For the treatment of mycotic vulvovaginitis and superinfections due to gram-positive bacteria

4.2 Posology and method of administration
Candizole vaginal cream is for vaginal administration.
Adults (aged 18 years and older)
Administer the contents of one applicator (about 5g of cream) once daily deeply into vagina for 1 O
- 14 days or twice daily for 7 days. For vulvitis the cream should be applied topically twice daily.
Continue the course of treatment even after pruritus and leukorrhoea have disappeared or
menstruation begins.
Pediatrics (aged under 18 years)
The safety and efficacy of Candizole vaginal cream in children and adolescents has not been
studied.

Severe hypersensitivity reactions, including anaphylaxis and angioedema, have been reported
during treatment with Candizole vaginal cream and with other miconazole formulations (sec section 4.8). If a reaction suggesting hypersensitivity or irritation should occur, the treatment
should be discontinued.

Appropriate therapy is indicated when the sexual partner is also infected.
Candizole vaginal cream does not stain skin or clothes.
The concurrent use of latex condoms or diaphragms with vaginal anti-infective preparations may
decrease the effectiveness of latex contraceptive agents. Therefore Candizole vaginal cream
should not be used concurrently with a latex condom or latex diaphragm.
Candizole vaginal cream contains benzoic acid and butylated hydroxyanisole, which may cause
local skin reactions (e.g. contact dermatitis), or irritation to the eyes and mucous membranes.

Miconazole administered systemically is known to inhibit CYP3A4/2C9. Due to the limited
systemic availability after vaginal application, clinically relevant interactions occur very rarely. In
patients on oral anticoagulants, such as warfarin, caution should be exercised and anticoagulant
effect should be monitored. The effects and side effects of other drugs metabolized by CYP2C9
(e.g.,oral hypoglycemics and phenytoin) and also CYP3A4 (e.g., HMG-CoA reductase inhibitors
such as simvastatin and lovastatin and calcium channel blockers such as dihydropyridines and
verapamil), when co-administered with miconazole, can be increased and caution should be
exercised.
Contact should be avoided between certain latex products such as contraceptive diaphragms or
condoms and Candizole vaginal cream since the constituents of the cream may damage the latex
(see section 4.4).
4.6. pregnancy and lactation

Pregnancy
Although intravaginal absorption is limited, Candizole vaginal cream should be used in the first
trimester of pregnancy only if, in the judgement of the physician, the potential benefits outweigh
the possible risks.
Breastfeeding
It is not known whether miconazole nitrate is excreted in human milk. Caution should be exercised
when using Candizole vaginal cream during breastfeeding.

None known.

The safety of Candizole Vaginal Cream was evaluated in a total of 537 women with
microbiologically confirmed candidiasis and symptoms (e.g., vulvovaginal itching,
burning/irritation), or signs of vulvar crythema, edema, excoriation, or vaginal erythema or edema
who participated in 2 single-blind clinical trials. Subjects were treated with miconazole
intravaginally, randomly assigned to either a single 1,200 mg capsule, or a 7-day application of
2% vaginal cream. Adverse reactions reported by 2'. l % of Candizole Vaginal Cream-treated
subjects in these trials are shown in Table 1.
In the table, the frequencies are provided according to the following convention:
Very common
Common
Uncommon
Rare
Very rare
2'.1/10 2'.1/10
2'.11100 and < 1/10
2'.111,000 and <l/100
2'.1110,000 and <1/1,000
<1/10,000

Body System/Organ Class Undesirable effects
Frequency Category
Skin and Subcutaneous Tissue
Disorders
Common Rash
Uncommon Rash pruritic, urticaria
[Reproductive System and Breast
Disorders
- J 'I I ' Pll ; ,' & L r. n IC: - ' - '_ c i
DC)E'rJX)J,;- <: lr1.1,.J,ll-
' 1 􀬛)( VALEANT
I
CANDIZOLE VAGINAL CREAM
(Miconazole Nitrate)
1.3 PRODUCT INFORMATION
!Very common Genital pruritus female, vaginal burning sensation,
vulvovaginal discomfort
Common Dysmenorrhoea

A range of additional reactions were reported during the clinical trials, such as: vaginal discharge,
vaginal haemorrhage, vaginal pain, headache, dysuria, urinary tract infection, abdominal pain,
rosacea, swelling of the face and nausea. However due to the design of these studies, a definitive
causal relationship could not be established.
Table 2. Adverse Reactions Identified During Postmarketing Experience with Candizole Vaginal
cream by Frequency Category Estimated from Spontaneous Reporting Rates
Immune System Disorders
Not known Hypersensitivity including Anaphylactic and Anaphylactoid
reactions
Skin and Subcutaneous Tissue Disorders
Not known Angioedema, Pruritus
Reproductive System and Breast Disorders
Not known Vaginal irritation, pelvic cramps

Symptoms
Candizole vaginal cream is intended for local application and not for oral use.
In case of accidental ingestion, no problems are expected.
Treatment
In the event of accidental ingestion oflarge quantities, use appropriate supportive care.

5.1 Pharmacodynamic properties
Phannacotherapeutic classification:
(Anti-infectives and antiseptics, excl. combinations with corticosteroids, imidazole derivatives)

A TC code: GO 1 A F04
Miconazole combines a potent antifungal activity against common dennatophytes and yeasts with
an antibacterial activity against certain gram-positive bacilli and cocci.
Miconazole inhibits the biosynsthesis of ergosterol in fungi and changes the composition of other
lipid components in the membrane, resulting in fungal cell necrosis.
In general, miconazole exerts a very rapid effect on pruritus, a symptom that frequently
accompanies dennatophyte and yeast infections.

Absorption: Miconazole persists in the vagina for up to 72 hours after a single dose. Systemic
absorption of miconazole after intravaginal administration is limited, with a bioavailability of 1 to
2% following intravaginal administration of a 1200 mg dose. Plasma concentrations of miconazole
arc measurable within 2 hours of administration in some subjects, with maximal levels seen 12 to
24 hours after administration. Plasma concentrations decline slowly thereafter and were still
measurable in most subjects 96 hours post-dose. A second dose administered 48 hours later resulted
in a plasma profile similar to that of the first dose. Distribution: Absorbed miconazole is bound to plasma proteins (88.2%) and red blood cells
( 10.6%).
Metabolism and Excretion: The small amount of miconazole that is absorbed is eliminated
predominantly in faeces as both unchanged drug and metabolites over a four-day postadministration
period. Smaller amounts of unchanged drug and metabolites also appear in urine.
The apparent elimination half-life ranges from 15 to 49 hours in most subjects and likely reflects
both absorption from the site of application and metabolism/excretion of the drug.

Preclinical data reveal no special hazard for humans based on studies of local irritation, single and
repeated dose toxicity, genotoxicity, and toxicity to reproduction.

6.1. List of Excipients
Benzoic Acid
Tefose 63
Labrafil M 1944 CS (Oleoyl Macrogolglycerides)
Liquid Paraffin
Butylated Hydroxyanisole
Purified Water

None known

Store below 30°C.
Keep out of the reach of children.

45 gm cream is white to off white homogenous smooth cream, 45gm cream filled in annealed
aluminum tube coated internally by an epoxide resin lacquer, packed in a carton box along with a
leaflet and applicator

For Vaginal use only