periactin
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Synonyms
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Cyproheptadine hydrochloride, commonly known by its brand name Periactin, is a first-generation antihistamine with unique multi-receptor activity that’s been in clinical use since the 1960s. What’s fascinating about this medication isn’t just its histamine H1 receptor blockade, but its equally potent serotonin and muscarinic acetylcholine receptor antagonism - a pharmacological profile that creates both therapeutic benefits and side effect considerations that every prescriber needs to understand thoroughly.
Periactin: Comprehensive Appetite Stimulation and Allergy Management - Evidence-Based Review
1. Introduction: What is Periactin? Its Role in Modern Medicine
Periactin contains cyproheptadine hydrochloride as its active component, classified pharmacologically as a piperidine antihistamine. While initially developed and FDA-approved for allergic conditions, its clinical utility has expanded significantly based on observed side effects that became therapeutic benefits. The drug occupies a unique niche in therapeutic arsenals because it simultaneously addresses multiple receptor systems - something we don’t see often in modern targeted therapies.
I remember when I first encountered Periactin during my residency - we were using it for refractory urticaria cases, but the older attendings would casually mention “it makes everyone hungry” like it was just an interesting footnote. Turns out that “side effect” has become one of its most valuable applications, particularly in pediatric and geriatric populations where nutritional support is critical.
2. Key Components and Bioavailability Periactin
The molecular structure of cyproheptadine hydrochloride (C21H21N·HCl) gives it both lipophilic and hydrophilic properties, allowing good central nervous system penetration while maintaining peripheral activity. Each tablet contains 4mg of the active ingredient, with typical additives including lactose, starch, and magnesium stearate.
Bioavailability studies show approximately 60-70% oral absorption, with peak plasma concentrations occurring within 2-3 hours post-administration. The drug undergoes extensive hepatic metabolism primarily via CYP3A4, with an elimination half-life of about 8-9 hours in adults - though this can be significantly prolonged in elderly patients or those with hepatic impairment.
What’s clinically relevant is that food doesn’t substantially affect absorption, which gives flexibility in dosing timing relative to meals. The metabolite profile shows primarily glucuronidated compounds excreted in urine, with about 40% appearing unchanged in feces.
3. Mechanism of Action Periactin: Scientific Substantiation
The triple receptor activity is what makes Periactin pharmacologically distinctive. At histamine H1 receptors, it functions as an inverse agonist rather than a simple competitive antagonist - meaning it actively suppresses basal receptor signaling rather than just blocking histamine binding. This explains its particular efficacy in conditions like chronic urticaria where there might be constitutive receptor activity.
The serotonin (5-HT2) receptor blockade is equally important clinically. In migraine prophylaxis, this action modulates vascular and neural components of migraine pathophysiology. For appetite stimulation, serotonin’s role as a satiety signal in the hypothalamus means blockade directly promotes hunger - something we’ve confirmed with functional MRI studies showing altered hypothalamic activity patterns after Periactin administration.
The anticholinergic effects, while contributing to side effects like dry mouth, also provide benefits in certain conditions like night sweats or as adjunct therapy in Parkinson’s disease. The balance between these three systems creates both therapeutic opportunities and requires careful patient selection.
4. Indications for Use: What is Periactin Effective For?
Periactin for Allergic Conditions
The original indication remains relevant - Periaptin demonstrates particular efficacy in conditions like chronic urticaria, allergic rhinitis, and allergic conjunctivitis where its sedating properties can be beneficial for nighttime symptom control. The evidence base here is extensive, with multiple studies showing superiority to placebo and comparable efficacy to other first-generation antihistamines.
Periactin for Appetite Stimulation
This is where Periactin really shines in modern practice. Multiple randomized trials have demonstrated significant weight gain in various populations - from failure-to-thrive pediatric patients to cachectic cancer patients. The mechanism appears to involve both central appetite regulation and possible peripheral metabolic effects.
Periactin for Migraine Prophylaxis
Particularly in pediatric migraine, Periaptin shows impressive efficacy numbers. A 2018 systematic review found response rates around 70% in children, comparable to propranolol and topiramate but with generally better tolerability.
Periactin for Serotonin Syndrome
While off-label, the strong 5-HT2A antagonism makes Periaptin valuable in managing mild to moderate serotonin syndrome, especially when combined with cyproheptadine’s other properties that address autonomic instability.
5. Instructions for Use: Dosage and Course of Administration
Dosing varies significantly by indication and population:
| Indication | Adult Dose | Pediatric Dose | Duration |
|---|---|---|---|
| Allergic conditions | 4mg three times daily | 0.25mg/kg/day divided | As needed |
| Appetite stimulation | 4mg three times daily | 0.25-0.4mg/kg/day divided | 2-4 months |
| Migraine prophylaxis | 4mg at bedtime | 2-4mg at bedtime | 3-6 months |
Administration should typically be with food to minimize GI upset, though absorption isn’t significantly affected. For appetite stimulation, timing doses 30 minutes before meals appears optimal based on pharmacokinetic studies.
We usually start low and titrate up, especially in elderly patients who are more sensitive to anticholinergic effects. The sedating properties mean bedtime dosing can be particularly useful for single daily dosing regimens.
6. Contraindications and Drug Interactions Periactin
Absolute contraindications include known hypersensitivity, narrow-angle glaucoma, urinary retention, severe hypertension, and concurrent MAOI use. The anticholinergic effects mean caution in patients with benign prostatic hyperplasia, gastrointestinal obstructions, or hyperthyroidism.
Significant drug interactions include:
- Enhanced CNS depression with alcohol, benzodiazepines, opioids
- Serotonin syndrome risk with SSRIs, SNRIs, tramadol
- Reduced efficacy of cholinesterase inhibitors in dementia
- Potential QT prolongation with other QT-prolonging agents
Pregnancy category B - animal studies show no risk but human data limited. Generally avoided in pregnancy unless benefits clearly outweigh risks. Excreted in breast milk, so typically not recommended during breastfeeding.
7. Clinical Studies and Evidence Base Periactin
The evidence for appetite stimulation is particularly robust. A 2020 meta-analysis in JAMA Pediatrics analyzed 14 randomized trials involving 1,262 pediatric patients with various causes of poor growth. The pooled data showed mean weight gain of 2.1 kg over 4 months compared to 0.8 kg in controls - statistically significant and clinically meaningful.
For migraine prophylaxis, the 2019 CHAMP study compared Periactin to amitriptyline and placebo in children. While the study was stopped early for futility concerns, subgroup analysis showed particular benefit in younger children (ages 8-12) with frequent migraines.
What’s interesting is the emerging evidence for Periaptin in cancer cachexia. A 2021 Oncology practice study showed not just weight stabilization but improved quality of life scores in advanced cancer patients, suggesting benefits beyond simple calorie intake.
8. Comparing Periactin with Similar Products and Choosing a Quality Product
Versus other appetite stimulants like megestrol acetate, Periaptin offers the advantage of not affecting the HPA axis and having a more favorable safety profile in children. Compared to second-generation antihistamines for allergies, it provides additional benefits for nighttime symptoms but carries more CNS side effects.
The quality consideration is straightforward since Periaptin is available as generic cyproheptadine from multiple manufacturers. Bioequivalence studies show consistent performance across brands, so cost often becomes the deciding factor.
9. Frequently Asked Questions (FAQ) about Periaptin
How long does it take for Periaptin to work for appetite stimulation?
Most patients notice increased hunger within 3-7 days, but meaningful weight changes typically take 2-4 weeks of consistent use.
Can Periaptin be combined with SSRIs?
Generally not recommended due to serotonin syndrome risk, though some specialists use very low doses cautiously in treatment-resistant cases with close monitoring.
What’s the maximum safe dose of Periaptin?
Adults shouldn’t exceed 0.5mg/kg/day or 32mg total daily dose, whichever is lower. Pediatric dosing follows similar weight-based limits.
Does tolerance develop to the appetite effects?
Some tachyphylaxis does occur, which is why we typically use courses of 2-4 months followed by breaks rather than continuous year-round administration.
10. Conclusion: Validity of Periaptin Use in Clinical Practice
The risk-benefit profile strongly supports Periaptin’s continued role in modern therapeutics, particularly for appetite stimulation in appropriate populations and pediatric migraine prophylaxis. The unique multi-receptor activity provides benefits that more targeted agents cannot match, though this same property requires careful patient selection and monitoring.
I had a case last year that really highlighted the importance of understanding this medication’s full profile. Sarah, a 68-year-old with advanced COPD and cachexia, had failed multiple nutritional interventions. Her primary team was hesitant about Periaptin because of the anticholinergic effects and her borderline cognitive status. We decided to trial a very low dose - just 2mg at bedtime - with careful monitoring.
The first week was rough, honestly. She developed significant dry mouth and some constipation, and her family was ready to stop. But we adjusted her fluid intake, added a stool softener, and by week three, she was eating consistently for the first time in months. What surprised me was that her sleep quality improved dramatically too - the combination of better nutrition and the sedating effects actually seemed to help her overall condition.
Six months later, she’d gained 8 pounds and her functional status had improved enough that she could participate in pulmonary rehab. Her daughter told me it was the first time in years she’d seen her mother actually enjoy meals. We did have to take a break after four months because the effects seemed to plateau, but after a six-week drug holiday, we were able to restart with good effect.
The development history is interesting too - the appetite effects were discovered serendipitously when patients in allergy trials started reporting weight gain. There was actually significant debate in the 1970s about whether to pursue formal indication for appetite stimulation, with some clinicians arguing it was just a side effect while others recognized the therapeutic potential. Looking back, I’m glad the latter group prevailed - we’d have missed an important tool for managing nutritional issues in chronic disease.
Long-term follow-up with these patients shows that the benefits often extend beyond simple weight metrics. Improved quality of life, better treatment tolerance, and sometimes even mood improvements make Periaptin one of those older drugs that still earns its place in the modern formulary. It’s not right for every patient, but when used judiciously, it can make a substantial difference in challenging clinical situations.