Schedule H

Oral

• Apremilast 10 mg tablets

• Apremilast 20 mg tablets

• Apremilast 30 mg tablets

• Apremilast Titration Starter Pack (contains 10 mg, 20 mg, and 30 mg tablets for 5-day titration)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

1. Plaque Psoriasis (Moderate to Severe)

Indicated in adults with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.

Titration Schedule (Days 1–5):

Day 1 10 mg —

Day 2 10 mg 10 mg

Day 3 10 mg 20 mg

Day 4 20 mg 20 mg

Day 5 20 mg 30 mg

Parameter Recommendation

Starting dose 10 mg once daily on Day 1 (as per titration schedule above)

Titration Gradual dose escalation over 5 days to reduce GI adverse effects

Usual maintenance dose 30 mg twice daily (from Day 6 onwards)

Maximum dose 30 mg twice daily

Clinical Notes:

• Titration pack recommended for all patients to improve tolerability

• Clinical response may take 8–12 weeks to become apparent

• Consider discontinuation if no improvement by 16–24 weeks

• Useful in patients who are not candidates for or prefer to avoid injectable biologics

1. Psoriatic Arthritis (Active Disease)

Indicated in adults with active psoriatic arthritis who have had inadequate response or intolerance to prior DMARD therapy.

Parameter Recommendation

Starting dose 10 mg once daily on Day 1 (as per titration schedule above)

Titration Same 5-day titration protocol as for plaque psoriasis

Usual maintenance dose 30 mg twice daily (from Day 6 onwards)

Maximum dose 30 mg twice daily

Clinical Notes:

• May be used as monotherapy or in combination with conventional DMARDs (e.g., methotrexate)

• Evaluate clinical response at 12–16 weeks

• Offers oral alternative when biologics are not accessible or contraindicated

Secondary Indications — Adults (Off-label, if any):

Behçet's Disease (Oral Ulcers) — OFF-LABEL

Parameter Details

Dose 30 mg twice daily (after standard 5-day titration)

Duration Long-term; individualized based on response

Specialist only Yes — rheumatologist or clinical immunologist supervision

Evidence basis Small RCTs (RELIEF trial); used in Indian tertiary rheumatology centres

Note May reduce frequency and severity of oral aphthous ulcers

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India):

Not approved for use in children below 18 years in India.

Safety and efficacy have not been established in the paediatric population.

Secondary Indications — Paediatrics (Off-label, if any):

Not applicable.

No adequate paediatric safety or efficacy data available. Use in children is not recommended even in off-label settings outside of clinical trial protocols.

Statement: Use in patients below 18 years is NOT RECOMMENDED. No paediatric formulation or dosing guidelines exist for India.

Day Dose

Day 1 10 mg once daily (morning only)

Day 2 20 mg once daily (morning only)

Day 3 30 mg once daily (morning only)

Maintenance (Day 4 onwards) 30 mg once daily

• Known hypersensitivity to apremilast or any excipient

• Pregnancy (teratogenic potential demonstrated in animal studies)

• Severe active depression or history of suicidal ideation/behaviour

• History of depression or mood disorders — monitor closely for worsening symptoms or emergence of suicidal thoughts

• Unexplained or significant weight loss (>5% of baseline body weight) — evaluate cause and consider discontinuation

• Pre-existing gastrointestinal disorders — may exacerbate diarrhoea, especially during initial weeks

• Elderly patients with reduced renal function — assess eGFR before initiating

• Underweight patients — baseline weight documentation essential

• Concurrent use with strong CYP3A4 inducers (see Major Drug Interactions) — significant reduction in efficacy

• Patients with history of recurrent infections

Parameter Details

Risk assessment Not recommended; avoid use during pregnancy

Fetal risk Animal studies demonstrate teratogenicity (embryofetal toxicity, skeletal abnormalities); insufficient human data

Contraception Women of childbearing potential must use effective contraception during treatment

Preferred alternatives Topical therapies, narrowband UVB phototherapy; cyclosporine or biologics (with specialist input) for severe disease

Specialist input Mandatory — dermatologist and obstetrician coordination if treatment during pregnancy is considered essential

Monitoring if exposed Detailed fetal anomaly scan; high-risk obstetric surveillance

Parameter Details

Breastfeeding compatibility Not recommended; unknown if excreted in human breast milk

Drug levels in milk Unknown; animal data suggest excretion in milk

Preferred alternatives Topical therapies; if systemic therapy essential, consider biologics with better lactation safety data (under specialist guidance)

Recommendation Discontinue breastfeeding if apremilast therapy is necessary

Monitoring in infant Not applicable — avoid exposure

Parameter Recommendation

Starting dose Standard adult titration protocol

Titration Consider slower titration if GI tolerability is poor

Specific risks Increased susceptibility to diarrhoea-induced dehydration, weight loss, and depression

Renal consideration Assess eGFR before initiation; use once-daily dosing if eGFR <30 mL/min

Monitoring Monitor weight, hydration status, and mood more frequently

Clinical note No pharmacokinetic differences in elderly, but clinical vigilance required for tolerability

Interacting Drug/Class Effect & Management

Strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, phenobarbital) Significantly decreases apremilast exposure (~70% reduction with rifampicin); avoid concomitant use — leads to loss of therapeutic efficacy

St. John's Wort (Hypericum perforatum) Strong CYP3A4 inducer; avoid combination

Interacting Drug/Class Effect & Management

Moderate CYP3A4 inhibitors (ketoconazole, erythromycin, fluconazole) Minimal effect on apremilast levels; no dose adjustment required

Methotrexate No significant pharmacokinetic interaction; can be used concomitantly; monitor for additive immunosuppressive effects

Oral contraceptives No clinically significant interaction; efficacy of hormonal contraception maintained

Immunosuppressants (azathioprine, cyclosporine) No pharmacokinetic interaction, but theoretical additive immunosuppression; monitor for infections

NSAIDs No direct interaction; monitor for additive GI effects if diarrhoea present

Antidepressants No pharmacokinetic interaction; however, monitor mood closely given apremilast's psychiatric adverse effects

• Diarrhoea (most common; ~15–17%; usually self-limiting within first 2 weeks)

• Nausea

• Headache

• Upper respiratory tract infections

• Nasopharyngitis

• Vomiting

• Decreased appetite

• Insomnia

• Fatigue

• Abdominal pain

• Back pain

• Weight loss (usually mild)

• Depression and suicidal ideation — requires immediate discontinuation and psychiatric evaluation; counsel all patients before initiation

• Severe weight loss (>10% of baseline body weight) — unexplained significant weight loss warrants discontinuation

• Severe diarrhoea with dehydration — may require cessation, especially in elderly or those with renal impairment

• Hypersensitivity reactions / angioedema — rare; discontinue immediately if occurs

• Severe gastrointestinal symptoms — persistent or severe GI disturbance may necessitate discontinuation

Phase Parameters

Baseline (before initiation) Body weight, renal function (serum creatinine/eGFR), mental health screening (depression history, suicidal ideation assessment)

During titration (first 2 weeks) GI tolerability (diarrhoea, nausea), mood changes, weight

At 4–8 weeks Weight, mood assessment, GI symptoms, clinical response

Every 3 months (long-term) Weight monitoring, mental health assessment, renal function (in elderly or at-risk patients)

Annually Renal function in patients >65 years or with baseline renal impairment

Ongoing Monitor for signs of depression, suicidal ideation, unexplained weight loss at each visit

• Otezla (Amgen — imported originator)

• Aprilast (Glenmark)

• Amprebel (Sun Pharma)

• Aplagra (Intas)

• Aprezo (Cipla)

• Aprist (Dr. Reddy's)

Most brands offer a titration starter pack containing all three strengths (10 mg, 20 mg, 30 mg) for initial therapy

Notes:

• Not included in National List of Essential Medicines (NLEM) 2022

• Not under NPPA price control

• Significant price variation between originator (Otezla) and Indian generic brands

• Monthly maintenance cost at 30 mg twice daily: approximately ₹10,000–₹19,000

• Always use titration pack: Initiating therapy with the 5-day titration regimen significantly reduces GI adverse effects (especially diarrhoea and nausea) and improves patient compliance

• Patience required: Counsel patients that clinical improvement in psoriasis may take 8–12 weeks; premature discontinuation is common if expectations are not set appropriately

• Depression screening mandatory: Screen all patients for depression and suicidal ideation at baseline and during follow-up; this is a black-box warning concern

• Weight monitoring essential: Document baseline weight; unexplained weight loss >5% warrants investigation and potential discontinuation

• Avoid with rifampicin: In India, concurrent TB treatment with rifampicin-based regimens renders apremilast ineffective; consider alternative TB regimens or defer apremilast until TB treatment completion

• Oral alternative to biologics: Apremilast offers a convenient oral option for patients who refuse or have contraindications to injectable biologics, though efficacy is generally lower than biologics

apremilast; PDE4 inhibitor; psoriasis; plaque psoriasis; psoriatic arthritis; oral immunomodulator; depression-risk; weight-loss-monitoring; renal-adjustment; biologic-alternative; Schedule H

RxIndia v1.0 — 02 Jun 2025

• CDSCO approved prescribing information

• Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) consensus guidelines on psoriasis management

• AIIMS Delhi Adult Psoriasis Treatment Protocol

• API Textbook of Medicine (Dermatology and Rheumatology sections)

• National Formulary of India (NFI)

• NLEM 2022 (Apremilast not listed)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th edition

• Manufacturer product information (Otezla, Aprilast)

• RELIEF trial data (off-label Behçet's disease reference)