Anectine Injection

1. Name Of The Medicinal Product

Anectine Injection.

2. Qualitative And Quantitative Composition

Suxamethonium Chloride Injection BP 100mg in 2ml.

3. Pharmaceutical Form

Injection.

4. Clinical Particulars

4.1 Therapeutic Indications

Used in anaesthesia as a muscle relaxant to facilitate endotracheal intubation, mechanical ventilation and a wide range of surgical and obstetric procedures.

It is also used to reduce the intensity of muscular contractions associated with pharmacologically or electrically-induced convulsions.

4.2 Posology And Method Of Administration

Usually by bolus intravenous injection.

Adults: The dose is dependent on body weight, the degree of muscular relaxation required, the route of administration, and the response of individual patients.

To achieve endotracheal intubation Anectine is usually administered intravenously in a dose of 1 mg/kg. This dose will usually produce muscular relaxation in about 30 to 60 seconds and has a duration of action of about 2 to 6 minutes. Larger doses will produce more prolonged muscular relaxation, but doubling the dose does not necessarily double the duration of relaxation. Supplementary doses of Anectine of 50% to 100% of the initial dose administered at 5 to 10 minute intervals will maintain muscle relaxation during short surgical procedures performed under general anaesthesia.

For prolonged surgical procedures Anectine may be given by intravenous infusion as a 0.1% to 0.2% solution, diluted in 5% glucose solution or sterile isotonic saline solution, at a rate of 2.5 to 4 mg per minute. The infusion rate should be adjusted according to the response of individual patients.

The total dose of Anectine given by repeated intravenous injection or continuous infusion should not exceed 500 mg per hour.

Children: Infants and young children are more resistant to Anectine compared with adults.

The recommended intravenous dose of Anectine for neonates and infants is 2 mg/kg. A dose of 1 mg/kg in older children is recommended.

When Anectine is given as intravenous infusion in children, the dosage is as for adults with a proportionately lower initial infusion rate based on body weight.

Anectine may be given intramuscularly to infants at doses up to 4 to 5mg/kg and in older children up to 4 mg/kg. These doses produce muscular relaxation within about 3 minutes. A total dose of 150 mg should not be exceeded.

Use in the elderly: Dosage requirements of Anectine in the elderly are comparable to those for younger adults.

The elderly may be more susceptible to cardiac arrhythmias, especially if digitalis-like drugs are also being taken. See also 'Special warnings and precautions for use'.

Instructions to open the ampoule

Ampoules are equipped with the OPC (One Point Cut) opening system and must be opened using the following instructions:

 hold with the hand the bottom part of the ampoule as indicated in picture 1

 put the other hand on the top of the ampoule positioning the thumb above the coloured point and press as indicated in picture 2

Picture 1

Picture 2

4.3 Contraindications

Anectine has no effect on the level of consciousness and should not be administered to a patient who is not fully anaesthetised.

Hypersensitivity to suxamethonium may exist in rare instances, and Anectine should not be administered to patients known to be hypersensitive to the drug.

As suxamethonium can act as a trigger of sustained myofibrillar contraction in susceptible individuals, Anectine is contra-indicated in patients with a personal or family history of malignant hyperthermia. If this condition occurs unexpectedly, all anaesthetic agents known to be associated with its development (including Anectine) must be immediately discontinued, and full supportive measures must be immediately instituted. Intravenous dantrolene sodium is the primary specific therapeutic drug and is recommended as soon as possible after the diagnosis is made.

Anectine is contra-indicated in patients known to have an inherited atypical plasma cholinesterase activity.

An acute transient rise in serum potassium often occurs following the administration of Anectine in normal individuals; the magnitude of this rise is of the order of 0.5 mmol/litre. In certain pathological states or conditions this increase in serum potassium following Anectine administration may be excessive and cause serious cardiac arrhythmias and cardiac arrest. For this reason the use of Anectine is contra-indicated in:

In patients recovering from major trauma or severe burns; the period of greatest risk of hyperkalaemia is from about 5 to 70 days after the injury and may be further prolonged if there is delayed healing due to persistent infection.

Patients with neurological deficits involving acute major muscle wasting (upper and/or lower motor neurone lesions); the potential for potassium release occurs within the first 6 months after the acute onset of the neurological deficit and correlates with the degree and extent of muscle paralysis. Patients who have been immobilised for prolonged periods of time may be at similar risk.

Patients with pre-existing hyperkalaemia. In the absence of hyperkalaemia and neuropathy, renal failure is not a contra-indication to the administration of a normal single dose of Anectine Injection, but multiple or large doses may cause clinically significant rises in serum potassium and should not be used.

Suxamethonium causes a significant transient rise in intra-ocular pressure, and should therefore not be used in the presence of open eye injuries or where an increase in intra-ocular pressure is undesirable unless the potential benefit of its use outweighs the potential risk to the eye.

Anectine should be avoided in patients with a personal or family history of congenital myotonic diseases such as myotonia congenita and dystrophia myotonica since its administration may on occasion be associated with severe myotonic spasms and rigidity.

Anectine should not be used in patients with skeletal muscle myopathies e.g. Duchenne muscular dystrophy since its administration may be associated with malignant hyperthermia, ventricular dysrhythmias and cardiac arrest secondary to acute rhabdomyolysis with hyperkalaemia.

4.4 Special Warnings And Precautions For Use

Anectine should be administered only by or under close supervision of an anaesthetist familiar with its action, characteristics and hazards, who is skilled in the management of artificial respiration and only where there are adequate facilities for immediate endotracheal intubation with administration of oxygen by intermittent positive pressure ventilation.

High rates of cross-sensitivity (greater than 50%) between neuromuscular blocking agents have been reported. Therefore, where possible, before administering suxamethonium, hypersensitivity to other neuromuscular blocking agents should be excluded. Suxamethonium, should only be used when absolutely essential in susceptible patients. Patients who experience a hypersensitivity reaction under general anaesthesia should be tested subsequently for hypersensitivity to other neuromuscular blockers.

Anectine should not be mixed in the same syringe with any other agent, especially thiopental.

During prolonged administration of Anectine, it is recommended that the patient is fully monitored with a peripheral nerve stimulator in order to avoid overdosage.

Anectine is rapidly hydrolysed by plasma cholinesterase which thereby limits the intensity and duration of the neuromuscular blockade.

Individuals with decreased plasma cholinesterase activity exhibit a prolonged response to suxamethonium . Approximately 0.05% of the population has an inherited cause of reduced cholinesterase activity. Prolonged and intensified neuromuscular blockade following Anectine Injection may occur secondary to reduced plasma cholinesterase activity in the following states or pathological conditions: physiological variation as in pregnancy and the puerperium; genetically determined abnormal plasma cholinesterase; severe generalised tetanus, tuberculosis, other severe or chronic infections; following severe burns; chronic debilitating disease, malignancy, chronic anaemia and malnutrition; end-stage hepatic failure, acute or chronic renal failure; auto-immune diseases: myxoedema, collagen diseases; iatrogenic: following plasma exchange, plasmapheresis, cardiopulmonary bypass, and as a result of concomitant drug therapy (see Interactions).

If Anectine is given over a prolonged period, the characteristic depolarising neuromuscular (or Phase I) block may change to one with characteristics of a non-depolarising (or Phase II) block. Although the characteristics of a developing Phase II block resemble those of a true non-depolarising block, the former cannot always be fully or permanently reversed by anticholinesterase agents. When a Phase II block is fully established, its effects will then usually be fully reversible with standard doses of neostigmine accompanied by an anticholinergic agent.

Tachyphylaxis occurs after repeated administration of Anectine.

Muscle pains are frequently experienced after administration of suxamethonium and most commonly occur in ambulatory patients undergoing short surgical procedures under general anaesthesia. There appears to be no direct connection between the degree of visible muscle fasciculation after Anectine administration and the incidence or severity of pain. The use of small doses of non-depolarising muscle relaxants given minutes before suxamethonium administration has been advocated for the reduction of incidence and severity of suxamethonium-associated muscle pains. This technique may require the use of doses of suxamethonium in excess of 1mg/kg to achieve satisfactory conditions for endotracheal intubation.

Caution should be exercised when using suxamethonium in children, since paediatric patients are more likely to have an undiagnosed myopathy or an unknown predisposition to malignant hyperthermia and rhabdomyolysis, which places them at increased risk of serious adverse events following suxamethonium (see section 4.3 Contraindications and section 4.8 Adverse Reactions).

In patients with severe sepsis, the potential for hyperkalaemia seems to be related to the severity and duration of infection.

It is inadvisable to administer Anectine to patients with advanced myasthenia gravis. Although these patients are resistant to suxamethonium they develop a state of Phase II block which can result in delayed recovery. Patients with myasthenic Eaton-Lambert syndrome are more sensitive than normal to Anectine, necessitating dosage reduction.

In healthy adults, Anectine occasionally causes a mild transient slowing of the heart rate on initial administration. Bradycardias are more commonly observed in children and on repeated administration of suxamethonium in both children and adults. Pre-treatment with intravenous atropine or glycopyrrolate significantly reduces the incidence and severity of suxamethonium-related bradycardia.

In the absence of pre-existing or evoked hyperkalaemia, ventricular arrhythmias are rarely seen following suxamethonium administration. Patients taking digitalis-like drugs are however more susceptible to such arrhythmias. The action of suxamethonium on the heart may cause changes in cardiac rhythm including cardiac arrest.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Certain drugs or chemicals are known to reduce normal plasma cholinesterase activity and may therefore prolong the neuromuscular blocking effects of Anectine. These include: organophosphorous insecticides and metriphonate; ecothiopate eye drops; trimetaphan; specific anticholinesterase agents: neostigmine, pyridostigmine, physostigmine, edrophonium; tacrine hydrochloride; cytotoxic compounds: cyclophosphamide, mechlorethamine, triethylene-melamine, and thiotepa; psychiatric drugs: phenelzine, promazine and chlorpromazine; anaesthetic agents and drugs: ketamine, morphine and morphine antagonists, pethidine, pancuronium, propanidid.

Other drugs with potentially deleterious effects on plasma cholinesterase activity include aprotinin, diphenhydramine, promethazine, oestrogens, oxytocin, high-dose steroids, and oral contraceptives, terbutaline and metoclopramide.

Certain drugs or substances may enhance or prolong the neuromuscular effects of Anectine by mechanisms unrelated to plasma cholinesterase activity. These include: magnesium salts; lithium carbonate; azathioprine; quinine and chloroquine; antibiotics such as the aminoglycosides, clindamycin and polymyxins; antiarrhythmic drugs: quinidine, procainamide, verapamil, beta-blockers, lidocaine and procaine; volatile inhalational anaesthetic agents: halothane, enflurane, desflurane, isoflurane, diethylether and methoxyflurane have little effect on the Phase I block of Anectine injection but will accelerate the onset and enhance the intensity of a Phase II suxamethonium-induced block.

Patients receiving digitalis-like drugs are more susceptible to the effects of suxamethonium-exacerbated hyperkalaemia.

4.6 Pregnancy And Lactation

No studies of the effect of suxamethonium on female fertility or pregnancy have been performed.

Suxamethonium has no direct action on the uterus or other smooth muscle structures. In normal therapeutic doses it does not cross the placental barrier in sufficient amounts to affect the respiration of the infant.

The benefits of the use of suxamethonium as part of a rapid sequence induction for general anaesthesia normally outweigh the possible risk to the foetus.

Plasma cholinesterase levels fall during the first trimester of pregnancy to about 70 to 80% of their pre-pregnancy values; a further fall to about 60 to 70% of the pre-pregnancy levels occurs within 2 to 4 days after delivery. Plasma cholinesterase levels then increase to reach normal over the next 6 weeks. Consequently, a high proportion of pregnant and puerperal patients may exhibit mildly prolonged neuromuscular blockade following Anectine injection.

It is not known whether suxamethonium or its metabolites are excreted in human milk.

4.7 Effects On Ability To Drive And Use Machines

This precaution is not relevant to the use of suxamethonium injection. Suxamethonium will always be used in combination with a general anaesthetic and therefore the usual precautions relating to performance of tasks following general anaesthesia apply.

4.8 Undesirable Effects

Adverse reactions are listed below by system organ class and frequency. Estimated frequencies were determined from published data. Frequencies are defined as follows: very common (

Immune system disorders

Very rare

Anaphylactic reactions.

Eye disorders

Common

Increased intraocular pressure.

Cardiac disorders

Common	Bradycardia, tachycardia.
Rare	Arrhythmias (including ventricular arrhythmias), cardiac arrest.

There are case reports of hyperkalaemia-related cardiac arrests following the administration of suxamethonium to patients with congenital cerebral palsy, tetanus, Duchenne muscular dystrophy, and closed head injury. Such events have also been reported rarely in children with hitherto undiagnosed muscular disorders.

Vascular disorders

Common

Skin flushing.

Hypertension and hypotension have also been reported.

Respiratory, thoracic and mediastinal disorders

Rare	Bronchospasm, prolonged respiratory depression†, apnoea.

Please refer to section 4.4 Special Warnings and Precautions for Use

Gastrointestinal disorders

Very common

Increased intragastric pressure.

Excessive salivation has also been reported

Skin and subcutaneous tissue disorders

Common

Rash.

Musculoskeletal and connective tissue disorders

Very common	Muscle fasciculation, post-operative muscle pains (Please refer to section 4.4 Special Warnings and Precautions for Use).
Common	Myoglobinaemia#, myoglobinuria#.
Rare	Trismus

# Rhabdomyolysis has also been reported (see section 4.3 Contraindications and section 4.4 Special Warnings and Precautions for Use)

General disorders and administration site conditions

Very rare

Malignant hyperthermia (Please refer to section 4.4 Special Warnings and Precautions for Use).

Investigations

Common

Transient blood potassium increase.

4.9 Overdose

Apnoea and prolonged muscle paralysis are the main serious effects of overdosage. It is essential, therefore, to maintain the airway and adequate ventilation until spontaneous respiration occurs.

The decision to use neostigmine to reverse a Phase II suxamethonium-induced block depends on the judgement of the clinician in the individual case. Valuable information in regard to this decision will be gained by monitoring neuromuscular function. If neostigmine is used its administration should be accompanied by appropriate doses of an anticholinergic agent such as atropine.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Short-acting depolarising neuromuscular blocking agent.

5.2 Pharmacokinetic Properties

None stated.

5.3 Preclinical Safety Data

Genotoxicity:-

No bacterial mutation assays have been conducted.

There are some data to suggest a weak clastogenic effect in mice, but not in patients who had received suxamethonium chloride.

Carcinogenicity:-

Carcinogenicity studies have not been performed.

Embryo-foetal Development:-

Animal reproduction studies have not been conducted with suxamethonium. It is also not known whether suxamethonium can affect reproductive capacity or cause foetal harm when administered to a pregnant woman.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Water for Injections EP.

6.2 Incompatibilities

None known.

6.3 Shelf Life

18 months.

6.4 Special Precautions For Storage

Store between 2 – 8 °C. Do not freeze. Keep in the outer carton.

6.5 Nature And Contents Of Container

Neutral glass. 2ml ampoules.

6.6 Special Precautions For Disposal And Other Handling

For intravenous injection under medical direction.

Administrative Data

7. Marketing Authorisation Holder

The Wellcome Foundation Limited

Glaxo Wellcome House

Berkeley Avenue

Greenford UB6 ONN

trading as

GlaxoSmithKline UK

Stockley Park West

Uxbridge

Middlesex UB11 1BT

8. Marketing Authorisation Number(S)

PL 00003/5203R

9. Date Of First Authorisation/Renewal Of The Authorisation

16 May 2008

10. Date Of Revision Of The Text

19 January 2009

11. Legal Status

POM

Iopidine Drops

Pronunciation: app-rah-KLOE-nih-deen
Generic Name: Apraclonidine
Brand Name: Iopidine

Iopidine Drops are used for:

Controlling or preventing high fluid pressure within the eye following certain types of eye surgery.

Iopidine Drops are an alpha-adrenergic agonist. It works by decreasing fluid formation inside the eye, which helps to lower the pressure inside the eye.

Do NOT use Iopidine Drops if:

• you are allergic to any ingredient in Iopidine Drops or to similar medicines (eg, clonidine)


• you are taking or have taken a monoamine oxidase (MAO) inhibitor (eg, phenelzine) within the last 14 days

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

Before using Iopidine Drops:

Some medical conditions may interact with Iopidine Drops. 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 recently had a heart attack or you have a history of heart disease or other heart problems, high or low blood pressure, blood vessel problems, brain blood vessel problems (eg, stroke), kidney problems, or liver problems


• if you have a history of rapid fall in heart rate or blood pressure

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

• Barbiturates (eg, phenobarbital), narcotic pain medicine (eg, codeine), or tricyclic antidepressants (eg, amitriptyline) because the risk of drowsiness may be increased


• Beta-blocker eye drops (eg, timolol), beta-blockers (eg, propranolol), digoxin, or medicines for high blood pressure because side effects such as low blood pressure and slow heartbeat may be increased by Iopidine Drops


• MAO inhibitors (eg, phenelzine) because the risk of high blood pressure may be increased

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

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

• Iopidine Drops are for use in the eye only. Avoid contact with other mucous membranes.


• To use Iopidine Drops, first, wash your hands. Tilt your head back. Using your index finger, pull the lower eyelid away from the eye to form a pouch. Drop the medicine into the pouch and gently close your eyes. Immediately use your finger to apply pressure to the inside corner of the eye for 1 to 2 minutes. Do not blink. Remove excess medicine around your eye with a clean tissue, being careful not to touch your eye. Wash your hands to remove any medicine that may be on them. To prevent germs from contaminating your medicine, do not touch the applicator tip to any surface, including your eye. Keep the container tightly closed.


• Wait 5 minutes before using any additional eye drop medicines to prevent Iopidine Drops from being washed out of the eye.


• If you miss a dose of Iopidine Drops, contact your doctor immediately.

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

Important safety information:

• Iopidine Drops may cause drowsiness, dizziness, or blurred vision. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Iopidine Drops. Using Iopidine Drops alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.


• Avoid drinking alcohol or taking other medications that cause drowsiness (eg, sedatives, tranquilizers) while taking Iopidine Drops. Iopidine Drops will add to the effects of alcohol and other depressants. Ask your pharmacist if you have questions about which medicines are depressants.


• Iopidine Drops may be harmful if swallowed. If you or someone you know may have taken Iopidine Drops by mouth, contact your local poison control center or emergency room immediately.


• Use Iopidine Drops with extreme caution in CHILDREN. Safety and effectiveness have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant while taking Iopidine Drops, discuss with your doctor the benefits and risks of using Iopidine Drops during pregnancy. It is unknown if Iopidine Drops are excreted in breast milk. Do not breast-feed while using Iopidine Drops.

Possible side effects of Iopidine Drops:

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:

Dry eye, mouth, or nose.

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; dizziness; drowsiness; eye pain, redness, itching, or swelling; foreign body sensation; light sensitivity; swelling of the eyelids; tearing or discharge from the eye; weakness.

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: Iopidine 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 of oral ingestion may include drowsiness; lower body temperature (hypothermia); slow or irregular heartbeat.

Proper storage of Iopidine Drops:

Store Iopidine Drops between 34 and 77 degrees F (2 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Iopidine Drops out of the reach of children and away from pets.

General information:

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


• Iopidine Drops are 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 Iopidine Drops. 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.

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• Iopidine Side Effects (in more detail)
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• Iopidine Drug Interactions
• Iopidine Support Group
• 0 Reviews for Iopidine - Add your own review/rating

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Imiglucerase

Pronunciation: eye-mih-GLOO-ser-ace
Generic Name: Imiglucerase
Brand Name: Cerezyme

Imiglucerase is used for:

Treatment of type I Gaucher disease that has caused anemia (eg, low red blood cell count), thrombocytopenia (low platelet count), bone disease, or enlargement of the liver or spleen.

Imiglucerase is an enzyme. It works by supplementing a deficiency of an enzyme that is found naturally in the body. Without the enzyme, substances accumulate in the liver, spleen, bone marrow, and sometimes the lung, kidney, and intestine, causing complications, such as anemia and thrombocytopenia.

Do NOT use Imiglucerase if:

• you are allergic to any ingredient in Imiglucerase

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

Before using Imiglucerase:

Some medical conditions may interact with Imiglucerase. 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 Imiglucerase. However, no specific interactions with Imiglucerase are known at this time.

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

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

• Imiglucerase is usually administered as an injection at your doctor's office, hospital, or clinic. If you are using Imiglucerase at home, carefully follow the injection procedures taught to you by your health care provider.


• Gently swirl Imiglucerase when mixing. Do not shake.


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


• After using Imiglucerase, discard any open vials.


• Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Dispose of properly after use. Ask your doctor or pharmacist to explain local regulations for proper disposal.


• If you miss a dose of Imiglucerase, contact your doctor for advice on when to schedule the next dose.

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

Important safety information:

• Imiglucerase may cause dizziness. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Imiglucerase. Using Imiglucerase alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.


• Several months may pass before Imiglucerase reaches its full effect. Continue to use Imiglucerase during this time.


• Limit alcohol intake while using Imiglucerase.


• LAB TESTS, including immunoglobulin G antibody levels, may be performed to monitor your progress or to check for side effects. Be sure to keep all doctor and lab appointments.


• PREGNANCY and BREAST-FEEDING: If you plan on becoming pregnant, discuss with your doctor the benefits and risks of using Imiglucerase during pregnancy. It is unknown if Imiglucerase is excreted in breast milk. If you are or will be breast-feeding while you are using Imiglucerase, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Imiglucerase:

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:

Backache; chills; diarrhea; dizziness; fever; general body discomfort; headache; nausea; rash; stomach pain; swelling of the legs and feet; tiredness; vomiting.

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); bluish skin discoloration; fast heartbeat.

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: Imiglucerase 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.

Proper storage of Imiglucerase:

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

General information:

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


• Imiglucerase 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 Imiglucerase. 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 Imiglucerase resources

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

• Imiglucerase Professional Patient Advice (Wolters Kluwer)


• Imiglucerase Monograph (AHFS DI)


• imiglucerase Intravenous Advanced Consumer (Micromedex) - Includes Dosage Information


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acidophilus

Generic Name: lactobacillus acidophilus (LAK toe ba SIL us AS sid OFF il us)

Brand Names: Acidophilus, Acidophilus Extra Strength, Bacid, Flora-Q 2, Novaflor, RisaQuad, RisaQuad 2, Superdophilus

What is lactobacillus acidophilus?

Lactobacillus acidophilus is a bacteria that exists naturally in the body, primarily in the intestines and the vagina. Lactobacillus acidophilus helps maintain an acidic environment in the body, which can prevent the growth of harmful bacteria.

Lactobacillus acidophilus has been used to treat or prevent vaginal yeast infections, yeast infections of the mouth, diarrhea caused by taking antibiotics, and urinary tract infections. Lactobacillus acidophilus may work by helping the body maintain normal consistency of bacteria in the stomach, intestines, and vagina.

Lactobacillus acidophilus has not been approved by the FDA to treat any disease, and it should not be substituted for prescription medications.

Lactobacillus acidophilus has not been evaluated by the FDA for safety, effectiveness, or purity. All potential risks and/or advantages of lactobacillus acidophilus may not be known. Additionally, there are no regulated manufacturing standards in place for these compounds. Some marketed herbal supplements have been found to be contaminated with toxic metals or other drugs. Herbal/health supplements should be purchased from a reliable source to minimize the risk of contamination.

Lactobacillus acidophilus may also have be used for other purposes not listed in this product guide.

What is the most important information I should know about lactobacillus acidophilus?

Lactobacillus acidophilus has not been approved by the FDA to treat any disease, and it should not be substituted for prescription medications.

Lactobacillus acidophilus has not been evaluated by the FDA for safety, effectiveness, or purity. All potential risks and/or advantages of lactobacillus acidophilus may not be known. Additionally, there are no regulated manufacturing standards in place for these compounds. Some marketed herbal supplements have been found to be contaminated with toxic metals or other drugs. Herbal/health supplements should be purchased from a reliable source to minimize the risk of contamination.

Talk to your doctor before taking lactobacillus acidophilus if you have any other medical conditions, allergies, or if you take other medicines or herbal/health supplements. Under certain conditions, it may be dangerous for you to take lactobacillus acidophilus.

Do not take lactobacillus acidophilus without first talking to your doctor if you are pregnant or may become pregnant during treatment. Do not take lactobacillus acidophilus without first talking to your doctor if you are breast-feeding a baby. Do not give any herbal/health supplement to a child without the advice of a doctor.

What should I tell my healthcare provider before taking lactobacillus acidophilus?

Talk to your doctor before taking lactobacillus acidophilus if you have any other medical conditions, allergies, or if you take other medicines or herbal/health supplements. Under certain conditions, it may be dangerous for you to take lactobacillus acidophilus.

Do not take lactobacillus acidophilus without first talking to your doctor if you are pregnant or may become pregnant during treatment. Do not take lactobacillus acidophilus without first talking to your doctor if you are breast-feeding a baby. Do not give any herbal/health supplement to a child without the advice of a doctor.

How should I take lactobacillus acidophilus?

When considering the use of herbal supplements, seek the advice of your doctor. You may also consider consulting a practitioner who is trained in the use of herbal/health supplements.

Do not take more of this product than is directed.

If you choose to take lactobacillus acidophilus, use it as directed on the package or as directed by your doctor, pharmacist, or other healthcare provider. Do not use more of this product than is recommended on the label.

Lactobacillus acidophilus is available in capsule and tablet form. Powder or liquid forms may also be available. Some dairy products, especially yogurt, also contain lactobacillus acidophilus.

Do not use many different forms (such as tablets, topical formulations, and others) of lactobacillus acidophilus at the same time, unless your healthcare professional has told you to. You may get too much of this product if you use different forms together.

Store lactobacillus acidophilus in a sealed container as directed on the product label, away from moisture, heat, and light.

What happens if I miss a dose?

No information is available about missing a dose of lactobacillus acidophilus. Consult your doctor, pharmacist, or healthcare provider for instructions if you miss a dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking lactobacillus acidophilus?

Follow your doctor's instructions about any restrictions on food, beverages, or activity while you are using lactobacillus acidophilus.

Lactobacillus acidophilus 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.

Less serious side effects may be more likely, and you may have none at all.

Tell your doctor, pharmacist, herbalist, or other healthcare provider about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect lactobacillus acidophilus?

There may be other drugs that can interact with lactobacillus acidophilus. Tell your healthcare provider 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 healthcare provider.

More Acidophilus resources

• Acidophilus Support Group
• 4 Reviews for Acidophilus - Add your own review/rating

Compare Acidophilus with other medications

• Clostridial Infection
• Diarrhea
• Irritable Bowel Syndrome
• Oral Thrush
• Traveler's Diarrhea
• Urinary Tract Infection
• Vaginal Yeast Infection

Where can I get more information?

• Consult with a licensed healthcare professional before using any herbal/health supplement. Whether you are treated by a medical doctor or a practitioner trained in the use of natural medicines/supplements, make sure all your healthcare providers know about all of your medical conditions and treatments.

Augmentin Oral Suspension

Generic Name: amoxicillin and clavulanate potassium

Dosage Form: powder, for oral suspension
AUGMENTIN®

(amoxicillin/clavulanate potassium)

Powder for Oral Suspension and Chewable Tablets

To reduce the development of drug-resistant bacteria and maintain the effectiveness of AUGMENTIN (amoxicillin/clavulanate potassium) and other antibacterial drugs, AUGMENTIN should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Augmentin Oral Suspension Description

AUGMENTIN is an oral antibacterial combination consisting of the semisynthetic antibiotic amoxicillin and the β-lactamase inhibitor, clavulanate potassium (the potassium salt of clavulanic acid). Amoxicillin is an analog of ampicillin, derived from the basic penicillin nucleus, 6-aminopenicillanic acid. The amoxicillin molecular formula is C16H19N3O5S•3H2O, and the molecular weight is 419.46. Chemically, amoxicillin is (2S,5R,6R ) - 6 - [(R) - ( - ) - 2 - Amino - 2 - (p - hydroxyphenyl)acetamido] - 3,3 - dimethyl - 7 - oxo - 4 - thia - 1 - azabicyclo[3.2.0]heptane - 2 - carboxylic acid trihydrate and may be represented structurally as:

Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus . It is a β-lactam structurally related to the penicillins and possesses the ability to inactivate a wide variety of β-lactamases by blocking the active sites of these enzymes. Clavulanic acid is particularly active against the clinically important plasmid-mediated β-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins. The clavulanate potassium molecular formula is C8H8KNO5, and the molecular weight is 237.25. Chemically, clavulanate potassium is potassium (Z)-(2R,5R )-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]-heptane-2-carboxylate and may be represented structurally as:

Inactive Ingredients

Powder for Oral Suspension—Colloidal silicon dioxide, flavorings (see HOW SUPPLIED), xanthan gum, and 1 or more of the following: Aspartamea, hypromellose, mannitol, silica gel, silicon dioxide, and sodium saccharin. Chewable Tablets—Colloidal silicon dioxide, flavorings (see HOW SUPPLIED), magnesium stearate, mannitol, and 1 or more of the following: Aspartamea, D&C Yellow No. 10, FD&C Red No. 40, glycine, sodium saccharin and succinic acid.

a  See PRECAUTIONS—Information for the Patient.

Each 125-mg chewable tablet and each 5 mL of reconstituted 125 mg/5 mL oral suspension of AUGMENTIN contains 0.16 mEq potassium. Each 250-mg chewable tablet and each 5 mL of reconstituted 250 mg/5 mL oral suspension of AUGMENTIN contains 0.32 mEq potassium. Each 200-mg chewable tablet and each 5 mL of reconstituted 200 mg/5 mL oral suspension of AUGMENTIN contains 0.14 mEq potassium. Each 400-mg chewable tablet and each 5 mL of reconstituted 400 mg/5 mL oral suspension of AUGMENTIN contains 0.29 mEq of potassium.

Augmentin Oral Suspension - Clinical Pharmacology

Amoxicillin and clavulanate potassium are well absorbed from the gastrointestinal tract after oral administration of AUGMENTIN. Dosing in the fasted or fed state has minimal effect on the pharmacokinetics of amoxicillin. While AUGMENTIN can be given without regard to meals, absorption of clavulanate potassium when taken with food is greater relative to the fasted state. In 1 study, the relative bioavailability of clavulanate was reduced when AUGMENTIN was dosed at 30 and 150 minutes after the start of a high-fat breakfast. The safety and efficacy of AUGMENTIN have been established in clinical trials where AUGMENTIN was taken without regard to meals.

Oral administration of single doses of 400-mg chewable tablets of AUGMENTIN and 400 mg/5 mL suspension to 28 adult volunteers yielded comparable pharmacokinetic data:

Dosea	AUC0-∞ (mcg.hr/mL)		Cmax (mcg/mL)b
(amoxicillin/clavulanate potassium)	amoxicillin (±S.D.)	clavulanate potassium (±S.D.)	amoxicillin (±S.D.)	clavulanate potassium (±S.D.)
400/57 mg (5 mL of suspension)	17.29 ± 2.28	2.34 ± 0.94	6.94 ± 1.24	1.10 ±  0.42
400/57 mg (1 chewable tablet)	17.24 ± 2.64	2.17 ± 0.73	6.67 ± 1.37	1.03 ±  0.33

a  Administered at the start of a light meal.

b  Mean values of 28 normal volunteers. Peak concentrations occurred approximately 1 hour after the dose.

Oral administration of 5 mL of 250 mg/5 mL suspension of AUGMENTIN or the equivalent dose of 10 mL of 125 mg/5 mL suspension of AUGMENTIN provides average peak serum concentrations approximately 1 hour after dosing of 6.9 mcg/mL for amoxicillin and 1.6 mcg/mL for clavulanic acid. The areas under the serum concentration curves obtained during the first 4 hours after dosing were 12.6 mcg.hr/mL for amoxicillin and 2.9 mcg.hr/mL for clavulanic acid when 5 mL of 250 mg/5 mL suspension of AUGMENTIN or equivalent dose of 10 mL of 125 mg/5 mL suspension of AUGMENTIN was administered to adult volunteers. One 250-mg chewable tablet of AUGMENTIN or two 125-mg chewable tablets of AUGMENTIN are equivalent to 5 mL of 250 mg/5 mL suspension of AUGMENTIN and provide similar serum levels of amoxicillin and clavulanic acid.

Amoxicillin serum concentrations achieved with AUGMENTIN are similar to those produced by the oral administration of equivalent doses of amoxicillin alone. The half-life of amoxicillin after the oral administration of AUGMENTIN is 1.3 hours and that of clavulanic acid is 1.0 hour. Time above the minimum inhibitory concentration of 1.0 mcg/mL for amoxicillin has been shown to be similar after corresponding every 12 hours and every 8 hours dosing regimens of AUGMENTIN in adults and children.

Approximately 50% to 70% of the amoxicillin and approximately 25% to 40% of the clavulanic acid are excreted unchanged in urine during the first 6 hours after administration of 10 mL of 250 mg/5 mL suspension of AUGMENTIN.

Concurrent administration of probenecid delays amoxicillin excretion but does not delay renal excretion of clavulanic acid.

Neither component in AUGMENTIN is highly protein-bound; clavulanic acid has been found to be approximately 25% bound to human serum and amoxicillin approximately 18% bound.

Amoxicillin diffuses readily into most body tissues and fluids with the exception of the brain and spinal fluid. The results of experiments involving the administration of clavulanic acid to animals suggest that this compound, like amoxicillin, is well distributed in body tissues.

Two hours after oral administration of a single 35 mg/kg dose of suspension of AUGMENTIN to fasting children, average concentrations of 3.0 mcg/mL of amoxicillin and 0.5 mcg/mL of clavulanic acid were detected in middle ear effusions.

Microbiology

Amoxicillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms. Amoxicillin is, however, susceptible to degradation by β-lactamases, and therefore, the spectrum of activity does not include organisms which produce these enzymes. Clavulanic acid is a β-lactam, structurally related to the penicillins, which possesses the ability to inactivate a wide range of β-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid-mediated β-lactamases frequently responsible for transferred drug resistance.

The formulation of amoxicillin and clavulanic acid in AUGMENTIN protects amoxicillin from degradation by β-lactamase enzymes and effectively extends the antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other β-lactam antibiotics. Thus, AUGMENTIN possesses the distinctive properties of a broad-spectrum antibiotic and a β-lactamase inhibitor.

Amoxicillin/clavulanic acid has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in INDICATIONS AND USAGE.

Gram-Positive Aerobes

Staphylococcus aureus (β-lactamase and non−β-lactamase−producing)c

c  Staphylococci which are resistant to methicillin/oxacillin must be considered resistant to amoxicillin/clavulanic acid.

Gram-Negative Aerobes

Enterobacter species (Although most strains of Enterobacter species are resistant in vitro, clinical efficacy has been demonstrated with AUGMENTIN in urinary tract infections caused by these organisms.)

Escherichia coli (β-lactamase and non−β-lactamase−producing)

Haemophilus influenzae (β-lactamase and non−β-lactamase−producing)

Klebsiella species (All known strains are β-lactamase−producing.)

Moraxella catarrhalis (β-lactamase and non−β-lactamase−producing)

The following in vitro data are available, but their clinical significance is unknown.

Amoxicillin/clavulanic acid exhibits in vitro minimal inhibitory concentrations (MICs) of 2 mcg/mL or less against most (≥ 90%) strains of Streptococcus pneumoniaed; MICs of 0.06 mcg/mL or less against most (≥ 90%) strains of Neisseria gonorrhoeae; MICs of 4 mcg/mL or less against most (≥ 90%) strains of staphylococci and anaerobic bacteria; MICs of 8 mcg/mL or less against most (≥ 90%) strains of other listed organisms. However, with the exception of organisms shown to respond to amoxicillin alone, the safety and effectiveness of amoxicillin/clavulanic acid in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

d  Because amoxicillin has greater in vitro activity against S. pneumoniae than does ampicillin or penicillin, the majority of S. pneumoniae strains with intermediate susceptibility to ampicillin or penicillin are fully susceptible to amoxicillin.

Gram-Positive Aerobes

Enterococcus faecalise

Staphylococcus epidermidis (β-lactamase and non−β-lactamase−producing)

Staphylococcus saprophyticus (β-lactamase and non−β-lactamase−producing)

Streptococcus pneumoniaee, f

Streptococcus pyogenese, f

viridans group Streptococcuse, f

Gram-Negative Aerobes

Eikenella corrodens (β-lactamase and non−β-lactamase−producing)

Neisseria gonorrhoeaee (β-lactamase and non−β-lactamase−producing)

Proteus mirabilise (β-lactamase and non−β-lactamase−producing)

Anaerobic Bacteria

Bacteroides species, including Bacteroides fragilis (β-lactamase and non−β-lactamase−producing)

Fusobacterium species (β-lactamase and non−β-lactamase−producing)

Peptostreptococcus speciesf

e  Adequate and well-controlled clinical trials have established the effectiveness of amoxicillin alone in treating certain clinical infections due to these organisms.

f  These are non−β-lactamase−producing organisms, and therefore, are susceptible to amoxicillin alone.

Susceptibility Testing

Dilution Techniques

Quantitative methods are used to determine antimicrobial MICs. These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of amoxicillin/clavulanate potassium powder.

The recommended dilution pattern utilizes a constant amoxicillin/clavulanate potassium ratio of 2 to 1 in all tubes with varying amounts of amoxicillin. MICs are expressed in terms of the amoxicillin concentration in the presence of clavulanic acid at a constant 2 parts amoxicillin to 1 part clavulanic acid. The MIC values should be interpreted according to the following criteria: INTERPRETIVE CRITERIA FOR AMOXICILLIN/CLAVULANIC ACID SUSCEPTIBILITY TESTING

For Gram-Negative Enteric Aerobes:

MIC (mcg/mL)	Interpretation
≤ 8/4	Susceptible (S)
16/8	Intermediate (I)
≥ 32/16	Resistant (R)

For Staphylococcus aureusg and Haemophilus influenzae:

MIC (mcg/mL)	Interpretation
≤ 4/2	Susceptible (S)
≥ 8/4	Resistant (R)

g Staphylococci which are susceptible to amoxicillin/clavulanic acid but resistant to methicillin or oxacillin must be considered as resistant.

For S. pneumoniae from non-meningitis sources:

Isolates should be tested using amoxicillin/clavulanic acid and the following criteria should be used:

MIC (mcg/mL)	Interpretation
≤ 2/1	Susceptible (S)
4/2	Intermediate (I)
≥ 8/4	Resistant (R)

Note: These interpretive criteria are based on the recommended doses for respiratory tract infections.

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentration usually achievable. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard amoxicillin/clavulanate potassium powder should provide the following MIC values:

Microorganism	MIC Range (mcg/mL)h
E. coli ATCC 25922	2 to 8
E. coli ATCC 35218	4 to 16
H. influenzae ATCC 49247	2 to 16
S. aureus ATCC 29213	0.12 to 0.5
S. pneumoniae ATCC 49619	0.03 to 0.12

h  Expressed as concentration of amoxicillin in the presence of clavulanic acid at a constant 2 parts amoxicillin to 1 part clavulanic acid.

Diffusion Techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30 mcg of amoxicillin/clavulanate potassium (20 mcg amoxicillin plus 10 mcg clavulanate potassium) to test the susceptibility of microorganisms to amoxicillin/clavulanic acid.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30-mcg amoxicillin/clavulanate potassium (20 mcg amoxicillin plus 10 mcg clavulanate potassium) disk should be interpreted according to the following criteria:

INTERPRETIVE CRITERIA FOR AMOXICILLIN/CLAVULANIC ACID SUSCEPTIBILITY TESTING

For Gram-Negative Enteric Aerobes:

Zone Diameter (mm)	Interpretation
≥ 18	Susceptible (S)
14 to 17	Intermediate (I)
≤ 13	Resistant (R)

For Staphylococcus aureusi and Haemophilus influenzaej:

Zone Diameter (mm)	Interpretation
≥ 20	Susceptible (S)
≤ 19	Resistant (R)

i  Staphylococcus aureus which are resistant to methicillin or oxacillin must be considered as resistant to amoxicillin/clavulanic acid.

j  A broth microdilution method should be used for testing Haemophilus influenzae. Beta-lactamase−negative, ampicillin-resistant strains must be considered resistant to amoxicillin/clavulanic acid.

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for amoxicillin/clavulanic acid.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30-mcg amoxicillin/clavulanate potassium (20 mcg amoxicillin plus 10 mcg clavulanate potassium) disk should provide the following zone diameters in these laboratory quality control strains:

Microorganism	Zone Diameter (mm)
E. coli ATCC 25922	18 to 24 mm
E. coli ATCC 35218	17 to 22 mm
S. aureus ATCC 25923	28 to 36 mm
H. influenza ATCC 49247	15 to 23 mm

Indications and Usage for Augmentin Oral Suspension

AUGMENTIN is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the conditions listed below:

Lower Respiratory Tract Infections − caused by β-lactamase−producing strains of H. influenzae and M. catarrhalis.

Otitis Media − caused by β-lactamase−producing strains of H. influenzae and M. catarrhalis.

Sinusitis − caused by β-lactamase−producing strains of H. influenzae and M. catarrhalis.

Skin and Skin Structure Infections − caused by β-lactamase−producing strains of S. aureus, E. coli, and Klebsiella spp.

Urinary Tract Infections − caused by β-lactamase−producing strains of E. coli, Klebsiella spp. and Enterobacter spp.

While AUGMENTIN is indicated only for the conditions listed above, infections caused by ampicillin-susceptible organisms are also amenable to treatment with AUGMENTIN due to its amoxicillin content. Therefore, mixed infections caused by ampicillin-susceptible organisms and β-lactamase−producing organisms susceptible to AUGMENTIN should not require the addition of another antibiotic. Because amoxicillin has greater in vitro activity against S. pneumoniae than does ampicillin or penicillin, the majority of S. pneumoniae strains with intermediate susceptibility to ampicillin or penicillin are fully susceptible to amoxicillin and AUGMENTIN. (See Microbiology.)

To reduce the development of drug-resistant bacteria and maintain the effectiveness of AUGMENTIN and other antibacterial drugs, AUGMENTIN should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Bacteriological studies, to determine the causative organisms and their susceptibility to AUGMENTIN, should be performed together with any indicated surgical procedures.

Contraindications

AUGMENTIN is contraindicated in patients with a history of allergic reactions to any penicillin. It is also contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with AUGMENTIN.

Warnings

SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH AUGMENTIN, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, AUGMENTIN SHOULD BE DISCONTINUED AND THE APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including AUGMENTIN, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

AUGMENTIN should be used with caution in patients with evidence of hepatic dysfunction. Hepatic toxicity associated with the use of AUGMENTIN is usually reversible. On rare occasions, deaths have been reported (less than 1 death reported per estimated 4 million prescriptions worldwide). These have generally been cases associated with serious underlying diseases or concomitant medications. (See CONTRAINDICATIONS and ADVERSE REACTIONS—Liver.)

Precautions

General

While AUGMENTIN possesses the characteristic low toxicity of the penicillin group of antibiotics, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic function, is advisable during prolonged therapy.

A high percentage of patients with mononucleosis who receive ampicillin develop an erythematous skin rash. Thus, ampicillin-class antibiotics should not be administered to patients with mononucleosis.

The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug should be discontinued and/or appropriate therapy instituted.

Prescribing AUGMENTIN in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Information for the Patient

AUGMENTIN may be taken every 8 hours or every 12 hours, depending on the strength of the product prescribed. Each dose should be taken with a meal or snack to reduce the possibility of gastrointestinal upset. Many antibiotics can cause diarrhea. If diarrhea is severe or lasts more than 2 or 3 days, call your doctor.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Keep suspension refrigerated. Shake well before using. When dosing a child with the suspension (liquid) of AUGMENTIN, use a dosing spoon or medicine dropper. Be sure to rinse the spoon or dropper after each use. Bottles of suspension of AUGMENTIN may contain more liquid than required. Follow your doctor’s instructions about the amount to use and the days of treatment your child requires. Discard any unused medicine.

Patients should be counseled that antibacterial drugs including AUGMENTIN, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When AUGMENTIN is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by AUGMENTIN or other antibacterial drugs in the future.

Phenylketonurics

Each 200-mg chewable tablet of AUGMENTIN contains 2.1 mg phenylalanine; each 400-mg chewable tablet contains 4.2 mg phenylalanine; each 5 mL of either the 200 mg/5 mL or 400 mg/5 mL oral suspension contains 7 mg phenylalanine. The other products of AUGMENTIN do not contain phenylalanine and can be used by phenylketonurics. Contact your physician or pharmacist.

Drug Interactions

Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with AUGMENTIN may result in increased and prolonged blood levels of amoxicillin. Coadministration of probenecid cannot be recommended.

Abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been reported rarely in patients receiving amoxicillin and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

The concurrent administration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients. There are no data with AUGMENTIN and allopurinol administered concurrently.

In common with other broad-spectrum antibiotics, AUGMENTIN may reduce the efficacy of oral contraceptives.

Drug/Laboratory Test Interactions

Oral administration of AUGMENTIN will result in high urine concentrations of amoxicillin. High urine concentrations of ampicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST®, Benedict’s Solution, or Fehling’s Solution. Since this effect may also occur with amoxicillin and therefore AUGMENTIN, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as CLINISTIX®) be used.

Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been noted. This effect may also occur with amoxicillin and therefore AUGMENTIN.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate carcinogenic potential.

Mutagenesis

The mutagenic potential of AUGMENTIN was investigated in vitro with an Ames test, a human lymphocyte cytogenetic assay, a yeast test and a mouse lymphoma forward mutation assay, and in vivo with mouse micronucleus tests and a dominant lethal test. All were negative apart from the in vitro mouse lymphoma assay where weak activity was found at very high, cytotoxic concentrations.

Impairment of Fertility

AUGMENTIN at oral doses of up to 1,200 mg/kg/day (5.7 times the maximum human dose, 1,480 mg/m2/day, based on body surface area) was found to have no effect on fertility and reproductive performance in rats, dosed with a 2:1 ratio formulation of amoxicillin:clavulanate.

Pregnancy

Teratogenic Effects

Pregnancy (Category B). Reproduction studies performed in pregnant rats and mice given AUGMENTIN at oral dosages up to 1,200 mg/kg/day, equivalent to 7,200 and 4,080 mg/m2/day, respectively (4.9 and 2.8 times the maximum human oral dose based on body surface area), revealed no evidence of harm to the fetus due to AUGMENTIN. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Labor and Delivery

Oral ampicillin-class antibiotics are generally poorly absorbed during labor. Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions, and duration of contractions. However, it is not known whether the use of AUGMENTIN in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary. In a single study in women with premature rupture of fetal membranes, it was reported that prophylactic treatment with AUGMENTIN may be associated with an increased risk of necrotizing enterocolitis in neonates.

Nursing Mothers

Ampicillin-class antibiotics are excreted in the milk; therefore, caution should be exercised when AUGMENTIN is administered to a nursing woman.

Pediatric Use

Because of incompletely developed renal function in neonates and young infants, the elimination of amoxicillin may be delayed. Dosing of AUGMENTIN should be modified in pediatric patients younger than 12 weeks (3 months). (See DOSAGE AND ADMINISTRATION—Pediatric.)

Adverse Reactions

AUGMENTIN is generally well tolerated. The majority of side effects observed in clinical trials were of a mild and transient nature and less than 3% of patients discontinued therapy because of drug-related side effects. From the original premarketing studies, where both pediatric and adult patients were enrolled, the most frequently reported adverse effects were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%) and vaginitis (1%). The overall incidence of side effects, and in particular diarrhea, increased with the higher recommended dose. Other less frequently reported reactions include: Abdominal discomfort, flatulence, and headache.

In pediatric patients (aged 2 months to 12 years), 1 US/Canadian clinical trial was conducted which compared 45/6.4 mg/kg/day (divided every 12 hours) of AUGMENTIN for 10 days versus 40/10 mg/kg/day (divided every 8 hours) of AUGMENTIN for 10 days in the treatment of acute otitis media. A total of 575 patients were enrolled, and only the suspension formulations were used in this trial. Overall, the adverse event profile seen was comparable to that noted above; however, there were differences in the rates of diarrhea, skin rashes/urticaria, and diaper area rashes. (See CLINICAL STUDIES.)

The following adverse reactions have been reported for ampicillin-class antibiotics:

Gastrointestinal

Diarrhea, nausea, vomiting, indigestion, gastritis, stomatitis, glossitis, black “hairy” tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. (See WARNINGS.)

Hypersensitivity Reactions

Skin rashes, pruritus, urticaria, angioedema, serum sickness−like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), erythema multiforme (rarely Stevens-Johnson syndrome), acute generalized exanthematous pustulosis, hypersensitivity vasculitis, and an occasional case of exfoliative dermatitis (including toxic epidermal necrolysis) have been reported. These reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, the drug should be discontinued, unless the opinion of the physician dictates otherwise. Serious and occasional fatal hypersensitivity (anaphylactic) reactions can occur with oral penicillin. (See WARNINGS.)

Liver

A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted in patients treated with ampicillin-class antibiotics, but the significance of these findings is unknown. Hepatic dysfunction, including hepatitis and cholestatic jaundice, (See CONTRAINDICATIONS.) increases in serum transaminases (AST and/or ALT), serum bilirubin and/or alkaline phosphatase, has been infrequently reported with AUGMENTIN. It has been reported more commonly in the elderly, in males, or in patients on prolonged treatment. The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular, or mixed cholestatic-hepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. On rare occasions, deaths have been reported (less than 1 death reported per estimated 4 million prescriptions worldwide). These have generally been cases associated with serious underlying diseases or concomitant medications.

Renal

Interstitial nephritis and hematuria have been reported rarely. Crystalluria has also been reported (see OVERDOSAGE).

Hemic and Lymphatic Systems

Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. A slight thrombocytosis was noted in less than 1% of the patients treated with AUGMENTIN. There have been reports of increased prothrombin time in patients receiving AUGMENTIN and anticoagulant therapy concomitantly.

Central Nervous System

Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity have been reported rarely.

Miscellaneous

Tooth discoloration (brown, yellow, or gray staining) has been rarely reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.

Overdosage

Following overdosage, patients have experienced primarily gastrointestinal symptoms including stomach and abdominal pain, vomiting, and diarrhea. Rash, hyperactivity, or drowsiness have also been observed in a small number of patients.

In the case of overdosage, discontinue AUGMENTIN, treat symptomatically, and institute supportive measures as required. If the overdosage is very recent and there is no contraindication, an attempt at emesis or other means of removal of drug from the stomach may be performed. A prospective study of 51 pediatric patients at a poison center suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying.3

Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin.

Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin crystalluria.

Renal impairment appears to be reversible with cessation of drug administration. High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of both amoxicillin and clavulanate. Both amoxicillin and clavulanate are removed from the circulation by hemodialysis.

Augmentin Oral Suspension Dosage and Administration

Dosage

Pediatric Patients

Based on the amoxicillin component, AUGMENTIN should be dosed as follows:

Neonates and infants aged < 12 weeks (3 months)

Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended dose of AUGMENTIN is 30 mg/kg/day divided every 12 hours, based on the amoxicillin component. Clavulanate elimination is unaltered in this age group. Experience with the 200 mg/5 mL formulation in this age group is limited and, thus, use of the 125 mg/5 mL oral suspension is recommended.

Patients aged 12 weeks (3 months) and older

INFECTIONS	DOSING REGIMEN
	q12ha	q8h
	200 mg/5 mL or 400 mg/5 mL oral suspensionb	125 mg/5 mL or 250 mg/5 mL oral suspension
Otitis mediac, sinusitis, lower respiratory tract infections, and more severe infections	45 mg/kg/day q12h	40 mg/kg/day q8h
Less severe infections	25 mg/kg/day q12h	20 mg/kg/day q8h

a  The q12h regimen is recommended as it is associated with significantly less diarrhea. (See CLINICAL STUDIES.) However, the q12h formulations (200 mg and 400 mg) contain aspartame and should not be used by phenylketonurics.

b  Each strength of suspension of AUGMENTIN is available as a chewable tablet for use by older children.

c  Duration of therapy studied and recommended for acute otitis media is 10 days.

Pediatric Patients Weighing 40 kg and More

Should be dosed according to the following adult recommendations: The usual adult dose is one 500-mg tablet of AUGMENTIN every 12 hours or one 250-mg tablet of AUGMENTIN every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one 875-mg tablet of AUGMENTIN every 12 hours or one 500-mg tablet of AUGMENTIN every 8 hours. Among adults treated with 875 mg every 12 hours, significantly fewer experienced severe diarrhea or withdrawals with diarrhea versus adults treated with 500 mg every 8 hours. For detailed adult dosage recommendations, please see complete prescribing information for tablets of AUGMENTIN.

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals. (See WARNINGS.)

Adults

Adults who have difficulty swallowing may be given the 125 m