Ponatinib (trade name Iclusig  eye-KLOO-sig, previously AP24534) is an oral drug developed by ARIAD Pharmaceuticals for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL). It is a multi-targeted tyrosine-kinase inhibitor. Some forms of CML, those that have the T315I mutation, are resistant to current therapies such as imatinib. Ponatinib has been designed to be effective against these types of tumors.The United States Food and Drug Administration approved the drug as a candidate in December 2012, but temporarily suspended sales on 31 October 2013 because of "the risk of life-threatening blood clots and severe narrowing of blood vessels". This suspension was partially lifted on Dec. 20, 2013 with ponatinib being issued revised prescribing information, a new "Black Box Warning" and a "Risk Evaluation and Mitigation Strategy" in place to better evaluate the risks and benefits of using the drug. In the US it can cost $138,000 a year, which has been criticized. Approvals and indications
Ponatinib was approved by the US FDA on December 14, 2012, for patients with resistant or intolerant CML and Ph+ ALL, based on results of the PACE phase II trial reported days earlier at the annual ASH meeting. Because the approval was under the FDA Accelerated Approval program the applicant was required to carry out additional studies.
Familial hypocalciuric hypercalcemia (FHH) is an inherited condition that can cause hypercalcemia, a serum calcium level typically above 10.2 mg/dL; although uncommon. It is also known as familial benign hypocalciuric hypercalcemia (FBHH) where there is usually a family history of hypercalcemia which is mild, a urine calcium to creatinine ratio <0.01, and urine calcium <200 mg/day. Signs and symptoms
Most cases of familial hypocalciuric hypercalcemia are asymptomatic. Laboratory signs of FHH include:
High blood levels of calcium (hypercalcemia)
A low amount of calcium excreted in the urine (Ca excretion rate < 0.02 mmol/L)
High blood levels of magnesium (hypermagnesemia)
High normal to mildly elevated parathyroid hormone

Causes
Types include:

Pathogenesis
Most cases of FHH are associated with loss of function mutations in the calcium-sensing receptor (CaSR) gene, expressed in parathyroid and kidney tissue. These mutations decrease the receptors sensitivity to calcium, resulting in reduced receptor stimulation at normal serum calcium levels. As a result, inhibition of parathyroid hormone release does not occur until higher serum calcium levels are attained, creating a new equilibrium. This is the opposite of what happens with the CaSR sensitizer, cinacalcet. Functionally, parathyroid hormone (PTH) increases calcium resorption from the bone and increases phosphate excretion from the kidney which increases serum calcium and decreases serum phosphate. Individuals with FHH, however, typically have normal PTH levels, as normal calcium homeostasis is maintained, albeit at a higher equilibrium set point. As a consequence, these individuals are not at increased risk of the complications of hyperparathyroidism.Another form has been associated with chromosome 3q.