieve anxiety and muscle tension}. • However, you would not be committing an offence if:

Ativan Injection is usually prescribed as ^{- has} _d^been p^{rescribed to treat a medical or}

pre-medication to help you to relax before an operation or ,,, ^prob^^{m and}.......

before uncomfortable or prolonged investigations. It may also ^{- You have taken it}. ^acp^{ording to the} _i^gi^ve^{n by} be used to relieve short periods of anxiety, excitement or t^hep^rescribe^{r or in the information provided with the}

agitation, and in the control of convulsions. ^{medicine and}

- It was not affecting your ability to drive safely

2.    BEFORE YOU TAKE ATIVAN INJECTION Talk to your doctor or pharmacist if you are not sure whether it

is safe for you to drive while taking this medicine.

You should not be given Ativan Injection if:

Important information about some of the ingredients of

•    You have severe breathing or chest problems. Ativ_an I_nj_ecti_on

- ^You rc Jegictooft^he ^c effects (incl uding seizures) caused by the ingredients SS- ^{Ativan Injection (see Section} 6 for a fu" ^{list of} conta ined in Ativan Injection (pdyethylen e g ly/col a^gnd propylene ^{g )}. glycol) have been reported following very high doses of Ativan

•    You have myasthenia gravis (a disease causing weakened I_nj_ecti_on. muscles and excessive tiredness).

•    You have serious liver problems. ³. ^{RECEIVING ATIVAN INJECTION}

•    You suffer from sleep apnoea (breathing problems when Your doctor will give you Ativan Injection, by injecting it into one you are asleep). of your veins (intravenously) or into one of your muscles. Ativan

Injection may be diluted with water or saline just before it is

f ^you ^{are an} out^-patI^{ent you sho}b^{uld n}t^ot be ^{g iven Ativa}^ g^o to you.The amount of Ativan Injection you are give; n _r ^{njection unless you have somebody to take you home}. will depend on how much you weigh UsU why it is being Ativan Injection contains benzyl alcohol and should not be given to you:

^{used in infants or young children up to} 3 years old. • Before an operation or investigation, you will usually be

Tell your doctor or pharmacist if: g^{iven 0}:°⁵ m of ^Ativan ^ct™ . f^{or each kilo}g^{ram that}

you weigh (e.g. if you weigh 70 kilograms you will receive

•    You are pregnant or trying to become pregnant. 3.5 mg of Ativan Injection).

•    ^{You are breast-feedin}g^{, since the dru}g ^may p^{ass into} • For anxiety or excitement, the usual dose is 0.025 to ^{breast milk}. 0.03 mg for each kilogram that you weigh (e.g. if you

•    You abuse or have in the past abused drugs or alcohol. weigh 70 kilograms you will probably receive 1.75 to

•    You have a personality disorder. If so, you have a greater ²^ ^{mg of Ativan Injection)}.

chance of becoming dependent on lorazepam. • When Ativan Injection is used to control convulsions a

•    You have any kidney or liver problems. ^{dose of} 4 mg ^{is usuall}y g^{iven intravenousl}y ^{to adults}.

A lower dose of 2 mg given intravenously is usually given

•    ^You ^{have suffered from} ^pram ^the p^{ast since} rt to control convulsions in children. could re-occur during treatment with lorazepam.

_•    You are currently suffering from depression, since ^{Your doctor may prescribe a different dose or length of} lorazepam may increase any suicidal feelings, which you ^{especially if you are elderly}.

^{may have}. Some people feel sleepy after receivisg Ativun

•    You suffer from breathing problems. Injection. Therefore, you muy neeU to stay in hospital

•    You suffer from an eye problem called glaucoma. for at least 8 hours, or overnight, after receiving your

•    You enter hospital for treatment. ^injection: f ^you ^ ^{to leuve} ’^hortly ^

receiving Ativun Injection you should have someone

Taking other medicines with you.

^You sh^ould tell y^our to ^or ph^armaci^st if yo^{u are} takmg Ativan Injection is usually only prescribed for one

^{any othe}r ^medici^{nes includingthose which} h^ ^fot teen or two doses, or for a short course of treatment. prescribed by a doctor, since they may affect the way Ativan

njection works. Ativan Injection tay also affect the vwajr other L^his ^U^ ^{the risk} ^ ^becomin9 ^on _h Ur_{ugs wor}k Ativun Injection, or suffering unpleusunt effects when

^g . you stop taking it (See 'Stopping your medicine',

n particular, you should tell your doctor if you are taking any below).

other sedative, anti-anxiety drugs, antidepressants, strong pain . 5 killers (e.g. methadone), drugs for epilepsy, antihistamines, ^{Instructions for use:} drugs for mood or mental disorders (e.g. chlorpromazine, Ativun umpoules ure equipped with the OPC (One clozapine and haloperidol), drugs for respiratory diseases, Point Cut) opening system and must be opened using 1 drugs for gout (probenecid). The dose of these drugs may the following instructions:

The benzodiazepines, including Ativan Injection, produce additive CNS * Benzodiazepine effects on the CNS are dose dependent, with more

depressant effects when co-administered with other medications which severe CNS depression occurring with higher doses.

hemselves produce CNS depression, e.g. barbiturates, antipsychotics,

sedatives/hypnotics, anxiolytics, antidepressants, narcotic analgesics, sedative y_{ascular disorders}

antihistamines, anticonvulsants and anaesthetics.

Concurrent administration of lorazepam with sodium valproate may result in ^{Undetermined: Hypotension}.

■educed clearance (20 to 40%) and increased concentrations of lorazepam. Respiratory thoracic and mediastinal disorders*

Therefore clinical monitoring is advised and lorazepam dosage should be

_{reduced when appropriate.} Undetermined: Respiratory depression, apnoea, worsening

of sleep

C^{oncurrent administrat}!^{on of} lorazeram ^with pratenecri ^may resit ^{in re}d^uced Worsening of obstructive pulmonary disease. clearance, increased elimination half-life and increased concentrations of _t

orazepam. Therefore clinical monitoring is advised and lorazepam dosage ,^{The e}!^<ten^t °^ff,^{respiratory depression with} terira^zepres is ^dose should be reduced when appropriate. dependent with more severe depression occurring with high doses.

An enhancement of the euphoria induced by narcotic analgesics may occur G^{astrointestinal disorders} with benzodiazepine use, leading to an increase in psychic dependence. Uncommon: Nausea.

Compounds which inhibit certain hepatic enzymes (particularly cytochrome Undetermined: Constipation.

P450) may enhance the activity of benzodiazepines. To a lesser degree this _{Hepatobiliary disorders} also applies to benzodiazepines which are metabolised only by conjugation. ^Hepatobiliary ^disorders

The addition of scopolamine to Ativan Injection is not recommended, since llnteimrred Incre^ h Motorr hcre^ein ^ to

heir combination has been observed to cause an increased incidence of ^{increase in alkaline phosphatase}.

sedation, hallucination and irrational behaviour. Skin and subcutaneous tissue disorders

Concomitant use of clozapine and lorazepam may produce marked sedation, Undetermined: Allergic skin reactions, alopecia.

excessive salivation, and ataxia.

Administration of theophylline or aminophylline may reduce the sedative ^{Reproductive system and breast disorders}

effects of benzodiazepines, including lorazepam. Uncommon: Change in libido, impotence, decreased

There have been reports of apnoea, coma, bradycardia, heart arrest and death ^orgasm.

with the concomitant use of lorazepam injection solution and haloperidol. General disorders and administration site conditions

4.6    F’regnancy and toctahon Very common: Fatigue.

Ativan Injection should not be used during pregnancy, especially during Common: Muscle weakness, asthenia. he first and last trimesters, unless in the judgement of the physician such Und^rnin^ Hyp_oth_ermia administration is clinically justifiable. Benzodiazepines may cause foetal

damage when administered to pregnant women ^{Tolerance at the in}j^{ection site is} g^enerally g^ood ^tagd ^rarely p^{ain and}

redness have been reported after Ativan Injection.

f the drug is prescribed to a woman of childbearing potential, she should

be warned to contact her physician about stopping the drug if she intends to T^{ransient antero}g^rade ^{amnesia or me}mory impam^ay crajr usung become, or suspects that she is, pregnant. ^ther^ap^{eutic the} nsk rereMg ^{at hi}g^her tas; (^see ^Speaa^l mrnitigs

and precautions for use).

Use of Ativan Injection during the late phase of pregnancy may require

v_entil_ati_{on o}f the i_nf_ant at birth Paradoxical reactions may be more likely to occur in children and the elderly

(see Special warnings and precautions for use). f, for compelling medical reasons, the product is administered during the late 4_{q O} ’ _d phase of pregnancy, or during labour at high doses, effects on the neonate, ⁴.^{q Overdose}

such as hypothermia, hypotonia and moderate respiratory depression, can be In the management of overdosage with any drug, it should be borne in mind expected, due to the pharmacological action of the compound. that multiple agents may have been taken. nfants of mothers who ingested benzodiazepines for several weeks or more Overdosage of benzodiazepines is usually manifested by degrees of central preceding delivery have been reported to have withdrawal symptoms during nervous system depression ranging from drowsiness to coma. In mild cases, h_e p_ost_nat_al p_eri_od symptoms include drowsiness, mental confusion and lethargy. In more serious

Symptoms such as hypotonia, hypothermia, respiratory depression, apnoea, ^cases; ^{and es}pf^ciallV ^when C^p^S ^{drugs or s|s} , eeding problems, and impaired metabolic response to cold stress have been touted ^{symptoms may hypoten}s^{ion, hypotonia,} re^ratoty reported in neonates born of mothers who have received benzodiazepines ^dep^ression, ^{cardiovascular de}p^ression, ^{coma and}, ^very ^rarely, ^death. during the late phase of pregnancy or at delivery. Propylene glycol toxicity and polyethylene glycol toxicity have been reported

There are insufficient data regarding obstetrical safety of parenteral Ativan, ,^higher ^ ^df^{s of} A^{tivan Injection} (see Section ncluding use in caesarean section. Such use, therefore, is not recommended. ^{44 Special warnings andprecautions for use)}.

Since benzodiazepines are found in breast milk, Ativan Injection should not T^^enⁿd^tc^C|0⁰_e^Veo^rC⁰f^agn^diO^Sn^mo^atⁿh^le^y S^AS aⁿd^Ce^Uqdia^ge^mn⁰_r,ⁿ,!n⁰,^risⁿh^go⁰f_ld^Vital re given to breastfeeding mothers; unless the expected benefit to the woman be^gnm^SnnSⁿt^dniS^l°_d^Sfa°_d^Sn^esrVa!e⁰Cr _l0,^fs^tp^hie_nt!0r!en,!_edⁿnn^dnddd_dat_d HyS/S'¹ _{the potential} risk _{to the infant} ^{be maintained and assisted res}p^{iration used as needed}. ^pto^d °^{utweighs the potential risk to the infant}. though unlikely, may be controlled with noradrenaline. Lorazepam is poorly

4.7    Effects on ability to drive and use machines dialysable.

Sedation, amnesia, impaired^ concentration and impaired muscular function The benzodiazepine antagonist, flumazenil, may be useful in hospitalised ^{may adversely affect the ability} to ^{drive or use machines}. ^{Therefore, patients} patients for the management of benzodiazepine overdosage. Flumazenil s^{hould not drive or operate machiner}y ^within 24-48 hours of administration product information should be consulted prior to use. The physician should be ^of A^{tivan Injection and should be advised not to take a|coho|} (see also aware of a risk of seizure in association with flumazenil treatment, particularly '^nteractions). in long-term benzodiazepine users and in tricyclic antidepressant overdose. This medicine can impair cognitive function and can affect a patient’s ability to 5 PHARMACOLOGICAL PROPERTIES drive safely. This class of medicine is in the list of drugs included in regulations

under 5a of the Road Traffic Act 1988. When prescribing this medicine, ⁵.¹ ^armacoctynamc ^pro^pert^ies

patients should be told: Ativan is a benzodiazepine with anxiolytic, sedative, hypnotic, anticonvulsant The medicine is likely to affect your ability to drive ^{and muscle relaxan}t ^properties.

Do not drive until you know how the medicine affects you ⁵² ^armacoldntfto ^pro^perti^es

_{It is an offence} to _{drve while under the influence of this medicine} Ativan Injection is readily absorbed when given intramuscularly. Peak ^{It is an offence to drve while under the influence of this medicine} plasma concentrations occur approximately 60-90 minutes following ¹ However, you would sot be committing as offence (called ‘statutory defence) if: i_nt_ramuscul_{ar a}d_mini_st_rati_on

-    You Sestet Ativan is metabolised by a simple one-step process to a pharmacologically S “Onnl^tan°^Cn⁰^Ov?d^t°d^thW^thⁿt^S^e^UCn^tle⁰dⁿi^SciSe aⁿnd^{by p} i^rrngda^Vdg^gl^:°W^!Cdd m^S "s^k o^f accumu^la^tion a^fter repea^te^d

-    at was not affecting your ability to drve safely ^doses, ^{giving a wide margin of safety}.

18 Und_esir_abl_{e e}ff_ects There are no major active metabolites. The elimination half-life is about ⁴.o un^desiram^{e effects} 12-16 hours when given intramuscularly or intravenously.

Adverse reactions are listed in the table in CIOMS frequency categories: 5 3 Pr_eclini_cal _saf_ety data

ter > ¹ %%and < 10% ^Nothing ^{of relevance to the} p^rescriber

Uncommon: > 0.1% and < 1% 6. PHARMACEUTICAL PARTICULARS

Rare: > 0.01% and < 0.1% ₆₁ ,._t . _evcipients Very rare: < 0.01% ⁶¹ List of evcipients

Undetermined: Insufficient data to calculate significant frequencies. Polyethylene glycol 400

System Organ Class Adverse Reaction P^eSpyierie^cocilv(!_ol and Frequency ^{propylene g|yco|}

6.2 Incompatibilities

Blood and lymphatic system disorders _{None known} Undetermined: Thrombocytopenia, agranulocytosis, pancytopenia. 6.3 Sh_elf lif_e

12 months

Immune system disorders

Undetermined: Hypersensitivity reactions, anaphylactic/ ⁶.⁴ Spe<cial precautions for s*°^rage

oid reactions, angioedema. Store and transport refrigerated (2°C to 8°C).

Keep ampoule in the outer carton.

^{Endocrine disorders} 6.5 Nature and contents of container

Undetermined: Syndrome of Inappropriate Antidiuretic 1ml solution in 2ml ampoules (Type I glass) with a one-point-cut opening, Hormone secretion (SIADH). position marked by red spot in pack sizes of 10.

Metabolism and nutrition disorders ⁶.⁶ Sp^ecial preca^ore; ^for d^po^ and ota handhng

Undetermined: Hyponatremia. ^None

7. MARKETING AUTHORISATION HOLDER

Psychiatric disorders _{Pfizer Limited} Common: Confusion, depression, unmasking of depression. Ramsgate Road Undetermined: Disinhibition, euphoria, suicidal ideation/attempt. ^Sandwich

Paradoxical reactions, including anxiety, ^iU ^CT13 9NJ agitation, excitation, hostility, aggression, rage, ^{United Kingdom} sleep disturbances/insomnia, sexual arousal, 8. MARKETING AUTHORISATION NUMBER and hallucinations. pL 00057/1279

Nervous system disorders* 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE

Very common: Sedation, drowsiness. ^AUTH°^RISATI°^N Common: Ataxia, dizziness. 11 August 2011

Undetermined: Extrapyramidal symptoms, tremor, vertigo, visual 10. DATE OF REVISION OF THE TEXT disturbances (including diplopia and blurred 05/2014 vision), dysarthria/slurred speech, headache, convulsions/seizures, amnesia, coma.

Ref: AT 6_1