I-Ret

I-Ret Uses, Dosage, Side Effects, Food Interaction and all others data.

I-Ret is a synthetic retinoid which reduces sebaceous gland size and inhibits sebum production. It also regulates cell proliferation and differentiation and has dermal anti-inflammatory effect.

The pharmacodynamics of isotretinoin are poorly understood.

Trade Name I-Ret
Availability Prescription only
Generic Isotretinoin
Isotretinoin Other Names 13-cis-retinoic acid, 13-cis-Vitamin A acid, 13-RA, cis-RA, Isotretinoin, Isotretinoína, Isotrétinoine, Isotretinoino, Isotretinoinum, Neovitamin A acid
Related Drugs doxycycline, clindamycin topical, erythromycin topical, tetracycline, Tazorac
Type
Formula C20H28O2
Weight Average: 300.4351
Monoisotopic: 300.20893014
Protein binding

Isotretinoin is >99.9% protein bound, mainly to serum albumin.

Groups Approved
Therapeutic Class Oral retinoids for Acne
Manufacturer
Available Country India
Last Updated: September 19, 2023 at 7:00 am
I-Ret
I-Ret

Uses

I-Ret is used for the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. Because of significant adverse effects associated with its use, I-Ret should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, I-Ret is used only for those female patients who are not pregnant, because I-Ret can cause severe birth defects.

A single course of therapy for 15 to 20 weeks has been shown to result in complete and prolonged remission of disease in many patients. If a second course of therapy is needed, it should not be initiated until at least 8 weeks after completion of the first course, because experience has shown that patients may continue to improve while off I-Ret . The optimal interval before re-treatment has not been defined for patients who have not completed skeletal growth

I-Ret is also used to associated treatment for these conditions: Acne Rosacea, Acne conglobata, Mycosis Fungoides (MF), Neuroblastomas, Sezary Syndrome, Refractory Acne vulgaris, Severe Recalcitrant nodular acne

How I-Ret works

I-Ret produces its effects through altering progress through the cell cycle, cell differentiation, survival, and apoptosis. These actions reduce sebum production, preventing the blockage of pores, and growth of acne causing bacteria. I-Ret and 4-oxo-isotretinoin both significantly reduce the production of sebum. I-Ret has little to no affinity for retinol binding proteins (RBPs) and retinoic acid nuclear receptors (RARs). Tretinoin and 4-oxo-tretinion bind to the RAR-γ receptor, which is suspected to be part of the action of acne treatment by isotretinoin. I-Ret induces apoptosis in sebocytes, leading to a decrease in sebum production. I-Ret also reduces the formation of comedones by reducing hyperkeratinization through an unknown mechanism. I-Ret does not directly kill bacteria but it does reduce the size of sebum ducts and makes the microenvironment less hospitable to acne causing bacteria. It may also increase immune mechanisms and alter chemotaxis of monocytes to reduce inflammation.

There is preliminary evidence suggesting isotretinoin may interact with FoxO1, which may explain a substantial number of isotretinoin's unexplained actions.

Dosage

I-Ret dosage

Oral-

  • Adult: Initially, 0.5 mg/kg daily in single or 2 divided doses, increased to 1 mg/kg daily if necessary. Usual duration of treatment: 16-24 wk. May repeat treatment course after at least 8 wk if relapse after first course.
  • Child: ≥12 yr Same as adult dose.

Topical:Apply I-Ret 0.05% gel cautiously over the affected area once or twice daily.Patients should be advised that 6-8 weeks of treatment may be required before a therapeuticeffect is observed. The safety and efficacy of I-Ret have not been established in children since acne vulgarisrarely present in this age group. There are no specific recommendations for use in the elderly.Acne vulgaris does not present in the elderly.

Side Effects

Erythema, skin exfoliation, stinging sensation, pruritus, irritation, tenderness, dry skin, hirsutism, photosensitivity, skin pigmentation, paronychia, nail dystrophy, pyogenic granuloma, increased sweating, corneal opacities, visual disturbances, headache, nausea and vomiting, arthralgia, myalgia, back pain, intracranial HTN, hyperostosis and calcinosis. Elevation of serum triglycerides, LFTs, ESR and blood glucose. Mood changes, psychotic symptoms, depression and suicidal behaviour.

Toxicity

Patients experiencing an overdose may present with vomiting, facial flushing, cheilosis, abdominal pain, headache, dizziness, and ataxia. These symptoms may rapidly resolve. Generally no treatment is required for these overdoses.

The oral lowest dose causing toxic effect (TDLO) for children is 30mg/kg/21W, oral TDLO for men is 24mg/kg/4W, oral TDLO for women is 56mg/kg/8W. The intraperitoneal LD50 for rats is 901mg/kg, oral LD50 for mice is 3389mg/kg, oral LD50 for rats is >4000mg/kg.

I-Ret is associated with major congenital malformations, spontaneous abortion, and premature birth. It is unknown if isotretinoin is expressed in breast milk but due to the associated hazards a decision should be made to either stop nursing or stop taking isotretinoin.

In animal studies, isotretinoin was associated with an increased risk of pheochromocytoma and adrenal medullary hyperplasia at doses above the recommended clinical dose. I-Ret was negative for the Ames test of mutagenicity once and weakly positive a second time. It has not been shown to be clastogenic. A study in dogs noted testicular atrophy after doses of 10-30 times the recommended clinical dose for 30 weeks. In trials with men there were no effects seen on sperm count, motility, morphology, ejaculate volume, and seminal plasma fructose.

Precaution

Women of childbearing potential; anorexia nervosa. History of photoallergy, psychiatric disorder (e.g. depression); pre-existing or predisposition to hypertriglyceridaemia (e.g. DM, obesity or increased alcohol intake). Genetic predisposition for age-related osteoporosis, history of childhood osteoporosis, osteomalacia or other bone metabolism disorders. Not intended for the treatment of prepubertal acne. Severe renal impairment.

Interaction

Additive adverse effects with vit A or its derivatives. Decreased efficacy of microdosed progesterone (use 2 forms of contraception).Increased risk of local irritation with topical keratolytic or exfoliative anti-acne agents. Oxidising agents (e.g. benzoyl peroxide) may reduce the efficacy of topical isotretinoin.

Food Interaction

  • Avoid alcohol. Alcohol with isotretinoin can lead to inflammation of the liver.
  • Avoid vitamin A supplements.
  • Take with food. High-fat food increases drug absorption.

I-Ret Alcohol interaction

[Moderate] GENERALLY AVOID:

The combined use of ethanol and isotretinoin may result in a disulfiram-like reaction.

The mechanism has not been established.



Alcohol consumption should be avoided during isotretinoin therapy.

I-Ret Cholesterol interaction

[Moderate] The use of retinoids is associated with elevations in serum triglycerides and cholesterol, and decreases in HDL.

In addition to cardiovascular risks, elevation of serum triglycerides to greater than 800 mg

Patients at increased risk for developing hypertriglyceridemia during retinoid therapy include those with diabetes mellitus, obesity, high alcohol consumption, or a family history of these conditions.

Blood lipid determinations should be performed prior to initiation of therapy and at 1- to 2- week intervals until the lipid response to the drug is established (usually 4 to 8 weeks).

Patients with preexisting hyperlipidemia may require closer monitoring during retinoid therapy, and adjustments made accordingly in their lipid-lowering regimen.

Volume of Distribution

The volume of distribution in humans is unknown because there is no intravenous preparation. In a study of pediatric patients with neuroblastoma the volume of distribution was found to be 85L. The volume of distribution was also found to be 2432mL/kg in guinea pigs and 1716mL/kg in obese rats.

Elimination Route

Patients reach a maximum concentration of 74-511ng/mL after 1-4 hours following a 100mg oral dose. I-Ret is better absorbed with a high fat meal and bioavailability may change from one brand to another.

Following a 40mg oral dose, fasted subjects reached a maximum concentration of 314ng/mL in 2.9 hours with an area under the curve of 4055ng/mL*hr. Subjects given a high fat meal and a 40mg oral doses reached a maximum concentration of 395ng/mL in 6.4 hours with an area under the curve of 6095ng/mL*mL.

Half Life

The half life ranges from 7-39 hours with a mean elimination half life of 20 hours. The half life of 4-oxo-13-cis-retinoic acid ranges from 17-50 hours with a mean elimination half life of 25 hours.

Clearance

The clearance of isotretinoin is 15.9L/h in pediatric patients with neuroblastoma. Clearance is also 21.3mL/min/kg in guinea pigs and 7.2mL/min/kg in obese rats.

Elimination Route

I-Ret and its metabolites are conjugated and excreted in the urine and feces in similar amounts. 53-74% of an oral dose is eliminated as unchanged isotretinoin in the feces.

Pregnancy & Breastfeeding use

Category X: Studies in animals or human beings have demonstrated foetal abnormalities or there is evidence of foetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

Contraindication

Hypervitaminosis A, hyperlipidaemia. Hepatic impairment. Pregnancy and lactation. Concomitant admin of tetracycylines.

Special Warning

Renal Impairment: Oral: Severe: Reduce initial dose (e.g. 10 mg daily), then gradually increase to 1 mg/kg as necessary.

Hepatic Impairment: Oral: Contraindicated.

Storage Condition

Store between 20-25° C. Protect from light.

Innovators Monograph

You find simplified version here I-Ret

I-Ret contains Isotretinoin see full prescribing information from innovator I-Ret Monograph, I-Ret MSDS, I-Ret FDA label

FAQ

What is I-Ret used for?

I-Ret is a medication primarily used to treat severe acne. It is also used to prevent certain skin cancers, and in the treatment of other cancers. This is acne with lots of pus-filled spots that may affect the back and chest, as well as the face. I-Ret capsules help severe acne by reducing the amount of natural oil made by your skin so blocked pores are less likely.

How safe is I-Ret ?

I-Ret is a closely monitored medication, and though considered safe by most, it requires patients to have monthly check-ins with their physician to monitor their health and well-being.

How does I-Ret work?

I-Ret works by shrinking the oil, or sebaceous, glands in the skin. This reduces the amount of oil that is produced. When your skin isn't producing excess oil, it isn't hanging around clogging up pores and creating pimples. By controlling the oil, acne is also controlled.

What are the common side effects of I-Ret?

Common side effects of I-Ret are include:

  • skin becoming more sensitive to sunlight.
  • dry eyes.
  • dry throat.
  • dry nose and nosebleeds.
  • headaches and general aches and pains.

Is I-Ret safe during pregnancy?

I-Ret must not be taken by patients who are pregnant or who may become pregnant. There is a high risk that I-Ret will cause loss of the pregnancy, or will cause the baby to be born too early, to die shortly after birth, or to be born with birth defects.

Is I-Ret safe during breastfeeding?

It is not known if I-Ret can get into breast milk but other similar medications can. We do not know what effect exposure to I-Ret through the breast milk can have on a nursing infant. Until more is known, women who are breastfeeding should not take I-Ret.

Can I drink alcohol with I-Ret?

It's best to avoid alcohol while taking I-Ret capsules, or at least keep the amount you drink to a minimum. This is because there's a risk of damage to your liver - and that your cholesterol levels will increase.

Can I drive after taking I-Ret?

I-Ret capsules can make you feel sleepy and dizzy. You also may not see as well at night. If this happens to you, do not drive, cycle, or use machinery or tools until you've stopped treatment.

When should be taken of I-Ret?

I-Ret is usually taken twice a day with meals for 4 to 5 months at a time.

Can I take I-Ret on an empty stomach?

I-Ret may be taken with or without food.

How long does I-Ret take to work?

I-Ret capsules start to work after a week to 10 days. 

Does I-Ret build up in my system?

I-Ret can build up in your bloodstream. You may develop problems with blood sugar and lipid levels. Because of the danger to pregnant women, you shouldn't donate blood while taking this medication or for a full month after you stop taking it.

Can I take I-Ret for a long time?

I-Ret  in the treatment of acne is a safe drug, with no serious long-term side-effects.

Who should not take I-Ret?

I-Ret must not be taken by patients who are pregnant or who may become pregnant. There is a high risk that I-Ret will cause loss of the pregnancy, or will cause the baby to be born too early, to die shortly after birth, or to be born with birth defects.

What happens if I overdose?

Seek emergency medical attention. Overdose symptoms may include headache, dizziness, vomiting, stomach pain, warmth or tingling in your face, swollen or cracked lips, and loss of balance or coordination.

What happens if I miss a dose?

Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time.

What happens when I stop taking I-Ret?

If these problems aren't treated, they could last even after you stop taking I-Ret. If you have any of the side effects listed below, stop taking isotretinoin and check with your doctor right away: Headaches, nausea, vomiting, or blurred vision.

Can I-Ret affects my heart ?

According to case reports, systemic I-Ret therapy can cause cardiac side effects, like atrial tachycardia, congenital heart disease, cardiac remodeling and sinus tachycardia.

Will I-Ret affect my fertility?

I-Ret does not appear to affect fertility.

Can I-Ret affect my kidneys?

The adverse reactions of systemic I-Ret on the kidney and urinary system are unlikely and rare.

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