Retin-A

Antineoplastic Retinoids
Anti-wrinkle Agents, Rx
Topical Retinoids for Acne

Hazardous Drugs Classification
NIOSH 2016 List: Group 3
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
ORAL CAPSULES: Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Eye/face and respiratory protection may be needed during preparation and administration.
TOPICAL: Use double chemotherapy gloves and protective gown. Eye/face and respiratory protection may be needed during preparation and administration.

Take tretinoin with or without food.

Topical tretinoin is a dermal irritant; the dermatologic response to greater than 48 weeks of chronic therapy is not known.
Before applying topical formulations of tretinoin, clean affected area with a mild soap, pat skin dry and wait 20—30 minutes before applying the product. The microsphere gel may be applied immediately after washing the face.

Cream: Rub cream gently into the affected area. Avoid over-application. Wash hands immediately after applying.
Lotion: Apply thin layer to cover affected areas. Wash hands immediately after applying.[63467]

Solution: Apply using clean fingertips, a gauze pad, or cotton swabs to the cleansed affected area. Avoid over-saturation of gauze or cotton to prevent the solution from running onto unaffected areas. Wash hands immediately after applying.
Gel: Apply lightly to the affected area. Excessive application results in pilling of the gel. Wash hands immediately after applying.
Microsphere gel: Apply lightly to the affected area. Excessive application results in caking of the gel. Wash hands immediately after applying.

GI bleeding / Delayed / 34.0-34.0
disseminated intravascular coagulation (DIC) / Delayed / 26.0-26.0
arrhythmia exacerbation / Early / 23.0-23.0
pleural effusion / Delayed / 20.0-20.0
visual impairment / Early / 17.0-17.0
increased intracranial pressure / Early / 9.0-9.0
intracranial bleeding / Delayed / 9.0-9.0
heart failure / Delayed / 6.0-6.0
hearing loss / Delayed / 6.0-6.0
pulmonary edema / Early / 3.0-3.0
laryngeal edema / Rapid / 3.0-3.0
peptic ulcer / Delayed / 3.0-3.0
cardiomyopathy / Delayed / 3.0-3.0
pericarditis / Delayed / 3.0-3.0
pulmonary hypertension / Delayed / 3.0-3.0
myocarditis / Delayed / 3.0-3.0
myocardial infarction / Delayed / 3.0-3.0
cardiac arrest / Early / 3.0-3.0
stroke / Early / 3.0-3.0
agnosia / Delayed / 3.0-3.0
seizures / Delayed / 3.0-3.0
coma / Early / 3.0-3.0
renal failure (unspecified) / Delayed / 3.0-3.0
renal tubular necrosis / Delayed / 3.0-3.0
erythema nodosum / Delayed / Incidence not known
differentiation syndrome / Delayed / Incidence not known
pericardial effusion / Delayed / Incidence not known
hypervitaminosis A / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
thrombosis / Delayed / Incidence not known
papilledema / Delayed / Incidence not known
spontaneous fetal abortion / Delayed / Incidence not known
teratogenesis / Delayed / Incidence not known

bone pain / Delayed / 77.0-77.0
dyspnea / Early / 60.0-60.0
elevated hepatic enzymes / Delayed / 50.0-60.0
hyperlipidemia / Delayed / 0-60.0
bleeding / Early / 60.0-60.0
fluid retention / Delayed / 29.0-52.0
peripheral edema / Delayed / 52.0-52.0
stomatitis / Delayed / 26.0-26.0
constipation / Delayed / 17.0-17.0
wheezing / Rapid / 14.0-14.0
hypotension / Rapid / 14.0-14.0
depression / Delayed / 14.0-14.0
phlebitis / Rapid / 11.0-11.0
hypertension / Early / 11.0-11.0
confusion / Early / 11.0-11.0
flank pain / Delayed / 9.0-9.0
hepatomegaly / Delayed / 9.0-9.0
splenomegaly / Delayed / 9.0-9.0
dysuria / Early / 9.0-9.0
edema / Delayed / 6.0-6.0
hallucinations / Early / 6.0-6.0
ascites / Delayed / 3.0-3.0
hepatitis / Delayed / 3.0-3.0
impaired cognition / Early / 3.0-3.0
ataxia / Delayed / 3.0-3.0
dysarthria / Delayed / 3.0-3.0
aphasia / Delayed / 3.0-3.0
encephalopathy / Delayed / 3.0-3.0
thrombocytosis / Delayed / 0-1.0
erythema / Early / 10.0
hypoxia / Early / Incidence not known
respiratory depression / Rapid / Incidence not known
pseudotumor cerebri / Delayed / Incidence not known
hypertriglyceridemia / Delayed / Incidence not known
hypercholesterolemia / Delayed / Incidence not known
hypercalcemia / Delayed / Incidence not known

headache / Early / 86.0-86.0
fever / Early / 83.0-83.0
fatigue / Early / 66.0-66.0
malaise / Early / 66.0-66.0
shivering / Rapid / 63.0-63.0
vomiting / Early / 57.0-57.0
nausea / Early / 57.0-57.0
rash / Early / 54.0-54.0
leukocytosis / Delayed / 40.0-40.0
abdominal pain / Early / 31.0-31.0
weight gain / Delayed / 23.0-23.0
diarrhea / Early / 23.0-23.0
flushing / Rapid / 23.0-23.0
otalgia / Early / 23.0-23.0
dizziness / Early / 20.0-20.0
diaphoresis / Early / 20.0-20.0
anorexia / Delayed / 17.0-17.0
weight loss / Delayed / 17.0-17.0
anxiety / Delayed / 17.0-17.0
paresthesias / Delayed / 17.0-17.0
alopecia / Delayed / 14.0-14.0
myalgia / Early / 14.0-14.0
dyspepsia / Early / 14.0-14.0
insomnia / Early / 14.0-14.0
agitation / Early / 9.0-9.0
pallor / Early / 6.0-6.0
asterixis / Delayed / 3.0-3.0
weakness / Early / 3.0-3.0
tremor / Early / 3.0-3.0
hyporeflexia / Delayed / 3.0-3.0
drowsiness / Early / 3.0-3.0
hypothermia / Delayed / 3.0-3.0
increased urinary frequency / Early / 3.0-3.0
skin hyperpigmentation / Delayed / 2.0-2.0
skin hypopigmentation / Delayed / 2.0-2.0
skin irritation / Early / 10.0
pruritus / Rapid / 20.0
xerosis / Delayed / 10.0
photosensitivity / Delayed / Incidence not known
vesicular rash / Delayed / Incidence not known

Oral tretinoin therapy requires an experienced clinician and requires a specialized care setting. Only clinicians experienced in the management of patients with acute leukemia should use oral tretinoin; patients who have acute promyelocytic leukemia are at high risk in general and may experience severe adverse reactions to tretinoin. Patients receiving oral tretinoin should be managed in facilities equipped and staffed with adequate laboratory and supportive medical services to monitor for drug toxicity and to care for patients compromised by these toxicities, including respiratory insufficiency.

Approximately 25% of patients who receive tretinoin for the treatment of acute promyelocytic leukemia have experienced acute promyelocytic leukemia differentiation syndrome. When seen in association with the use of tretinoin, this syndrome is also known as retinoic acid-acute promyelocytic leukemia (RA-APL) syndrome (see Adverse Reactions for more detailed description of RA-APL syndrome). Patients must be carefully monitored for any signs or symptoms of this syndrome.

In the treatment of acute promyelocytic leukemia, approximately 40% of patients will develop rapidly evolving leukocytosis, and these patients have a higher risk of life-threatening complications. High initial leukocyte counts or rapidly increasing leukocyte counts during treatment may be predictive of retinoic acid-acute promyelocytic leukemia (RA-APL) syndrome (see Adverse Reactions). However, RA-APL syndrome has been observed with or without concomitant leukocytosis. The manufacturer recommends the immediate initiation of high-dose steroids if signs and symptoms of RA-APL are present together with leukocytosis. Some clinicians routinely add chemotherapy to oral tretinoin therapy when patients present with a WBC count > 5000/mm3 or in the case of a rapid increase in WBC count in leukopenic patients at the start of treatment. Consideration could be given to adding chemotherapy (usually cytarabine and an anthracycline, if not contraindicated) to tretinoin therapy on day 1 or 2 for patients presenting with a WBC count > 5000/mm3 or immediately, for patients presenting with a WBC count of < 5000/mm3, if the WBC count reaches >= 6000/mm3 by day 5, >= 10,000/mm3 by day 10, or >= 15,000/mm3 by day 28. The majority of patients do not require discontinuation of tretinoin therapy during RA-APL syndrome.

Teratogenic and embryotoxic effects have been demonstrated in animals receiving oral tretinoin or large doses (i.e., many times greater than the normal human dose) of topical tretinoin. Adequate and well-controlled trials have not been performed in humans, but increased spontaneous abortions and major human fetal abnormalities have occurred when pregnant women received other retinoids. There have been 30 case reports of temporally-associated, congenital malformations during 25 years of clinical use of Retin-A. The significance of these spontaneous reports in terms of risk to the fetus is not known. Avoid use of topical tretinoin over large areas of skin or for prolonged periods. The benefit-risk profile should be considered before prescribing. Reproductive risk should be discussed. There is a high risk of birth defects if oral tretinoin is administered during pregnancy. Females of childbearing potential must use two reliable forms of contraception simultaneously during oral tretinoin therapy and for one month following discontinuation of therapy, unless abstinence is the chosen method. Contraception requirements must be followed even when there is a history of infertility or menopause, unless a hysterectomy has been performed. Within one week of beginning tretinoin oral therapy, the patient should have a negative pregnancy test; if possible, treatment with tretinoin should be delayed until pregnancy testing results are known. Pregnancy testing and counseling should occur monthly during oral tretinoin therapy.[48166] [48167] [63467]

Altinac, Altreno, Atralin, AVITA, Refissa, Renova, Retin-A, Retin-A Micro, Tretin-X, Vesanoid

Rx

Naturally occurring retinoid analog; also known as all-trans-retinoic acid (aTRA)
Oral form used in acute promyelocytic leukemia; topical form used for cutaneous disorders like acne and photoaging
Treatment with oral form may cause acute promyelocytic leukemia differentiation syndrome

Apply a thin layer of topical tretinoin to the affected area(s) once daily at bedtime. Temporary discontinuation or reduction in application frequency may be necessary until the patient is able to tolerate the treatment. Frequency of application should be closely monitored by careful observation of the clinical response and skin tolerance; efficacy has not been established for less than once daily application frequency. Application of excessive amounts may result in 'caking' or 'pilling' and will not provide incremental efficacy. During the early weeks of treatment, an apparent exacerbation of inflammatory lesions may occur. If tolerated, this should not be considered a reason to discontinue therapy. Up to 7 weeks of therapy may be required before improvement is evident. This may be followed by a reduced dosage schedule.

Apply a thin layer of topical tretinoin to the affected area(s) once daily at bedtime. Temporary discontinuation or reduction in application frequency may be necessary until the patient is able to tolerate the treatment. Frequency of application should be closely monitored by careful observation of the clinical response and skin tolerance; efficacy has not been established for less than once daily application frequency. Application of excessive amounts may result in 'caking' or 'pilling' and will not provide incremental efficacy. During the early weeks of treatment, an apparent exacerbation of inflammatory lesions may occur. If tolerated, this should not be considered a reason to discontinue therapy. Up to 7 weeks of therapy may be required before improvement is evident. This may be followed by a reduced dosage schedule.[48167] [55916]

Apply a thin layer to the affected area(s) once daily at bedtime. Temporary discontinuation or reduction in application frequency may be necessary until the patient is able to tolerate the treatment. Frequency of application should be closely monitored by careful observation of the clinical response and skin tolerance; efficacy has not been established for less than once daily application frequency. Application of excessive amounts may result in 'caking' or 'pilling' and will not provide incremental efficacy. During the early weeks of treatment, an apparent exacerbation of inflammatory lesions may occur. If tolerated, this should not be considered a reason to discontinue therapy. Up to 6 weeks of therapy may be required before improvement is evident. This may be followed by a reduced dosage schedule.

Apply a thin layer to the affected area(s) once daily at bedtime. Temporary discontinuation or reduction in application frequency may be necessary until the patient is able to tolerate the treatment. Frequency of application should be closely monitored by careful observation of the clinical response and skin tolerance; efficacy has not been established for less than once daily application frequency. Application of excessive amounts may result in 'caking' or 'pilling' and will not provide incremental efficacy. During the early weeks of treatment, an apparent exacerbation of inflammatory lesions may occur. If tolerated, this should not be considered a reason to discontinue therapy. Up to 6 weeks of therapy may be required before improvement is evident. This may be followed by a reduced dosage schedule.[55917]

Apply a thin layer to the affected area(s) once daily. Temporary discontinuation or reduction in application frequency may be necessary until the patient is able to tolerate the treatment.

Apply a thin layer to the affected area(s) once daily. Temporary discontinuation or reduction in application frequency may be necessary until the patient is able to tolerate the treatment.

Apply a pea-sized amount to cover the entire affected area once daily before bedtime for 24 to 48 weeks. Most improvement is noted during the first 24 weeks of treatment. Use in combination with comprehensive skin care and sun avoidance programs. Brown spots begin to fade at around 6—8 weeks and there is a decrease in fine lines and wrinkles around 3 to 6 months. Discontinuation of treatment usually results in a loss of effect. The safety and efficacy of tretinoin therapy beyond 48 weeks has not been established.

45 mg/m2/day PO in 2 equally divided doses until complete remission is documented. Therapy should be discontinued 30 days after remission or after 90 days of treatment, whichever occurs first. After induction therapy with tretinoin, all patients should receive standard consolidation and/or maintenance therapy for APL unless otherwise contraindicated.

45 mg/m2/day PO in 2 divided doses after meals until complete remission is documented. Therapy should be discontinued 30 days after remission or after 90 days of treatment, whichever occurs first. A decrease in the recommended dosage may be considered for patients who experience serious or intolerable toxicity. However, the safety and efficacy of lower doses have not been established. After induction therapy with tretinoin, all patients should receive standard consolidation and/or maintenance therapy for APL unless otherwise contraindicated.

45 mg/m2/day PO once daily or divided every 12 hours alone or with regimens containing 6-mercaptopurine and methotrexate for 1 to 2 years following induction and consolidation therapy has been studied in randomized clinical trials. Tretinoin was given daily for 1 year or for 15 days every 3 months alone or with 6-MP 90 mg/m2 PO daily plus methotrexate 15 mg/m2 PO once weekly for 2 years, or alternating every 3 months with 6-MP/methotrexate for 2 years. In one 4-arm trial, the 12-year disease-free survival (DFS) rates were not significantly different in patients who received 2 years of chemotherapy compared with no chemotherapy (68.9% vs. 69%) or in patients who received 2 years of tretinoin compared with no tretinoin (68.3% vs. 69.7%) in 318 patients who were (PCR)-negative for the PML-RARA fusion gene following induction therapy with tretinoin and idarubicin and 3 cycles of intensive consolidation therapy.The 10-year cumulative incidence of relapse was significantly decreased with 2 years of chemotherapy- and tretinoin-containing maintenance therapy in patients with a hematologic complete remission (CR) following either tretinoin or chemotherapy induction therapy and 2 cycles of consolidation therapy in another 4-arm trial; however, the 10-year overall survival rate was significantly improved with chemotherapy compared with no chemotherapy maintenance therapy (85.2% vs. 79.2%) but not with tretinoin compared with no tretinoin maintenance therapy (82.7% vs. 79.4%). The 5-year DFS rate was significantly improved with 1 year of tretinoin maintenance therapy compared with observation only (61% vs. 36%) in patients who achieved a CR following either tretinoin or chemotherapy induction therapy and 2 cycles of consolidation therapy in another randomized study.

22.5 mg/m2 orally twice daily (dose rounded to the nearest 10-mg increment) in combination with arsenic 0.15 mg/kg IV over 2 hours once daily until bone marrow remission or for up to a maximum of 60 days as induction therapy followed by consolidation therapy with tretinoin 22.5 mg/m2 orally twice daily (dose rounded to the nearest 10-mg increment) as continuous therapy during weeks 1 and 2 (on all 4 cycles) and during weeks 5 and 6 (on cycles 1, 2, and 3 only) in combination with arsenic trioxide 0.15 mg/kg IV daily given 5 days per week for 4 consecutive weeks (total of 20 doses/cycle). Consolidation therapy is repeated every 8 weeks for 4 cycles. During induction therapy, all patients should receive differentiation syndrome prophylaxis with prednisone 0.5 mg/kg orally once daily.

45 mg/m2/day PO in 2 divided doses until complete remission (CR) to a maximum of 45 or 90 days plus idarubicin 12 mg/m2/dose IV on days 2, 4, 6, and 8 has been evaluated in 2 clinical trials (AIDA 0493 study; AIDA 2000 study). Adults less than 20 years of age received tretinoin 25 mg/m2/day PO in the AIDA 0493 study. Patients who achieved a hematologic CR received 3 anthracycline-containing consolidation therapy courses. Additionally, most patients in these studies who achieved a molecular CR after consolidation received up to 2 years of tretinoin-containing maintenance therapy. Prophylactic use of corticosteroids was recommended during induction therapy to help prevent differentiation (retinoic acid) syndrome.

25 mg/m2/day PO in 2 divided doses until complete remission (CR) or a maximum of 90 days plus idarubicin 12 mg/m2/dose IV on days 2, 4, 6, and 8 has been evaluated in a clinical trial (AIDA 0493 study). Patients who achieved a hematologic CR received 3 multi-agent chemotherapy consolidation courses containing anthracyclines and cytarabine. Additionally, most patients who achieved a molecular CR after consolidation received up to 2 years of tretinoin-containing maintenance therapy. In a subgroup analysis of the AIDA 0493 study, induction therapy with tretinoin plus idarubicin resulted in a post-induction hematologic CR rate of 96% in 107 evaluable pediatric patients (median age, 11.6 years; range, 1.4 to 17.9 years). Tretinoin was administered for a median of 32 days (range, 1 to 56 days) during induction therapy. The 10-year event-free survival and overall survival rates were 76% and 89%, respectively. Retinoic acid syndrome was reported in 8 patients (definitely present, n = 2; indeterminate, n = 6) and pseudotumor cerebri developed in 10 patients. There were 4 deaths during induction therapy.

Following induction therapy with tretinoin (45 mg/m2/day PO in 2 divided daily doses until complete remission (CR) or a maximum of 45 days) plus idarubicin (12 mg/m2/dose IV on days 2, 4, 6, and 8), patients who achieved a hematologic CR received 3 risk-adapted tretinoin- and anthracycline-based consolidation therapy courses in a clinical study (AIDA 2000 study). All patients in this study received tretinoin 45 mg/m2/day PO for 15 days starting on day 1 of each consolidation cycle. Patients with low- or intermediate-risk APL (defined as initial WBC less than 10 x 109/L) received: idarubicin 5 mg/m2/dose IV on days 1, 2, 3, and 4 (course 1), mitoxantrone 10 mg/m2/dose IV on days 1, 2, 3, 4, and 5 (course 2); and idarubicin 12 mg/m2/dose on day 1 (course 3). Patients with high-risk APL received: idarubicin 5 mg/m2/dose IV on days 1, 2, 3, 4, and 4 and cytarabine 1,000 mg/m2/day IV on days 1, 2, 3, and 4 (course 1); mitoxantrone 10 mg/m2/dose IV on days 1, 2, 3, 4, and 5 and etoposide 100 mg/m2/dose IV on days 1, 2, 3, 4, and 5 (course 2); and idarubicin 12 mg/m2/dose IV on day 1, cytarabine 150 mg/m2 subcutaneously every 8 hours on days 1, 2, 3, 4, and 5, and 6-thioguanine 70 mg/m2 PO every 8 hours on days 1, 2, 3, 4, and 5 (course 3). Intrathecal methotrexate 12 mg and methylprednisone 40 mg were administered prior to each consolidation course in patients with high-risk disease. Additionally, patients who achieved a molecular CR after consolidation received up to 2 years of tretinoin-containing maintenance therapy.

Topical tretinoin 0.05% to 0.1% applied once daily to affected areas in combination with hydroquinone with or without hydrocortisone has been effective. Treatment should also include avoidance of sun exposure and use of sunscreens. To decrease side effects, some studies have applied tretinoin twice weekly instead of daily.

Topical tretinoin 0.025% to 0.1% applied once daily to affected areas has been used in the treatment of various diseases of keratinization, often in combination with other agents.

Dose is not established; however, 45 mg/m2/day PO divided in 2 daily doses x12 weeks was studied in one phase II study; escalating doses up to 150 mg/m2/day divided in 3 daily doses have also been studied. Tretinoin resulted in a partial response (PR) rate of 42% in 19 patients with low-risk AIDS-related Kaposi sarcoma in a multicenter, phase II study; additionally, 37% of patients had stable disease (SD). Six patients also received concurrent antiretroviral therapy, although no patients received a protease inhibitor. Responding patients continued tretinoin therapy beyond 12 weeks (mean duration, 27 +/- 7 weeks; range, 16 to 36 weeks) and the median time to response and time to disease progression in these patients were 56 and 332 days, respectively. Treatment with escalating doses of tretinoin (initial dosage of 45 mg/m2/day in 2 daily doses given every 12 hours on week 1 titrated weekly to a target dosage of 150 mg/m2/day in 3 daily doses given every 8 hours by week 5; median dosage of 90 mg/m2/day; range, 70-300 mg/day) led to a PR rate of 17% in 24 evaluable patients with mucocutaneous, nonvisceral AIDS-related Kaposi’s sarcoma in another phase II trial; additionally, 13% of patients achieved a minor response and 29% of patients had SD. Most patients (74%) in this study had not received prior treatment for AIDS-related Kaposi sarcoma and 89% of patients were receiving concurrent antiretroviral therapy. The median time to response was 22 weeks (range, 12 to 28 weeks). At a median follow-up of 5 months (range, 1 to 17 months), the median disease-free survival time was 5 months and the median overall survival time was 27.3 months.

†Indicates off-label use

Specific guidelines for dosage adjustments of systemic tretinoin therapy in hepatic impairment are not available; it appears that no dosage adjustments are needed. Consider temporarily discontinuing oral tretinoin therapy in patients who develop liver function test abnormalities greater than 5-times the upper limit of normal.

Specific guidelines for dosage adjustments of systemic tretinoin therapy in renal impairment are not available; it appears that no dosage adjustments are needed.

Adapalene; Benzoyl Peroxide: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided.
Albuterol; Budesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Alpha interferons: (Moderate) Use of alpha interferons are associated with myelosuppression; additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Aminocaproic Acid: (Major) Rare cases of fatal thrombotic complications have been reported in patients treated with systemic tretinoin, and antifibrinolytic agents. This is thought to be due to the persistent procoagulant tendency often associated with systemic tretinoin, ATRA therapy. Monitor patients closely and avoid if possible.
Aminolevulinic Acid: (Moderate) Tretinoin, ATRA may increase the effects of photosensitizing agents used during photodynamic therapy; concurrent use of photosensitizing agents is often recommended against by the specific photodynamic therapy, or doses of the therapy may require adjustment.
Amiodarone: (Moderate) Monitor for pseudotumor cerebri (benign intracranial hypertension) during concomitant amiodarone and tretinoin use due to increased risk for the condition. Both lithium and tretinoin are associated with pseudotumor cerebri.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Aprotinin: (Major) Rare cases of fatal thrombotic complications have been reported in patients treated with systemic tretinoin and antifibrinolytic agents. This is thought to be due to the persistent procoagulant tendency often associated with systemic tretinoin therapy. Monitor patients closely and avoid if possible.
Atenolol; Chlorthalidone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Azelastine; Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Azilsartan; Chlorthalidone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Barbiturates: (Moderate) Barbiturates may increase the CYP450 metabolism of tretinoin, ATRA, potentially resulting in decreased plasma concentrations of tretinoin, ATRA. Monitor for decreased clinical effects of tretinoin, ATRA while receiving concomitant therapy.
Beclomethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Benzalkonium Chloride: (Major) Sodium chloride (saline solutions) should not be used to dilute benzalkonium chloride as saline solutions may decrease the antibacterial potency of the antiseptic. Stored tap water should also not be used for dilution since it may contain microorganisms. Resin deionized water may also contain pathogens and it may inactivate benzalkonium chloride.
Benzalkonium Chloride; Benzocaine: (Major) Sodium chloride (saline solutions) should not be used to dilute benzalkonium chloride as saline solutions may decrease the antibacterial potency of the antiseptic. Stored tap water should also not be used for dilution since it may contain microorganisms. Resin deionized water may also contain pathogens and it may inactivate benzalkonium chloride.
Benzoyl Peroxide: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided.
Benzoyl Peroxide; Clindamycin: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided.
Benzoyl Peroxide; Erythromycin: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided.
Benzoyl Peroxide; Sulfur: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided.
Betamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Budesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Budesonide; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Budesonide; Glycopyrrolate; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Carbamazepine: (Moderate) Concurrent use of hepatic cytochrome P450 inducers, such as carbamazepine, with oral tretinoin therapy may result in significant decreases in serum tretinoin levels. Patients should be closely monitored for decreased clinical effects of tretinoin while receiving concomitant therapy. Also monitor for potential additive side effects, such as risk of infection.
Chlorothiazide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Chlorpromazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Chlorpropamide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Chlorthalidone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Chlorthalidone; Clonidine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cholestyramine: (Moderate) Cholestyramine can bind with and possibly decrease the oral absorption of tretinoin. To minimize drug interactions, administer other drugs at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
Ciclesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Ciprofloxacin: (Major) Avoid the concomitant use of tretinoin with other drugs known to cause photosensitivity, such as ciprofloxacin. Concomitant use with other photosensitizing agents may increase the risk of a photosensitivity reaction.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Codeine; Phenylephrine; Promethazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Codeine; Promethazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Colestipol: (Moderate) The bile-acid sequesterant colestipol is well-known to cause drug interactions by binding and decreasing the oral administration of many drugs, which may include interaction with oral tretinoin; to minimize drug interactions, administer other drugs at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine or colestipol.
Corticosteroids: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Cortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Cyclosporine: (Moderate) Patients should be closely monitored for tretinoin toxicity if concurrent therapy with cyclosporine is necessary; increased tretinoin exposure is possible, which may increase risks for adverse reactions. Cyclosporine is a moderate CYP3A4 inhibitor and tretinoin is metabolized by the hepatic CYP450 system. In a small study of patients stabilized on oral tretinoin therapy, a 72% increase in mean tretinoin plasma AUC was observed when a strong CYP3A4 inhibitor was given 1 hour before the tretinoin dose. To date there no data to determine if cyclosporine increases the toxicity of tretinoin capsules.
Danazol: (Moderate) The concomitant use of systemic tretinoin, ATRA and danazol should be done cautiously due to the potential for increased intracranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Early signs and symptoms of pseudotumor cerebri include papilledema, headache, nausea, vomiting, and visual disturbances.
Deflazacort: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Dexamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Eravacycline: (Major) Avoid the concomitant use of systemic tretinoin and eravacycline due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Early signs and symptoms include papilledema, headache, nausea, vomiting, and visual disturbances. In addition, a manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking photosensitizers, such as eravacycline, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Felbamate: (Moderate) Felbamate may increase the CYP450 metabolism of tretinoin, ATRA, potentially resulting in decreased plasma concentrations of tretinoin, ATRA. Monitor for decreased clinical effects of tretinoin, ATRA while receiving concomitant therapy.
Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Fludrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Flunisolide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fluphenazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fluticasone; Salmeterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fluticasone; Umeclidinium; Vilanterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fluticasone; Vilanterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Formoterol; Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Gemifloxacin: (Major) Avoid the concomitant use of tretinoin with other drugs known to cause photosensitivity, such as gemifloxacin. Concomitant use with other photosensitizing agents may increase the risk of a photosensitivity reaction.
Gentamicin: (Moderate) The concomitant use of systemic tretinoin, ATRA and systemic gentamicin should be done cautiously due to the potential for increased intracranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Early signs and symptoms of pseudotumor cerebri include papilledema, headache, nausea, vomiting, and visual disturbances.
Glimepiride: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Glipizide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Glipizide; Metformin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Glyburide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Glyburide; Metformin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Griseofulvin: (Moderate) Griseofulvin may increase the CYP450 metabolism of tretinoin, ATRA, potentially resulting in decreased plasma concentrations of tretinoin, ATRA. No specific studies have been done with oral tretinoin and griseofulvin, however, patients should be closely monitored for decreased clinical effects of tretinoin, ATRA while receiving concomitant therapy. Additionally, a manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as griseofulvin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Hydrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Indapamide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Interferon Alfa-2b: (Moderate) Use of alpha interferons are associated with myelosuppression; additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Interferon Alfa-n3: (Moderate) Use of alpha interferons are associated with myelosuppression; additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin may increase the CYP450 metabolism of tretinoin, ATRA, potentially resulting in decreased plasma concentrations of tretinoin, ATRA. No specific studies have been done with oral tretinoin and rifampin, however, patients should be closely monitored for decreased clinical effects of tretinoin, ATRA while receiving concomitant therapy.
Isoniazid, INH; Rifampin: (Moderate) Rifampin may increase the CYP450 metabolism of tretinoin, ATRA, potentially resulting in decreased plasma concentrations of tretinoin, ATRA. No specific studies have been done with oral tretinoin and rifampin, however, patients should be closely monitored for decreased clinical effects of tretinoin, ATRA while receiving concomitant therapy.
Ketoconazole: (Moderate) Patients should be closely monitored for tretinoin toxicity if concurrent therapy with ketoconazole is necessary. In a small study of patients stabilized on oral tretinoin therapy, a 72% increase in mean tretinoin plasma AUC was observed when ketoconazole (400 mg to 1,200 mg PO) was given 1 hour before the tretinoin dose.
Levofloxacin: (Major) Avoid the concomitant use of tretinoin with other drugs known to cause photosensitivity, such as levofloxacin. Concomitant use with other photosensitizing agents may increase the risk of a photosensitivity reaction.
Levoketoconazole: (Moderate) Patients should be closely monitored for tretinoin toxicity if concurrent therapy with ketoconazole is necessary. In a small study of patients stabilized on oral tretinoin therapy, a 72% increase in mean tretinoin plasma AUC was observed when ketoconazole (400 mg to 1,200 mg PO) was given 1 hour before the tretinoin dose.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Lithium: (Moderate) Monitor for pseudotumor cerebri (benign intracranial hypertension) during concomitant lithium and tretinoin use due to increased risk for the condition. Both lithium and tretinoin are associated with pseudotumor cerebri.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Methotrexate: (Moderate) Concomitant use of systemic retinoids, such as tretinoin, and methotrexate could increase risk of liver-related side effects of methotrexate and such patients should be monitored closely during methotrexate therapy. Topical retinoid products do not appear to pose this increased risk for liver problems.
Methoxsalen: (Moderate) Use methoxsalen and retinoids together with caution; the risk of severe burns/phototoxicity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
Methyclothiazide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Methylprednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Metolazone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Moxifloxacin: (Major) Avoid the concomitant use of tretinoin with other drugs known to cause photosensitivity, such as moxifloxacin. Concomitant use with other photosensitizing agents may increase the risk of a photosensitivity reaction.
Ofloxacin: (Major) Avoid the concomitant use of tretinoin with other drugs known to cause photosensitivity, such as ofloxacin. Concomitant use with other photosensitizing agents may increase the risk of a photosensitivity reaction.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Olopatadine; Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Rifabutin may increase the CYP450 metabolism of tretinoin, ATRA, potentially resulting in decreased plasma concentrations of tretinoin, ATRA. No specific studies have been done with oral tretinoin and rifabutin, however, patients should be closely monitored for decreased clinical effects of tretinoin, ATRA while receiving concomitant therapy.
Orlistat: (Moderate) The bioavailability of orally administered retinoids may be decreased if coadministered with orlistat. In patients receiving orally-administered retinoids along with orlistat, close monitoring is recommended. In addition, the manufacturer recommends that fat-soluble vitamin analogues be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption.
Palovarotene: (Major) Avoid concomitant use of palovarotene and other retinoids, such as tretinoin, due to the risk for hypervitaminosis A.
Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Peginterferon Alfa-2a: (Moderate) Use of alpha interferons are associated with myelosuppression; additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Peginterferon Alfa-2b: (Moderate) Use of alpha interferons are associated with myelosuppression; additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Perphenazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Perphenazine; Amitriptyline: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Phenothiazines: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Photosensitizing agents (topical): (Moderate) Tretinoin, ATRA may increase the effects of photosensitizing agents used during photodynamic therapy; concurrent use of photosensitizing agents is often recommended against by the specific photodynamic therapy, or doses of the therapy may require adjustment.
Pioglitazone; Glimepiride: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Porfimer: (Major) Avoid coadministration of porfimer with retinoids due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like retinoids may increase the risk of a photosensitivity reaction.
Prednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Prednisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Prochlorperazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Promethazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Promethazine; Dextromethorphan: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Promethazine; Phenylephrine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Rifabutin: (Moderate) Rifabutin may increase the CYP450 metabolism of tretinoin, ATRA, potentially resulting in decreased plasma concentrations of tretinoin, ATRA. No specific studies have been done with oral tretinoin and rifabutin, however, patients should be closely monitored for decreased clinical effects of tretinoin, ATRA while receiving concomitant therapy.
Rifampin: (Moderate) Rifampin may increase the CYP450 metabolism of tretinoin, ATRA, potentially resulting in decreased plasma concentrations of tretinoin, ATRA. No specific studies have been done with oral tretinoin and rifampin, however, patients should be closely monitored for decreased clinical effects of tretinoin, ATRA while receiving concomitant therapy.
Rifapentine: (Moderate) Rifapentine may increase the CYP450 metabolism of tretinoin, ATRA, potentially resulting in decreased plasma concentrations of tretinoin, ATRA. No specific studies have been done with oral tretinoin and rifapentine, however, patients should be closely monitored for decreased clinical effects of tretinoin, ATRA while receiving concomitant therapy.
Ropeginterferon alfa-2b: (Moderate) Use of alpha interferons are associated with myelosuppression; additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Salicylic Acid: (Moderate) Dryness of the skin and mucus membranes are common side effects of retinoid therapy. Simultaneous use of retinoids and topical drying agents, such as salicylic acid, can potentiate the drying effects of retinoids on the skin. Be alert for signs of skin irritation, the offending topical agents may need to be used less often or discontinued during retinoid therapy.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Sodium Thiosulfate; Salicylic Acid: (Moderate) Dryness of the skin and mucus membranes are common side effects of retinoid therapy. Simultaneous use of retinoids and topical drying agents, such as salicylic acid, can potentiate the drying effects of retinoids on the skin. Be alert for signs of skin irritation, the offending topical agents may need to be used less often or discontinued during retinoid therapy.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Sulfonylureas: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Tetracyclines: (Major) Avoid the concomitant use of tretinoin and systemic tetracyclines due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with both systemic retinoid and tetracycline use alone. Early signs and symptoms include papilledema, headache, nausea, vomiting, and visual disturbances.
Thiazide diuretics: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Thioridazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Thrombolytic Agents: (Moderate) Patients with thrombocytopenia are at increased risk of bleeding complications. An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Thyroid hormones: (Moderate) The concomitant use of systemic tretinoin, ATRA and thyroid hormones should be done cautiously due to the potential for increased intracranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Early signs and symptoms of pseudotumor cerebri include papilledema, headache, nausea, vomiting, and visual disturbances.
Tolazamide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Tolbutamide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Tranexamic Acid: (Major) Rare cases of fatal thrombotic complications have been reported in patients treated with systemic all-trans retinoic acid (ATRA) or tretinoin and the use of antifibrinolytic agents, like tranexamic acid. This is thought to be due to the persistent procoagulant tendency often associated with systemic tretinoin therapy.
Tretinoin; Benzoyl Peroxide: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided.
Triamcinolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Trifluoperazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with retinoids is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like retinoids may increase the risk of a photosensitivity reaction.
Voriconazole: (Moderate) Monitor frequently for signs of pseudotumor cerebri or hypercalcemia during coadministration of voriconazole and tretinoin. Although this interaction has not been studied, voriconazole may increase tretinoin concentrations and increase the risk of adverse reactions. Voriconazole is a strong CYP3A4 inhibitor, and tretinoin is a CYP3A4 substrate. Administration of tretinoin with another strong CYP3A4 inhibitor resulted in a 72% increase in the mean tretinoin plasma AUC.

Altinac/AVITA/Refissa/Renova/Retin-A/Tretinoin/Tretin-X Topical Cream: 0.02%, 0.025%, 0.0375%, 0.05%, 0.075%, 0.1%
Altreno Topical Lotion: 0.05%
Atralin/AVITA/Retin-A/Retin-A Micro/Tretinoin/Tretin-X Topical Gel: 0.01%, 0.025%, 0.04%, 0.05%, 0.06%, 0.08%, 0.1%
Tretinoin/Vesanoid Oral Cap: 10mg
Tretin-X Topical Sol
Tretin-X Topical Susp

45 mg/m2 per day PO.

45 mg/m2 per day PO.

45 mg/m2 per day PO.

45 mg/m2 per day PO.

Safety and efficacy not established.

Safety and efficacy not established.

Mechanism of Action: Retinoids are intracrine and paracrine mediators of cell differentiation and proliferation, apoptosis (programmed cell death), and reproduction. Cells regulate the formation of specific retinoid isomers depending upon the cellular action required. The numerous effects of retinoids reflect the complex biology of the nuclear receptors that mediate retinoid activity. Retinoid receptors are divided into retinoid X receptors (RXRs) and retinoic acid receptors (RARs); both types can be further divided into 3 subtypes: Alpha, beta, and gamma. These receptor subtypes are further divided into many isoforms. Retinoid receptors are structurally similar but have different affinities for different types of retinoids and distribution varies throughout the body resulting in a wide range of actions. Tretinoin binds to all three RARs, but does not bind to RXRs except at very high concentrations. RAR-alpha and RAR-beta have been associated with the development of acute promyelocytic leukemia and squamous cell cancers, respectively. RAR-gamma is associated with retinoid effects on mucocutaneous tissues and bone.•Skin Disorders: By binding to RARs, tretinoin modifies gene expression, subsequent protein synthesis, and epithelial cell growth and differentiation. It has not been established whether the clinical effects of tretinoin are mediated through activation of RARs, other mechanisms such as irritation, or both. Tretinoin appears to prevent horny cell cohesion and to increase epidermal cell turnover and mitotic activity. Subsequently, in patients with acne, expulsion of existing comedones occurs, and formation of new comedones is prevented through sloughing and expulsion of horny cells from the follicle. Tretinoin reduces the cell layers of the stratum corneum. The bacterium involved in acne, Propionibacterium acnes, and sebum production are unaffected. An additional action of tretinoin may involve keratinization inhibition, which would explain its effectiveness in treating keratinization disorders.•Photodamage: Topical tretinoin is effective in reducing fine wrinkling, mottled hyperpigmentation, roughness, and laxity associated with photodamaged skin. Ultraviolet irradiation induces three metalloproteinases in human skin: collagenase, 92-kd gelatinase, and stromelysin-1. The combined actions of these enzymes can fully degrade skin collagen. Pretreatment of skin with tretinoin inhibits the induction of these skin matrix metalloproteinase proteins and activity by 70—80% in both connective tissue and outer layers of irradiated skin.•Acute Promyelocytic Leukemia: Similar to other retinoids, tretinoin induces cellular differentiation in malignant cells. Acute promyelocytic leukemia (APL) is caused by a genetic lesion that disrupts the alpha retinoic acid receptor (RAR-alpha) gene found on the long arm of chromosome 17 and the PML gene found on chromosome 15. The fusion protein that is formed, PML-RAR-alpha, inhibits apoptotic pathways and blocks myeloid differentiation when present in levels greater than those of the normal RAR-alpha protein. The presence of this gene translocation [t(15;17)] is used for diagnosis of APL and as a marker of response following treatment with either cytotoxic agents or tretinoin. During tretinoin treatment, cells expressing PML/RAR-alpha undergo cellular differentiation at a rate higher than normal cells. At therapeutic doses of tretinoin, the activity of the fusion protein on differentiation converts from inhibitory to stimulatory. Terminal differentiation of APL cells as the mechanism of tretinoin therapy is supported by 1) the absence of bone marrow aplasia during treatment; 2) the appearance of cells during treatment with the morphologic characteristics of maturation stages intermediate between promyelocytes and neutrophils; 3) the presence, during treatment, of PML and RAR-alpha rearrangements in peripheral blood neutrophils that disappear after treatment. Treatment with tretinoin reverses the bleeding diathesis seen in APL, before any morphologic response is noted. A retinoic acid syndrome, similar to capillary leak syndrome, may be seen in some patients (see Adverse Reactions). The etiology of this syndrome is unknown, but may be due to decreases in leukocyte adhesion protein activity. Resistance to tretinoin may develop due to pharmacokinetic reasons (decreased bioavailability) and/or changes in proteins involved in the cellular activity of tretinoin.

Tretinoin is administered topically and orally; an intravenous formulation is under investigation. 
 
Systemic tretinoin is greater than 95% bound to plasma proteins, primarily albumin. The distribution of tretinoin has not been determined. Tretinoin is metabolized by the cytochrome P450 hepatic enzyme system. The metabolites include 13-cis retinoic acid, 4-oxo trans retinoic acid, 4-oxo cis retinoic acid, and 4-oxo trans retinoic acid glucuronide. Tretinoin appears to induce its own metabolism. An approximately 10-fold increase in the urinary excretion of 4-oxo trans retinoic acid glucuronide is observed after 2—6 weeks of continuous dosing when compared with baseline.

After administration of a single oral dose, tretinoin is well absorbed, with peak plasma concentrations showing considerable interpatient variability. Mean peak plasma concentrations are 347 +/- 266 ng/ml and occur between 1 and 3 hours after dosing.
 
About 90% of an oral dose is excreted in the urine and feces within 72 hours and 6 days, respectively.

One of the proposed benefits of the liposomal injection form of tretinoin, is the ability to overcome excessively rapid hepatic clearance and subsequent drug resistance associated with oral administration.

Following topical application, a minimal amount of drug is absorbed systemically. There is no expected difference in the systemic absorption of tretinoin from the microsphere formulation. Prolonged treatment or application to large body surface areas can enhance systemic absorption.
 
Approximately 1—5% of a topically applied dose is excreted in the urine within 24 hours.

Teratogenic and embryotoxic effects have been demonstrated in animals receiving oral tretinoin or large doses (i.e., many times greater than the normal human dose) of topical tretinoin. Adequate and well-controlled trials have not been performed in humans, but increased spontaneous abortions and major human fetal abnormalities have occurred when pregnant women received other retinoids. There have been 30 case reports of temporally-associated, congenital malformations during 25 years of clinical use of Retin-A. The significance of these spontaneous reports in terms of risk to the fetus is not known. Avoid use of topical tretinoin over large areas of skin or for prolonged periods. The benefit-risk profile should be considered before prescribing. Reproductive risk should be discussed. There is a high risk of birth defects if oral tretinoin is administered during pregnancy. Females of childbearing potential must use two reliable forms of contraception simultaneously during oral tretinoin therapy and for one month following discontinuation of therapy, unless abstinence is the chosen method. Contraception requirements must be followed even when there is a history of infertility or menopause, unless a hysterectomy has been performed. Within one week of beginning tretinoin oral therapy, the patient should have a negative pregnancy test; if possible, treatment with tretinoin should be delayed until pregnancy testing results are known. Pregnancy testing and counseling should occur monthly during oral tretinoin therapy.[48166] [48167] [63467]