Comprehensive medication guide to Tolak including estimated pricing, availability information, side effects, and how to find it in stock at your local pharmacy.
Estimated Insurance Pricing
$25–$80 copay on most commercial plans; Tier 3–4 placement common; prior authorization frequently required; step therapy may apply.
Estimated Cash Pricing
$235 average retail for Tolak brand (40g tube); as low as $43.78 with GoodRx coupons; $40 flat cash price with shipping direct from Hill Derm pharmacy (manufacturer).
Medfinder Findability Score
72/100
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Tolak is a brand-name prescription topical cream containing fluorouracil at a 4% concentration (40 mg per gram of cream). It is manufactured by Hill Dermaceuticals, Inc. and classified as a nucleoside metabolic inhibitor — a form of topical chemotherapy. Tolak is FDA-approved for the treatment of actinic keratosis (AK) lesions on the face, ears, and scalp.
Actinic keratosis consists of rough, scaly, precancerous skin patches caused by chronic ultraviolet radiation exposure. While not all AKs progress to skin cancer, they are considered precursors to squamous cell carcinoma and dermatologists routinely treat them topically to prevent progression.
Tolak is available in a 40-gram tube and is applied once daily for 4 weeks to the treatment area. The initial U.S. FDA approval for fluorouracil as a drug class dates to 1962, making it one of the most long-standing topical treatments in dermatology.
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Tolak's active ingredient, fluorouracil, is an antimetabolite that interferes with the DNA and RNA synthesis of rapidly dividing cells. When applied to actinic keratosis lesions, fluorouracil is incorporated into dividing cells where it blocks the enzyme thymidylate synthetase — a critical enzyme for DNA synthesis. Without the ability to replicate DNA, abnormal cells cannot divide and subsequently die.
Because rapidly dividing cells absorb fluorouracil more readily than normal cells, Tolak preferentially targets the precancerous cells in AK lesions. As those cells die, the body mounts an inflammatory response — visible as redness, crusting, and peeling — to clear the dead cells. This reaction is expected and indicates the medication is working.
The enzyme dihydropyrimidine dehydrogenase (DPD) is responsible for breaking down fluorouracil in the body. Patients with DPD deficiency cannot safely metabolize fluorouracil, and even topical Tolak can lead to life-threatening systemic toxicity in these individuals — making DPD deficiency an absolute contraindication.
4% (40 mg/g) — cream
Applied once daily for 4 weeks to actinic keratosis lesions of the face, ears, and/or scalp. Available in 40-gram tube (NDC 28105-421-40).
As of 2026, Tolak is not on the FDA drug shortage list. However, because it is a specialty brand-name product with no generic equivalent at the 4% concentration, not every pharmacy stocks it on their shelves. Many large chain pharmacies do not routinely carry Tolak and would need to special-order it — typically a 1-3 business day wait. Independent pharmacies and dermatology-affiliated pharmacies tend to have better availability.
Insurance prior authorization is a common barrier — many plans require PA before covering Tolak, adding days of delay. Cash-pay patients can access Tolak most reliably through Hill Derm Pharmacy (the manufacturer's direct pharmacy) at a flat $40 cash price including shipping.
If you're having trouble locating Tolak at a pharmacy near you, medfinder calls pharmacies on your behalf to find which ones can fill your prescription, then texts you the results — saving you hours of phone time.
Because Tolak (fluorouracil) is not a controlled substance and carries no DEA scheduling, any licensed prescriber with an active medical license can prescribe it without special registration or additional licensing. This makes it broadly accessible across a range of clinical settings.
Tolak is also available via telehealth dermatology platforms. Because it is not a controlled substance, there are no telehealth-specific prescribing restrictions. Video or asynchronous (photo-based) teledermatology visits with licensed providers can result in a valid Tolak prescription, which can be filled at any pharmacy.
No. Tolak (fluorouracil 4% cream) is not a controlled substance. It has no DEA scheduling — it is not listed under Schedule I, II, III, IV, or V. Prescribers do not need a DEA number to prescribe it, and there are no federally mandated refill restrictions or special dispensing requirements associated with its controlled substance status.
Tolak can be prescribed by any licensed prescriber including physicians, nurse practitioners, and physician assistants. It can also be prescribed via telehealth platforms without the additional restrictions that apply to controlled substances. Prescriptions are typically valid for 12 months under standard state pharmacy laws, though specific validity periods may vary by state.
Skin reactions at the application site occur in nearly all patients and are an expected part of how Tolak works. The most common side effects (occurring in more than 68% of patients) include:
Serious side effects — stop use and seek medical attention immediately if you experience:
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Fluorouracil 5% cream (Efudex / generic)
Same active ingredient at higher concentration; applied twice daily for 2-6 weeks; widely available as generic for ~$29-37 with GoodRx; also treats superficial basal cell carcinoma.
Carac (fluorouracil 0.5% cream)
Lower fluorouracil concentration; once-daily application for up to 4 weeks; may be better tolerated but less effective for thicker lesions; no generic at this strength.
Klisyri (tirbanibulin 1% ointment)
Newer microtubule inhibitor; once daily for only 5 consecutive days; FDA-approved for AK on face or scalp; good option for adherence-challenged patients.
Imiquimod (Aldara / Zyclara)
Immune response modifier; different mechanism from fluorouracil; applied 2-3 times per week for several months; generic imiquimod 5% widely available; option for DPD-deficient patients.
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Topical corticosteroids (in treatment area)
moderateMay interfere with the inflammatory response fluorouracil relies on; excluded from Tolak clinical trials; avoid applying to the same treatment areas.
Systemic immunosuppressants (methotrexate, cyclosporine, biologics)
moderateMay reduce the efficacy of Tolak by suppressing the immune-mediated clearance of destroyed lesion cells; these patients were excluded from clinical trials.
Topical retinoids (tretinoin, adapalene, tazarotene)
moderateCan significantly increase skin irritation and inflammation when used in the same treatment area as Tolak; excluded from clinical trials.
Glycolic acid / AHA products
moderateAlpha-hydroxy acid products dramatically worsen local skin reactions when applied to Tolak treatment areas; should be avoided during the entire treatment course.
Chemical peeling agents
majorCan cause severe additive irritation in Tolak treatment areas; not to be used concurrently.
DPD-inhibiting compounds and DPD deficiency
majorDPD deficiency (not a drug-drug interaction but a patient factor) causes life-threatening systemic fluorouracil toxicity even with topical use; absolute contraindication.
Tolak (fluorouracil 4% cream) is a well-established, FDA-approved treatment for actinic keratosis with a long clinical track record dating back to 1962. Its once-daily dosing regimen offers a convenience advantage over twice-daily fluorouracil alternatives, which can support patient adherence during the 4-week treatment course. While its brand-name-only status and specialty distribution can make it harder to find at some pharmacies, the medication itself is commercially available and not in a formal shortage.
Patients who experience difficulty filling their Tolak prescription have several practical options: using the Hill Derm pharmacy (manufacturer direct) at $40 with shipping, applying GoodRx coupons for savings at local pharmacies, or discussing insurance prior authorization with their dermatologist's office. For patients who cannot use Tolak due to contraindications or persistent unavailability, several clinically validated alternatives exist.
If you're struggling to find Tolak at a pharmacy near you, medfinder can help. Our service contacts pharmacies in your area to find which ones have Tolak available, so you can get your prescription filled quickly without spending hours on the phone.
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Our medication guides are researched and written to help patients make informed decisions. All content is reviewed for accuracy and updated regularly. Learn more about our standards
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