alitretinoin and Headache

Topics: Abnormalities, Drug-Induced; Adult; Alitretinoin; Anti-Inflammatory Agents; Capsules; Clinical Trials as Topic; Contraception; Contraindications; Drug Administration Routes; Drug Costs; Eczema; Female; France; Headache; Humans; Hyperlipidemias; Immunologic Factors; Male; Pregnancy; Retinoid X Receptors; Social Security; Tretinoin

Alitretinoin (9-cis-retinoic acid) is an endogenous derivative of vitamin A and functions as an agonist of both families of nuclear receptors (retinoic acid receptor-α, -β, -γ; retinoid X receptor-α, -β, -γ). It has been investigated in the treatment of chronic hand eczema in many studies in recent years and the results have been promising.. To evaluate the efficacy and safety of oral alitretinoin in the treatment of chronic hand eczema that is refractory to treatment with potent topical corticosteroids and to analyze the long-term response to treatment.. A prospective, observational, descriptive study was undertaken in 15 patients with chronic hand eczema that was refractory to treatment with potent topical corticosteroids. Patients were administered oral alitretinoin 30 mg/d for 3 months followed by 6 months of follow-up.. A complete response, with "clear" hands was obtained in 7 patients (47%), 5 patients (33%) achieved a partial response (almost clear hands), 1 patient (7%) showed substantial improvement, 1 (7%) showed moderate improvement, and 1 patient (7%) did not respond to treatment. Relapse occurred within 6 months of treatment suspension in 54% of cases. The treatment was well tolerated. Side effects, observed in 50% of cases, were mild (headache, elevated lipid levels, slightly elevated transaminase levels, and epigastric pain), except in 1 patient, who had a substantial reduction in thyroid stimulating hormone levels.. The results of our study support the proposal of alitretinoin as an effective and safe short-term and medium-term treatment for chronic hand eczema in patients whose disease is refractory to treatment with potent topical corticosteroids.

Topics: Administration, Cutaneous; Administration, Oral; Adrenal Cortex Hormones; Adult; Aged; Alitretinoin; Child; Chronic Disease; Drug Resistance; Eczema; Female; Hand Dermatoses; Headache; Humans; Hypercholesterolemia; Middle Aged; Occupational Diseases; Prospective Studies; Thyrotropin; Treatment Outcome; Tretinoin

To determine the maximum tolerated dose and describe the toxicities of 9-cis-retinoic acid (9cRA, ALRT1057) administered p.o. tid in pediatric patients with refractory cancer and to study the pharmacokinetics of 9cRA and determine whether systemic drug exposure changes with chronic dosing.. Children with refractory cancer (stratified by age, < or =12 and >12 years) were treated with p.o. 9cRA for 28 consecutive days. The starting dose was 50 mg/m(2)/day divided into 3 doses with planned escalations to 65, 85, and 110 mg/m(2)/day. Pharmacokinetic sampling was performed on days 1 and 29 of the first cycle.. Of the 37 patients entered, 18 patients < or =12 years of age and 11 patients >12 years of age were evaluable for toxicity. In patients >12 years of age, dose-limiting headache occurred in 2/2 patients at the 110 mg/m(2)/day dose level; 1/8 patients at 85 mg/m(2)/day developed dose-limiting pseudotumor cerebri. In patients < or =12 years of age, 3/5 patients at the starting dose level of 50 mg/m(2)/day developed dose-limiting pseudotumor cerebri; and 0/6 patients experienced dose-limiting toxicity at 35 mg/m(2)/day. Reversible non-dose-limiting hepatotoxicity was observed in 15 patients across all of the dose levels. There was considerable interpatient variability in 9cRA plasma concentrations. Peak plasma concentrations of 9cRA occurred at a median of 1.5 h after a p.o. dose, and the harmonic-mean terminal half-life was 43 min. By day 29 of 9cRA administration, the plasma 9cRA area under the curve declined by an average of 65% from day 1 values.. The dose-limiting toxicity of 9cRA in pediatric patients was neurotoxicity, primarily pseudotumor cerebri. Younger children tolerate significantly lower doses of 9cRA than older children. Similar to all-trans-retinoic acid, the pharmacokinetics of 9cRA demonstrated a wide degree of interpatient variability and decreased over time when administered on a daily basis. The recommended Phase II dose of 9cRA in patients < or =12 and >12 years of age is 35 and 85 mg/m(2)/day, respectively.

Topics: Adolescent; Adult; Age Factors; Alitretinoin; Antineoplastic Agents; Area Under Curve; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Headache; Humans; Liver; Male; Nausea; Neoplasms; Skin Diseases; Transaminases; Treatment Outcome; Tretinoin; Triglycerides; Vomiting

9-cis-Retinoic acid (9-cis-RA) has a particular pattern of binding and activating retinoid receptors. Treatment of chronic hand eczema is often refractory to conventional treatment.. Evaluation of oral 9-cis-RA therapy in chronic hand eczema in a pilot study.. Thirty-eight patients with refractory chronic hand eczema were treated in an exploratory open-label study with oral 9-cis-RA.. Twenty-one (55%) showed a very good response, 13 (34%) a good response, 2 (5.5%) a moderate response and 2 (5.5%) no response. Side effects were mild.. 9-cis-RA is a valuable drug when given at low doses to patients with chronic hand eczema.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Alitretinoin; Antineoplastic Agents; Cheilitis; Chronic Disease; Eczema; Female; Flushing; Hand Dermatoses; Headache; Humans; Male; Middle Aged; Patient Satisfaction; Pilot Projects; Severity of Illness Index; Skin; Treatment Outcome; Tretinoin

It is generally accepted that the inhibition of sebum excretion has a predictive value for anti-acne activity. Whereas oral 13-cisretinoic acid (13-cis-RA) decreases sebum excretion, it has not been shown so far if oral all-trans-retinoic acid (tretinoin, tRA) does so. The aim of this exploratory study was to investigate the effect of oral tRA on the sebum excretion rate (SER) in young male subjects.. 12 healthy volunteers with a baseline SER above 1.0 microgram/cm2/min were treated with 20 mg/day tRA for 4 weeks. The SER was measured at weeks 2 and 4. Adverse reactions were recorded.. The mean SER varied from 1.56 at baseline to 1.65 at week 2 and to 1.49 micrograms/cm2/min at week 4. Comparison with values obtained in the same subjects previously treated with either 13-cis-RA or 9-cis-retinoic acid indicated that tRA less sebosuppressive. Mucocutaneous reactions and headache were the most frequent side effects of oral tRA.. The lack of effect on the SER suggests that oral tRA would probably be ineffective against acne. The fact that, of the three isomers tested, only 13-cis-RA (which does not bind to nuclear receptors) shows activity may suggest that sebosuppression is not nuclear receptor mediated. We discuss other hypotheses related to pharmacokinetics.

Topics: Acne Vulgaris; Administration, Oral; Adult; Alitretinoin; Drug Eruptions; Facial Dermatoses; Headache; Humans; Isotretinoin; Keratolytic Agents; Lip Diseases; Male; Mucous Membrane; Retinoids; Sebum; Skin; Tretinoin

Topics: Abortion, Induced; Adult; Adverse Drug Reaction Reporting Systems; Alitretinoin; Contraception; Dermatologic Agents; Dyslipidemias; Eczema; Female; France; Glycoproteins; Headache; Humans; Mental Disorders; Middle Aged; Myocardial Infarction; Pharmacovigilance; Pregnancy; Suicidal Ideation; Thyroxine

Alitretinoin is approved for the treatment of adults with severe chronic hand eczema (CHE) refractory to potent topical steroids. In the 6 years since launch, approximately 250 000 patients have been treated with alitretinoin.. To compare the postmarketing safety surveillance experience of alitretinoin with data from clinical trials and key safety issues with other retinoids.. An integrated safety analysis of the pivotal studies of alitretinoin and postmarketing adverse event (AE) reports received since approval for alitretinoin were analyzed.. In the pivotal trials, headache, erythema, nausea, increased blood triglycerides and increased blood creatinine phosphokinase were the most frequently reported AEs. Headache, hyperlipidemia and nausea were also frequently reported postmarketing AEs, but depression was relatively more frequently reported than in the pivotal trials. Inflammatory bowel disease and benign intracranial hypertension were rare, and very few cases have been reported in postmarketing surveillance. There have been no reports of teratogenicity in humans consequent to fetal exposure.. Safety data collected in pivotal trials and postmarketing surveillance suggest that alitretinoin is well tolerated by patients with CHE with a relatively low incidence of serious reactions. The adverse reaction profile is congruent with reported effects of other marketed oral retinoids.

Topics: Adult; Alitretinoin; Chronic Disease; Eczema; Female; Hand Dermatoses; Headache; Humans; Pregnancy; Tretinoin

Topics: Adult; Alitretinoin; Dermatologic Agents; Eczema; Follow-Up Studies; Hand Dermatoses; Headache; Humans; Male; Time Factors; Tretinoin