| GHS-Einstufung | WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 24 reports by companies from 4 notifications to the ECHA C&L Inventory. |
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| Hazard Classes and Categories | Acute Tox. 4 (100%) |
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| Treatment | If overdosage occurs, symptomatic hypocalcemia could also resultsuch patients should be treated with short-term intravenous calcium. (L1712) |
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| Gesundheitliche Auswirkungen | Rare cases of uveitis, iritis, scleritis, and episcleritis have been reported, including one case of scleritis, and one case of uveitis upon separate rechallenges. |
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| Unerwünschte Wirkungen | Pamidronate correlates with numerous adverse effects, including hypocalcemia and resulting secondary hyperparathyroidism, acute phase response, musculoskeletal pain, various ocular events, and osteonecrosis of the jaw. |
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| Expositionspfade | Parenteral (intravenous).
Plasma concentration rises rapidly upon IV administration. |
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| Toxizitätsübersicht | A small number of cases describe symptomatic hypocalcemia following pamidronate administration. In each case, however, patients had pre-existing derangements contributing to their symptoms, including renal insufficiency and low vitamin D levels secondary to lifestyle, previous GI surgery, and medication history. Recommendations for the management of pamidronate overdose include appropriate correction of the electrolyte disturbance and pre-treatment supplementation with calcium and Vitamin D.The mechanism of action of pamidronate is inhibition of bone resorption. Pamidronate adsorbs to calcium phosphate (hydroxyapatite) crystals in bone and may directly block dissolution of this mineral component of bone. In vitro studies also suggest that inhibition of osteoclast activity contributes to inhibition of bone resorption. Pamidronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass. |
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| Signs and Symptoms | Side effects include an allergic reaction, kidney problems, seizures, low levels of calcium, magnesium, or phosphorus in the blood |
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| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
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| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)pamidronateDILI NegativeIntravenousDOI:10.1016/j.drudis.2019.09.022 |
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| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
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