Hikma Pharmaceuticals Regulatory News (HIK)

PRESS RELEASE

Hikma launches Dihydroergotamine Mesylate Injection, USP

London, 13 December 2017 - Hikma Pharmaceuticals PLC (Hikma, Group) (LSE: HIK) (NASDAQ Dubai: HIK) (OTC: HKMPY) (rated Ba1 Moody's / BB+ S&P, both stable) announces that its wholly-owned US subsidiary West-Ward Pharmaceuticals Corp. (West-Ward), has launched Dihydroergotamine Mesylate Injection, USP, 1mg/mL.

West-Ward's Dihydroergotamine Mesylate Injection, USP is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes.

According to IMS Health, US sales of Dihydroergotamine Mesylate Injection, USP were approximately $34.8 million in the 12 months ending October 2017.

Riad Mechlaoui, Chief Executive Officer of Injectables said, "We are pleased to be adding Dihydroergotamine Mesylate Injection, USP to our Injectables portfolio in the US. We have a large portfolio of products and a pipeline of differentiated products to support future growth."

Important safety information

Warning

Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of DIHYDROERGOTAMINE with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP 3A4 inhibition elevates the serum levels of DIHYDROERGOTAMINE, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of these medications is contraindicated.

Warnings and Precautions

Dihydroergotamine Mesylate Injection, USP should not be given to patients with ischemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischemia) or to patients who have clinical symptoms or findings consistent with coronary artery vasospasm including Prinzmetal's variant angina.

There have been reports of pleural and retroperitoneal fibrosis in patients following prolonged daily use of injectable Dihydroergotamine Mesylate. Rarely, prolonged daily use of other ergot alkaloid drugs has been associated with cardiac valvular fibrosis. Rare cases have also been reported in association with the use of injectable Dihydroergotamine Mesylate; however, in those cases, patients also received drugs known to be associated with cardiac valvular fibrosis.

Dihydroergotamine Mesylate Injection, USP should not be used by patients with documented ischemic or vasospastic coronary artery disease. It is strongly recommended that Dihydroergotamine Mesylate Injection, USP not be given to patients in whom unrecognized coronary artery disease (CAD) is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, females who are surgically or physiologically postmenopausal, or males who are over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease.

The potential for adverse cardiac events exists. Serious adverse cardiac events, including acute myocardial infarction, life-threatening disturbances of cardiac rhythm, and death have been reported to have occurred following the administration of Dihydroergotamine Mesylate Injection, USP. Considering the extent of use in patients with migraine, the incidence of these events is extremely low.

Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients; and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the Dihydroergotamine Mesylate Injection, USP having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not. Patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, transient ischemic attack).

Dihydroergotamine Mesylate Injection, USP, like other ergot alkaloids, may cause vasospastic reactions other than coronary artery vasospasm. Myocardial, peripheral vascular, and colonic ischemia have been reported.

Dihydroergotamine Mesylate Injection, USP associated vasospastic phenomena may also cause muscle pains, numbness, coldness, pallor, and cyanosis of the digits. In patients with compromised circulation, persistent vasospasm may result in gangrene or death. Administration should be discontinued immediately if signs or symptoms of vasoconstriction develop.

As Dihydroergotamine Mesylate Injection, USP may increase blood pressure, it should not be given to patients with uncontrolled hypertension. Significant elevation in blood pressure has been reported on rare occasions in patients with and without a history of hypertension.

Dihydroergotamine Mesylate Injection, USP 5-HT1 agonists (e.g., sumatriptan), ergotamine-containing or ergot-type medications or Methysergide should not be used within 24 hours of each other.

Dihydroergotamine Mesylate Injection, USP should not be administered to patients with hemiplegic or basilar migraine.

Dihydroergotamine Mesylate Injection, USP is contraindicated in patients with known peripheral arterial disease, sepsis, following vascular surgery and severely impaired hepatic or renal function.

Administration may cause fetal harm when administered to a pregnant woman. Dihydroergotamine possesses oxytocic properties and, therefore, should not be administered during pregnancy. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Dihydroergotamine Mesylate Injection, USP should not be used by nursing mothers.

Dihydroergotamine Mesylate Injection, USP should not be used with peripheral vasoconstrictors because the combination may cause synergistic elevation of blood pressure.

Adverse Reactions

Serious cardiac events, including some that have been fatal, have occurred following use of Dihydroergotamine Mesylate injection, USP but are extremely rare. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation. Fibrotic complications have been reported in association with long term use of injectable Dihydroergotamine Mesylate.

The following events derived from postmarketing experience have been occasionally reported in patients receiving Dihydroergotamine Mesylate Injection, USP: vasospasm, paraesthesia, hypertension, dizziness, anxiety, dyspnea, headache, flushing, diarrhea, rash, increased sweating, and pleural and retroperitoneal fibrosis after long-term use of Dihydroergotamine. Extremely rare cases of myocardial infarction and stroke have been reported. A causal relationship has not been established.

For additional information, please refer to the Package Insert for full prescribing information, available on www.west-ward.com.

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About Hikma

Hikma Pharmaceuticals PLC is a multinational pharmaceutical group focused on developing, manufacturing and marketing a broad range of both branded and non-branded generic and in-licensed products. Hikma's operations are conducted through three businesses: 'Injectables,' 'Generics' and 'Branded,' based primarily in the Middle East and North Africa (MENA) region, where it is a market leader, the United States and Europe. In 2016, Hikma achieved revenues of $1,950 million and profit attributable to shareholders of $155 million.