Fenactol 50mg

1. Name Of The Medicinal Product

Fenactol tablets 50mg

(own label name for distributor for Whatdrug T/A Discovery Pharmaceuticals)

2. Qualitative And Quantitative Composition

Diclofenac sodium 50 mg

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Gastro-resistant tablet.

Round, biconvex, reddish-brown coloured tablet, marked "DICL50" on one face.

4. Clinical Particulars

4.1 Therapeutic Indications

Adults and elderly

Relief of all grades of pain and inflammation in a wide range of conditions, including:

i) arthritic conditions: rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute gout,

ii) acute musculo-skeletal disorders such as periarthritis (for example frozen shoulder), tendinitis, tenosynovitis, bursitis,

iii) other painful conditions resulting from trauma, including fracture, low back pain, sprains, strains, dislocations, orthopaedic, dental and other minor surgery.

Children

Diclofenac Sodim tablets 50mg are not suitable for children.

4.2 Posology And Method Of Administration

For oral administration.

To be taken whole with liquid, preferably with or after food.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).

Adults: 75 mg to 150 mg daily in two or three divided doses.

The recommended maximum daily dose of diclofenac sodium is 150mg.

Children: This medicine is not suitable for children.

Elderly: The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.

4.3 Contraindications

• Hypersensitivity to diclofenac sodium or to any of the excipients.

• Active, or history of recurrent peptic ulcer/haemorrhage or perforation (two or more distinct episodes of proven ulceration or bleeding).

• NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin or other non-steroidal anti-inflammatory drugs.

• Severe heart failure, hepatic failure and renal failure (see section 4.4).

• During the last trimester of pregnancy (see section 4.6)

• History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.

4.4 Special Warnings And Precautions For Use

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).

The use of diclofenac sodium tablets with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5).

Elderly:

The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2).

Respiratory disorders:

Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.

Cardiovascular, Renal and Hepatic Impairment:

The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. Renal function should be monitored in these patients (see also section 4.3).

Cardiovascular and cerebrovascular effects:

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Clinical trial and epidemiological data suggest that use of diclofenac, particularly at high dose (150mg daily) and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with diclofenac after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, and smoking).

Gastrointestinal bleeding, ulceration and perforation:

GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in the elderly. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4.5).

Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5).

When GI bleeding or ulceration occurs in patients receiving diclofenac, the treatment should be withdrawn.

NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8).

SLE and mixed connective tissue disease:

In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (see section 4.8).

Dermatological:

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Diclofenac sodium tablets should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.

Impaired female fertility:

The use of diclofenac sodium tablets may impair female fertility and is not recommended in women attempting to conceive. In women who may have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of diclofenac sodium tablets should be considered.

Sensitivity or intolerance to milk sugars:

This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Other analgesics including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects (see section 4.4).

Anti-hypertensives: Reduced anti-hypertensive effect.

Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

Lithium: Decreased elimination of lithium

Methotrexate: Decreased elimination of methotrexate.

Ciclosporin: Increased risk of nephrotoxicity.

Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.

Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding (see section 4.4).

Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see section 4.4).

Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding (see section 4.4).

Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Zidovudine: Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

4.6 Pregnancy And Lactation

Pregnancy:

Congenital abnormalities have been reported in association with NSAID administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (risk of closure of the ductus arteriosus), use in the last trimester of pregnancy is contraindicated. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child (see section 4.3). NSAIDs should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the foetus.

Lactation:

In limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breast- feeding.

See section 4.4 Special warnings and precautions for use, regarding female fertility.

4.7 Effects On Ability To Drive And Use Machines

Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.

4.8 Undesirable Effects

Gastrointestinal:

The most commonly-observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4) have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.

Hypersensitivity:

Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angiodema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Cardiovascular and cerebrovascular:

Clinical trial and epidemiological data suggest that use of diclofenac, particularly at high doses (150 mg daily) and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

Other adverse reactions reported less commonly include:

Renal:

Nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.

Hepatic:

Abnormal liver function, hepatitis and jaundice.

Neurological and special senses:

Visual disturbances, optic neuritis, headaches, paraesthesia, reports of aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematosus, mixed connective tissue disease), with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation (see section 4.4), depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.

Haematological:

Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.

Dermatological:

Bullous reactions including Stevens Johnson syndrome and Toxic Epidermal Necrolysis (very rare). Photosensitivity.

4.9 Overdose

a) Symptoms

Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, coma, drowsiness, dizziness, tinnitus, fainting, and occasionally, convulsions. In cases of significant poisoning acute renal failure and liver damage are possible.

b) Therapeutic measure

Patients should be treated symptomatically as required.

Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose.

Good urine output should be ensured.

Renal and liver function should be closely monitored.

Patients should be observed for at least four hours after ingestion of potentially toxic amounts.

Frequent or prolonged convulsions should be treated with intravenous diazepam. Other measures may be indicated by the patient's clinical condition.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Diclofenac sodium is a non-steroidal anti-inflammatory agent which has analgesic and antipyretic properties. It is a prostaglandin synthetase (cyclo- oxygenase) inhibitor.

5.2 Pharmacokinetic Properties

Following ingestion, diclofenac sodium is completely absorbed from the intestinal tract but undergoes first pass metabolism and peak plasma concentrations occur in about 2 to 4 hours; at therapeutic concentrations it is more than 99% bound to plasma proteins. Diclofenac is almost entirely metabolised in the liver and the terminal plasma half-life is about 1-2 hours, with metabolic excretion mainly via the kidneys and also in the bile.

5.3 Preclinical Safety Data

Diclofenac sodium is a well established drug for which there are adequate published safety data. This application is an abridged authorisation application submitted under Article 4.8a(iii) of Directive 65/65/EEC and therefore preclinical data have not been submitted.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Granulating fluid:-

Copolyvidone

Core:-

Lactose

Microcrystalline cellulose

Maize starch

Crospovidone

Colloidal silicon dioxide

Magnesium stearate

Enteric coat:-

Triethyl citrate

Methacrylic acid-ethylacrylate copolymer

Talc

Pigmented film coat:-

Hydroxypropyl methyl cellulose

Iron oxide yellow (E172)

Iron oxide red (E172)

Polyethylene glycol

Titanium dioxide (E171)

Sunset Yellow (E110)

Polish:-

Carnauba wax

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

Do not store above 25oC

6.5 Nature And Contents Of Container

The tablets are presented in aluminium/PVC or PVDC-coated-PVC blisters, strips of which are contained within a printed cardboard carton. Pack sizes of 28, 84 and 100 tablets per carton are available.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Dexcel-Pharma Ltd.

1 Cottesbroke Park

Heartlands Business Park

Daventry

Northants

NN11 8YL

UK

8. Marketing Authorisation Number(S)

PL 14017/0019

9. Date Of First Authorisation/Renewal Of The Authorisation

03/12/1996 / 04/03/2009

10. Date Of Revision Of The Text

19/05/2009

TRAVATAN

1. Name Of The Medicinal Product

TRAVATAN 40 micrograms/ml eye drops, solution

2. Qualitative And Quantitative Composition

1 ml of solution contains 40 micrograms of travoprost.

Excipients: benzalkonium chloride 0.15 mg, polyoxyethylene hydrogenated castor oil 40 (HCO-40) 5 mg (see section 4.4.)

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Eye drops, solution .

Clear, colourless solution.

4. Clinical Particulars

4.1 Therapeutic Indications

Decrease of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma (see section 5.1).

4.2 Posology And Method Of Administration

For ocular use.

Use in adults, including the elderly

The dose is one drop of TRAVATAN in the conjunctival sac of the affected eye(s) once daily. Optimal effect is obtained if the dose is administered in the evening.

Nasolacrimal occlusion or gently closing the eyelid after administration is recommended. This may reduce the systemic absorption of medicinal products administered via the ocular route and result in a decrease in systemic adverse reactions.

If more than one topical ophthalmic medicinal product is being used, the medicinal products must be administered at least 5 minutes apart (see section 4.5).

If a dose is missed, treatment should be continued with the next dose as planned. The dose should not exceed one drop in the affected eye(s) daily.

When substituting another ophthalmic antiglaucoma agent with TRAVATAN, the other agent should be discontinued and TRAVATAN should be started the following day.

Paediatric patients

The efficacy and safety of TRAVATAN in patients below the age of 18 years have not been established and its use is not recommended in these patients until further data become available.

Use in hepatic and renal impairment

TRAVATAN has been studied in patients with mild to severe hepatic impairment and in patients with mild to severe renal impairment (creatinine clearance as low as 14 ml/min). No dosage adjustment is necessary in these patients.

The patient should remove the protective overwrap immediately prior to initial use. To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip of the bottle.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

4.4 Special Warnings And Precautions For Use

TRAVATAN may gradually change the eye colour by increasing the number of melanosomes (pigment granules) in melanocytes. Before treatment is instituted, patients must be informed of the possibility of a permanent change in eye colour. Unilateral treatment can result in permanent heterochromia. The long term effects on the melanocytes and any consequences thereof are currently unknown. The change in iris colour occurs slowly and may not be noticeable for months to years. The change in eye colour has predominantly been seen in patients with mixed coloured irides, i.e., blue-brown, grey-brown, yellow-brown and green-brown; however, it has also been observed in patients with brown eyes. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery in affected eyes, but the entire iris or parts of it may be become more brownish. After discontinuation of therapy, no further increase in brown iris pigment has been observed.

In controlled clinical trials, periorbital and/or eyelid skin darkening in association with the use of TRAVATAN has been reported in 0.4% of patients.

TRAVATAN may gradually change eyelashes in the treated eye(s); these changes were observed in about half of the patients in clinical trials and include: increased length, thickness, pigmentation, and/or number of lashes. The mechanism of eyelash changes and their long term consequences are currently unknown.

TRAVATAN has been shown to cause slight enlargement of the palpebral fissure in studies in the monkey. However, this effect was not observed during the clinical trials and is considered to be species specific.

There is no experience of TRAVATAN in inflammatory ocular conditions; nor in neovascular,

angle-closure, narrow-angle or congenital glaucoma and only limited experience in thyroid eye disease, in open-angle glaucoma of pseudophakic patients and in pigmentary or pseudoexfoliative glaucoma.

Caution is recommended when using Travatan in aphakic patients, pseudophakic patients with a torn posterior lens capsule or anterior chamber lenses, or in patients with known risk factors for cystoid macular oedema.

Skin contact with TRAVATAN must be avoided as transdermal absorption of travoprost has been demonstrated in rabbits .

Benzalkonium chloride, which is commonly used as a preservative in ophthalmic products, has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Since TRAVATAN contains benzalkonium chloride, close monitoring is required with frequent or prolonged use.

In patients with known predisposing risk factors for iritis/uveitis, TRAVATAN can be used with caution.

Prostaglandins and prostaglandin analogues are biologically active materials that may be absorbed through the skin. Women who are pregnant or attempting to become pregnant should exercise appropriate precautions to avoid direct exposure to the contents of the bottle. In the unlikely event of coming in contact with a substantial portion of the contents of the bottle, thoroughly cleanse the exposed area immediately

TRAVATAN contains benzalkonium chloride which may cause irritation and is known to discolour soft contact lenses. Contact with soft contact lenses is to be avoided.

Patients must be instructed to remove contact lenses prior to application of TRAVATAN and wait 15 minutes after instillation of the dose before reinsertion.

TRAVATAN contains polyoxyethylene hydrogenated castor oil 40 which may cause skin reactions.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No interaction studies have been performed.

4.6 Pregnancy And Lactation

Women of child-bearing potential/contraception

TRAVATAN must not be used in women of child bearing age/potential unless adequate contraceptive measures are in place (see section 5.3).

Pregnancy

Travoprost has harmful pharmacological effects on pregnancy and/or the foetus/new-born child. TRAVATAN should not be used during pregnancy unless clearly necessary.

Lactation

It is unknown whether travoprost from eye drops is excreted in human breast milk. Animal studies have shown excretion of travoprost and metabolites in breast milk. The use of TRAVATAN by breast-feeding mothers is not recommended.

4.7 Effects On Ability To Drive And Use Machines

As with any eye drop, temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machinery.

4.8 Undesirable Effects

In clinical studies involving over 4200 patients, TRAVATAN was administered once daily as monotherapy or adjunctive therapy to timolol 0.5%. No serious ophthalmic or systemic undesirable effects related to TRAVATAN were reported in any of the clinical studies. The most frequently reported treatment-related undesirable effect with TRAVATAN monotherapy was hyperaemia of the eye (22.3%), which included ocular, conjunctival, or scleral hyperaemia. Hyperaemia was mild in 83.0% of those patients who experienced it. Almost all patients (98%) who experienced hyperaemia did not discontinue therapy as a result of this event. In phase III clinical studies ranging from 6 to 12 months in duration, hyperaemia decreased over time.

The following undesirable effects were assessed to be treatment-related (with TRAVATAN monotherapy) and are classified according to the following convention: very common (

Infections and infestations:

Uncommon: herpes simplex

Immune system disorders:

Uncommon: hypersensitivity, seasonal allergy

Nervous system disorders:

Common: headache

Uncommon: dysgeusia

Eye disorders:

Very common: conjunctival hyperaemia, ocular hyperaemia

Common: punctate keratitis, anterior chamber cell, anterior chamber flare, eye pain, photophobia, eye discharge, ocular discomfort, eye irritation, abnormal sensation in eye, foreign body sensation in eyes, visual acuity reduced, vision blurred, dry eye, eye pruritus, lacrimation increased, erythaema of eyelid, eyelid oedema, eyelids pruritis, growth of eyelashes, iris hyperpigmentation, eyelash discolouration

Uncommon: corneal erosion, iridocyclitis, iritis, uveitis, visual field defect, keratitis, anterior chamber inflammation, eye swelling, corneal staining, photopsia, blepharitis, conjunctival oedema, conjunctivitis allergic, conjunctival disorder, conjunctivitis, conjunctival follicles, hypoaesthesia eye, ectropion, keratoconjunctivitis sicca, madarosis, cataract, eye allergy, eyelid pain, eyelid disorder, eyelid margin crusting, scleral hyperaemia, asthenopia

Cardiac disorders:

Uncommon: heart rate irregular, palpitations, heart rate decreased

Vascular disorders:

Uncommon: blood pressure decreased, blood pressure increased, hypotension

Respiratory, thoracic and mediastinal disorders:

Uncommon: dysponea, asthma, respiratory disorder, pharyngolaryngeal pain, cough, dysphonia, nasal congestion, throat irritation

Gastrointestinal disorders:

Uncommon: peptic ulcer reactivated, gastrointestinal disorder, constipation

Skin and subcutaneous tissue disorders:

Common: skin hyperpigmentation (periocular)

Uncommon: dermatitis allergic, periorbital oedema, dermatitis contact, erythaema, hair colour changes, hair texture abnormal, hypertrichosis

Musculoskeletal, connective tissue and bone disorders:

Uncommon: shoulder pain

General disorders and administrative site conditions:

Uncommon: asthenia, malaise

Adverse reactions identified from post-marketing experience that have not been reported previously in clinical trials with TRAVATAN as monotherapy include the following.

Ocular: macular oedema (see also section 4.4)

Systemic: bradycardia, tachycardia, asthma aggravated, vertigo, tinnitus, PSA increased, hair growth abnormal.

4.9 Overdose

No cases of overdose have been reported. A topical overdose is not likely to occur or to be associated with toxicity. A topical overdose of TRAVATAN may be flushed from the eye(s) with lukewarm water. Treatment of a suspected oral ingestion is symptomatic and supportive.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic Group: Ophthalmologicals – antiglaucoma preparations and

miotics – prostaglandin analogues

ATC code: S01E E04

Mechanism of action

Travoprost, a prostaglandin F_2α analogue, is a highly selective full agonist which has a high affinity for the prostaglandin FP receptor, and reduces the intraocular pressure by increasing the outflow of aqueous humour via trabecular meshwork and uveoscleral pathways. Reduction of the intraocular pressure in man starts about 2 hours after administration and maximum effect is reached after 12 hours. Significant lowering of intraocular pressure can be maintained for periods exceeding 24 hours with a single dose.

Data on adjunctive administration of TRAVATAN with timolol 0.5% and limited data with brimonidine 0.2% were collected during clinical trials that showed an additive effect of TRAVATAN with these glaucoma medications. No clinical data are available on adjunctive use with other ocular hypotensive medications.

Secondary pharmacology

Travoprost significantly increased optic nerve head blood flow in rabbits following 7 days of topical ocular administration (1.4 micrograms, once-daily)

5.2 Pharmacokinetic Properties

Absorption

Travoprost is an ester prodrug. It is absorbed through the cornea where the isopropyl ester is hydrolysed to the active free acid. Studies in rabbits have shown peak concentrations of 20 ng/g of the free acid in aqueous humour one to two hours after topical dosing of TRAVATAN. Aqueous humour concentrations declined with a half-life of approximately 1.5 hours.

Distribution

Following topical ocular administration of TRAVATAN to healthy volunteers, low systemic exposure to active free acid was demonstrated. Peak active free acid plasma concentrations of 25 pg/ml or less were observed between 10 and 30 minutes post-dose. Thereafter, plasma levels declined rapidly to below the 10 pg/ml assay quantitation limit before 1 hour post-administration. Due to the low plasma concentrations and rapid elimination following topical dosing, the elimination half-life of active free acid in man could not be determined.

Metabolism

Metabolism is the major route of elimination of both travoprost and the active free acid. The systemic metabolic pathways parallel those of endogenous prostaglandin F_2α which are characterised by reduction of the 13-14 double bond, oxidation of the 15-hydroxyl and β-oxidative cleavages of the upper side chain.

Excretion

Travoprost free acid and its metabolites are mainly excreted by the kidneys. TRAVATAN has been studied in patients with mild to severe hepatic impairment and in patients with mild to severe renal impairment (creatinine clearance as low as 14 ml/min). No dosage adjustment is necessary in these patients.

5.3 Preclinical Safety Data

In ocular toxicity studies in monkeys, administration of travoprost at a dose of 0.45 microgram, twice a day, was shown to induce increased palpebral fissure. Topical ocular administration of travoprost to monkeys at concentrations of up to 0.012% to the right eye, twice daily for one year resulted in no systemic toxicity.

Reproduction toxicity studies have been undertaken in rat, mice and rabbit by systemic route. Findings are related to FP receptor agonist activity in uterus with early embryolethality, post-implantation loss, foetotoxicity. In pregnant rat, systemic administration of travoprost at doses more than 200 times the clinical dose during the period of organogenesis resulted in an increased incidence of malformations. Low levels of radioactivity were measured in amniotic fluid and foetal tissues of pregnant rats administered ³H

6. Pharmaceutical Particulars

6.1 List Of Excipients

Benzalkonium chloride

Polyoxyethylene hydrogenated castor oil 40 (HCO-40)

Trometamol

Disodium edetate

Boric acid (E284)

Mannitol (E421)

Sodium hydroxide and/or hydrochloric acid (to adjust pH)

Purified water

6.2 Incompatibilities

None known.

Specific in vitro interaction studies were performed with TRAVATAN and medicinal products containing thiomersal. No evidence of precipitation was observed.

6.3 Shelf Life

3 years.

Discard 4 weeks after first opening.

6.4 Special Precautions For Storage

This medicinal product does not require any special storage conditions.

6.5 Nature And Contents Of Container

2.5 ml oval bottle with dispensing plug and screw cap, all polypropylene, presented in an overwrap.

Cartons containing 1 or 3 bottles.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Alcon Laboratories (UK) Ltd.

Boundary Way

Hemel Hempstead

Herts HP2 7UD

United Kingdom.

8. Marketing Authorisation Number(S)

EU/1/01/199/001-002

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of first authorisation :27.11.2001

Date of last renewal: 27.11.2006

10. Date Of Revision Of The Text

Adderall

Pronunciation: am-FET-a-meen/DEX-troe-am-FET-a-meen
Generic Name: Amphetamine/Dextroamphetamine
Brand Name: Adderall

Adderall has a high potential for abuse and may be habit-forming if used for a long period of time. Use Adderall only as prescribed and do not share it with others. Abuse of Adderall may cause serious heart problems, blood vessel problems, or sudden death.

Adderall is used for:

Treating attention deficit hyperactivity disorder (ADHD) and narcolepsy (sudden and uncontrollable attacks of drowsiness and sleepiness). It may also be used for other conditions as determined by your doctor.

Adderall is an amphetamine. Exactly how it works is not known. Adderall affects certain chemicals in the brain that may affect attention span and behavior.

Do NOT use Adderall if:

• you are allergic to any ingredient in Adderall or to similar medicines


• you have severe hardening of the arteries; active heart or blood vessel disease; moderate, severe, or uncontrolled high blood pressure; an overactive thyroid; glaucoma; or agitation, anxiety, or tension


• you have serious heart problems (eg, heart defect, irregular heartbeat)


• you have a history of alcohol or other substance abuse


• you have taken furazolidone or a monoamine oxidase inhibitor (MAOI) (eg, phenelzine) within the last 14 days


• you are taking guanethidine or guanadrel

Contact your doctor or health care provider right away if any of these apply to you.

Before using Adderall:

Some medical conditions may interact with Adderall. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a history of heart problems (eg, heart failure, fast or irregular heartbeat), heart defects, a recent heart attack, high blood pressure, hardening of the arteries, or blood vessel problems, or if a family member has a history of irregular heartbeat or sudden death


• if you have a history of liver or kidney problems, growth problems, thyroid problems, uncontrolled muscle movements (eg, tics), Tourette syndrome, anorexia, or the blood disease porphyria


• if you have a history of seizures or abnormal electroencephalograms (EEGs)


• if you have a history of mood or mental problems (eg, agitation, anxiety, bipolar disorder, depression, psychosis, tension), abnormal thoughts, hallucinations, suicidal thoughts or attempts, or alcohol or other substance abuse or dependence or if a family member has a history of any of these problems

Some MEDICINES MAY INTERACT with Adderall. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Furazolidone or MAOIs (eg, phenelzine) because side effects, such as increased blood pressure, headache, fever, and irregular heartbeat, may occur


• Alkalinizing agents (eg, antacids, sodium bicarbonate, acetazolamide), decongestants (eg, pseudoephedrine), propoxyphene, proton pump inhibitors (PPIs) (eg, lansoprazole, omeprazole), or sympathomimetic medicines (eg, albuterol) because they may increase the risk of Adderall's side effects


• Glutamic acid, haloperidol, lithium carbonate, phenothiazines (eg, chlorpromazine), PPIs (eg, lansoprazole, omeprazole), reserpine, urinary acidifiers (eg, methenamine, ammonium chloride), or vitamin C (ascorbic acid) because they may decrease Adderall's effectiveness


• Meperidine, norepinephrine, selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine), tramadol, or tricyclic antidepressants (eg, desipramine) because the risk of their side effects may be increased by Adderall


• Alpha-blockers (eg, prazosin), antihistamines (eg, diphenhydramine), beta-blockers (eg, metoprolol), ethosuximide, guanadrel, guanethidine, medicines for high blood pressure, phenobarbital, or phenytoin because their effectiveness may be decreased by Adderall

This may not be a complete list of all interactions that may occur. Ask your health care provider if Adderall may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Adderall:

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

• Adderall comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Adderall refilled.


• Take Adderall by mouth with or without food.


• Take your last dose of the day 4 to 6 hours before bedtime unless your doctor tells you differently.


• Do not take antacids (eg, calcium carbonate) or certain alkalinizing agents (eg, sodium bicarbonate) with Adderall without first talking with your doctor. They may increase the risk of Adderall's side effects.


• If you miss a dose of Adderall, 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 Adderall.

Important safety information:

• Adderall may cause dizziness, drowsiness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Adderall with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• When used to treat ADHD, Adderall should be used as part of an ADHD treatment program that includes a variety of treatment measures (eg, psychological, educational, social).


• Certain foods and medicines can affect the amount of acid in your stomach and intestine. This can increase or decrease (depending on the medicine) the absorption of Adderall. Tell your doctor if you take any of these products: fruit juice, ascorbic acid (vitamin C), sodium bicarbonate, ammonium chloride, sodium acid phosphate, ulcer medicines (eg, H₂ blockers such as famotidine and ranitidine, PPIs such as omeprazole and lansoprazole), antacids, methenamine, or acetazolamide.


• Serious effects, including a heart attack, stroke, and sudden death, have occurred with the use of stimulant medicines in patients with heart defects or other serious heart problems. If you have a heart defect or other serious problem, talk with your doctor about other therapies to treat your condition.


• Avoid large amounts of food or drink that have caffeine (eg, coffee, tea, cocoa, cola, chocolate).


• Before you start any new medicine, check the label to see if it has a decongestant in it. If it does or if you are not sure, check with your doctor or pharmacist.


• Do NOT take more than the recommended dose without checking with your doctor.


• Tell your doctor or dentist that you take Adderall before you receive any medical or dental care, emergency care, or surgery.


• Adderall may cause you to become sunburned more easily. Avoid the sun, sunlamps, or tanning booths until you know how you react to Adderall. Use a sunscreen or wear protective clothing if you must be outside for more than a short time.


• Adderall may interfere with certain lab tests. Be sure your doctor and lab personnel know you are taking Adderall.


• Lab tests, including blood pressure, pulse, and heart function, may be performed while you use Adderall. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Adderall should not be used in CHILDREN younger than 3 years old; safety and effectiveness in these children have not been confirmed.


• Adderall may affect growth rate and weight gain in CHILDREN and teenagers in some cases. They may need regular growth and weight checks while they take Adderall.


• PREGNANCY and BREAST-FEEDING: Adderall may cause harm to the fetus. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Adderall while you are pregnant. Adderall is found in breast milk. Do not breast-feed while taking Adderall.

When used for long periods of time or at high doses, Adderall may not work as well and may require higher doses to obtain the same effect as when originally taken. This is known as TOLERANCE. Talk with your doctor if Adderall stops working well. Do not take more than prescribed.

When used for longer than a few weeks or at high doses, some people develop a need to continue taking Adderall. This is known as DEPENDENCE or addiction.

Do not suddenly stop taking Adderall. If you do, you may have WITHDRAWAL symptoms. These may include feeling unwell or unhappy, anxious or irritable, dizzy, confused, or sluggish. You may also have nausea, unusual skin sensations, mood swings, headache, trouble sleeping, or sweating. If you need to stop Adderall, your doctor will lower your dose over time.

Possible side effects of Adderall:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; diarrhea; dizziness; dry mouth; headache; loss of appetite; nausea; nervousness; restlessness; stomach pain or upset; trouble sleeping; unpleasant taste; vomiting; weakness; weight loss.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blurred vision or other vision problems; change in sexual ability or desire; chest pain; confusion; fainting; fast or irregular heartbeat; fever, chills, or sore throat; new or worsening mental or mood problems (eg, aggression, agitation, anxiety, delusions, depression, hallucination, hostility); numbness or tingling of an arm or leg; one-sided weakness; painful or frequent urination; red, swollen, peeling, or blistered skin; seizures; severe or persistent headache; severe stomach pain; severe weight loss; shortness of breath; sudden, severe dizziness or vomiting; slurred speech; uncontrolled muscle movement; unusual weakness or tiredness.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Adderall side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include confusion; fast breathing; fever; hallucinations; irregular heartbeat; muscle pain or tenderness; seizures; severe mental or mood changes; severe or persistent headache or dizziness; severe restlessness.

Proper storage of Adderall:

Store Adderall at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, light, and moisture. Keep Adderall out of the reach of children and away from pets.

General information:

• If you have any questions about Adderall, please talk with your doctor, pharmacist, or other health care provider.


• Adderall is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Adderall. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Adderall resources

• Adderall Side Effects (in more detail)
• Adderall Dosage
• Adderall Use in Pregnancy & Breastfeeding
• Drug Images
• Adderall Drug Interactions
• Adderall Support Group
• 108 Reviews for Adderall - Add your own review/rating

• Adderall Prescribing Information (FDA)


• Adderall Consumer Overview


• Adderall Monograph (AHFS DI)


• Adderall Advanced Consumer (Micromedex) - Includes Dosage Information


• Adderall XR Prescribing Information (FDA)

Compare Adderall with other medications

• ADHD
• Narcolepsy

Petrem

Dosage Form: FOR ANIMAL USE ONLY
Petrem®(sevoflurane, USP) Inhalation Anesthetic For Use in Dogs              

Petrem Description

Petrem® (sevoflurane, USP), a volatile liquid, is a halogenated general inhalation anesthetic drug. Its chemical name is fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl) ethyl ether, and its structural formula is:

 

 

Sevoflurane, USP Physical Constants are:

Molecular weight 200.05

point at 760 mm Hg 58.6°C

Specific gravity at 20°C 1.520-1.525 g/mL

Vapor pressure in mm Hg at  20°C 157

                                           at 25°C 197

                                           at 36°C 317

Distribution Partition Coefficients at 37°C:

Blood/Gas 0.63-0.69

Water/Gas 0.36

Olive Oil/Gas 47-54

Brain/Gas 1.15

Mean Component/Gas Partition Coefficients at 25°C for Polymers Used Commonly in Medical Applications:

Conductive rubber 14.0

Butyl rubber 7.7

Polyvinyl chloride 17.4

Polyethylene 1.3

Sevoflurane, USP is nonflammable and nonexplosive as defined by the requirements of

International Electrotechnical Commission 601-2-13.

Sevoflurane, USP is a clear, colorless, stable liquid containing no additives or chemical stabilizers.

Sevoflurane, USP is nonpungent. It is miscible with ethanol, ether, chloroform and petroleum benzene, and it is slightly soluble in water. Sevoflurane, USP is stable when stored under normal room lighting condition according to instructions.

Petrem - Clinical Pharmacology

Sevoflurane, USP is an inhalational anesthetic agent for induction and maintenance of general anesthesia. The Minimum Alveolar Concentration (MAC) of sevoflurane, USP as determined in 18 dogs is 2.36%.2 MAC is defined as that alveolar concentration at which 50% of healthy patients fail to respond to noxious stimuli. Multiples of MAC are used as a guide for surgical levels of anesthesia, which are typically 1.3 to 1.5 times the MAC value. Because of the low solubility of sevoflurane, USP in blood (blood/gas partition coefficient at 37°C = 0.63-0.69), a minimal amount of sevoflurane, USP is required to be dissolved in the blood before the alveolar partial pressure is in equilibrium with the arterial partial pressure. During sevoflurane, USP induction, there is a rapid increase in alveolar concentration toward the inspired concentration.

 

Sevoflurane, USP produces only modest increases in cerebral blood flow and metabolic rate, and has little or no ability to potentiate seizures.3 Sevoflurane, USP has a variable effect on heart rate, producing increases or decreases depending on experimental conditions.4,5 Sevoflurane, USP produces dose-dependent decreases in mean arterial pressure, cardiac output and myocardial contraction.6 Among inhalation anesthetics, sevoflurane, USP has low arrhythmogenic potential.7

 

Sevoflurane, USP is chemically stable. No discernible degradation occurs in the presence of strong acids or heat. Sevoflurane, USP reacts through direct contact with CO2 absorbents (soda lime and barium hydroxide lime) producing pentafluoroisopropenyl fluoromethyl ether (PIFE, C4H2F60), also known as Compound A, and trace amounts of pentafluoromethoxy isopropyl fluoromethyl ether (PMFE, C5H6F60), also known as Compound B.

 

Compound A:

The production of degradants in the anesthesia circuit results from the extraction of the acidic proton in the presence of a strong base (potassium hydroxide and/or NaOH) forming an alkene (Compound A) from sevoflurane, USP. Compound A is produced when sevoflurane, USP interacts with soda lime or barium hydroxide lime. Reaction with barium hydroxide lime results in a greater production of Compound A than does reaction with soda lime. Its concentration in a circle absorber system increases with increasing sevoflurane, USP concentrations and with decreasing fresh gas flow rates. Sevoflurane, USP degradation in soda lime has been shown to increase with temperature. Since

the reaction of carbon dioxide with absorbents is exothermic, this temperature increase will be determined by the quantities of CO2 absorbed, which in turn will depend on fresh gas flow in the anesthetic circle system, metabolic status of the patient and ventilation. Although Compound A is a dose-dependent nephrotoxin in rats, the mechanism of this renal toxicity is unknown. Two spontaneously breathing dogs under sevoflurane, USP anesthesia showed increases in concentrations of Compound A as the oxygen flow rate was decreased at hourly intervals, from 500 mL/min (36 and 18 ppm Compound A) to 250 mL/min (43 and 31 ppm) to 50 mL/min (61 and 48 ppm).8

 

 

Fluoride ion metabolite:

Sevoflurane, USP is metabolized to hexafluoroisopropanol (HFIP) with release of inorganic fluoride and CO2. Fluoride ion concentrations are influenced by the duration of anesthesia and the concentration of sevoflurane, USP. Once formed, HFIP is rapidly conjugated with glucuronic acid and eliminated as a urinary metabolite. No other metabolic pathways for sevoflurane, USP have been identified. In humans, the fluoride ion half-life was prolonged in patients with renal impairment, but human clinical trials contained no reports of toxicity associated with elevated fluoride ion levels. In a study in which 4 dogs were exposed to 4% sevoflurane, USP for 3 hours, maximum serum fluoride concentrations of 17.0-27.0 mcmole/L were observed after 3 hours of anesthesia. Serum fluoride fell quickly after anesthesia ended, and had returned to baseline

by 24 hours post-anesthesia.

 

In a safety study, eight healthy dogs were exposed to sevoflurane, USP for 3 hours/day, 5 days/week for 2 weeks (total 30 hours exposure) at a flow rate of 500 mL/min in a semi-closed, rebreathing system with soda lime. Renal toxicity was not observed in the study evaluation of clinical signs, hematology, serum chemistry, urinalysis, or gross or microscopic pathology.

INDICATIONS & USAGE

Petrem® is indicated for induction and maintenance of general anesthesia in dogs.

Contraindications

Petrem® is contraindicated in dogs with a known sensitivity to sevoflurane, USP or other

halogenated agents.

Warnings

sevoflurane, USP is a profound respiratory depressant. DUE TO THE RAPID AND DOSE DEPENDENT CHANGES IN ANESTHETIC DEPTH, RESPIRATION MUST BE MONITORED CLOSELY IN THE DOG AND SUPPORTED WHEN NECESSARY WITH SUPPLEMENTAL OXYGEN AND/OR ASSISTED VENTILATION.

 

In cases of severe cardiopulmonary depression, discontinue drug administration, ensure the existence of a patent airway and initiate assisted or controlled ventilation with pure oxygen. Cardiovascular depression should be treated with plasma expanders, pressor agents, antiarrhythmic agents or other techniques as appropriate for the observed abnormality. Due to sevoflurane, USP’s low solubility in blood, increasing the concentration may result in rapid hemodynamic changes (dose dependent decreases in blood pressure) compared to other volatile anesthetics. Excessive decreases in blood pressure or respiratory depression may be corrected by decreasing or discontinuing the inspired concentration of sevoflurane, USP.

Potassium hydroxide containing CO2 absorbents (e.g. BARALYME) are not recommended for use with sevoflurane, USP.

Precautions

Halogenated volatile anesthetics can react with desiccated carbon dioxide (CO2) absorbents to produce carbon monoxide (CO) that may result in elevated carboxyhemoglobin levels in some patients. To prevent this reaction, sevoflurane should not be passed through desiccated soda lime or barium hydroxide lime.

 

Replacement of Desiccated Co2 Absorbents:

When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced before administration of sevoflurane. The exothermic reaction that occurs with sevoflurane and CO2 absorbent is increased when the CO2 extended period of dry gas flow through the CO2 absorbent canisters. Extremely rare cases of spontaneous fire in the respiratory circuit of the anesthesia machine have been reported during sevoflurane use in conjunction with the use of desiccated CO2 absorbent, specifically those containing potassium hydroxide (e.g. BARALYME). Potassium hydroxide-containing CO2 absorbents are not recommended for use with sevoflurane. An unusually delayed rise in the inspired gas concentration (decrease delivery) of sevoflurane compared with the

vaporizer setting may indicate excessive heating of the CO2 absorbent canister

and chemical breakdown of sevoflurane. The color indicator of most CO2 absorbent may not change upon desiccation. Therefore, the lack of significant color change should not be taken as an assurance of adequate hydration. CO2 absorbents should be replaced routinely regardless of the state of the color indicator.

The use of some anesthetic regimens that include sevoflurane may result in bradycardia that is reversible with anticholinergics. Studies using sevoflurane anesthetic regimens that included atropine or glycopyrrolate as premedicants showed these anticholinergics to be compatible with sevoflurane in dogs.

During the maintenance of anesthesia, increasing the concentration of sevoflurane produces dose dependent decreases in blood pressure. Due to sevoflurane's low solubility in blood, these hemodynamic changes may occur more rapidly than with other volatile anesthetics. Excessive decreases in blood pressure or respiratory depression may be related to depth of anesthesia and may be corrected by decreasing the inspired concentration of sevoflurane. RESPIRATION MUST BE MONITORED CLOSELY IN THE DOG AND SUPPORTED WHEN NECESSARY WITH SUPPLEMENTAL OXYGEN AND/OR ASSISTED VENTILATION.

The low solubility of sevoflurane also facilitates rapid elimination by the lungs.

The use of sevoflurane in humans increases both the intensity and duration of neuromuscular blockade induced by nondepolarizing muscle relaxants. The use of sevoflurane with nondepolarizing muscle relaxants has not been evaluated in dogs.

 

Compromised or debilitated dogs: Doses may need adjustment for geriatric or debilitated dogs. Because clinical experience in administering sevoflurane to dogs with renal, hepatic and cardiovascular insufficiency is limited, its safety in these dogs has not been established.

 

Breeding dogs: The safety of sevoflurane in dogs used for breeding purposes, during pregnancy, or in lactating bitches, has not been evaluated.

Neonates: The safety of sevoflurane in young dogs (less than 12 weeks of age) has not been evaluated.

 

Caution:

Federal law restricts this drug to use by or on the order of a licensed veterinarian.

 

General Precautions

HUMAN SAFETY:

Not for human use. Keep out of reach of children.

 

Operating rooms and animal recovery areas should be provided with adequate ventilation to prevent the accumulation of anesthetic vapors.

There is no specific work exposure limit established for sevoflurane. However, the National Institute for Occupational Safety and Health has recommended an 8 hour time-weighted average limit of 2 ppm for halogenated anesthetic agents in general.

 

Direct exposure to eyes, may result in mild irritation. If eye exposure occurs, flush with plenty of water for 15 minutes. Seek medical attention if irritation persists.

Symptoms of human overexposure (inhalation) to sevoflurane, USP vapors include respiratory depression, hypotension, bradycardia, shivering, nausea and headache. If these symptoms occur, remove the individual from the source of exposure and seek medical attention. The material safety data sheet (MSDS) contains more detailed occupational safety information.

For customer service, adverse effects reporting, and/or a copy of the MSDS, call (610) 974-9760.

Drug Interactions

In the clinical trial, sevoflurane, USP was used safely in dogs that received frequently used veterinary products including steroids and heartworm and flea preventative products.

Intravenous Anesthetics: Sevoflurane, USP administration is compatible with barbiturates, propofol and other commonly used intravenous anesthetics.

 

Benzodiazepines and Opioids: Benzodiazepines and opioids would be expected to decrease the MAC of sevoflurane, USP in the same manner as other inhalational anesthetics. Sevoflurane, USP is compatible with benzodiazepines and opioids as commonly used in surgical practice.

Phenothiazines and Alpha2-Agonists: Sevoflurane, USP is compatible with  phenothiazines and alpha2-agonists as commonly used in surgical practice.

In a laboratory study, the use of the acepromazine/oxymorphone/thiopental/sevoflurane, USP anesthetic regimen resulted in prolonged recoveries in eight (of 8) dogs compared to recoveries from sevoflurane, USP alone.

STORAGE CONDITIONS:

Store at controlled room temperature 15°C-30°C (59°F-86°F).

Adverse Reactions

The most frequently reported adverse reactions during maintenance anesthesia were hypotension, followed by tachypnea, muscle tenseness, excitation, apnea, muscle fasciculations and emesis.

Infrequent adverse reactions include paddling, retching, salivation, cyanosis, premature ventricular contractions and excessive cardiopulmonary depression. Transient elevations in liver function tests and white blood cell count may occur with sevoflurane, USP, as with the use of other halogenated anesthetic agents.

DOSAGE & ADMINISTRATION

Inspired Concentration: The delivered concentration of Petrem® should be known. Since the depth of anesthesia may be altered easily and rapidly, only vaporizers producing predictable percentage concentrations of sevoflurane, USP should be used. Sevoflurane, USP should be vaporized using a precision vaporizer specifically calibrated for sevoflurane. Sevoflurane, USP contains no stabilizer.

Nothing in the drug product alters calibration or operation of these vaporizers. The administration of general anesthesia must be individualized based on the patient's response.

WHEN USING SEVOFLURANE, USP PATIENTS SHOULD BE CONTINUOSLY MONITORED AND FACILITIES FOR MAINTENANCE OF PATENT AIRWAY, ARTIFICIAL VENTILATION, AND OXYGEN SUPPLEMENTATION MUST BE IMMEDIATELY AVAILABLE.

 

Replacement of Desiccated CO2 Absorbents: When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced. An exothermic reaction occurs when sevoflurane, USP is exposed to CO2 absorbents. This reaction is increased when the CO2 absorbent becomes desiccated (see PRECAUTIONS).

 

Premedication: No specific premedication is either indicated or contraindicated with sevoflurane, USP. The necessity for and choice of premedication is left to the discretion of the veterinarian. Preanesthetic doses for premedicants may be lower than the label directions for their use as a single medication.1

 

Induction: For mask induction using sevoflurane, USP alone, inspired concentrations of up to 7% sevoflurane, USP with oxygen are employed to induce surgical anesthesia in the healthy dog. These concentrations can be expected to produce surgical anesthesia in 3 to 14 minutes.

Due to the rapid and dose dependent changes in anesthetic depth, care should be taken to prevent overdosing. Respiration must be monitored closely in the dog and supported when necessary with supplemental oxygen and/or assisted ventilation.

 

Maintenance: Petrem® may be used for maintenance anesthesia following mask induction using sevoflurane, USP or following injectable induction agents. The concentration of vapor necessary to maintain anesthesia is much less than that required to induce it.

 

Surgical levels of anesthesia in the healthy dog may be maintained with inhaled concentrations of 3.7-4.0% sevoflurane, USP in oxygen in the absence of premedication and 3.3-3.6% in the presence of premedication. The use of injectable induction agents without premedication has little effect on the concentrations of sevoflurane, USP required for maintenance. Anesthetic regimens that include opioid, alpha2- agonist, benzodiazepine or phenothiazine premedication will allow the use of lower sevoflurane, USP maintenance concentrations.

How is Petrem Supplied

Petrem® (sevoflurane, USP) is packaged in amber colored bottles containing 250 mL

sevoflurane, USP, NDC 66794-018-25.

Clinical Studies

CLINICAL EFFECTIVENESS:

The effectiveness of sevoflurane, USP was investigated in a clinical study involving 196 dogs. Thirty dogs were mask-induced with sevoflurane, USP using anesthetic regimens that included various premedicants. During the clinical study, one hundred sixty-six dogs received sevoflurane, USP maintenance anesthesia as part of several anesthetic regimens that used injectable induction agents and various premedicants. The duration of anesthesia and the choice of anesthetic regimens were dependent upon the procedures that were performed. Duration of anesthesia ranged from 16 to 424 minutes among the

individual dogs. Sevoflurane, USP vaporizer concentrations during the first 30 minutes of maintenance anesthesia were similar among the various anesthetic regimens. The quality of maintenance anesthesia was considered good or excellent in 169 out of 196 dogs.

The table shows the average vaporizer concentrations and oxygen flow rates during the first 30 minutes for all sevoflurane, USP maintenance anesthesia regimens:

______________________________________________________________________

 

Average Vaporizer      Average Vaporizer       Average                         Average

Concentrations            Concentrations             Oxygen Flow                 Oxygen Flow

among Anesthetic       among Individual         Rates among                  Rates among

Regimens                    Dogs                             Anesthetic Regimens     Individual Dogs

_____________________________________________________________________

3.31 -3.63%                       1.6 - 5.1%                  0.97 - 1.31 L/minute     0.5-3.0 L / minute                                                                                                                                             

______________________________________________________________________

During the clinical trial, when a barbiturate was used for induction, the times to extubation, sternal recumbency and standing recovery were longer for dogs that received anesthetic regimens containing two preanesthetics compared to regimens containing one preanesthetic. Recovery times were shorter when anesthetic regimens used sevoflurane, USP or propofol for induction. The quality of recovery was considered good or excellent in 184 out of 196 dogs. Anesthetic regimen drug dosages, physiological responses, and the quality of induction, maintenance and recovery were comparable between 10 sighthounds and other breeds evaluated in the study. During the clinical study there was no indication of prolonged recovery times in the sighthounds.

REFERENCES

1. Plumb, D.C. ed., Veterinary Drug Handbook, Second Edition, University of Iowa Press, Ames, IA: p. 424 (1995).

2. Kazama, T. and Ikeda, K., Comparison of MAC and the rate of rise of alveolar concentration of sevoflurane with halothane and isoflurane in the dog. Anesthesiology. 68: 435-437 (1988).

3. Scheller, M.S., Nakakimura, K., Fleischer, J.E. and Zornow, M.H., Cerebral effects of

sevoflurane in the dog: Comparison with isoflurane and enflurane. Brit. J. Anesthesia 65:

388-392 (1990).

4. Frink, E.J., Morgan, S.E., Coetzee, A., Conzen, P.F. and Brown, B.R., Effects of sevoflurane, halothane, enflurane and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs. Anesthesiology 76: 85-90 (1992).

5. Kazama, T. and Ikeda, K., The comparative cardiovascular effects of sevoflurane with halothane and isoflurane. J. Anesthesiology 2: 63-8 (1988).

6. Bernard, J. M., Wouters, P.F., Doursout, M.F., Florence, B., Chelly, J.E. and Merin, R.G., Effects of sevoflurane on cardiac and coronary dynamics in chronically instrumented dogs. Anesthesiology 72: 659-662 (1990).

7. Hayaski, Y., Sumikawa, K., Tashiro, C., Yamatodani, A. and Yoshiya, I., Arrhythmogenic threshold of epinephrine during sevoflurane, enflurane and isoflurane anesthesia in dogs. Anesthesiology 69: 145-147 (1988).

8. Muir, W.W. and Gadawski, J., Cardiorespiratory effects of low-flow and closed circuit inhalation anesthesia, using sevoflurane delivered with an in-circuit vaporizer and concentrations of compound A. Amer. J. Vet. Res. 59 (5): 603-608 (1998).

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL -Bottle Label - 250ml

PACKAGE LABEL. PRINCIPAL DISPLAY PANELBottle -Label - 250ml

 

NDC 66794-018-25

Petrum

Sevoflurane, USP

Inhalation Anesthetic

For use in dogs

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL -Carton- 250ml

PACKAGE LABEL. PRINCIPAL DISPLAY PANEL- Carton- 250ml

 

 

NDC 66794-018-25

Petrum

Sevoflurane, USP

Inhalation Anesthetic

For use in dogs

Petrem  sevoflurane   inhalant

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 66794-018 Route of Administration NASAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength SEVOFLURANE (SEVOFLURANE) SEVOFLURANE 99.9 mL  in 100 mL

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 66794-018-25 250 mL In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANADA	ANADA200438	07/06/2010

Labeler - Piramal Critical Care Inc. (160044640)

Registrant - Piramal Critical Care Inc. (160044640)

Establishment
Name	Address	ID/FEI	Operations
Piramal Critical Care Inc.		160044640	ANALYSIS, MANUFACTURE

Revised: 06/2010Piramal Critical Care Inc.

Cytarabine

Pronunciation: sye-TAR-a-been
Generic Name: Cytarabine
Brand Name: DepoCyt

Cytarabine will be given in a setting where you can be closely monitored by your doctor because it may cause a side effect called chemical arachnoiditis. Symptoms include nausea, vomiting, headache, and fever. This can be fatal if left untreated. Your doctor will usually give you another medicine called dexamethasone to decrease the risk and severity of this side effect.

Cytarabine is used for:

Treating lymphomatous meningitis.

Cytarabine is an antimetabolite. The way Cytarabine works is not completely understood. It may work by binding to the RNA or DNA of certain cancer cells, which helps to slow down their growth and reproduction. It may also act by inhibiting an enzyme that works in the cancer cell reproduction.

Do NOT use Cytarabine if:

• you are allergic to any ingredient in Cytarabine


• you have an infection in the covering of your brain and spinal cord (meningeal infection)


• you have taken or will be taking palifermin within 24 hours before or after using Cytarabine

Contact your doctor or health care provider right away if any of these apply to you.

Before using Cytarabine:

Some medical conditions may interact with Cytarabine. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are able to become pregnant


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have diabetes or spinal fluid problems, or you are receiving chemotherapy or radiation treatment


• if you cannot take dexamethasone

Some MEDICINES MAY INTERACT with Cytarabine. Tell your health care provider if you are taking any other medicines, especially any of the following: Palifermin because if mouth or tongue sores develop, they may be more severe or last longer

This may not be a complete list of all interactions that may occur. Ask your health care provider if Cytarabine may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Cytarabine:

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

• Cytarabine is usually administered as an injection at your doctor's office, hospital, or clinic. Ask your doctor or pharmacist any questions you have about Cytarabine.


• Do not shake Cytarabine.


• If the medicine contains particles or is discolored, or if the vial/container is cracked or damaged in any way, do not use it.


• Your doctor will usually prescribe another medicine called dexamethasone to reduce the risk of side effects from Cytarabine. It is important to take it. If you develop side effects from dexamethasone or cannot take it, contact your doctor immediately.


• If you miss a dose of Cytarabine, contact your doctor immediately for instructions.

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

Important safety information:

• Cytarabine may cause drowsiness or dizziness. These effects may be worse if you take it with alcohol or certain medicines. Use Cytarabine with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do not receive a live vaccine (eg, measles, mumps) while you are taking Cytarabine. Talk with your doctor before you receive any vaccine.


• Cytarabine may cause spinal cord problems or severe nerve problems, which may rarely lead to permanent nerve problems. The risk may be increased if Cytarabine is used along with other chemotherapy medicines or with head or spine radiation therapy. Discuss any questions or concerns with your doctor.


• Cytarabine may reduce the number of clot-forming cells (platelets) in your blood. To prevent bleeding, avoid situations in which bruising or injury may occur. Report any unusual bleeding, bruising, blood in stools, or dark, tarry stools to your doctor.


• If you spill Cytarabine on your skin, wash it off right away with soap and water. If Cytarabine comes into contact with your eyes, nose, or mouth, flush thoroughly with water. Clean any areas (tables, counters) where the medicine may have been spilled or sprayed.


• Cytarabine may lower the ability of your body to fight infection. Avoid contact with people who have colds or infections. Tell your doctor if you notice signs of infection like fever, sore throat, rash, or chills.


• Diabetes patients - Cytarabine may raise your blood sugar. High blood sugar may make you feel confused, drowsy, or thirsty. It can also make you flush, breathe faster, or have a fruit-like breath odor. If these symptoms occur, tell your doctor right away.


• If you are able to become pregnant, talk with your doctor about using an effective form of birth control.


• Lab tests, including liver and kidney function tests and complete blood cell count, may be performed to monitor your progress or to check for side effects. Be sure to keep all doctor and lab appointments.


• Use Cytarabine with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: Cytarabine has been shown to cause harm to the fetus. Avoid becoming pregnant while you are taking it. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of using Cytarabine while you are pregnant. It is not known if Cytarabine is found in breast milk. Do not breast feed while taking Cytarabine.

Possible side effects of Cytarabine:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Change in appetite; constipation; cough; diarrhea; dizziness; drowsiness; mouth or tongue sores; stomach pain; tiredness; weakness.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); back pain; bowel or bladder problems; burning, pain, numbness, or tingling; confusion; decreased sense of touch; difficult or painful urination; difficulty walking; fast or irregular heartbeat; fainting; fever, chills, or persistent sore throat; headache; hearing problems (eg, hearing loss); joint pain; memory problems; mental or mood changes (eg, agitation, anxiety, depression); muscle pain, weakness, or cramping; nausea; neck pain or rigidity; one-sided weakness; pain, redness, or swelling at the injection site; seizures; severe or persistent dizziness, drowsiness, or light-headedness; severe or persistent dry mouth or eyes; shortness of breath; sluggishness; swelling of the hands, ankles, or feet; tremor; trouble sleeping; trouble swallowing; unusual bruising or bleeding; unusual tiredness or weakness; vision problems (eg, blurred vision, vision loss); vomiting.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include fever; severe or persistent headache, nausea, or vomiting.

Proper storage of Cytarabine:

Cytarabine is usually handled and stored by a health care provider. If you are using Cytarabine at home, store Cytarabine as directed by your pharmacist or health care provider. Keep Cytarabine out of the reach of children and away from pets.

General information:

• If you have any questions about Cytarabine, please talk with your doctor, pharmacist, or other health care provider.


• Cytarabine is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Cytarabine. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Cytarabine resources

• Cytarabine Use in Pregnancy & Breastfeeding
• Cytarabine Drug Interactions
• Cytarabine Support Group
• 0 Reviews for Cytarabine - Add your own review/rating

• Cytarabine Prescribing Information (FDA)


• Cytarabine Monograph (AHFS DI)


• Cytarabine Professional Patient Advice (Wolters Kluwer)


• cytarabine Concise Consumer Information (Cerner Multum)


• cytarabine Advanced Consumer (Micromedex) - Includes Dosage Information

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