People with achondroplasia are often born to parents that do not have the condition due to spontaneous mutation.Achondroplasia can be inherited through autosomal dominance. In couples where one partner has achondroplasia there is a 50% chance of passing the disorder on to their child every pregnancy. In situations where both parents have achondroplasia there is a 50% chance the child will have achondroplasia, 25% chance the child will not, and a 25% chance that the child will inherit the gene from both parents resulting in double dominance and leading to severe or lethal bone dysplasia.Studies have demonstrated that new gene mutations for achondroplasia are exclusively inherited from the father and occur during spermatogenesis; it has been theorized that sperm carrying the mutation in FGFR3 have a selective advantage over sperm with normal FGFR3. The frequency of mutations in sperm leading to achondroplasia increases in proportion to paternal age, as well as in proportion to exposure to ionizing radiation. The occurrence rate of achondroplasia in the children of fathers over 50 years of age is 1 in 1,875, compared to 1 in 15,000 in the general population. Research by urologist Harry Fisch of the Male Reproductive Center at Columbia Presbyterian Hospital in 2013 indicated that in humans this defect may be exclusively inherited from the father and becomes increasingly probable with paternal age, specifically males reproducing after 35.There are two other syndromes with a genetic basis similar to achondroplasia: hypochondroplasia and thanatophoric dysplasia.
Netupitant/palonosetron, sold under the brand name Akynzeo, is a fixed-dose combination medication used for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. It is marketed and distributed by Helsinn Therapeutics. Netupitant is an NK1 receptor antagonist and palonosetron is a 5-HT3 receptor antagonist.The capsules contain netupitant and palonosetron hydrochloride. The intravenous version is a combination of fosnetupitant chloride hydrochloride and palonosetron hydrochloride. Contraindications
Netupitant/palonosetron may be contraindicated during pregnancy. Adverse effects
The most common side effects include headache, weakness, fatigue, upset stomach, constipation, and skin redness. The overall profile of adverse effects is comparable to that of palonosetron (see Palonosetron#Adverse effects); no common adverse effects can be attributed to netupitant. Interactions
Pharmacology
History
Netupitant/palonosetron was approved for use in the United States in October 2014. It was approved for use in the European Union in May 2015. The intravenous version, which contains the prodrug fosnetupitant in place of netupitant, was approved in the United States in April 2018. References
External links
"Netupitant mixture with palonosetron". Drug Information Portal. U.S. National Library of Medicine. "Fosnetupitant". Drug Information Portal. U.S. National Library of Medicine. "Fosnetupitant and Palonosetron (Professional Patient Advice)". Drugs.com.