Consumer medicine information

Stromectol

Ivermectin

BRAND INFORMATION

Brand name

Stromectol

Active ingredient

Ivermectin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Stromectol.

SUMMARY CMI

STROMECTOL®

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 STROMECTOL?

STROMECTOL contains the active ingredient ivermectin. STROMECTOL is used to treat river blindness (onchocerciasis), threadworm involving the intestines (intestinal strongyloidiasis) and scabies which is caused by the Sarcoptes scabiei mite.

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

2. What should I know before I use STROMECTOL?

Do not use if you have ever had an allergic reaction to Ivermectin 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 STROMECTOL? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with STROMECTOL 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 STROMECTOL?

Your doctor will tell you how many tablets you need to take. The dose depends on your infection and your weight or height. Take STROMECTOL as a single dose with a full glass of water.

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

5. What should I know while using STROMECTOL?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using STROMECTOL. Visit your doctor if scheduled, to check the progress of your infection. This is to help make sure that the infection has cleared up completely
Things you should not do
  • Do not give STROMECTOL to anyone else, even if they have the same condition as you.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how STROMECTOL affects you
Looking after your medicine
  • Keep your tablets in the aluminium foil blister pack until it is time to take them.
  • Store it in a cool dry place (below 30°C) away from moisture, heat or sunlight

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

6. Are there any side effects?

Like all medicines, STROMECTOL can cause side effects, although not everybody gets them. Your doctor will discuss these with you and will explain the risks and benefits of using STROMECTOL.

When you take STROMECTOL, you can have some serious side effects.

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

STROMECTOL®

Active ingredient: Ivermectin

Consumer Medicine Information (CMI)

This leaflet provides important information about using STROMECTOL.

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 STROMECTOL.

Where to find information in this leaflet:

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

1. Why am I using STROMECTOL?

STROMECTOL contains the active ingredient Ivermectin. Ivermectin is derived from a class of antiparasitic agents called avermectins.

STROMECTOL is used to treat river blindness (onchocerciasis) and threadworm involving the intestines (intestinal strongyloidiasis). These are caused by worm infections. In onchocerciasis the worm infection mainly affects the skin, glands (lymph nodes) and eyes. Changes to the skin may include an itchy rash, pale or dark patches, nodules (small lumps under the skin), thickening of the skin and/or loss of elasticity. The infection can cause enlarged glands in the neck, armpits or groin. The infection can also affect the eye and may cause conjunctivitis, a gritty or painful eye and may lead to blindness.

In the form of strongyloidiasis that is treated with STROMECTOL, the worm infection mainly affects the intestines and skin. Symptoms which may occur include itchy rash, vomiting, diarrhoea and stomach pain.

STROMECTOL works by killing the developing worms.

STROMECTOL is also used to treat scabies which is caused by the Sarcoptes scabiei mite.

Infection with the scabies mite causes discomfort and often intense itching of the skin, particularly at night, with irritating blisters or lumps on the skin. Classical sites of infestation are between the fingers, the wrists, underarm areas, female breasts (particularly the skin of the nipples), stomach area, penis, scrotum, and buttocks. Infants are usually affected on the face, scalp, palms and soles.

Scabies is usually spread person to person via direct skin contact, including sexual contact, though transfer via objects such as clothing or furnishings is also possible. Each person in contact with the infected person should seek treatment immediately. Note that the blisters or lumps on your skin may not go way immediately.

Bed linen and clothing should be washed in hot water, no bleaching is required. Shoes and other non washable items should be placed in a tightly sealed plastic bag for at least 3 days.

There are 2 types of scabies: typical scabies and crusted scabies (more severe).

Your doctor may have prescribed STROMECTOL for another reason. Ask your doctor if you have any questions about why STROMECTOL has been prescribed for you.

2. What should I know before I use STROMECTOL?

Warnings

Do not use STROMECTOL if:

  • you are allergic to Ivermectin, or any of the ingredients listed at the end of this leaflet
    Always check the ingredients to make sure you can use this medicine
  • you are pregnant, or intend to become pregnant
  • the expiry date (EXP) printed on the pack has passed.
    If you take this medicine after the expiry date has passed, it may not work.

Check with your doctor if you:

  • are breastfeeding or plan to breastfeed.
  • have or have had any medical conditions, especially:
    - liver disease
  • have been treated for river blindness before.
    You may be more likely than others to experience serious side effects with STROMECTOL.
  • have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes.

If you have not told your doctor about any of the above, tell them before you take STROMECTOL.

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.

Safety of the use of STROMECTOL in pregnancy has not been established.

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

Your doctor will discuss the possible risks to your baby if you take STROMECTOL while you are breastfeeding.

Paediatric

  • For the treatment of river blindness, do not give STROMECTOL to children under 5 years of age.
    For this worm infection, the safety of STROMECTOL in children under 5 years of age has not been established
  • For the treatment of strongyloidiasis, do not give STROMECTOL to children under 12 years of age.
    For this worm infection, the effectiveness of STROMECTOL in children under 12 years of age has not been established.
  • For the treatment of scabies, do not give STROMECTOL to children under 5 years of age or weighing less than 15 kg.
    The safety of STROMECTOL in children under 5 years of age or less than 15 kg in weight has not been established.

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 and STROMECTOL may interfere with each other. These include warfarin, used to prevent blood clots.

Your doctor or pharmacist has more information on medicines to be careful with or to avoid while taking STROMECTOL.

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

4. How do I use STROMECTOL?

How much to take

Your doctor will tell you how many tablets you need to take.

The dose depends on your infection and your weight or height. The dose usually ranges from one tablet to five tablets taken as a single dose.

For river blindness, you may need to take another dose in 6 to 12 months' time.

Depending on whether you have typical or crusted scabies, your doctor will decide the best treatment for you.

The most common course of treatment is two doses, 8-15 days apart. STROMECTOL can be used alone or in combination with other treatments for scabies.

How to take STROMECTOL

Take STROMECTOL as a single dose with a full glass of water.

Always take STROMECTOL only as prescribed by your doctor.

If you use too much STROMECTOL

If you think that you have used too much STROMECTOL, you may need urgent medical attention.

If you take too many tablets, you may experience some of the following :

  • skin rash, hives;
  • swelling of the legs, ankles or feet;
  • headache, dizziness, feeling sleepy;
  • loss of consciousness
  • nausea, vomiting, diarrhoea; stomach pain
  • dilated pupils of your eyes
  • shortness of breath;
  • walking unsteadily; decreased activity; shaking (or tremors); unusual weakness; tingling or numbness of the hands or feet; seizure.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using STROMECTOL?

Things you should do

Visit your doctor if scheduled, to check the progress of your infection.

This is to help make sure that the infection has cleared up completely. For threadworm, your doctor may do a follow-up examination of your stools.

For scabies, your doctor may take skin scrapings and check whether the number of mites has decreased. Your doctor may also take blood samples to monitor your liver function.

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

Things you should not do

  • Do not give STROMECTOL to anyone else, even if they have the same condition as you.

Driving or using machines

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

Depressed level of consciousness and coma have been reported with the use of STROMECTOL.

STROMECTOL may cause dizziness, light headedness, spinning sensation (vertigo), tremor, tiredness or sleepiness in some people.

Make sure you know how you react to STROMECTOL before you drive a car, operate machinery or perform any other tasks that require you to be alert.

Looking after your medicine

Keep your tablets in the aluminium foil blister pack until it is time to take them.

If you take the tablets out of the box or aluminium foil blister pack they may not keep well.

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

Store it in a cool dry place (below 30°C) away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

A locked cupboard at least one and half metres above the ground is a good place to store medicines.

When to discard your medicine and how to get 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?

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking STROMECTOL.

STROMECTOL helps most people with river blindness, threadworm or scabies, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

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 for patients being treated for river blindness

Less serious side effectsWhat to do
Muscles and joint related
  • painful joints or muscles
Skin related
  • skin rash, itching or swelling
Lung related
  • worsening asthma
Eye related
  • swelling of the eyelids, conjunctivitis, a gritty or painful eye, redness of the eye, visual impairment
Heart related
  • fast heart beat
Other
  • painful and tender glands in the neck, armpits or groin
  • fever
  • light headedness or dizziness, especially when standing up
  • headache
  • swelling of the face, legs, ankles or feet
Some of these are symptoms of an allergic reaction which may occur as a result of the death of the worms after taking STROMECTOL for river blindness. They are usually not serious side effects.		Speak to your doctor if you have any of these less serious side effects and they worry you.

Less serious side effects for patients being treated for threadworm

Less serious side effectsWhat to do
Gastrointestinal related
  • nausea, vomiting, diarrhoea, constipation
  • lack or loss of appetite
  • stomach pain
Skin related
  • skin rash, itching or hives
Lung related
  • worsening asthma
Other
  • unusual tiredness or weakness
  • sleepiness
  • dizziness
  • spinning sensation, also called vertigo
  • shaking or tremors
  • light headedness or dizziness, especially when standing up
These are usually not serious side effects.		Speak to your doctor if you have any of these less serious side effects and they worry you.

Less serious side effects for patients being treated for scabies

Less serious side effectsWhat to do
Gastrointestinal related
  • stomach discomfort
Skin related
  • rash
Other
  • tiredness
  • dizziness
The most common side effects reported are due to the death of the mites and include:
  • headache
  • joint pain
  • loss of appetite
  • worsening of the itching.
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects for patients being treated for river blindness, threadworm or scabies

Serious side effectsWhat to do
Allergic reaction related
  • severe skin reaction which starts with painful red areas, then large blisters and ends with peeling of layers of skin. This is accompanied by fever and chills, aching muscles and generally feeling unwell.
  • skin condition with severe blisters and bleeding in the lips, eyes, mouth, nose and genitals
These are serious side effects. You may need urgent medical attention. These side effects are rare.		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.

If the patient has intestinal worms, ivermectin may kill the worms and patients may notice them being expelled during defaecation.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

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 STROMECTOL contains

Active ingredient
(main ingredient)		ivermectin 3 mg per tablet
Other ingredients
(inactive ingredients)		microcrystalline cellulose
pregelatinised maize starch
magnesium stearate
butylated hydroxyanisole
citric acid

STROMECTOL does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

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

What STROMECTOL looks like

STROMECTOL is a white, round tablet with 'MSD' marked on one side and '32' on the other side (AUST R 181338).

A pack contains 4 tablets.

Who distributes STROMECTOL

Merck Sharp & Dohme (Australia) Pty Limited
Level 1, Building A 26 Talavera Road
Macquarie Park NSW 2113
Australia

This leaflet was prepared in October 2023.

RCN000024542-AU

Copyright © 2023 Merck & Co., Inc., Rahway, NJ, USA, and its affiliates. All rights reserved.

Published by MIMS November 2023

BRAND INFORMATION

Brand name

Stromectol

Active ingredient

Ivermectin

Schedule

S4

 

1 Name of Medicine

Ivermectin.

2 Qualitative and Quantitative Composition

Ivermectin 3 mg tablets.
Ivermectin is derived from the avermectins, a class of highly active broad-spectrum antiparasitic agents isolated from fermentation broths of Streptomyces avermitilis.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Stromectol (ivermectin) is available as white, round, flat tablets with a bevelled edge, engraved with 'MSD' on one side and '32' on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Stromectol (ivermectin) is indicated for the treatment of:
a) onchocerciasis and intestinal strongyloidiasis (anguillulosis);
b) crusted scabies in conjunction with topical therapy;
c) human sarcoptic scabies when prior topical treatment has failed or is contraindicated.
Treatment is only justified when the diagnosis of scabies has been established clinically and/or by parasitological examination. Without formal diagnosis, treatment is not justified in case of pruritus alone.

4.2 Dose and Method of Administration

Stromectol is available as white tablets each containing 3 mg ivermectin. Treatment is administered as a single oral dose given with water.
The dose is determined by the patient's weight as shown in Tables 1 to 3.

Strongyloidiasis.

The dosage aims to provide approximately 200 microgram ivermectin/kg body weight.
In general, additional doses are not necessary, however, a follow-up examination of stool to verify efficacy should be performed.

Onchocerciasis.

The dosage aims to provide approximately 150 microgram ivermectin/kg body weight.
The suggested dose interval for most patients is 12 months. At some sites it may be preferable to use a 6 months interval depending on such considerations as density of skin microfilariae and/or prevalence.

Sarcoptes scabiei (scabies).

The dosage aims to provide approximately 200 microgram ivermectin/kg body weight per dose.
Classic/typical scabies. 2 doses (1 dose on day 1 and another dose between day 8 and day 15). Ivermectin can be used alone or in combination with a topical scabicide.
Crusted scabies. (Ivermectin in combination with a topical scabicide administered as):

Mild cases.

2 doses (1 dose on day 1 and another dose between day 8 and day 15).

Moderate to severe cases.

More than 3 doses may be required for effective treatment.
Patients with crusted scabies should use keratolytics on days they are not treated with topical scabicides to assist with the reduction of scaling that harbours the mite. Consultation with a dermatologist or infectious diseases physician is recommended.
The life cycle of S. scabiei begins with the pregnant female laying two to three eggs a day in burrows several millimetres to several centimetres in length in the stratum corneum (outermost layer) of the skin. The eggs hatch in two weeks. The larvae form intra-epidermal lesions whilst they mature into the adult form. This maturation takes 2-3 weeks.

4.3 Contraindications

Hypersensitivity to any component of the product.

4.4 Special Warnings and Precautions for Use

If any hypersensitivity reaction to this product occurs, no further dose should be given.
Neurological toxicity, including depressed level of consciousness and coma, has also been reported in patients with the use of ivermectin in the absence of Loa loa infection. These events have generally resolved with supportive care and the discontinuation of ivermectin. (See Section 4.9 Overdose.)

For treatment of onchocerciasis.

Ivermectin should be used only when infections with O. volvulus have been diagnosed or are suspected. No data are available to support its use prophylactically.
After treatment with microfilaricidal drugs, patients with hyperreactive onchodermatitis (sowda) may be more likely than others to experience severe adverse reactions, especially oedema and aggravation of onchodermatitis.
Rarely, patients with onchocerciasis who are also heavily infected with Loa loa may develop a serious or even fatal encephalopathy either spontaneously or following treatment with an effective microfilaricide. In these patients, the following adverse experiences have also been reported: pain (including neck and back pain), red eye, conjunctival haemorrhage, dyspnoea, urinary and/or faecal incontinence, difficulty in standing/walking, mental status changes, confusion, lethargy, stupor, seizures or coma. This syndrome has been seen very rarely following the use of ivermectin.

Use in hepatic impairment.

Ivermectin has not been studied in patients with impaired hepatic function. As ivermectin is extensively metabolised by the liver, caution should be exercised if ivermectin is administered to patients with impaired hepatic function.

Use in renal impairment.

Ivermectin has not been studied in patients with impaired renal function.

Use in the elderly.

Clinical studies of Stromectol did not include sufficient numbers of elderly subjects aged 65 years and over to determine whether they respond differently from younger subjects. In general, treatment of elderly patients should be cautious, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Paediatric use.

Onchocerciasis.

Ivermectin should not be used in children under five years of age as safety in this age group has not been established.
The safety profile of ivermectin in children 5 to 12 years of age is similar to that observed in adults (see Section 4.8 Adverse Effects (Undesirable Effects), Onchocerciasis).

Strongyloidiasis.

Efficacy has not been established in children under twelve years of age.

Sarcoptes scabiei (scabies).

Ivermectin should not be used in children under 15 kg and under 5 years of age as safety in these groups has not been established.

Effects on laboratory tests.

No data are available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Interactions between ivermectin and other drugs have not been studied in clinical trials.
Very rare post-marketing reports of increased INR (International Normalised Ratio) have been reported when ivermectin was co-administered with warfarin.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data are available.
(Category B3)
Ivermectin should not be used in pregnancy as safety in pregnancy has not been established. Ivermectin caused cleft palates in mice and rats at oral doses of 0.4 and 10 mg/kg/day respectively, and cleft palates and clubbed feet in rabbits dosed at 3 mg/kg/day.
 Ivermectin is excreted in breast milk and safety in newborn infants has not been established. In rats, reduced survival occurred in control pups and pups exposed in utero that were cross-fostered to treated dams, but not in control pups or pups exposed in utero cross-fostered to control dams.
The drug should be given to nursing mothers only if the benefit to the mother outweighs the potential risk to the breast-fed infant, and the treatment of mothers who intend to breast-feed their infants should be delayed until at least one week after the birth of the child.

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)

Clinical trial and published data.

Strongyloidiasis. Ivermectin has been demonstrated to be generally well tolerated in the treatment of strongyloidiasis.
In three clinical studies involving a total of 109 patients given either one or two doses of 170-200 microgram/kg of ivermectin, the following adverse reactions were reported as possibly, probably, or definitely related to ivermectin:

Body as a whole.

Asthenia/fatigue (0.9%), abdominal pain (0.9%).

Gastrointestinal.

Anorexia (0.9%), constipation (0.9%), diarrhoea (1.8%), nausea (1.8%), vomiting (0.9%).

Nervous system/psychiatric.

Dizziness (2.8%), somnolence (0.9%), vertigo (0.9%), tremor (0.9%).

Skin.

Pruritus (2.8%), rash (0.9%), and urticaria (0.9%).
Ivermectin was better tolerated than thiabendazole in comparative studies involving 37 patients treated with thiabendazole.
In a WHO sponsored study, children and adults (9-22 years) with strongyloidiasis were treated with ivermectin 200 microgram/kg as a single dose or albendazole 200 mg twice daily for 3 days. The safety results are summarised in Table 4.
The Mazzotti-type and ophthalmologic reactions associated with the treatment of onchocerciasis or the disease itself would not be expected to occur in strongyloidiasis patients treated with ivermectin (see Section 4.8 Adverse Effects (Undesirable Effects), Onchocerciasis).

Laboratory test findings.

In clinical trials involving 109 patients given either one or two doses of 170-200 microgram/kg ivermectin, the following laboratory abnormalities were seen irrespective of drug relationship: elevation in ALT and/or AST (2%), decrease in leukocyte count (3%). Leukopenia and anaemia were seen in one patient.
Onchocerciasis. Ivermectin has been demonstrated to be generally well tolerated in the treatment of onchocerciasis.
Historical data have shown that microfilaricidal drugs, such as diethylcarbamazine citrate (DEC-C), might cause cutaneous and/or systemic reactions of varying severity (the Mazzotti-type reaction) and ophthalmological reactions in patients with onchocerciasis. These reactions are probably due to allergic and inflammatory responses to the death of microfilariae. Patients treated with ivermectin for onchocerciasis may experience these reactions in addition to clinical adverse reactions possibly, probably, or definitely related to the drug itself.
In clinical trials involving 963 adult patients treated with 100 to 200 microgram/kg ivermectin and 315 patients on placebo, worsening of the following Mazzotti-type reactions during the first 4 days post-treatment were reported (ivermectin, placebo, respectively): arthralgia/synovitis (9.3%, 4.4%), axillary lymph node enlargement (11.0%, 2.9%), axillary lymph node tenderness (4.4%, 1.0%), cervical lymph node enlargement (5.3%, 4.1%), cervical lymph node tenderness (1.2%, 0.6%), inguinal lymph node enlargement (12.6%, 6.7%), inguinal lymph node tenderness (13.9%, 5.7%), other lymph node enlargement (3.0%, 1.6%), other lymph node tenderness (1.9%, 0.6%), pruritus (27.5%, 17.2%), skin involvement including oedema, papular and pustular or frank urticarial rash (22.7%, 9.2%), and fever (22.6%, 4.8%).
In clinical trials, ophthalmological conditions were examined in 963 adult patients before treatment, at day 3 and months 3 and 6 after treatment with 100 to 200 microgram/kg ivermectin. Changes observed were primarily deterioration from baseline 3 days post-treatment. Most changes either returned to baseline condition or improved over baseline severity at the month 3 and 6 visits. The percentages of patients with worsening of the following conditions at day 3, month 3 and 6, respectively, were: limbitis: 5.5%, 4.8%, and 3.5% and punctate opacity: 1.8%, 1.8%, and 1.4%. The corresponding percentages for patients treated with placebo were: limbitis: 6.2%, 9.9% and 9.4% and punctate opacity: 2.0%, 6.4% and 7.2%.
In clinical trials involving 963 adult patients who received 100 to 200 microgram/kg ivermectin and 315 patients on placebo, the following clinical adverse reactions were reported as possibly, probably, or definitely related to the drug in ≥ 1% of the patients (ivermectin and placebo, respectively): facial oedema (1.2%, 0%), peripheral oedema (3.2%, 0.6%), orthostatic hypotension (1.1%, 0%), and tachycardia (3.5%, 0.6%). Drug-related headache and myalgia occurred in < 1% of patients given ivermectin (0.2%, and 0.4%, respectively). However, these were the most common adverse experiences reported overall during these trials regardless of causality (22.3%, and 19.7%, respectively).
A similar safety profile was observed in an open study in paediatric patients ages 5 to 12.
The following ophthalmological side effects do occur due to the disease itself but have also been reported after treatment with ivermectin: abnormal sensation in the eyes, eyelid oedema, anterior uveitis, conjunctivitis, limbitis, keratitis, and chorioretinitis or choroiditis. These have rarely been severe or associated with loss of vision and have generally resolved without corticosteroid treatment.

Laboratory test findings.

In controlled clinical trials, the following laboratory adverse experiences were reported as possibly, probably, or definitely related to the drug in ≥ 1% of the patients (ivermectin and placebo, respectively): eosinophilia (3%, 0%) and haemoglobin increase (1%, 0%).
Sarcoptes scabiei (scabies). Adverse effects reported in the literature review were similar to those reported in clinical trials for the other indications. The most common adverse drug reactions reported with ivermectin in the review involved the transient exacerbation of pruritus that can sometimes occur as a result of sensitisation of the human host to mite antigens, with a consequent immunologic reaction (1.4%). Sensitisation also frequently results in delayed resolution of symptoms. Patients should be warned that itching may persist for one to two weeks after treatment, even if the mite is successfully eradicated. Other frequently reported reactions consisted of headache (< 1.0%), arthralgia (< 1.0%) and anorexia (< 1.0%). Additionally, lethargy (< 1.0%), listlessness (< 1.0%), abdominal discomfort (< 1.0%), rash (< 1.0%), and dizziness (< 1.0%) were reported. Up to 1.86% of patients noticed that they had passed Ascaris worms during the week after treatment.

Post-marketing experience.

Onchocerciasis.

Conjunctival haemorrhage.

All indications.

Very rarely, hypotension (mainly orthostatic hypotension), worsening of bronchial asthma, toxic epidermal necrolysis, Stevens-Johnson syndrome, seizures, elevation of liver enzymes and elevation of bilirubin.
Neurological toxicity including depressed level of consciousness and coma (see Section 4.4 Special Warnings and Precautions for Use).

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 http://www.tga.gov.au/reporting-problems.

4.9 Overdose

It is important to adhere to recommended dosages. Cases of depressed level of consciousness and coma have been reported with overdosage of ivermectin.
In significant accidental intoxication with unknown quantities of a veterinary formulation, symptoms have resembled those seen in animal toxicology studies, which were chiefly rash, contact dermatitis, oedema, headache, dizziness, asthenia, nausea, vomiting, diarrhoea, mydriasis, somnolence, depressed motor activity, tremors and ataxia. Other adverse effects that have been reported include: seizure, dyspnoea, abdominal pain, paraesthesia and urticaria.
In case of accidental poisoning, supportive therapy, if indicated, should include parenteral fluids and electrolytes, respiratory support (oxygen and mechanical ventilation if necessary) and pressor agents if clinically significant hypotension is present. Induction of emesis and/or gastric lavage as soon as possible, followed by purgatives and other routine antipoison measures may be indicated if needed to prevent absorption of ingested material. Although data are not available for man, it would appear advisable to avoid GABA-agonistic drugs in the treatment of accidental ivermectin intoxication.
In a study in which healthy volunteers were orally administered up to 2000 microgram/kg ivermectin in a fasted state or up to 600 microgram/kg ivermectin following a high-fat (48.6 g of fat) meal, there were no indications of central nervous system toxicity observed at any dose irrespective of food intake.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Ivermectin inhibits signal transmission from the ventral cord interneurons to the excitatory motor neurones in nematodes by stimulating release of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) from pre-synaptic nerve terminals. In arthropods, a similar mechanism inhibits signal transmission at the neuromuscular junction. Ivermectin does not readily penetrate the CNS of mammals, and thus does not interfere with mammalian GABA-dependent neurotransmission.

Clinical trials.

Onchocerciasis in adults. A total of 758 adult patients with onchocerciasis received a single oral dose of 150-220 microgram/kg ivermectin in three studies. In these studies, a significant reduction in microfilarial counts was reported in evaluable patients who received ivermectin, compared to those who received diethylcarbamazine or placebo. At 2-4 days after ivermectin dosing, microfilariae (mf) counts less than 5 per mg skin were reported in 29% to 96% of evaluable subjects, at 3 months after dosing < 5 mf/mg were reported in 88% to 96% of evaluable subjects, and at 12 months after dosing < 5 mf/mg were reported in 48% to 62% of evaluable patients. In patients with ocular involvement there was a significant reduction in intraocular microfilariae maintained for up to 12 months.
Onchocerciasis in children. In an open study, ivermectin reduced skin microfilaria in children with onchocerciasis for up to 12 months. One hundred and three (103) children aged between 5 to 12 years were treated with the targeted dose of 150 microm/kg ivermectin as a single oral dose. Resulting geometric mean microfilariae (mf) counts fell from a pre-treatment value of 36.4 mf/mg skin to 5.8%, 0.7%, 2.2% and 5.4% of the pre-treatment value on day 3, month 3, month 6 and month 12 respectively.
Intestinal strongyloidiasis. Two controlled clinical studies using albendazole as the comparative agent were carried out in countries where albendazole is approved for the treatment of strongyloidiasis of the gastrointestinal tract, and two controlled studies were carried out using thiabendazole as the comparative agent. Efficacy, as measured by cure rate, was defined as the absence of larvae in follow-up stool examinations post-therapy. Based on this criterion, efficacy was significantly greater for ivermectin (a single dose of 170 to 200 microgram/kg) than for albendazole (200 mg b.i.d. for 3 days). Ivermectin administered as a single dose of 200 microgram/kg for 1 day was as efficacious as thiabendazole administered at 25 mg/kg b.i.d. for 3 days. See Table 5.
Sarcoptes scabiei.

Classic variety/typical scabies.

The clinical data evaluated for this indication were from a literature-based submission which uncovered 8 randomized controlled trials of ivermectin in typical scabies (see References), as well as a number of reviews, including a 2010 Cochrane Review (Strong and Johnstone, 2010).

Placebo-controlled studies.

Macotela-Ruiz et al. (1993) conducted a trial comparing a single dose of ivermectin 200 microgram/kg body weight with placebo in the treatment of scabies in 55 patients. The authors found that 26 (79.3%) patients were cured, defined as absence of itching and no dermatologically active lesions, with ivermectin on their first follow-up visit vs. 4 (16%) in the placebo group (p < 0.001). The overall cure rates were 37 (74%) and 4 (16%) for ivermectin and placebo, respectively (p < 0.001).

Active-comparator trials.

Bachewar et al. (2009) conducted a non-blinded, prospective, randomized trial comparing benzyl benzoate 25% lotion (applied nightly for 2 nights), permethrin 5% cream (applied once), and a single dose of ivermectin 200 microgram/kg body weight in 103 patients with noncrusted scabies. The primary outcome of interest was cure rate, defined as no lesions, measured after 1 and 2 weeks.
After 1 week, the cure rates were 76%, 82.1%, and 55.6% for benzyl benzoate, permethrin, and ivermectin, respectively (p < 0.05 for permethrin vs. ivermectin). After 2 weeks, the cure rates were 92% for benzyl benzoate, 96.4% for permethrin, and 100% for ivermectin.
Chouela et al. (1999) compared ivermectin and lindane in a randomized, controlled, double-blind study in 53 patients with scabies. Patients received either a single oral dose of ivermectin 150-200 microgram/kg body weight or topical application of 1% lindane solution. Treatment was repeated if clinical cure had not occurred, with clinical cure defined as absence of both pruritus and clinical lesions or a reduction in severity of signs and symptoms to 'mild'.
At day 15, 14/19 (74%) patients in the ivermectin group showed healing compared with 13/24 (54%) in the lindane group (p = 0.22). At day 29, 18/19 (95%) patients receiving ivermectin were healed, and 23/24 (96%) receiving lindane were healed (p > 0.99). Further analysis of the equivalence of therapeutic efficacy showed that ivermectin was statistically no less efficacious than lindane (p < 0.02).
Ly et al. (2009) compared 2 regimens of benzyl benzoate (BB) and ivermectin in a randomized, open-label trial in 181 patients with scabies. BB was administered as either one application of 12.5% benzyl benzoate which was not removed for 24 hours (BB1), or as two such applications, each over 24 hours (BB2). Ivermectin was administered as a single oral dose of 150-200 microgram/kg body weight.
The primary outcome measure was complete disappearance of visible lesions and itching at day 14. Patients who had clearly worsened at day 7 were given the same treatment as the week before. If no change was noted at day 7 or if the patient had improved, nothing further was done until day 14. If treatment failure was observed at day 14, the treatment was applied again. If treatment failure was observed again at day 28, patients in the BB1 and ivermectin groups were switched to the BB2 application, and those in the BB2 group were switched to ivermectin.
For the primary endpoint of efficacy at day 14, cure rates were 37/68 (54.4%) with BB1, 33/48 (68.8%) with BB2, and 16/65 (24.6%) with ivermectin, with a significance level of p < 10-6 overall. The comparison of BB1 and BB2 combined was also superior to ivermectin (p < 10-5). At day 28, cure rates were 52/68 (76.5%) for BB1, 46/48 (95.8%) for BB2, and 28/65 (43.1%) for ivermectin (p < 10-5 overall).
Madan et al. (2001) compared ivermectin and 1% topical lindane solution in a randomized trial in 200 patients with scabies. Patients received either a single dose of ivermectin 200 microgram/kg body weight or 1% lindane topical solution applied overnight for 1 night. Efficacy was evaluated over the first 3 days, and at 2 weeks and 4 weeks. Improvement was measured on a categorical scale of: Complete/100% (no signs or symptoms of scabies); Good/75% (itching absent, lesions except burrows present; Moderate/50% (Itching markedly reduced, burrows +); Slight/25% (Itching slightly reduced, burrows ++); Poor/0% (no improvement); Negative (Further aggravation/exacerbation).
After 48 hours of treatment, no patients in either treatment group reported complete improvement, but 17.5% of patients in the ivermectin group and 7.1% in the lindane group reported good improvement. After 2 weeks, 36.1% of patients in the ivermectin group had complete improvement compared with 22.4% in the lindane group. At 4 weeks, 82.6% of patients in the ivermectin group had complete improvement compared with 44.4% in the lindane group. After 4 weeks, 2.8% of patients in the ivermectin group reported negative improvement compared with 4.9% in the lindane group.
Mushtaq et al. (2010) compared ivermectin and permethrin 5% cream in 100 patients with scabies. Patients received either a single dose of ivermectin 200 microgram/kg body weight or a single application of topical permethrin 5% cream at night on the whole body for 12 hours. Patients not responding after the 1 week dose were given a second dose. Efficacy was determined by disappearance of itching, clearance of skin lesions, and absence of mites on microscopy of skin lesions.
Two weeks after the first dose, 24 (54.5%) patients in the ivermectin group were cured of disease, and 20 (47.6%) were cured in the permethrin group (p = 0.5). Cure rates at 4 weeks were 79.5% and 88.1%, respectively (p = 0.157). Itching at 4 weeks was mild in 6.8% of patients in the ivermectin group, and 2.4% in the permethrin group. No patients in either group had positive mite scrapings at week 2.
Nnoruka and Ague (2001) evaluated ivermectin and 25% benzyl benzoate topical application in an uncontrolled prospective study in 58 patients with scabies. Patients received ivermectin as a single oral dose at 200 microgram/kg body weight or 25% benzyl benzoate applied from neck to toes for 72 hours. Clinical scores were calculated using skin lesions located in 16 different locations of the body. An area was given a score of 2 if there was at least one active lesion, a score of 1 if the most important lesion was healed, and a score of 0 if there was no lesion present. A classical burrow was scored a 2. A patient's clinical score was the sum off all individual area scores, which could range from 2 to 30 at study entry and from 0 to 30 at subsequent visits. In addition, pruritus was measured on a 10 cm visual analogue scale, where 0 = not present and 10 = extremely severe.
Mean clinical scores at baseline were 16.1 for ivermectin and 16 for benzyl benzoate. At day 7, scores were 5.4 and 10.3, respectively. At day 14 scores were 2.3 and 6.1, respectively, and at day 30 scores were 1.1 and 3.5 respectively. Analysis of variance showed a significant decrease in scores with ivermectin (p = 0.004). At day 7, 31% of patients receiving ivermectin had complete disappearance of lesions and pruritus. On day 14, 65.3% of patients receiving ivermectin and 34.5% of patients receiving benzyl benzoate were healed. By day 30, 93.7% of patients receiving ivermectin were healed. By day 30, response to pruritus was rated as excellent in 93.1% of patients receiving ivermectin, and 48.3% in patients receiving benzyl benzoate.
Usha and Nair (2000) conducted a randomized trial comparing ivermectin and permethrin cream in the treatment of scabies in 85 patients and their family contacts. Ivermectin was administered as a single oral dose of 200 microgram/kg body weight, and 5% permethrin cream was given as a single overnight topical application. Treatment was considered to be effective if, after 2 weeks, there was improvement in pruritus (measured on a visual analogue scale), clinical improvement in skin lesions with no new lesions, and absence of mites or the products on microscopy. Improvement was considered mild if there was less than 50% reduction in the number of lesions and pruritus; moderate if there was more than 50% reduction; and good if there was complete clearance. Treatment was considered a failure if, after 2 weeks, there was no improvement in pruritus and skin lesions, appearance of new lesions, or presence of mites or their products on microscopy. In the case of treatment failure, another dose of the randomized treatment was repeated. If the repeat treatment failed, patients were crossed over to the other treatment group. The primary endpoint was the complete disappearance of clinical signs and symptoms and no appearance of new lesions at the end of 2 months after the last dose was taken.
After the first week, 50% of patients in the ivermectin group and 84.3% of patients in the permethrin group had symptom improvement. By the second week, 70% in the ivermectin group and 97.8%, in the permethrin group improved. By the fourth week, 95% of patients in the ivermectin and 100% of patients in the permethrin groups improved. Two (5%) patients did not respond to 2 doses of ivermectin; both were cured after crossing over to permethrin after a single application. There was no recurrence of scabies at the end of 2 months of follow-up in either group. Complete clearance of lesions (graded as "good" improvement) occurred earlier with permethrin than with ivermectin, with significant differences at weeks 1 (p = 0.03), 2 (p = 0.003), and 4 (p = 0.0005). At 8 weeks, all patients were completely cured (p = 0.21).

Crusted variety.

No randomised controlled trials in crusted scabies have been reported in the literature. A systematic review of the literature on crusted scabies identified observational studies, case series and individual case reports in which 260 patients (mean age (range) 41.7 years (2-94 years)) received ivermectin. Of these cases, 182 received ivermectin at a dose of 200 microgram/kg of body weight.
Seventy eight percent (78%) of all patients were managed in a clinic setting following confirmation of high mite count. The majority of patients for whom this was reported (70%) received ivermectin after proving refractory to classical topical treatments.
At least 72% of cases were treated with combination ivermectin and topical scabicide. In the large Australian cohort studies, all patients were administered topical keratolytic therapy in keeping with Australian clinical protocols.
Ivermectin was shown to have an overall clinical efficacy across these publications of an 87% cure rate, however, this must be interpreted with caution because of the potential for publication bias (i.e. publication of cases with good outcomes). The majority of patients presenting with mild to severe forms of crusted scabies were adequately managed with one to two oral doses of 200 microgram/kg ivermectin. One to two doses may not be adequate in treating very severe cases of crusted scabies.

5.2 Pharmacokinetic Properties

Absorption and distribution.

Ivermectin is incompletely absorbed (~50% bioavailable relative to an oral hydroalcoholic solution) following oral doses of ivermectin tablets, with a Tmax of ~4 hours. With 12 mg single dose tablets administered in healthy male volunteers, the mean peak plasma concentration of the major component was 46.6 (± 21.9) nanogram/mL (range 16.4-101.1 nanogram/mL).
Administration of 30 mg (333 to 600 microgram/kg) ivermectin following a high-fat meal resulted in an approximate 2.5-fold increase in bioavailability relative to administration of 30 mg ivermectin in the fasted state in healthy volunteers.

Metabolism and excretion.

Ivermectin is metabolised in humans, and ivermectin and/or its metabolites are excreted almost exclusively in the faeces over an estimated 12 days with less than 1% of the administered dose being excreted in the urine. The plasma half-life of ivermectin in man is about 12 hours (9.8-14.3 h) and that of the metabolites is about 3 days.
The pharmacokinetics of ivermectin has not been studied in patients with impaired hepatic or renal function.

5.3 Preclinical Safety Data

Genotoxicity.

Ivermectin was negative in three in vitro assays for genotoxicity (mutagen assays in bacteria and mouse cells, and unscheduled DNA synthesis in human cells). No tests have been done to test the potential of ivermectin for producing clastogenicity.

Carcinogenicity.

There have been no carcinogenicity studies with ivermectin. Ninety-four and 105 week carcinogenicity studies on mice and rats respectively were conducted with the closely related compound abamectin and were negative at up to 8 mg/kg/day in mice and up to 2 mg/kg/day in rats.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each tablet of Stromectol contains the following inactive ingredients: microcrystalline cellulose, pregelatinised maize starch, magnesium stearate, butylated hydroxyanisole and citric acid.

6.2 Incompatibilities

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

6.3 Shelf Life

The expiry date can be found on the packaging. In Australia, information on the shelf life can be found on the public summary of the ARTG.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

The tablets are packaged in aluminium foil blister packs in cardboard cartons. Pack size: 4 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Ivermectin is a white to yellowish-white non-hygroscopic crystalline powder which is practically insoluble in water, freely soluble in methanol, and soluble in 95% ethanol.
Molecular Formula: 22, 23-dihydroavermectin B1a; C48H74O14 (R=C2H5). Molecular Weight: 875.10.
Molecular Formula: 22, 23-dihydroavermectin B1b; C47H72O14 (R=CH3). Molecular Weight: 861.07.
Ivermectin contains a minimum of 90% of 22, 23-dihydroavermectin B1a (where the R group is ethyl) and a maximum of 10% of 22, 23-dihydroavermectin B1b (the R group is methyl).

Chemical structure.


CAS number.

70288-86-7.

References

Bachewar N P, et al. Comparison of safety, efficacy, and cost effectiveness of benzyl benzoate, permethrin, and Ivermectin in patients of scabies. Indian J Pharmacol. Feb 2009;41(1):9-14.
Chouela E N, et al. Equivalent therapeutic efficacy and safety of Ivermectin and lindane in the treatment of human scabies. Archives of Dermatology. 1999;135(6):651-5.
Ly F, et al. Ivermectin versus benzyl benzoate applied once or twice to treat human scabies in Dakar, Senegal: a randomized controlled trial. Bull World Health Organ. 2009;87:424-30.
Macotela-Ruiz E, et al. The treatment of scabies with oral ivermectin [Tratamiento de la escabiasis con ivermectina por via oral]. Gaceta Medica de Mexico 1993;129(3):201-5.
Madan V, et al. Oral Ivermectin in scabies patients: A comparison with 1% topical lindane lotion. The Journal of Dermatol. 2001;28(9):481-84.
Mushtaq A, et al. Comparison of efficacy and safety of oral Ivermectin with topical permethrin in treatment of scabies. Journal of Pakistan Association of Dermatologists. 2010;20:227-31.
Nnoruka EN, et al. Successful treatment of scabies with oral Ivermectin in Nigeria. Tropical Doctor. 2001;31(1):15-18.
Strong M, Johnstone P. Interventions for treating scabies (Review). The Cochrane Collaboration. 2010, Issue 10.
Usha V, et al. A comparative study of oral Ivermectin and topical permethrin cream in the treatment of scabies. J Am Acad Dermatol. 2000;42(2)(Part1):236-40.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (S4).

Summary Table of Changes