Consumer medicine information

Soolantra Cream

Ivermectin

BRAND INFORMATION

Brand name

Soolantra

Active ingredient

Ivermectin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Soolantra Cream.

What is in this leaflet

This leaflet answers some common questions about SOOLANTRA.

It does not contain all the available information. It does not use the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using SOOLANTRA against the benefits they expect it will have for you.

If you have any concerns about this medicine, ask your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What SOOLANTRA is used for

SOOLANTRA contains the active substance ivermectin that belongs to a group of medicines called avermectins.

SOOLANTRA is used to treat pimples and spots found with rosacea.

Your doctor, however may prescribe it for another purpose.

Ask your doctor if you have any questions about why SOOLANTRA has been prescribed for you.

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

SOOLANTRA is not addictive.

Before you use SOOLANTRA

When you must not use it

Do not use SOOLANTRA:

  • if you have an allergy to any medicine containing ivermectin
  • if you have an allergy to any of the ingredients listed at the end of this leaflet
  • for any children under 18 years of age

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives of the skin

Do not use SOOLANTRA after the use by (expiry) date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

Before you start to use it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

SOOLANTRA contains cetyl alcohol and stearyl alcohol which may cause local skin reactions (e.g. contact dermatitis), methyl hydroxybenzoate (E218) and propyl hydroxybenzoate (E217) which may cause allergic reactions (possibly delayed), and propylene glycol which may cause skin irritation.

Tell your doctor if you have or have had any of the following medical conditions:

  • Kidney disease
  • Liver disease

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you start taking SOOLANTRA.

SOOLANTRA should only be used on the skin of the face. At the start of the treatment, some patients may experience worsening of the symptoms of rosacea, however this is uncommon and usually resolves within 1 week of the treatment. Talk to your doctor if this happens.

SOOLANTRA should not be used on the following areas:

  • eyes or eyelids
  • mouth
  • lips

If SOOLANTRA comes into contact with these areas, the area should be rinsed immediately with plenty of water.

SOOLANTRA is not recommended for use in children under 18 years.

Using other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop. Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to use SOOLANTRA

How much to use

Five small pea size amounts of SOOLANTRA is the daily recommended dose (approximately 1 gram).

Ask your doctor or pharmacist if you are not sure how much to apply. They will tell you exactly how much to use for each application.

Follow the instructions they give you.

How to use it

SOOLANTRA is only intended for use on the skin of the face.

It is recommended that SOOLANTRA be applied once per day after your usual cleansing routine, and before any cosmetics or sunscreens are applied.

Apply a small, pea size amount of SOOLANTRA to each of the following five areas of the face: forehead, chin, nose, and to each cheek, avoiding the eyes, eyelids, lips and mouth. The product should be applied smoothly and evenly as a thin layer across your face.

Hands should be washed after applying SOOLANTRA.

After applying SOOLANTRA use a non-comedogenic, broad spectrum, SPF 50+ sunscreen and wear protective clothing to protect your skin from UV rays.

Cosmetics can also be applied after SOOLANTRA has dried.

How to open the tube with a child-resistant cap.

To avoid spillage, do not squeeze the tube while opening or closing. Push down on the cap and turn in a counter clockwise (to the left) a quarter of a turn.

  1. Push down the cap

  1. twist in the direction of the arrow as shown below (counterclockwise).

How to close the tube with a child-resistant cap.

Gently press down on the child resistant cap and twist to the right (clockwise).

How long to use it

Your doctor or pharmacist will tell you how long to use SOOLANTRA.

Continue using your medicine for as long as your doctor tells you. You should use SOOLANTRA daily over the treatment course. The doctor may decide that the treatment course should be repeated. The duration of treatment can vary from person to person and depends on the severity of your skin condition.

Pimples and spots will be reduced only after several applications of this medicine. It is important that you continue using SOOLANTRA as long as prescribed by your doctor.

If you are not sure how long to use SOOLANTRA, talk to your doctor or pharmacist.

If you forget to use it

If it is almost time for your next dose, skip the dose you missed and use your next dose when you are meant to.

Do not use a double dose to make up for the dose that you missed.

If you have trouble remembering to use your medicine, ask your pharmacist for some hints.

If you swallow it

Immediately telephone your doctor, or Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at your nearest hospital, if you think you or anyone else may have taken too much SOOLANTRA.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are using SOOLANTRA

Things you must do

Tell all doctors and pharmacists who are treating you that you are using SOOLANTRA.

If you feel that SOOLANTRA is not helping your condition, tell your doctor or pharmacist.

Tell your doctor if, for any reason, you have not used SOOLANTRA exactly as prescribed. Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

If you become pregnant while using SOOLANTRA, tell your doctor.

Things you must not do

Do not use SOOLANTRA under dressings or on large areas of skin unless your doctor tells you.

Do not use SOOLANTRA in or near the eyes.

Do not give SOOLANTRA to anyone else, even if they have the same symptoms as yours.

Do not use SOOLANTRA to treat other complaints unless your doctor or pharmacist tells you to.

Things to be careful of

Avoid contact with the eyes, eyelids, lips and mouth. If SOOLANTRA comes into contact with these areas, the area should be rinsed immediately with plenty of water.

Ask your doctor or pharmacist if you are concerned about the length of time you have been using SOOLANTRA.

Side effects

All medicines may have some unwanted side effects. Sometimes they are serious, but most of the time they are not. Your doctor has weighed the risks of using this medicine against the benefits they expect it will have for you.

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

Tell your doctor if you notice any of the following and they worry you:

  • skin burning sensation
  • skin irritation
  • itching of the skin
  • dry skin
  • redness
  • Rosacea aggravation
  • Swelling of the face

These are mild side effects of the medicine and are usually mild and short-lived.

If any of the following happen, stop using SOOLANTRA and tell your doctor immediately, or go to Accident and Emergency at your nearest hospital:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives of the skin
  • Liver enzyme elevations (ALAT/ASAT)

These are very serious side effects. If you have them, you may have had a serious allergic reaction to SOOLANTRA. You may need urgent medical attention or hospitalisation. Serious side effects are very rare.

Tell your doctor if you notice anything else that is making you feel unwell. Other side effects not listed above may occur in some patients.

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

After using SOOLANTRA

If you have queries about any aspect of your medicine, or any questions regarding the information in this leaflet, discuss them with your doctor or pharmacist.

Storage

Keep the medicine in a cool dry place where the temperature stays below 30°C. Do not freeze.

Do not store it, or any other medicine, in a bathroom, near a sink, or on a window-sill.

Do not leave it in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop using SOOLANTRA or it has passed its expiry date, ask your pharmacist what to do with any that is left over.

Return any unused medicine to your pharmacist.

Product description

What it looks like

SOOLANTRA is a white to light yellow cream. It is supplied in plastic tube with a plastic cap containing 2 g, 15 g, 30 g, 45 g or 60 g of cream. For tube sizes greater than 2 g, the cap is a childresistant closure.

Not all pack sizes may be available.

Ingredients

Each gram of SOOLANTRA contains 10 mg (or 1.0% w/w) of ivermectin as the active ingredient.

Inactive ingredients:

  • glycerol
  • isopropyl palmitate
  • carbomer copolymer (type B)
  • dimethicone 20
  • disodium edetate
  • citric acid monohydrate
  • cetyl alcohol
  • stearyl alcohol
  • ceteareth-20
  • sorbitan stearate
  • methyl hydroxybenzoate (E218)
  • propyl hydroxybenzoate (E217)
  • phenoxyethanol
  • propylene glycol
  • oleyl alcohol
  • sodium hydroxide
  • purified water.

Sponsor

Galderma Australia Pty Ltd
Suite 4, 13B Narabang Way
Belrose NSW 2085
Ph 1800 800 765

Distributed in New Zealand by:

Healthcare Logistics
58 Richard Pearse Drive
Airport Oaks
Auckland
Ph: 0800 174 104

Made in France

Australian Registration Number: AUST R 227125

® Registered Trademark

This leaflet was updated on 11 March 2020.

Published by MIMS May 2020

BRAND INFORMATION

Brand name

Soolantra

Active ingredient

Ivermectin

Schedule

S4

 

1 Name of Medicine

Ivermectin.

2 Qualitative and Quantitative Composition

One gram of Soolantra cream contains 10 mg (or 1.0% w/w) of ivermectin.

Excipients with known effect.

Methyl hydroxybenzoate, propyl hydroxybenzoate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Soolantra is a white to pale yellow hydrophilic cream.

4 Clinical Particulars

4.1 Therapeutic Indications

Soolantra is indicated for the topical treatment of inflammatory lesions of rosacea (papulopustular) in adult patients 18 years and over.

4.2 Dose and Method of Administration

Dosage.

One application a day for up to 4 months. Soolantra should be applied daily over the treatment course. The treatment course may be repeated.
In case of no improvement after 3 months, the treatment should be discontinued. For optimal facial treatment, it is recommended that five small pea size amounts, the total estimated to be no more than 1 g, are applied to the main areas of the face (i.e. forehead, chin, nose, each cheek) daily. The cream should be spread as a thin layer across the entire face, avoiding the eyes and lips.
After Soolantra has dried, a high sunscreen protection factor (SPF) sunscreen should be applied to treated areas that are likely to be exposed to the sun, or other sun exposure reduction methods should be used (e.g. hats, clothing). Cosmetics and sunscreens may also be applied after Soolantra has dried.
Soolantra should be applied only to the face.
Hands should be washed after applying Soolantra.
Soolantra is not for oral, ophthalmic, or intravaginal use.

Special populations.

Elderly patients.

No dosage adjustment is necessary in the geriatric population (see Section 4.4 Special Warnings and Precautions for Use, Use in the elderly).

Paediatric population.

The safety and efficacy of Soolantra in children and adolescents aged less than 18 years have not been established. No data are available.

4.3 Contraindications

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

4.4 Special Warnings and Precautions for Use

Soolantra contains cetyl alcohol and stearyl alcohol which may cause local skin reactions (e.g. contact dermatitis), methyl parahydroxybenzoate and propyl parahydroxybenzoate which may cause allergic reactions (possibly delayed), and propylene glycol which may cause skin irritation. If severe irritation or contact allergy occurs, treatment with Soolantra should be discontinued.
Safety and efficacy have not been established in patients suffering a particular forms of rosacea (rosacea conglobata, rosacea fulminans, isolated rhinophyma, isolated pustulosis of the chin) or other facial dermatoses that may be confounded with papulopustular rosacea, such as perioral dermatitis, facial keratosis pilaris, seborrheic dermatitis and acne.
Patients may experience transient aggravation of rosacea, which usually resolves within 1 week under continuation of the treatment as might be expected due to a reaction to the dying Demodex mites.
In case of severe worsening with a strong dermal reaction, the treatment should be discontinued.
High sunscreen protection factor (SPF) sunscreens or other sun exposure reduction methods should be used when Soolantra is applied to the face or other sun exposed areas.
Patients should wash their hands immediately after applying Soolantra.
As Soolantra has not been studied in patients with renal or hepatic impairment, caution should be used with such patients.

Use in hepatic impairment and use in renal impairment.

Soolantra has not been studied in patients with renal or hepatic impairment. Thus, caution should be used in treating such patients.

Use in the elderly.

Approximately 300 participants aged 65 years and older were treated over all clinical trials with the medicinal product. No meaningful differences in the efficacy and safety profile were observed between elderly participants and participants 18 to 65 years of age. In pivotal trials, effectiveness and safety in participants ≥ 65 were found to be comparable to the < 65 year old adults.

Paediatric use.

The safety and efficacy of Soolantra in children aged less than 18 years have not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interaction studies have been performed. Concomitant use of Soolantra with other topical or systemic medicinal products for the treatment of rosacea has not been investigated.
In vitro studies have shown that ivermectin is primarily metabolised by CYP3A4. Consequently, caution is advised when ivermectin is administered concomitantly with potent CYP3A4 inhibitors as the plasma exposure may be significantly increased.
In vitro studies have also shown that Soolantra cream, at therapeutic concentrations, neither inhibits nor induces cytochrome P450 (CYP450) enzymes.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No human data on the effect of ivermectin on fertility are available. Ivermectin was found to have no effect on the fertility of male and female rats at oral doses up to 9 mg/kg/day (animal:human AUC ratio ≈ 484).
(Category B3)
There are no adequate and well controlled studies in pregnant women. Soolantra should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Oral terategenotoxicity studies in the rabbit demonstrated maternal toxicity and carpal flexures in the fetus at a dose of 4.5 mg/kg/day. The NOAEL was established at 3.5 mg/kg/day, a dose corresponding to plasma levels 68 times higher than those obtained at the maximum recommended human dose by topical route (1 g application of Soolantra once daily).
In the rat, cleft palates were observed at the oral dose of 12 mg/kg/day. The dose of 4 mg/kg/day was the NOAEL for maternal toxicity and embryofetal development, a dose corresponding to plasma levels 334 times higher than those obtained at the maximum recommended human dose by topical route (1 g application of Soolantra once daily).
Following oral administration, ivermectin is excreted in human milk in low concentrations. Excretion in human milk following topical administration has not been evaluated. Available pharmacokinetic/toxicological data in animals have also shown excretion of ivermectin in milk. A risk to a breastfeeding child cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from Soolantra therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

4.7 Effects on Ability to Drive and Use Machines

Soolantra has no or negligible influence on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

Overall, Soolantra gel was shown to be well tolerated, with the most commonly reported adverse drug reactions being skin burning sensation, skin irritation, pruritus and dry skin, all occurring in 1% or less of patients treated during clinical trials. They are usually transient, mild to moderate in severity, and usually do not require discontinuation of treatment. No meaningful differences in the safety profile were observed between participants 18 to 65 years and participants ≥ 65 years of age.
During clinical trials, 2047 participants with inflammatory lesions of rosacea received Soolantra once daily. A total of 1555 participants were treated once daily for more than 12 weeks, and 519 for approximately one year.
Tabulated list of adverse events reported in ≥ 1% of patients during treatment with Soolantra in 2 phase 3 vehicle controlled studies, by system organ class, preferred terms and frequency are shown in Table 1.
Adverse reactions (considered as related) reported by < 1% of patients during treatment with Soolantra in 2 phase 3 vehicle controlled studies:

Skin and subcutaneous tissue disorders.

Uncommon (≥ 1/1,000 to < 1/100): skin irritation, pruritus, dry skin, rosacea aggravation.
Not known: erythema, dermatitis allergic, dermatitis contact, swelling of the face, transaminases increased.

Post-marketing experience.

Adverse reactions reported during post-marketing period include: erythema.

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

There are no reports of overdosage with Soolantra.
In accidental or significant exposure to unknown quantities of veterinary formulations of ivermectin in humans, either by ingestion, inhalation, injection, or exposure to body surfaces, the following adverse effects have been reported most frequently: rash, oedema, headache, dizziness, asthenia, nausea, vomiting, and diarrhoea. Other adverse effects that have been reported include: seizure, ataxia, dyspnea, abdominal pain, paresthesia, urticaria, and contact dermatitis.
In case of accidental ingestion, 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.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The mechanism of action of Soolantra cream in treating rosacea lesions is unknown. Ivermectin is a member of the avermectin class. Avermectin has been reported to exert anti-inflammatory effects by inhibiting lipopolysaccharide induced production of inflammatory cytokines. Anti-inflammatory properties of cutaneous ivermectin have also been observed in animal models of skin inflammation. Ivermectin also causes death of parasites, primarily through binding selectively and with high affinity to glutamate-gated chloride channels, which occur in invertebrate nerve and muscle cells. The mechanism of action of Soolantra in treating the inflammatory lesions of rosacea may be linked to anti-inflammatory effects of ivermectin as well as causing the death of Demodex mites that have been reported to be a factor in inflammation of the skin.

Clinical trials.

Soolantra applied once daily at bedtime was evaluated in the treatment of inflammatory lesions of rosacea in two randomised, double blind, vehicle controlled clinical studies, which were identical in design. The studies were conducted in 1371 participants aged 18 years and older who were treated once daily for 12 weeks with either Soolantra or vehicle.
Overall, 96% of participants were Caucasian and 67% were female. Using the 5 point Investigator Global Assessment (IGA) scale, 79% of participants were scored as moderate (IGA = 3) and 21% scored as severe (IGA = 4) at baseline.
The coprimary efficacy endpoints in both clinical studies were the success rate based on the IGA outcome (percentage of participants 'clear' and 'almost clear' at week 12 of the study) and absolute change from baseline in inflammatory lesion counts. The IGA scale is based on the following definitions (see Table 2).
The results from both clinical studies demonstrated that Soolantra applied once daily for 12 weeks was significantly more effective than vehicle in clearing lesions (as demonstrated by IGA success rate) and reduction in inflammatory lesion counts (p < 0.001; see Table 3 and Figures 1, 2, 3 and 4). Soolantra demonstrated a significantly superior efficacy versus vehicle on both coprimary endpoints (reduction of inflammatory lesions and IGA success rate) which occurred as early as week 4 and continued up to and including the 12 week time point.
Table 3 and Figures 1-4 present efficacy outcomes from both studies.
IGA was assessed during the 40 week extension of the two clinical studies and the percentages of participants treated with Soolantra achieving an IGA score of 0 or 1 continued to increase up to week 52. The success rate (IGA = 0 or 1) at week 52 was 71% and 76% in studies 1 and 2, respectively.
The efficacy and safety of topical ivermectin in the treatment of inflammatory lesions of rosacea was also evaluated in a randomised, investigator blinded, active controlled clinical study. Study 3 was conducted in 962 participants aged 18 years and older who were treated for 16 weeks with either Soolantra once daily or metronidazole 7.5 mg/g cream twice daily. In this study, 99.7% of participants were Caucasian and 65.2% were female; on the IGA scale, 83.3% of participants were scored as moderate (IGA = 3) and 16.7% scored as severe (IGA = 4) at baseline (see Figure 5).
The results of study 3 demonstrated that Soolantra was statistically more effective than metronidazole 7.5 mg/g cream on the primary efficacy endpoint (mean percent change in inflammatory lesion counts) with a reduction of 83.0% and 73.7% from baseline after 16 weeks of treatment for the ivermectin and metronidazole groups respectively (p < 0.001). The superiority of Soolantra at week 16 was confirmed on success rate based on IGA and absolute change in inflammatory lesion counts (secondary endpoints (p < 0.001).
The safety profile remained stable with long-term use for up to one year (see Section 4.8 Adverse Effects (Undesirable Effects)).

5.2 Pharmacokinetic Properties

Absorption.

The absorption of ivermectin from Soolantra was evaluated in a clinical trial in adult participants with severe papulopustular rosacea under maximal use conditions. At steady state (after 2 weeks of treatment), the highest mean (± standard deviation) plasma concentrations of ivermectin peaked within 10 ± 8 hours postdose (Cmax: 2.10 ± 1.04 nanogram/mL range: 0.69-4.02 nanogram/mL) and the highest mean (± standard deviation) AUC0-24hr was 36.14 ± 15.56 nanogram.hr/mL (range: 13.69-75.16 nanogram.hr/mL). In addition, systemic exposure assessment in longer treatment durations (phase 3 studies) evidenced that there was no plasma accumulation of ivermectin over the 52 week treatment period.

Distribution.

An in vitro study demonstrated that ivermectin is greater than 99% bound to plasma proteins and is bound primarily to human serum albumin. No significant binding of ivermectin to erythrocytes was observed. Ivermectin distribution into the brain, retina, and testis and distribution across the placenta is limited by ABC B1 (p-glycoprotein) efflux transporters. Pharmacokinetic interactions at these efflux transporters may increase the distribution of ivermectin into these tissues.

Metabolism.

In vitro studies using human hepatic microsomes and recombinant CYP450 enzymes have shown that ivermectin is primarily metabolized by CYP3A4.
In vitro studies show that ivermectin does not inhibit the CYP450 isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, 4A11 or 2E1. Ivermectin does not induce CYP450 enzyme expression (1A2, 2B6, 2C9 or 3A4) in cultured human hepatocytes.
Two major metabolites of ivermectin were identified in a maximal use clinical pharmacokinetic study and assessed during phase 2 clinical studies (3''-O-demethyl ivermectin and 4a-hydroxy ivermectin). Similar to the parent compound, metabolites reached steady-state conditions by 2 weeks of treatment, with no evidence of accumulation up to 12 weeks. Furthermore, the metabolites systemic exposures (estimated with Cmax and AUC) obtained at steady state were much lower than those observed following oral administration of ivermectin.

Excretion.

The apparent terminal half-life averaged 6 days (mean: 145 hours, range 92-238 hours) in subjects receiving a once daily topical application of the medicinal product for 28 days, in the maximal use clinical pharmacokinetic study.

5.3 Preclinical Safety Data

Genotoxicity.

Ivermectin was not mutagenic in vitro in bacterial and photobacterial reverse mutation assays, in the mouse lymphoma assay, in the photochromosomal aberration assay in Chinese hamster ovary cells, and in vivo in the oral micronucleus test in rats.

Carcinogenicity.

Chronic (1 year) repeated topical application of Soolantra enhanced simulated solar ultraviolet radiation induced nonmelanoma skin carcinogenesis in albino Skh HR-1 hairless mouse (tumour potency factor in both sexes combined was 1.69; and 1.74 in male mice and 1.51 in female mice; compared with an expected no adverse effect tumour potency factor of 1.00). The albino Skh HR-1 hairless mouse is more sensitive to ultraviolet radiation induced carcinogenesis than humans. Accordingly the clinical relevance of these findings is uncertain. However repeated unprotected exposure of Soolantra treated skin to ultraviolet radiation sources (including sunlight) should be avoided (see Section 4.4 Special Warnings and Precautions for Use).
In a 2 year topical carcinogenicity study in mice (without simulated solar light exposure), Soolantra was not tumorigenic when applied daily at doses corresponding to up to 10 mg/kg/day of ivermectin. At this dose, the plasma AUC in mice was 645.54 (m)/352 (f) times the human plasma AUC associated with the maximum recommended topical use of Soolantra.
In a 2 year oral carcinogenicity study in rats, ivermectin was considered not tumorigenic when administered daily at doses up to 3 mg/kg/day. At this dose, the plasma exposure of animals represented at least 282 times the human plasma AUC associated with the maximum recommended topical use of Soolantra.
At the oral dose of 9 mg/kg/day (corresponding to 832 (m)/924 (f) times the human plasma AUC associated with the maximum recommended topical use of Soolantra), an increase in the incidence of benign hepatocellular adenomas and related hepatic preneoplastic changes were reported in males only. There was also a higher incidence of pancreatic benign islet cell adenomas in males, and islet cell carcinoma with no evidence of distant metastasis in females. These neoplastic changes in rodents are not currently considered to be relevant to humans.

6 Pharmaceutical Particulars

6.1 List of Excipients

Glycerol, isopropyl palmitate, carbomer copolymer (type B), dimeticone 20, disodium edetate, citric acid monohydrate, cetyl alcohol, stearyl alcohol, ceteareth-20, sorbitan stearate, methyl hydroxybenzoate (E218), propyl hydroxybenzoate (E217), phenoxyethanol, propylene glycol, oleyl alcohol, sodium hydroxide, purified water.

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 30°C. Do not freeze.

6.5 Nature and Contents of Container

Soolantra is supplied in laminated (PE/Al/PE) plastic tubes with a high density polyethylene (HDPE) head and polypropylene (PP) cap for the 2 g, 15 g, 30 g, 45 g or 60 g tubes. The PP cap is a child resistant closure for tube sizes 15 g and larger.
AUST R 227125.
Not all pack sizes may be marketed.

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

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).
Ivermectin is a white or yellowish white crystalline powder. It is freely soluble in methylene chloride, soluble in ethanol (96%) and practically insoluble in water. It presents a specific optical rotation between -20 to -17 measured at 20°C. It is a semisynthetic product derived from fermentation of the bacterium Streptomyces avermitilis.

Chemical structure.


Australian Approved Name (AAN): Ivermectin.
Chemical Names: 5-O-demethyl-22,23-dihydroavermectin A1a; 5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl)-22,23-dihydroavermectin A1a.
Molecular Formula and Molecular Weight: 22, 23-dihydroavermectin B1a C48H74O14 (R=C2H5) 875.10.
22, 23-dihydroavermectin B1b C47H72O14 (R=CH3) 861.07.

CAS number.

70288-86-7 (ivermectin), 71827-03-7 (ivermectin B1a), 70209-81-3 (ivermectin B1b).

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes