Alitretinoin

Alitretinoin
Names
Trade namesPanretin, Toctino, other
Other names9-cis-retinoic acid
IUPAC name
  • (2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-
    1-cyclohexenyl)nona-2,4,6,8-tetraenoic acid
Clinical data
Drug classRetinoid[1]
Main usesKaposi’s sarcoma, eczema[2][3]
Side effectsTopical: Itchiness, skin peeling, rash[2]
By mouth: Hair loss, low red blood cells, tiredness, high blood pressure, high cholesterol, ringing in the ears[3]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Routes of
use		Topical, by mouth
External links
AHFS/Drugs.comMonograph
MedlinePlusa601012
Legal
License data
Legal status
Pharmacokinetics
Protein bindingHighly bound, no exact figure available[4]
MetabolismLiver (CYP3A4-mediated oxidation, also isomerised to tretinoin)[4]
Elimination half-life2-10 hours[4]
ExcretionUrine (64%), faeces (30%)[4]
Chemical and physical data
FormulaC20H28O2
Molar mass300.442 g·mol−1
3D model (JSmol)
SMILES
  • O=C(O)\C=C(\C=C\C=C(/C=C/C1=C(/CCCC1(C)C)C)C)C
InChI
  • InChI=1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8-,16-14+ checkY
  • Key:SHGAZHPCJJPHSC-ZVCIMWCZSA-N checkY

Alitretinoin, sold under the brand name Panretin among others, is a medication used to treat Kaposi’s sarcoma due to AIDS and eczema of the hands.[2][3] It is only used to treat disease involving the skin.[2] It is applied to the skin or take by mouth.[1]

Common side effects include when applied to the skin include itchiness, skin peeling, and rash.[2] Common side effects when taken by mouth include hair loss, low red blood cells, tiredness, high blood pressure, high cholesterol, and ringing in the ears.[3] Other side effects may include sunburns.[2] Use in pregnancy may harm the baby.[2] It is a retinoid.[1]

Alitretinoin was approved for medical use in the United States in 1999.[2] While it was approved for use in Europe in 2000, this has subsequently been withdrawn.[5] It is available as a generic medication.[3] In the United Kingdom a month of pills costs the NHS about £500 as of 2021.[3] In the United States a 60 gram tube costs about 5,600 USD as of 2022.[6]

Medical uses

Kaposi’s sarcoma

In the United States, topical alitretinoin is indicated for the treatment of skin lesions in AIDS-related Kaposi's sarcoma. Alitretinoin is not indicated when systemic therapy against Kaposi's sarcoma is required.[7] It has received EMA (11 October 2000) and FDA (2 March 1999) approval for this indication.[8][9]

Chronic hand eczema

Alitretinoin has been granted prescription rights in the UK (08/09/2008) for in chronic hand eczema as used by mouth.[10] In May 2009 the National Institute for Health and Clinical Excellence (NICE) issued preliminary guidance[11] on the use of alitretinoin for the treatment of severe chronic hand eczema in adults. The recommendation stated that only patients with severe chronic hand eczema who are unresponsive to potent topical corticosteroids, oral immunosuppressants or phototherapy should receive the drug. Final NICE guidance is expected in August 2009.

Dosage

By mouth it is taken at a dose of 30 mg once per day.[3]

Side effects

Systemic use

[4][9]

Very common (>10% frequency):

Common (1-10% frequency):

Uncommon (0.1-1% frequency):

Rare (<0.1% frequency):

Unknown frequency:

  • Anaphylactic reactions
  • Hypersensitivity
  • Depression
  • Mood changes
  • Suicidal ideation
  • Decreased night vision

Topical use

[12]

Very common (>10% frequency):

Common (1-10% frequency):

Contraindications

Pregnancy is an absolute contraindication as with most other vitamin A products, it should also be avoided when it comes to systemic use in any women that is of childbearing potential and not taking precautions to prevent pregnancy.[4] Toctino (the oral capsule formulation of alitretinoin) contains soya oil and sorbitol. Patients who are allergic to peanut, soya or with rare hereditary fructose intolerance should not take this medicine.[4] It is also contraindicated in nursing mothers.[4] The oral formulation of alitretinoin is contraindicated in patients with:[4]

Interactions

It is a CYP3A4 substrate and hence any inhibitor or inducer of this enzyme may alter plasma levels of alitretinoin.[4] It should not be given to patients with excess vitamin A in their system as there is a potential for its actions on the retinoid X receptor to be exacerbated.[4] It may also interact with tetracyclines to cause benign intracranial hypertension.[4]

Overdose

Alitretinoin is a form of vitamin A. Alitretinoin has been administered in oncological clinical studies at dosages of more than 10-times of the therapeutic dosage given for chronic hand eczema. The adverse effects observed were consistent with retinoid toxicity, and included severe headache, diarrhoea, facial flushing and hypertriglyceridemia. These effects were reversible.[4]

Mechanism of action

Alitretinoin is believed to be the endogenous ligand (a substance that naturally occurs in the body that activates this receptor) for retinoid X receptor, but it also activates the retinoic acid receptor.[4][13][14]

References

  1. 1 2 3 "DailyMed - panretin- alitretinoin gel". dailymed.nlm.nih.gov. Archived from the original on 15 January 2021. Retrieved 14 January 2022.
  2. 1 2 3 4 5 6 7 8 "Alitretinoin Monograph for Professionals". Drugs.com. Archived from the original on 19 August 2021. Retrieved 14 January 2022.
  3. 1 2 3 4 5 6 7 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 1306. ISBN 978-0857114105.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 "Toctino 10mg and 30mg soft capsules - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Stiefel. 30 August 2013. Archived from the original on 23 May 2018. Retrieved 1 February 2014.
  5. ↑ "Panretin". Archived from the original on 26 June 2021. Retrieved 14 January 2022.
  6. ↑ "Alitretinoin Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 14 January 2022.
  7. ↑ "Panretin (Alitretinoin) Drug Information". RxList. November 21, 2000. Archived from the original on 18 December 2008. Retrieved 2009-01-14.
  8. ↑ "Panretin : EPAR - Product Information" (PDF). European Medicines Agency. Eisai Ltd. 14 September 2012. Archived (PDF) from the original on 23 May 2018. Retrieved 16 June 2021.
  9. 1 2 "PANRETIN (alitretinoin) gel [Eisai Inc.]". DailyMed. Eisai Inc. March 2012. Archived from the original on 2 February 2014. Retrieved 1 February 2014.
  10. ↑ Ruzicka T, Larsen FG, Galewicz D, Horváth A, Coenraads PJ, Thestrup-Pedersen K, et al. (December 2004). "Oral alitretinoin (9-cis-retinoic acid) therapy for chronic hand dermatitis in patients refractory to standard therapy: results of a randomized, double-blind, placebo-controlled, multicenter trial". Archives of Dermatology. 140 (12): 1453–9. doi:10.1001/archderm.140.12.1453. PMID 15611422.
  11. ↑ "NICE guidance documentation". Archived from the original on 2012-05-28. Retrieved 2021-06-16.
  12. ↑ "Panretin, (alitretinoin topical), dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 23 May 2018. Retrieved 1 February 2014.
  13. ↑ Rowe A (February 1997). "Retinoid X receptors". The International Journal of Biochemistry & Cell Biology. 29 (2): 275–8. doi:10.1016/S1357-2725(96)00101-X. PMID 9147128.
  14. ↑ Dawson MI, Xia Z (January 2012). "The retinoid X receptors and their ligands". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1821 (1): 21–56. doi:10.1016/j.bbalip.2011.09.014. PMC 4097889. PMID 22020178.
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