Zyclara

Keep all appointments with your doctor. If you are using imiquimod cream to treat superficial basal cell carcinoma, it is important to have regular follow-up visits with your doctor. Ask your doctor how often you should have your skin checked.

Do not let anyone else use your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Zyclara is a prescription medication used to treat warts around the genital and anal areas and actinic keratosis (flaking and discoloration of the skin from sun exposure). Zyclara belongs to a group of drugs called immune response modifiers, which stimulate the body's immune response to treat warts. The exact way Zyclara works to treat other conditions is unknown.

This medication comes in the form of a cream to be applied to the affected area once daily, just before your bedtime.

The dose schedule will differ and depend on what Zyclara is being used for. 

Common side effects include redness, swelling, sores, blisters and other changes to the area where Zyclara cream is applied. 

Zyclara cream is a prescription medicine used to treat:

• external genital and perianal warts in people 12 years and older. Imiquimod cream is not a cure for genital warts.
• actinic keratosis in adults with normal immune systems. 

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

• Medicis Pharmaceutical Corp.

The most common side effects with Zyclara are skin reactions where it is applied (treatment area) including:

• local skin reactions including: skin redness, scabbing, crusting, flaking, scaling, dryness, swelling
• headache
• itching at the treatment area
• tiredness
• nausea
• skin irritation
• pain at the treatment area

This is not a complete list of Zyclara side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088

Tell your doctor if you are breastfeeding or if you are planning to breastfeed.

It is not known if Zyclara is excreted in breast milk or if it will harm your baby. Because many drugs are excreted in human milk, caution should be exercised when Zyclara Cream is administered to nursing women.

Using too much of this medicine, or using it for too long can increase your risk of severe skin reactions. Follow your doctor's instructions.

Do not use imiquimod topical on areas of broken, wounded, or burned skin. Wait until these conditions have healed before using imiquimod topical.

Before using this medication, tell your doctor if you have a weak immune system, an autoimmune disorder, graft-versus-host disease, or if you have recently received a bone marrow transplant or cord blood transplant.

When treating genital warts around the vagina, avoid getting the cream on the more sensitive inner layers of vaginal tissue. This could result in vaginal swelling or irritation and painful urination.

Avoid exposure to sunlight or tanning beds. Imiquimod topical can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Imiquimod topical is not a cure for genital warts and it may not keep you from spreading this condition to others through vaginal, anal, or oral sex. You may develop new lesions during treatment with imiquimod topical. For best results, keep using the medicine for the entire length of time prescribed by your doctor.

Imiquimod will not protect against sexually transmitted diseases such as chlamydia, gonorrhea, herpes, HIV, syphilis, and trichomoniasis.

If you are treating the genital or rectal area with imiquimod topical, avoid sexual activity while the medicine is on your skin. Imiquimod topical can weaken the rubber that condoms or diaphragms are made out of. If you use a condom or diaphragm for birth control, these items could break if the rubber weakens and an unplanned pregnancy could result.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Wash off the medicine and call your doctor at once if you have a serious skin reaction such as severe itching, burning, oozing, bleeding, or skin changes where the medicine is applied.

Stop using imiquimod topical and call your doctor at once if you have a serious side effect such as flu symptoms such as fever, chills, body aches, tired feeling, swollen glands.

When treating genital warts around the vagina, if you have severe swelling or urination problems, stop using imiquimod topical and call your doctor right away.

Less serious side effects may include:

• mild skin irritation, itching, dryness, flaking, scabbing, crusting, redness, or hardening of the skin where the medicine was applied;

• changes in the color of treated skin;

• headache, dizziness, chest pain, back pain;

• cold sores, fever blisters;

• cold symptoms such as stuffy nose, sneezing, sore throat;

• nausea, diarrhea, loss of appetite; or

• vaginal itching or discharge.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

It is not likely that other drugs you take orally or inject will have an effect on topically applied imiquimod topical. But many drugs can interact with each other. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Zyclara Cream, 2.5% is a white to faintly yellow cream available in pump bottles. Each pump bottle, when actuated after priming, delivers 0.235 grams of cream.

Zyclara Cream, 3.75% is a white to faintly yellow cream available in single-use packets and pump bottles. Each packet administers 0.25 grams of cream and each pump bottle, when actuated after priming, delivers 0.235 grams of cream (a similar amount as one packet).

Topical overdosing of Zyclara Cream could result in an increased incidence of severe local skin reactions and may increase the risk for systemic reactions.

Hypotension was reported in a clinical trial following multiple oral imiquimod doses of >200 mg (equivalent to ingestion of the imiquimod content of more than 21 packets or pump actuations of Zyclara Cream, 3.75% or more than 32 pump actuations of Zyclara Cream, 2.5%). The hypotension resolved following oral or intravenous fluid administration.

Avoid getting this medication in your eyes, mouth, and nose, or on your lips. Do not place the cream in your rectum, vagina, or urethra. If it does get into any of these areas, rinse with water. Do not use Zyclara on sunburned, windburned, dry, chapped, irritated, or broken skin.

Avoid using other medications on the areas you treat with Zyclara unless your doctor tells you to.

Avoid exposure to sunlight or tanning beds. Zyclara can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Avoid having unprotected sex. Zyclara is not a cure for genital warts, and it will not protect against sexually transmitted diseases such as chlamydia, gonorrhea, herpes, HIV, syphilis, and trichomoniasis. Talk with your doctor about safe ways to prevent transmission during sex.

Applies to imiquimod topical: topical cream

General

In general, the side effects associated with imiquimod topical (the active ingredient contained in Zyclara) may vary depending on the condition being treated.[Ref]

Local

Local skin reactions were recorded as adverse reactions only if they extended beyond the treatment area, if they required any medical intervention, or they resulted in patient discontinuation from a study.

In studies involving treatment of actinic keratosis or superficial basal cell carcinoma, the dermatologic side effects classified as local and application site most frequently resulted in clinical intervention (e.g., rest periods, withdrawal from study, treatment site infections requiring treatment with antibiotics).

Flaking/scaling was reported in 40% of males and 26% of females and scabbing/crusting was reported in 34% of males and 18% of females; otherwise, frequency and severity of local skin reactions were similar in both genders.[Ref]

Local side effects have included application site reaction (up to 33%), application site pain (up to 7%), application site irritation (up to 6%), application site pruritus (up to 4%), application site bleeding, application site swelling, treatment site infection, scarring, application site rash, application site cellulitis, and application site excoriation. Local skin reactions have included erythema (all grades: up to 100%; severe: up to 31%), scabbing/crusting (all grades: up to 93%; severe: up to 19%), flaking/scaling/dryness (all grades: up to 93%; severe: up to 8%), flaking/scaling (all grades: 91% ; severe: 4%), induration (all grades: up to 84% ; severe: up to 6%), edema (all grades: up to 78%; severe: up to 7%), erosion (all grades: up to 66% ; severe: up to 14%), erosion/ulceration (all grades: up to 62%; severe: up to 13%), exudate (all grades: up to 51%; severe: 6%), ulceration (all grades: up to 40% ; severe: up to 6%), weeping/exudate (all grades: up to 22%), vesicles (all grades: up to 31%; severe: up to 2%), excoriation/flaking (all grades: up to 26%; severe: up to 1%), and scabbing (all grades: up to 13%). Application site reactions have included itching (up to 20%), burning (6%), bleeding (up to 3%), stinging (3%), pain (3%), erythema (2%), papule(s) (2%), induration (2%), tenderness (up to 2%), irritation (2%), and infection (1%). Application site disorders reported in more than 1% of patients have included burning, hypopigmentation, rash, sensitivity, soreness, stinging, and tenderness. Itching (32% in females, 22% in males), burning (26% in females, 9% in males), pain (8% in females, 2% in males), and soreness (3% in females) were reported at the wart site. Tingling at the application site has been reported during postmarketing experience.[Ref]

Respiratory

Respiratory side effects have included upper respiratory tract infection (up to 15%), sinusitis (up to 7%), rhinitis (3%), coughing (2%), and pharyngitis (1%). Pulmonary congestion and bronchitis have been reported. Dyspnea and pulmonary edema have been reported during postmarketing experience.[Ref]

Immunologic

Immunologic side effects have included fungal infection (11% in females, 2% in males), herpes simplex (up to 3%), oral herpes (up to 3%), viral infection (1%), herpes zoster, and infection. Herpes simplex has also been reported during postmarketing experience.[Ref]

Nervous system

Two cases involving the development of chronic neuropathic pain following initiation of imiquimod topical (the active ingredient contained in Zyclara) therapy for the treatment of warts have been reported. In the first case, a 53-year-old man with genital warts reported an erosion with substantial pain on the left lateral glans of the penis approximately 1 week following initiation of therapy with imiquimod applied topically 3 times a week. Imiquimod therapy was discontinued; however, the patient continued to report a burning-like pain and erythema in the area for approximately 2 years. The condition may have been exacerbated by aerobic exercise, sweating, and sexual activity. In the second case report, a 64-year-old woman with plantar warts developed numbness and pain in all toes and the balls of both feet following approximately 5 months of therapy with imiquimod topical applied each night with tape occlusion. Imiquimod topical was discontinued. This condition may have been exacerbated by a daily paring of the warts by the patient prior to imiquimod application. Approximately 2 years later, the patient reported a gradual improvement in the numbness and an absence of the burning-like pain. Neither patient had diabetes mellitus, or any other condition known to result in possible neuropathic pain.[Ref]

Nervous system side effects have included headache (up to 8%), dizziness (up to 3%), insomnia, and lethargy. Nervous system side effects have rarely included neuropathic pain. Agitation, convulsions (including febrile convulsions), insomnia, multiple sclerosis aggravation, and paresis have been reported during postmarketing experience.[Ref]

Other

Other side effects have included back pain (up to 4%), fatigue (up to 4%), influenza-like illness (up to 4%), pyrexia (up to 3%), pain (up to 3%), influenza-like symptoms (3% in females, 1% in males), rigors (1%), and chills. Hernia, inflicted injury, and postoperative pain have been reported.[Ref]

Gastrointestinal

Gastrointestinal side effects have included nausea (up to 4%), anorexia (up to 3%), diarrhea (up to 3%), dyspepsia (2%), cheilitis (up to 2%), and vomiting (up to 1%). Gastrointestinal disorder and aphthous ulcers (rare) have been reported. Abdominal pain has been reported during postmarketing experience.[Ref]

A review of 3 case reports involving patients receiving imiquimod topical applied 2 or 3 times weekly for treatment of actinic cheilitis in the lip region reported the formation of aphthous ulcers approximately 2 to 3 weeks following initiation of treatment. In each case, the aphthous ulcers resolved upon discontinuation of imiquimod topical and treatment with a topical steroid. None of the patients consented to a rechallenge.[Ref]

Oncologic

An 87-year-old Caucasian woman developed invasive amelanotic melanoma with satellite lesions within 14 weeks after initiation of treatment with imiquimod three times per week. It is unknown if this was a probable side effect of imiquimod or a progressive event of melanoma in situ.[Ref]

Oncologic side effects have included squamous cell carcinoma (up to 4%). Basal cell carcinoma has been reported. Oncologic side effects reported during non-FDA approved treatment of melanoma in situ have included a single case report of the development of invasive melanoma.[Ref]

Hematologic

Hematologic side effects have included lymphadenopathy (up to 3%) and pancytopenia. Decreases in red cell, white cell, and platelet counts (including idiopathic thrombocytopenic purpura), and lymphoma have been reported during postmarketing experience.[Ref]

Cardiovascular

Cardiovascular side effects have included chest pain (up to 2%), atrial fibrillation (1%), and hypertension. Capillary leak syndrome, cardiac failure, cardiomyopathy, cerebrovascular accident, arrhythmias (tachycardia, supraventricular tachycardia, atrial fibrillation, palpitations), chest pain, ischemia, myocardial infarction, syncope, and Henoch-Schonlein purpura syndrome have been reported during postmarketing experience.[Ref]

Dermatologic

In the studies involving treatment of genital/perianal warts, the skin reactions reported were more frequent and more intense with daily application of the cream than with the application of the cream three times per week.

In studies involving treatment of actinic keratosis or superficial basal cell carcinoma, the dermatologic side effects classified as local and application site most frequently resulted in clinical intervention (e.g., rest periods, withdrawal from study, treatment site infections requiring treatment with antibiotics).[Ref]

Dermatologic side effects have included eczema (2%), alopecia (1%), dermatitis, and pruritus. Remote site skin reaction were reported and included erythema (3% in females, 1% in males), ulceration (2% in females), erosion (2% in males), edema (1% in females, 1% in males), induration (1% in males), and excoriation/flaking (1% in males). Remote site reactions reported in more than 1% of patients have included bleeding, burning, itching, pain, tenderness, and tinea cruris. Hyperkeratosis, rash, skin disorder, photosensitivity reaction, verruca, and remote site irritation have been reported. Imiquimod-induced psoriasis and at least 1 case each of vitiligo-like hyperpigmentation, contact pemphigus, pityriasis rubra pilaris exacerbation, erosive pustular dermatosis of the scalp, and eruptive keratoacanthoma have been reported. Exfoliative dermatitis, erythema multiforme, hyperpigmentation, hypopigmentation, and hypertrophic scar have been reported during postmarketing experience.[Ref]

Musculoskeletal

Musculoskeletal side effects have included arthralgia (up to 3%) and myalgia (up to 1%). Arthritis and skeletal pain have been reported. Arthralgia has also been reported during postmarketing experience.[Ref]

Genitourinary

Genitourinary side effects have included bacterial vaginitis (up to 3% of females), urinary tract infections (1%), scrotal pain, scrotal erythema, scrotal ulcer, and scrotal edema. Proteinuria, urinary retention, and dysuria have been reported during postmarketing experience.[Ref]

Psychiatric

Psychiatric side effects have included anxiety (1%). Depression and suicide have been reported during postmarketing experience.[Ref]

Ocular

Ocular side effects have included conjunctivitis and eye abnormality.[Ref]

Hypersensitivity

Hypersensitivity side effects have included angioedema during postmarketing experience. Aggravation of allergy has been reported.[Ref]

A 61-year-old man developed angioedema 3 weeks into treatment for squamous cell carcinoma in situ located on the right forearm. One week prior he had developed ulceration over the application site. The angioedema started in the right hand at which time the imiquimod therapy was discontinued. Within 36 hours of discontinuation the angioedema had encompassed both hands and feet and the ulcerated application site. Fifty-four hours following discontinuation of therapy the patient was awakened by severe swelling of the tongue, diagnosed by the emergency room physician as angioedema of the tongue. The patient experienced difficulty talking and swallowing, but no respiratory distress. The patient denied presence of chills, fever, or influenza-like symptoms. The patient denied history of urticaria, angioedema, or anaphylaxis. The patient was stable on all medications prior to initiation of imiquimod therapy. The patient improved following treatment with intravenous diphenhydramine and methylprednisolone. It is thought that the large application site (16.7 m2) and the ulceration may have facilitated in the absorption of imiquimod resulting in the angioedema.[Ref]

Metabolic

Metabolic side effects have included hypercholesterolemia and gout.[Ref]

Hepatic

Hepatic side effects have included abnormal liver function during postmarketing experience.[Ref]

Endocrine

Endocrine side effects have included thyroiditis during postmarketing experience.[Ref]

Some side effects of Zyclara may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.