Consumer medicine information

Colistin Link

Colistin

BRAND INFORMATION

Brand name

Colistin Link

Active ingredient

Colistin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Colistin Link.

SUMMARY CMI

COLISTIN LINK®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using COLISTIN LINK?

COLISTIN LINK contains the active ingredient colistimethate sodium. COLISTIN LINK is used to treat certain types of bacterial infections.

For more information, see Section 1. Why am I using COLISTIN LINK? in the full CMI.

2. What should I know before I use COLISTIN LINK?

Do not use if you have ever had an allergic reaction to COLISTIN LINK or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use COLISTIN LINK? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with COLISTIN LINK and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use COLISTIN LINK?

  • COLISTIN LINK is given as an injection by a doctor or other healthcare professional into a vein or muscle. You may receive doses of this medicine as injections, or infusions (via drip).

More instructions can be found in Section 4. How do I use COLISTIN LINK? in the full CMI.

5. What should I know while using COLISTIN LINK?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using COLISTIN LINK.
  • Tell your doctor if symptoms of your infection do not improve within a few days, or they become worse.
Driving or using machines
  • Be careful driving or operating machinery until you know how this medicine affects you.
  • This medicine may cause temporary numbness, tingling in the fingers and toes, and dizziness. If you have any of these symptoms, do not drive, or operate machinery.
Drinking alcohol
  • Be careful when drinking alcohol whilst being given this medicine.
Looking after your medicine
  • COLISTIN LINK vials should be kept in a cool dry place below 25°C.
  • Once the vial is opened, the prepared solution should be stored in the refrigerator between 2°C-8°C for a maximum of 24 hours.

For more information, see Section 5. What should I know while using COLISTIN LINK? in the full CMI.

6. Are there any side effects?

Side effects that require urgent medical attention include: difficulty breathing; decreased urine output or difficulty passing urine. Other possible side effects include dizziness, tingling or numbness of the mouth or tongue, itching, upset tummy, slurred speech, fever.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

COLISTIN LINK®

Active ingredient(s): colistimethate sodium

Consumer Medicine Information (CMI)

This leaflet provides important information about using COLISTIN LINK. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using COLISTIN LINK.

Where to find information in this leaflet:

1. Why am I using COLISTIN LINK?
2. What should I know before I use COLISTIN LINK?
3. What if I am taking other medicines?
4. How do I use COLISTIN LINK?
5. What should I know while using COLISTIN LINK?
6. Are there any side effects?
7. Product details

1. Why am I using COLISTIN LINK?

COLISTIN LINK contains the active ingredient colistin (as colistimethate sodium). COLISTIN LINK is an antibiotic that belongs to a group of medicines called polymixins. These antibiotics work by killing a type of bacteria that causes infections.

COLISTIN LINK is used to treat some types of bacterial infection.

2. What should I know before I use COLISTIN LINK?

Warnings

Do not use COLISTIN LINK if:

  • you are allergic to colistin, colistimethate sodium, or similar medicines (other polymyxin antibiotics).

Check with your doctor if you:

  • have any other medical conditions
  • have kidney problems
  • take any medicines for any other condition

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant. Your doctor will discuss with you the risks and benefits involved.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with COLISTIN LINK and affect how it works.

These medicines include:

  • Certain antibiotics (kanamycin, streptomycin, dihydrostreptomycin, polymyxin, neomycin.
  • A particular type of muscle relaxant (curariform muscle relaxants)
  • Ether
  • Tubocurarine succinylcholine
  • Gallamine
  • Decamethonium
  • Sodium citrate

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect COLISTIN LINK.

4. How do I use COLISTIN LINK?

How much is given

Your doctor will determine the amount of medicine you need based on

  • the severity of your infection,
  • your body weight, and
  • your kidney function

The usual dose in adults and children who have normal kidney function is 2.5 mg to 5 mg per kilogram of body weight per day, given in 2 to 4 divided doses.

How the medicine is given

This medicine is given by injection into a vein or muscle by your doctor or nurse. This medicine may be given to you in one of two ways as decided by your doctor:

Intermittently:
As two injections given 12 hours apart. Each injection will take between 3 and 5 minutes.

Continuous infusion: One injection which will take between 3 and 5 minutes, followed 1 to 2 hours later by a slow infusion where medicine is given in a drip.

If you have reduced kidney function, your doctor may decide to give you these injections more slowly, or less frequently.

COLISTIN LINK is a powder. Your hospital pharmacist or nurse will reconstitute the powder by mixing it with water for injection before it is used.

If you forget to use COLISTIN LINK

COLISTIN LINK will be given to you under close medical supervision. It is unlikely that a dose will be missed. However, tell your doctor or nurse if you think a dose has been forgotten.

If you use too much COLISTIN LINK

COLISTIN LINK will be given to you under close medical supervision and it is unlikely that you will receive too much.

Symptoms of overdose include:

  • passing urine a lot less frequently
  • muscle weakness
  • difficulty breathing

If you have any concerns about how much COLISTIN LINK you are being given, speak to your doctor.

5. What should I know while using COLISTIN LINK?

Things you should do

Tell your doctor straight away if:

  • The symptoms of your infection do not improve within a few days, or if they become worse.
  • You are about to start taking any new medications, be given any new treatments, or are going to have surgery, remind your doctor and pharmacist that you are taking COLISTIN LINK

Remind any doctor, dentist or pharmacist you visit that you are using COLISTIN LINK.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how COLISTIN LINK affects you.

COLISTIN LINK may cause dizziness, slurred speech, temporary numbness and/or tingling in the fingers and toes in some people. If you have any of these symptoms, do not drive, operate machinery, or do anything else that could be dangerous.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

  • It is unlikely that you will be asked to store COLISTIN LINK yourself. It will usually be stored by your doctor or pharmacist.
  • Keep COLISTIN LINK a cool dry place below 25°C
  • A prepared solution of COLISTIN LINK should be stored in the refrigerator between 2°C and 8°C and used within 24 hours.

Follow the instructions in the carton on how to take care of your medicine properly.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • Dizziness
  • Tingling or numbness of the mouth or tongue
  • Slurred speech
  • Upset tummy
  • Generalised itching
  • Fever
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Signs of kidney problems such as:
  • Swelling of the hands, ankles, or feet
  • Changes to the frequency of urination
  • Absence of urination
Signs of lung problems such as:
  • Difficulty breathing
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What COLISTIN LINK contains

Active ingredient
(main ingredient)		Colistimethate sodium
Other ingredients
(inactive ingredients)		COLISTIN LINK does not contain any ingredients, other than the active ingredient colistimethate sodium.
Potential allergensCOLISTIN LINK does not contain any ingredients, other than the active ingredient colistimethate sodium.

Do not take this medicine if you are allergic to any of these ingredients.

What COLISTIN LINK looks like

COLISTIN LINK is a white to slightly yellow powder in a clear glass vial. The powder is reconstituted with Water for Injection to give a clear solution before being used.

Each vial contains colistimethate sodium equivalent to colistin 150 mg, or 4,500,000 IU antibiotic activity.

(Aust R 14667).

Who distributes COLISTIN LINK

Link Medical Products Pty Ltd
5 Apollo Street
Warriewood, NSW 2102
Australia
Ph: 1800 181 060
linkhealthcare.com.au

Link Pharmaceuticals Ltd
Suite 32, Level 26
188 Quay Street
Auckland 1010
New Zealand
Ph: +64(9) 358 7146

This leaflet was prepared in September 2021.

Published by MIMS December 2021

BRAND INFORMATION

Brand name

Colistin Link

Active ingredient

Colistin

Schedule

S4

 

1 Name of Medicine

Colistin (as colistimethate sodium).

2 Qualitative and Quantitative Composition

Colistin Link contains the sodium salt of colistimethate, a polypeptide antibiotic. Each dose contains colistimethate sodium equivalent to colistin 150 mg. When reconstituted each dose provides 150 mg of colistin in 2 mL equivalent to 4,500,000 IU antibiotic activity.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for injection.
White to slightly yellow lyophilised powder cake.

4 Clinical Particulars

4.1 Therapeutic Indications

Colistimethate sodium is indicated for the treatment of acute or chronic infections due to sensitive strains of certain Gram-negative bacilli. It is particularly indicated when the infection is caused by sensitive strains of Pseudomonas aeruginosa. This antibiotic is not indicated for infections due to Proteus or Neisseria. Colistimethate sodium has proven clinically effective in treatment of infections due to the following Gram-negative organisms: Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa.
Pending results of appropriate bacteriologic cultures and sensitivity tests, colistimethate sodium may be used to initiate therapy in serious infections that are suspected to be due to Gram-negative organisms.

4.2 Dose and Method of Administration

Important.

Colistin Link is supplied in vials containing colistin 150 mg (as colistimethate sodium).
Contains no additional antimicrobial agent. Use in one patient on one occasion only, as soon as practicable after reconstitution.

Reconstitution.

The vial should be reconstituted with 2.0 mL water for injections. The reconstituted solution provides 150 mg colistin in 2 mL.
During reconstitution swirl gently to avoid frothing.

Dosage (dose and interval).

Adults and children-intravenous or intramuscular administration.

Colistin Link should be given in 2 to 4 divided doses at dose levels of 2.5 to 5 mg/kg per day for patients with normal renal function, depending on the severity of the infection.
The daily dose should be reduced in the presence of any renal impairment, which can often be anticipated from the history.
Modifications of dosage in the presence of renal impairment are presented in Table 1.

Intravenous administration.

1. Direct intermittent administration.

Slowly inject one-half of the total daily dose over a period of 3 to 5 minutes every 12 hours.

2. Continuous infusion.

Slowly inject one-half of the total daily dose over 3 to 5 minutes. Add the remaining half of the total daily dose of Colistin Link to one of the following: 0.9% NaCl, 5% glucose in 0.9% NaCl, 5% glucose in water, 5% glucose in 0.45% NaCl, 5% glucose in 0.225% NaCl, lactated Ringer's solution, 10% invert sugar solution.
There are not sufficient data to recommend usage of Colistin Link with other drugs or other than the above listed infusion solutions.
Administer by slow intravenous infusion starting 1 to 2 hours after the initial dose at a rate of 5-6 mg/hr in the presence of normal renal function. In the presence of impaired renal function, reduce the infusion rate depending on the degree of renal impairment.
The choice of intravenous solution and the volume to be employed are dictated by the requirements of fluid and electrolyte management.
Any infusion solution containing colistimethate sodium should be freshly prepared and used for no longer than 24 hours.

4.3 Contraindications

The use of colistimethate sodium is contraindicated for patients with a history of sensitivity to the drug.

Warning.

Maximum daily dose should not exceed 5 mg/kg/day with normal renal function.
Transient neurological disturbances may occur. These include circumoral paresthesias or numbness, tingling or formication of the extremities, generalised pruritus, vertigo, dizziness, and slurring of speech. For these reasons, patients should be warned not to drive vehicles or use hazardous machinery while on therapy. Reduction of dosage may alleviate symptoms. Therapy need not be discontinued, but such patients should be observed with particular care. Overdosage can result in renal insufficiency, muscle weakness and apnoea. See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions for use concomitantly with curariform drugs; see Section 4.2 Dose and Method of Administration for use in renal impairment.

4.4 Special Warnings and Precautions for Use

Since colistimethate sodium is eliminated mainly by renal excretion, it should be used with caution when the possibility of impaired renal function exists. The decline in renal function with advanced age should be considered.
When actual renal impairment is present, colistimethate sodium may be used but the greatest caution should be exercised and the dosage should be reduced in proportion to the extent of the impairment. Administration of amounts of colistimethate sodium in excess of renal excretory capacity will lead to high serum levels and can result in further impairment of renal function, initiating a cycle which, if not recognised, can lead to acute renal insufficiency, renal shutdown and further concentration of the antibiotic to toxic levels in the body. At this point, interference of nerve transmission at neuromuscular junctions may occur and result in muscle weakness and apnoea.
Easily recognised signs indicating the development of impaired renal function are diminishing urine output, rising BUN and serum creatinine. If present, therapy with colistimethate sodium should be discontinued immediately.
If a life-threatening situation exists, therapy may be reinstated at a lower dosage after blood levels have fallen.
If apnoea occurs, it may be treated with assisted respiration, oxygen and calcium chloride Injections.

Use in the elderly.

No data available.

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Certain other antibiotics (kanamycin, streptomycin, dihydrostreptomycin, polymyxin, neomycin) have also been reported to interfere with the nerve transmission at the neuromuscular junction. Based on this reported activity, they should not be given concomitantly with colistimethate sodium except with the greatest caution. The antibiotics with a Gram-positive antimicrobial spectrum, e.g. penicillin, tetracycline, cephalothin sodium, have not been reported to interfere with the nerve transmission and, accordingly, would not be expected to potentiate this activity of colistimethate sodium.
Other drugs, including curariform muscle relaxants (ether, tubocurarine, succinylcholine, gallamine, decamethonium and sodium citrate) potentiate the neuromuscular blocking effect and should be used with extreme caution in patients being treated with colistimethate sodium.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B2)
The safety of colistimethate sodium during human pregnancy has not been established.
Colistimethate sodium has been used to treat bacteriuria and overt urinary infections in pregnant women during the third trimester. However, in view of the evidence of possible embryotoxic and teratogenic effects of colistimethate sodium in pregnant rabbits, caution should be exercised in use of this drug in women of child-bearing potential.
 No data available.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Respiratory arrest has been reported following intramuscular administration of colistimethate sodium. Impaired renal function increases the possibility of apnoea and neuromuscular blockade following administration of colistimethate sodium. This has been generally due to failure to follow recommended guidelines, usually overdosage, failure to reduce dose commensurate with degree of renal impairment, and/or concomitant use of other antibiotics or drugs with neuromuscular blocking potential.
A decrease in urine output or increase in blood urea nitrogen or serum creatinine can be interpreted as signs of nephrotoxicity, which is probably a dose-dependent effect of colistimethate sodium. These manifestations of nephrotoxicity are reversible following discontinuation of the antibiotic.
Increases of blood urea nitrogen have been reported for patients receiving colistimethate sodium at dose levels of 1.6-5 mg/kg per day. The BUN values returned to normal following cessation of colistimethate sodium administration.
Paresthesia, tingling of the extremities or tingling of the tongue and generalised itching or urticaria have been reported by patients who received colistimethate sodium by intravenous or intramuscular injection. In addition the following adverse reactions have been reported for colistimethate sodium: drug fever and gastrointestinal upset, vertigo and slurring of speech. The subjective symptoms reported by the adult may not be manifest in infants or young children, thus requiring close attention to renal function.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdose can result in renal insufficiency, muscle weakness and apnoea. As in any case of overdose, colistimethate sodium therapy should be discontinued and general supportive measures should be utilised.
In albino rabbits and beagle dogs, IV doses of 5, 10 and 20 mg/kg/day for 28 days resulted in elevated blood urea nitrogen in the dog (10 mg/kg/day dose group) and in both 20 mg/kg dose groups.
For information on the management of overdose, contact the Poison Information Centre on 131 126 (Australia) or 0800 764 766 (New Zealand).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology.

Colistimethate sodium has bactericidal activity against the following Gram-negative bacilli: Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa.

Human pharmacology.

Typical serum and urine levels following a single dose of colistimethate sodium equivalent to colistin 150 mg IM or IV in normal adult subjects are shown in Figure 1.
Higher serum levels were obtained at 10 minutes following IV administration. Serum concentration declined with a half-life of 2-3 hours following either intravenous or intramuscular administration in adults and children including premature infants.
Colistimethate sodium is transferred across the placental barrier, and blood levels of about 1 microgram/mL are obtained in the fetus following intravenous administration to the mother.
Average urine levels ranged from about 270 microgram/mL at 2 hours to about 15 microgram/mL at 8 hours after intravenous administration and from 200 to about 25 microgram/mL during a similar period following intramuscular administration.

Clinical trials.

Clinically, colistimethate sodium has been of particular therapeutic value in acute and chronic urinary tract infections caused by sensitive strains of Pseudomonas aeruginosa. Colistimethate sodium is clinically effective in the treatment of infections due to other sensitive Gram-negative pathogenic bacilli which have become resistant to broad spectrum antibiotics.

5.2 Pharmacokinetic Properties

No data available.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Does not contain any other ingredients.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.
Store reconstituted solution at 2°C to 8°C (Refrigerate. Do not freeze).

6.5 Nature and Contents of Container

Colistin Link is supplied in single dose glass vials.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.


Molecular formula: C56H106N16Na6O26S6. Molecular weight: 1750.

CAS number.

8068-28-8.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes