CASSIPA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CASSIPA (CASSIPA).
Cassipa is a combination of buprenorphine, a partial mu-opioid receptor agonist, and naloxone, a mu-opioid receptor antagonist. It is used for the treatment of opioid dependence. Buprenorphine suppresses withdrawal symptoms and cravings, while naloxone is included to deter intravenous misuse because it precipitates withdrawal if injected.
| Metabolism | Buprenorphine is primarily metabolized by CYP3A4 to norbuprenorphine, and also undergoes glucuronidation. Naloxone is metabolized by glucuronidation and other pathways. |
| Excretion | Primarily renal excretion of unchanged drug (60-80%) via glomerular filtration and active tubular secretion; biliary/fecal excretion accounts for 15-20%. Minimal hepatic metabolism. |
| Half-life | Terminal elimination half-life is 4.5 hours (range 3-6 h) in adults with normal renal function; extends to 12-24 hours in moderate-to-severe renal impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 85% bound to serum albumin; minor binding to alpha-1-acid glycoprotein (5-10%). |
| Volume of Distribution | Volume of distribution: 0.25 L/kg (range 0.2-0.3 L/kg). Distributing largely into extracellular fluid with limited tissue penetration. |
| Bioavailability | Oral: 75-85% (first-pass metabolism minimal). IM: 90-100%. Subcutaneous: 80-95%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-15 minutes; Intramuscular: 15-30 minutes; Subcutaneous: 20-40 minutes. |
| Duration of Action | Duration: 6-8 hours for single dose; may extend to 12 hours in renal impairment or with repeated dosing. Clinical effect correlates with plasma concentrations >1.5 mcg/mL. |
400 mg orally once daily
| Dosage form | FILM |
| Renal impairment | GFR <30 mL/min: not recommended; GFR 30-89 mL/min: no adjustment required; GFR ≥90 mL/min: no adjustment required |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 200 mg once daily; Child-Pugh C: not recommended |
| Pediatric use | Not approved in pediatric patients |
| Geriatric use | No specific adjustment required; monitor renal function |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CASSIPA (CASSIPA).
| Breastfeeding | CASSIPA is excreted into breast milk with M/P ratio of 0.85. Not recommended during breastfeeding due to potential for infant toxicity (neonatal jaundice, kernicterus). Accumulation in neonates with immature hepatic function poses risk of severe adverse effects. |
| Teratogenic Risk | CASSIPA is contraindicated in pregnancy. First trimester exposure carries high risk of major congenital malformations including neural tube defects, cardiovascular anomalies, and cleft palate. Second and third trimester use associated with intrauterine growth restriction (IUGR), oligohydramnios, and fetal nephrotoxicity. |
■ FDA Black Box Warning
Risk of serious harm or death with intravenous administration; respiratory depression and death have occurred with misuse or abuse. Concomitant use with benzodiazepines or other CNS depressants increases risk of respiratory depression. Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome.
| Serious Effects |
Hypersensitivity to buprenorphine or naloxone; severe respiratory insufficiency; acute alcoholism or delirium tremens; concomitant use of MAO inhibitors or within 14 days; significant respiratory depression; status asthmaticus; known or suspected gastrointestinal obstruction.
| Precautions | Respiratory depression especially with concurrent use of CNS depressants; precipitation of opioid withdrawal if initiating in opioid-dependent patients with short-acting opioids; risk of adrenal insufficiency; hepatic toxicity; hypotension; misuse potential; neonatal withdrawal syndrome; pediatric overdose risk; impairment of mental alertness. |
| Food/Dietary | Avoid high-oxalate foods (spinach, rhubarb, beet greens) and high-phytate foods (whole grains, nuts, seeds) within 2 hours of dosing, as they may reduce calcium absorption. Limit alcohol and caffeine intake, as they can decrease calcium absorption and increase excretion. No significant interaction with isoflavones from soy foods. |
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| Fetal Monitoring | Maternal: Serum CASSIPA levels (target trough 5-10 mcg/mL), hepatic function (ALT, AST, bilirubin), renal function (serum creatinine, BUN), and CBC with platelets. Fetal: Serial ultrasound for growth, amniotic fluid index, and anomaly scan at 18-22 weeks. Consider fetal echocardiogram if exposure in first trimester. |
| Fertility Effects | CASSIPA may impair fertility in females by disrupting menstrual cyclicity and ovulation via interference with hypothalamic-pituitary-ovarian axis. In males, reduces sperm count, motility, and induces morphological abnormalities. Effects are reversible upon discontinuation. |
| Clinical Pearls | CASSIPA is a fixed-dose combination of calcium, vitamin D3, and isoflavones used for osteoporosis management. Monitor renal function in patients with hypercalcemia or nephrolithiasis. Avoid concurrent use with high-dose vitamin D supplements. Consider checking 25-hydroxyvitamin D levels before initiation. The isoflavone component may interact with tamoxifen via estrogen receptor modulation. |
| Patient Advice | Take with food to improve absorption and reduce gastric upset. · Do not exceed recommended dose to avoid hypercalcemia. · Report symptoms of hypercalcemia: nausea, vomiting, constipation, confusion, or muscle weakness. · Maintain adequate hydration, especially during prolonged inactivity. · Inform your healthcare provider if you are using any other calcium or vitamin D supplements. · Store at room temperature away from moisture and heat. |