Dysport 300 units

1. Name Of The Medicinal Product

Dysport.

2. Qualitative And Quantitative Composition

Clostridium botulinum type A toxin-haemagglutinin complex 300 units*

* One unit (U) is defined as the median lethal intraperitoneal dose in mice.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Injection.

4. Clinical Particulars

4.1 Therapeutic Indications

Dysport is indicated for focal spasticity, including the treatment of:

- arm symptoms associated with focal spasticity in conjunction with physiotherapy;

and

- dynamic equinus foot deformity due to spasticity in ambulant paediatric cerebral palsy patients, two years of age or older, only in hospital specialist centres with appropriately trained personnel.

Dysport is also indicated for the following treatments:

- Spasmodic torticollis in adults

- Blepharospasm in adults

- Hemifacial spasm in adults.

4.2 Posology And Method Of Administration

The units of Dysport are specific to the preparation and are not interchangeable with other preparations of botulinum toxin.

Training: Dysport should only be administered by appropriately trained physicians.

Ipsen can facilitate training in administration of Dysport injections.

The exposed central portion of the rubber stopper should be cleaned with alcohol immediately prior to piercing the septum. A sterile 23 or 25 gauge needle should be used.

Arm spasticity

Posology

Adults: The recommended dose is 1000 units in total, distributed amongst the following five muscles:

Biceps brachii (BB)	Flexor digitorum profundus (FDP)	Flexor digitorum superficialis (FDS)	Flexor carpi ulnaris (FCU)	Flexor carpi radialis (FCR)	Total Dose
300-400 units (0.6-0.8 mL)	150 units (0.3 mL)	150-250 units (0.3-0.5 mL)	150 units (0.3 mL)	150 units (0.3 mL)	1000 units (2.0 mL)

The sites of injection should be guided by standard locations used for electromyography, although actual location of the injection site will be determined by palpation. All muscles except the biceps brachii (BB) should be injected at one site, whilst the biceps should be injected at two sites. The maximum dose administered must not exceed 1000 units.

The dose should be lowered if there is evidence to suggest that this dose may result in excessive weakness of the target muscles, such as for patients whose target muscles are small, where the BB muscle is not to be injected or patients who are to be administered multi-level injections. Clinical improvement may be expected within two weeks after injection. Data on repeated and long term treatment are limited.

Children: The safety and effectiveness of Dysport in the treatment of arm spasticity in children have not been demonstrated.

Method of administration

When treating arm spasticity, Dysport 300U vial is reconstituted with 0.6 mL of sodium chloride injection B.P. (0.9%) to yield a solution with a concentration equivalent to 500 units per mL of botulinum toxin type A.

Dysport is administered by intramuscular injection into the five muscles detailed above when treating arm spasticity.

Paediatric cerebral palsy spasticity

Posology

The initial recommended dose is 20 units/kg body weight given as a divided dose between both calf muscles. If only one calf is affected, a dose of 10 units/kg bodyweight should be used. Consideration should be given to lowering this starting dose if there is evidence to suggest that this dose may result in excessive weakness of the target muscles, such as for patients whose target muscles are small or patients who require concomitant injections to other muscle groups. Following evaluation of response to the starting dose subsequent treatment may be titrated within the range 10 units/kg and 30 units/kg divided between both legs. The maximum dose administered must not exceed 1000 units/patient.

Administration should primarily be targeted to the gastrocnemius, although injections of the soleus and injection of the tibialis posterior should also be considered.

The use of electromyography (EMG) is not routine clinical practice but may assist in identifying the most active muscles.

Clinical improvement may be expected within two weeks after injection. Injections may be repeated approximately every 16 weeks or as required to maintain response, but not more frequently than every 12 weeks.

Method of administration

When treating paediatric cerebral palsy spasticity, Dysport 300U vial is reconstituted with 0.6 mL of sodium chloride injection B.P. (0.9%) to yield a solution with a concentration equivalent to 500 units per mL of botulinum toxin type A.

Dysport is administered by intramuscular injection into the calf muscles when treating spasticity.

Spasmodic torticollis

Posology

Adults and elderly: The doses recommended for torticollis are applicable to adults of all ages providing the adults are of normal weight with no evidence of low neck muscle mass. A reduced dose may be appropriate if the patient is markedly underweight or in the elderly, where reduced muscle mass may exist.

The initial recommended dose for the treatment of spasmodic torticollis is 500 units per patient given as a divided dose and administered to the two or three most active neck muscles.

• For rotational torticollis distribute the 500 units by administering 350 units into the splenius capitis muscle, ipsilateral to the direction of the chin/head rotation and 150 units into the sternomastoid muscle, contralateral to the rotation.

• For laterocollis, distribute the 500 units by administering 350 units into the ipsilateral splenius capitis muscle and 150 units into the ipsilateral sternomastoid muscle. In cases associated with shoulder elevation the ipsilateral trapezoid or levator scapulae muscles may also require treatment, according to visible hypertrophy of the muscle or electromyographic (EMG) findings. Where injections of three muscles are required, distribute the 500 units as follows, 300 units splenius capitis, 100 units sternomastoid and 100 units to the third muscle.

• For retrocollis distribute the 500 units by administering 250 units into each of the splenius capitis muscles. This may be followed by bilateral trapezius injections (up to 250 units per muscle) after 6 weeks, if there is insufficient response. Bilateral splenii injections may increase the risk of neck muscle weakness.

• All other forms of torticollis are highly dependent on specialist knowledge and EMG to identify and treat the most active muscles. EMG should be used diagnostically for all complex forms of torticollis, for reassessment after unsuccessful injections in non complex cases, and for guiding injections into deep muscles or in overweight patients with poorly palpable neck muscles.

On subsequent administration, the doses may be adjusted according to the clinical response and side effects observed. Doses within the range of 250-1000 units are recommended, although the higher doses may be accompanied by an increase in side effects, particularly dysphagia. The maximum dose administered must not exceed 1000 units.

The relief of symptoms of torticollis may be expected within a week after the injection. Injections should be repeated approximately every 12 weeks or as required to prevent recurrence of symptoms.

Children: The safety and effectiveness of Dysport in the treatment of spasmodic torticollis in children have not been demonstrated.

Method of administration

When treating spasmodic torticollis Dysport 300U vial is reconstituted with 0.6 mL of sodium chloride injection B.P. (0.9%) to yield a solution with a concentration equivalent to 500 units per mL of botulinum toxin type A.

Dysport is administered by intramuscular injection as above when treating spasmodic torticollis.

Blepharospasm and hemifacial spasm

Posology

Adults and elderly: In the treatment of bilateral blepharospasm the recommended initial dose is 120 units per eye.

Injection of 0.1 mL (20 units) should be made medially and of 0.2 mL (40 units) should be made laterally into the junction between the preseptal and orbital parts of both the upper and lower orbicularis oculi muscles of each eye.

For injections into the upper lid the needle should be directed away from its centre to avoid the levator muscle. A diagram to aid placement of these injections is provided. The relief of symptoms may be expected to begin within two to four days with maximal effect within two weeks.

Injections should be repeated approximately every 12 weeks or as required to prevent recurrence of symptoms. On such subsequent administrations the dose may need to be reduced to 80 units per eye - viz -: 0.1 mL (20 units) medially and 0.1 mL (20 units) laterally above and below each eye in the manner previously described. The dose may be further reduced to 60 units per eye by omitting the medial lower lid injection.

In cases of unilateral blepharospasm the injections should be confined to the affected eye. Patients with hemifacial spasm should be treated as for unilateral blepharospasm. The doses recommended are applicable to adults of all ages including the elderly.

Children: The safety and effectiveness of Dysport in the treatment of blepharospasm and hemifacial spasm in children have not been demonstrated.

Method of administration

When treating blepharospasm and hemifacial spasm, Dysport 300U vial is reconstituted with 1.5 mL of sodium chloride injection BP (0.9%) to yield a solution containing 200 units per mL of botulinum toxin type A.

Dysport is administered by subcutaneous injection medially and laterally into the junction between the preseptal and orbital parts of both the upper and lower orbicularis oculi muscles of the eyes.

4.3 Contraindications

Dysport is contraindicated in individuals with known hypersensitivity to any components of Dysport.

4.4 Special Warnings And Precautions For Use

Side effects related to spread of toxin distant from the site of administration have been reported (see section 4.8) which, in some cases, was associated with dysphagia, pneumonia and/or significant debility resulting, very rarely, in death. Patients treated with therapeutic doses may present with excessive muscle weakness. The risk of occurrence of such undesirable effects may be reduced by using the lowest effective dose and by not exceeding the recommended dose.

Dysport should only be used with caution and under close supervision in patients with subclinical or clinical evidence of marked defective neuro-muscular transmission (e.g. myasthenia gravis). Such patients may have an increased sensitivity to agents such as Dysport which may result in excessive muscle weakness with therapeutic doses. Patients with underlying neurological disorders are at increased risk of this side effect.

Patients with a history of dysphagia and aspiration should be treated with extreme caution. Swallowing or breathing disorders can worsen due to the spread of toxin distant from the site of administration. Aspiration has occurred in rare cases and is a risk when treating patients who have a chronic respiratory disorder. Dysport should be used under specialist supervision in all such patients and should only be used if the benefit of treatment is considered to outweigh the risk.

The recommended posology and frequency of administration for Dysport must not be exceeded (see section 4.2).

Patients and their care-givers must be warned of the necessity of immediate medical treatment in case of problems with swallowing, speech or respiratory disorders.

For the treatment of spasticity associated with cerebral palsy in children, Dysport should only be used in children over 2 years of age.

As with any intramuscular injection, Dysport should be used only where strictly necessary in patients with prolonged bleeding times, infection or inflammation at the proposed injection site.

Dysport should only be used to treat a single patient, during a single session. Specific precautions must be taken for the preparation and administration of the product (see section 4.2) and for the inactivation and disposal of any unused reconstituted solution (see section 6.6).

This product contains a small amount of human albumin. The risk of transmission of viral infection cannot be excluded with absolute certainty following the use of human blood or blood products.

Antibody formation to botulinum toxin has been noted rarely in patients receiving Dysport. Clinically, neutralising antibodies might be detected by substantial deterioration in response to therapy and/or the need for consistent use of increased doses.

Careful consideration should be given before the injection of patients who have experienced a previous allergic reaction to a product containing botulinum toxin type A. The risk of a further allergic reaction must be considered in relation to the benefit of treatment.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

The effects of botulinum toxin may be enhanced by drugs interfering directly or indirectly with the neuromuscular function (e.g. aminoglycosides, curare-like non-depolarising blockers) and such drugs should be used with caution in patients treated with botulinum toxin.

4.6 Pregnancy And Lactation

Pregnancy:

There are limited data from the use of Clostridium botulinum type A toxin-haemagglutinin complex in pregnant women. Studies in animals have shown reproductive toxicity at doses causing maternal toxicity (see section 5.3).

Dysport should be used during pregnancy only if the benefit justifies any potential risk to the fœtus. Caution should be exercised when prescribing to pregnant women.

Lactation:

It is not known whether Clostridum botulinum type A toxin-haemagglutinin complex is excreted in human milk. The excretion of Clostridum botulinum type A toxin-haemagglutinin complex in milk has not been studied in animals. The use of Clostridum botulinum type A toxin-haemagglutinin complex during lactation cannot be recommended.

4.7 Effects On Ability To Drive And Use Machines

There is a potential risk of muscle weakness or visual disturbances which, if experienced, may temporarily impair the ability to drive or operate machinery.

4.8 Undesirable Effects

Very common>1/10: Common>1/100, <1/10: Uncommon>1/1000, <1/100: Rare>1/10 000, < 1/1000: Very rare <1/10 000.

Side effects related to spread of toxin distant from the site of administration have been reported (exaggerated muscle weakness, dysphagia, aspiration/aspiration pneumonia, with fatal outcome in some very rare cases) (see section 4.4).

General

In the clinical trial programme, approximately 28% of the patients treated with Dysport experienced an adverse event.

The following adverse reactions were seen in patients treated across a variety of indications including blepharospasm, hemifacial spasm, torticollis and spasticity associated with either cerebral palsy or stroke:

Nervous system disorders

Rare: Neuralgic amyotrophy

Skin and subcutaneous tissue disorders

Uncommon: Itching

Rare: Skin rashes

General disorders and administration site conditions

Common: Generalised weakness, fatigue, flu-like syndrome, pain / bruising at injection site.

In addition, the following adverse reactions specific to individual indications were reported:

Arm spasticity

Gastrointestinal disorders

Common: Dysphagia

Musculoskeletal and connective tissue disorders

Common: Arm muscle weakness

Injury, poisoning and procedural complications

Common: Accidental injury/falls

Paediatric cerebral palsy spasticity

Gastrointestinal disorders

Common: Diarrhoea, vomiting

Musculoskeletal and connective tissue disorders

Common: Leg muscle weakness

Renal and urinary disorders

Common: Urinary incontinence

General disorders and administration site conditions

Common: Abnormal gait

Injury, poisoning and procedural complications

Common: Accidental injury due to falling

Accidental injury due to falling and abnormal gait may have been due to the over-weakening of the target muscle and / or the local spread of Dysport to other muscles involved in ambulation and balance.

Spasmodic torticollis

Nervous system disorders

Common: Dysphonia

Uncommon: Headache

Eye disorders

Uncommon: Diplopia, blurred vision

Respiratory, thoracic and mediastinal disorders

Rare: Respiratory disorders

Gastrointestinal disorders

Very common: Dysphagia

Uncommon: Dry mouth

Musculoskeletal and connective tissue disorders

Common: Neck muscle weakness

Dysphagia appeared to be dose related and occurred most frequently following injection into the sternomastoid muscle. A soft diet may be required until symptoms resolve.

These side effects may be expected to resolve within two to four weeks.

Blepharospasm and hemifacial spasm

Nervous system disorders

Common: Facial muscle weakness

Uncommon: Facial nerve paresis

Eye disorders

Very common: Ptosis

Common: Diplopia, dry eyes, tearing

Rare: Ophthalmoplegia

Skin and subcutaneous tissue disorders

Common: Eyelid oedema

Rare: Entropion

Side effects may occur due to deep or misplaced injections of Dysport temporarily paralysing other nearby muscle groups.

Post-marketing experience

The profile of adverse reactions reported to the company during post-marketing use reflects the pharmacology of the product and those seen during clinical trials. In addition, hypersensitivity reactions have been reported.

4.9 Overdose

Excessive doses may produce distant and profound neuromuscular paralysis. Overdose could lead to an increased risk of the neurotoxin entering the bloodstream and may cause complications associated with the effects of oral botulinum poisoning (e.g dysphagia and dysphonia). Respiratory support may be required where excessive doses cause paralysis of respiratory muscles. There is no specific antidote; antitoxin should not be expected to be beneficial and general supportive care is advised. In the event of overdose the patient should be medically monitored for signs of excessive muscle weakness or muscle paralysis. Symptomatic treatment should be instigated if necessary.

Symptoms of overdose may not present immediately following injection. Should accidental injection or oral ingestion occur, the person should be medically supervised for several weeks for signs and symptoms of excessive muscle weakness or muscle paralysis.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic Group: Other muscle relaxants, peripherally acting agents.

ATC code: M03AX01

Clostridium botulinum type A toxin-haemagglutinin complex blocks peripheral cholinergic transmission at the neuromuscular junction by a presynaptic action at a site proximal to the release of acetylcholine. The toxin acts within the nerve ending to antagonise those events that are triggered by Ca²⁺ which culminate in transmitter release. It does not affect postganglionic cholinergic transmission or postganglionic sympathetic transmission.

The action of toxin involves an initial binding step whereby the toxin attaches rapidly and avidly to the presynaptic nerve membrane. Secondly, there is an internalisation step in which toxin crosses the presynaptic membrane, without causing onset of paralysis. Finally the toxin inhibits the release of acetylcholine by disrupting the Ca²⁺ mediated acetylcholine release mechanism, thereby diminishing the endplate potential and causing paralysis.

Recovery of impulse transmission occurs gradually as new nerve terminals sprout and contact is made with the post synaptic motor endplate, a process which takes 6-8 weeks in the experimental animal.

5.2 Pharmacokinetic Properties

Pharmacokinetic studies with botulinum toxin pose problems in animals because of the high potency, the minute doses involved, the large molecular weight of the compound and the difficulty of labelling toxin to produce sufficiently high specific activity. Studies using I125 labelled toxin have shown that the receptor binding is specific and saturable, and the high density of toxin receptors is a contributory factor to the high potency. Dose and time responses in monkeys showed that at low doses there was a delay of 2-3 days with peak effect seen 5-6 days after injection. The duration of action, measured by changes of ocular alignment and muscle paralysis varied between 2 weeks and 8 months. This pattern is also seen in man, and is attributed to the process of binding, internalisation and changes at the neuromuscular junction.

5.3 Preclinical Safety Data

Reproductive toxicity studies in pregnant rats and rabbits given Clostridium botulinum type A toxin-haemagglutinin complex by daily intramuscular injection, at doses of 6.6 units/kg (79 units/kg total cumulative dose) and 3.0 units/kg (42 units/kg total cumulative dose) in rats and rabbits respectively, did not result in embryo/foetal toxicity. Implantation losses at maternally toxic doses were observed at higher doses in both species. Clostridium botulinum type A toxin-haemagglutinin complex demonstrated no teratogenic activity in either rats or rabbits and no effects were observed in the pre- and postnatal study on the F1 generation in rats. Fertility of male and female rats was decreased due to reduced mating secondary to muscle paralysis at doses of 29.4 units/kg weekly in males and increased implantation loss at 20 units/kg weekly in females.

In a chronic toxicity study performed in rats up to 12 units/animal, there was no indication of systemic toxicity. Effects in chronic toxicity non-clinical studies were limited to changes on injected muscles related to the mechanism of action of Clostridium botulinum type A toxin-haemagglutinin complex. There was no ocular irritation following administration of Clostridium botulinum type A toxin-haemagglutinin complex into the eyes of rabbits.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Human albumin solution,

Lactose.

6.2 Incompatibilities

None known.

6.3 Shelf Life

The shelf life of the packaged product is 24 months at 2-8°C.

The product may be stored for up to 8 hours at 2-8°C following reconstitution.

Since the product does not contain an antimicrobial agent, from a microbiological point of view, it is recommended that the product should be used immediately following reconstitution.

6.4 Special Precautions For Storage

Unopened vials must be maintained at temperatures between 2°C and 8°C. Dysport must be stored in a refrigerator at the hospital where the injections are to be carried out and should not be given to the patient to store.

Reconstituted Dysport may be stored in a refrigerator (2-8°C) for up to 8 hours prior to use. Dysport should not be frozen.

6.5 Nature And Contents Of Container

Nature of container/closure:

Type 1 glass vials 3 mL capacity. 13 mm bromobutyl freeze-drying closures oversealed by 13 mm aluminium overseals with centre hole, crimped over.

Contents of container:

A white lyophilised powder for reconstitution.

6.6 Special Precautions For Disposal And Other Handling

Immediately after treatment of the patient, any residual Dysport which may be present in either vial or syringe should be inactivated with dilute hypochlorite solution (1% available chlorine). Thereafter, all items should be disposed of in accordance with standard hospital practice.

Spillage of Dysport should be wiped up with an absorbent cloth soaked in dilute hypochlorite solution.

7. Marketing Authorisation Holder

Ipsen Limited

190 Bath Road

Slough

Berkshire

SL1 3XE

United Kingdom

8. Marketing Authorisation Number(S)

PL 34926/0014

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of First Authorisation: 09 December 1990

Date of Latest Renewal: 17 Dec 2002

10. Date Of Revision Of The Text

05 January 2011

Seroquel

Generic Name: Quetiapine Fumarate
Class: Atypical Antipsychotics
VA Class: CN709
Chemical Name: (E)-2-Butenedioate-2-[2-(4-dibenzo[b,f] [1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]-ethanol (2:1) (salt)
Molecular Formula: (C₂₁H₂₅N₃O₂S)₂^•C₄H₄O₄
CAS Number: 111974-72-2

Special Alerts:

[Posted 02/22/2011] ISSUE: FDA notified healthcare professionals that the Pregnancy section of drug labels for the entire class of antipsychotic drugs has been updated. The new drug labels now contain more and consistent information about the potential risk for abnormal muscle movements (extrapyramidal signs or EPS) and withdrawal symptoms in newborns whose mothers were treated with these drugs during the third trimester of pregnancy.

The symptoms of EPS and withdrawal in newborns may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty in feeding. In some newborns, the symptoms subside within hours or days and do not require specific treatment; other newborns may require longer hospital stays.

BACKGROUND: Antipsychotic drugs are used to treat symptoms of psychiatric disorders such as schizophrenia and bipolar disorder.

RECOMMENDATION: Healthcare professionals should be aware of the effects of antipsychotic medications on newborns when the medications are used during pregnancy. Patients should not stop taking these medications if they become pregnant without talking to their healthcare professional, as abruptly stopping antipsychotic medications can cause significant complications for treatment. For more information visit the FDA website at: and .

[Posted 05/02/2007] FDA notified healthcare professionals that the Agency proposed that makers of all antidepressant medications update the existing black box warning on the prescribing information for their products to include warnings about the increased risks of suicidal thinking and behavior in young adults ages 18 to 24 years old during the first one to two months of treatment. The proposed labeling changes also state that scientific data did not show this increased risk in adults older than 24 years of age and that adults 65 years of age and older taking antidepressants have a decreased risk of suicidality. The proposed updates apply to the entire category of antidepressants. Individuals currently taking prescribed antidepressant medications should not stop taking them and should notify their healthcare professional if they have concerns. Manufacturers of antidepressant medications will have 30 days to submit their revised product labeling and revised Medication Guides to FDA for review. See the FDA press release for the list of products affected by the proposed antidepressant product labeling changes. For more information visit the FDA website at: , and .

REMS:

FDA approved a REMS for quetiapine to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of quetiapine and consists of the following: medication guide. See the FDA REMS page () or the ASHP REMS Resource Center ().

• Increased Mortality in Geriatric Patients


• 
  

  Substantially higher mortality rate (4.5%) in geriatric patients with dementia-related psychosis† receiving atypical antipsychotic agents (e.g., quetiapine, aripiprazole, olanzapine, risperidone) compared with those receiving placebo (2.6%).^{a 97 98}

  
  


• 
  

  Most fatalities resulted from cardiac-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).^{a 97 98}

  
  


• 
  

  Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.^{a 97 98} (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

  
  

Introduction

Atypical or second-generation antipsychotic agent.^{1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 21 22 23 26 27 28}

Uses for Seroquel

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Schizophrenia

Symptomatic management of schizophrenia.^{1 2 3 4 5 6 18 22 23 26}

Bipolar Disorder

Management (alone or in combination with lithium or divalproex sodium) of acute manic episodes associated with bipolar I disorder.^{1 a}

Seroquel Dosage and Administration

Administration

Oral Administration

Administer orally, generally 2–3 times daily without regard to meals.^{1 25}

When switching from other antipsychotic agents to quetiapine, abrupt discontinuance of previous agent may be acceptable for some patients with schizophrenia, but gradual discontinuance may be appropriate for others.¹ In all cases, minimize period of overlapping antipsychotic administration.¹

In patients being switched from long-acting (depot) parenteral antipsychotic therapy to oral quetiapine therapy, administer first oral dose in place of next scheduled depot injection of the long-acting preparation.¹

Periodically reevaluate need for continuing any existing drug therapy for symptomatic relief of adverse extrapyramidal effects.¹

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as quetiapine fumarate; dosage is expressed in terms of quetiapine.¹

Reinitiating therapy: In patients previously treated with quetiapine, dosage titration is not necessary if reinitiated after a drug-free period <1 week;¹ if reinitiated after a drug-free period >1 week, generally titrate dosage as with initial therapy.¹

Adults

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Schizophrenia

Oral

Initially, 25 mg twice daily.^{1 23}

Increase dosage in increments of 25–50 mg 2 or 3 times daily on the second or third day, as tolerated, to a target dosage of 300–400 mg daily in 2 or 3 divided doses by the fourth day.^{1 23}

Make subsequent dosage adjustments at intervals of not less than 2 days, usually in increments or decrements of 25–50 mg twice daily.^{1 20}

Dosages ranging from 150–750 mg daily were effective in clinical trials.^{1 4 5 6 7 8 11 18 22} Dosages >300 mg daily usually do not result in greater efficacy, but dosages of 400–500 mg daily have been required in some patients.¹

Optimum duration of therapy currently not known, but efficacy of maintenance therapy with antipsychotics is well established.^{1 22} Continue therapy in responsive patients as long as clinically necessary and tolerated but at lowest possible effective dosage; reassess need for continued therapy and optimal dosage periodically (e.g., at least annually).^{1 22}

If discontinuance is considered, precautions include slow, gradual dose reduction over many months, more frequent clinician visits, and use of early intervention strategies.²²

Bipolar Disorder

Acute Mania

Oral

Initially, 100 mg daily in 2 divided doses.¹ Increase dosage (in increments of ≤100 mg daily in 2 divided doses) to 400 mg daily on the fourth day of therapy.¹ Make subsequent adjustments in increments of ≤200 mg daily to reach a dosage of up to 800 mg daily by the sixth day of therapy.¹

Majority of patients respond to 400–800 mg daily.¹

Optimum duration not established; efficacy has been demonstrated in two 12-week monotherapy trials and one 3-week adjunct therapy trial.^a If used for extended periods, periodically reevaluate long-term risks and benefits for the individual patient.^{1 a}

Prescribing Limits

Adults

Schizophrenia

Oral

Safety of dosages >800 mg daily not established.¹

Bipolar Disorder

Acute Mania

Oral

Safety of dosages >800 mg daily not established.¹

Special Populations

Hepatic Impairment

Initially, 25 mg daily; increase dosage by 25–50 mg daily according to clinical response and tolerability until an effective dosage is reached.¹

Renal Impairment

No dosage adjustment necessary.¹

Patients at Risk of Orthostatic Hypotension

Consider a slower rate of dosage titration and a lower target dosage in geriatric patients and in patients who are debilitated or have a predisposition to hypotensive reactions.¹ Adjust dosage with caution.¹

Initially, 25 mg twice daily to minimize risk of orthostatic hypotension and associated syncope.¹ If hypotension occurs during dosage titration, return to previous dosage in titration schedule.¹

Cautions for Seroquel

Contraindications

• 
  

  Known hypersensitivity to quetiapine or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Possible increased risk of death with use of atypical antipsychotics in geriatric patients with dementia-related psychosis.^{a 97 98}

Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.^{a 97 98} (See Boxed Warning and see Geriatric Use under Cautions.)

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment, reported rarely.¹

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary dyskinetic movements, reported infrequently.¹ Consider discontinuance of quetiapine.¹

Hyperglycemia and Diabetes Mellitus

Severe hyperglycemia, sometimes associated with ketoacidosis, hyperosmolar coma, or death, reported in patients receiving atypical antipsychotic agents, including quetiapine.^{1 34 35 36 37 38 39 40 41 42 43 44 45 47 60 61 62 63 67 87} Closely monitor patients with preexisting diabetes mellitus for worsening of glucose control and perform fasting glucose tests at baseline and periodically for patients with risk factors for diabetes (e.g., obesity, family history of diabetes).^{1 34 35 36 37 38 39 40 41 42 43 44 45} If manifestations of hyperglycemia occur in any patient, test for diabetes mellitus.^{1 34 35 36 37 38 39 40 41 42 43 44 45}

General Precautions

Orthostatic Hypotension

Orthostatic hypotension reported.¹ Use with caution in patients with known cardiovascular or cerebrovascular disease and/or conditions that would predispose patients to hypotension (e.g., dehydration, hypovolemia, concomitant antihypertensive therapy).¹ (See Patients at Risk of Orthostatic Hypotension under Dosage and Administration.)

Ocular Effects

Possible lenticular changes; ophthalmologic examination of the lens by methods adequate to detect cataract formation (e.g., slit lamp exam) recommended at initiation of therapy, or shortly thereafter, and at 6-month intervals during chronic therapy.¹

Nervous System Effects

Possible risk of seizures; use with caution in patients with a history of seizures or with conditions known to lower the seizure threshold (e.g., dementia of the Alzheimer’s type, geriatric patients).¹

Disruption of ability to reduce core body temperature possible; use with caution in patients exposed to conditions that may contribute to an elevation in core body temperature (e.g., dehydration, extreme heat, strenuous exercise, concomitant use of anticholinergic agents).¹

Somnolence reported.¹ Potential impairment of judgment, thinking, or motor skills.¹

Endocrine Effects

Hypothyroidism possible.¹

Elevated prolactin concentrations reported with some atypical antipsychotic agents; not observed in clinical trials with quetiapine but reported in animals.¹

Metabolic Effects

Weight gain possible.¹

Increases in cholesterol and triglyceride concentrations possible; weakly related to weight gain.¹

Hepatic Effects

Asymptomatic, transient, and reversible increases in serum transaminases (principally ALT) reported; usually occurred within first 3 weeks and resolved despite continued quetiapine therapy.¹

Sexual Dysfunction

Priapism possible.¹

GI Effects

Esophageal dysmotility and aspiration possible; use with caution in patients at risk for aspiration pneumonia (e.g., geriatric patients, those with advanced Alzheimer’s dementia).¹

Suicide

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Attendant risk with psychotic illnesses; closely supervise high-risk patients.¹ Prescribe in the smallest quantity consistent with good patient management to reduce the risk of overdosage.¹

Possible Prescribing and Dispensing Precautions

Ensure accuracy of prescription; similarity in spelling of Seroquel (quetiapine) and Serzone (former trade name for nefazodone hydrochloride, an antidepressant agent) may result in errors associated with adverse CNS (e.g., mental status deterioration, hallucination, paranoia, muscle weakness, lethargy, dizziness) and GI (e.g., nausea, vomiting, diarrhea) effects.^{29 30 31}

Specific Populations

Pregnancy

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Category C.¹

Lactation

Distributed into milk in animals; not known whether distributed into human milk.¹ Women receiving quetiapine should not breast-feed.¹

Pediatric Use

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Safety and efficacy not established in children <18 years of age.¹

Geriatric Use

No substantial differences in safety relative to younger adults, but factors that decrease pharmacokinetic clearance, increase the pharmacodynamic response, or cause poorer tolerance or orthostasis may be present.¹ (See Patients at Risk of Orthostatic Hypotension under Dosage and Administration.)

Possible increased risk of death in geriatric patients with dementia-related psychosis.^{a 97 98} Substantial (1.6- to 1.7-fold) increase in mortality rate reported in geriatric patients with dementia who received atypical antipsychotic agents (e.g., aripiprazole, olanzapine, quetiapine, risperidone) for treatment of behavioral disorders; most fatalities resulted from cardiac-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).^{a 97 98}

Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.^{a 97 98} (See Boxed Warning and see Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

Hepatic Impairment

Increased plasma concentrations expected in patients with hepatic impairment; dosage adjustment may be necessary.¹

Renal Impairment

Clearance may be decreased in severe renal impairment, but dosage adjustment not necessary.¹

Common Adverse Effects

Somnolence, dizziness, dry mouth, constipation, increased ALT, weight gain, dyspepsia.^a

Interactions for Seroquel

Metabolized principally by CYP3A4.^{1 b} Does not appear to inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 in vitro; pharmacokinetic interaction with substrates of these isoenzymes unlikely.^{1 b}

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP3A4; potential pharmacokinetic interaction (altered quetiapine metabolism).^{1 b}

Specific Drugs

Drug	Interaction	Comments
Alcohol	Potentiation of cognitive and motor effects of alcohol1	Avoid alcohol during therapy with quetiapine1
Antifungals, azole (e.g., fluconazole, itraconazole, ketoconazole)	Substantial decrease in quetiapine clearance with concomitant use of ketoconazole, resulting in increased peak plasma quetiapine concentrations1	Use concomitantly with caution; dosage adjustment of quetiapine may be necessary1
Barbiturates	Possible increased quetiapine clearance1	Increased quetiapine dosage may be required1
Carbamazepine	Possible increased quetiapine clearance1	Increased quetiapine dosage may be required1
Cimetidine	Decreased quetiapine mean clearance1	No dosage adjustment of quetiapine required1
CNS agents	Possible additive CNS effects1	Use with caution1
Divalproex sodium	Increased peak plasma quetiapine concentrations, with no effect on extent of absorption or mean quetiapine clearance; decreased peak plasma valproic acid concentrations and extent of absorption, but not significant1
Dopamine agonists	Antagonistic effects1
Erythromycin	Decreased quetiapine clearance1	Use concomitantly with caution1
Fluoxetine	No effect on quetiapine pharmacokinetics1
Glucocorticoids	Possible increased quetiapine clearance1	Increased quetiapine dosage may be required1
Haloperidol	No effect on quetiapine pharmacokinetics1
Hypotensive agents	Additive hypotensive effects1
Imipramine	No effect on quetiapine pharmacokinetics1
Levodopa	Antagonistic effects1
Lithium	No effect on lithium pharmacokinetics1
Lorazepam	Decreased lorazepam clearance1
Phenytoin	Substantially increased quetiapine clearance1	Increased quetiapine dosage may be required;1 23 caution advised if phenytoin is withdrawn and replaced with a non-inducer (e.g., valproate)1
Rifampin	Possible increased quetiapine clearance1	Increased quetiapine dosage may be required1
Risperidone	No effect on quetiapine pharmacokinetics1
Thioridazine	Substantially increased quetiapine clearance1

Seroquel Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed after oral administration, with peak plasma concentrations attained within 1.5 hours.^{1 b} Bioavailability of tablet formulation is 100% relative to an oral solution (not commercially available in US).^{1 b}

Food

Bioavailability is marginally affected by food.^{1 b}

Distribution

Extent

Widely distributed throughout the body.¹

Distributed into milk in animals; not known whether distributed into human milk.¹

Plasma Protein Binding

83%.^{1 b}

Elimination

Metabolism

Extensively metabolized to inactive metabolites, principally via CYP3A4.^{1 b}

Elimination Route

Excreted in urine (73%) and feces (20%), with <1% of the drug excreted unchanged.^{1 b}

Half-life

Approximately 6 hours.^{1 b}

Special Populations

In patients with hepatic impairment, clearance is 30% lower and AUC and peak plasma concentrations are 3 times higher than those of healthy individuals.¹

In patients with severe renal impairment (Cl_cr 10–30 mL/minute), clearance may be reduced by 25% compared with healthy individuals; however, plasma concentrations in patients with renal impairment were within the range of those seen in healthy patients.¹

In geriatric patients, clearance is decreased by about 40% compared with younger patients.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹

Actions

• 
  

  Exact mechanism of antipsychotic action is not known; may involve antagonism at serotonin type 1 (5-hydroxytryptamine [5-HT_1A]),^{1 6 7 15 17} type 2 (5-HT_2A, 5-HT_2C),^{1 2 3 4 5 6 7 8 9 10 11 12 14 15 16 17 23} and type 6 (5-HT₆) receptors,¹⁷ and at dopamine receptors.^{1 2 3 4 5 6 7 8 9 10 11 12 14 15 16 17 26 28}

  
  


• 
  

  Antagonism at other receptors (e.g., α₁-adrenergic receptors, histamine H₁ receptors) may contribute to other therapeutic and adverse effects (e.g., orthostatic hypotension, somnolence).¹

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Risk of orthostatic hypotension, especially during initial dosage titration and at times of re-initiation of therapy or increases in dosage.¹

  
  


• 
  

  Risk of somnolence and impairment of judgment, thinking, or motor skills; avoid driving, operating machinery, or performing hazardous tasks until effects on the individual are known.¹

  
  


• 
  

  Importance of avoiding alcohol during quetiapine therapy.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of avoiding overheating or dehydration.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., diabetes mellitus, seizures, dementia).¹

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Quetiapine Fumarate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	25 mg (of quetiapine)	Seroquel (with povidone)	AstraZeneca
		50 mg (of quetiapine)	Seroquel (with povidone)	AstraZeneca
		100 mg (of quetiapine)	Seroquel (with povidone)	AstraZeneca
		200 mg (of quetiapine)	Seroquel (with povidone)	AstraZeneca
		300 mg (of quetiapine)	Seroquel (with povidone)	AstraZeneca
		400 mg (of quetiapine)	Seroquel (with povidone)	AstraZeneca

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

SEROquel 100MG Tablets (ASTRAZENECA): 60/$364.98 or 180/$1,063.93

SEROquel 200MG Tablets (ASTRAZENECA): 60/$683.97 or 180/$2,012.08

SEROquel 25MG Tablets (ASTRAZENECA): 60/$212.09 or 180/$607.90

SEROquel 300MG Tablets (ASTRAZENECA): 60/$902.01 or 180/$2,652.93

SEROquel 400MG Tablets (ASTRAZENECA): 30/$551.01 or 90/$1,506.89

SEROquel 50MG Tablets (ASTRAZENECA): 100/$584.01 or 300/$1,709.97

SEROquel XR 150MG 24-hr Tablets (ASTRAZENECA): 60/$597.99 or 180/$1,685.97

SEROquel XR 200MG 24-hr Tablets (ASTRAZENECA): 60/$673.96 or 180/$1,980.98

SEROquel XR 400MG 24-hr Tablets (ASTRAZENECA): 60/$983.96 or 180/$2,893.85

SEROquel XR 50MG 24-hr Tablets (ASTRAZENECA): 60/$337.99 or 180/$953.01

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. AstraZeneca Pharmaceuticals. Seroquel (quetiapine fumarate) tablets prescribing information. Wilmington, DE; 2004 Jul.

2. Small JG, Hirsch SR, Arvanitis LA et al and the Seroquel Study Group. Quetiapine in patients with schizophrenia: a high- and low-dose double-blind comparison with placebo. Arch Gen Psychiatry. 1997; 54:549-557. [IDIS 388276] [PubMed 9193196]

3. Borison RL, Arvanitis LA, Miller BG and the U.S. SEROQUEL Study Group. ICI 204,636, an atypical antipsychotic: efficacy and safety in a multicenter, placebo-controlled trial in patients with schizophrenia. J Clin Psychopharmacol. 1996; 16:158-169. [IDIS 365790] [PubMed 8690831]

4. Arvanitis LA, Miller BG and the Seroquel Trial 13 Study Group. Multiple fixed doses of “Seroquel” (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. Biol Psychiatry. 1997; 42:233-246. [PubMed 9270900]

5. Anon. Academic highlights: Seroquel: a putative atypical antipsychotic drug with serotonin- and dopamine-receptor antagonist properties: preclinical and early clinical trials in schizophrenia. J Clin Psychiatry. 1995; 56:438-445. [PubMed 7665549]

6. Casey DE. ’seroquel’ (quetiapine): preclinical and clinical findings of a new atypical antipsychotic. Exp Opin Invest Drugs. 1996; 5:939-957.

7. Robinson CP, Robinson KA, Castaner J. Quetiapine fumarate. Drugs Future. 1996; 21:483-489.

8. Fleischhacker WW, Hummer M. Drug treatment of schizophrenia in the 1990s: achievements and future possibilities in optimising outcomes. Drugs. 1997; 53:915-929. [PubMed 9179524]

9. Richelson E. Preclinical pharmacology of neuroleptics: focus on new generation compounds. J Clin Psychiatry. 1996; 57(Suppl 11):4-11. [IDIS 376643] [PubMed 8941166]

10. Fabre LF, Arvanitis L, Pultz J et al. ICI 204,636, a novel, atypical antipsychotic: early indication of safety and efficacy in patients with chronic and subchronic schizophrenia. Clin Ther. 1995; 17:366-378. [IDIS 350568] [PubMed 7585841]

11. Buckley PF. New dimensions in the pharmacologic treatment of schizophrenia and related psychoses. J Clin Pharmacol. 1997; 37:363-378. [IDIS 386525] [PubMed 9156369]

12. Kuperberg GR. Advances in the treatment of schizophrenia. Br J Clin Pract. 1996; 50:315-323. [IDIS 374314] [PubMed 8983320]

13. Citrome L. New antipsychotic medications: what advantages do they offer? Postgrad Med. 1997; 101:207-210,213,214. (IDIS 380687)

14. Lieberman JA. Atypical antipsychotic drugs as a first-line treatment of schizophrenia: a rationale and hypothesis. J Clin Psychiatry. 1996; 57(Suppl 11):68-71. [IDIS 376650] [PubMed 8941173]

15. Hirsch SR, Link CGG, Goldstein JM et al. ICI 204,636: a new atypical antipsychotic drug. Br J Psychiatry. 1996; 168(Suppl 29):45-56.

16. Meltzer HY. Pre-clinical pharmacology of atypical antipsychotic drugs: a selective review. Br J Psychiatry. 1996; 168(Suppl 29):23-31.

17. Goldstein JM. Preclinical profile of Seroquel (quetiapine): an atypical antipsychotic with clozapine-like pharmacology. In: Holliday SG, Ancill RJ, MacEwan GW eds. Schizophrenia: Breaking Down the Barriers. New York: John Wiley & Sons Ltd; 1996:177-208.

18. Arvanitis LA. Clinical profile of Seroquel™ (quetiapine): an overview of recent clinical studies. In: Holliday SG, Ancill RJ, MacEwan GW eds. Schizophrenia: Breaking Down the Barriers. New York: John Wiley & Sons Ltd; 1996:209-236.

19. Lahti AC, Tamminga CA. Recent developments in the neuropharmacology of schizophrenia. Am J Health-Syst Pharm. 1995; 52(Suppl 1):S5-8. [IDIS 341484] [PubMed 7749964]

20. Casey DE. Will the new antipsychotics bring hope of reducing the risk of developing extrapyramidal syndromes and tardive dyskinesia? Int Clin Psychopharmacol. 1997; 12(Suppl 1):S19-27.

21. Link C, Smith A, Miller B et al and the European Seroquel Study Group. A multicentre, double-blind, controlled comparison of Seroquel and chlorpromazine in the treatment of hospitalised patients with acute exacerbation of subchronic and chronic schizophrenia. Eur Neuropsychopharmacol. 1994; 4:385.

22. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2004; 161(Suppl):1-56.

23. Anon. Quetiapine for schizophrenia. Med Lett Drugs Ther. 1997; 39:117-8. [PubMed 9422044]

24. American Psychiatric Association. DSM-IV: diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994:273-86.

25. Zeneca, Wilmington, DE: Personal communication.

26. Meats P. Quetiapine (’seroquel’); an effective and well-tolerated atypical antipsychotic. Int J Psychiatry Clin Pract. 1997; 1:231-9.

27. Borison RL, Arvanitis LA, Miller BG. A comparison of five fixed doses of ’seroquel’ (ICI 204,636) with haloperidol and placebo in patients with schizophrenia. Schizophr Res. 1996; 18:132A.

28. Fleischhacker WW, Linkz CGG, Hurst BC. ICI 204636 (’seroquel’)—a putative new atypical antipsychotic: results from phase III trials. Schizophr Res. 1996; 18:132A.

29. Block G. Dear healthcare professional letter: dispensing errors alert. Wilmington, DE: AstraZeneca LP; 2002 May 20.

30. Kim H, Phillips J. Medication errors associated with Serzone and Seroquel. Drug Topics. 2002;1:38. From the Drug Topics website.

31. Jody D. Dear healthcare provider letter: dispensing error alert involving Serzone (nefazodone) and Seroquel (quetiapine) tablets. Princeton, NJ: Bristol Myer Squibb; 2002 Dec 9. From the FDA website

32. Cheer SM, Wagstaff AJ. Quetiapine. A review of its use in the management of schizophrenia. CNS Drugs. 2004; 18:173-99. [PubMed 14871161]

33. American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry. 2002; 159(4 Suppl):1-50.

34. Otsuka America Pharmaceutical, Inc. Abilify (aripiprazole) tablets prescribing information. Rockville, MD; 2004 Sep.

35. Novartis Pharmaceuticals. Clozaril (clozapine) prescribing information. East Hanover, NJ; 2003 Dec.

36. Eli Lilly and Company. Zyprexa (olanzapine) tablets and Zyprexa Zydis (olanzapine) orally disintegrating tablets prescribing information. Indianapolis, IN; 2004 Sep 22.

37. Janssen Pharmaceutica. Risperdal (risperidone) tablets and oral solution prescribing information. Titusville, NJ; 2003 Oct.

38. Pfizer Inc. Geodon (ziprasidone) prescribing information. New York, NY; 2004 Aug.

39. Lewis-Hall F. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Princeton, NJ: Briston-Myers Squibb Company; 2004 Mar 25. From FDA website.

40. Bess AL, Cunningham SR. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2004 Apr 1. From the FDA website.

41. Eli Lilly and Company. Lilly announces FDA notification of class labeling for atypical antipsychotics regarding hyperglycemia and diabetes. Indianapolis, IN; 2003 Sep 17. Press release.

42. Eisenberg P. Dear health care professional letter regarding safety data on Zyprexa (olanzapine) – hyperglycemia and diabetes. Indianapolis, IN: Eli Lilly and Company; 2004 Mar 1. From the FDA website.

43. Macfadden W. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Wilmington, DE: AstraZeneca Pharmaceuticals; 2004 Apr 22. From the FDA website.

44. Mahmoud RA. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Titusville, NJ: Janssen Pharmaceutica, Inc; 2004. From the FDA website.

45. Clary CM. Dear health care practitioner letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. New York NY: Pfizer Global Pharmaceuticals; 2004 Aug. From the FDA website.

46. Cunningham F, Lambert B, Miller DR et al. Antipsychotic induced diabetes in veteran schizophrenic patients. In: Abstracts of the 1st International Conference on Therapeutic Risk Management and 19th International Conference on Pharmacoepidemiology, Philadelphia, PA, 2003 Aug 21-24. Pharmacoepidemiol Drug Saf. 2003; 12(suppl 1): S154-5.

47. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004; 27:596-601. [PubMed 14747245]

48. Melkersson K, Dahl ML. Adverse metabolic effects associated with atypical antipsychotics. Drugs. 2004; 64:701-23. [PubMed 15025545]

49. Citrome LL, Jaffe AB. Relationship of atypical antipsychotics with development of diabetes mellitus. Ann Pharmacother. 2003; 37:1849-57. [IDIS 510453] [PubMed 14632602]

50. Sumiyoshi T, Roy A, Anil AE et al. A comparison of incidence of diabetes mellitus between atypical antipsychotic drugs. J Clin Psychopharmacol. 2004; 24:345-8. [IDIS 515736] [PubMed 15118492]

51. Expert Group. ’Schizophrenia and Diabetes 2003’ expert consensus meeting, Dublin, 3–4 October 2003: consensus summary. Br J Psychiatry. 2004; 47(Suppl):S112-4.

52. Marder SR, Essock SM, Miller AL et al. Physical health m

Sodium Chloride Ointment

Pronunciation: SOE-dee-um KLOR-ide
Generic Name: Sodium Chloride
Brand Name: Muro 128

Sodium Chloride Ointment is used for:

Temporarily treating swelling of the cornea of the eye.

Sodium Chloride Ointment is a hypertonic salt solution. It works by drawing water out of the cornea, decreasing swelling.

Do NOT use Sodium Chloride Ointment if:

• you are allergic to any ingredient in Sodium Chloride Ointment

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

Before using Sodium Chloride Ointment:

Some medical conditions may interact with Sodium Chloride Ointment. 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

Some MEDICINES MAY INTERACT with Sodium Chloride Ointment. However, no specific interactions with Sodium Chloride Ointment are known at this time.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Sodium Chloride Ointment 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 Sodium Chloride Ointment:

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

• To use Sodium Chloride Ointment in the eye, first, wash your hands. Pull the lower eyelid away from your eye to form a pouch. Squeeze a thin strip of ointment into the pouch. After using the medicine, gently close your eyes for 1 to 2 minutes. Wash your hands to remove any medicine that may be on them. Wipe the applicator tip with a clean, dry tissue. To prevent germs from contaminating your medicine, do not touch the applicator tip to any surface, including the eye. Keep the container tightly closed.


• Do not use Sodium Chloride Ointment if it changes color or is cloudy.


• If you miss a dose of Sodium Chloride Ointment, use 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 use 2 doses at once.

Ask your health care provider any questions you may have about how to use Sodium Chloride Ointment.

Important safety information:

• Sodium Chloride Ointment may cause temporary blurred vision. Do not drive, operate machinery, or do anything else that could be dangerous unless you can see clearly.


• Sodium Chloride Ointment may be harmful if swallowed. If you may have taken Sodium Chloride Ointment by mouth, contact your local poison control center or emergency room immediately.


• PREGNANCY and BREAST-FEEDING: If you plan on becoming pregnant, discuss with your doctor the benefits and risks of using Sodium Chloride Ointment during pregnancy. If you are or will be breast-feeding while you are using Sodium Chloride Ointment, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Sodium Chloride Ointment:

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:

Mild burning or irritation.

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

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); changes in vision; continued redness, burning, or irritation; eye pain; feeling that something is in the eye.

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.

Proper storage of Sodium Chloride Ointment:

Store Sodium Chloride Ointment at room temperature, between 59 and 86 degrees F (15 and 30 degrees C), in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Sodium Chloride Ointment out of the reach of children and away from pets.

General information:

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


• Sodium Chloride Ointment 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 Sodium Chloride Ointment. 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.

Sesame St. Vitamins Plus Iron

Generic Name: multivitamin with iron (MUL tee VYE ta mins with i ron)

Brand Names:

What is Sesame St. Vitamins Plus Iron (multivitamin with iron)?

Multivitamin are a combination of many different vitamins that are normally found in foods and other natural sources.

Iron is normally found in foods like red meat. In the body, iron becomes a part of your hemoglobin (HEEM o glo bin) and myoglobin (MY o glo bin). Hemoglobin carries oxygen through your blood to tissues and organs. Myoglobin helps your muscle cells store oxygen.

Multivitamin and iron are used to provide vitamins and iron that are not taken in through the diet. They are also used to treat iron or vitamin deficiencies caused by illness, pregnancy, poor nutrition, digestive disorders, and many other conditions.

Multivitamin and iron may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Sesame St. Vitamins Plus Iron (multivitamin with iron)?

Never take more than the recommended dose of a multivitamin. Avoid taking any other multivitamin product within 2 hours before or after you take multivitamin with iron. Taking similar vitamin products together at the same time can result in a vitamin overdose or serious side effects. Seek emergency medical attention if you think you have used too much of this medicine. An overdose of vitamins A, D, E, or K can cause serious or life-threatening side effects. Iron and other minerals contained in a multivitamin can also cause serious overdose symptoms if you take too much.

Overdose symptoms may include severe stomach pain, vomiting, bloody diarrhea, coughing up blood, constipation, loss of appetite, hair loss, peeling skin, warmth or tingly feeling, changes in menstrual periods, weight loss, severe headache, muscle or joint pain, severe back pain, blood in your urine or stools, black and tarry stools, pale skin, easy bruising or bleeding, weakness, shallow breathing, weak and rapid pulse, pale skin, blue lips, and seizure (convulsions).

Do not take this medication with milk, other dairy products, calcium supplements, or antacids that contain calcium. Calcium may make it harder for your body to absorb certain ingredients of the multivitamin with iron.

What should I discuss with my healthcare provider before taking Sesame St. Vitamins Plus Iron (multivitamin with iron)?

Iron and certain vitamins can cause serious or life-threatening side effects if taken in large doses. Do not take more of this medication than directed on the label or prescribed by your doctor.

If you have any medical conditions, ask your doctor before taking a multivitamin with iron. If you have certain conditions, you may need a certain vitamin formulation or special tests while taking this product.

Do not take multivitamin with iron without telling your doctor if you are pregnant or plan to become pregnant. Some vitamins and minerals can harm an unborn baby if taken in large doses. You may need to use a prenatal vitamin specially formulated for pregnant women. Multivitamin can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Sesame St. Vitamins Plus Iron (multivitamin with iron)?

Use this medication as directed on the label, or as your doctor has prescribed. Do not use the medication in larger amounts or for longer than recommended.

Never take more than the recommended dose of multivitamin with iron. Avoid taking any other multivitamin product within 2 hours before or after you take multivitamin with iron. Taking similar vitamin products together at the same time can result in a vitamin overdose or serious side effects.

Many multivitamin products also contain minerals such as calcium, magnesium, potassium, and zinc. Minerals (especially taken in large doses) can cause side effects such as tooth staining, increased urination, stomach bleeding, uneven heart rate, confusion, and muscle weakness or limp feeling. Read the label of any multivitamin product you take to make sure you are aware of what it contains.

Take your multivitamin with a full glass of water. You may take the multivitamin with food if it upsets your stomach.

The chewable tablet must be chewed or allowed to dissolve in the mouth before swallowing.

Measure the liquid form of this multivitamin using a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist where you can get one.

Liquid multivitamin may sometimes be mixed with water, fruit juice, or infant formula (but not milk or other dairy products). Follow the directions on the medicine label.

Do not crush, chew, break, or open an extended-release tablet or capsule. Swallow the pill whole. Breaking or opening the pill may cause too much of the drug to be released at one time.

It is important to take multivitamin with iron regularly to get the most benefit.

Store this medication at room temperature away from moisture and heat. Keep the liquid medicine from freezing.

Store multivitamin in their original container. Storing multivitamin in a glass container can ruin the medication.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine. An overdose of vitamins A, D, E, or K can cause serious or life-threatening side effects. Iron and other minerals contained in a multivitamin can also cause serious overdose symptoms.

Overdose symptoms may include severe stomach pain, vomiting, bloody diarrhea, coughing up blood, constipation, loss of appetite, hair loss, peeling skin, warmth or tingly feeling, changes in menstrual periods, weight loss, severe headache, muscle or joint pain, severe back pain, blood in your urine or stools, black and tarry stools, pale skin, easy bruising or bleeding, weakness, shallow breathing, weak and rapid pulse, pale skin, blue lips, and seizure (convulsions).

What should I avoid while taking Sesame St. Vitamins Plus Iron (multivitamin with iron)?

Avoid taking any other multivitamin product within 2 hours before or after you take multivitamin with iron. Taking similar vitamin products together at the same time can result in a vitamin overdose or serious side effects.

Avoid the regular use of salt substitutes in your diet if your multivitamin contains potassium. If you are on a low-salt diet, ask your doctor before taking a vitamin or mineral supplement.

Avoid taking an antibiotic medicine within 2 hours before or after you take multivitamin with iron. This is especially important if you are taking an antibiotic such as ciprofloxacin (Cipro), demeclocycline (Declomycin), doxycycline (Adoxa, Doryx, Oracea, Vibramycin), levofloxacin (Levaquin), lomefloxacin (Maxaquin), minocycline (Dynacin, Minocin, Solodyn, Vectrin), norfloxacin (Noroxin), ofloxacin (Floxin), or tetracycline (Brodspec, Panmycin, Sumycin, Tetracap).

Certain foods can also make it harder for your body to absorb iron. Avoid taking this multivitamin within 1 hour before or 2 hours after eating fish, meat, liver, and whole grain or "fortified" breads or cereals.

Do not take this medication with milk, other dairy products, calcium supplements, or antacids that contain calcium. Calcium may make it harder for your body to absorb certain ingredients of the multivitamin.

Sesame St. Vitamins Plus Iron (multivitamin with iron) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor if you have serious side effects such as:

• 
  

  bright red blood in your stools; or

  
  


• 
  

  pain in your chest or throat when swallowing a ferrous fumarate tablet.

  
  

When taken as directed, multivitamin are not expected to cause serious side effects. Less serious side effects may include:

• 
  

  constipation, diarrhea;

  
  


• 
  

  nausea, vomiting, heartburn;

  
  


• 
  

  stomach pain, upset stomach;

  
  


• 
  

  black or dark-colored stools or urine;

  
  


• 
  

  temporary staining of the teeth;

  
  


• 
  

  headache; or

  
  


• 
  

  unusual or unpleasant taste in your mouth.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Sesame St. Vitamins Plus Iron (multivitamin with iron)?

Vitamin and mineral supplements can interact with certain medications, or affect how medications work in your body. Before taking multivitamin with iron, tell your doctor if you also use:

• 
  

  acetohydroxamic acid (Lithostat);

  
  


• 
  

  cimetidine (Tagamet);

  
  


• 
  

  deferoxamine (Desferal);

  
  


• 
  

  etidronate (Didronel);

  
  


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  diuretics (water pills);

  
  


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  heart or blood pressure medications;

  
  


• 
  

  tretinoin (Vesanoid);

  
  


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  isotretinoin (Accutane, Amnesteen, Clavaris, Sotret);

  
  


• 
  

  dimercaprol (an injection used to treat poisoning by arsenic, lead, or mercury);

  
  


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  penicillamine (Cuprimine);

  
  


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  pancrelipase (Cotazym, Creon, Ilozyme, Pancrease, Ultrase);

  
  


• 
  

  trimethoprim and sulfamethoxazole (Cotrim, Bactrim, Septra, TMP/SMX); or

  
  


• 
  

  an NSAID (non-steroidal anti-inflammatory drug) such as ibuprofen (Motrin, Advil), naproxen (Aleve, Naprosyn), diclofenac (Cataflam, Voltaren), etodolac (Lodine), indomethacin (Indocin), ketoprofen (Orudis), and others.

  
  

This list is not complete and there may be other medications that can interact with or be affected by multivitamin with iron. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Sesame St. Vitamins Plus Iron resources

• Sesame St. Vitamins Plus Iron Side Effects (in more detail)
• Sesame St. Vitamins Plus Iron Use in Pregnancy & Breastfeeding
• Sesame St. Vitamins Plus Iron Drug Interactions
• 0 Reviews for Sesame St. Vitamins Plus Iron - Add your own review/rating

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Compare Sesame St. Vitamins Plus Iron with other medications

• Anemia
• Vitamin/Mineral Supplementation and Deficiency

Where can I get more information?

• Your pharmacist can provide more information about multivitamin with iron.

See also: Sesame St. Vitamins Plus Iron side effects (in more detail)