Hiprex
Hiprex
Generic Name
Hiprex
Mechanism
- Selective glucocorticoid receptor agonist: Dexa‑Hiprex binds the cytosolic glucocorticoid receptor (GR) with high affinity and specificity.
- Nuclear translocation & gene modulation:
- Transactivation: GR–dexa dimer recruits co‑activators (p300/CBP) to promote transcription of anti‑inflammatory proteins (e.g., lipocortin‑1, annexin A1).
- Transrepression: The GR complex interferes with NF‑κB, AP‑1, and STAT signaling, down‑regulating pro‑inflammatory cytokines (IL‑1β, TNF‑α, IL‑6).
- Direct inhibition of phospholipase A₂ and suppression of arachidonic acid pathways, reducing prostaglandin and leukotriene synthesis.
- Rapid onset (30–60 min) and prolonged duration (≈36 h) due to minimal hepatic metabolism of the active form.
Pharmacokinetics
| Parameter | Detail |
| Absorption | Oral bioavailability > 95 % |
| Distribution | Volume of distribution ≈ 5 L/kg; high protein binding (≤ 25 % free due to saturable albumin sites) |
| Metabolism | Hepatic CYP‑3A4 oxidation to inactive metabolites; minimal entero‑hepatic recycling |
| Elimination | Primarily renal excretion of metabolites; plasma half‑life ≈ 36 h (clinical effect > 60 h) |
| Drug interactions | Potentiates CYP‑3A4 inhibitors (e.g., ketoconazole, clarithromycin); reduces efficacy of CYP‑3A4 inducers (e.g., rifampicin, phenytoin) |
Indications
- Allergic: severe allergic reactions, anaphylaxis (adjunct to epinephrine), urticaria, atopic dermatitis.
- Inflammatory & Autoimmune: rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis.
- Pulmonary & ENT: asthma exacerbations, chronic obstructive pulmonary disease (COPD), chronic sinusitis, allergic rhinitis.
- Gastrointestinal: inflammatory bowel disease flare (colitis, Crohn’s).
- Dermatologic: eczema, psoriasis, cutaneous vasculitis.
- Neurologic: optic neuritis, multiple sclerosis relapses (short courses).
Contraindications
- Absolute contraindications: live–attenuated vaccines, systemic infection, severe bacterial sepsis.
- Relative contraindications: peptic ulcer disease, uncontrolled diabetes, hypertension, osteoporosis, cataracts, glaucoma, pregnancy (Category C), lactation (small amounts excreted in milk).
- Warnings:
- Adrenal suppression: Must taper gradually after 7 days of oral use.
- Infection risk: monitor for fungal, bacterial, or opportunistic infections.
- Metabolic effects: hyperglycemia, dyslipidemia.
- Psychiatric: mood swings, psychosis.
Dosing
| Indication | Regimen | Notes |
| Acute allergic reaction | 4–10 mg orally or buccally once | Single dose; consider 5 mg/10 mg tablets. |
| Asthma exacerbation | 10–20 mg orally or 6–10 mg IV *in a slow infusion* | Taper over 7‑10 days. |
| Rheumatoid arthritis | 10–20 mg daily (single dose) | Max 40 mg/day; taper as remission achieved. |
| Lupus flare | 20–40 mg/day for 2–3 weeks, then reduce | Avoid > 10 mg for > 7 days. |
| Inflammatory bowel disease | 10–30 mg 4×/day for 7–14 days | Taper gradually; monitor CRP. |
| Neuropathic conditions (e.g., optic neuritis) | 1 mg/kg IV over 20 min daily for 3 days | Rapid taper afterward. |
• Form: Tablets (1.5–5 mg), IV solution 4 mg/mL; buccal film for rapid absorption.
• Administration: Oral tablets with food to reduce GI upset; IV infusion over 20–30 min; avoid rapid IV bolus.
Adverse Effects
- Common (≥ 10 %):
- Gastro‑intestinal irritation, dyspepsia, nausea.
- Fluid retention, hypertension.
- Hyperglycemia, glucose intolerance.
- Mood changes, insomnia.
- Acneiform rash, hirsutism.
- Headache, dizziness.
- Serious (rare, ≤ 1 %):
- Osteoporosis (long‑term use).
- Cataract, glaucoma.
- Opportunistic infections (Mycobacterium tuberculosis, fungal).
- Suppression of the hypothalamic‑pituitary‑adrenal axis.
- Acute psychosis, severe mood swings.
- Steroid‑induced ulcers or GI bleeding.
Monitoring
| Parameter | Frequency | What to Watch |
| Blood glucose | Baseline, then weekly for first month | Hyperglycemia, diabetic ketoacidosis |
| Blood pressure | Baseline, then weekly | Hypertension crisis |
| Weight & BMI | Monthly | Fluid retention, metabolic syndrome |
| Serum electrolytes | Every 2–4 weeks (if prolonged therapy) | Hypokalemia, sodium shifts |
| Bone density | Baseline, then yearly (≥ 6 months) | Osteoporosis risk |
| Adrenal function | Baseline, then after 7‑10 days of cessation | Signs of adrenal insufficiency |
| Vision & eye exam | Baseline, then yearly | Cataract, glaucoma |
Clinical Pearls
- Rapid IV infusion: Slow, 20–30 min, reduces the risk of GI irritation and hypotension.
- Timing with vaccinations: For patients requiring live vaccines, pause Hiprex 4 weeks before and 2 weeks after.
- Dose‑reduction strategy: A 20 % step‑down every 3–5 days during tapering prevents adrenal crises.
- Use with caution in diabetes: Tight glycemic control is essential due to glucocorticoid‑induced hyperglycemia.
- Pediatric dosing: 0.05–0.1 mg/kg/day (max 5 mg) depending on severity; pediatric monitoring is critical for growth suppression.
- Drug‑drug interaction checklist: Avoid concurrent use with ketoconazole or clarithromycin (increased peak levels) or rifampicin (decreased efficacy).
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• *Hiprex remains a cornerstone glucocorticoid for rapid anti‑inflammatory control; careful monitoring and individualized dosing can mitigate its well‑characterized adverse effect profile.*