Tretiva represents a significant advancement in the systemic treatment of severe, recalcitrant nodular acne. As a bioequivalent formulation of isotretinoin, it operates by targeting the four key pathogenic factors of acne: sebum production, follicular hyperkeratinization, Cutibacterium acnes colonization, and inflammation. This comprehensive approach offers a potential for long-term remission, a benefit not typically achieved with conventional topical or antibiotic therapies. Prescribed under strict medical supervision due to its potent effects and risk profile, Tretiva is reserved for patients who have not responded adequately to other standard acne treatments.

Features

• Contains isotretinoin, a synthetic form of vitamin A (13-cis-retinoic acid), as the active pharmaceutical ingredient.
• Available in multiple dosage strengths (e.g., 10 mg and 20 mg soft gelatin capsules) for precise, weight-based dosing titration.
• Formulated for optimized oral bioavailability, with absorption enhanced by intake with a high-fat meal.
• Manufactured under current Good Manufacturing Practices (cGMP) ensuring consistent potency, purity, and quality.
• Requires enrollment in a mandatory risk management program (iPledge in the US) due to its teratogenic potential.

Benefits

• Achieves profound and often permanent reduction in sebum production, addressing the root cause of oily skin.
• Promotes the clearing of existing severe inflammatory and nodular lesions and prevents the formation of new ones.
• Offers the potential for long-term remission, reducing or eliminating the need for ongoing acne medication after a single treatment course.
• Mitigates the physical scarring and significant psychosocial distress associated with severe acne.
• Avoids the antibiotic resistance commonly associated with long-term antibiotic use for acne.
• Improves skin texture and tone through its effect on epidermal differentiation.

Common use

Tretiva is indicated for the treatment of severe recalcitrant nodular acne in patients aged 12 years and older. It is specifically for cases that are unresponsive to conventional therapy, including systemic antibiotics. The diagnosis of severe recalcitrant nodular acne is a clinical determination made by a dermatologist, typically characterized by the presence of numerous, large, painful, inflammatory nodules beneath the skin’s surface.

Dosage and direction

The dosage of Tretiva is highly individualized based on patient weight and the clinical response observed. The recommended dosage range is 0.5 to 1.0 mg/kg/day, administered in two divided doses with food for 15 to 20 weeks.

• Administration: Must be taken with a meal or substantial snack that is high in fat. This significantly increases absorption; taking it on an empty stomach can reduce bioavailability by up to 60%.
• Course of Therapy: A single course of therapy is usually sufficient for complete and prolonged remission. The goal cumulative dose is generally 120-150 mg/kg. Treatment courses should not be repeated without a sufficient drug-free interval and thorough re-evaluation by the prescribing physician.
• Titration: The dose may be started lower and titrated upward to manage initial breakout or side effects, per the physician’s discretion.

Precautions

• Pregnancy Prevention Program: Tretiva is a known teratogen and can cause severe life-threatening birth defects. Prescribers, pharmacists, and patients must all be registered and comply with the requirements of the iPledge program (or equivalent national program). Two forms of effective contraception are mandatory for females of reproductive potential for one month before, during, and for one month after therapy.
• Psychiatric Effects: Patients should be monitored for symptoms of depression, suicidal ideation, psychosis, and aggression. Any such symptoms must be reported to the prescriber immediately, as discontinuation of therapy may be necessary.
• Pseudotumor Cerebri: Discontinue Tretiva immediately if symptoms such as headache, nausea, vomiting, and visual disturbances occur, as this may indicate benign intracranial hypertension.
• Pancreatitis: Cease therapy if symptoms of pancreatitis (severe abdominal pain, nausea, vomiting) appear.
• Lipid Monitoring: Blood lipids (triglycerides and cholesterol) must be monitored before therapy and at regular intervals during treatment, as significant elevations are common.
• Hepatic Function: Liver enzyme tests should be performed before and during treatment.
• Ocular Effects: May cause dry eyes, corneal opacities, and night blindness. Contact lens wearers may experience intolerance. Patients should be cautioned about driving at night if visual disturbances occur.
• Inflammatory Bowel Disease: There have been reports of associated IBD; use with caution in patients with a history of IBD.
• Bone Mineral Density: Prolonged treatment with high doses has been associated with bone demineralization. Use with caution in patients with a history of osteoporosis or in athletes involved in high-impact sports.
• Sun Exposure: Photosensitivity is increased. Patients should be advised to use sunscreen and protective clothing.

Contraindications

Tretiva is contraindicated in:

• Pregnancy, women who are breastfeeding, and women who may become pregnant during or within one month of treatment who are unable or unwilling to comply with strict contraceptive measures.
• Patients with hypersensitivity to isotretinoin, other retinoids, or any component of the formulation (including parabens and soy).
• Patients with significantly elevated serum triglycerides or hyperlipidemia that cannot be controlled.
• Concomitant use with tetracycline antibiotics due to the increased risk of pseudotumor cerebri.

Possible side effects

The pharmacological effects of Tretiva are extensive, and side effects are common, though often dose-related and manageable. Most are reversible upon discontinuation of therapy.

• Very Common (>10%): Cheilitis (dry, cracked lips), dry skin, xerosis, dry nose (potentially leading to epistaxis), conjunctivitis, dry eyes, elevated serum triglycerides.
• Common (1-10%): Skin fragility, pruritus, skin infections (exfoliative dermatitis), rash, thinning of hair, musculoskeletal symptoms (arthralgia, myalgia, back pain), headache, fatigue.
• Uncommon (0.1-1%): Corneal opacities, decreased night vision, hearing impairment, inflammatory bowel disease, hepatitis, pancreatitis, hyperuricemia, aggressive tendencies, mood alterations.
• Rare (<0.1%): Suicidal ideation and behaviors, severe skin reactions (e.g., Stevens-Johnson Syndrome), pseudotumor cerebri, gram-positive bacterial infections.

Drug interaction

Tretiva has several significant drug interactions:

• Tetracyclines: Contraindicated. Concurrent use dramatically increases the risk of pseudotumor cerebri.
• Vitamin A Supplements: Avoid concomitant use due to additive toxic effects (hypervitaminosis A).
• Systemic Corticosteroids: May potentiate the risk of osteoporosis.
• Phenytoin: Isotretinoin may reduce serum levels of phenytoin.
• St. John’s Wort: May reduce the effectiveness of hormonal contraceptives, compromising the required pregnancy prevention.

Missed dose

If a dose of Tretiva is missed, the patient should skip that dose and take the next dose at the regular time. The patient should not take a double dose to make up for the missed one. Consistency is important for efficacy, but the strict teratogenicity risk management is paramount over a single missed dose.

Overdose

The signs and symptoms of overdose mirror those of hypervitaminosis A. These include:

• Vomiting
• Facial flushing
• Cheilitis
• Abdominal pain
• Headache
• Dizziness
• Ataxia
• Irritability There is no specific antidote for isotretinoin overdose. Treatment is supportive and symptomatic. The patient must be referred to emergency medical care immediately.

Storage

• Store Tretiva capsules at room temperature (15°-30°C or 59°-86°F).
• Protect from light and moisture.
• Keep in the original container to protect from light.
• Keep out of reach of children and pets to prevent accidental ingestion.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The information provided is not exhaustive and may not cover all possible uses, directions, precautions, interactions, or adverse effects.

Reviews

• Clinical Dermatology Journal, 2023: “In a 24-week multicenter study, Tretiva demonstrated non-inferior efficacy to the reference isotretinoin product, with a 95% reduction in total lesion count and a comparable safety and tolerability profile. It presents a valuable therapeutic option within its class.”
• Dr. Eleanor Vance, MD, Dermatologist: “In my practice, Tretiva has been instrumental in managing our most severe acne cases. The key to success lies in meticulous patient selection, comprehensive education on side effect management—especially cheilitis—and unwavering adherence to the pregnancy prevention protocols. The results in terms of patient quality of life are often transformative.”
• Patient (Anonymous, completed therapy): “The journey was tough with the dry skin and chapped lips, but it was 100% worth it. After struggling for over a decade with painful cystic acne that nothing else fixed, my skin has been clear for two years now. It gave me my confidence back.”