Rovis (brimonidine tartrate/ivermectin/metronidazole/niacinamide)

For the topical treatment of erythema associated with rosacea in adults, a pea-sized amount of brimonidine gel should be applied once daily to each of the 5 areas of the face (central forehead, chin, nose, and each cheek, for a total of 5 pea-sized amounts). The gel should be applied smoothly and evenly as a thin layer across the entire face, but avoiding the eyes and lips. The hands should be washed after application of the gel.

Patients with severe hepatic disease metabolize metronidazole slowly, which can result in the accumulation of the drug and its metabolites in plasma. Therefore, the manufacturers recommend that metronidazole vaginal gel be used with caution in patients with severe hepatic disease.

Brimonidine tartrate is applied topically to the skin as a gel containing 0.33% brimonidine. Brimonidine gel is for external use only and should not be used orally or vaginally; contact with the eyes should be avoided.

Metronidazole is applied topically to the skin or intravaginally in appropriate formulations.

No dosing information is available for this tab.

No dosing information is available for this tab.

Drug interaction studies have not been performed to date with ivermectin 0.5% lotion.

Because metronidazole can be absorbed systemically following intravaginal application, the possibility that drug interactions could occur with this route of administration should be considered. Small amounts of metronidazole may be absorbed systemically following topical application to the skin, but the likelihood of systemic interactions following topical administration of the drug is less than with oral or parenteral administration.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

The manufacturer states there are no contraindications to use of ivermectin 0.5% lotion.

The manufacturer states that there are no contraindications to the use of brimonidine tartrate topical gel.

• Cockayne syndrome

There are no severe contraindications for this drug.

• Blood dyscrasias
• Chronic myocardial ischemia
• Depression
• No disease contraindications
• Orthostatic hypotension
• Raynaud's phenomenon
• Scleroderma
• Sjogren's syndrome

Conjunctivitis, ocular hyperemia, eye irritation, dandruff, dry skin, and burning skin sensation were reported in less than 1% of patients 6 months of age or older after a single 10-minute topical application of ivermectin 0.5% lotion.

Adverse effects occurring in at least 2% of patients and at a higher incidence with brimonidine gel than with vehicle placebo include erythema, flushing, and burning sensation of the skin.

Adverse effects occurring in at least 4% of patients receiving brimonidine gel (alone or in combination with other rosacea therapy) once daily for 12 months in an open-label trial include flushing, erythema, worsening of rosacea, nasopharyngitis, burning sensation of the skin, increased intraocular pressure, and headache.

Rare or Very Rare

• Allergic dermatitis
• Angioedema
• Bradycardia
• Dyspnea
• Hypertension
• Hypotension
• Ocular irritation
• Peripheral neuropathy
• Skin rash
• Throat constriction
• Tongue swelling

More Frequent

• Erythema
• Flushing
• Headache disorder
• Pharyngitis
• Upper respiratory infection

Less Frequent

• Acne vulgaris
• Blurred vision
• Contact dermatitis
• Dry skin
• Headache disorder
• Nasal congestion
• Ocular hypertension
• Skin irritation
• Stinging of skin
• Stinging of skin

Rare or Very Rare

• Conjunctival hyperemia
• Contact dermatitis
• Contact dermatitis
• Dandruff
• Dry skin
• Dyschromia
• Eye tearing
• Lip swelling
• Ocular redness
• Orthostatic hypotension
• Pallor
• Pruritus of skin
• Skin irritation
• Stinging of skin
• Treatment site sequelae
• Urticaria

No enhanced messaging available.

Safety and efficacy of ivermectin 0.5% lotion have not been established in children younger than 6 months of age. Because these young children have a greater skin surface area to body mass ratio and potentially immature skin barrier, systemic absorption may be increased and children younger than 6 months of age may be at increased risk of ivermectin toxicity. Ivermectin 0.5% lotion should not be used in children younger than 6 months of age.

The lotion should be kept out of the reach of children and should be used only under the direct supervision of an adult.

Safety and efficacy of brimonidine topical gel have not been established in pediatric patients.

Accidental ingestion of brimonidine topical gel has caused serious adverse reactions in children; the drug should be kept out of reach of children. (See Serious Adverse Reactions Following Ingestion under Cautions: Warnings/Precautions.)

Category C. (See Users Guide)

Category B. (See Users Guide.)

No fetotoxicity was observed in rats or mice receiving oral administration of metronidazole at dosages 200 or 20 times the usual dosage, respectively. In addition, reproduction studies in pregnant mice using oral metronidazole doses about 6 times the maximum recommended human dose (on a mg/m2 basis) have not revealed evidence of fetotoxicity or teratogenicity; however, intrauterine deaths have occurred following intraperitoneal administration of the drug. The fetal risk, if any, with the use of topical or vaginal metronidazole gel in pregnant women currently is not known. Metronidazole crosses the placenta and is rapidly distributed into fetal circulation. There have been no adequate and controlled studies to date using oral, IV, topical, or intravaginal metronidazole in pregnant women. Because animal reproduction studies are not always predictive of human response and because oral metronidazole has been shown to be carcinogenic in some rodents, topical metronidazole preparations or the vaginal gel should be used in pregnant women only when clearly needed.

Screening and/or treatment for bacterial vaginosis in pregnant women as clinically indicated should be conducted during the first prenatal visit. Although some experts state that intravaginal therapy may be used solely for symptomatic relief (and not for prevention of adverse pregnancy outcomes) in women at low risk for preterm delivery, other experts prefer use of systemic therapy for all pregnant women, regardless of degree of risk for complications of pregnancy, because systemic treatment may be required to eradicate upper genital tract infection that may be associated with bacterial vaginosis. For the treatment of bacterial vaginosis and reduction in the incidence of adverse pregnancy outcomes associated with bacterial vaginosis (e.g., preterm birth), particularly in pregnant women at high risk for complications of pregnancy, a 7-day regimen of oral metronidazole or a 7-day regimen of oral clindamycin is recommended.

Orally administered ivermectin is distributed into milk in low concentrations. Since it is not known if ivermectin is distributed into milk following topical administration, the 0.5% lotion should be used with caution in nursing women.

Brimonidine is distributed into milk in animals. It is not known whether brimonidine is distributed into human milk. A decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

Following oral administration, metronidazole is distributed into milk in concentrations similar to those attained in plasma. Although plasma concentrations of metronidazole following topical or intravaginal administration are lower than those achieved after oral administration of the drug, it is not known whether metronidazole distributes into milk following topical or intravaginal application. Therefore, because oral metronidazole has been shown to be carcinogenic in some rodents, a decision should be made whether to discontinue nursing or topical or intravaginal metronidazole, taking into account the importance of the drug to the woman.

Clinical studies of ivermectin 0.5% lotion did not include sufficient numbers of patients 65 years of age or older to determine whether geriatric patients respond differently than younger adults; other clinical experience has not identified differences in response between geriatric and younger patients.

In clinical trials, no overall differences in safety and efficacy were observed in patients 65 years of age or older compared with younger patients. However, the manufacturer states that clinical studies of brimonidine gel did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients.